Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin for the Treatment of HCV (ION-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01768286
First received: January 10, 2013
Last updated: April 23, 2014
Last verified: April 2014

January 10, 2013
April 23, 2014
January 2013
November 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 drug.
  • Incidence of adverse events leading to permanent discontinuation of study drug(s) [ Time Frame: Up to 24 weeks ] [ 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: No ]
    Frequency and severity of adverse events
Complete list of historical versions of study NCT01768286 on ClinicalTrials.gov Archive Site
  • Proportion 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 ] [ Designated as safety issue: No ]
    SVR4 and SVR24 are defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
  • Proportion of participants with HCV RNA < LLOQ on treatment [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
  • Change in HCV RNA from Baseline [ Time Frame: Baseline to 8 weeks of treatment ] [ Designated as safety issue: No ]
  • Proportion of participants with virologic failure [ Time Frame: Baseline to posttreatment Week 24 ] [ Designated as safety issue: No ]

    Virologic failure is defined as:

    • Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (note: second confirmation value can be posttreatment), or last available on-treatment measurement with no subsequent follow up values, OR
    • Rebound: > 1 log10IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (note: second confirmation value can be posttreatment), or last available on-treatment measurement with no subsequent follow up values, OR
    • Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment, OR
    • Relapse: 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
  • Sustained virologic response after discontinuation of therapy [ Time Frame: 4 and 24 weeks after discontinuation of therapy ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ 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 steady state pharmacokinetics of sofosbuvir and GS-5885 [ 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 Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin for the Treatment of HCV
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis C Virus
  • Drug: Ledipasvir/sofosbuvir
    Ledipasvir 90 mg/sofosbuvir 400 mg FDC tablet administered orally once daily
    Other Names:
    • Sofosbuvir is also known as GS-7977, PSI-7977, or Sovaldi®
    • Ledipasvir is also known as GS-5885.
  • 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: Ledipasvir/sofosbuvir 24 Weeks
    Participants will receive ledipasvir/sofosbuvir FDC for 24 weeks.
    Intervention: Drug: Ledipasvir/sofosbuvir
  • Experimental: Ledipasvir/sofosbuvir+RBV 24 Weeks
    Participants will receive ledipasvir/sofosbuvir FDC plus RBV for 24 weeks.
    Interventions:
    • Drug: Ledipasvir/sofosbuvir
    • Drug: RBV
  • Experimental: Ledipasvir/sofosbuvir 12 Weeks
    Participants will receive ledipasvir/sofosbuvir FDC for 12 weeks.
    Intervention: Drug: Ledipasvir/sofosbuvir
  • Experimental: Ledipasvir/sofosbuvir+RBV 12 Weeks
    Participants will receive ledipasvir/sofosbuvir FDC plus RBV for 12 weeks.
    Interventions:
    • Drug: Ledipasvir/sofosbuvir
    • Drug: RBV
Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P; ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014 Apr 17;370(16):1483-93. doi: 10.1056/NEJMoa1316366. Epub 2014 Apr 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
441
February 2014
November 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age> 18, with chronic genotype 1 HCV infection
  • HCV treatment-experienced, including patients who have previously failed a NS3/4A Protease Inhibitor plus 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
  • 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01768286
GS-US-337-0109
Yes
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Jenny Yang, PharmD Gilead Sciences
Gilead Sciences
April 2014

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