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

November 10, 2012
March 17, 2014
October 2012
July 2013   (final data collection date for primary outcome measure)
  • 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 ]
  • Sustained virologic response after discontinuation of therapy [ Time Frame: 12 weeks after discontinuation of therapy ] [ Designated as safety issue: No ]
    Sustained virologic response (SVR) 12 weeks after the end of treatment (SVR12 defined as HCV RNA < lower limit of quantification [LLOQ] 12 weeks after last dose of study drug).
  • Safety and tolerability of combination treatment with sofosbuvir (SOF)/GS-5885 fixed-dose combination (FDC) +/- RBV as measured by review of the accumulated safety data. [ Time Frame: Safety and tolerability on treatment and 30 days post last dose. ] [ Designated as safety issue: Yes ]
    Frequency and severity of adverse events.
Complete list of historical versions of study NCT01726517 on ClinicalTrials.gov Archive Site
  • 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.
  • Sustained virologic response after discontinuation of therapy. [ Time Frame: 2,4,8, and 24 weeks after discontinuation of therapy ] [ Designated as safety issue: No ]
    Sustained virologic response (SVR) at 2,4,8, and 24 weeks after discontinuation of therapy (SVR 2, SVR4, SVR 8, and SVR24 defined as HCV RNA < lower limit of quantification [LLOQ] after last dose of study drug).
  • Viral resistance to sofosbuvir and GS-5885 combination therapy during and after treatment. [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
    To evaluate the emergence of viral resistance to sofosbuvir and GS-5885 during treatment and after treatment discontinuation
  • Characterization of viral dynamics during treatment and after treatment discontinuation. [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
    To characterize viral dynamics during treatment and after treatment discontinuation.
  • Characterization of steady state pharmacokinetics of sofosbuvir and GS-5885 during treatment and after treatment discontinuation. [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
    To characterize steady state pharmacokinetics of sofosbuvir and GS-5885 during treatment and after treatment discontinuation.
Not Provided
Not Provided
 
Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects
A Phase 2, Randomized, Open-Label Study of Sofosbuvir/GS-5885 Fixed-Dose Combination ± Ribavirin in Subjects With Chronic Genotype 1 HCV Infection

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis C Virus
  • 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 8 Week TN
    Treatment-naive (TN) participants will receive LDV/SOF for 8 weeks.
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF+RBV 8 Weeks
    Treatment-naive participants will receive LDV/SOF plus RBV for 8 weeks.
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
  • Experimental: LDV/SOF 12 Weeks TN
    Treatment-naive participants will receive LDV/SOF for 12 weeks.
    Intervention: Drug: LDV/SOF
  • 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.
    Intervention: Drug: LDV/SOF
  • 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.
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23. doi: 10.1016/S0140-6736(13)62121-2. Epub 2013 Nov 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
100
January 2014
July 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01726517
GS-US-337-0118
No
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Rob Hyland Gilead Sciences
Gilead Sciences
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP