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Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin for the Treatment of HCV (ION-3)

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ClinicalTrials.gov Identifier: NCT01851330
Recruitment Status : Completed
First Posted : May 10, 2013
Results First Posted : December 30, 2014
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE May 3, 2013
First Posted Date  ICMJE May 10, 2013
Results First Submitted Date  ICMJE December 18, 2014
Results First Posted Date  ICMJE December 30, 2014
Last Update Posted Date November 16, 2018
Study Start Date  ICMJE May 2013
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2014)
  • Percentage of Participants With Sustained Virologic Response 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 12 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: May 8, 2013)
  • Sustained virologic response after discontinuation of therapy. [ Time Frame: 12 weeks after discontinuation of therapy. ]
    To determine the proportion of subjects who attain 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 treatment with SOF/LDV FDC +/- RBV as measured by review of accumulated safety data. Specifically: number of adverse events including severity grading on a scale of 1 to 4; treatment emergent graded laboratory abnormalities. [ Time Frame: Safety and tolerability from start of on treatment and through 30 days post last dose. ]
    Assess safety laboratory tests and the number, frequency and severity of adverse events from start of treatment through 30 days post last dose of study drug. Specifically: number of adverse events including severity grading on a scale of 1 to 4; treatment emergent graded laboratory abnormalities.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2014)
  • Percentage of Participants With Sustained Virologic Response 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 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 Experiencing 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: May 8, 2013)
  • Evaluate the efficacy of the SOF/LDV FDC + RBV for 8 weeks versus the SOF/LDV FDC for 12 weeks. [ Time Frame: 12 weeks after discontinuation of therapy ]
    To evaluate the efficacy (number of subjects achieving SVR12, as defined by HCV RNA < lower limit of quanititation 12 weeks after discontinuing therapy) of the SOF/LDV FDC + RBV for 8 weeks versus the SOF/LDV FDC for 12 weeks, in HCV genotype 1 treatment-naive subjects without cirrhosis.
  • Evaluate the efficacy of the SOF/LDV FDC for 8 weeks versus the SOF/LDV FDC for 12 weeks. [ Time Frame: 12 weeks after discontinuation of therapy. ]
    To evaluate the efficacy (number of subjects achieving SVR12, as defined by HCV RNA < lower limit of quanititation 12 weeks after discontinuing therapy) of the SOF/LDV FDC for 8 weeks versus the SOF/LDV FDC for 12 weeks, in HCV genotype 1 treatment-naive subjects without cirrhosis.
  • Evaluate the efficacy of the SOF/LDV FDC for 8 weeks versus the SOF/LDV FDC + RBV for 8 weeks. [ Time Frame: 12 weeks after discontinuation of therapy. ]
    To evaluate the efficacy (number of subjects achieving SVR12, as defined by HCV RNA < lower limit of quanititation 12 weeks after discontinuing therapy) of the SOF/LDV FDC for 8 weeks versus the SOF/LDV FDC + RBV for 8 weeks, in HCV genotype 1 treatment-naive subjects without cirrhosis.
  • Sustained virologic response after discontinuation of therapy. [ Time Frame: 4 and 24 weeks after discontinuation of therapy. ]
    To determine the proportion of subjects who attain 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: On treatment up to either week 8 or 12 and off treatment up to post-treatment week 24. ]
    To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation.
  • Number of subjects with viral resistance associated variants to Sofosbuvir or Ledipasvir combination therapy during and after treatment. [ Time Frame: On treatment up to either week 8 or 12 and off treatment up to post-treatment week 24. ]
    To evaluate the number of subjects with emergence of viral resistance associated variants to Sofosbuvir or Ledipasvir 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 for the Treatment of HCV (ION-3)
Official Title  ICMJE A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin for 8 Weeks and Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks in Treatment-Naive 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 in treatment-naive participants 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 90 mg/SOF 400 mg FDC tablet administered orally once daily
    Other Names:
    • Harvoni®
    • GS-5885/GS-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)
Study Arms  ICMJE
  • Experimental: LDV/SOF 8 Week
    Participants will receive LDV/SOF FDC for 8 weeks.
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF+RBV 8 Week
    Participants will receive LDV/SOF FDC plus RBV for 8 weeks.
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
  • Experimental: LDV/SOF 12 Week
    Participants will receive LDV/SOF FDC for 12 weeks.
    Intervention: Drug: LDV/SOF
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: March 10, 2014)
647
Original Estimated Enrollment  ICMJE
 (submitted: May 8, 2013)
600
Actual Study Completion Date  ICMJE March 2014
Actual Primary Completion Date December 2013   (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
  • 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
  • Presence of cirrhosis
  • Coinfection with HIV or hepatitis B virus (HBV)
  • Current or prior history of clinical hepatic decompensation
  • 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 NCT01851330
Other Study ID Numbers  ICMJE GS-US-337-0108
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: Robert H. Hyland, DPhil Gilead Sciences
PRS Account Gilead Sciences
Verification Date December 2014

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