Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders

October 13, 2016 updated by: Gilead Sciences

A Phase 2b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders

The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in participants with genotypes 1 and 4 hepatitis C virus (HCV) infection and sofosbuvir (SOF) plus ribavirin (RBV) in participants with genotypes 2 and 3 HCV infection. Participants with an inherited bleeding disorder and chronic HCV infection (either monoinfected or HIV-1/HCV coinfected) will be enrolled.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

122

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Sacramento, California, United States, 95817
      • San Diego, California, United States, 92103-8651
      • San Francisco, California, United States, 94143
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
    • Georgia
      • Atlanta, Georgia, United States, 30308
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
      • Boston, Massachusetts, United States, 02115
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
    • New Jersey
      • Newark, New Jersey, United States, 07112
    • New York
      • New York, New York, United States, 10029
      • Rochester, New York, United States, 14621
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7584
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Hemophilia A, B or C, or Von Willebrand's disease
  • Chronic genotype 1, 2, 3 or 4 HCV infection
  • HCV RNA ≥ 1000 IU/mL at screening
  • Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male
  • Screening laboratory values within defined thresholds

  • For HIV-1/HCV co-infected individuals:

    • Suppressed HIV-1 RNA on an antiretroviral (ARV) regimen for at least 6 months prior to screening
    • Stable protocol-approved ARV regimen for > 8 weeks prior to screening
    • CD4 T-cell count > 200 cells/mm^3 at screening

Exclusion Criteria:

  • Clinically-significant illness (other than HCV, inherited bleeding disorder or HIV-1) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

  • Current or prior history of any of the following:

    • Hepatic decompensation
    • Chronic liver disease of a non-HCV etiology
    • Hepatocellular carcinoma (HCC)
    • Infection with hepatitis B virus (HBV)
  • Pregnant or nursing female
  • Prior treatment with inhibitors of nonstructural protein 5A (NS5A) or the NS5B polymerase
  • Chronic use of systemically administered immunosuppressive agents

  • For HIV-1/HCV co-infected individuals:

    • Opportunistic infection within 6 months prior to screening
    • Active, serious infection (other than HIV-1 or HCV) requiring parental antibiotics, antivirals or antifungals within 30 days prior to baseline

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LDV/SOF GT 1 or 4
Participants with chronic genotypes (GT) 1 or 4 HCV infection will receive LDV/SOF for 12 or 24 weeks. Treatment-experienced cirrhotic participants with genotype 1 HCV infection will receive LDV/SOF for 24 weeks.
Drug: LDV/SOF
90/400 mg FDC tablet administered orally
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Experimental: SOF+RBV 12 wks GT 2
Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
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)
Experimental: SOF+RBV 24 wks GT 3
Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Time Frame: Posttreatment Week 12
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Posttreatment Week 12
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time Frame: Up to 24 weeks
Up to 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
Time Frame: Posttreatment Week 4
SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
Posttreatment Week 4
Percentage of Participants With Virologic Failure
Time Frame: Up to Posttreatment Week 24

Virologic failure was defined as:

  • On-treatment virologic failure:

    • Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
    • Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
    • Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)

  • Virologic relapse:

    • Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
Up to Posttreatment Week 24
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Time Frame: Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL at Weeks 4, 8, 12, 16, 20, and 24 (HIV-1/HCV Co-infected Participants Only)
Time Frame: Weeks 4, 8, 12, 16, 20, and 24
Weeks 4, 8, 12, 16, 20, and 24
Change From Baseline in Serum Creatinine at the End of Treatment and at Posttreatment Week 12 (HIV-1/HCV Co-infected Participants Only)
Time Frame: Baseline; Weeks 12, 24, and Posttreatment Week 12
Baseline; Weeks 12, 24, and Posttreatment Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Walsh C, Workowski K, Terrault N, Sax S, Cohen A, et al. Approved All-Oral Sofosbuvir Regimens Are Safe and Highly Effective in Patients With Hereditary Bleeding Disorders. (2015). Hepatology, 62 (S1): 714A-807A. doi:10.1002/hep.28228

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

April 18, 2014

First Submitted That Met QC Criteria

April 18, 2014

First Posted (Estimate)

April 22, 2014

Study Record Updates

Last Update Posted (Estimate)

December 6, 2016

Last Update Submitted That Met QC Criteria

October 13, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-334-1274

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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