A Study of Response-Guided Duration of Combination Therapy With GS-9451, Pegasys® and Copegus® With and Without Tegobuvir (GS-9190) in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C
Phase 2
Completed
- Conditions
- Hepatitis C, Chronic
- Interventions
- Drug: GS-9451 placeboBiological: Pegasys®
- Registration Number
- NCT01271790
- Lead Sponsor
- Gilead Sciences
- Brief Summary
This phase 2b study will evaluate the efficacy and safety of 16 and 24 weeks of a 4-drug regimen with GS-9451 and Tegobuvir and 24 weeks of a 3-drug regimen of GS-9451 without Tegobuvir, all with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 245
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 for alanine aminotransferase (ALT), aspartate aminotransferase (AST), leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH), potassium, magnesium
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 who are on or are expected to be on a potent cytochrome P450 (CYP) 3A4 or Pgp inhibitor, or a QT prolonging medication within 2 weeks of Baseline (Day 1) or during the study
- 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
Group Intervention Description Arm 2 Tegobuvir placebo GS-9451 (active) and Tegobuvir (GS-9190) placebo in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 1 Copegus® GS-9451 and Tegobuvir (GS-9190) in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 2 GS-9451 GS-9451 (active) and Tegobuvir (GS-9190) placebo in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 2 Pegasys® GS-9451 (active) and Tegobuvir (GS-9190) placebo in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 2 Copegus® GS-9451 (active) and Tegobuvir (GS-9190) placebo in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 3 Tegobuvir placebo Placebo matching Tegobuvir (GS-9190) and GS-9451 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration Arm 3 GS-9451 placebo Placebo matching Tegobuvir (GS-9190) and GS-9451 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration Arm 3 Pegasys® Placebo matching Tegobuvir (GS-9190) and GS-9451 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration Arm 1 Tegobuvir (GS-9190) GS-9451 and Tegobuvir (GS-9190) in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 1 Pegasys® GS-9451 and Tegobuvir (GS-9190) in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 3 Copegus® Placebo matching Tegobuvir (GS-9190) and GS-9451 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration Arm 1 GS-9451 GS-9451 and Tegobuvir (GS-9190) in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
- Primary Outcome Measures
Name Time Method Sustained virologic response 24 weeks of off-treatment follow-up Sustained virologic response (SVR) defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after treatment cessation
- Secondary Outcome Measures
Name Time Method Safety and tolerability of therapy Through treatment period and 24 weeks of off-treatment follow-up Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events
Emergence of viral resistance following initiation of therapy with GS 9190 and GS 9451 Through treatment period, 24 weeks of off-treatment follow-up, and up to 48 weeks of follow-up in the Resistance Registry Substudy Viral dynamics and steady state pharmacokinetics Through Week 4 of therapy Viral dynamics and steady state pharmacokinetics of GS 9190 and GS 9451 when administered in combination with PEG and RBV; measured by HCV RNA levels and plasma concentrations of GS-9190 and GS-9451 over time
Durability of response in subjects who achieve SVR 36 months following Week 72
Trial Locations
- Locations (142)
Digestive Health Specialists of the Southeast
🇺🇸Dothan, Alabama, United States
Alabama Liver and Digestive Specialists
🇺🇸Montgomery, Alabama, United States
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
Pacific Oaks Medical Group
🇺🇸Beverly Hills, California, United States
eStudySite
🇺🇸Oceanside, California, United States
Scripps Clinic
🇺🇸La Jolla, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Synergy Clinical Research Center
🇺🇸National City, California, United States
RESEARCH and EDUCATION, INC
🇺🇸San Diego, California, United States
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