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
  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: Ledipasvir/sofosbuvir
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:
  • 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 ]

Secondary Outcome Measures:
  • 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


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: Ledipasvir/sofosbuvir 24 Weeks
Participants will receive ledipasvir/sofosbuvir FDC for 24 weeks.
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.
Experimental: Ledipasvir/sofosbuvir+RBV 24 Weeks
Participants will receive ledipasvir/sofosbuvir FDC plus RBV for 24 weeks.
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 12 Weeks
Participants will receive ledipasvir/sofosbuvir FDC for 12 weeks.
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.
Experimental: Ledipasvir/sofosbuvir+RBV 12 Weeks
Participants will receive ledipasvir/sofosbuvir FDC plus RBV for 12 weeks.
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)

  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 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
  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

  Hide Study Locations
Locations
United States, Arizona
Phoenix, Arizona, United States
Tuscon, Arizona, United States, 94404
United States, California
La Jolla, California, United States
Los Angeles, California, United States
Palo Alto, California, United States
San Diego, California, United States
San Francisco, California, United States
United States, Colorado
Aurora, Colorado, United States
Englewood, Colorado, United States
United States, District of Columbia
Washington DC, District of Columbia, United States
United States, Florida
Gainesville, Florida, United States
Jacksonville, Florida, United States
Miami, Florida, United States
Orlando, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
Marietta, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Kentucky
Bowling Green, Kentucky, United States
United States, Louisiana
Baton Rouge, Louisiana, United States
United States, Maryland
Baltimore, Maryland, United States
Lutherville, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
Springfield, Massachusetts, United States
United States, Michigan
Detroit, Michigan, United States
United States, Minnesota
Rochester, Minnesota, United States
St. Louis, Minnesota, United States
St. Paul, Minnesota, United States
United States, Missouri
Kansas City, Missouri, United States
United States, New Jersey
Berlin, New Jersey, United States
Hillsborough, New Jersey, United States
United States, New Mexico
Alburquerque, New Mexico, United States
Santa Fe, New Mexico, United States
United States, New York
Binghampton, New York, United States
Manhasset, New York, United States
New York, New York, United States
United States, North Carolina
Asheville, North Carolina, United States
Charlotte, North Carolina, United States
Durham, North Carolina, United States
Fayetteville, North Carolina, United States
Statesville, North Carolina, United States
Winston-Salem, North Carolina, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Rhode Island
Providence, Rhode Island, United States
United States, Tennessee
Germantown, Tennessee, United States
Nashville, Tennessee, United States
United States, Texas
Arlington, Texas, United States
Dallas, Texas, United States
Houston, Texas, United States
San Antonio, Texas, United States
United States, Virginia
Fairfax, Virginia, United States
Newport News, Virginia, United States
Norfolk, Virginia, United States
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
Last Updated: April 23, 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:
Hepatitis
Hepatitis A
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
Anti-Infective Agents
Ribavirin
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Antimetabolites

ClinicalTrials.gov processed this record on July 29, 2014