Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV

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: NCT01701401
Recruitment Status : Completed
First Posted : October 5, 2012
Results First Posted : March 27, 2015
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE October 2, 2012
First Posted Date  ICMJE October 5, 2012
Results First Submitted Date  ICMJE March 17, 2015
Results First Posted Date  ICMJE March 27, 2015
Last Update Posted Date November 16, 2018
Study Start Date  ICMJE September 2012
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 17, 2015)
  • Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Study Drug (SVR12) [ Time Frame: Posttreatment Week 12 ]
    SVR12 was defined as HCV RNA level < the lower limit of quantification (LLOQ, ie, < 25 copies/mL) 12 weeks after last dose of study drug.
  • Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug [ Time Frame: Up to 24 weeks ]
    The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.
Original Primary Outcome Measures  ICMJE
 (submitted: October 4, 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: March 17, 2015)
  • Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Study Drug [ Time Frame: Posttreatment Weeks 4 and 24 ]
    SVR4 and SVR24 were defined as HCV RNA level < LLOQ at 4 and 24 weeks after discontinuation of study drug, respectively.
  • Percentage of Participants With HCV RNA < LLOQ at Week 2 [ Time Frame: Week 2 ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 4 [ Time Frame: Week 4 ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 8 [ Time Frame: Week 8 ]
  • Change From Baseline in HCV RNA at Week 2 [ Time Frame: Baseline; Week 2 ]
  • Change From Baseline in HCV RNA at Week 4 [ Time Frame: Baseline; Week 4 ]
  • Change From Baseline in HCV RNA at Week 8 [ Time Frame: Baseline; Week 8 ]
  • Percentage of Participants With Virologic Failure [ Time Frame: Baseline to posttreatment Week 24 ]
    On-treatment virologic failure was defined as:
    • Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow- up values, OR
    • Rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow-up values, OR
    • Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment
    Virologic 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: October 4, 2012)
  • Sustained virologic response after discontinuation of therapy. [ Time Frame: 4 and 24 weeks after discontinuation of therapy. ]
    Sustained virologic response (SVR) at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24 defined as HCV RNA < lower limit of quantification [LLOQ] 12 weeks after last dose of study drug).
  • Kinetics of circulating HCV RNA during and after treatment discontinuation. [ Time Frame: 12 and 24 weeks ]
    To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation.
  • 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 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 Ledipasvir/Sofosbuvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV
Official Title  ICMJE A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5885 Fixed-Dose Combination (FDC) +/- Ribavirin for 12 and 24 Weeks in Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection.
Brief Summary The purpose of this study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir (LDV)/sofosbuvir (SOF) fixed-dose combination (FDC) tablets with or without ribavirin (RBV) administered for 12 and 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
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/SOF 90/400 mg FDC tablet administered orally once daily
    Other Names:
    • Harvoni®
    • GS-5885/GS-7977
  • 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 12 weeks
    LDV/SOF administered for 12 weeks
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF+RBV 12 weeks
    LDV/SOF+RBV administered for 12 weeks.
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
  • Experimental: LDV/SOF 24 weeks
    LDV/SOF administered for 24 weeks
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF+RBV 24 weeks
    LDV/SOF+RBV administered for 24 weeks.
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
Publications *

*   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: May 12, 2014)
870
Original Estimated Enrollment  ICMJE
 (submitted: October 4, 2012)
800
Actual Study Completion Date  ICMJE April 2014
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18, with chronic genotype 1 HCV infection
  • HCV treatment-naive
  • HCV RNA > 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
  • Co-infection with HIV or hepatitis B virus (HBV)
  • 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 France,   Germany,   Italy,   Puerto Rico,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01701401
Other Study ID Numbers  ICMJE GS-US-337-0102
2012-003387-43 ( EudraCT Number )
Has Data Monitoring Committee Yes
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
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jenny Yang, Pharm D Gilead Sciences
PRS Account Gilead Sciences
Verification Date March 2015

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