Chronic Hepatitis C
Conditions
Keywords
Chronic Hepatitis C, IL28B CC Genotype, Treatment naive, Peginterferon α-2a (PEG), Genotype 1a/b, GS 9451, GS 5885, Ribavirin (RBV), HCV NS5A inhibitor, HCV NS3 protease inhibitor
Brief summary
This is a Phase 2, randomized, open-label exploratory study that will examine the antiviral efficacy, safety, and tolerability of Response guided treatment (RGT) with GS-5885 + GS-9451 + PEG/RBV (6 or 12 weeks), or Peginterferon Alfa 2a (PEG)/Ribavirin (RBV)alone (24 weeks) in treatment naïve subjects with chronic Hep C (HCV) infection with genotype (GT) 1 and IL28B CC genotype.
Interventions
DRUGGS-5885
GS-5885 30 mg tablet administered orally once daily
DRUGGS-9451
GS-9451 200 mg tablet administered orally once daily
DRUGRBV
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)
DRUGPEG
Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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 (≤ 3 years prior to screening) indicating the absence of cirrhosis. Alternatively a non-invasive alternative to liver biopsy (such as FibroTest, FibroScan, or Acoustic Radiation Force Impulse imaging) within 6 months of Screening in countries where allowed * Monoinfection with HCV genotype 1a or 1b * HCV RNA \> 10\^4 IU/mL at Screening * IL28B CC genotype * HCV treatment naïve * Candidate for PEG/RBV therapy * Body mass index (BMI) between 18 and 36 kg/m2 * Creatinine clearance \>= 50 mL/min * Agree to use two forms of highly effective contraception methods for the duration of the study and for 7 months after the last dose study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline
Exclusion criteria
* Exceed defined thresholds for key laboratory parameters at Screening * 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 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. Subjects on stable methadone maintenance treatment for at least 6 months prior to Screening may be included into the study * Use of prohibited concomitant medications two weeks prior to baseline through the end of treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained virologic response (SVR) | 30 , 36 or 48 weeks | Sustained virologic response (SVR, defined as plasma HCV RNA \< lower limit of quantification \[LLoQ\] at 24 weeks after treatment cessation) following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 or 12 weeks, or PEG/RBV for 24 weeks in IL28B CC subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare SVR | Weeks 30 and 36 | Compare SVR following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 weeks versus 12 weeks. |
| Safety and tolerability of therapy | Up to 48 weeks | Safety and tolerability of the therapy is measured by frequency of laboratory abnormalities , reported adverse events and discontinuations due to adverse events. |
| Virologic response | Weeks 2, 4, 6, 8, 10, and 12 | Virologic response at Weeks 2, 4, 6, 8, 10, and 12 (depending on treatment arm) as measured by the rates of HCV RNA \< LLoQ and viral breakthrough and relapse |
| Viral resistance | Up to 96 Weeks | Characterize viral resistance to GS-5885 and GS-9451 when administered in combination with PEG/RBV |
Countries
Australia, Canada, New Zealand, United States
Outcome results
None listed