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Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin in Treatment-Experienced Subjects With Genotype 1 HCV Infection (ION-2)

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ClinicalTrials.gov Identifier: NCT01768286
Recruitment Status : Completed
First Posted : January 15, 2013
Results First Posted : November 26, 2014
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE January 10, 2013
First Posted Date  ICMJE January 15, 2013
Results First Submitted Date  ICMJE November 21, 2014
Results First Posted Date  ICMJE November 26, 2014
Last Update Posted Date November 16, 2018
Study Start Date  ICMJE January 2013
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2014)
  • Percentage of Participants With Sustained Virologic Response (SVR) 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 following the 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: January 11, 2013)
  • 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 21, 2014)
  • Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
    SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
  • Percentage of Participants With HCV RNA < LLOQ at Week 1 [ Time Frame: Week 1 ]
  • 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 ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 12 [ Time Frame: Week 12 ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 24 [ Time Frame: Week 24 ]
  • Change From Baseline in HCV RNA at Week 1 [ Time Frame: Baseline; Week 1 ]
  • 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 ]
    Virologic failure was defined as on-treatment virologic failure or virologic relapse.
    • On-Treatment Virologic Failure was defined as
      • 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 was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2013)
  • 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 ]
    On treatment and post treatment HCV RNA levels over time will be used to characterize the kinetics of circulating HCV RNA during 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 [ 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 ± Ribavirin in Treatment-Experienced Subjects With Genotype 1 HCV Infection
Official Title  ICMJE A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5885 Fixed-Dose Combination ± Ribavirin for 12 and 24 Weeks in Treatment-Experienced Subjects With Chronic Genotype 1 HCV Infection
Brief Summary This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir fixed dose combination (FDC) with or without ribavirin (RBV) administered for 12 or 24 weeks in treatment-experienced subjects with chronic genotype 1 hepatitis C virus (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
    Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet administered orally once daily
    Other Names:
    • Harvoni®
    • GS-5885/GS-7997
  • 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)
Study Arms  ICMJE
  • Experimental: LDV/SOF 12 Weeks
    Participants will receive LDV/SOF FDC for 12 weeks.
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF+RBV 12 Weeks
    Participants will receive LDV/SOF FDC plus RBV for 12 weeks.
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
  • Experimental: LDV/SOF 24 Weeks
    Participants will receive LDV/SOF FDC for 24 weeks.
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF+RBV 24 Weeks
    Participants will receive LDV/SOF FDC plus RBV 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: February 27, 2014)
441
Original Estimated Enrollment  ICMJE
 (submitted: January 11, 2013)
400
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age > 18, with chronic genotype 1 HCV infection
  • HCV treatment-experienced, including patients who have previously failed a nonstructural protein (NS)3/4A protease inhibitor plus pegylated interferon (PEG)/RBV regimen
  • 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
  • Coinfection with HIV or hepatitis B virus
  • Current or prior history of clinical hepatic decompensation
  • Hepatocellular carcinoma 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 NCT01768286
Other Study ID Numbers  ICMJE GS-US-337-0109
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, PharmD 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