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-5885, GS-9451, Tegobuvir
Brief summary
The purpose of this phase 2 study is to determine whether 30 mg or 90 mg of GS-5885 when given with GS-9451, Tegobuvir and Ribavirin (RBV) for 12 or 24 weeks is effective, safe and tolerable in the treatment of Chronic Genotype 1 HCV Infection.
Interventions
DRUGGS-5885
tablet, 30 mg QD
DRUGTegobuvir
capsule, 30 mg BID
DRUGGS-9451
tablet, 200 mg QD
DRUGribavirin tablet
(weight based: 1000 mg/day \<75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
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
* 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
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 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 |
|---|---|
| Sustained virologic response (SVR) | 24 weeks of off-treatment follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | through 24 weeks of off-treatment follow-up | To evaluate the safety and tolerability of 30 mg or 90 mg GS-5885 when given with GS-9451, Tegobuvir and RBV for 12 or 24 weeks. Safety endpoints will be analyzed by the number and percent of subjects with events or abnormalities for categorical values or 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment group. |
| HCV RNA < Lower Limit Of Quantification | Weeks 1, 2, 4, 12 and 24 | To evaluate the antiviral efficacy at Weeks 1, 2, 4, 12 and 24, as measured by the rates of HCV RNA \< LLoQ and viral breakthrough and relapse. |
| Rescue Therapy Substudy SVR | 24 Weeks | To evaluate the antiviral efficacy (as defined by SVR) of the addition of pegylated interferon (PEG) for 24 weeks to GS-5885, GS-9451, tegobuvir and RBV in subjects who experience viral breakthrough on treatment. |
| Emergence of viral resistance | 12 or 24 weeks | To evaluate the emergence of viral resistance during treatment with GS-9451, Tegobuvir and RBV when given with 30 mg or 90 mg GS-5885 for 12 or 24 weeks. |
| Viral dynamics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV | Through Week 2 of therapy | HCV RNA levels, pharmacokinetics and viral sequencing |
| Pharmacokinetics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV | Through Week 2 of therapy | Pharmacokinetics (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed and summarized for GS-5885, GS-9451 and Tegobuvir using descriptive statistics (e.g., sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and maximum). Plasma concentrations of the study drug over time will be summarized using descriptive statistics |
Countries
Puerto Rico, United States
Outcome results
None listed