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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01726517
Recruitment Status : Completed
First Posted : November 15, 2012
Results First Posted : November 17, 2014
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE November 10, 2012
First Posted Date  ICMJE November 15, 2012
Results First Submitted Date  ICMJE November 7, 2014
Results First Posted Date  ICMJE November 17, 2014
Last Update Posted Date November 16, 2018
Study Start Date  ICMJE October 2012
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2014)
  • Percentage of Participants With Sustained Virologic Response (SVR) at 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, 25 IU/mL) 12 weeks after stopping study treatment.
  • Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [ Time Frame: Baseline to Week 12 ]
    The number of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was summarized.
Original Primary Outcome Measures  ICMJE
 (submitted: November 10, 2012)
  • Sustained virologic response after discontinuation of therapy [ Time Frame: 12 weeks after discontinuation of therapy ]
    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. ]
    Frequency and severity of adverse events.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2014)
  • Percentage of Participants With SVR 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 ]
    SVR2, SVR4, SVR8, and SVR24 was defined as HCV RNA < LLOQ at 2, 4, 8, and 24 weeks following the last dose of study drug, respectively.
  • Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse [ Time Frame: Baseline to Posttreatment Week 24 ]
    • Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values.
    • Viral relapse was defined as 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2012)
  • Sustained virologic response after discontinuation of therapy. [ Time Frame: 2,4,8, and 24 weeks after discontinuation of therapy ]
    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 ]
    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 ]
    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 ]
    To characterize steady state pharmacokinetics of sofosbuvir and GS-5885 during treatment and after treatment discontinuation.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects
Official Title  ICMJE A Phase 2, Randomized, Open-Label Study of Sofosbuvir/GS-5885 Fixed-Dose Combination ± Ribavirin in Subjects With Chronic Genotype 1 HCV Infection
Brief Summary This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis C Virus
Intervention  ICMJE
  • Drug: LDV/SOF
    LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily
    Other Name: Harvoni®
  • Drug: RBV
    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)
Study Arms  ICMJE
  • Experimental: LDV/SOF 8 Weeks (TN)
    Treatment-naive (TN) participants will be randomized to receive LDV/SOF for 8 weeks.
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF+RBV 8 Weeks (TN)
    Treatment-naive participants will be randomized to receive LDV/SOF plus RBV for 8 weeks.
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
  • Experimental: LDV/SOF 12 Weeks (TN)
    Treatment-naive participants will be randomized to receive LDV/SOF for 12 weeks.
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF 12 Weeks (TE)
    Treatment-experienced (TE) participants (had virologic failure following prior therapy with a protease-inhibitor [PI]+pegylated interferon [PEG]+RBV regimen) will be randomized to receive LDV/SOF for 12 weeks.
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF+RBV 12 Weeks (TE)
    Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) will be randomized to receive LDV/SOF plus RBV for 12 weeks.
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
Publications * 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. Erratum In: Lancet. 2014 Mar 8;383(9920):870.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 7, 2012)
100
Original Estimated Enrollment  ICMJE
 (submitted: November 10, 2012)
60
Actual Study Completion Date  ICMJE January 2014
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01726517
Other Study ID Numbers  ICMJE GS-US-337-0118
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency
Current Responsible Party Gilead Sciences
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Gilead Sciences
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Rob Hyland Gilead Sciences
PRS Account Gilead Sciences
Verification Date November 2014

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