This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

Size: px
Start display at page:

Download "This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data."

Transcription

1 abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the clinical study report had been prepared in accordance with best practice and applicable legal and regulatory requirements at the time of study completion. The synopsis may include approved and non approved uses, doses, formulations, treatment regimens and/or age groups; it has not necessarily been submitted to regulatory authorities. A synopsis is not intended to provide a comprehensive analysis of all data currently available regarding a particular drug. More current information regarding a drug is available in the approved labeling information which may vary from country to country.. Additional information on this study and the drug concerned may be provided upon request based on s Policy on Transparency and Publication of Clinical Study Data. The synopsis is supplied for informational purposes only in the interests of scientific disclosure. It must not be used for any commercial purposes and must not be distributed, published, modified, reused, posted in any way, or used for any other purpose without the express written permission of.

2

3 Page 2 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 2 of International GmbH or one or more of its affiliated companies. All rights reserved. Objectives: The main objective of Parts 1 to 4 of this trial was to investigate safety, antiviral effect, and pharmacokinetics of deleobuvir (DBV/BI ) in combination with faldaprevir (FDV/BI ) and ribavirin (RBV) for 4, 16, 24, 28, or 40 weeks in patients with chronic hepatitis C virus (HCV) Genotype 1 (GT-1) infection. Part 1 Part 1 investigated the safety, antiviral short-term activity, and pharmacokinetic interactions of DBV in combination with FDV and RBV. This part was aimed to establish the 'proof of principle' that a pegylated interferon alfa (PegIFN)-sparing regimen with FDV and DBV (± RBV) suppresses the emergence of resistance mutations that were observed with monotherapy of FDV or DBV. Part 2 Part 2 assessed long-term safety and antiviral activity of DBV in combination with FDV, with or without RBV. This part was conducted to establish the proof-of-concept (i.e. achievement of sustained virological response) with a PegIFN-sparing oral-oral treatment regimen. In addition, the therapeutic benefit of the different treatment regimens formed the basis for the selection of treatment regimens and target population in the Phase III clinical development programme. Part 3 Part 3 explored the safety, antiviral effect, and pharmacokinetics of additional dosing regimens of FDV and DBV combination therapy with RBV and without DBV induction dose (1200 mg of DBV as first intake at Day 1) in treatment-naïve GT-1a chronic HCV patients with the unfavourable IL28B non-cc alleles. In addition, a regimen of 16 weeks of combination therapy with DBV 600 mg twice daily (BID) was explored in patients with GT-1b infection or GT-1a infection who carry the IL28B CC allele. Part 4 Part 4 explored the safety, antiviral effect, and pharmacokinetics of FDV 120 mg once daily (QD) and DBV 600 mg BID combination therapy with RBV in treatmentexperienced patients with chronic HCV GT-1b infection and previous null-response to combined PegIFN and RBV treatment. The sponsor decided to discontinue the clinical developmental programmes of DBV and FDV. Therefore, Part 4 of this trial had been terminated early and only 3 patients were entered.

4 Page 3 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 3 of International GmbH or one or more of its affiliated companies. All rights reserved. Methodology: Trial was a randomised, open-label, parallel-group trial assessing different PegIFN-sparing regimens combining a protease with a polymerase inhibitor (with or without RBV) for treatment of chronic HCV infection. Part 1 Treatment-naïve patients were randomised in a 1:1 ratio into 2 treatments groups. The patients received either DBV 400 mg or 600 mg 3 times daily (TID) and FDV 120 mg QD in combination with standard weight-based dose of RBV for 4 weeks (combination therapy period). A loading dose of FDV 240 mg was given on the first day of FDV administration, followed by 120 mg QD starting at Day 2. An induction dose of DBV 1200 mg was given on the first day of DBV administration, followed by 2 more doses of 400 mg (DBV 400 mg dose group) or 600 mg (DBV 600 mg dose group) on the first day. From Week 5 to Week 24, patients received treatment with FDV 120 mg QD in combination with standard of care (SOC) PegIFN/RBV (triple therapy period). Patients presenting with plasma HCV RNA <25 IU/mL at Week 4 and undetectable HCV RNA after that up to Week 18 then entered the follow-up phase directly. Patients not meeting these criteria received additional treatment with PegIFN/RBV (without FDV) from Week 25 to Week 48 (SOC therapy period) before entering the follow-up phase. After end of all treatment, the follow-up phase lasted 24 weeks. Part 2 Part 2 assessed treatment durations of 16, 28, or 40 weeks. Treatment-naïve patients were randomised in a 1:1:1:1:1 ratio into 5 treatment groups. In 3 groups, patients received DBV 600 mg TID and FDV 120 mg QD in combination with standard weightbased dose of RBV for 16, 28, or 40 weeks. In the BID 28 wks group, patients received DBV 600 mg BID and FDV 120 mg QD in combination with standard weight-based dose of RBV for 28 weeks. In the NRBV group, patients received DBV 600 mg TID and FDV 120 mg QD without RBV for 28 weeks. A loading dose of FDV 240 mg was given on the first day of FDV administration, followed by 120 mg QD starting at Day 2. An induction dose of DBV 1200 mg was given on the first day of DBV administration, followed by 2 more doses (DBV 600 mg TID dose groups) or 1 more dose of 600 mg (DBV 600 mg BID dose group) on the first day.

5 Page 4 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 4 of International GmbH or one or more of its affiliated companies. All rights reserved. Methodology After end of all treatment, the follow-up phase lasted 144 weeks for patients with FDV and DBV in combination with RBV treatment. Patients who discontinued their assigned treatment early due to lack of antiviral activity, could receive additional treatment with PegIFN/RBV for up to 24 weeks. Patients receiving SOC were followed up for 24 weeks or, if SOC was discontinued prematurely, for 72 weeks. For patients not receiving SOC treatment the follow-up phase lasted 48 weeks. Part 3 Part 3 evaluated treatment durations of 16 and 24 weeks. Treatment-naïve patients were assigned, depending on GT-1 subgenotype (1a and 1b) and IL28B genotype (CC vs. non-cc), to 1 of the 3 following treatment groups: BID 600 mg 16wks: 16 weeks of DBV 600 mg BID and FDV 120 mg QD in combination with standard weight-based dose of RBV in patients with HCV GT-1b (any IL28B genotype) or GT-1a with IL28 CC BID 800 mg 24wks: 24 weeks of DBV 800 mg BID and FDV 120 mg QD in combination with standard weight-based dose of RBV in patients with HCV GT-1a with IL28B non-cc TID 600 mg 24wks: 24 weeks of DBV 600 mg TID and FDV 120 mg QD in combination with standard weight-based dose of RBV in patients with HCV GT-1a with IL28B non-cc A loading dose of FDV 240 mg was given on the first day of FDV administration for the 3 treatment groups. After end of all treatment, the follow-up phase lasted 96 weeks for patients with DBV and FDV in combination with RBV treatment. Patients who discontinued their assigned treatment early due to lack of antiviral activity, could receive additional treatment with PegIFN/RBV for 24 weeks before entering the 24-week follow-up phase. Part 4 Treatment-experienced patients with HCV GT-1b (any IL28B) were assigned to 2 treatment groups, receiving DBV 600 mg BID and FDV 120 mg QD in combination with RBV for 16 or 24 weeks. A loading dose of FDV 240 mg was given on the first day of FDV administration. After end of all treatment, the follow-up phase lasted 24 weeks.

6 Page 5 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 5 of International GmbH or one or more of its affiliated companies. All rights reserved. No. of patients: Part 1 planned: entered: 32 actual: enrolled: 56 entered: 34 No. of patients: Part 2 planned: entered: 400 actual: enrolled: 469 DBV 400 mg TID + FDV 120 mg QD (BI combi) + RBV: entered: 17 treated: 15 analysed (for primary endpoint): 15 DBV 600 mg TID + FDV 120 mg QD (BI combi) + RBV: entered: 17 treated: 17 analysed (for primary endpoint): 17 entered: 368 treated: 362 TID 16wks (DBV 600 mg TID + FDV 120 mg QD + RBV): entered: 81 treated: 81 analysed for primary endpoint: 81 TID 28wks (DBV 600 mg TID + FDV 120 mg QD + RBV): entered: 80 treated: 80 analysed for primary endpoint: 80 TID 40wks (DBV 600 mg TID + FDV 120 mg QD + RBV): entered: 79 treated: 77 analysed for primary endpoint: 77 BID 28wks (DBV 600 mg BID + FDV 120 mg QD + RBV): entered: 79 treated: 78 analysed for primary endpoint: 78 NRBV 28wks (DBV 600 mg TID + FDV 120 mg QD): entered: 49 treated: 46 analysed for primary endpoint: 46

7 Page 6 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 6 of International GmbH or one or more of its affiliated companies. All rights reserved. No. of patients: Part 3 planned: entered: 90 actual: enrolled: 169 entered: 83 treated: 83 No. of patients: Part 4 planned: entered: 30 actual: enrolled: 13 BID 600 mg 16wks (DBV 600 mg BID + FDV 120 mg QD + RBV): entered: 32 treated: 32 analysed for primary endpoint: 32 BID 800 mg 24wks (DBV 800 mg BID + FDV 120 mg QD + RBV): entered: 26 treated: 26 analysed for primary endpoint: 26 TID 600 mg 24wks (DBV 600 mg TID + FDV 120 mg QD + RBV): entered: 25 treated: 25 analysed for primary endpoint: 25 entered: 3 treated: 3 BID 16 wks (DBV 600 mg BID + FDV 120 mg QD + RBV): entered: 1 treated: 1 analysed: 1 BID 24 wks (DBV 600 mg BID + FDV 120 mg QD + RBV): entered: 2 treated: 2 analysed: 2

8 Page 7 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 7 of International GmbH or one or more of its affiliated companies. All rights reserved. Diagnosis and main criteria for inclusion: Test product 1: dose: mode of admin.: Patients, 18 to 75 years of age, with chronic HCV GT-1 infection, diagnosed by positive HCV antibody or detectable HCV RNA in blood at least 6 months prior to randomisation or by a liver biopsy typical of chronic hepatitis C in combination with positive HCV serology could be included. HCV infection of GT-1 had to be confirmed by genotypic testing at screening: in Parts 1 to 3 subgenotype 1a or 1b, in Part 4 subgenotype b had to be verified. Patients were to be treatment-naïve in Parts 1 to 3, and treatment-experienced in Part 4. In Parts 1 to 3, treatment-naïve was defined as no prior treatment with any interferon, PegIFN and/or RBV, and no prior treatment with at least 1 dose of any direct antiviral agent for acute or chronic HCV infection. In Part 4, treatment-experienced patients had to have confirmed prior virological failure to an approved dose of PegIFN/RBV (null-response) defined as: absence of HCV RNA drop by 2log10 from baseline at treatment Week 12. Note: no prior treatment with any direct antiviral agent for acute or chronic HCV infection was allowed. Patients had to have a plasma HCV RNA IU/mL at screening and a liver biopsy within 2 years or fibroscan within 6 months prior to baseline; if cirrhosis was demonstrated by a biopsy more than 3 years ago it needed not to be repeated. Note: In Part 1, cirrhosis had to be excluded, whereas in Parts 2, 3, and 4 patients with Child- Pugh A cirrhosis were eligible. Deleobuvir (DBV) tablet (200 mg tablets) Part 1: 2 doses, dose strengths: 400 mg TID, 600 mg TID Part 2: 2 doses, dose strengths: 600 mg TID, 600 mg BID Part 3: 3 doses, dose strengths: 600 mg TID, 600 mg BID, 800 mg BID Part 4: 1 dose, dose strength: 600 mg BID In Parts 1 and 2, an induction dose of DBV 1200 mg was given on the first day of administration, followed by 1 or 2 more doses of 400 mg or 600 mg on Day 1 (dependent on group assignment). Oral

9 Page 8 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 8 of International GmbH or one or more of its affiliated companies. All rights reserved. batch no.: Test product 2: dose: mode of admin.: batch no.: Test product 3: dose: mode of admin.: batch no.: Part 1: B and B Part 2: B and B Part 3: B , B , B , B , B , B , B Part 4: B Faldaprevir (FDV) soft gelatin capsule (120 mg capsules) A loading dose of 240 mg FDV was given on the first day of FDV administration. 120 mg QD Oral Part 1: B Part 2: B Part 3: B Part 4: B Ribavirin (RBV) (Copegus ) tablet (200 mg tablets) 1000 mg if <75kg, or 1200 mg if 75kg, distributed in 2 divided doses Oral Part 1: B Part 2: B , B , B , B Part 3: B (130315/U8048), B (130428/B0023), B (950168) Part 4: B

10 Page 9 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 9 of International GmbH or one or more of its affiliated companies. All rights reserved. Test product 4 (Part 1 only): dose: mode of admin.: batch no.: Duration of treatment: Criteria for evaluation: Pegylated interferon alfa 2a (Pegasys ) solution for injection 180 µg per week Subcutaneous injection B Efficacy: Part 1 Part 1: 4 weeks of DBV, 24 weeks of FDV, 24 or 48 weeks of RBV, and 20 or 44 weeks of PegIFN Part 2: 16, 28, or 40 weeks of DBV in combination with FDV and RBV, except in the NRBV 28wks group which did not include RBV Parts 3 and 4: 16 or 24 weeks of DBV in combination with FDV and RBV The primary efficacy endpoint in Part 1 was a plasma HCV RNA level <25 IU/mL (detectable or not detectable) at Week 4. The secondary efficacy endpoints were: Time to virological response: time point of the first measurement of undetectable plasma HCV RNA level Plasma HCV RNA level not detectable at Week 4 (below limit of detection [BLD] Week 4)

11 Page 10 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 10 of International GmbH or one or more of its affiliated companies. All rights reserved. Efficacy Part 2 The primary efficacy endpoint in Part 2 was a sustained virological response (SVR) at 12 weeks after completion of all therapy: plasma HCV RNA not detectable at 12 weeks after completion of all therapy (SVR12). The secondary efficacy endpoints were: Time to virological response: timepoint of the first measurement of undetectable plasma HCV RNA level Plasma HCV RNA level not detectable at Week 4 (BLD Week 4) SVR4: plasma HCV RNA level not detectable at 4 weeks after completion of all therapy SVR24: plasma HCV RNA level not detectable at 24 weeks after completion of all therapy Parts 3 and 4 The primary efficacy endpoint in Parts 3 and 4 was SVR12: plasma HCV RNA not detectable at 12 weeks after completion of all therapy. The secondary efficacy endpoints were: Plasma HCV RNA level <25 IU/mL at Weeks 4 and 12 SVR4: plasma HCV RNA level not detectable at 4 weeks after completion of all therapy

12 Page 11 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 11 of International GmbH or one or more of its affiliated companies. All rights reserved. Pharmacokinetics: Pharmacokinetics (PK) of DBV, its metabolites, and FDV: Part 1 After first dose (Day 1): AUC 0-6,1, AUC 0-24,1, C pre,1, C pre,2, C avg,0-24 Trough PK: C pre,n On Day 10: C max,ss, t max, C pre,n, AUC 0-6,ss, AUC 0-12,ss, AUC 0-24,ss, R A,Cmax, R A,AUC Part 2 Trough PK: C pre,n (predose concentration of the analyte in plasma immediately before administration of the Nth dose after N-1 doses were administered [ng/ml]) Parts 3 and 4 Safety: Parts 1 to 4 Trough PK: C pre,n (predose concentration of the analyte in plasma immediately before administration of the Nth dose after N-1 doses were administered [ng/ml]) On trial days 1 (Visit 2), 12 (Visit 5), and 57 (Visit 10): C pre,n and 4 post dose samples At all other visits: blood samples for plasma drug concentrations (DBV and metabolites, FDV and RBV) Safety was assessed in a descriptive way and no primary safety endpoints were defined. Safety endpoints were: Tolerability, vital signs, and physical examination Adverse events (AEs) Discontinuations due to AEs Laboratory abnormalities Laboratory test value changes over time

13 Page 12 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 12 of International GmbH or one or more of its affiliated companies. All rights reserved. Statistical methods: Part 1 Descriptive statistics for efficacy, safety, and PK endpoints were calculated. The proportion of patients achieving the primary endpoint was calculated together with its confidence intervall (CI) based on the Beta function. Relationship between changes in plasma HCV RNA and PK parameters were explored. Part 2 Descriptive statistics: stratified Cochran-Mantel-Haenszel method, logistic regression for efficacy. The proportion of patients achieving the primary endpoint was calculated together with its CI based on the normal approximation to the binomial distribution. Differences between treatment regimens were estimated using stratified CMH method adjusting for IL28B genotype and HCV subtype. Descriptive statistics for safety and PK endpoints were calculated. Part 3 Descriptive statistics: The proportion of patients achieving the primary endpoint was calculated together with its CI based on the normal approximation to the binomial distribution. Kaplan-Meier method for time to first plasma HCV RNA undetected. Standard descriptive statistics and simple proportions for other endpoints. Descriptive statistics for safety and PK endpoints were calculated. Part 4 Part 4 had been terminated early and only 3 patients were entered. Therefore, no formal analyses of efficacy data were performed. Descriptive results of HCV RNA viral load, adverse events, laboratory data, and vital signs are presented in this clinical trial report.

14 Page 13 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 13 of International GmbH or one or more of its affiliated companies. All rights reserved. SUMMARY CONCLUSIONS: Efficacy results: Part 1 Disposition, demographics, and baseline characteristics At total of 56 patients were enrolled, 34 patients were randomised, and 32 patients were treated (DBV 400 mg: 15 patients, DBV 600 mg: 17 patients). Of these, 30 patients (93.8%) completed the planned observation time (DBV 400 mg: 86.7%, DBV 600 mg: 100%); 2 patients (6.3%) in the DBV 400 mg group did not complete the planned observation time. One patient (6.7%) in the DBV 400 mg group prematurely discontinued trial medication due to lack of antiviral response. The demographic characteristics were generally balanced between the 2 treatment groups. Overall, all patients with the exception of one, were White (31 of 32 patients [96.9%]). The majority of patients were male (18 males; 14 females). The age of patients was equal in both treatment groups with a mean age of 50.8 years. Mean HCV viral load at baseline did not differ substantially between the groups. The majority of patients had a baseline viral load of IU/mL. Efficacy results The number of patients who achieved the primary endpoint (plasma HCV RNA <25 IU/mL at Week 4) was 73.3% (11/15) and 100% (17/17) in the DBV 400 mg and 600 mg groups respectively. For all the patients who achieved SVR, the time to virological response was slightly shorter in the DBV 600 mg group, with similar rate of viral load BLD within the first 2 Weeks (6.3% [1/16] in the DBV 600 mg group versus 9.1% [1/11] in the DBV 400 mg group) but slightly more patients achieving a viral load BLD within the first 4 Weeks in the 600 mg compared to the 400 mg dose group (50.0% [8/16] versus 27.3% [3/11], respectively). A plasma HCV RNA level not detectable at Week 4 was achieved by 20% (3/15) of patients in the DBV 400 mg group and by 70.6% (12/17) of patients in the DBV 600 mg group. Analysis of the response in the different GTs revealed that the lower dose was less effective in patients with GT-1a. However, the higher dosage evoked a similar response in patients with GT-1a and -1b.

15 Page 14 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 14 of International GmbH or one or more of its affiliated companies. All rights reserved. Efficacy results Part 2 Disposition, demographics, and baseline characteristics At total of 469 patients were enrolled, 368 patients were randomised, and 362 patients were treated (TID 16wks: 81 patients, TID 28wks: 80 patients, TID 40wks: 77 patients, BID 28wks: 78 patients, NRBV 28wks: 46 patients). Of the treated patients, 279 patients (77.1%) completed the planned observation time (TID 16wks: 71.6%, TID 28wks: 85.0%, TID 40wks: 66.2%, BID 28wks: 80.8%, NRBV 28wks: 84.8%). 146 patients (40.3%) prematurely discontinued trial medication (TID 16wks: 24.7%, TID 28wks: 40.0%, TID 40wks: 55.8%, BID 28wks: 30.8%, NRBV 28wks: 58.7%). Overall, the most frequent reasons for premature discontinuation were AEs (total 12.2%), ranging from 4.9% (TID 16wks) to 24.7% (TID 40wks), and lack of antiviral response (total 24.0%), ranging from 14.8% (TID 16wks) to 45.7% (NRBV 28wks). The demographic characteristics were generally balanced between the 5 treatment groups. The majority of patients were White (98.3%), 1 patient was Asian (0.3%), 4 patients were African American (1.1%), and for 1 patient the race was specified as other (0.3%). There was a balance between male patients (51.7%) and female patients (48.3%). The mean age of the patients was 47.8 years. The mean viral load (VL) at baseline was 6.6log 10 IU/mL for all groups except the TID 28wks group (6.5log 10 IU/mL). The proportion of patients that had a baseline VL of IU/mL ranged from 78.3% in the NRBV 28wks group to 87.0% in the TID 40wks group. As patients were stratified for genotype (1a, 1b) and IL28B (CC, non-cc), genotype and IL28B categories were evenly distributed among treatment groups. Efficacy results The primary endpoint (SVR12) was reached in more than 50% of patients receiving FDV and DBV combined with RBV compared to a lower SVR12 rate in patients not receiving RBV (39.1%). The highest response rate was observed in the BID 28wks group with 69.2%. Higher doses of FDV/DBV and longer treatment duration did not lead to improvement of treatment response. Higher SVR was associated with GT-1b, female sex, or IL28B CC genotype in patients receiving treatment regimens containing RBV. A baseline viral load < IU/mL was shown to be a further indicator for higher response rates in patients.

16 Page 15 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 15 of International GmbH or one or more of its affiliated companies. All rights reserved. Efficacy results While higher rates of SVR12 were observed in non-cirrhotic patients, there was a lower number of cirrhotic patients in the trial (33 patients, 9.1% of all treated patients) so conclusions could not be drawn. The most frequent reason for patients not achieving SVR12 was lack of antiviral response. The highest proportion of breakthroughs (treatment failure on-treatment) occurred in the NRBV 28wks group and the BID 28wks group. Most patients with breakthrough had achieved a viral load below the limit of quantification (BLQ) before breakthrough occurred. Relapse (treatment failure after end of all therapy) occurred mainly in the TID 16wks group (11 patients, 13.6%); a relapse was observed in the TID 28wks and TID 40wks groups for 1 patient (1.3%) each, in the BID 28wks group for no patient, and in the NRBV 28wks for 2 patients (4.3%). Treatment discontinuations were least frequent under BID 28wks. In this treatment group, the highest SVR12 rates were observed. For secondary endpoints, the time to first virological response was similar in all treatment groups. On Day 57, all patients showing virological response achieved BLD, except for 1 patient each in the NRBV, TID 40wks, and TID 28wks treatment groups. The plasma HCV level was BLD at Week 4 for more than 60% in all TID treatment regimens containing RBV. The lowest response at Week 4 was observed in patients with NRBV treatment. After completion of all therapy, SVR4 was achieved by about 55% to 70% of patients in the treatment regimens containing RBV (TID 16 wks: 60.5%, TID 28wks: 62.5%, TID 40wks: 54.5%, BID 28wks: 69.2%); in the NRBV 28wks group 43.5% of patients achieved SVR4. SVR24 was achieved by about 50% to 70% of patients in the treatment regimens containing RBV (TID 16 wks: 58.0%, TID 28wks: 58.8%, TID 40wks: 49.4%, BID 28wks: 69.2%); in the NRBV 28wks group 39.1% of patients achieved SVR24. For the predictability of treatment success, the positive predictive value (PPV), defined as the probability of achieving SVR12 having met a specific earlier endpoint was observed to be high for the combination of BLD Week 4 and Week 12, ranging from 81.3% to 92.3%. Patients were discontinued when detectable plasma HCV RNA at Week 6 was observed. Concluding, all patients finishing treatment had BLQ at Week 6.

17 Page 16 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 16 of International GmbH or one or more of its affiliated companies. All rights reserved. Efficacy results Part 3 Disposition, demographics, and baseline characteristics At total of 169 patients were enrolled, 83 patients were randomised and treated (BID 600 mg 16wks: 32 patients, BID 800 mg 24wks: 26 patients, TID 600 mg 24wks: 25 patients). Of these, 51 patients (61.4%) completed the planned observation time (BID 600 mg 16wks: 68.8%, BID 800 mg 24wks: 57.7%, TID 600 mg 24wks: 56.0%). 49 patients (59.0%) prematurely discontinued trial medication (BID 600 mg 16wks: 25.0%, BID 800 mg 24wks: 80.8%, TID 600 mg 24wks: 80.0%). Overall, the most frequent reasons for premature discontinuation were AEs (total 14.5%), ranging from 8.0% (TID 600 mg 24wks) to 26.9% (BID 800 mg 24wks), and lack of antiviral response (total 39.8%), ranging from 9.4% (BID 600 mg 16wks) to 64.0% (TID 600 mg 24wks). The demographic characteristics were generally balanced across the randomised groups (the BID 800 mg 24wks and TID 600 mg 24wks groups; the patients in the BID 600 mg 16wks group were not assigned in a randomised fashion). The majority of patients were White (94.0%), 4 patients were Black or African American (4.8%) and 1 patient was Asian (1.2%). The distribution of gender was balanced, with 50.6% female and 49.4% male patients (of note: the proportion of female patients assigned to the BID 600 mg 16wks group appeared to be higher [62.5%]). The mean age of the patients was 47.6 years (range 46.5 to 48.9 years). The mean VL at baseline was 6.3log 10 IU/mL for the BID 800 mg 24wks group and 6.4log 10 IU/mL for the other 2 groups. Only patients with HCV GT-1a and IL28B non-cc GT were randomised to the BID 800 mg 24wks and TID 600 mg 24wks groups (with 69.2% and 68.0% IL28B CT, respectively). Patients with either GT-1a (37.5%, all having IL28B CC) or GT-1b (62.5%, having any IL28B type) were assigned to the BID 600 mg 16wks group. 13 patients (15.7%) with liver cirrhosis were included in the trial (BID 600 mg 16 wks: 12.5%, BID 800 mg 24 wks: 11.5%, TID 600 mg 24wks: 24.0%).

18 Page 17 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 17 of International GmbH or one or more of its affiliated companies. All rights reserved. Efficacy results Efficacy results The combination treatment of DBV, FDV, and RBV was highly efficacious in patients infected with HCV GT-1b. The primary endpoint SVR12 was achieved in 95.0% of GT-1b patients of the BID 16wks group including those with liver cirrhosis. Overall SVR12 rate in this group was 65.6% including both GT-1a and GT-1b patients. The patients with GT-1a had lower SVR12 response rates, ranging from 8.0% in the TID 600 mg 24wks group to 19.2% in the BID 800 mg 24wks group. The percentage of patients achieving both Week 4 and Week 12 HCV RNA undetected was: 59.4% in the BID 600 mg 16wks (41.7% of GT-1a patients and 70% of GT-1b patients in this group), 11.5% in the BID 800 mg 24wks, and 12.0% in the TID 600 mg 24wks group. SVR4 was achieved in 24 patients (75.0%) of the BID 600 mg 16wks group but only in 5 (19.2%) and 3 patients (12.0%) of the BID 800 mg 24wks and TID 600 mg 24wks groups, respectively. For the interpretation and comparison of the efficacy data with Part 2 and also other trials, it should be noted that this trial included 15.7% of patients with liver cirrhosis (ranging from 11.5 to 24.0%), 25.3% of the patients had liver fibrosis of F3 and 84.3% of patients had high baseline HCV RNA ( IU/mL) and no induction dose of DBV was used in this trial. Overall, the efficacy results were comparable with the Part 2 of this trial without the induction dose of DBV (69.2% SVR12 in the BID 28wks group of Part 2). The high SVR12 rates achieved in GT-1b patients could be reproduced in this trial without the use of the induction dose and with the shortening of the treatment duration. 85.4% of GT-1b patients of BID 28wks of Part 2 achieved SVR12. The efficacy in GT-1a patients was low (43.3% in the BID 28wks group of Part 2) and not improved with an increased dose or treatment duration and therefore was not carried over for further investigations of this triple combination. The most frequent reason for patients not achieving SVR12 was lack of antiviral response: None of the GT-1b patients displayed lack of response but 57.7% of BID 800 mg 24wks and 76.0% of TID 600 mg 24wks group (both GT-1a). All 4 cirrhotic patients with GT-1b in the BID 600 mg 16wks group achieved SVR12 whereas none of the cirrhotic patients with GT-1a achieved SVR12. Due to the low sample size these results are to be interpreted with caution. For other parameters no influence was discernible.

19 Page 18 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 18 of International GmbH or one or more of its affiliated companies. All rights reserved. Efficacy results The patients in the BID 600 mg 16wks group and especially the GT-1b patients of this group had faster viral load decline during the first weeks of treatment as compared to GT-1a patients in the 24wks groups and many of these GT-1b patients carried over the end of treatment response to SVR4 and SVR12. In contrast, the GT-1a patients responded slower and had higher rates of breakthrough in both 24wks groups. In conclusion, the regimen of DBV 600 mg BID and FDV (plus RBV) over 16 weeks of treatment without an initial induction dose resulted in a sustained antiviral response in GT-1b patients, comparable to results obtained in Part 2 of this trial which was given with an induction dose. Treatment of GT-1a patients with a similar regimen was less effective. Part 4 Disposition, demographics, and baseline characteristics A total of 13 patients were enrolled and 3 patients were randomised and treated with DBV 600 mg BID + FDV 120 mg QD + RBV either for 16 weeks (1 patient) or 24 weeks (2 patients). The patient in the BID 16wks group prematurely discontinued trial medication due to lack of antiviral response. The planned follow-up period was completed by 2 patients (1 patient each in the BID 16wks and BID 24wks group) and 1 patient in the BID 24wks group was lost to follow-up. All patients entered in Part 4 were female; 2 patients were Black or African American (1 patient each in the BID 16wks and BID 24wks group) and 1 patient was White (BID 24wks group). The patients' age ranged from 49 to 59 years and the body mass index was between 22.4 and 25.8 kg/m 2. The mean viral load (VL) at baseline ranged from 6.2log 10 IU/mL to 6.8log 10 IU/mL. Efficacy results As Part 4 had been terminated early, no analysis of efficacy was performed for the primary endpoint; only descriptive results of HCV RNA viral load were evaluated. In the BID 24wks group, 1 patient had a virological relapse (treatment failure after end of all therapy) and 1 patient achieved SVR12. For the patient in the BID 16wks group a virological breakthrough (treament failure on-treatment) was observed.

20 Page 19 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 19 of International GmbH or one or more of its affiliated companies. All rights reserved. Pharmacokinetic results: Part 1 Steady state plasma levels of DBV were more than dose proportionally higher in the DBV 600 mg dose group, which was, however, not reflected in an enhanced pharmacodynamic response as viral load reduction was comparable in both dose groups. PK of FDV and RBV was not affected by different dose levels of DBV. All three substances showed higher plasma levels in females than males. Part 2 Geometric mean plasma concentrations for DBV, its 3 metabolites, and FDV showed a significant increase in their concentration in combination therapy compared to their exposure achieved when they were given either in monotherapy or with PegIFN/RBV particularly during the first days of treatment. Furthermore, their exposure decreased over the first weeks of treatment, becoming more stable after 4 weeks (for DBV exposure) and 8 weeks (for FDV exposure). The decrease in the exposure over time demonstrated an induction phenomenon of their metabolism, which mechanism has not yet been elucidated. Part 3 The PK blood sampling scheme was designed to provide analyte concentration results for pharmacometrics analysis, therefore relatively few predose trough plasma analyte concentrations were available for descriptive and graphical pharmacokinetic analysis. However, consistent with previous observations, the available DBV and FDV trough concentrations initially increased for a few days, followed by a gradual decrease with time, up to Day 57. Overall, because of the limited amount of available data and the observed variability, no meaningful conclusions can be drawn based on the descriptive and graphical analyses regarding potential differences in DBV and FDV trough concentrations between the treatment arms. Similarly, no meaningful conclusions can be drawn regarding gender differences or the influence of liver cirrhosis on DBV and FDV trough concentrations. Part 4 PK was not evaluated in Part 4 due to the low number of patients.

21 Page 20 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 20 of International GmbH or one or more of its affiliated companies. All rights reserved. Pharmacodynamic results: Part 2 Data of the analysis at Week 12 suggested that the increased exposure obtained when DBV and FDV are combined exceeds the exposure-response threshold for both GT-1 subtypes during the first week of treatment. On the other hand, at Week 4, the analysis suggested that the exposure of both DBV and FDV is associated with an increased probability to achieve HCV RNA <LLOD (lower level of detection) in GT-1a patients. Vomiting and photosensitivity reactions occurring the first week have been associated with high exposure of both DBV and FDV during same period. Part 3 Safety results: Part 1 A strong and rapid viral load reduction was observed in all three DBV treatment groups. The maximum mean drop in HCV RNA levels was reached around Day 12, after which the mean levels remained relatively stable. Overall, the mean viral load reduction was similar for three treatment arms. Viral load reductions close to or just over 5log 10 reduction were reached in each treatment group. Exposure For patients in the DBV 400 mg dose group, the mean exposure time was 29.1 ± 0.5, ± 44.4, and ± 82.7 days for combination, triple, and SOC therapy, respectively. The mean exposure time for patients in the DBV 600 mg dose group was 28.8 ± 0.4, ± 34.4, and 64.9±93.6 days for combination, triple, and SOC therapy, respectively. Adverse events Overall, all patients reported at least one AE during the combination therapy period; during the triple therapy period 96.8% of patients and during the SOC therapy period 62.5% of patients reported at least one AE. The system organ class with the highest rates of AEs occurring during the combination therapy period with DBV and FDV was general disorders and administration site conditions (DBV 400 mg: 80.0%, DBV 600 mg: 82.4%), as compared to a rate of 61.3% during the triple therapy period and 18.8% during SOC therapy.

22 Page 21 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 21 of International GmbH or one or more of its affiliated companies. All rights reserved. Safety results The second most common system organ class was gastrointestinal disorders (DBV 400 mg: 73.3%, DBV 600 mg: 82.4% during combination therapy). During the triple therapy period, only 29.0% of patients reported AEs of this category and 18.8% during the SOC therapy period. The third most common system organ class was skin and subcutaneous tissue disorders (DBV 400 mg: 66.7%, DBV 600 mg: 70.6%). However, this was the system organ class with the highest rate of patients experiencing AEs in the triple therapy period (77.4%). The rate during SOC therapy was 12.5%. Premature discontinuation from trial medication was reported for 1 of 15 patients in the DBV 400 mg dose group (6.7%) and for 1 of 17 patients in the DBV 600 mg dose group (5.9%.); in both cases, the discontinuation occurred several weeks after the switch to triple therapy. All of the AEs reported in the combination therapy period were assessed as drug-related by the investigator; during the triple therapy period 93.5% and during SOC therapy 43.8% of AEs were considered drug-related. During the combination therapy period, severe AEs were reported for none of the patients in the DBV 400 mg group and for 1 (5.9%) patient in the DBV 600 mg group. During triple therapy period, 5 (16.1%) patients had severe AEs and 1 (6.3%) patient was reported with severe AEs during SOC therapy. No serious AEs (SAEs) were observed during the combination therapy period. 6.5% (2/31) of patients experienced an SAE during the triple therapy period. During the SOC therapy period, 1 patient died (6.3%, [1/16]); the event was deemed drug-related as the patient seemed to have a not recorded depression at the time of event. Adverse events of special interest Rash was observed during combination therapy in 26.7% (4/15) of patients in the DBV 400 mg dose group and 23.5% (4/17) of patients in the DBV 600 mg dose group. The frequency of rash was 35.5% (11/31) during triple therapy. All cases of rash were assessed as drug-related. Only one case was considered as severe. For photosensitivity all cases, except 1 case of sunburn, were drug-related. No severe cases were reported. As in previous trials with either FDV or DBV, gastrointestinal (GI) disorders were frequently reported in this trial. The rate of GI disorders was 73.3% of patients in the DBV 400 mg dose group and 82.4% in the DBV 600 mg dose group. The number of patients with GI events decreased during triple therapy (29.0%) and SOC treatment (18.8%). Nausea and vomiting were reported in a lower frequency in the DBV 400 mg

23 Page 22 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 22 of International GmbH or one or more of its affiliated companies. All rights reserved. Safety results dose group compared with the DBV 600 mg dose group: for nausea 26.7% (4/15) vs. 64.7% (11/17) and for vomiting 26.7% (4/15) vs. 47.1% (8/17). The incidence of diarrhoea was 26.7% (4/15) in the DBV 400 mg dose group and 17.6% (3/17) in the DBV 600 mg dose group. All cases of nausea, vomiting, and diarrhoea during combination treatment were assessed as drug-related. None of the GI AEs was of severe intensity or led to treatment discontinuation. Laboratory evaluation and tolerability The clinical laboratory evaluation did not indicate substantial changes in relative and absolute differential blood count, coagulation, electrolytes, plasma proteins, protein electrophoresis, urinalysis, hormones, tumour markers, and inflammatory parameters. Read blood cell (RBC) count, haemoglobin, and haematocrit decreased below lower limit of normal in more than half of the patients during combination treatment. Total bilirubin increased above the upper limit (DBV 400 mg dose group: 53.8%; DBV 600 mg dose group: 64.3%) from normal range during combination treatment. Total bilirubin dropped during triple therapy and came back to baseline values during SOC. The changes in total bilirubin values were mainly driven by an increase in indirect bilirubin. The bilirubin profile indicates that the observed hyperbilirubinaemia may be related to pre-hepatic processes, such as increased haemolysis. This is supported by the observed decrease in red blood cell count, haemoglobin, and haematocrit. An alternative explanation for the observed hyperbilirubinaemia may be a reduced conjugation of indirect bilirubin as in vitro studies have shown a competitive inhibition of uridine diphosphate (UDP)-glucoronosyltransferase-1A1 by FDV. Intra- and posthepatic reasons for the hyperbilirubinaemia are unlikely because of the following reasons: Firstly, direct bilirubin increased only slightly compared to indirect bilirubin. Secondly, liver enzymes (alanine aminotransferase [ALT] and aspartate transaminase [AST]) improved during treatment, indicating an improved liver metabolism (see below). And lastly, plasma levels of bile acids dropped during treatment, so that obstruction of the bile ducts as a reason for hyperbilirubinaemia may be excluded.

24 Page 23 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 23 of International GmbH or one or more of its affiliated companies. All rights reserved. Safety results There were no substantial changes in the white blood cells during oral combination treatment and subsequently decreased after introducing PegIFN as part of the regimen during triple therapy and SOC treatment. Up to 92.9% of patients dropped below lower limit of normal during the different treatment phases. However, this effect was only transient, and the values improved again post-treatment. Global Clinical Assessment (GCA) tolerability at Week 4 was reported as good or satisfactory in all but 1 patient. At Week 24 the investigators assessed tolerability as good or satisfactory for more than half of the patients (DBV 400 mg dose group: 86.7%; DBV 600 mg dose group: 64.7%). Part 2 Exposure The mean exposure time for FDV/DBV for patients in the TID 28wks group was ± 69.0 days, ± 59.4 days in the BID 28wks group and ± 71.2 days in the NRBV 28wks group. In the TID 16wks group it was 96.8 ± 29.7 days and ± days in the TID 40wks group. Exposure times for RBV were identical to exposure times for FDV/DBV, except for 1 patient in the TID 16wks dose group, who discontinued FDV/DBV first and RBV only later. By definition, patients in the NRBV 28wks group did not receive RBV. Adverse events The safety evaluation was carried out on 362 patients who received FDV/DBV at least once. Most of the patients in all treatment groups reported at least one AE, with similar frequencies across treatment groups (TID 16wks: 96.3%, TID 28wks: 88.8%, TID 40wks: 96.1%, BID 28wks: 93.6%, NRBV 28wks: 95.7%). The most frequently reported system organ class was GI disorder. The proportion of patients reporting AEs for that system organ class was highest in the TID 40wks group (85.7%) and lowest in the BID 28wks group (71.8%). The proportion was similar between the TID 16wks group (80.2%) and the NRBV 28wks group (80.4%). The rate of patients experiencing AEs in this system organ class in the TID 28wks group (76.3%) was slightly lower than in the NRBV 28wks group.

25 Page 24 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 24 of International GmbH or one or more of its affiliated companies. All rights reserved. Safety results The second most common system organ class was skin and subcutaneous tissue disorders. The proportion of patients reporting AEs in this system organ class was lowest in the TID 16wks group (59.3%) and highest in the NRBV 28wks group (78.3%), thereby higher than in the other 28wks groups (TID 28wks: 66.3%, BID 28wks: 66.7%). The proportion in the TID 40wks group (74.0%) was consistent with the longer treatment duration in comparison to lower frequencies in most treatment groups with shorter treatment duration. The third most commonly reported system organ class was general disorders and administration site conditions. Generally, frequencies were similar among all treatment groups receiving RBV (TID 16wks: 60.5%, TID 28wks: 57.5%, TID 40wks: 63.6%, BID 28wks: 65.4%). AEs of this system organ class were less frequently reported in the NRBV 28wks group (43.5%). The frequency of patients with AEs leading to discontinuation increased with treatment duration and ranged between 4.9% (TID 16wks) and 24.7% (TID 40wks). Frequencies were similar in all 28wks groups (7.7, 10.9%, and 12.5% in the BID 28wks, the NRBV group and the TID 28wks group, respectively). Overall, almost all reported AEs were assessed as drug-related by the investigator (TID 16wks: 96.3%, TID 28wks: 83.8%, TID 40wks: 96.1%, BID 28wks: 93.6%, NRBV 28wks: 91.3%). The frequency of severe AEs increased with treatment duration and was lowest in patients of the TID 16wks group (1.2%) and highest in patients of the TID 40wks group (15.6%). The frequency of severe AEs was slightly lower in patients in the NRBV 28wks group (8.7%) than in the 2 other groups treated for 28 weeks with FDV/DBV in combination with ribavirin. SAEs were most common in patients in the TID 28wks and BID 28wks group (10.0% and 10.3% respectively). The frequencies of SAEs in the other groups were below 7%. One patient experienced an AE with a fatal outcome in the BID 28wks group, which was not deemed related to the study drugs.

26 Page 25 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 25 of International GmbH or one or more of its affiliated companies. All rights reserved. Safety results Adverse events of special interest GI disorders were the most frequently reported AEs in this study and affected most patients in all treatment groups at similar rates from 72 to 86%. Nausea, diarrhoea, and vomiting were most common on a preferred term level. These events began within the first weeks of treatment in most patients in all treatment groups, possibly due to patients receiving loading doses of FDV and DBV on the first day of treatment. GI events leading to discontinuation were reported more often with increased treatment duration or dose in the RBV groups (1.2 to 7.8%, no cases in the NRBV group). GI disorders of severe intensity occurred in less than 6% of the patients in all treatment groups. Rash by special search category (SSC) occurred in 18.8 to 39.0% of the patients in all treatment groups. The frequency did not increase with treatment duration or dose. Most rash AEs were of mild or moderate intensity, and severe AEs occurred only in less than 3.9% of the patients in any treatment group. Rash AEs leading to treatment discontinuation increased with treatment duration and dose and were lowest in the BID 28wks group (0%). Photosensitivity (SSC) occurred in 29.5 to 35.1% of the patients, most events were of mild intensity. Laboratory evaluation and tolerability Mean reductions of haemoglobin were slightly more pronounced in the RBV groups (between -2.5 and -2.6 g/dl, standard deviations [SD] from 1.4 to 1.7 g/dl) than in the NRBV 28wks group (-1.0 ± 0.9 g/dl). Correspondingly, rates of anaemia (haemoglobin <10 g/l) were higher in the RBV groups (4.9% to 15.4%) than in the NRBV 28wks group (0.0%). The observed drop of haemoglobin, RBC count, and haematocrit was mirrored by a drop in haptoglobin, indicating haemolysis under RBV treatment. Notably, substantial reductions in RBC, white blood cell (WBC), and platelet counts associated with interferon-based HCV treatments were not observed in this study. Mean total bilirubin increased in all treatment groups and was more pronounced in the RBV groups (increases between 12.1 and 18.0 µmol/l, SD from 18.0 to 19.2 µmol/l) than in the NRBV 28wks group (increase by 7.9 ± 9.5 µmol/l). The changes in total bilirubin values were mainly driven by an increase in indirect bilirubin. Reasons for the observed increase of indirect bilirubin were most likely RBV-induced increased haemolysis and inhibition of UDP-glucuronosyltransferase-1A1 by FDV/DBV. The lower rates of hyperbilirubinaemia and jaundice in the RBV-sparing treatment group may be explained by the absence of RBV-induced haemolysis.

27 Page 26 of 30 BI Trial No.: International GmbH or one or more of its affiliated companies 26 of International GmbH or one or more of its affiliated companies. All rights reserved. Safety results An improvement in liver enzymes was observed in all treatment groups. This appears to indicate that the HCV-dependent cell destruction was decreased during combination treatment and the liver metabolism recovered. No signs of liver toxicity due to treatment with FDV/DBV were observed. GCA demonstrated good or satisfactory tolerability in more than 50% of patients in all treatment groups with the highest observed tolerability in the BID 28wks and TID 16wks groups (>80% good or satisfactory). Lowest tolerability was shown in the TID 40wks group. Part 3 Exposure The mean exposure time for FDV/DBV for patients in the BID 600 mg 16wks group was ± 23.1 days, 82.9 ± 54.8 days in the BID 800 mg 24wks group and 89.4 ± 48.4 days in the TID 600 mg 24wks group. Exposure time for RBV was almost identical to exposure time for FDV/DBV. Adverse events Baseline conditions entered in the patient medical history were generally balanced across the groups. Almost all of the patients (97.6%) had at least one AE during the treatment period (BID 600 mg 16wks: 93.8%, BID 800 mg 24wks: 100.0%, TID 600 mg 24wks 100.0%). For all treatment groups AEs were most frequently reported for the system organ class gastrointestinal disorders, skin and subcutaneous tissue disorders, and general disorders and administration site conditions in this order of overall incidence (see below). Most of the reported AEs (92.8%) were considered drug-related by the investigator (BID 600 mg 16wks: 90.6%, BID 800 mg 24wks: 92.3%, TID 600 mg 24wks 96.0%). Overall, the treatment was well tolerated with AEs predominantly mild to moderate in intensity. No DAIDS (Division of Acquired Immuno Deficiency Syndrome) grade 4 AEs were reported. For DAIDS grade 3 AEs, AEs leading to treatment discontinuation, and SAEs, the BID 800 mg 24wks group had the highest incidences suggesting an influence of the highest single doses of DBV (800 mg) administered in this group. The higher AE and discontinuation rate in the 24wks groups could be attributed to the longer exposure to the treatment or the higher total daily dose.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the clinical

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. The synopsis

More information

SYNOPSIS Final Clinical Study Report for Study AI444031

SYNOPSIS Final Clinical Study Report for Study AI444031 Name of Sponsor/Company: Bristol-Myers Squibb Name of Finished Product: Name of Active Ingredient: () Individual Study Table Referring to the Dossier (For National Authority Use Only) SYNOPSIS for Study

More information

Referring to Part of Dossier: Volume: Page:

Referring to Part of Dossier: Volume: Page: Synopsis AbbVie Inc. Name of Study Drug: ABT-450, ritonavir, ABT-333, ribavirin Name of Active Ingredient: ABT-450: (2R,6S,12Z,13aS,14aR,16aS)-N- (cyclopropylsulfonyl)-6-{[(5- methylpyrazin-2-yl)carbonyl]amino}-

More information

Hepatitis C: Management of Previous Non-responders with First Line Protease Inhibitors

Hepatitis C: Management of Previous Non-responders with First Line Protease Inhibitors Hepatitis C: Management of Previous Non-responders with First Line Protease Inhibitors Fred Poordad, MD The Texas Liver Institute Clinical Professor of Medicine University of Texas Health Science Center

More information

46th EASL Congress, Berlin, Germany March 30 April 3, 2011 Abstract 66

46th EASL Congress, Berlin, Germany March 30 April 3, 2011 Abstract 66 SILEN-C2: Sustained Virologic Response (SVR) and Safety of BI21335 Combined with Peginterferon Alfa-2a and Ribavirin (P/R) in Chronic HCV Genotype-1 Patients with Non-response To P/R M.S. Sulkowski, M.

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

2.0 Synopsis. ABT-333 M Clinical Study Report R&D/09/956

2.0 Synopsis. ABT-333 M Clinical Study Report R&D/09/956 2.0 Synopsis Abbott Laboratories Individual Study Table Referring to Part of Dossier: (For National Authority Use Only) Name of Study Drug: ABT-333 Volume: Name of Active Ingredient: Page: Sodium N-{6-[3-tert-butyl-5-(2,4-

More information

2.0 Synopsis. ABT-450/r, ABT-267 M Clinical Study Report R&D/17/0539. (For National Authority Use Only)

2.0 Synopsis. ABT-450/r, ABT-267 M Clinical Study Report R&D/17/0539. (For National Authority Use Only) 2.0 Synopsis AbbVie Inc. Name of Study Drug: ABT-450, ritonavir, ABT-267, ribavirin, pegylated interferon Name of Active Ingredient: ABT-450, Ritonavir, ABT-267, Ribavirin, Pegylated interferon Individual

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the clinical

More information

Simeprevir + PEG + RBV in Treatment-Naïve Genotype 1 QUEST-1 Trial

Simeprevir + PEG + RBV in Treatment-Naïve Genotype 1 QUEST-1 Trial Phase 3 Treatment Naïve Simeprevir + in Treatment-Naïve Genotype 1 QUEST-1 Trial Jacobson IM, et al. Lancet. 2014;384:403-13. Simeprevir + PEG + Ribavirin for Treatment-Naïve HCV GT1 QUEST-1 Trial QUEST-1

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. The synopsis

More information

1.0 Abstract. Title. Keywords

1.0 Abstract. Title. Keywords 1.0 Abstract Title Real World Evidence of the Effectiveness of Paritaprevir/r Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients with Chronic Hepatitis C - An Observational Study in Austria (REAL) Keywords

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

Clinical Study Report AI Final 28 Feb Volume: Page:

Clinical Study Report AI Final 28 Feb Volume: Page: Study Design, Continued Electrocardiogram (ECG) and vital sign assessments were done at select times during the study. Blood and urine samples for clinical laboratory evaluations were collected at specified

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the clinical

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of the clinical

More information

Glecaprevir-Pibrentasvir in Non-Cirrhotic Genotype 2 ENDURANCE-2

Glecaprevir-Pibrentasvir in Non-Cirrhotic Genotype 2 ENDURANCE-2 Phase 3 Treatment Naïve or Experienced Glecaprevir-Pibrentasvir in Non-Cirrhotic Genotype 2 ENDURANCE-2 *ENDURANCE-2: Study Features ENDURANCE-2 Trial Design: Randomized, double-blind, placebo-controlled

More information

ABT-493/ABT-530 M Clinical Study Report Post-Treatment Week 12 Primary Data R&D/16/0145. Referring to Part of Dossier: Volume: Page:

ABT-493/ABT-530 M Clinical Study Report Post-Treatment Week 12 Primary Data R&D/16/0145. Referring to Part of Dossier: Volume: Page: 2.0 Synopsis AbbVie Inc. Name of Study Drug: ABT-493/ABT-530 Name of Active Ingredient: ABT-493: (3aR,7S,10S,12R,21E,24aR)- 7-tert-butyl-N-{(1R,2R)-2- (difluoromethyl)-1-[(1- methylcyclopropane-1- sulfonyl)carbamoyl]cyclopropyl}-20,20-

More information

VII CURSO AVANCES EN INFECCIÓN VIH Y HEPATITIS VIRALES

VII CURSO AVANCES EN INFECCIÓN VIH Y HEPATITIS VIRALES VII CURSO AVANCES EN INFECCIÓN VIH Y HEPATITIS VIRALES REGIMENES TERAPÊUTICOS DE LA HEPATITIS C, INTERFERÓN FREE A Coruña 2 Febrero 2013 Rui Sarmento e Castro Centro Hospitalar do Porto HJU ECS Universidade

More information

Protocol. This trial protocol has been provided by the authors to give readers additional information about their work.

Protocol. This trial protocol has been provided by the authors to give readers additional information about their work. Protocol This trial protocol has been provided by the authors to give readers additional information about their work. Protocol for: Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral

More information

from 29 March 2012 Effect estimates [95% CI] Telaprevir + PegIFN/RBV vs. PegIFN/RBV

from 29 March 2012 Effect estimates [95% CI] Telaprevir + PegIFN/RBV vs. PegIFN/RBV Resolution by the Federal Joint Committee on an amendment to the Pharmaceutical Directive (AM-RL): Appendix XII Resolutions on the benefit assessment of pharmaceuticals with new active ingredients, in

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the clinical

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

2.0 Synopsis. ABT-450/r/ABT-267, ABT-333 M Clinical Study Report Final R&D/17/0174. (For National Authority Use Only)

2.0 Synopsis. ABT-450/r/ABT-267, ABT-333 M Clinical Study Report Final R&D/17/0174. (For National Authority Use Only) 2.0 Synopsis AbbVie Inc. Name of Study Drug: paritaprevir/ritonavir/ombitasvir, dasabuvir (ABT-450/r/ABT-267, ABT-333) Name of Active Ingredient: Paritaprevir (ABT-450): (2R,6S,12Z,13aS,14aR,16aS)-N- (cyclopropylsulfonyl)-6-{[(5-

More information

TECHNICAL SUMMARY OF RESULTS

TECHNICAL SUMMARY OF RESULTS TECHNICAL SUMMARY OF RESULTS 2008-004605-34 [Debio 025-HCV-205] Sponsor: Debiopharm S.A. Name of Finished Product: Tabulated Study Report (For National Authority Use Only) Name of Active Ingredient: Debio

More information

Phase 3. Treatment Experienced. Ledipasvir-Sofosbuvir +/- Ribavirin in HCV Genotype 1 ION-2. Afdhal N, et al. N Engl J Med. 2014;370:

Phase 3. Treatment Experienced. Ledipasvir-Sofosbuvir +/- Ribavirin in HCV Genotype 1 ION-2. Afdhal N, et al. N Engl J Med. 2014;370: Phase 3 Treatment Experienced Ledipasvir-Sofosbuvir +/- Ribavirin in HCV Genotype 1 ION-2 Afdhal N, et al. N Engl J Med. 2014;370:1483-93. Ledipasvir-Sofosbuvir +/- Ribavirin in Treatment-Experienced HCV

More information

Introduction. The ELECTRON Trial

Introduction. The ELECTRON Trial 63rd AASLD November 9-13, 12 Boston, Massachusetts Faculty Douglas T. Dieterich, MD Professor of Medicine and Director of CME Department of Medicine Director of Outpatient Hepatology Division of Liver

More information

Bristol-Myers Squibb. HCV Full Development Portfolio Overview. Richard Bertz Int Workshop CP HIV Meeting Amsterdam, Netherlands 24 April 2013

Bristol-Myers Squibb. HCV Full Development Portfolio Overview. Richard Bertz Int Workshop CP HIV Meeting Amsterdam, Netherlands 24 April 2013 Bristol-Myers Squibb HCV Full Development Portfolio Overview Richard Bertz Int Workshop CP HIV Meeting Amsterdam, Netherlands 24 April 2013 1 BMS Agents in Clinical Development: DAAs and INF Lambda Lambda

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

Hepatitis C: Management of Treatment Naïve Patients with First Line Protease Inhibitors

Hepatitis C: Management of Treatment Naïve Patients with First Line Protease Inhibitors Hepatitis C: Management of Treatment Naïve Patients with First Line Protease Inhibitors Eric Lawitz, MD, AGAF, CPI The Texas Liver Institute Clinical Professor of Medicine University of Texas Health Science

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of the clinical

More information

PEARL-I. Ombitasvir + Paritaprevir + Ritonavir +/- Ribavirin in HCV GT4. Treatment Naïve and Treatment Experienced

PEARL-I. Ombitasvir + Paritaprevir + Ritonavir +/- Ribavirin in HCV GT4. Treatment Naïve and Treatment Experienced Phase 2b Treatment Naïve and Treatment Experienced Ombitasvir + Paritaprevir + Ritonavir +/- Ribavirin in HCV GT4 PEARL-I Hézode C, et al. Lancet. 2015 March 30. [Epub ahead of print] PEARL-I: Study Design

More information

Evolution of Therapy in HCV

Evolution of Therapy in HCV Hepatitis C: Update on New Therapies and AASLD 13 David Bernstein, MD, FACP, AGAF, FACP Professor of Medicine Hofstra North Shore-LIJ School of Medicine Evolution of Therapy in HCV 199 1999 1 13 (%) SVR

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

Horizon Scanning Centre November Faldaprevir with BI for chronic hepatitis C infection, genotype 1 SUMMARY NIHR HSC ID: 7688

Horizon Scanning Centre November Faldaprevir with BI for chronic hepatitis C infection, genotype 1 SUMMARY NIHR HSC ID: 7688 Horizon Scanning Centre November 2012 Faldaprevir with BI 207127 for chronic hepatitis C infection, genotype 1 SUMMARY NIHR HSC ID: 7688 This briefing is based on information available at the time of research

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the

More information

IFN-free for Genotype 1 HCV: the current landscape. Prof. Graham R Foster

IFN-free for Genotype 1 HCV: the current landscape. Prof. Graham R Foster IFN-free for Genotype 1 HCV: the current landscape Prof. Graham R Foster Wonderful new drugs are coming Poordad F, et al. New Engl J Med 2014; online DOI: 10.1056/NEJMoa1402869. 2 The New Drugs Two treatment

More information

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 14 December 2011

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 14 December 2011 The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 14 December 2011 INCIVO 375 mg, film-coated tablet B/4 bottles of 42 tablets (CIP code: 217 378-5) B/1 bottle of 42

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of the clinical

More information

Final Clinical Study Report. to the Dossier SYNOPSIS. Final Clinical Study Report for Study AI463110

Final Clinical Study Report. to the Dossier SYNOPSIS. Final Clinical Study Report for Study AI463110 BMS-475 AI463 Name of Sponsor/Company: Bristol-Myers Squibb Individual Study Table Referring to the Dossier For National Authority Use Only) Name of Finished Product: Baraclude Name of Active Ingredient:

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the

More information

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2)

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2) Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2) Goals for Hepatitis C Therapy Compared to PegIFN α/rbv, new treatment regimens for chronic hepatitis C should offer: Improved efficacy Efficacy

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of the clinical

More information

Glecaprevir-Pibrentasvir in HCV GT 1 or 4 & Prior DAA Treatment MAGELLAN-1 (Part 2)

Glecaprevir-Pibrentasvir in HCV GT 1 or 4 & Prior DAA Treatment MAGELLAN-1 (Part 2) Phase 3 Treatment-Experienced in HCV GT 1 or 4 & Prior DAA Treatment MAGELLAN-1 (Part 2) in HCV GT 1 or 4 & Prior DAA Treatment MAGELLAN-1 (Part 2): Study Features MAGELLAN-1 (Part 2) Trial Design: Randomized,

More information

5/12/2016. Learning Objectives. Management of Hepatitis C Virus Genotype 2 or 3 Infected Treatment-Naive or Experienced Patients

5/12/2016. Learning Objectives. Management of Hepatitis C Virus Genotype 2 or 3 Infected Treatment-Naive or Experienced Patients 5/12/216 Management of Hepatitis C Virus Genotype 2 or 3 Infected Treatment-Naive or Experienced Patients Alexander Monto, MD Professor of Clinical Medicine University of California San Francisco San Francisco,

More information

From 19 February 2015

From 19 February 2015 Resolution by the Federal Joint Committee on an amendment to the Pharmaceutical Directive (AM-RL): Appendix XII Resolutions on the benefit assessment pharmaceuticals with new active ingredients, in accordance

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

Pharmacological management of viruses in obese patients

Pharmacological management of viruses in obese patients Cubist Pharmaceuticals The Shape of Cures to Come Pharmacological management of viruses in obese patients Dr. Dimitar Tonev, Medical Director UKINORD 1 Disclosures } The author is a pharmaceutical physician

More information

Strategies towards cure of HCV infection: a personalized approach. Heiner Wedemeyer Hannover Medical School Hannover, Germany

Strategies towards cure of HCV infection: a personalized approach. Heiner Wedemeyer Hannover Medical School Hannover, Germany Strategies towards cure of HCV infection: a personalized approach Heiner Wedemeyer Hannover Medical School Hannover, Germany 1 Disclosures Honoraria for consulting or speaking (last 5 years): Abbott, Biolex,

More information

ABT-493, ABT-530, ABT-493/ABT-530 M Clinical Study Report Primary Analysis R&D/16/0160. Referring to Part of Dossier: Volume: Page:

ABT-493, ABT-530, ABT-493/ABT-530 M Clinical Study Report Primary Analysis R&D/16/0160. Referring to Part of Dossier: Volume: Page: 2.0 Synopsis AbbVie Inc. Name of Study Drug: ABT-493, ABT-530, ABT-493/ABT-530 Name of Active Ingredient: ABT-493: (3aR,7S,10S,12R,21E,24aR)- 7-tert-butyl-N-{(1R,2R)-2- (difluoromethyl)-1-[(1- methylcyclopropane-1-

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of the clinical

More information

Bristol-Myers Squibb

Bristol-Myers Squibb A Study of the Safety and Efficacy of plus Tenofovir in Adults with Chronic Hepatitis B Virus Infection with Previous Nucleoside/Nucleotide Treatment Failure () FINAL CLINICAL STUDY REPORT EUDRACT Number:

More information

ةي : لآا ةرقبلا ةروس

ةي : لآا ةرقبلا ةروس سورة البقرة: اآلية HCV RELAPSERS AND NONRESPONDERS: How to deal with them? BY Prof. Mohamed Sharaf-Eldin Prof. of Hepatology and Gastroenterology Tanta University Achieving SVR The ability to achieve a

More information

MEDIC CENTER. Case 2

MEDIC CENTER. Case 2 Case 2 Case history 57 year old Vietnamese man He lives in HCM city and works as a engineer The patient presented in July 2012 with fatigue Diagnosed with HCV in 2004 Negative for both HBV and HIV antibodies

More information

Should Elderly CHC Patients (>70 years old) be Treated?

Should Elderly CHC Patients (>70 years old) be Treated? Should Elderly CHC Patients (>70 years old) be Treated? Deepak Amarapurkar Consultant Gastroenterologist & Hepatologist Bombay Hospital & Medical Research Center, Mumbai & Jagjivanram Western Railway Hospital,

More information

ICVH 2016 Oral Presentation: 28

ICVH 2016 Oral Presentation: 28 Ledipasvir/Sofosbuvir Is Safe and Effective for the Treatment of Patients with Genotype 1 Chronic HCV Infection in Both HCV Mono- and HIV/HCV Coinfected Patients A Luetkemeyer 1, C Cooper 2, P Kwo 3, K

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the

More information

CENTENE PHARMACY AND THERAPEUTICS DRUG REVIEW 3Q17 July August

CENTENE PHARMACY AND THERAPEUTICS DRUG REVIEW 3Q17 July August BRAND NAME Technivie GENERIC NAME Ombitasvir/paritaprevir/ritonavir MANUFACTURER AbbVie, Inc. DATE OF APPROVAL February 27, 2017 PRODUCT LAUNCH DATE Already available on the market REVIEW TYPE Review type

More information

ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: June 25, ClinicalTrials.gov ID: NCT

ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: June 25, ClinicalTrials.gov ID: NCT ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: June 25, 2014 ClinicalTrials.gov ID: NCT00372385 Study Identification Unique Protocol ID: VX05-950-104EU Brief Title:

More information

ABT-493/ABT-530 M Clinical Study Report Post-Treatment Week 12 Primary Data R&D/16/0162. Referring to Part of Dossier: Volume: Page:

ABT-493/ABT-530 M Clinical Study Report Post-Treatment Week 12 Primary Data R&D/16/0162. Referring to Part of Dossier: Volume: Page: 2.0 Synopsis AbbVie Inc. Name of Study Drug: ABT-493/ABT-530 Name of Active Ingredient: ABT-493: (3aR,7S,10S,12R,21E,24aR)- 7-tert-butyl-N-{(1R,2R)-2- (difluoromethyl)-1-[(1- methylcyclopropane-1- sulfonyl)carbamoyl]cyclopropyl}-20,20-

More information

Program Disclosure. Provider is approved by the California Board of Registered Nursing, Provider #13664, for 1.5 contact hours.

Program Disclosure. Provider is approved by the California Board of Registered Nursing, Provider #13664, for 1.5 contact hours. Program Disclosure This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint-sponsorship

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the

More information

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2)

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2) Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 2) PegIFN and RBV remain vital components of HCV therapy-- selected presentations from: Program Disclosure This activity has been planned and

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. The synopsis

More information

2.0 Synopsis. Ombitasvir/Paritaprevir/Ritonavir, Dasabuvir, RBV M Clinical Study Report R&D/16/1328. (For National Authority Use Only)

2.0 Synopsis. Ombitasvir/Paritaprevir/Ritonavir, Dasabuvir, RBV M Clinical Study Report R&D/16/1328. (For National Authority Use Only) 2.0 Synopsis AbbVie Inc. Name of Study Drug: ombitasvir (OBV), paritaprevir (PTV), ritonavir (r), dasabuvir (DSV), ribavirin (RBV) Name of Active Ingredient: ombitasvir: Dimethyl ([(2S,5S)-1-(4-tert- butylphenyl)pyrrolidine-2,5-

More information

STATISTICAL ANALYSIS PLAN FOR HCV DAA

STATISTICAL ANALYSIS PLAN FOR HCV DAA STATISTICAL ANALYSIS PLAN FOR HCV DAA A PHASE 3 EVALUATION OF A DACLATASVIR/ASUNAPREVIR/BMS-791325 FIXED DOSE COMBINATION IN SUBJECTS WITH GENOTYPE 1 CHRONIC HEPATITIS C AND COMPENSATED CIRRHOSIS PROTOCOL

More information

Hepatitis C Treatment 2014

Hepatitis C Treatment 2014 Hepatitis C Treatment 214 Brendan M. McGuire, MD UAB Liver Center Outline Epidemiology/National History Terminology for Treatment Treatment Considerations Current Treatment Options Genotype 1 (GT 1) Genotype

More information

Glecaprevir-Pibrentasvir in Cirrhotic Genotype 1, 2, 4, 5, and 6 EXPEDITION-1

Glecaprevir-Pibrentasvir in Cirrhotic Genotype 1, 2, 4, 5, and 6 EXPEDITION-1 Phase 3 Treatment-Naïve and Treatment-Experienced Glecaprevir-Pibrentasvir in Cirrhotic Genotype 1, 2, 4, 5, and 6 EXPEDITION-1 EXPEDITION-1: Study Features EXPEDITION-1 Trial Design: Open-label, single-arm,

More information

Individual Study Table Referring to the Dossier SYNOPSIS. Final Clinical Study Report for Study AI424138

Individual Study Table Referring to the Dossier SYNOPSIS. Final Clinical Study Report for Study AI424138 Name of Sponsor/Company: Bristol-Myers Squibb Name of Finished Product: Reyataz Name of Active Ingredient: Atazanavir () Individual Study Table Referring to the Dossier (For National Authority Use Only)

More information

How to optimize current therapy for GT1 patients Shortened therapy with IFNa-based therapy

How to optimize current therapy for GT1 patients Shortened therapy with IFNa-based therapy How to optimize current therapy for GT1 patients Shortened therapy with IFNa-based therapy Thomas Berg Sektion Hepatologie Klinik und Poliklinik für Gastroenterologie und Rheumatologie Leber- und Studienzentrum

More information

Future strategies with new DAAs

Future strategies with new DAAs Future strategies with new DAAs Ola Weiland professor New direct antiviral drugs Case no 1 male with genotype 2b Male with gt 2b chronic HCV Male with gt 2b relapse afer peg-ifn + RBV during 24 weeks

More information

ABT-493/ABT-530 M Clinical Study Report Post-Treatment Week 12 Primary Data R&D/16/0144. Referring to Part of Dossier: Volume: Page:

ABT-493/ABT-530 M Clinical Study Report Post-Treatment Week 12 Primary Data R&D/16/0144. Referring to Part of Dossier: Volume: Page: 2.0 Synopsis AbbVie Inc. Name of Study Drug: ABT-493/ABT-530 Name of Active Ingredient: ABT-493: (3aR,7S,10S,12R,21E,24aR)- 7-tert-butyl-N-{(1R,2R)-2- (difluoromethyl)-1-[(1- methylcyclopropane-1- sulfonyl)carbamoyl]cyclopropyl}-20,20-

More information

Synopsis. ABT-450/r/ABT-267, ABT-333 M Clinical Study Report Final R&D/14/1305. Individual Study Table Referring to Part of Dossier: Volume:

Synopsis. ABT-450/r/ABT-267, ABT-333 M Clinical Study Report Final R&D/14/1305. Individual Study Table Referring to Part of Dossier: Volume: Synopsis AbbVie Inc. Name of Study Drug: ABT-450, ritonavir, ABT-267, ABT-333, ribavirin Name of Active Ingredient: ABT-450: (2R,6S,12Z,13aS,14aR,16aS)-N- (cyclopropylsulfonyl)-6-{[(5- methylpyrazin-2-

More information

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data.

This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the clinical

More information

EASL 2013 Interferon Free, All Oral Regimens for Hepatitis C. Maria Buti Hospital Universitario Valle Hebron Barcelona Spain

EASL 2013 Interferon Free, All Oral Regimens for Hepatitis C. Maria Buti Hospital Universitario Valle Hebron Barcelona Spain EASL 2013 Interferon Free, All Oral Regimens for Hepatitis C Maria Buti Hospital Universitario Valle Hebron Barcelona Spain The first Results with Oral therapy: a Protease Inhibitor and NS5A inhibitor

More information

Emerging Approaches for the Treatment of Hepatitis C Virus

Emerging Approaches for the Treatment of Hepatitis C Virus Emerging Approaches for the Treatment of Hepatitis C Virus Gap Analysis 1 Physicians may not be sufficiently familiar with the latest guidelines for chronic HCV treatment, including the initiation and

More information

Individual Study Table Referring to the Dossier SYNOPSIS. Final Clinical Study Report for Study AI424136

Individual Study Table Referring to the Dossier SYNOPSIS. Final Clinical Study Report for Study AI424136 Name of Sponsor/Company: Bristol-Myers Squibb Name of Finished Product: Reyataz Name of Active Ingredient: Individual Study Table Referring to the Dossier (For National Authority Use Only) SYNOPSIS for

More information

Oral combination therapy: future hepatitis C virus treatment? "Lancet Oct 30;376(9751): Oral combination therapy with a nucleoside

Oral combination therapy: future hepatitis C virus treatment? Lancet Oct 30;376(9751): Oral combination therapy with a nucleoside Author manuscript, published in "Journal of Hepatology 2011;55(4):933-5" DOI : 10.1016/j.jhep.2011.04.018 Oral combination therapy: future hepatitis C virus treatment? Commentary article on the following

More information

Latest Treatment Updates for GT 2 and GT 3 Patients

Latest Treatment Updates for GT 2 and GT 3 Patients Latest Treatment Updates for GT 2 and GT 3 Patients Eric Lawitz, MD, AGAF, CPI Vice President, Scientific and Research Development The Texas Liver Institute Clinical Professor of Medicine University of

More information

Treatement Experienced patients without cirrhosis. Rafael Esteban Hospital Universitario Valle Hebron Barcelona

Treatement Experienced patients without cirrhosis. Rafael Esteban Hospital Universitario Valle Hebron Barcelona Treatement Experienced patients without cirrhosis Rafael Esteban Hospital Universitario Valle Hebron Barcelona Agenda With IFN PegIFN+ Ribavirin + Simeprevir PegIFN+ Ribavirin+ Sofosbuvir Without IFN Sofosbuvir

More information

Update on Real-World Experience With HARVONI

Update on Real-World Experience With HARVONI Update on Real-World Experience With A RESOURCE FOR PAYERS MAY 217 This information is intended for payers only. The HCV-TARGET study was supported by Gilead Sciences, Inc. Real-world experience data were

More information

SYNOPSIS. Study centre(s) The study was performed in Denmark, Norway and Sweden at 20 sites.

SYNOPSIS. Study centre(s) The study was performed in Denmark, Norway and Sweden at 20 sites. Drug substance(s): AZD0837 Edition No.: 1 Study code: D1250C00007 Date: 22 May, 2006 SYNOPSIS (For national authority use only) A Controlled, Randomised, Parallel, Multicentre Study to Assess Safety and

More information

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 1)

Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 1) Emerging Therapies for HCV: Highlights from AASLD 2012 (Part 1) Goals for Hepatitis C Therapy Compared to PegIFN/RBV, new products should offer: Improved efficacy Efficacy in all patient types including

More information

Summary ID#7029. Clinical Study Summary: Study F1D-MC-HGKQ

Summary ID#7029. Clinical Study Summary: Study F1D-MC-HGKQ CT Registry ID# 7029 Page 1 Summary ID#7029 Clinical Study Summary: Study F1D-MC-HGKQ Clinical Study Report: Versus Divalproex and Placebo in the Treatment of Mild to Moderate Mania Associated with Bipolar

More information

2.0 Synopsis. ABT-450/r/ABT-267, ABT-333 M Clinical Study Report Final R&D/15/0573. (For National Authority Use Only)

2.0 Synopsis. ABT-450/r/ABT-267, ABT-333 M Clinical Study Report Final R&D/15/0573. (For National Authority Use Only) 2.0 Synopsis AbbVie Inc. Name of Study Drug: ABT-450, ritonavir, ABT-267, ABT-333, ribavirin Name of Active Ingredient: ABT-450: (2R,6S,12Z,13aS,14aR,16aS)-N- (cyclopropylsulfonyl)-6-{[(5- methylpyrazin-2-

More information

Handelsbanken November Bertil Samuelsson VP Discovery Research Rein Piir CFO / IR

Handelsbanken November Bertil Samuelsson VP Discovery Research Rein Piir CFO / IR Handelsbanken November 18 2009 Bertil Samuelsson VP Discovery Research Rein Piir CFO / IR Pipeline Project Indication(s) Partners/- date of Explorati Optimiz agreement Terms Medivir's markets ve phase

More information

Clinical Cases Hepatitis C Naïve Patients. Rafael Esteban Liver Unit. Hospital General Universitari Vall Hebron. Barcelona.

Clinical Cases Hepatitis C Naïve Patients. Rafael Esteban Liver Unit. Hospital General Universitari Vall Hebron. Barcelona. Clinical Cases Hepatitis C Naïve Patients Rafael Esteban Liver Unit. Hospital General Universitari Vall Hebron. Barcelona. Case study 1 27 year old woman, Diagnosed with Chronic Hepatitis C 3 years ago

More information

Management of CHC G1 patients who are relapsers or non-responders to Peg IFN and RBV therapy: Wait or Triple Therapy?

Management of CHC G1 patients who are relapsers or non-responders to Peg IFN and RBV therapy: Wait or Triple Therapy? Management of CHC G1 patients who are relapsers or non-responders to Peg IFN and RBV therapy: Wait or Triple Therapy? Prof. Teerha Piratvisuth NKC Institute of Gastroenterology and Hepatology Prince of

More information

Update in the Management of Hepatitis C: What Does the Future Hold

Update in the Management of Hepatitis C: What Does the Future Hold Update in the Management of Hepatitis C: What Does the Future Hold Paul Y Kwo, MD, FACG Professor of Medicine Mdi Medical ldirector, Liver Transplantation tti Gastroenterology/Hepatology Division Indiana

More information

1. SYNOPSIS. AWB-ML21645 Date: April 20, 2016 Title of the observational study

1. SYNOPSIS. AWB-ML21645 Date: April 20, 2016 Title of the observational study 1. SYNOPSIS AWB-ML21645 Date: April 20, 2016 Title of the observational study INVESTIGATORS SPONSOR Noninterventional study on the quality assurance of the therapy of chronic hepatitis C with Peg-(40kd)-Interferon

More information

Pivotal New England Journal of Medicine papers 2014 Phase 3 Trial data

Pivotal New England Journal of Medicine papers 2014 Phase 3 Trial data 4 th HCV Therapy Advances Meeting Paris, December 12-13, 14 Pivotal New England Journal of Medicine papers 14 Phase 3 Trial data Stefan Zeuzem, MD University of Frankfurt Germany Disclosures Consultancies:

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. The synopsis

More information

Scottish Medicines Consortium

Scottish Medicines Consortium Scottish Medicines Consortium pegylated interferon α 2b (ViraferonPeg ), 50, 80, 100, 120 or 150 micrograms powder for solution for injection in pre-filled pen, in combination with ribavirin (Rebetol ),

More information

M (SAPPHIRE-II)

M (SAPPHIRE-II) PRESS RELEASE AbbVie Demonstrates 96 percent SVR 12 in its Phase III Study of Treatment- Experienced Patients with Genotype 1 Hepatitis C Results further confirm phase II studies, with consistent virologic

More information