Hepatitis C, Chronic
Conditions
Keywords
Hepatitis C, HCV, Rapid Virologic Response, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, HCV RNA, Polymerase inhibitor, Protease inhibitor, Treatment naïve, GS-9190, GS-9451
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®).
Interventions
DRUGCopegus®
ribavirin tablet (weight based: 1000 mg/day \<75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
DRUGTegobuvir (GS-9190)
Tegobuvir (GS-9190) capsule, 30 mg BID
DRUGGS-9451
GS-9451 tablet, 200 mg once daily (QD)
BIOLOGICALPegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week
DRUGTegobuvir placebo
placebo matching Tegobuvir (GS-9190) capsule BID
DRUGGS-9451 placebo
placebo matching GS-9451 tablet QD
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
Austria, Belgium, France, Germany, Netherlands, Poland, United Kingdom, United States
Outcome results
None listed