Chronic Hepatitis C
Conditions
Keywords
Chronic hepatitis C, genotype 2 or 3, relapse, pegylated interferon, ribavirin
Brief 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.
Interventions
Arm A: Pegylated interferon alfa-2a Injection, 180 µg sc x 1/w for 48 weeks Ribavirin Tablet 200 mg weight based 5 or 6 per day for 48 weeks
Sponsors
Hoffmann-La Roche
Göteborg University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sustained viral response (SVR) rate defined as percentage of patients with non-detectable HCV-RNA 24 weeks after completion of the 24 or 48 week treatment period. | 24 weeks after completion of the 24 or 48 week treatment period. |
Secondary
| Measure | Time frame |
|---|---|
| Sustained viral response (SVR)rate and percentage of patients with normal serum ALT levels and its association with prespecified factors e.g. viral load | 24 weeks after complection of the 24 or 48 week treatment |
Countries
Sweden
Outcome results
None listed