Back to resultsSofosbuvir + 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 (POSITRON)
Primary Purpose
Chronic Hepatitis C
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
SOF
RBV
Placebo to match SOF
Placebo to match RBV
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C focused on measuring HCV genotype 2 (GT-2), HCV genotype 3 (GT-3), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, Interferon intolerant, Interferon ineligible, GS-7977, Ribavirin
Eligibility Criteria
Inclusion Criteria:
- Infection with HCV genotype 2 or 3
- Cirrhosis determination
Subject meets one of the following classifications:
- IFN unwilling
- IFN ineligible
- 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
Sites / Locations
- University of Alabama Birmingham
- SCTI Research Foundation Liver Center
- Kaiser Permanente
- Lightspeed Medical
- Anthony Mills MD, Inc.
- Medical Associates Research Group
- UCSD Antiviral Research Center
- Kaiser Permanente
- Quest Clinical Research
- University of Colorado
- South Denver Gastroenterology
- Whitman Walker Clinic
- University of Florida
- Borland-Groover Clinic
- University of Miami, Center for Liver Diseases
- Advanced Research Institute
- Orlando Immunology Center (ACH)
- Internal Medicine Specialists
- South Florida Center of Gastroenterology, P.A.
- Digestive Healthcare of Georgia
- Gastrointestinal Specialists of Georgia, PC
- Indianapolis Gastroenterology Research Foundation
- Graves-Gilbert Clinic
- Gastroenterology Associates, LLC
- Johns Hopkins University
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
- The Research Institute
- Henry Ford Health System
- Minnesota Gastroenterology, P.A.
- Kansas City Gastroenterology and Hepatology
- Comprehensive Clinical Research
- ID Care
- Binghamton Gastroenterology Associates
- Weill Cornell Medical College
- Mount Sinai School of Medicine
- Duke University
- Digestive Health Specialists, PA
- University of Pennsylvania
- University Gastroenterology
- Gastro One
- Nashville Gastrointestinal Specialists, Inc
- Southwest Infectious Disease Clinical Research, Inc.
- Therapeutic Concepts, PA
- Alamo Medical Research
- Metropolitan Research
- Inova Fairfax Hospital Center for Liver Diseases
- Liver Institute of Virginia, Bon Secours St.Mary's
- Digestive and Liver Disease Specialists
- Virginia Mason Medical Center
- Westmead Hospital
- Royal Brisbane & Women's Hospital
- St. Vincent's Hospital
- Monash Medical Centre
- University of Calgary
- Gordon & Leslie Diamond Health Care Centre
- (G.I.R.I.) Gastrointestinal Research Institute
- Toronto Liver Centre
- CHUM - The Research Centre
- Auckland Clinical Studies Limited
- Christchurch Hospital
- Clinical Research Puerto Rico Inc
- Fundacion De Investigacion De Diego
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
SOF+RBV
Placebo
Arm Description
Participants were randomized to receive SOF+RBV for 12 weeks.
Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks.
Outcomes
Primary Outcome Measures
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
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.
Secondary Outcome Measures
Percentage of Participants Achieving SVR4
SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy
Percentage of Participants Achieving SVR24
SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01542788
Brief Title
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
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C
Keywords
HCV genotype 2 (GT-2), HCV genotype 3 (GT-3), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, Interferon intolerant, Interferon ineligible, GS-7977, Ribavirin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
278 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SOF+RBV
Arm Type
Experimental
Arm Description
Participants were randomized to receive SOF+RBV for 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
SOF
Other Intervention Name(s)
Sovaldi®, GS-7977, PSI-7977
Intervention Description
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RBV
Intervention Description
Ribavirin (RBV) was administered as a tablet orally according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).
Intervention Type
Drug
Intervention Name(s)
Placebo to match SOF
Intervention Description
Placebo to match SOF was administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Placebo to match RBV
Intervention Description
Placebo to match RBV was administered orally twice daily.
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving SVR12
Description
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ, ie, < 25 IU/mL) 12 weeks after cessation of therapy
Time Frame
Post-treatment Week 12
Title
Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug
Description
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.
Time Frame
Baseline to Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving SVR4
Description
SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy
Time Frame
Post-treatment Week 4
Title
Percentage of Participants Achieving SVR24
Description
SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy
Time Frame
Post-treatment Week 24
Title
Percentage of Participants Experiencing Viral Breakthrough
Description
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
Time Frame
Baseline to Week 12
Title
Percentage of Participants Experiencing Viral Relapse
Description
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
Time Frame
End of treatment to post-treatment Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Infection with HCV genotype 2 or 3
Cirrhosis determination
Subject meets one of the following classifications:
IFN unwilling
IFN ineligible
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
Facility Information:
Facility Name
University of Alabama Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-2170
Country
United States
Facility Name
SCTI Research Foundation Liver Center
City
Coronado
State/Province
California
ZIP/Postal Code
92118
Country
United States
Facility Name
Kaiser Permanente
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Lightspeed Medical
City
Los Angeles
State/Province
California
ZIP/Postal Code
90036
Country
United States
Facility Name
Anthony Mills MD, Inc.
City
Los Angeles
State/Province
California
ZIP/Postal Code
90069
Country
United States
Facility Name
Medical Associates Research Group
City
San Diego
State/Province
California
ZIP/Postal Code
912123
Country
United States
Facility Name
UCSD Antiviral Research Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Kaiser Permanente
City
San Diego
State/Province
California
ZIP/Postal Code
92154
Country
United States
Facility Name
Quest Clinical Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
South Denver Gastroenterology
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Whitman Walker Clinic
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20009
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0277
Country
United States
Facility Name
Borland-Groover Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
University of Miami, Center for Liver Diseases
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Advanced Research Institute
City
New Port Richey
State/Province
Florida
ZIP/Postal Code
34653
Country
United States
Facility Name
Orlando Immunology Center (ACH)
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803-1851
Country
United States
Facility Name
Internal Medicine Specialists
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
South Florida Center of Gastroenterology, P.A.
City
Wellington
State/Province
Florida
ZIP/Postal Code
33414
Country
United States
Facility Name
Digestive Healthcare of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Gastrointestinal Specialists of Georgia, PC
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
Indianapolis Gastroenterology Research Foundation
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
Graves-Gilbert Clinic
City
Bowling Green
State/Province
Kentucky
ZIP/Postal Code
42101
Country
United States
Facility Name
Gastroenterology Associates, LLC
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Facility Name
Johns Hopkins University
City
Lutherville
State/Province
Maryland
ZIP/Postal Code
21093
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114-2696
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
The Research Institute
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01105
Country
United States
Facility Name
Henry Ford Health System
City
Novi
State/Province
Michigan
ZIP/Postal Code
48377
Country
United States
Facility Name
Minnesota Gastroenterology, P.A.
City
St. Paul
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Kansas City Gastroenterology and Hepatology
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
Comprehensive Clinical Research
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Facility Name
ID Care
City
Hillsborough
State/Province
New Jersey
ZIP/Postal Code
08844
Country
United States
Facility Name
Binghamton Gastroenterology Associates
City
Binghamton
State/Province
New York
ZIP/Postal Code
13903
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Digestive Health Specialists, PA
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University Gastroenterology
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
Gastro One
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Nashville Gastrointestinal Specialists, Inc
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37211
Country
United States
Facility Name
Southwest Infectious Disease Clinical Research, Inc.
City
Dallas
State/Province
Texas
ZIP/Postal Code
75219
Country
United States
Facility Name
Therapeutic Concepts, PA
City
Houston
State/Province
Texas
ZIP/Postal Code
77004
Country
United States
Facility Name
Alamo Medical Research
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Metropolitan Research
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Inova Fairfax Hospital Center for Liver Diseases
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Liver Institute of Virginia, Bon Secours St.Mary's
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
Digestive and Liver Disease Specialists
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
Virginia Mason Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Westmead Hospital
City
Westmead,
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Royal Brisbane & Women's Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
St. Vincent's Hospital
City
Melbourne
ZIP/Postal Code
3065
Country
Australia
Facility Name
Monash Medical Centre
City
Melbourne
ZIP/Postal Code
3168
Country
Australia
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
Gordon & Leslie Diamond Health Care Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Facility Name
(G.I.R.I.) Gastrointestinal Research Institute
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2K5
Country
Canada
Facility Name
Toronto Liver Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6H 3M1
Country
Canada
Facility Name
CHUM - The Research Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 3J4
Country
Canada
Facility Name
Auckland Clinical Studies Limited
City
Auckland
ZIP/Postal Code
1640
Country
New Zealand
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
Facility Name
Clinical Research Puerto Rico Inc
City
San Juan
ZIP/Postal Code
00909-1711
Country
Puerto Rico
Facility Name
Fundacion De Investigacion De Diego
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
12. IPD Sharing Statement
Citations:
PubMed Identifier
25040192
Citation
Stepanova M, Nader F, Cure S, Bourhis F, Hunt S, Younossi ZM. Patients' preferences and health utility assessment with SF-6D and EQ-5D in patients with chronic hepatitis C treated with sofosbuvir regimens. Aliment Pharmacol Ther. 2014 Sep;40(6):676-85. doi: 10.1111/apt.12880. Epub 2014 Jul 15.
Results Reference
derived
PubMed Identifier
23607593
Citation
Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, Shiffman ML, Lawitz E, Everson G, Bennett M, Schiff E, Al-Assi MT, Subramanian GM, An D, Lin M, McNally J, Brainard D, Symonds WT, McHutchison JG, Patel K, Feld J, Pianko S, Nelson DR; POSITRON Study; FUSION Study. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013 May 16;368(20):1867-77. doi: 10.1056/NEJMoa1214854. Epub 2013 Apr 23.
Results Reference
derived
Learn more about this trial
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
We'll reach out to this number within 24 hrs