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 (POSITRON)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01542788
First received: February 17, 2012
Last updated: May 8, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C
Drug: SOF
Drug: RBV
Drug: Placebo to match SOF
Drug: Placebo to match RBV
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants Achieving SVR12 [ Time Frame: Post-treatment Week 12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Post-treatment Week 4 ] [ Designated as safety issue: No ]
    SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy

  • Percentage of Participants Achieving SVR24 [ Time Frame: Post-treatment Week 24 ] [ Designated as safety issue: No ]
    SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy

  • Percentage of Participants Experiencing Viral Breakthrough [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment to post-treatment Week 24 ] [ Designated as safety issue: No ]
    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


Enrollment: 278
Study Start Date: March 2012
Study Completion Date: February 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SOF+RBV
Participants were randomized to receive SOF+RBV for 12 weeks.
Drug: SOF
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
Drug: 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 Comparator: Placebo
Participants were randomized to receive placebo to match SOF plus placebo to match RBV for 12 weeks.
Drug: Placebo to match SOF
Placebo to match SOF was administered orally once daily.
Drug: Placebo to match RBV
Placebo to match RBV was administered orally twice daily.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01542788

  Show 63 Study Locations
Sponsors and Collaborators
Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01542788     History of Changes
Other Study ID Numbers: GS-US-334-0107
Study First Received: February 17, 2012
Results First Received: January 6, 2014
Last Updated: May 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
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

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferons
Ribavirin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 11, 2014