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: Phase 2 Study of VX-950, Pegasys With and Without Copegus in Hepatitis C Official Title: A Phase 2 Study of VX-950 in Combination With Peginterferon Alfa-2a (Pegasys ), With and Without Ribavirin (Copegus ) in Subjects With Hepatitis C Secondary IDs: Study Status Record Verification: June 2014 Overall Status: Completed Study Start: August 2006 Primary Completion: May 2008 [Actual] Study Completion: June 2008 [Actual] Sponsor/Collaborators Sponsor: Vertex Pharmaceuticals Incorporated Responsible Party: Sponsor Collaborators: Oversight FDA Regulated?: Yes Applicable Trial?: Section 801 Clinical Trial? Yes Page 1 of 20
IND/IDE Protocol?: Delayed Posting? Review Board: Approval Status: Approved Approval Number: 06/13/2006 Board Name: Consultative Committee for the Protections of Persons in Biomedical Research (CCPPRB) Board Affiliation: CHU Henri Mondor Phone: (33) 01 49 81 22 61 Email: CCPPRB.Henri.Mondor@wanadoo.fr Data Monitoring?: Yes Plan to Share IPD?: Oversight Authorities: Germany: Federal Institute for Drugs and Medical Devices France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Austria: Agency for Health and Food Safety United Kingdom: Medicines and Healthcare Products Regulatory Agency Study Brief Summary: Compare the effectiveness of telaprevir (VX-950) in combination with Pegylated Interferon Alfa 2a (Peg-IFN-alfa-2a) with and without Ribavirin (RBV) in reducing plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels Detailed : Conditions Conditions: Chronic Hepatitis C Keywords: Study Design Study Type: Interventional Primary Purpose: Treatment Study Phase: Phase 2 Intervention Model: Parallel Assignment Number of Arms: 4 Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Allocation: Randomized Page 2 of 20
Endpoint Classification: Safety/Efficacy Study Enrollment: 334 [Actual] Arms and Interventions Arms Placebo Comparator: PBO +Peg-IFN-alfa-2a, RBV 48 Week Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Experimental: Telaprevir +Peg-IFN-alfa-2a,RBV Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet orally thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 weeks. Experimental: Telaprevir +Peg-IFN-alfa-2a,RBV Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 12 weeks. Experimental: Telaprevir +Peg-IFN-alfa-2a Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 12 weeks. Assigned Interventions Drug: Ribavirin tablet Drug: Pegylated Interferon Alfa 2a Solution for injection Drug: Placebo tablet Drug: Ribavirin tablet Drug: Pegylated Interferon Alfa 2a Solution for injection Drug: Telaprevir tablet Other Names: VX-950 Drug: Ribavirin tablet Drug: Pegylated Interferon Alfa 2a Solution for injection Drug: Telaprevir tablet Other Names: VX-950 Drug: Pegylated Interferon Alfa 2a Solution for injection Drug: Telaprevir tablet Other Names: VX-950 Outcome Measures [See Results Section.] Page 3 of 20
Eligibility Minimum Age: 18 Years Maximum Age: 65 Years Gender: Both Accepts Healthy Volunteers?: Criteria: Inclusion Criteria: Hepatitis C virus Genotype 1 with detectable plasma hepatitis C virus RNA Have been infected with Hepatitis C virus for greater than (>) 6 months Seronegative for hepatitis B surface antigen and human immunodeficiency virus 1 and 2 Must agree to use 2 methods of contraception, including 1 barrier method, during and for 24 weeks after the completion of the study (unless the subject is a female of documented non-child-bearing potential) Female subjects must have a negative pregnancy test at all visits before the first dose. Exclusion Criteria: Received any approved or investigational drug or drug regimen for the treatment of hepatitis C. Any medical contraindications to Peg-IFN-alfa-2a or Ribavirin therapy Any other cause of significant liver disease in addition to hepatitis C; this may include but is not limited to, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nalcoholic Steatohepatitis or primary biliary cirrhosis. Diagnosed or suspected hepatocellular carcinoma. Histologic evidence of hepatic cirrhosis (including compensated cirrhosis) based on a liver biopsy taken within 2 years before Study start. Alcohol/drug abuse or excessive use in the last 12 months. Participation in any investigational drug study within 90 days before drug administration or participation in more than 2 drug studies in the last 12 months (exclusive of the current study). Contacts/Locations Study Officials: Medical Monitor Study Director Vertex Pharmaceuticals Incorporated Locations: France Call For Information Call For Information, France Germany Call For Information Call For Information, Germany Page 4 of 20
Austria Call For Information Call For Information, Austria United Kingdom Call for Information Call for Information, United Kingdom References Citations: Links: Study Data/Documents: Study Results Participant Flow Pre-Assignment Details Reporting Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFN-alfa-2a A total of 334 subjects were enrolled, of which 11 subjects discontinued the study prior to study drug administration. A total of 323 subjects started treatment. Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet orally thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 12 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 12 weeks. Page 5 of 20
Overall Study PBO +Peg-IFNalfa-2a, RBV 48 Week Telaprevir +Peg- IFN-alfa-2a,RBV Telaprevir +Peg- IFN-alfa-2a,RBV Telaprevir +Peg- IFN-alfa-2a Started 82 81 82 78 Completed 49 61 72 70 t Completed 33 20 10 8 Adverse Event ncompliance Physician Decision Lost to Follow-up Withdrawal by Subject Refusal of Treatment Response Ineligibility due to Exclusion Criterion Virologic Stopping Rule 6 11 9 7 0 1 1 1 1 0 0 0 2 0 0 0 2 1 0 0 3 6 0 0 1 1 0 0 1 0 0 0 17 0 0 0 Baseline Characteristics Baseline Analysis Population The Full Analysis set included all randomized subjects who received at least 1 dose of study drug. Page 6 of 20
Reporting Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFN-alfa-2a Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet orally thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 12 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 12 weeks. Baseline Measures PBO +Peg-IFN-alfa-2a, RBV 48 Week Week +Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a Overall Number of Participants 82 81 82 78 323 Age, Categorical Measure Count of Type: Participants Unit of participants measure: Number Analyzed 82 participants 81 participants 82 participants 78 participants 323 participants <=18 years 1 1.22% 0 0% 0 0% 0 0% 1 0.31% Between 18 and 65 years 81 98.78% 80 98.77% 81 98.78% 78 100% 320 >=65 years 0 0% 1 1.23% 1 1.22% 0 0% 2 0.62% Total 99.07% Age, Continuous Mean (Standard Deviation) Unit of years measure: Number Analyzed 82 participants 81 participants 82 participants 78 participants 323 participants 44.4 (10.6) 44.3 (10.0) 44.1 (10.2) 44.3 (10.8) 44.3 (10.3) Page 7 of 20
Gender, Male/ Female Measure Count of Type: Participants Unit of participants measure: Number Analyzed PBO +Peg-IFN-alfa-2a, RBV 48 Week Week +Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a 82 participants 81 participants 82 participants 78 participants 323 participants Female 36 43.9% 27 33.33% 33 40.24% 35 44.87% 131 40.56% Male 46 56.1% 54 66.67% 49 59.76% 43 55.13% 192 Total 59.44% Region of Enrollment Measure Number Type: Unit of participants measure: Number Analyzed 82 participants 81 participants 82 participants 78 participants 323 participants Outcome Measures Europe 82 81 82 78 323 1. Primary Outcome Measure: Measure Title Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing Measure The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). Time Frame 24 weeks after the completion of study drug dosing (up to Week 72) Safety Issue? Analysis Population The Full Analysis set included all randomized subjects who received at least 1 dose of study drug. Reporting Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Page 8 of 20
Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFN-alfa-2a Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet orally thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 12 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 12 weeks. Measured Values PBO +Peg-IFN-alfa-2a, RBV 48 Week Week +Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a Number of Participants Analyzed 82 81 82 78 Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing Number (95% Confidence Interval) Unit of measure: percentage of participants 46.3 (35 to 58) 69.1 (58 to 79) 59.8 (48 to 70) 35.9 (25 to 48) Analysis 1 for Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing Analysis Overview Comparison Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week, Telaprevir +Peg-IFN-alfa-2a,RBV 24 Week n-inferiority or Equivalence Analysis? Test of Hypothesis P-Value 0.0026 Method Regression, Logistic Page 9 of 20
Method of Estimation Estimation Parameter Estimated Value 2.758 Odds Ratio (OR) Confidence Interval (2-Sided) 95% 1.424 to 5.340 Estimation Analysis 2 for Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing Analysis Overview Comparison Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week, Telaprevir +Peg-IFN-alfa-2a,RBV 12 Week n-inferiority or Equivalence Analysis? Test of Hypothesis Method of Estimation P-Value 0.959 Method Regression, Logistic Estimation Parameter Estimated Value 1.709 Odds Ratio (OR) Confidence Interval (2-Sided) 95% 0.910 to 3.212 Estimation Analysis 3 for Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing Comparison Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week, Telaprevir +Peg-IFN-alfa-2a Analysis Overview n-inferiority or Equivalence Analysis? Page 10 of 20
Test of Hypothesis Method of Estimation P-Value 0.1089 Method Regression, Logistic Estimation Parameter Estimated Value 0.589 Odds Ratio (OR) Confidence Interval (2-Sided) 95% 0.309 to 1.125 Estimation 2. Secondary Outcome Measure: Measure Title Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing Measure The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). Time Frame 12 weeks after the completion of study drug dosing (up to Week 60) Safety Issue? Analysis Population The Full Analysis set included all randomized subjects who received at least 1 dose of study drug. Reporting Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFNalfa-2a,RBV Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet orally thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 12 weeks. Page 11 of 20
Telaprevir +Peg-IFN-alfa-2a in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 12 weeks. Measured Values PBO +Peg-IFN-alfa-2a, RBV 48 Week Week +Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a Number of Participants Analyzed 82 81 82 78 Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing Number (95% Confidence Interval) Unit of measure: percentage of participants 47.6 (36 to 59) 69.1 (58 to 79) 59.8 (48 to 70) 37.2 (26 to 49) Analysis 1 for Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing Analysis Comparison Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week, Telaprevir +Peg-IFN-alfa-2a,RBV 24 Week Overview n-inferiority or Equivalence Analysis? Test of Hypothesis Method of Estimation P-Value 0.0041 Method Regression, Logistic Estimation Parameter Estimated Value 2.632 Odds Ratio (OR) Confidence Interval (2-Sided) 95% 1.359 to 5.097 Estimation Page 12 of 20
Analysis 2 for Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing Analysis Comparison Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week, Telaprevir +Peg-IFN-alfa-2a,RBV 12 Week Overview n-inferiority or Equivalence Analysis? Test of Hypothesis Method of Estimation P-Value 0.1324 Method Regression, Logistic Estimation Parameter Estimated Value 1.623 Odds Ratio (OR) Confidence Interval (2-Sided) 95% 0.864 to 3.050 Estimation Analysis 3 for Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing Comparison Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week, Telaprevir +Peg-IFN-alfa-2a Analysis Overview n-inferiority or Equivalence Analysis? Test of Hypothesis Method of Estimation P-Value 0.1099 Method Regression, Logistic Estimation Parameter Odds Ratio (OR) Estimated Value 0.591 Confidence Interval (2-Sided) 95% Page 13 of 20
0.311 to 1.126 Estimation 3. Secondary Outcome Measure: Measure Title Percentage of Subjects With Undetectable Plasma HCV RNA at Completion of Study Drug Dosing Measure The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). Time Frame Completion of study drug dosing (up to Week 48) Safety Issue? Analysis Population The Full Analysis set included all randomized subjects who received at least 1 dose of study drug. Reporting Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFN-alfa-2a Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet orally thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 12 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 12 weeks. Measured Values PBO +Peg-IFN-alfa-2a, RBV 48 Week Week +Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a Number of Participants Analyzed 82 81 82 78 Page 14 of 20
Percentage of Subjects With Undetectable Plasma HCV RNA at Completion of Study Drug Dosing Number (95% Confidence Interval) Unit of measure: percentage of participants PBO +Peg-IFN-alfa-2a, RBV 48 Week Week +Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a 54.9 (43 to 66) 70.4 (59 to 80) 80.5 (70 to 88) 61.5 (50 to 72) 4. Secondary Outcome Measure: Measure Title Measure Time Frame Baseline up to Week 48 Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. "Study drug" includes all investigational agents (including placebo, if applicable) administered during the course of the study. Safety Issue? Yes Analysis Population The Full Analysis set included all randomized subjects who received at least 1 dose of study drug. Reporting Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week Telaprevir +Peg-IFNalfa-2a,RBV Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet orally thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 weeks. Page 15 of 20
Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFN-alfa-2a in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 12 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 12 weeks. Measured Values PBO +Peg-IFN-alfa-2a, RBV 48 Week Week +Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a Number of Participants Analyzed 82 81 82 78 Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) Measure Type: Unit of measure: Number participants AEs 81 80 82 78 SAEs 8 16 11 9 5. Secondary Outcome Measure: Measure Title Measure Number of Subjects With Viral Relapse Viral relapse was defined as having detectable HCV RNA during antiviral follow-up. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). Time Frame After last dose of study drug up to antiviral follow-up (up to Week 72) Safety Issue? Analysis Population Analysis population included subjects who completed their assigned study drug treatment and had undetectable HCV RNA at the completion of treatment (up to Week 48). Page 16 of 20
Reporting Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFN-alfa-2a Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet orally thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 12 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 12 weeks. Measured Values PBO +Peg-IFN-alfa-2a, RBV 48 Week Week +Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a Number of Participants Analyzed 45 57 63 46 Number of Subjects With Viral Relapse Measure Type: Unit of measure: Number participants 10 8 19 22 6. Secondary Outcome Measure: Measure Title Measure Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir Only subjects who received telaprevir were to be analyzed for this outcome. Maximum, minimum and average plasma concentrations observed during assessment period were reported. Time Frame Day 1, 4, 8, 15, 22, 29, 43, 57, 71, 85 Safety Issue? Analysis Population Pharmacokinetic population included all subjects who provided pharmacokinetic assessments and had evaluable and interpretable data. Page 17 of 20
Reporting Groups Telaprevir All Subjects from Telaprevir +Peg-IFN-alfa-2a,RBV, Telaprevir +Peg-IFN- alfa- 2a,RBV and Telaprevir +Peg-IFN-alfa-2a reporting groups who received single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 12 weeks. Measured Values Telaprevir Number of Participants Analyzed 239 Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir Mean (Standard Deviation) Unit of measure: nanogram per milliliter (ng/ml) Cmax 3370 (755) Cmin 2510 (604) Cavg 3055 (694) Reported Adverse Events Time Frame Adverse Events during Baseline through Week 48 Additional In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Reporting Groups PBO +Peg-IFN-alfa-2a, RBV 48 Week Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Page 18 of 20
Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFNalfa-2a,RBV Telaprevir +Peg-IFN-alfa-2a Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet orally thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 12 weeks. in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 12 weeks. Serious Adverse Events PBO +Peg-IFNalfa-2a, RBV 48 Week Week +Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a Affected/At Risk (%) Affected/At Risk (%) Affected/At Risk (%) Affected/At Risk (%) Total 8/82 (9.76%) 16/81 (19.75%) 11/82 (13.41%) 9/78 (11.54%) Other Adverse Events Frequency Threshold Above Which Other Adverse Events are Reported: 5% PBO +Peg-IFN- alfa-2a, RBV 48 Week Week +Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a,RBV Week+Peg-IFNalfa-2a Affected/At Risk (%) Affected/At Risk (%) Affected/At Risk (%) Affected/At Risk (%) Total 81/82 (98.78%) 80/81 (98.77%) 82/82 (100%) 78/78 (100%) More Information Certain Agreements: Principal Investigators are NOT employed by the organization sponsoring the study. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo. b - Page 19 of 20 -
Results Point of Contact: Name/Official Title: Jeff Chodakewitz, M.D. Organization: Vertex Pharmaceuticals Incorporated Phone: 617-341-6777 Email: Jeff_Chodakewitz@vrtx.com U.S. National Library of Medicine U.S. National Institutes of Health U.S. Department of Health & Human Services - Page 20 of 20 -