E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic hepatitis c infection genotype 2/3 |
|
E.1.1.1 | Medical condition in easily understood language |
chronic infection with a particular hepatits c virus (genotype 2/3) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008914 |
E.1.2 | Term | Chronic hepatitis C without mention of hepatic coma |
E.1.2 | System Organ Class | 100000004862 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or 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 2. Age ≥ 18 years 3. Compensated liver disease (Child-Pugh Grade A clinical classification) 4. 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 5. Ongoing treatment with 1.5 µg/kg Peg-Interferon alpha-2b (PegIntron®) and > 10.6 mg/kg ribavirin (Rebetol®) 6. No rapid virological response (HCV-RNA positive after week 4 of the ongoing therapy) 7. Willingness to give written informed consent and willingness to participate to and to comply with the study protocol |
|
E.4 | Principal exclusion criteria |
1. Women with ongoing pregnancy or breast feeding 2. Male partners of women who are pregnant 3. Coinfection with HIV or HBV 4. 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) 5. History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease 6. Patients with liver cirrhosis with a lesion suspicious for hepatic malignancy on the screening 7. Absolute neutrophil count (ANC) <750 cells/mm3 at screening 8. Platelet count <50,000 cells/mm3 at screening 9. Hb <10 g/dl at screening 10. Dose modification of Peg-Interferon alpha-2b (PegIntron®) or ribavirin (Rebetol®) during the first 4 weeks of the ongoing therapy 11. Interferon alpha or ribavirin therapy at any time point before the actual ongoing treatment 12. Less than 80% adherence to treatment of the ongoing treatment until randomization (week 20-22 of ongoing treatment) 13. Serum creatinine level >1.5 times the upper limit of normal at screening 14. 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 15. History of a severe seizure disorder or current anticonvulsant use 16. History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis) 17. History or any other evidence of autoimmune diseases 18. History or other evidence of chronic pulmonary disease associated with functional limitation 19. 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) 20. Evidence of thyroid disease that is poorly controlled on prescribed medications 21. Evidence of severe retinopathy (e.g. CMV retinitis, macular degeneration) 22. History of major organ transplantation with an existing functional graft 23. 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 24. 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 25. Patients with evidence for tuberculosis 26. 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 27. Any investigational drug and/or participation in another clinical study prior 6 months to the actual ongoing antiviral treatment 28. Limited contractual capability |
|
E.5 End points |
E.5.1 | Primary end point(s) |
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 und thus improvement of sustained virological response rates (SVR)
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 weeks after the end of treatment |
|
E.5.2 | Secondary end point(s) |
1. 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 2. Biochemical responses as determined by ALT and AST levels at the end of treatment and at the end of follow up. 3. Severity and frequency of adverse event 4. Analysis of quality of life (with questionnaire SF-36)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. end of treatment 2. end of treatment and end of follow up 3. throughout the study, beginning with treatment week 0 4. Treatment weeks 0, 12, 24 and follow up at 12 and 24 months |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
different treatment duration |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 30 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |