A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating 16 and 24 Weeks of Four-Drug Regimen and 24 Weeks of a Three-Drug Regimen of GS-9451, Peginterferon Alfa 2a (PEG, Pegasys®) and Ribavirin (RBV, Copegus®) With and Without Tegobuvir (GS-9190) Followed by Response Guided PEG and RBV in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS US 196 0140
Overview
- Phase
- Phase 2
- Intervention
- Tegobuvir (GS-9190)
- Conditions
- Hepatitis C, Chronic
- Sponsor
- Gilead Sciences
- Enrollment
- 245
- Locations
- 142
- Primary Endpoint
- Sustained virologic response
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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®).
Investigators
Eligibility 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 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
Arms & Interventions
Arm 1
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
Intervention: Tegobuvir (GS-9190)
Arm 1
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
Intervention: GS-9451
Arm 1
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
Intervention: Pegasys®
Arm 1
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
Intervention: Copegus®
Arm 2
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
Intervention: GS-9451
Arm 2
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
Intervention: Tegobuvir placebo
Arm 2
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
Intervention: Pegasys®
Arm 2
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
Intervention: Copegus®
Arm 3
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
Intervention: Tegobuvir placebo
Arm 3
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
Intervention: GS-9451 placebo
Arm 3
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
Intervention: Pegasys®
Arm 3
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
Intervention: Copegus®
Outcomes
Primary Outcomes
Sustained virologic response
Time Frame: 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 Outcomes
- Safety and tolerability of therapy(Through treatment period and 24 weeks of off-treatment follow-up)
- 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)
- Durability of response in subjects who achieve SVR(36 months following Week 72)