Hepatitis C, Chronic
Conditions
Keywords
Chronic HCV-genotype 2/3, Efficacy of treatment extension, PegIntron, pegylated interferon alpha-2b, Rebetol, ribavirin
Brief 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.
Interventions
1.5 µg/kg once weekly, syringe, 24 weeks
DRUGRibavirin
800-1400 mg per os, daily, tablets, 24 weeks
1.5 µg/kg once weekly, syringe, 12 weeks
Sponsors
Hannover Medical School
HepNet Study House, German Liverfoundation
Study design
Allocation
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Reduction of Relapse rate (HCV-RNA positive in serum by a standard HCV-PCR with a detection limit of at least 15 IU/ml) 24 weeks after the end of treatment and thus improvement of sustained virological response rates (SVR) | 48 weeks (arm A) or 36 weeks (arm B) |
Secondary
| Measure | Time frame |
|---|---|
| Virological response rates (HCV-RNA negative in serum by a standard HCV-PCR with a detection limit of at least 15 IU/ml) at the end of therapy | 24 weeks (arm A) or 12 weeks (arm B) |
| Biochemical responses as determined by ALT and AST levels at the end of treatment and at the end of follow up. | Arm A: 24 and 24 weeks, arm B: 12 and 24 weeks |
| Severity and frequency of adverse event | 48 weeks (arm A) or 36 weeks (arm B) |
| Analysis of quality of life | 48 weeks (arm A) or 36 weeks (arm B) |
Countries
Germany
Outcome results
None listed