study to assess the efficacy of 12 versus 24 weeks of extended treatment in hcv-genotype 2/3 patients

Conditions: Hepatitis C, Chronic

Summary: 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.


Eligibility criteria:
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

Keywords: chronic hcv-genotype 2/3 efficacy of treatment extension pegintron pegylated interferon alpha-2b rebetol ribavirin