Chronic Hepatitis C Virus Infection MedDRA version: 14.0 Level: LLT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Gilead Sciences Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for participation in this study. 1. Male or female, aged from 18 to 70 years old, inclusive. 2. Willing and able to provide written informed consent. 3. Body mass index (BMI) from 18 to 36 kg/m^2, inclusive. Note: BMI may be calculated according to either of the following formulae: BMI = weight in pounds x 703/(height in inches)^2 or weight in kilograms/(height in meters)^2 4. HCV infection limited to genotype 1. 5. Subjects must have baseline plasma HCV RNA = 3 log10 IU/mL at screening, but < 7.2 log10 IU/mL. 6. Liver biopsy results (or combined results of FibroTest or FibroScan, if considered acceptable by regulators and ethics committess on a country-by-country basis) within the past 2 years prior to screening indicating the absence of cirrhosis. If a liver biopsy or combined FibroTest and FibroScan 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 procedure to enrollment). Alternative methods to evaulate cirrohosis may be used provided they are approved in advance by the Medical Monitor. 7. Chronic HCV infection will be documented by (1) a positive anti-HCV antibody test or evidence of HCV RNA (i.e., viral load or genotype) (2) a liver biopsy (or FibroTest or FibroScan results where appropriate) consistent with chronic HCV infection, or (3) elevated ALT values (i.e. above the normal range) at any point in within one year prior to screening. On a case-by-case the sponsor will consider permitting enrollment of patients with clear cut clinical histories of chronic infection in circumstances where laboratory documentation cannot be retrieved. 8. Eligible subjects must also be HCV treatment-naïve, defined as no prior exposure to IFNa, RIBA, or experimental HCV therapy, with imminent plans to start standard of care therapy with PEG/RIBA. 9. QTcF interval (QT corrected using Fridericia’s formula) must be =450 msec as determined from screening ECG. 10. Subjects must have the following laboratory parameters at screening: ALT, AST, and GGT = 5 x the upper limit of normal (reference) range (ULN); white blood cell count = 2,500 cells/µL; absolute neutrophil count (ANC) = 1,500 cells/mm3 (unless considered a physiologic variant discussed with and approved by the Gilead medical monitor); potassium and magnesium within normal limits; TSH within normal limits (unless currently being treated for hypothyroidism or the TSH abnormality is not considered to be clinically significant after consultation with the Gilead Medical Monitor); hemoglobin (Hb) = 13 g/dL for males and Hb = 12 g/dL for females. 11. Creatinine clearance (CLcr) = 50 mL/min, as calculated by the Cockcroft-Gault equation using lean body weight: CLer (mL)/min)= (140-Age) x LBW/72 x Scr (x0.85 for female subjects) where: Age is calculated in years and Scr is the subject’s measured serum creatinine (in mg/dL). LBW is the subject’s lean body weight in kilograms, calculated as: Male: LBW = 50 + 2.3*[(height in cm – 152.4) / 2.54] OR 50 + 2.3*(height in inches – 60) Female: LBW = 45.5 + 2.3*[(height in cm – 152.4) / 2.54] OR 45.5 + 2.3*(height in inches – 60) If a subject’s height is less than or equal to 152.4 cm (60 inches), then his LBW is 50 kg and her LBW is 45.5
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following exclusion criteria are not to be enrolled in this study. 1. Female of child-bearing potential (defined as a non-menopausal female or a female who is menopausal 9 or fasting glucose = 150 mg/dL) . 6. History of hemoglobinopathy (e.g. thalassemia), retinal disese, sarcoidosis 7. 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 8. Untreated or significant psychiatric illnesses including severe depression, schizophrenia, psychosis, or a history of a suicide attempt 9. Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) or multiple HCV genotypes 10. Chronic use of systemic immunosuppressive agents 11. Presence of autoimmune disorders (e.g. systemic lupus erythematosus, rheumatoid arthritis, psoriasis of greater than mild severity). Subjects with treated hypothyroidism with normal TSH may be enrolled. 12. Severe chronic obstructive pulmonary disease 13. History of significant cardiac disease (including history of myocardial infarction based on ECG and/or clinical history, any history of ventricular tachycardia, congestive heart failure, or dilated cardiomyopathy with left ventricular ejection fraction 450 msec; QRS > 120 msec (left or right hemiblock is not exclusionary); bradycardia (50 ng/mL, enrollment is only allowed if results of appropriate diagnostic studies are inconsistent with a diagnosis of hepatocellular tumor 17. Total bilirubin > ULN or known diagnosis of Gilbert’s syndrome 18. Other signs of decompensated liver disease, as indicated by prothrombin time > 1.5 < ULN, platelets < 90,000/mm3 or albumin < 3 g/dL at screening OR current or prior history of clinical hepatic decompensation 19. Subjects with or a history of clinically
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are as follows: • To describe the antiviral efficacy of GS 9256 plus GS 9190 alone and in combination with ribavirin (RIBA) against genotype 1 hepatitis C virus (HCV), as measured by the percentage of subjects achieving rapid virologic response (RVR; that is HCV RNA undetectable at Day 28). • To evaluate the safety and tolerability of GS 9256 plus GS 9190 alone and in combination with RIBA for 28 days in subjects with chronic genotype 1 HCV infection. ;Secondary Objective: The secondary objectives of this study are as follows: • To characterize the pharmacokinetics of GS 9256 and GS 9190 following administration of multiple oral doses of GS 9256 plus GS 9190 alone, in combination with RIBA, and in combination with PEG/RIBA. Exploratory objectives of this study include the following: • To describe the aniviral efficacy of and to evaluate the safety and tolerability of GS 2956 plus GS 9190 in combination with PEG/RIBA against genotyple 1 HCV. • To evaluate the emergence of viral resistance during and following treatment with GS 9256 plus GS 9190 alone, in combination with RIBA, and in combination with PEG/RIBA for 28 days and for 72 weeks following discontinuation of study drugs (GS-9256 plus GS-9190). ;Primary end point(s): The primary efficacy endpoint will be viral load suppression at day 28, as measured by the proportion of subjects achieving RVR (i.e. HCV RNA undetectable at Day 28). Plasma HCV RNA reduction from baseline will be evaluated as well.;Timepoint(s) of evaluation of this end point: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): n/a;Timepoint(s) of evaluation of this end point: n/a | — |
Countries
Belgium, France, Germany, United Kingdom
Contacts
Public ContactMedical Monitor
Gilead Sciences Inc
Outcome results
None listed