Chronic Hepatitis C MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Interventions
Product Code: RO5024048/F06
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: RO5024048
Other descriptive name: HCV Polymerase Inhibitor Prodrug
Concentration unit: mg milligram(s)
Concen
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age 18 – 65 years 2.Serologic evidence of CHC infection by an anti-HCV antibody test (current or historical) 3.Evidence of chronic hepatitis C infection > 6 months duration 4.Evidence of hepatitis C genotype 1 or 4 infection by molecular assay 5.Serum HCV RNA quantifiable at =50,000 IU/mL as demonstrated by the Roche COBAS TaqMan HCV Test 6.Chronic liver disease consistent with chronic hepatitis C infection on a biopsy obtained within the past 24 months (36 months for patients with cirrhosis or incomplete/transition to cirrhosis), using one of the scoring methods in Appendix 2 7.Patients with cirrhosis or incomplete/transition to cirrhosis must have an abdominal ultrasound, computerized tomography (CT) scan, or magnetic resonance imaging (MRI) scan without evidence of hepatocellular carcinoma (within 2 months prior to randomization) and a serum alpha-fetoprotein (AFP) =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Females who are pregnant or breast feeding 2.Male partners of females who are pregnant 3.Body mass index (BMI) 1.5 times the upper limit of normal 15.Serum total bilirubin = 2 times the upper limit of normal 16.History of pre-existing renal disease. Patients with a history of nephrolithiasis will be allowed. 17.Estimated creatinine clearance of = 80 mL/min (= 1.34 mL/sec), calculated by the Cockcroft-Gault formula 18.Serum creatinine > 1.5 times the upper limit of normal 19.Greater than trace hematuria (=1+ or >10 RBC/HPF, unless related to menstruation) 20.Microproteinuria with protein/creatinine ratio = 0.3 (= 33.89 mg/mmol) as determined by urine chemistry test (see Appendix 6 for details) 21. One or more of the following: (i) poorly controlled hypertension, OR (ii) poor adherence to antihypertensive therapy, OR (iii) current use of > 2 antihypertensive agents required, OR (iv) screening or baseline blood pressure =140 mmHg for systolic OR (v) = 90 mmHg for diastolic blood pressure 22.The use of colony stimulating factors such as granulocyte colony stimulating factor (G-CSF), erythropoietin, blood transfusion or other therapeutic agents to elevate hematology parameters to facilitate patient entry into the study within the last 6 months 23.History of severe psychiatric disease, including psychosis and/or depression, characterized by a suicide attempt, hospitalization for psychiatric disease, or a period of disability as a result of psychiatric disease 24.History of immunologically mediated disease (e.g., vasculitis, cryoglobulinemia, inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis (d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study the effects of dose and duration of the HCV polymerase inhibitor prodrug (RO5024048) in combination with PEG-IFN and RBV versus the currently approved combination of PEG-IFN and RBV (SOC) in treatment-naive patients with chronic hepatitis C genotype 1 and 4 virus infection.;Secondary Objective: - To evaluate the safety and tolerability of HCV polymerase inhibitor prodrug (RO5024048) in combination with PEG-IFN and RBV versus the currently approved combination of SOC - To determine virologic response at defined time points (Week 4, 12, 24, 48 and 60). - To evaluate the pharmacokinetics of RO4995855 when RO5024048 is administered in combination with SOC - To evaluate the resistance profile of RO5024048 in combination with SOC - To evaluate safety and efficacy of open-label HCV polymerase inhibitor Prodrug (RO5024048) in combination with SOC in the subset of patients who only received currently approved combination of SOC (Group E) and who did not demonstrate an early virologic response (Treatment Failures) ;Primary end point(s): The primary measure of efficacy is SVR defined as the percentage of patients with undetectable HCV RNA as measured by the Roche COBAS TaqMan HCV Test (detection limit = 15 IU/mL) 24 weeks after end of treatment (SVR-24; a single last HCV RNA undetectable =20 weeks after last dose). Patients without HCV RNA measurements at the end of the 24-week treatment-free follow-up period will be considered non-responders. This definition of SVR will be “SVR according to actual treatment period”. Additional analyses will be performed using the definition of SVR defined as the percentage of patients with undetectable HCV RNA as measured by Roche COBAS TaqMan HCV test at or after week 44 (=study day 309) for treatment groups A, B and C with total treatment duration of 24 weeks or at or after week 68 (= study day 477) for treatment groups with total treatment duration of 48 weeks. This definition of SVR will be “SVR according to sc | — |
Countries
Austria, France, Germany, Italy, Spain, United Kingdom
Outcome results
None listed