Genotype-1 Chronic Hepatitis C Virus (HCV) Infection MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Interventions
Product Name: GS-9190
Product Code: GS-9190
Pharmaceutical Form: Capsule*
Current Sponsor code: GS-9190
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmac
Sponsors
Gilead Sciences Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female aged 18 to 65 years • Chronic HCV infection (i.e., anti-HCV antibody positive; positive for plasma HCV RNA; medical history consistent with chronicity accepted by the investigator), • HCV treatment-naive, defined as no prior exposure to PEG, RIBA, or experimental HCV therapy • Mono-infection with HCV genotype 1a or 1b • BMI between 19 and 36 kg/m2 as calculated per protocol • Subjects must have the following laboratory parameters: hemoglobin = 11 g/dL, platelets > 100,000/mm3, white blood cell count > 2,500 cells/ µL, neutrophils > 1500/mm3 (unless considered a physiologic variant discussed with and approved by the Gilead Medical Monitor), and TSH within normal limits (can be controlled on medications) • Creatinine clearance (CLcr) = 50 mL/min, as calculated by the Cockcroft-Gault equation (please refer to the protocol) • FibroTest analysis and eligibility will be determined by the results of these procedures and the liver function requirements below: Eligibility based on FibroTest results: FibroTest values indicating Stage 0 liver disease - Corresponding liver function necessary for eligibility: AST and ALT > ULN, and 40 mIU/mL. If the FSH is = 40 mIU/mL, the subject must agree to use highly effective method of birth control (as described above) to participate in the study. - Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condom with spermicide) during heterosexual intercourse from screening through completion of the study and continue for 24 weeks after the last dose of RIBA. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Pregnant or breast feeding women or women who may wish to become pregnant during the course of the study • Males who have partners planning to become pregnant • Males and females of reproductive potential who are unwilling to use two forms of effective birth control through Study Week 72. One method should include a condom with spermicide for males • Infection with non-genotype 1 HCV • Poorly controlled diabetes mellitus (hemoglobin A1c > 7) unless treatment intervention has been reviewed with the Gilead Medical Monitor and improved glucose control is anticipated • History of sarcoidosis • History of invasive malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screen) • Evidence of hepatocelluar carcinoma (e.g., a-fetoprotein > 50 ng/mL) • Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, cholangitis) • Evidence of cirrhosis (Stage 4 fibrosis based on FibroTest [unless liver biopsy performed within the prior year indicates absence of Stage 4 disease]) • Decompensated liver disease defined as conjugated bilirubin > 1.5 × ULN, prothrombin time (PT) > 1.5 × ULN, serum albumin 450 msec; complete or incomplete left or right bundle branch block; intraventricular conduction delay with QRS duration of > 120 msec; bradycardia ( 40 msec or depth of > 0.4 to 0.5 V); arrhythmia (an isolated premature ventricular contraction on screening/Day 1 is not exclusionary) ; ventricular pre-excitation; second or third degree heart block Fridericia’s formula: QTcF=QT/RR0.333 • Positive urine screen for amphetamines or cocaine • Known hypersensitivity to the study drugs, their metabolites or formulation excipients • In the judgment of the Investigator, should not participate in the study due to potential clinical or compliance issues
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the early antiviral activity (complete early virologic response rate; cEVR) of GS-9190 versus placebo, in combination with peginterferon alfa 2a (PEG) and ribavirin (RIBA), following 12 weeks of therapy To compare the antiviral activity (sustained virologic response; SVR) of GS-9190 versus placebo, in combination with PEG and RIBA, administered for 48 weeks;Secondary Objective: To determine SVR rates among subjects receiving GS-9190 in combination with PEG and RIBA who stop therapy at 24 weeks after achieving a rapid virologic response (RVR; defined by HCV RNA undetectable at Week 4) and maintain that response through Week 24 To evaluate and compare the safety (including QTcF assessment) and tolerability of GS-9190 versus placebo, in combination with PEG and RIBA To compare the antiviral activity at 4 weeks (RVR) of GS-9190 versus placebo, in combination with PEG and RIBA To compare the antiviral activity at 24 and 48 weeks of GS-9190 versus placebo, in combination with PEG and RIBA To evaluate the incidence of mutations in HCV NS5B polymerase gene in each treatment arm of the study;Primary end point(s): The co-primary efficacy endpoints are: EVR: cEVR (HCV RNA undetectable at Week 12) in all randomized and treated subjects (Treatment Arm 1 vs combined Treatment Arms 2 and 3); and SVR: (HCV RNA undetectable 24 weeks after last on-treatment visit) in all randomized and treated subjects (Treatment Arm 1 vs Treatment Arm 2) The primary safety and tolerability endpoint is any AE leading to permanent discontinuation of study drug. | — |
Countries
Belgium, Germany, Ireland, United Kingdom
Outcome results
None listed