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1 Clinical Trial Details (PDF Generation Date :- Tue, 30 Oct :56:54 GMT) CTRI Number Last Modified On 27/10/2015 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study CTRI/2014/02/ [Registered on: 14/02/2014] - Trial Registered Prospectively No Interventional Drug Randomized, Parallel Group Trial Study to Evaluate the Safety and Efficacy of Sofosbuvir Plus Ribavirin in Treatment-Naïve Adults with Chronic Genotype 1 or 3 Hepatitis C Virus Infection A Phase 3b, Multi-Center, Randomized, Open-Label, Study to Evaluate the Safety and Efficacy of Sofosbuvir Plus Ribavirin in Treatment-Naïve Adults with Chronic Genotype 1 or 3 Hepatitis C Virus Infection Secondary IDs if Any Secondary ID Identifier Details of Principal Investigator or overall Trial Coordinator (multi-center study) GS-US Original 03 April 2013 Name Designation Affiliation Address Protocol Number Details of Principal Investigator Details Contact Person (Scientific Query) Details Contact Person (Public Query) Phone Fax Name Designation Affiliation Address Details Contact Person (Scientific Query) Dr Vikram Vora Medical Monitor Klinera Corporation India Phone Fax Name Designation Affiliation Address Klinera Corporation India, 401, Hill View Industrial Estate, LBS Marg, Ghatkopar West, Mumbai Maharashtra, India Klinera Corporation India, 401, Hill View Industrial Estate, LBS Marg, Ghatkopar West, Mumbai Maharashtra, India Mumbai MAHARASHTRA India vvora@klinera.com Details Contact Person (Public Query) Pravin Moily Project Manager Klinera Corporation India Klinera Corporation India, 401, Hill View Industrial Estate, LBS Marg, Ghatkopar West, Mumbai Maharashtra, India Klinera Corporation India, 401, Hill View Industrial Estate, LBS Marg, Ghatkopar West, Mumbai Maharashtra, India Mumbai MAHARASHTRA page 1 / 10

2 Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Sites of Study India Phone Fax > Gilead Sciences, Inc. Name Source of Monetary or Material Support Primary Sponsor Details Gilead Sciences Inc Address Gilead Sciences, Inc. 333 Lakeside Drive Foster City, CA USA USA. Type of Sponsor Name Klinera Corporation India List of Countries India Name of Principal Investigator Dr S K Acharya Dr Ajit Sood Dr Pawan Rawal Pharmaceutical industry-global Address 401, Hill View Industrial Estate, LBS Marg,Ghatkopar West, Mumbai MAHARASHTRA India Name of Site Site Address Phone/Fax/ All India Institute of Medical Sciences Dayanand Medical College & Hospital Fortis Memorial Research Institute Department of Gastroenterology and Human Nutrition, Room No: 3105, 3rd Floor, Teaching Block, All India Institute of Medical Sciences, Ansari Nagar,New Delhi,Delhi New Delhi DELHI Department of Gastroenterology,3rd Floor,Tagore Nagar,Civil Lines,Ludhiana , Punjab Ludhiana PUNJAB Department of Gastro and Hepatobiliary Sciences, Sector 44, Opp. HUDA City Centre Metro Station, Gurgaon , Haryana, India Gurgaon HARYANA Dr Dharmesh Kapoor Global Hospitals Department of Gastroenterology, Ground Floor,Lakdi ka Pul, Hyderabad , Andhra Pradesh Hyderabad acharya@aiims.ac.in ajitsood10@sify.com pawan.rawal@fortisheal thcare.com dharmesh_kapoor@yah oo.com page 2 / 10

3 ANDHRA PRADESH Dr Samir Shah Global Hospitals Department of Hepatology, Institute of Liver Diseases, HPB Surgery and Transplant, Global Hospitals, Dr. E. Borges Road, Hospital A venue, Opp. Shirodkar High School, Parel, Mumbai , India Mumbai MAHARASHTRA drshahsamir@gmail.co m Dr S K Sarin Dr Abhijit Chowdhury Dr Abraham Koshy Institute of Liver and Biliary Sciences Institute of Post Graduate Medical Education And Research Lakeshore Hospital and Research Centre Ground Floor, OPD Block,D-1 Vasant Kunj,New Delhi, Delhi New Delhi DELHI Ronald ross building, 9th Floor,244 A,J.C. Bose Road, Kolkata , West Bengal Kolkata WEST BENGAL shivsarin@gmail.com chaudhuria@gmail.com Lakeshore Hospital and Research Centre,NH-47,Bypass, koshyabe@yahoo.com Maradu,Nettoor,Ernakul um ,Kerala Ernakulam KERALA Dr Randhir Sud Medanta-The Medicity Institute of Digestive & Hepatobiliary Sciences, Sector 38,Gurgaon , Haryana Gurgaon HARYANA Dr Rajiv Mehta Dr Ajay Duseja Dr Vivek Saraswat Nirmal Hospital Pvt. Ltd. Postgraduate Institute of Medical Education and Research Sanjay Gandhi Postgraduate Institute of Medical Sciences Ring Road, Surat , Gujarat Surat GUJARAT Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh ,(UT) Chandigarh CHANDIGARH Department of Gastroenterology, Raebareli Road,Lucknow , Uttar Pradesh Lucknow UTTAR PRADESH randhir.sud@medanta. org rmgastro@yahoo.com ajayduseja@yahoo.co.i n profviveksaraswat@gm ail.com Dr Sandeep Nijhawan Sawai Man Singh Department of page 3 / 10

4 Details of Ethics Committee Dr Akash Shukla (SMS) Hospital Seth GS Medical College and KEM Hospital Gastroenterology, Sawai Man Singh (SMS) Hospital, JLN Marg, Jaipur , Rajasthan Jaipur RAJASTHAN 9th Floor, Dept of Gastroenterology, Acharya Donde Marg,Parel, Mumbai ,Maharashtra Mumbai MAHARASHTRA Dr Madhura Prasad VGM Hospital 2100, Trichy Road, Rajalakshmi Mills Stop, Coimbatore ,Tamil Nadu Coimbatore TAMIL NADU mail.com com om Name of Committee Approval Status Date of Approval Is Independent Ethics Committee? Drugs Trial Ethics Committee; Dr. Ajit Sood Ethics Committee of SMS Medical College and Attached Hospital; Dr. Sandeep Nijhawan IEC I, Seth G.S. Medical College and KEM Hospital; Dr. Akash Shukla IEC, Global Hospitals, Mumbai; Dr. Samir Shah Institute of Liver and Biliary Sciences Ethics committee; Dr. S.K. Sarin Institution Ethics Committee, All India Institute of Medical Sciences; Dr. S. K. Acharya Institutional Ethics Committe for Human Research, Institute of Post Graduate Medical Education And Research; Dr. Abhijit Chowdhury Institutional Ethics Committee, Fortis Memorial Research Institute, Dr. Pawan Rawal Approved 02/08/2013 No Approved 10/06/2014 No Approved 11/09/2014 No Approved 26/08/2014 Yes Approved 26/08/2013 No Approved 08/08/2013 No Approved 24/03/2014 No Approved 28/08/2014 No Institutional Ethics Approved 17/07/2013 No page 4 / 10

5 Regulatory Clearance Status from DCGI Health Condition / Problems Studied Intervention / Comparator Agent Committee, Global Hospital; Dr. Dharmesh Kapoor Institutional Ethics Committee, VGM Hospital ; Dr. Madhura Prasad Institutional Ethics Committee- Postgraduate Institute of Medical Education and Research; Dr. Ajay Duseja Institutional Ethics Committee- Sanjay Gandhi Postgraduate Institute of Medical Sciences; Dr. Vivek Saraswat Lakeshore Ethics Committee; Dr. Abraham Koshy Medanta Institutional Ethics Committee; Dr. Randhir Sud Nirmal Hospital Private Limited Ethics Committee; Dr. Rajiv Mehta Status Approved 26/05/2014 No Approved 09/06/2014 No Approved 02/09/2013 No Approved 19/11/2013 No Submittted/Under Review No Date Specified No Approved 14/09/2013 No Date Approved/Obtained 29/01/2014 Health Type Patients Condition Chronic hepatitis C virus (HCV) infection Type Name Details Intervention Intervention 1. Genotype 1, treatment-naïve, receiving 16 weeks of SOF Plus RBV 2. Genotype 1, treatment-naïve, receiving 24 weeks of SOF Plus RBV 30 subject will be enrolled in this arm and will receive RBV at a total daily oral dose of sofosbuvir 400 mg QD Plus RBV (1000 to 1200 mg per day) (1000 mg for Subjects weighing less than 75 kg and 1200 mg for subjects weighing??75 kg) divided BID for 16 weeks. The morning dose of RBV will be taken with sofosbuvir and food. The evening dose of RBV will be taken with food. 30 subject will be enrolled in this arm and will receive RBV at a total daily oral dose of sofosbuvir 400 mg QD Plus RBV (1000 to 1200 mg per day) (1000 mg for Subjects weighing less than 75 kg and 1200 mg for subjects weighing??75 kg) divided BID for 24 weeks. The morning dose of RBV will be page 5 / 10

6 Inclusion Criteria Intervention Intervention Age From Age To Gender Details 3. Genotype 3, treatment-naïve, receiving 16 weeks of SOF Plus RBV 4. Genotype 3, treatment-naïve, receiving 24 weeks of SOF Plus RBV Year(s) Year(s) Both Inclusion Criteria taken with sofosbuvir and food. The evening dose of RBV will be taken with food. 30 subject will be enrolled in this arm and will receive RBV at a total daily oral dose of sofosbuvir 400 mg QD Plus RBV (1000 to 1200 mg per day) (1000 mg for Subjects weighing less than 75 kg and 1200 mg for subjects weighing??75 kg) divided BID for 16 weeks. The morning dose of RBV will be taken with sofosbuvir and food. The evening dose of RBV will be taken with food. 30 subject will be enrolled in this arm and will receive RBV at a total daily oral dose of sofosbuvir 400 mg QD Plus RBV (1000 to 1200 mg/day) (1000 mg for Subjects weighing 75 kg and 1200 mg for subjects weighing??75 kg) divided BID for 24 weeks. The morning dose of RBV will be taken with sofosbuvir and food. The evening dose of RBV will be taken with food. Inclusion Criteria Subjects must meet all of the following inclusion criteria to be eligible for participation in this study 1 Willing and able to provide written informed consent 2 Male or female age greater than or is equal to 18 years 3 HCV RNA greater than or is equal to 10raise to 4 IU per ml at screening 4 Confirmed chronic HCV infection as documented by either a a positive anti HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline per Day 1 visit or b a liver biopsy prior to the Baseline per Day 1 visit with evidence of chronic HCV infection 5 HCV genotype 1 or 3 at screening as determined by the Central Laboratory Any non definitive results will exclude the subject from study participation 6 Documented HCV treatment naive defined as no prior exposure to any IFN RBV or other approved or experimental direct acting antiviral targeting HCV 7 Approximately 30 percent of subjects may have compensated cirrhosis at screening a Cirrhosis is defined as any one of the following Liver biopsy showing cirrhosis eg Metavir score is equal to 4 or Ishak score greater than or is equal to 5 Fibroscan showing cirrhosis or results greater than 12.5 kpa page 6 / 10

7 FibroTest score of greater than 0.75 AND an AST platelet ratio index APRI of greater than 2 performed during Screening b Absence of cirrhosis is defined as any one of the following Liver biopsy within 2 years of Screening showing absence of cirrhosis Fibroscan with a result of less than or is equal to 12.5 kpa within 6 months of Baseline per Day1 FibroTest score of less than or is equal to 0.48 AND APRI of less than or is equal to 1 performed during Screening In the absence of a definitive diagnosis of the presence or absence of cirrhosis by the above criteria a liver biopsy is required Liver biopsy results supersede the results obtained by Fibroscan or FibroTest 8 For subjects with cirrhosis Results from liver imaging done within 6 months of Baselin per Day 1that exclude hepatocellular carcinoma HCC 9 Body mass index BMI greater than or is equal to 18 kg per m2 10 Screening ECG without clinically significant abnormalities 11 Subjects must have the following laboratory parameters at screening a ALT less than or is equal to 10 of the upper limit of normal ULN b AST less than or is equal to 10 of ULN c Hemoglobin greater than or is equal to 12 g per dl for male greater than or is equal to 11 g per dl for female subjects d Platelets greater than or is equal to cells per mm3 e INR less than or is equal to 1.5 of ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR f Albumin greater than or is equal to 3 g per dl g Direct bilirubin less than or is equal to 1.5 of ULN h HbA1c less than or is equal to 10 percent i Creatinine clearance greater than or is equal to 60 ml per min as calculated by the Cockcroft Gault equation 12 A female subject is eligible to enter the study if it is confirmed that she is a Not pregnant or nursing b Of non-childbearing potential ie women who have had a hysterectomy both ovaries removed or medically documented ovarian failure, or are postmenopausal women greater than 50 years of age with cessation for greater than or is equal to 12 months of previously occurring menses or c Of childbearing potential ie women who have not had a hysterectomy both ovaries removed or medically documented ovarian failure Women less than or is equal to 50 years of age with amenorrhea will be considered to be of childbearing potential These women must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the Baseline Day 1 visit prior to randomization They must also agree to one of the following from 3 weeks prior to Baseline Day 1 until 6 months after last dose of RBV Complete abstinence from intercourse Periodic abstinence from intercourse eg calendar ovulation symptothermal post ovulation methods is not permitted Or Consistent and correct use of 1 of the following methods of birth control listed below in addition to a male partner who correctly uses a condom from the date of screening until 6 months after the last dose page 7 / 10

8 Exclusion Criteria Details of RBV Women of childbearing potential must not rely on hormone containing contraceptives as a form of birth control during the study Female subjects using a hormone containing contraceptive prior to screening may continue their contraceptive regimen in addition to the study specified methods of birth control intrauterine device IUD with a failure rate of less than 1 percent per year female barrier method cervical cap or diaphragm with spermicidal agent tubal sterilization vasectomy in male partner 13. All male study participants must agree to consistently and correctly use a condom, while their female partner agrees to use either 1 of the non hormonal methods of birth control listed above or a hormone containing contraceptive listed below, from the date of screening until 7 months after their last dose of RBV implants of levonorgestrel injectable progesterone oral contraceptives (either combined or progesterone only) contraceptive vaginal ring transdermal contraceptive patch 14. Male subjects must agree to refrain from sperm donation for at least 7 months after the last dose of RBV. 15. Subject must be of generally good health as determined by the Investigator. 16. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments. NOTE: Protocol does not specify the upper age limit, however in order to enter the inclusion and exclusion criteria in CTRI, upper age limit of 99 years has been entered, as CTRI does not accept other data without entering upper age limit. Exclusion Criteria Exclusion Criteria Subjects who meet any of the following exclusion criteria are not to be enrolled in this study. 1. Pregnant or nursing female or male with pregnant female partner 2. Chronic liver disease of a non HCV etiology (eg, hemochromatosis, Wilson s disease, alpha 1 antitrypsin deficiency, cholangitis) 3. Infection with hepatitis B virus HBV or human immunodeficiency virus HIV 4. Contraindication to RBV therapy, eg. history of clinically significant hemoglobinopathy (sickle cell disease, thalassemia. 5. History of malignancy diagnosed or treated within 5 years recent localized treatment of squamous or non invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screening; subjects under evaluation for malignancy are not eligible. 6. Chronic use of systemically administered immunosuppressive agents eg, prednisone equivalent 10 mg per day 7. Clinically relevant drug or alcohol abuse within 12 months of screening. A positive drug screen will exclude subjects unless it can be explained by a page 8 / 10

9 Method of Generating Random Sequence Method of Concealment Blinding/Masking Computer generated randomization Other Open Label prescribed medication; the diagnosis and prescription should be approved by the investigator. 8. Excessive alcohol ingestion, defined as 3 glasses per day 1 glass is equivalent to 284 ml beer, 125 ml wine, or 25 ml distilled spirits for females and 4 glasses per day for males. 9. History of solid organ transplantation 10. Current or prior history of clinical hepatic decompensation eg, ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome and hepatopulmonary syndrome 11. History of clinically significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol 12. History of a gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug 13. History of significant pulmonary disease, significant cardiac disease or porphyria 14. History of difficulty with blood collection and or poor venous access for the purposes of phlebotomy 15. Use of any prohibited concomitant medications as described in Section Known hypersensitivity to RBV, the study investigational medicinal product, the metabolites, or formulation excipients Primary Outcome Outcome Timepoints To determine the antiviral efficacy of SOF plus RBV in treatment naive subjects with chronic genotype 1 HCV infection and in treatment naive subjects with chronic genotype 3 HCV infection, as measured by the proportion of subjects with sustained viral response 12 weeks after discontinuation of therapy (SVR12) To assess the safety and tolerability of SOF plus RBV in treatment naive subjects with chronic genotype 1 or 3 HCV infection as measured by review of the accumulated safety data 16 and 24 weeks Secondary Outcome Outcome Timepoints Target Sample Size To determine the proportion of subjects who attain sustained virologic response(svr) at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24) To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation To evaluate the emergence of viral resistance to sofosbuvir during treatment and after treatment discontinuation Total Sample Size= and 24 weeks page 9 / 10

10 Powered by TCPDF ( PDF of Trial Phase of Trial Phase 3 Date of First Enrollment (India) Date of First Enrollment (Global) Estimated Duration of Trial Recruitment Status of Trial (Global) Recruitment Status of Trial (India) Publication Details Brief Summary Sample Size from India=120 05/03/2014 No Date Specified Years=1 Months=5 Days=30 Completed Completed Not Applicable - It is planned that 120 subjects will be enrolled in the study and receive Sofosbuvir 400 mg QD + RBV (1000 to 1200 mg/day) for either 16 or 24 weeks. - There are 4 subject groups, defined by genotype and treatment arm: 1. Genotype 1, treatment-naïve, receiving 16 weeks of SOF + RBV ( N = 30) 2. Genotype 1, treatment-naïve, receiving 24 weeks of SOF + RBV (N = 30) 3. Genotype 3, treatment-naïve, receiving 16 weeks of SOF + RBV (N = 30) 4. Genotype 3, treatment-naïve, receiving 24 weeks of SOF + RBV (N = 30) Approximately 30% of enrolled subjects in each group may have compensated cirrhosis at screening. Subjects will be randomized in a 1:1 ratio to 1 of 2 treatment arms, stratified by genotype and presence/absence of cirrhosis. page 10 / 10