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Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 HCV and HIV-1 Co-infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02073656
First received: February 25, 2014
Last updated: August 30, 2016
Last verified: August 2016
  Purpose

This study will evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) administered for 12 weeks in hepatitis C virus (HCV) treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic genotype 1 or 4 HCV infection who are co-infected with HIV-1.

Participants who experience confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 may be eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF plus ribavirin (RBV) for 24 weeks.


Condition Intervention Phase
Hepatitis C Virus
HIV
Drug: LDV/SOF
Drug: RBV
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)-1 Co-infection

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ] [ Designated as safety issue: No ]
    SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.

  • Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, and 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, and 8 [ Time Frame: Baseline; Weeks 1, 2, 4, 6, and 8 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ] [ Designated as safety issue: No ]

    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.

  • Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment [ Time Frame: Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in Serum Creatinine at the End of Treatment (Week 12) and at Posttreatment Weeks 12 and 24 [ Time Frame: Baseline; Week 12, Posttreatment Weeks 12 and 24 ] [ Designated as safety issue: No ]
  • For Participants in the Retreatment Substudy, Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) [ Time Frame: Posttreatment Weeks 4, 12, and 24 of Retreatment Substudy ] [ Designated as safety issue: No ]
    SVR4, SVR12, and SVR 24 were defined as HCV RNA < LLOQ at 4, 12, and 24 weeks after stopping study treatment, respectively.

  • For Participants in the Retreatment Substudy, Percentage of Participants With HCV RNA < LLOQ at Retreatment Weeks 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 of the Retreatment Substudy ] [ Designated as safety issue: No ]
  • For Participants in the Retreatment Substudy, Change From Baseline in HCV RNA at Retreatment Weeks 2, 4, and 8 [ Time Frame: Baseline; Weeks 2, 4, and 8 of Retreatment Substudy ] [ Designated as safety issue: No ]
  • For Participants in the Retreatment Substudy, Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 of Retreatment Substudy ] [ Designated as safety issue: No ]

    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.


Enrollment: 335
Study Start Date: February 2014
Study Completion Date: December 2015
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDV/SOF 12 Weeks
LDV/SOF for 12 weeks
Drug: LDV/SOF
90/400 mg FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Experimental: Retreatment Substudy
LDV/SOF plus RBV for 24 weeks
Drug: LDV/SOF
90/400 mg FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: 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   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HCV RNA ≥ 10,000 IU/mL at screening
  • HCV genotype 1 or 4
  • HIV-1 infection
  • Cirrhosis determination, a fibroscan or liver biopsy may be required
  • Screening laboratory values within defined thresholds
  • Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male

Exclusion Criteria:

  • Clinically-significant illness (other than HCV or HIV) or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol
  • Current or prior history of clinical hepatic decompensation, hepatocellular carcinoma (HCC), or other malignancy (with the exception of certain resolved skin cancers)
  • Hepatitis B virus (HBV) infection
  • Pregnant or nursing female
  • Chronic use of systemically administered immunosuppressive agents
  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: NCT02073656

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35294-2170
United States, California
Los Angeles, California, United States, 90027
Newport Beach, California, United States, 92663
Palo Alto, California, United States, 94304-5350
Sacramento, California, United States, 95817
San Diego, California, United States, 92103
San Francisco, California, United States, 94110
Torrance, California, United States, 90502
United States, Colorado
Denver, Colorado, United States, 80209
United States, District of Columbia
Washington, District of Columbia, United States, 20815
United States, Florida
Bradenton, Florida, United States, 34209
Miami, Florida, United States, 33136
Orlando, Florida, United States, 32803
Tampa, Florida, United States, 33614
United States, Georgia
Atlanta, Georgia, United States, 30312
Decatur, Georgia, United States, 30033
United States, Illinois
Chicago, Illinois, United States, 60612
United States, Maryland
Lutherville, Maryland, United States, 21093
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, Missouri
Kansas City, Missouri, United States, 64111
United States, New Mexico
Santa Fe, New Mexico, United States, 87505
United States, New York
Bronx, New York, United States, 10468
New York, New York, United States, 10065
United States, North Carolina
Chapel Hill, North Carolina, United States, 27599
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati, Ohio, United States, 45267-0595
United States, Pennsylvania
Allentown, Pennsylvania, United States, 18102
Philadelphia, Pennsylvania, United States, 19107
United States, Rhode Island
Providence, Rhode Island, United States, 02906
United States, Texas
Dallas, Texas, United States, 75235
Houston, Texas, United States, 77004
United States, Virginia
Annandale, Virginia, United States, 22003
Richmond, Virginia, United States, 23298-0341
United States, Washington
Seattle, Washington, United States, 98104
Canada, British Columbia
Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Ontario
Ottawa, Ontario, Canada, K1H 8L6
Toronto, Ontario, Canada, M5G 2N2
Canada, Quebec
Montreal, Quebec, Canada, H2L 5B1
New Zealand
Auckland, New Zealand, 1142
Christchurch, New Zealand, 8011
Puerto Rico
San Juan, Puerto Rico, 00936-5607
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Jenny Yang, PharmD Gilead Sciences
  More Information

Publications:
Cooper C, Naggie S, Saag M, Yang JC, Stamm LM, Dvory-Sobol H, et al. Retreatment of Patients Who Failed 12 Weeks of Ledipasvir/Sofosbuvir-Based Regimens with Ledipasvir/Sofosbuvir with Ribavirin for 24 Weeks [Poster Presentation]. 23nd Conference on Retroviruses and Opportunistic Infections (CROI); 2016 February 22-25; Boston, MA.
Naggie S, Cooper C, Saag M, Stamm LM, Yang JC, Pang PS, et al. Ledipasvir/Sofosbuvir for 12 Weeks in Patients Coinfected With HCV and HIV-1 [Oral Presentation]. 22nd Conference on Retroviruses and Opportunistic Infections (CROI); 2015 February 23-26; Seattle, WA.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02073656     History of Changes
Other Study ID Numbers: GS-US-337-0115 
Study First Received: February 25, 2014
Results First Received: August 30, 2016
Last Updated: August 30, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
New Zealand: Medsafe

Keywords provided by Gilead Sciences:
genotype 1
genotype 4
HIV

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Coinfection
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Infection
Parasitic Diseases
Ledipasvir
Sofosbuvir
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on December 06, 2016