genotype 1 chronic hepatitis C infection of high viral titer and baseline body weight greater than or equal to 85 kg MedDRA version: 8.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Interventions
Trade Name: Pegasys
Product Name: Pegasys 180 micrograms solution for injection
Product Code: RO 25-8310
Pharmaceutical Form: Solution for injection
Product Name: Pegasys 360 micrograms solution for
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for this trial, patients must have documentation of the following: • Age >=18 years • Body weight >= 85 kg • Serologic evidence of CHC infection by an anti-HCV antibody test (current or historical) • Evidence of hepatitis C genotype 1 infection by molecular assay • Serum HCV RNA quantifiable at >= 400,000 IU/mL by the Roche TaqMan HCV Test • Chronic liver disease consistent with CHC infection on a biopsy obtained within the past 24 calendar months as judged by a central pathologist. For patients with incomplete/transition to cirrhosis or cirrhosis, a biopsy within 36 calendar months before the first dose is sufficient. A maximum of 20% of patients with cirrhosis or incomplete/transition to cirrhosis will be permitted to enroll in the trial. • 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) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients with any of the following will not be eligible for participation: • Infection with HCV genotype 1 mixed with a genotype other than genotype 2 or genotype 3 or infection with an indeterminate genotype. Patients with indeterminate or mixed genotype 1 subtypes will be allowed. • History of having received interferon alpha (IFN), PEG-IFN, ribavirin, viramidine, levovirin, or investigational HCV protease or polymerase inhibitors at any previous time, or any other systemic antiviral therapy with established or perceived activity against the hepatitis C virus =1.5 times the upper limit of normal at screening • The use of colony stimulating factors such as granulocyte colony stimulating factor (G-CSF), erythropoetin or other therapeutic agents to elevate hematology arameters to facilitate patient entry into the study • 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 • Beck Depression Inventory (BDI) score of >= 20 • History of immunologically mediated disease (eg, inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis (defined as affecting >10% of the body, here the palm of one hand equals 1%, or if the hands and feet are affected), rheumatoid arthritis requiring more than intermittent nonsteroidal anti-inflammatory medications for management • History or other evidence of decompensated liver disease or a Child-Pugh score >6. Coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices are conditions consistent with decompensated liver disease • History or other evidence of chronic pulmonary disease associated with functional limitation • History of severe cardiac disease (eg, NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases). In addition, patients with documented or presumed coronary arte
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy and safety of 360 µg induction dosing of Pegasys for 12 weeks followed by a 180 µg maintenance dose of Pegasys for 36 weeks in combination with Copegus for 48 weeks with the efficacy and safety of 180 µg fixed dosing of Pegasys in combination with Copegus for 48 weeks in patients with genotype 1 chronic hepatitis C infection of high viral titer and baseline body weight equal to or greater than 85 kg;Secondary Objective: Compare efficacy and safety of higher dose Copegus (Cop) in combination with Pegasys (Peg) for 48 wks with efficacy and safety of standard dose Cop in combination with Peg for 48 wks. Compare efficacy and safety of 360 µg induction dosing of Peg for 12 wks followed by a 180 µg maintenance dose of Peg for 36 wks in combination with higher dose Cop with efficacy and safety of the approved Peg plus Cop dosing regimen. Determine if treatment-related lymphopenia and neutropenia are associated with the occurrence of serious infections. Evaluate Peg and ribavirin drug exposures and their relationship to viral response in a subset treated with 360 µg induction dosing of Peg and with higher doses of Cop within the four study groups. Evaluate effect of combination of Peg and Cop on gene expression in responders and nonresponders to treatment. Evaluate association between mutations of the NS5A and NS5B genes of HCV and virological response in a subset of responders and nonresponders.;Primary end point(s): The primary measure of efficacy will be SVR defined as the percentage of patients with undetectable HCV RNA as measured by the Roche TaqMan HCV Test (detection limit = 15 IU/mL) at 24 weeks after completion of the treatment period (a single last HCV RNA PCR = week 68 (ie, >= study day 477)). Patients without measurements at the end of the 24-week untreated follow-up period will be considered as non-responders. This endpoint will be labeled as "the SVR-24 according to the scheduled treatment period". | — |
Countries
Belgium, Denmark, France, Germany, Hungary, Netherlands, Sweden, United Kingdom
Outcome results
None listed