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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02120300
First received: April 18, 2014
Last updated: October 20, 2014
Last verified: October 2014
  Purpose

This study will determine the HCV antiviral efficacy, safety, and tolerability of treatment with Ledipasvir/Sofosbuvir (LDV/SOF) fixed-dose combination (FDC) for participants with genotypes 1 and 4 HCV infection and Sofosbuvir (SOF) + Ribavirin (RBV) for 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.


Condition Intervention Phase
Chronic HCV Infection
Drug: LDV/SOF
Drug: Sofosbuvir
Drug: Ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12) [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
    SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.

  • Incidence of adverse events leading to permanent discontinuation of study drug(s) [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of participants with sustained virologic response (SVR) at 4 weeks after discontinuation of therapy (SVR4) [ Time Frame: Posttreatment Week 4 ] [ Designated as safety issue: No ]
    SVR4 is defined as HCV RNA < LLOQ at 4 weeks following the last dose of study drug.

  • Proportion of participants with HCV RNA < LLOQ on treatment [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
  • HCV RNA change from baseline [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: No ]
  • Proportion of participants with virologic failure [ Time Frame: Baseline to posttreatment Week 12 ] [ Designated as safety issue: No ]

    Virologic failure is defined as:

    • Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (note: second confirmation value can be posttreatment), or last available on-treatment measurement with no subsequent follow up values, OR
    • Rebound: > 1 log10IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (note: second confirmation value can be posttreatment), or last available on-treatment measurement with no subsequent follow up values, OR
    • Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment, OR
    • Relapse: 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

  • For HIV-1/HCV co-infected participants, the proportion of subjects that maintain HIV-1 RNA < 50 copies/mL while on HCV treatment [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
  • For HIV-1/HCV co-infected participants, change from baseline of serum creatinine at the end of treatment [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: No ]
  • For HIV-1/HCV co-infected participants, change from baseline of serum creatinine at posttreatment Week 12 [ Time Frame: Baseline to posttreatment Week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 125
Study Start Date: April 2014
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Genotypes 1 or 4
Participants with chronic genotypes 1 or 4 HCV infection will receive LDV/SOF for 12 weeks.
Drug: LDV/SOF
LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
Experimental: Genotype 2
Participants with chronic genotype 2 HCV infection will receive sofosbuvir plus ribavirin for 12 weeks.
Drug: Sofosbuvir
Sofosbuvir 400 mg tablet administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
Drug: Ribavirin
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: Genotype 3
Participants with chronic genotype 3 HCV infection will receive sofosbuvir plus ribavirin for 24 weeks.
Drug: Sofosbuvir
Sofosbuvir 400 mg tablet administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
Drug: Ribavirin
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)

  Eligibility

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

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 subjects:

    • 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 NS5A or the NS5B polymerase
  • Chronic use of systemically administered immunosuppressive agents
  • For HIV-1/HCV co-infected subjects:

    • 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
  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: NCT02120300

Contacts
Contact: Gilead Study Team 334-1274alerts@gilead.com

Locations
United States, California
Recruiting
Sacramento, California, United States, 95817
Recruiting
San Diego, California, United States, 92103-8651
Recruiting
San Francisco, California, United States, 94143
United States, District of Columbia
Recruiting
Washington, District of Columbia, United States, 20007
United States, Georgia
Recruiting
Atlanta, Georgia, United States, 30308
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02114
Recruiting
Boston, Massachusetts, United States, 02115
United States, Minnesota
Recruiting
Minneapolis, Minnesota, United States, 55407
United States, New Jersey
Recruiting
Newark, New Jersey, United States, 07112
United States, New York
Recruiting
New York, New York, United States, 10029
Recruiting
Rochester, New York, United States, 14621
United States, North Carolina
Recruiting
Chapel Hill, North Carolina, United States, 27599-7584
United States, Pennsylvania
Recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Luisa Stamm, MD, PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02120300     History of Changes
Other Study ID Numbers: GS-US-334-1274
Study First Received: April 18, 2014
Last Updated: October 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Blood Coagulation Disorders
Hemostatic Disorders
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Cardiovascular Diseases
Digestive System Diseases
Flaviviridae Infections
Hematologic Diseases
Hemorrhagic Disorders
Hepatitis
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Vascular Diseases
Virus Diseases
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014