Sofosbuvir + Ribavirin for 12 Weeks in Subjects With Chronic Genotype 2 or 3 Hepatitis C Infection Who Are Interferon Intolerant, Interferon Ineligible or Unwilling to Take Interferon

Chronic Hepatitis C Clinical Trial

— POSITRON  

Official title:

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of GS-7977 + Ribavirin for 12 Weeks in Subjects With Chronic Genotype 2 or 3 HCV Infection Who Are Interferon Intolerant, Interferon Ineligible or Unwilling to Take Interferon

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01542788
• Other study ID #: GS-US-334-0107
• Status: Completed
• Phase: Phase 3
• First received: February 17, 2012
• Last updated: May 8, 2014
• Start date: March 2012
• Est. completion date: February 2013

Study information

• Verified date: May 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This multicenter study was to evaluate subjects with chronic genotype 2 or 3 HCV infection who were interferon (IFN) ineligible, IFN intolerant or unwilling to take IFN. Participants were randomized in a 3:1 ratio to receive sofosbuvir (SOF)+ribavirin (RBV), or placebo to match SOF+placebo to match RBV. Randomization was stratified by presence/absence of cirrhosis. Approximately 20% of participants may have had evidence of cirrhosis at screening.

Description:

Participants who were randomized to the placebo arm and completed all scheduled study procedures were eligible to receive active SOF+RBV in open-label Study GS-US-334-0109.

Participants who do not achieve sustained virologic response (SVR) were eligible for enrollment in the Sequence Registry Study GS-US-248-0123. The purpose of the Sequence Registry Study is to monitor the persistence of resistant mutations for up to 3 years.

Participants who achieved SVR were eligible for enrollment in the SVR Registry Study GS-US-248-0122. The purpose of the SVR Registry Study is to evaluate durability of SVR for up to 3 years after treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 278
• Est. completion date: February 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Infection with HCV genotype 2 or 3

• Cirrhosis determination

• Subject meets one of the following classifications:

1. IFN unwilling

2. IFN ineligible

3. IFN intolerant

• Screening laboratory values within defined thresholds

• Subject has not been treated with any investigational drug or device within 30 days of the Screening visit

• Use of highly effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

• Prior exposure to an direct-acting antiviral targeting the HCV nonstructural protein (NS)5B polymerase

• Pregnant or nursing female or male with pregnant female partner

• Current or prior history of clinical hepatic decompensation

• History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

• Excessive alcohol ingestion or significant drug abuse

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• SOF
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
• RBV
Ribavirin (RBV) was administered as a tablet orally according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and = 75 kg = 1200 mg).
• Placebo to match SOF
Placebo to match SOF was administered orally once daily.
• Placebo to match RBV
Placebo to match RBV was administered orally twice daily.

Locations

Country	Name	City	State
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Monash Medical Centre	Melbourne
Australia	St. Vincent's Hospital	Melbourne
Australia	Westmead Hospital	Westmead,	New South Wales
Canada	University of Calgary	Calgary	Alberta
Canada	CHUM - The Research Centre	Montreal	Quebec
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	(G.I.R.I.) Gastrointestinal Research Institute	Vancouver	British Columbia
Canada	Gordon & Leslie Diamond Health Care Centre	Vancouver	British Columbia
New Zealand	Auckland Clinical Studies Limited	Auckland
New Zealand	Christchurch Hospital	Christchurch
Puerto Rico	Clinical Research Puerto Rico Inc	San Juan
Puerto Rico	Fundacion De Investigacion De Diego	San Juan
United States	Digestive Healthcare of Georgia	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Gastroenterology Associates, LLC	Baton Rouge	Louisiana
United States	Comprehensive Clinical Research	Berlin	New Jersey
United States	Binghamton Gastroenterology Associates	Binghamton	New York
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Graves-Gilbert Clinic	Bowling Green	Kentucky
United States	SCTI Research Foundation Liver Center	Coronado	California
United States	Southwest Infectious Disease Clinical Research, Inc.	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	South Denver Gastroenterology	Englewood	Colorado
United States	Metropolitan Research	Fairfax	Virginia
United States	Inova Fairfax Hospital Center for Liver Diseases	Falls Church	Virginia
United States	University of Florida	Gainesville	Florida
United States	Gastro One	Germantown	Tennessee
United States	ID Care	Hillsborough	New Jersey
United States	Therapeutic Concepts, PA	Houston	Texas
United States	Indianapolis Gastroenterology Research Foundation	Indianapolis	Indiana
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	Kansas City Gastroenterology and Hepatology	Kansas City	Missouri
United States	Anthony Mills MD, Inc.	Los Angeles	California
United States	Kaiser Permanente	Los Angeles	California
United States	Lightspeed Medical	Los Angeles	California
United States	Johns Hopkins University	Lutherville	Maryland
United States	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia
United States	University of Miami, Center for Liver Diseases	Miami	Florida
United States	Nashville Gastrointestinal Specialists, Inc	Nashville	Tennessee
United States	Advanced Research Institute	New Port Richey	Florida
United States	Mount Sinai School of Medicine	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Liver Institute of Virginia, Bon Secours St.Mary's	Newport News	Virginia
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	Henry Ford Health System	Novi	Michigan
United States	Internal Medicine Specialists	Orlando	Florida
United States	Orlando Immunology Center (ACH)	Orlando	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University Gastroenterology	Providence	Rhode Island
United States	Alamo Medical Research	San Antonio	Texas
United States	Kaiser Permanente	San Diego	California
United States	Medical Associates Research Group	San Diego	California
United States	UCSD Antiviral Research Center	San Diego	California
United States	Quest Clinical Research	San Francisco	California
United States	Virginia Mason Medical Center	Seattle	Washington
United States	The Research Institute	Springfield	Massachusetts
United States	Minnesota Gastroenterology, P.A.	St. Paul	Minnesota
United States	Whitman Walker Clinic	Washington	District of Columbia
United States	South Florida Center of Gastroenterology, P.A.	Wellington	Florida
United States	Digestive Health Specialists, PA	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving SVR12	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ, ie, < 25 IU/mL) 12 weeks after cessation of therapy	Post-treatment Week 12	No
Primary	Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug	The number of subjects experiencing adverse events leading to permanent discontinuation of study drug was summarized. Adverse events may or may not have been related to study treatment.	Baseline to Week 12	No
Secondary	Percentage of Participants Achieving SVR4	SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy	Post-treatment Week 4	No
Secondary	Percentage of Participants Achieving SVR24	SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy	Post-treatment Week 24	No
Secondary	Percentage of Participants Experiencing Viral Breakthrough	Viral breakthrough was defined as HCV RNA = LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values	Baseline to Week 12	No
Secondary	Percentage of Participants Experiencing Viral Relapse	Viral relapse was defined as HCV RNA = LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement	End of treatment to post-treatment Week 24	No