GS 5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) in Chronic Genotype 1 Hepatitis C Virus (HCV) Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01353248
First received: April 22, 2011
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

The purpose of this phase 2 study is to determine whether 30 mg or 90 mg of GS-5885 when given with GS-9451, Tegobuvir and Ribavirin (RBV) for 12 or 24 weeks is effective, safe and tolerable in the treatment of Chronic Genotype 1 HCV Infection.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: GS-5885
Drug: Tegobuvir
Drug: GS-9451
Drug: ribavirin tablet
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Open-Label Study of GS-5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) to Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Sustained virologic response (SVR) [ Time Frame: 24 weeks of off-treatment follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability [ Time Frame: through 24 weeks of off-treatment follow-up ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of 30 mg or 90 mg GS-5885 when given with GS-9451, Tegobuvir and RBV for 12 or 24 weeks. Safety endpoints will be analyzed by the number and percent of subjects with events or abnormalities for categorical values or 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment group.

  • HCV RNA < Lower Limit Of Quantification [ Time Frame: Weeks 1, 2, 4, 12 and 24 ] [ Designated as safety issue: No ]
    To evaluate the antiviral efficacy at Weeks 1, 2, 4, 12 and 24, as measured by the rates of HCV RNA < LLoQ and viral breakthrough and relapse.

  • Rescue Therapy Substudy SVR [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    To evaluate the antiviral efficacy (as defined by SVR) of the addition of pegylated interferon (PEG) for 24 weeks to GS-5885, GS-9451, tegobuvir and RBV in subjects who experience viral breakthrough on treatment.

  • Emergence of viral resistance [ Time Frame: 12 or 24 weeks ] [ Designated as safety issue: No ]
    To evaluate the emergence of viral resistance during treatment with GS-9451, Tegobuvir and RBV when given with 30 mg or 90 mg GS-5885 for 12 or 24 weeks.

  • Viral dynamics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV [ Time Frame: Through Week 2 of therapy ] [ Designated as safety issue: No ]
    HCV RNA levels, pharmacokinetics and viral sequencing

  • Pharmacokinetics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV [ Time Frame: Through Week 2 of therapy ] [ Designated as safety issue: No ]

    Pharmacokinetics (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed

    and summarized for GS-5885, GS-9451 and Tegobuvir using descriptive statistics (e.g.,

    sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation,

    median, minimum, and maximum). Plasma concentrations of the study drug over time will be

    summarized using descriptive statistics



Enrollment: 141
Study Start Date: May 2011
Study Completion Date: March 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 24 weeks.
Drug: GS-5885
tablet, 30 mg QD
Drug: Tegobuvir
capsule, 30 mg BID
Drug: GS-9451
tablet, 200 mg QD
Drug: 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 and Tegobuvir in combination with ribavirin (Copegus®) for 12 or 24 weeks.
Drug: Tegobuvir
capsule, 30 mg BID
Drug: GS-9451
tablet, 200 mg QD
Drug: ribavirin tablet
(weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
Drug: GS-5885
tablet, 90 mg QD

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult subjects 18 to 70 years of age
  • Chronic HCV infection for at least 6 months prior to Baseline (Day 1)
  • Liver biopsy results (performed no more than 2 years prior to Screening) indicating the absence of cirrhosis
  • Monoinfection with HCV genotype 1a or 1b
  • HCV treatment-naïve
  • Body mass index (BMI) between 18 and 36 kg/m2
  • Creatinine clearance ≥ 50 mL/min
  • Subject agrees to use highly effective contraception methods if female of childbearing potential or sexually active male.
  • Screening laboratory values within defined thresholds

Exclusion Criteria:

  • Autoimmune disease
  • Decompensated liver disease or cirrhosis
  • Poorly controlled diabetes mellitus
  • Severe psychiatric illness
  • Severe chronic obstructive pulmonary disease (COPD)
  • Serological evidence of co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype
  • Suspicion of hepatocellular carcinoma or other malignancy (with exception of certain skin cancers)
  • History of hemoglobinopathy
  • Known retinal disease
  • Subjects who are immunosuppressed
  • Subjects with known, current use of amphetamines, cocaine, opiates (i.e., morphine, heroin), methadone, or ongoing alcohol abuse
  • Subjects must have no history of clinically significant cardiac disease, including a family history of Long QT syndrome, and no relevant electrocardiogram (ECG) abnormalities at screening
  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: NCT01353248

  Hide Study Locations
Locations
United States, Alabama
Birmingham Gastroenterology Associates, P.C.
Birmingham, Alabama, United States, 35209
Digestive Health Specialists of the Southeast
Dothan, Alabama, United States, 36305
United States, California
Advanced Clinical Research Institute
Anaheim, California, United States, 92801
Southern California Liver Centers
Coronado, California, United States, 92118
UCSF Fresno Medical Education Program (MEP)
Fresno, California, United States, 93721
Stanford University School of Medicine
Palo Alto, California, United States, 94304
University of California San Diego
San Diego, California, United States, 92103
Kaiser Permanente
San Diego, California, United States, 92154
UCSF
San Francisco, California, United States, 94143
United States, District of Columbia
Walter Reed Army Medical Center
Washington, District of Columbia, United States, 20307
United States, Florida
Bach and Godofsky Infectious Diseases
Bradenton, Florida, United States, 34209
University of Florida - Gainesville
Gainesville, Florida, United States, 32610
Borland-Groover Clinic
Jacksonville, Florida, United States, 32256
University of Miami School of Medicine
Miami, Florida, United States, 33136
Orlando Clinical Research Center
Orlando, Florida, United States, 32809
Orlando Immunology Center
Orlando, Florida, United States, 32803
United States, Georgia
Gastrointestinal Specialists of Georgia PC
Marietta, Georgia, United States, 30060
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Private Practice
Opelousas, Louisiana, United States, 70570
United States, Maryland
Johns Hopkins University
Lutherville, Maryland, United States, 21093
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Mississippi
Gastrointestinal Associates, PA
Jackson, Mississippi, United States, 39202
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7584
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Oklahoma
Options Health Research, LLC
Tulsa, Oklahoma, United States, 74104
United States, Pennsylvania
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Gastro One
Germantown, Tennessee, United States, 38138
Memphis Gastroenterology Group
Germantown, Tennessee, United States, 38138
Columbia Medical Group, The Frist Clinic
Nashville, Tennessee, United States, 37203
Nashville Gastrointestinal Specialists, Inc
Nashville, Tennessee, United States, 37211
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
Research Specialists of Texas
Houston, Texas, United States, 77030
Alamo Medical Research
San Antonio, Texas, United States, 78215
United States, Utah
Lifetree Clinical Research, LC
Salt Lake City, Utah, United States, 84106
United States, Virginia
Inova Fairfax Hospital - Center for Liver Diseases
Falls Church, Virginia, United States, 22042
Liver Institute of Virginia, Bon Secours Health System
Newport News, Virginia, United States, 23602
Puerto Rico
Fundacion de Investigacion de Diego
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Benedetta Massetto, MD, PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01353248     History of Changes
Other Study ID Numbers: GS-US-248-0120
Study First Received: April 22, 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
HCV RNA
Polymerase inhibitor
Protease inhibitor
Treatment naïve
GS-5885
GS-9451
Tegobuvir

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

ClinicalTrials.gov processed this record on September 18, 2014