GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) in Interferon Ineligible or Intolerant Subjects With Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01434498
First received: September 9, 2011
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin; GS-5885, GS-9451 and Tegobuvir; GS-5885, GS-9451 and Ribavirin in Interferon Ineligible or Intolerant Subjects with Chronic Genotype 1a or 1b HCV Infection.


Condition Intervention Phase
Chronic Genotype 1a or 1b HCV Infection
Drug: GS-5885 tablet
Drug: GS-9451 tablet
Drug: tegobuvir capsule
Drug: ribavirin tablet
Drug: placebo matching ribavirin tablet
Device: placebo matching tegobuvir capsule
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin; GS-5885, GS-9451 and Tegobuvir; GS-5885, GS-9451 and Ribavirin in Interferon Ineligible or Intolerant Subjects With Chronic Genotype 1a or 1b HCV Infection (Protocol No. GS US 248 0132)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Safety and Tolerability [ Time Frame: Through 24 weeks of off-treatment follow-up ] [ Designated as safety issue: Yes ]
    To evaluate safety and tolerability of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin. Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study.

  • Antiviral Activity [ Time Frame: Through 24 weeks of off-treatment follow-up ] [ Designated as safety issue: No ]
    To evaluate antiviral efficacy as measured by sustained virologic response (defined as HCV RNA < lower limit of quantitation 24-weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin.


Secondary Outcome Measures:
  • Viral Dynamics [ Time Frame: Through 10 days of therapy ] [ Designated as safety issue: No ]
    To characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 10 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir.

  • Composite (or Profile) of Pharmacokinetics [ Time Frame: predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose ] [ Designated as safety issue: No ]
    To characterize the steady state pharmacokinetics of GS-5885, GS-9451, tegobuvir and ribavirin (if appropriate). Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau and T ½


Enrollment: 163
Study Start Date: September 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
GS-5885, GS-9451, tegobuvir (GS-9190), and Copegus® for 24 weeks
Drug: GS-5885 tablet
GS-5885 tablet, 90 mg, QD
Drug: GS-9451 tablet
GS-9451 tablet, 200 mg QD
Drug: tegobuvir capsule
tegobuvir capsule, 30 mg BID
Drug: ribavirin tablet
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
Active Comparator: Arm 2
GS-5885, GS-9451, tegobuvir (GS-9190), and a placebo matching ribavirin for 24 weeks
Drug: GS-5885 tablet
GS-5885 tablet, 90 mg, QD
Drug: GS-9451 tablet
GS-9451 tablet, 200 mg QD
Drug: tegobuvir capsule
tegobuvir capsule, 30 mg BID
Drug: placebo matching ribavirin tablet
placebo matching ribavirin tablet, BID
Active Comparator: Arm 3
GS-5885, GS-9451, a placebo matching tegobuvir, and Copegus® for 24 weeks
Drug: GS-5885 tablet
GS-5885 tablet, 90 mg, QD
Drug: GS-9451 tablet
GS-9451 tablet, 200 mg QD
Drug: ribavirin tablet
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
Device: placebo matching tegobuvir capsule
placebo matching tegobuvir capsule, BID

  Eligibility

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

Inclusion Criteria:

  • Adult subjects 18 and older with chronic HCV infection
  • Liver biopsy results (performed no more than 3 years prior to Screening) indicating the absence of cirrhosis
  • Monoinfection with HCV genotype 1a or 1b
  • Interferon ineligible or intolerant
  • Body mass index (BMI) between 18 and 40 kg/m2
  • Use of highly effective contraception methods if female of childbearing potential or sexually active male
  • Screening laboratory values within defined thresholds
  • Has not been exposed to any investigational drug or device within 30 days of the Screening visit
  • Able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments

Exclusion Criteria:

  • Prior treatment of HCV with any direct-acting antiviral (whether approved or experimental)
  • Decompensated liver disease or cirrhosis
  • Co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype
  • History of difficulty with blood collection and/or poor venous access
  • Pregnant or nursing female or male with pregnant female partner
  • Chronic liver disease of a non-HCV etiology
  • Suspicion of hepatocellular carcinoma
  • Clinically-relevant drug abuse
  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: NCT01434498

  Hide Study Locations
Locations
United States, California
California Liver Institute
Beverly Hills, California, United States, 90211
SCTI Research Foundation Liver Center
Coronado, California, United States, 92118
Scripps Clinic
La Jolla, California, United States, 92037
University of California, San Diego
La Jolla, California, United States, 92161
Kaiser Permanente Medical Center
Los Angeles, California, United States, 90027
Lightsource Medical
Los Angeles, California, United States, 90036
Medical Associates Research Group, Inc.
San Diego, California, United States, 92123
Kaiser Permanente
San Diego, California, United States, 92154
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Florida
University of Miami, Center for Liver Diseases
Miami, Florida, United States, 33136
Orlando Immunology Center (ACH)
Orlando, Florida, United States, 32803-1851
United States, Georgia
Gastrointestinal Specialists of Georgia, PC
Marietta, Georgia, United States, 30060
United States, Indiana
Indianapolis Gastroenterology Research Foundation
Indianapolis, Indiana, United States, 46237
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Johns Hopkins University
Lutherville, Maryland, United States, 21093
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deconess Medical Center
Boston, Massachusetts, United States, 02215
The Research Institute
Springfield, Massachusetts, United States, 01105
United States, Michigan
Henry Ford Health System
Novi, Michigan, United States, 48377
United States, New Jersey
Saint Michael's Medical Center
Newark, New Jersey, United States, 07102
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
United States, North Carolina
Asheville Gastroenterology Associates, P.A.
Asheville, North Carolina, United States, 28801
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
United States, Rhode Island
University Gastroenterology
Providence, Rhode Island, United States, 02905
United States, Tennessee
Gastro One
Germantown, Tennessee, United States, 38138
United States, Texas
The North Texas Research Institute
Arlington, Texas, United States, 76012
The University of Texas Medical Branch
Galveston, Texas, United States, 77555
The University of Texas Health Sciences Center at Houston
Houston, Texas, United States, 77030
Alamo Medical Research
San Antonio, Texas, United States, 78215
United States, Virginia
Inova Fairfax Hospital Center for Liver Diseases
Falls Church, Virginia, United States, 22042
Bon Secours St. Mary's Hospital of Richmond, Inc.
Newport News, Virginia, United States, 23602
Digestive and Liver Disease Specialists
Norfolk, Virginia, United States, 23502
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N 4Z6
University of Alberta
Edmonton, Alberta, Canada, T6G 2X8
University Of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2C8
Canada, British Columbia
GIRI GI Research Institute
Vancouver, British Columbia, Canada, V6Z 2K5
University of British Columbia
Vancouver, British Columbia, Canada, V6Z 2C9
Gordon & Leslie Diamond Health Care Centre
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Manitoba
University of Manitoba
Winnipeg, Manitoba, Canada, R3E 3P4
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A 5A5
The Ottawa Hospital
Ottawa, Ontario, Canada, K1H 8L6
Toronto General Hospital, University Health Network
Toronto, Ontario, Canada, M5G 2N2
Toronto General Hospital, University Health Network
Toronto, Ontario, Canada, M5G 2C4
Toronto Western Hospital
Toronto, Ontario, Canada, M5T2S8
Canada, Quebec
Hospital Saint-Luc DU CHUM
Montreal, Quebec, Canada, H2X3J4
Puerto Rico
Clinical Research Puerto Rico Inc
San Juan, Puerto Rico, 00909-1711
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: John McNally, PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01434498     History of Changes
Other Study ID Numbers: GS-US-248-0132
Study First Received: September 9, 2011
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Hepatitis C
HCV
Rapid Virologic Response
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy
Tegobuvir
Treatment naïve
HCV RNA
Polymerase inhibitor
Protease inhibitor
Interferon intolerant
Interferon ineligible
GS-9190
GS-9451
GS-5885

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

ClinicalTrials.gov processed this record on August 21, 2014