Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01726517
First received: November 10, 2012
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

This study is to evaluate the safety, tolerability and antiviral efficacy of ledipasvir (formerly GS-5885)/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV) administered for 8 or 12 weeks of treatment in participants with chronic genotype 1 hepatitis C virus (HCV) infection who are treatment-naive and for 12 weeks in participants who had previously received a regimen containing a protease inhibitor for the treatment of HCV.


Condition Intervention Phase
Chronic Hepatitis C Virus
Drug: LDV/SOF
Drug: RBV
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Open-Label Study of Sofosbuvir/GS-5885 Fixed-Dose Combination ± Ribavirin in Subjects With Chronic Genotype 1 HCV Infection

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 medication.

  • Incidence of adverse events leading to permanent discontinuation of study drug(s) [ Time Frame: Baseline up to Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of participants with sustained virologic response at 2, 4, 8, and 24 weeks after discontinuation of therapy (SVR2, SVR4, SVR8, and SVR24) [ Time Frame: Posttreatment Weeks 2, 4, 8, and 24 ] [ Designated as safety issue: No ]
    SVR2, SVR4, SVR8, and SVR24 is defined as HCV RNA < LLOQ at 2, 4, 8, and 24 weeks following the last dose of study medication, respectively.

  • Proportion of participants experiencing viral breakthrough [ Time Frame: Baseline up to Week 12 ] [ Designated as safety issue: No ]
    Viral breakthrough is defined as having confirmed detectable HCV RNA levels (HCV RNA > LLOQ) after having previously had undetectable HCV RNA levels (HCV RNA < LLOQ) while on treatment.

  • Proportion of participants experiencing viral relapse [ Time Frame: Up to Posttreatment Week 24 ] [ Designated as safety issue: No ]
    Viral relapse is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR.


Enrollment: 100
Study Start Date: October 2012
Study Completion Date: January 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDV/SOF 8 Week TN
Treatment-naive (TN) participants will receive LDV/SOF for 8 weeks.
Drug: LDV/SOF
Ledipasvir 90 mg/sofosbuvir 400 mg FDC tablet administered orally once daily
Other Names:
  • GS-5885
  • GS-7977
  • PSI-7977
Experimental: LDV/SOF+RBV 8 Weeks
Treatment-naive participants will receive LDV/SOF plus RBV for 8 weeks.
Drug: LDV/SOF
Ledipasvir 90 mg/sofosbuvir 400 mg FDC tablet administered orally once daily
Other Names:
  • GS-5885
  • 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: LDV/SOF 12 Weeks TN
Treatment-naive participants will receive LDV/SOF for 12 weeks.
Drug: LDV/SOF
Ledipasvir 90 mg/sofosbuvir 400 mg FDC tablet administered orally once daily
Other Names:
  • GS-5885
  • GS-7977
  • PSI-7977
Experimental: LDV/SOF 12 Weeks
Participants who were virologic failures following prior therapy with a protease-inhibitor (PI)+pegylated interferon (PEG)+RBV regimen received LDV/SOF for 12 weeks.
Drug: LDV/SOF
Ledipasvir 90 mg/sofosbuvir 400 mg FDC tablet administered orally once daily
Other Names:
  • GS-5885
  • GS-7977
  • PSI-7977
Experimental: LDV/SOF+RBV 12 Weeks
Participants who were virologic failures following prior therapy with a PI+PEG+RBV regimen received LDV/SOF plus RBV for 12 weeks.
Drug: LDV/SOF
Ledipasvir 90 mg/sofosbuvir 400 mg FDC tablet administered orally once daily
Other Names:
  • GS-5885
  • 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)

  Eligibility

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

Inclusion Criteria:

  • Age equal to or greater than 18 years, with chronic genotype 1 HCV infection
  • HCV RNA equal to or greater than 10,000 IU/mL at Screening
  • Cirrhosis determination; a liver biopsy may be required
  • Screening laboratory values within defined thresholds
  • Use of two effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

  • Pregnant or nursing female or male with pregnant female partner
  • Current or prior history of clinical hepatic decompensation
  • Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain -resolved skin cancers)
  • Chronic use of systemic immunosuppressive agents
  • History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
  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: NCT01726517

Locations
United States, Texas
San Antonio, Texas, United States, 78215
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Rob Hyland Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01726517     History of Changes
Other Study ID Numbers: GS-US-337-0118
Study First Received: November 10, 2012
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HCV genotype 1 (GT-1)
HCV
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy
GS-7977
GS-5885
Ribavirin
Open Label
Sofosbuvir
Treatment-Naïve
Protease Inhibitors
PI

Additional relevant MeSH terms:
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Ribavirin
Protease Inhibitors
HIV Protease Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Enzyme Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on October 16, 2014