Chronic Hepatitis CPhase 3POSITRONNCT01542788
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
A Phase 3 study testing SOF and RBV in people with Chronic Hepatitis C, run by Gilead Sciences at 63 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- SOF and RBV
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 278 participants
- Where
- 63 sitesin 5 countries
- Study dates
- Mar 2012to Feb 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Infection with HCV genotype 2 or 3
- Cirrhosis determination
- Subject meets one of the following classifications:
- IFN unwilling
- IFN ineligible
- IFN intolerant
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
63 sites in 5 countries.
63 sites in 5 countries
United States50 sites
Digestive Healthcare of Georgia
Atlanta, Georgia, 30309
University of Colorado
Aurora, Colorado, 80045
Gastroenterology Associates, LLC
Baton Rouge, Louisiana, 70809
Comprehensive Clinical Research
Berlin, New Jersey, 08009
Binghamton Gastroenterology Associates
Binghamton, New York, 13903
University of Alabama Birmingham
Birmingham, Alabama, 35294-2170
Massachusetts General Hospital
Boston, Massachusetts, 02114-2696
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Graves-Gilbert Clinic
Bowling Green, Kentucky, 42101
SCTI Research Foundation Liver Center
Coronado, California, 92118
Southwest Infectious Disease Clinical Research, Inc.
Dallas, Texas, 75219
Duke University
Durham, North Carolina, 27710
South Denver Gastroenterology
Englewood, Colorado, 80113
Metropolitan Research
Fairfax, Virginia, 22031
Inova Fairfax Hospital Center for Liver Diseases
Falls Church, Virginia, 22042
University of Florida
Gainesville, Florida, 32610-0277
Gastro One
Germantown, Tennessee, 38138
ID Care
Hillsborough, New Jersey, 08844
Therapeutic Concepts, PA
Houston, Texas, 77004
Indianapolis Gastroenterology Research Foundation
Indianapolis, Indiana, 46237
Borland-Groover Clinic
Jacksonville, Florida, 32256
Kansas City Gastroenterology and Hepatology
Kansas City, Missouri, 64131
Kaiser Permanente
Los Angeles, California, 90027
Lightspeed Medical
Los Angeles, California, 90036
Anthony Mills MD, Inc.
Los Angeles, California, 90069
Johns Hopkins University
Lutherville, Maryland, 21093
Gastrointestinal Specialists of Georgia, PC
Marietta, Georgia, 30060
University of Miami, Center for Liver Diseases
Miami, Florida, 33136
Nashville Gastrointestinal Specialists, Inc
Nashville, Tennessee, 37211
Advanced Research Institute
New Port Richey, Florida, 34653
Weill Cornell Medical College
New York, New York, 10021
Mount Sinai School of Medicine
New York, New York, 10029
Liver Institute of Virginia, Bon Secours St.Mary's
Newport News, Virginia, 23602
Digestive and Liver Disease Specialists
Norfolk, Virginia, 23502
Henry Ford Health System
Novi, Michigan, 48377
Orlando Immunology Center (ACH)
Orlando, Florida, 32803-1851
Internal Medicine Specialists
Orlando, Florida, 32806
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University Gastroenterology
Providence, Rhode Island, 02905
Minnesota Gastroenterology, P.A.
Saint Paul, Minnesota, 55407
Alamo Medical Research
San Antonio, Texas, 78215
Medical Associates Research Group
San Diego, California, 912123
UCSD Antiviral Research Center
San Diego, California, 92103
Kaiser Permanente
San Diego, California, 92154
Quest Clinical Research
San Francisco, California, 94115
Virginia Mason Medical Center
Seattle, Washington, 98101
The Research Institute
Springfield, Massachusetts, 01105
Whitman Walker Clinic
Washington D.C., District of Columbia, 20009
South Florida Center of Gastroenterology, P.A.
Wellington, Florida, 33414
Digestive Health Specialists, PA
Winston-Salem, North Carolina, 27103
Canada5 sites
University of Calgary
Calgary, Alberta, T2N 4Z6
CHUM - The Research Centre
Montreal, Quebec, H2X 3J4
Toronto Liver Centre
Toronto, Ontario, M6H 3M1
Gordon & Leslie Diamond Health Care Centre
Vancouver, British Columbia, V5Z 1M9
(G.I.R.I.) Gastrointestinal Research Institute
Vancouver, British Columbia, V6Z 2K5
Australia4 sites
Royal Brisbane & Women's Hospital
Herston, Queensland, 4029
St. Vincent's Hospital
Melbourne, 3065
Monash Medical Centre
Melbourne, 3168
Westmead Hospital
Westmead, New South Wales, 2145
New Zealand2 sites
Auckland Clinical Studies Limited
Auckland, 1640
Christchurch Hospital
Christchurch, 8011
Puerto Rico2 sites
Fundacion De Investigacion De Diego
San Juan, Puerto Rico, 00927
Clinical Research Puerto Rico Inc
San Juan, 00909-1711
About this study
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
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.
Read the 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.
- Conditions
- Chronic Hepatitis C
- Being tested
- SOF, RBV, Placebo to match SOF, Placebo to match RBV
- 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
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SOFDrug
Also called Sovaldi®, GS-7977, PSI-7977
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
RBVDrug
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 SOFDrug
Placebo to match SOF was administered orally once daily.
Placebo to match RBVDrug
Placebo to match RBV was administered orally twice daily.
| Study group | Role | What they receive |
|---|---|---|
| SOF+RBV | Experimental | Participants were randomized to receive SOF+RBV for 12 weeks. Receives: Drug: SOF; Drug: RBV |
| Placebo | Placebo comparator | Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. Receives: Drug: Placebo to match SOF; Drug: Placebo to match RBV |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Post-treatment Week 12
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.
Measured: Baseline to Week 12
Secondary outcomes (4)
Percentage of Participants Achieving SVR4
SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy
Measured: Post-treatment Week 4
Percentage of Participants Achieving SVR24
SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy
Measured: Post-treatment Week 24
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
Measured: Baseline to Week 12
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
Measured: End of treatment to post-treatment Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionNov 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 278 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01542788
- Sponsor's protocol ID
- GS-US-334-0107
- Acronym
- POSITRON
- Status last verified
- May 2014
- First submitted
- 17 Feb 2012
- Last updated
- 19 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 25040192Jacobson 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.
PubMed 23607593
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01542788
- Acronym / sponsor ID
- POSITRON / GS-US-334-0107
- Conditions
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 278 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Mar 2012
- Primary completion
- Nov 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 2 Mar 2012 (estimated)
- Results
- Posted 17 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SOF+RBV | Experimental | Drug: SOF, Drug: RBVParticipants were randomized to receive SOF+RBV for 12 weeks. |
| Placebo | Placebo comparator | Drug: Placebo to match SOF, Drug: Placebo to match RBVParticipants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Infection with HCV genotype 2 or 3
- Cirrhosis determination
- Subject meets one of the following classifications:
- Screening laboratory values within defined thresholds
- Subject has not been treated with any investigational drug or device within 30 days of the Screening visit
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SOFAlso: Sovaldi®, GS-7977, PSI-7977Sofosbuvir (SOF) 400 mg tablet administered orally once daily | Drug | SOF+RBV |
| RBVRibavirin (RBV) was administered as a tablet orally according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg). | Drug | SOF+RBV |
| Placebo to match SOFPlacebo to match SOF was administered orally once daily. | Drug | Placebo |
| Placebo to match RBVPlacebo to match RBV was administered orally twice daily. | Drug | Placebo |
Primary outcome
Percentage of Participants Achieving SVR12
Time frame: Post-treatment Week 12
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
Time frame: Baseline to Week 12
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.
4 secondary outcomes
Percentage of Participants Achieving SVR4
Time frame: Post-treatment Week 4
Percentage of Participants Achieving SVR24
Time frame: Post-treatment Week 24
Percentage of Participants Experiencing Viral Breakthrough
Time frame: Baseline to Week 12
Percentage of Participants Experiencing Viral Relapse
Time frame: End of treatment to post-treatment Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25040192Stepanova 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.
- Derived from this study: PubMed 23607593Jacobson 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.
Related trials for Chronic Hepatitis C
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
63 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SOF and RBV in people with Chronic Hepatitis C, run by Gilead Sciences at 63 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 63 sites in United States, Canada, Australia, New Zealand, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving SVR12 (time frame: Post-treatment Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01542788, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2014.