Chronic Genotype 1a or 1b HCV Infection
Conditions
Keywords
Hepatitis C, HCV, Rapid Virologic Response, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, Tegobuvir, Treatment naïve, HCV RNA, Polymerase inhibitor, Protease inhibitor, Interferon intolerant, Interferon ineligible, GS-9190, GS-9451, GS-5885
Brief summary
This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin; GS-5885, GS-9451 and Tegobuvir; GS-5885, GS-9451 and Ribavirin in Interferon Ineligible or Intolerant Subjects with Chronic Genotype 1a or 1b HCV Infection.
Interventions
DRUGGS-5885 tablet
GS-5885 tablet, 90 mg, QD
DRUGGS-9451 tablet
GS-9451 tablet, 200 mg QD
DRUGtegobuvir capsule
tegobuvir capsule, 30 mg BID
DRUGribavirin tablet
ribavirin tablet (weight based: 1000 mg/day \<75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
DRUGplacebo matching ribavirin tablet
placebo matching ribavirin tablet, BID
DEVICEplacebo matching tegobuvir capsule
placebo matching tegobuvir capsule, BID
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Adult subjects 18 and older with chronic HCV infection * Liver biopsy results (performed no more than 3 years prior to Screening) indicating the absence of cirrhosis * Monoinfection with HCV genotype 1a or 1b * Interferon ineligible or intolerant * Body mass index (BMI) between 18 and 40 kg/m2 * Use of highly effective contraception methods if female of childbearing potential or sexually active male * Screening laboratory values within defined thresholds * Has not been exposed to any investigational drug or device within 30 days of the Screening visit * Able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments
Exclusion criteria
* Prior treatment of HCV with any direct-acting antiviral (whether approved or experimental) * Decompensated liver disease or cirrhosis * Co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype * History of difficulty with blood collection and/or poor venous access * Pregnant or nursing female or male with pregnant female partner * Chronic liver disease of a non-HCV etiology * Suspicion of hepatocellular carcinoma * Clinically-relevant drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | Through 24 weeks of off-treatment follow-up | To evaluate safety and tolerability of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin. Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study. |
| Antiviral Activity | Through 24 weeks of off-treatment follow-up | To evaluate antiviral efficacy as measured by sustained virologic response (defined as HCV RNA \< lower limit of quantitation 24-weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Viral Dynamics | Through 10 days of therapy | To characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 10 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir. |
| Composite (or Profile) of Pharmacokinetics | predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | To characterize the steady state pharmacokinetics of GS-5885, GS-9451, tegobuvir and ribavirin (if appropriate). Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau and T ½ |
Countries
Canada, Puerto Rico, United States
Outcome results
None listed