combination therapy with pegylated interferon and ribavirin in patients with chronic hepatitis c genotype 2 or 3 infection who previously have relapsed after therapy with pegylated interferon and ribavirin

Conditions: Chronic Hepatitis C

Summary: to evaluate the efficacy of pegylated interferon alfa-2a 40 kd (pegasys) combination therapy with ribavirin (copegus)given for 24 or 48 weeks in patients with chronic hepatitis c (chc) virus infection genotype 2 or 3 who responded during (i.e. had hcv-rna \<50 iu/ml at the end of previous therapy), but relapsed after (i.e. had detectable hcv-rna after the end of prior treatment) previous therapy with pegylated interferon and ribavirin given for at least 12 weeks and at most 24 weeks.


Eligibility criteria:
inclusion criteria: * male and female patients ≥ 18 years of age * serologic evidence of chronic hepatitis c infection by an anti-hcv antibody test * serum hcv-rna ≥ 15 iu/ml. hcv genotype 2 or/and 3 infection confirmed within the past 6 months preceding the initiation of test drug dosing. the hcv genotype must have been reconfirmed after the termination of the previous treatment period * previous relapse (i.e. hcv-rna \< 50 iu/ml at end of previous therapy) after one treatment period with pegylated interferon alfa-2a or alfa-2b combination therapy with ribavirin for at least 12 weeks and at most 24 weeks * a minimum of 24 weeks must have elapsed since the last dose of pegylated interferon or ribavirin in the previous treatment period before the patients can be included in this study * compensated liver disease (child-pugh grade a clinical classification) * patients with suspected cirrhosis or transition to cirrhosis must have an abdominal ultrasound, ct scan, or mri scan without evidence of hepatocellular carcinoma and a serum afp \< 100 ng/ml within 2 months of randomization * negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug * all fertile males and females receiving ribavirin must be using effective contraception during treatment and during the 6 months after treatment end * having a liver biopsy obtained within 5 years of this study is encouraged, but optional in accordance with local treatment traditions. exclusion criteria: * women with ongoing pregnancy or breast feeding * previous non-response during treatment (as defined as having detectable hcv rna ≥ 50 iu/ml at the end of previous treatment) with pegylated interferon alfa-2a or alfa-2b combination therapy with ribavirin for at least 12 weeks and at most 24 weeks * less than 24 weeks have elapsed since the last dose of pegylated interferon or ribavirin in the previous treatment period prior to inclusion in this study. * therapy with any systemic anti-viral * anti-neoplastic * immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤ 6 months prior to the first dose of study drug * any investigational drug ≤ 6 weeks prior to the first dose of study drug. hcv genotype 1, 4, 5 or 6 infection * positive test at screening for anti-hav igm ab * hbsag * anti-hbc igm ab * anti-hiv ab * evidence of a medical condition associated with chronic liver disease other than hcv (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures) * history or other evidence of decompensated liver disease * neutrophil count \< 1500 cells/mm3 or platelet count \< 75,000 cells/mm3 at screening * serum creatinine level \> 2 mg/dl (\> 124 µmol/l) or creatinine clearance \< 50 ml/minute at screening * severe psychiatric disease, especially depression, as judged by the treating physician * history of a severe seizure disorder or current anticonvulsant use * history of immunologically mediated disease * severe chronic pulmonary disease associated with functional limitation * severe cardiac disease * major organ transplantation or other evidence of severe illness * malignancy * any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study * thyroid dysfunction not adequately controlled (tsh and t4 levels out of normal range) * evidence of severe retinopathy (e.g. cmv retinitis, macula degeneration) or * clinically relevant ophthalmological disorder due to diabetes mellitus or * hypertension * evidence of drug abuse (including excessive alcohol consumption) in accordance with local therapeutic traditions. (patients receiving methadone or subutex therapy may be included in this study.) * inability or unwillingness to provide informed consent or abide by the requirements of the study * male partners of women who are pregnant * hemoglobin \< 11.3 g/dl (\< 7.0 mmol/l) in women or \< 12.9 g/dl (\< 8.0 mmol/l) in men at screening. * any patient with an increased baseline risk for anemia (e.g. thalassemia, spherocytosis, etc) or for whom anemia would be medically problematic * patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dl (as may be seen with ribavirin therapy) would not be well-tolerated

Keywords: chronic hepatitis c genotype 2 or 3 relapse pegylated interferon ribavirin