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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01768286
First received: January 10, 2013
Last updated: November 21, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C Virus
Drug: LDV/SOF
Drug: RBV
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.


Secondary Outcome Measures:
  • Percentage of Participants With SVR 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 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 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change From Baseline in HCV RNA at Week 1 [ Time Frame: Baseline; Week 1 ] [ Designated as safety issue: No ]
  • Change From Baseline in HCV RNA at Week 2 [ Time Frame: Baseline; Week 2 ] [ Designated as safety issue: No ]
  • Change From Baseline in HCV RNA at Week 4 [ Time Frame: Baseline; Week 4 ] [ Designated as safety issue: No ]
  • Change From Baseline in HCV RNA at Week 8 [ Time Frame: Baseline; Week 8 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Virologic Failure [ Time Frame: Baseline to posttreatment Week 24 ] [ Designated as safety issue: No ]

    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.



Enrollment: 441
Study Start Date: January 2013
Study Completion Date: February 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDV/SOF 12 Weeks
Participants will receive LDV/SOF FDC for 12 weeks.
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
Experimental: LDV/SOF+RBV 12 Weeks
Participants will receive LDV/SOF FDC plus RBV for 12 weeks.
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)
Experimental: LDV/SOF 24 Weeks
Participants will receive LDV/SOF FDC for 24 weeks.
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
Experimental: LDV/SOF+RBV 24 Weeks
Participants will receive LDV/SOF FDC plus RBV for 24 weeks.
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01768286

  Show 53 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Jenny Yang, PharmD Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01768286     History of Changes
Other Study ID Numbers: GS-US-337-0109
Study First Received: January 10, 2013
Results First Received: November 21, 2014
Last Updated: November 21, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Gilead Sciences:
HCV genotype 1 (GT-1)
HCV
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy
GS-7977
GS-5885
Ribavirin
Open Label
Sofosbuvir
Additional relevant MeSH terms:
Hepatitis
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Additional relevant MeSH terms:
Communicable Diseases
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Infection
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Molecular Mechanisms of Pharmacological Action
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014