Hepatitis C, Chronic
Conditions
Keywords
Hepatitis C, HCV, Rapid Virologic Response, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy HCV RNA, Protease inhibitor, Treatment naïve, GS-5885, GS-9451
Brief summary
This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy with GS-5885 Alone or in Combination with GS-9451 with Peginterferon Alfa 2a and Ribavirin in Treatment Naïve Subjects with Chronic Genotype 1 Hepatitis C Virus Infection.
Interventions
DRUGGS-5885
tablet, 30 mg QD
DRUGGS-9451
tablet, 200 mg QD
BIOLOGICALpeginterferon alfa-2a
(solution for injection) 180 µg/week
DRUGribavirin tablet
ribavirin tablet (weight based: 1000 mg/day \<75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
DRUGGS-9451 Placebo
Placebo to match GS-9451 QD
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Males and females 18-70 years of age * Chronic HCV infection * Subjects must have liver biopsy results (≤ 2 years prior to Screening) indicating the absence of cirrhosis. * Monoinfection with HCV genotype 1 * HCV RNA \> 10\^4 IU/mL at Screening * HCV treatment naïve * Candidate for PEG/RBV therapy * Body mass index (BMI) 18-36 kg/m2, inclusive * Agree to use two forms of highly effective contraception methods for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline.
Exclusion criteria
* Pregnant female or male with pregnant female partner * Exceed defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH) * Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed. * Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Patients on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to Screening may be included into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the antiviral efficacy of response guided therapy. | Through 24 weeks post-treatment | To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as plasma HCV RNA \< Lower Limit of Quantification (LLoQ) at 24 weeks post-treatment) of response guided therapy (RGT) with GS-5885 + GS-9451 + PEG/RBV, or GS-5885 + PEG/RBV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety and tolerability of each regimen. | Through 24 weeks post-treatment | The primary safety endpoint is any AE leading to permanent discontinuation of study drugs. |
| To characterize viral dynamics of GS-5885 and GS-9451 when administered with PEG and RBV. | Through Day 10 on study | HCV RNA levels, pharmacokinetics and viral sequencing |
| To characterize the viral resistance to GS-5885 and GS-9451 when administered in combination with PEG and RBV. | 12 or 24 weeks | Plasma samples will be collected and stored at each visit for possible resistance analysis. |
| To characterize steady state pharmacokinetics of GS-5885 and GS-9451 when administered with PEG and RBV. | Through 48 weeks of treatment | Plasma concentrations of the study drug over time will be summarized using descriptive statistics. |
Countries
Australia, Puerto Rico, United States
Outcome results
None listed