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

An Open-label Multicenter Study Evaluating the Efficacy and Safety of 24 or 48 Weeks Pegylated Interferon Alfa-2a 40 kD (PEGASYS) Combination Therapy With Ribavirin (Copegus) in Patients With Chronic Hepatitis C Genotype 2 or 3 Infection Who Previously Have Relapsed After a Minimum of 12 Weeks and a Maximum of 24 Weeks of Therapy With Pegylated Interferon and Ribavirin

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.

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