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

Phase 2
Completed
Conditions
Hepatitis C, Chronic
Interventions
Registration Number
NCT01353248
Lead Sponsor
Gilead Sciences
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
141
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1ribavirin tabletGS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 24 weeks.
Arm 1GS-5885GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 24 weeks.
Arm 2TegobuvirGS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 12 or 24 weeks.
Arm 2GS-9451GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 12 or 24 weeks.
Arm 2ribavirin tabletGS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 12 or 24 weeks.
Arm 2GS-5885GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 12 or 24 weeks.
Arm 1GS-9451GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 24 weeks.
Arm 1TegobuvirGS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 24 weeks.
Primary Outcome Measures
NameTimeMethod
Sustained virologic response (SVR)24 weeks of off-treatment follow-up
Secondary Outcome Measures
NameTimeMethod
HCV RNA < Lower Limit Of QuantificationWeeks 1, 2, 4, 12 and 24

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.

Emergence of viral resistance12 or 24 weeks

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.

Pharmacokinetics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBVThrough Week 2 of therapy

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

Rescue Therapy Substudy SVR24 Weeks

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.

Safety and tolerabilitythrough 24 weeks of off-treatment follow-up

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.

Viral dynamics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBVThrough Week 2 of therapy

HCV RNA levels, pharmacokinetics and viral sequencing

Trial Locations

Locations (43)

Baylor University Medical Center

🇺🇸

Dallas, Texas, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Digestive Health Specialists of the Southeast

🇺🇸

Dothan, Alabama, United States

UCSF Fresno Medical Education Program (MEP)

🇺🇸

Fresno, California, United States

Birmingham Gastroenterology Associates, P.C.

🇺🇸

Birmingham, Alabama, United States

Stanford University School of Medicine

🇺🇸

Palo Alto, California, United States

Advanced Clinical Research Institute

🇺🇸

Anaheim, California, United States

Fundacion de Investigacion de Diego

🇵🇷

San Juan, Puerto Rico

Borland-Groover Clinic

🇺🇸

Jacksonville, Florida, United States

Kaiser Permanente

🇺🇸

San Diego, California, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

Nashville Gastrointestinal Specialists, Inc

🇺🇸

Nashville, Tennessee, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Lifetree Clinical Research, LC

🇺🇸

Salt Lake City, Utah, United States

Columbia Medical Group, The Frist Clinic

🇺🇸

Nashville, Tennessee, United States

Orlando Immunology Center

🇺🇸

Orlando, Florida, United States

Southern California Liver Centers

🇺🇸

Coronado, California, United States

Walter Reed Army Medical Center

🇺🇸

Washington, District of Columbia, United States

UCSF

🇺🇸

San Francisco, California, United States

Bach and Godofsky Infectious Diseases

🇺🇸

Bradenton, Florida, United States

University of Florida - Gainesville

🇺🇸

Gainesville, Florida, United States

University of Miami School of Medicine

🇺🇸

Miami, Florida, United States

Gastrointestinal Specialists of Georgia PC

🇺🇸

Marietta, Georgia, United States

Orlando Clinical Research Center

🇺🇸

Orlando, Florida, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Johns Hopkins University

🇺🇸

Lutherville, Maryland, United States

University of New Mexico

🇺🇸

Albuquerque, New Mexico, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Mount Sinai Medical Center

🇺🇸

New York, New York, United States

Gastrointestinal Associates, PA

🇺🇸

Jackson, Mississippi, United States

Options Health Research, LLC

🇺🇸

Tulsa, Oklahoma, United States

University of Pennsylvania Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

Gastro One

🇺🇸

Germantown, Tennessee, United States

Memphis Gastroenterology Group

🇺🇸

Germantown, Tennessee, United States

Research Specialists of Texas

🇺🇸

Houston, Texas, United States

Alamo Medical Research

🇺🇸

San Antonio, Texas, United States

Inova Fairfax Hospital - Center for Liver Diseases

🇺🇸

Falls Church, Virginia, United States

Liver Institute of Virginia, Bon Secours Health System

🇺🇸

Newport News, Virginia, United States

Private Practice

🇺🇸

Opelousas, Louisiana, United States

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

University of California San Diego

🇺🇸

San Diego, California, United States

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