Chronic hepatitis C MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Interventions
Product Name: HCV Polymerase Inhibitor Prodrug
Product Code: RO4588161
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: RO4588161
Other descriptive name: HCV Polymerase Inhibitor Prodrug
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 hepatitis C genotype 1 infection by molecular assay 4) Serum HCV RNA quantifiable at = 50,000 IU/mL as demonstrated by the Roche COBAS TaqMan HCV Test 5) 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 of the protocol 6) Patients with cirrhosis or incomplete/transition to cirrhosis must have an abdominal ultrasound, computerized tomographic (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) Infection with any HCV genotype other than genotype 1 or an indeterminate or mixed genotype 2) History of having received any IFN, PEG-IFN, RBV, viramidine, levovirin, or investigational HCV polymerase or protease inhibitors at any previous time 3) History of having received any investigational drug less than or equal to 3 months prior to the first dose of study 4) Patients who are expected to need systemic antiviral therapy with established or perceived activity against HCV 5) Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, or anti-HIV Ab 6) History or other evidence of a medical condition associated with chronic liver disease other than HCV 7) Females who are pregnant or breast feeding 8) Male partners of females who are pregnant 9) Body mass index (BMI) =36 or 1.5 times the upper limit of normal at screening. 14) The use of colony stimulating factors such as granulocyte colony stimulating factor (G-CSF), erythropoietin or other therapeutic agents to elevate hematology parameters to facilitate patient entry into the study 15) History of severe psychiatric disease, including psychosis and/or depression 16) History of immunologically mediated disease 17) History or other evidence of decompensated liver disease or a Child-Pugh score >6 18) History or other evidence of chronic pulmonary disease associated with functional limitation 19) History of severe cardiac disease. In addition, patients with documented or presumed coronary artery disease, stable or unstable cardiovascular disease or cerebrovascular disease should not be enrolled as an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin or RO4588161 therapy) may occur. 20) Patients with higher potential for QTC prolongation; patients with any clinical condition that increases the risk of QTC prolongation; personal or family history of congenital long QT syndrome or sudden death, which would make the patient, in the opinion of the investigator, unsuitable for the study 21) History of uncontrolled severe seizure disorder 22) Evidence of an active or suspected cancer, or a history of malignancy where the risk of recurrence is = 20% within 2 years 23) History of any systemic anti-neoplastic or immunomodulatory treatment 24) Poorly controlled thyroid dysfunction 25) History or other evidence of a clinically relevant ophthalmologic disorder due to diabetes mellitus or hypertension or history or other evidence of severe retinopathy 26) History of major organ transplantation with an existing functional graft 27) History or other evidence of severe illness, malignancy or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study 28) Evidence of excessive alcohol, drug or substance abuse within 1 year of first dose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the optimal treatment combination based on the efficacy and safety of the HCV Polymerase Inhibitor Prodrug (RO4588161) in combination with Pegasys and Copegus versus the currently approved combination of Pegasys and Copegus in treatment-naive patients with chronic hepatitis C genotype 1 virus infection;Secondary Objective: - To evaluate the pharmacokinetics of RO1048297 (parent compound of RO4588161) when administering RO4588161 in combination with Pegasys and Copegus - To evaluate the resistance profile of RO4588161 in combination with Pegasys and Copegus ;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 Group C with total 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 scheduled treatment period”. All primary and secondary analyses of SVR will be performed using both definitions. Subgroup analysis and explorative analysis for SVR will be performed only for “SVR according to actual treatment period”. | — |
Countries
Austria, France, Germany, Italy, Spain
Outcome results
None listed