Study to Assess the Efficacy of 12 Versus 24 Weeks of Extended Treatment in HCV-Genotype 2/3 Patients

Optimization of Treatment for Patients With Chronic Hepatitis C Infected With HCV-genotype 2 or 3: 12 vs. 24 Weeks of Treatment Extension for Patients Without Rapid Virological Response

In this study we intend to treat patients with chronic hepatitis C of genotype 2 or 3 having characteristics associated with poor treatment response for additional 12 or 24 weeks beyond the standard treatment of PEG-IFN alpha-2b plus ribavirin.

The objective of this study is to compare the efficacy of a treatment extension of 12 versus 24 weeks in patients with HCV-genotypes 2 and 3 who are treated with 1.5 µg/kg PEG-IFN alpha-2b and 800-1400 mg ribavirin (standard dose) for 24 weeks (standard duration) and who are not HCV-RNA negative (< 15 IU/ml) after 4 weeks of standard treatment but HCV-RNA negative after 16-24 weeks of standard treatment.

Inclusion Criteria:

• Male and female patients with HCV-genotype 2/3 chronic hepatitis C documented by detectable plasma HCV RNA (> 15 IU/mL) and positivity of anti-HCV antibodies
• Age ≥ 18 years
• Compensated liver disease (Child-Pugh Grade A clinical classification)
• Negative urine or blood pregnancy test (one of the both; for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug. Additionally, all fertile males and females must be using two forms of effective contraception during treatment and during the 7 months after treatment end. This includes using birth control pills (no interaction with investigational drugs), IUDs, condoms, diaphragms, or implants, being surgically sterilized, or being in a post-menopausal state. At least one contraception method must be of barrier method
• Ongoing treatment with 1.5 µg/kg Peg-Interferon alpha-2b (PegIntron®) and > 10.6 mg/kg ribavirin (Rebetol®)
• No rapid virological response (HCV-RNA positive after week 4 of the ongoing therapy)
• Willingness to give written informed consent and willingness to participate to and to comply with the study protocol

Exclusion Criteria:

• Women with ongoing pregnancy or breast feeding
• Male partners of women who are pregnant
• Positive tests at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, HBeAg, anti-HIV, HIV-RNA
• History or other evidence of a medical condition associated with chronic liver disease other than HCV associated (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures)
• History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
• Patients with liver cirrhosis with a lesion suspicious for hepatic malignancy on the screening
• Absolute neutrophil count (ANC) <750 cells/mm3 at screening
• Platelet count <50,000 cells/mm3 at screening
• Hb <10 g/dl at screening
• Dose modification of Peg-Interferon alpha-2b (PegIntron®) or ribavirin (Rebetol®) during the first 4 weeks of the ongoing therapy
• Interferon alpha or ribavirin therapy at any time point before the actual ongoing treatment
• Less than 80% adherence to treatment of the ongoing treatment until randomization (week 20-22 of ongoing treatment)
• Serum creatinine level >1.5 times the upper limit of normal at screening
• History of severe psychiatric disease, especially depression (ICD 10 codes F30-F33). 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. Patients are excluded if any history of suicidal attempts is evident. If hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease are documented, psychiatric consultation is mandatory. Patients with a mild or moderate psychiatric disease (ICD 10 codes F32.0, F32.1, F33.0, F33.1) are only allowed to be included into the trial if a regular monitoring by a psychiatrist is performed during the trial
• History of a severe seizure disorder or current anticonvulsant use
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis)
• History or any other evidence of autoimmune diseases
• History or other evidence of chronic pulmonary disease associated with functional limitation
• History of significant cardiac disease that could be worsened by acute anemia (e.g. NYHA Functional Class III or IV, myocardial infarction within 6 months prior to treatment with Peg-Interferon/ribavirin therapy, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina)
• Evidence of thyroid disease that is poorly controlled on prescribed medications
• Evidence of severe retinopathy (e.g. CMV retinitis, macular degeneration)
• History of major organ transplantation with an existing functional graft
• 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 any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
• Patients with evidence for tuberculosis
• Drug abuse within 6 months prior to the first dose of study drug and excessive alcohol consumption. Patients on methadone/polamidone/buprenorphine programs are not excluded
• Any investigational drug and/or participation in another clinical study prior 6 months to the actual ongoing antiviral treatment
• Limited contractual capability