Efficacy and Safety of Sofosbuvir+Ribavirin in Genotype 2 HCV-infected U.S. Veterans With Cirrhosis

Phase 4

Completed

• Conditions: Hepatitis C Virus Infection
• Interventions: Drug: Sofosbuvir; Drug: RBV

• Registration Number: NCT02128542
• Lead Sponsor: Gilead Sciences

Brief Summary

This study will examine the safety, tolerability, and antiviral efficacy of sofosbuvir (SOF)+ribavirin (RBV) in treatment-naive and treatment-experienced United States Veterans with compensated cirrhosis and genotype 2 HCV infection.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-04-29
• Study First Submitted QC: 2014-04-29
• Study First Posted: 2014-05-01
• Study Start: 2014-06
• Primary Completion: 2015-06
• Study Completion: 2015-06
• Status Verified: 2016-06
• Results First Submitted: 2016-06-21
• Results First Submitted QC: 2016-06-21
• Last Update Submitted: 2016-06-21
• Results First Posted: 2016-08-03
• Last Update Posted: 2016-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

• Willing and able to provide written informed consent.

• Treatment-naive or treatment-experienced adult, U.S. Veteran

• Chronic genotype 2 (GT2) HCV infection Classified as:

  • Eligible for treatment with interferon (IFN)-based therapy
  • Ineligible for IFN treatment
  • Intolerant to IFN.

• Cirrhosis determination

• Laboratory parameters within prespecified ranges at screening:

• A negative serum pregnancy test is required for females of childbearing potential

• Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

• Lactating females must agree to discontinue nursing before study drug is administered.

• Males must agree to refrain from sperm donation from the date of screening until at least 7 months after the last dose of RBV, or 90 days after their last dose of study drug if not taking RBV.

• Must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.

• Must be of generally good health as determined by the Investigator.

Exclusion Criteria

• Current participation in an interventional clinical trial.
• Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
• History of any other clinically significant chronic liver disease (e.g., hemochromatosis; Wilson's disease; α1-antitrypsin deficiency), except nonalcoholic steatohepatitis (NASH).
• Decompensated liver
• History of hemoglobinopathies
• Contraindication or hypersensitivity to RBV
• History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the participation for the full duration of the study, such that it is not in the best interest of the individual to participate.
• Clinically significant ECG abnormality at screening.
• History of solid organ transplantation.
• Presence of hepatocellular carcinoma (HCC) Malignancy within 5 years prior to screening, with the exception of specific cancers that are entirely cured by surgical resection (basal cell skin cancer and prostate cancer in remission). Individuals under evaluation for possible malignancy are not eligible.
• Prior treatment with an NS5B polymerase inhibitor.
• Chronic use of systemic immunosuppressive agents or immunomodulatory agents (e.g., prednisone equivalent > 10 mg/day).
• Concomitant disallowed as per the Sovaldi Packet Insert.
• Known hypersensitivity to the study drug, the metabolites, or formulation excipient.
• History of difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
• Use of any prohibited concomitant medications as described in the study protocol
• Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug.
• Male with pregnant female partner.
• In the judgment of the investigator any clinically-relevant drug or alcohol abuse within 12 months of screening that may interfere with treatment, assessment or compliance with the protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sofosbuvir+RBV 12 weeks	Sofosbuvir	Participants will receive sofosbuvir+RBV for 12 weeks.
Sofosbuvir+RBV 12 weeks	RBV	Participants will receive sofosbuvir+RBV for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	Up to 12 weeks

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response at 4 Weeks After Discontinuation of Therapy (SVR4)	Posttreatment Week 4	SVR4 was defined as HCV RNA \< LLOQ at 4 weeks following the last dose of study drug.
Percentage of Participants Experiencing Viral Breakthrough	Up to Posttreatment Weak 12	Viral breakthrough was defined as either: * HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment; * HCV RNA ≥ LLOQ at the last available on-treatment measurement with no subsequent follow-up values
Percentage of Participants Experiencing Viral Relapse	Up to Posttreatment Week 12	Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period after having achieved HCV RNA \< LLOQ at end of treatment.
Number of Participants With Nonstructural Protein 5B (NS5B) Nucleoside Inhibitor (NI) Resistance-Associated Variants (RAVs) and RBV RAVs at Pretreatment and Posttreatment	Pretreatment and Posttreatment Week 12	Deep sequencing of the HCV NS5B gene was attempted for all participants who had virologic failure at pretreatment and posttreatment time points if the level of HCV RNA in the plasma sample was ≥ 1000 IU/L.