A Study of Peginterferon Alfa-2a (Pegasys) When Administered in Combination With Ribavirin in Patients With Chronic Hepatitis C (CHC)

Randomized, Multicenter Study to Find Optimal Treatment Duration in Patients With Chronic Hepatitis C and Subtype 1 or 4 Depending on HCV RNA Level at Week 8 and Week 12

This study will compare the efficacy and safety of 2 different treatment durations of peginterferon alfa-2a (Pegasys) plus ribavirin in patients with CHC. The anticipated time on study treatment is 1-2 years, and the target sample size is greater than (>) 500 individuals.

Inclusion Criteria:

• Male and female patients with chronic hepatitis C and genotype 1 (1a or 1b) or genotype 4
• Age between 18 and 70 years
• Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
• Present with at least one elevated serum alanine-aminotransferase (ALT) level higher than normal in the last 6 months before therapy start including the screening period
• Positive HCV-RNA level in serum
• Laboratory parameters (within 35 days prior to study start): -Hepatitis A anti - IgM negativity, HIV-Ab negativity, HBsAg negativity, Hemoglobin values > 12 g/dl in women or > 13 g/dl in men, Leukocyte count (WBC) > 3 000 /mcl, Platelets count > 100 000/mcl, Creatinine not 1.5 times higher than normal, normal TSH, normal uric acid with a maximum tolerance of 15 % in patients without history of gout
• Liver biopsy findings within 6 months prior to study therapy consistent with the diagnosis of chronic hepatitis C infection with or without compensated cirrhosis. Biopsies older than 1 year are eligible only after direct communication with the principal investigator
• 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. If there is no laboratory report existing, the physician should make an entry in the medical history that the pregnancy test was negative.
• All fertile females receiving ribavirin must be using two forms of effective contraception during treatment and during the 6 months after treatment end. All fertile men with female partners must be using two forms of effective contraception during treatment and during the 7 months after treatment end.
• Written informed consent obtained

Exclusion Criteria:

• Any IFN and / or Pegylated IFN and ribavirin therapy at any previous time
• Class B or C cirrhosis as coded by Child Pugh classification
• Women with ongoing pregnancy or breast feeding
• Therapy with any systemic anti-neoplastic or 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
• Drug addiction within 1 year prior to study start (patients participating in an official methadone program are eligible)
• Diabetes mellitus in patients receiving an insulin therapy
• Hemophiliac patients (due to the increased risk of requested liver biopsy)
• History or other 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 bleeding from esophageal varices or other conditions consistent with decompensated liver disease
• History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease. Exception: if there is a current psychiatric report which certifies there is no contraindication to interferon therapy, patient may be included
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis etc.)
• History or other evidence of chronic pulmonary disease associated with functional limitation
• History of a severe seizure disorder or current anticonvulsant use
• History of severe cardiac disease and severe coronary heart disease within the last 6 months (angina pectoris, congestive heart failure, recent myocardial infarction, severe hypertension or significant arrhythmia). If there is clinical suspicion of coronary heart disease cardiologic workup of the patient prior to study entry is recommended.
• History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
• 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
• History of major organ transplantation with an existing functional graft
• Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration)
• Inability or unwillingness to provide informed consent or abide by the requirements of the study

Additional exclusion criteria concerning ribavirin:

• Male partners of women who are pregnant
• Any patient with an increased baseline risk for anemia (e.g. thalassemia, spherocytosis, history of GI bleeding, 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 would not be well-tolerated