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

A Phase 4, Multicenter, Open Label Study to Investigate the Efficacy and Safety of an All Oral Combination of Sofosbuvir+Ribavirin in Genotype 2 HCV-infected U.S. Veterans With Cirrhosis VALOR-HCV: Veterans Affairs alL Oral Regimen of SOF+RBV in GT2 HCV

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus Infection
• Intervention / Treatment: Drug: RBV; Drug: Sofosbuvir

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90822
    • Los Angeles, California, United States, 90073
    • Palo Alto, California, United States, 94394
    • San Diego, California, United States, 92102
    • San Francisco, California, United States, 94121
  • Connecticut
    • New Haven, Connecticut, United States, 06520
  • Florida
    • Miami, Florida, United States, 33125
  • Georgia
    • Decatur, Georgia, United States, 30033
  • Maryland
    • Baltimore, Maryland, United States, 21201
  • Missouri
    • Kansas City, Missouri, United States, 64128
  • North Carolina
    • Durham, North Carolina, United States, 27705
  • Oregon
    • Portland, Oregon, United States, 97239
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
    • Pittsburgh, Pennsylvania, United States, 15240
  • Texas
    • Dallas, Texas, United States, 75216
    • Houston, Texas, United States, 77030
  • Virginia
    • Richmond, Virginia, United States, 23249

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sofosbuvir+RBV 12 weeks; Participants will receive sofosbuvir+RBV for 12 weeks.	Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: Sofosbuvir; Sofosbuvir 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; PSI-7977

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response at 4 Weeks After Discontinuation of Therapy (SVR4)	SVR4 was defined as HCV RNA < LLOQ at 4 weeks following the last dose of study drug.	Posttreatment Week 4
Percentage of Participants Experiencing Viral Breakthrough	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	Up to Posttreatment Weak 12
Percentage of Participants Experiencing Viral Relapse	Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period after having achieved HCV RNA < LLOQ at end of treatment.	Up to Posttreatment Week 12
Number of Participants With Nonstructural Protein 5B (NS5B) Nucleoside Inhibitor (NI) Resistance-Associated Variants (RAVs) and RBV RAVs at Pretreatment and Posttreatment	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.	Pretreatment and Posttreatment Week 12

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Lorenzo Rossaro, MD, Gilead Sciences

Publications and helpful links

General Publications

• Ho SB, Monto A, Peyton A, Kaplan DE, Byrne S, Moon S, Copans A, Rossaro L, Roy A, Le H, Dvory-Sobol H, Zhu Y, Brainard DM, Guyer W, Shaikh O, Fuchs M, Morgan TR; VALOR study team. Efficacy of Sofosbuvir Plus Ribavirin in Veterans With Hepatitis C Virus Genotype 2 Infection, Compensated Cirrhosis, and Multiple Comorbidities. Clin Gastroenterol Hepatol. 2017 Feb;15(2):282-288. doi: 10.1016/j.cgh.2016.05.024. Epub 2016 May 27.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: April 29, 2014
• First Submitted That Met QC Criteria: April 29, 2014
• First Posted (Estimate): May 1, 2014

Study Record Updates

• Last Update Posted (Estimate): August 3, 2016
• Last Update Submitted That Met QC Criteria: June 21, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Veterans HCV
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir
• Other Study ID Numbers: GS-US-334-1379