Chronic Hepatitis C Virus Infection MedDRA version: 12.0 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Interventions
Product Name: GS-9190
Product Code: GS-9190
Pharmaceutical Form: Capsule, hard
Current Sponsor code: GS-9190
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pha
Sponsors
Gilead Sciences Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female = 18 years of age 2. Chronic HCV infection for at least 6 months prior to Baseline (Day 1) documented by • a positive anti-HCV antibody test, positive HCV RNA assay, or HCV genotype test at least 6 months prior to Baseline (Day 1) and currently positive for HCV RNA and anti-HCV antibody, or •currently anti-HCV antibody positive and positive for HCV RNA and a liver biopsy performed = 6 months prior to Baseline (Day 1) with evidence of HCV infection 3. Liver biopsy results (performed no more than 2 years prior to Screening) indicating the absence of cirrhosis. If a liver biopsy performed more than 1 year prior to Screening indicates Stage 3 fibrosis, the medical monitor must be consulted prior to enrollment (i.e., consensus must be reached that progression to cirrhosis with hepatic impairment is unlikely to have occurred in the time interval from liver biopsy to enrollment). 4. HCV treatment-naive, defined as no prior exposure to PEG, RIBA, any interferon alfa, or experimental HCV therapy 5. Mono-infection with HCV genotype 1 6. Detectable plasma HCV RNA at Screening 7. BMI between 18 and 36 kg/m2 8. Subjects must have the following laboratory parameters: hemoglobin = 12 g/dL for females and = 13 g/dL for males, platelets = 90,000/mm3, white blood cell count > 2,500 cells/microlitre, neutrophils > 1500/mm3 (unless considered a physiologic variant discussed with and approved by the Gilead Medical Monitor), potassium and magnesium within normal limits, and TSH within normal limits (unless currently being treated for hypothyroidism in which case the medical monitor must be consulted prior to enrollment) 9. Creatinine clearance (CLcr) = 50 mL/min 10. Willing and able to provide written informed consent and to comply with all study requirements 11. Has not been treated with any investigational drug within 45 days of the randomization visit in this study. 12. Of generally good health as determined by the Investigator, based upon physical examination, laboratory parameters, ECG findings, vital signs, and medical history; physical examination must be inclusive of retinal exam (e.g., opthalmoscopic or slit lamp evaluation) 13. Women of childbearing potential (i.e., a non-menopausal female or a female with menopausal < 2 years, who has not had a hysterectomy, bilateral oophorectomy or medically documented ovarian failure) must have negative serum beta-human chorionic gonadotropin (hCG) at screening and negative urine beta-hCG at Baseline (Day 1) prior to the first study drug administration. Female subjects of childbearing potential and male subjects with a female partner of childbearing potential must agree that they and their partner will use effective contraception (two separate forms of contraception simultaneously, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study treatment and for at least 7 months after the last dose of RIBA. • Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing. • Female subjects who are postmenopausal for less than two years are required to have FSH = 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 stud
Exclusion criteria
Exclusion criteria: 1. Pregnant women or women who may wish to become pregnant during the course of the study 2. Males who have partners who are pregnant or are planning to become pregnant 3. Males and females of reproductive potential who are unwilling to use two forms of effective birth control throughout the duration of study treatment and for at least 7 months after the last dose of RIBA. One method should include a condom with spermicide for males. 4. Infection with non-genotype 1 HCV 5. Poorly controlled diabetes mellitus (hemoglobin A1c > 9) unless treatment intervention has been reviewed with the Gilead Medical Monitor and improved glucose control is anticipated 6. History of hemoglobinopathy (e.g. thalassemia) 7. History of known retinal disease 8. History of sarcoidosis 9. 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); subjects under evaluation for malignancy are not eligible 10. Suspicion of hepatocelluar carcinoma; if alpha-fetoprotein > 50 ng/mL, enrollment is only allowed if results of appropriate diagnostic studies are inconsistent with a diagnosis of hepatocellular tumor 11. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, cholangitis) 12. Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, prothrombin time (PT) > 1.5 x ULN, serum albumin 450 msec; QRS > 120 msec (left or right hemiblock is not exclusionary); bradycardia ( 3 drinks/day for females and > 4 drinks/day for males) or current binge drinking 22. Receiving a known potent CYP 3A4 inhibitor within 2 weeks of study drug dosing or are expected to receiv
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the antiviral efficacy (sustained virologic response; SVR) of 48 weeks of GS-9190 versus placebo when administered in combination with 48 weeks of peginterferon alfa 2a (PEG) and ribavirin (RIBA);Secondary Objective: • To evaluate and compare the safety (including QTcF interval assessment) and tolerability of 48 weeks of GS-9190 versus placebo in combination with PEG and RIBA • To compare the antiviral efficacy of GS-9190 versus placebo in combination with PEG and RIBA at 4 weeks (rapid virologic response; RVR), 12 weeks (early virologic response; EVR), 24 weeks, and 48 weeks • To evaluate the incidence of mutations in HCV NS5B polymerase gene ;Primary end point(s): The primary efficacy endpoint is SVR (HCV RNA undetectable 24 weeks after the last scheduled on-treatment visit [i.e., at Week 72]) in all randomized and treated subjects. | — |
Countries
Austria, Belgium, Ireland
Outcome results
None listed