| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Hepatitis C; Genotype 1 Infection |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10057212 |
| E.1.2 | Term | Hepatitis viral infections |
|
| 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 |
| Evaluation and comparison of HCV RNA virus kinetic models with various asumptions to the Ribavirin mechanism of action based on the various forms and phases of treatment |
|
| E.2.2 | Secondary objectives of the trial |
1. Comparison of the treatment arms by comparing the kinetic parameters of the various treatment groups
2. Influence of Ribavirin saturation compared to placebo on the initial virological response (quantitative HCV RNA measuring using Cobas Ampliprep/Cobas TaqMan (Detection limit 12 IU/ml, Roche Diagnostics, Mannheim) after 12 weeks of combination treatment
3. Correlation of the virus kinetics with the GPT kinetics and test parameters for mutagenesis, immunology, predictive host factors and pharmacokinetics
4. Evaluation of various parameters that could be invoked in addition to body weight to determine the optimum Ribavirin dosage |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Serological evidence of chronic hepatitis C infection with positive anti-HCV test and evidence of HCV-RNA in the serum
2. Evidence of genotype HCV-1 based on the reverse hybridisation assay Inno LiPA from Bayer Versant (Innogenetics);
3. If possible, histological evidence of inflammatory activity in the liver with or without evidence of compensated cirrhosis (Child-Pugh grade A) during the 24 months before the start of the study or evaluation of liver fibrosis by transient elastography (FibroScan)
4. Untreated patients with chronic HCV infection
5. Caucasian men and women aged from 18 to 70 years
6. Negative urine or serum pregnancy test in women of childbearing potential within 24 hours before taking the first dose of the drug
7. Whilst taking the drug and for fertile female patients during the 16 weeks after discontinuation and for fertile female partners of a patient during the 28 weeks after last study-drug application, two safe methods of contraception must be used, one of which must be a condom worn by the man to provide an effective barrier
8. Informed consent for participation on the clinical trial, signed by patient
9. For all patients an ophtalmological examination is indicated during the screening period for documentation of baseline-status |
|
| E.4 | Principal exclusion criteria |
1. Known hypersensitivity to interferon or Ribavirin or any other ingredients
2. Patients who are underage or patients who are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 und Abs. 3 AMG)
3. Women lactating, pregnant or of childbearing potential not using a highly effective contraceptive method (allowed methods of birth control, i.e. with a failure rate of less than 1 % per year, are implants, injectables, combined oral contraceptives, IUDs (only hormonspirals), sexual abstinence or vasectomized partner. Women of childbear-ing potential must have a negative pregnancy test (serum, β-HCG) at visit 0 (Baseline))
4. Male partners of pregnant women
5. Patients who participates currently in another clinical trial or patients who participated in another clinical trial within the last 3 months
6. Patients who have participated in this study before
7. Patients who possibly are dependent on the sponsor or investigator
8. Infection with HCV-Genotype-2, -3, -4, -5 or -6
9. Previous treatment with interferon and/or Ribavirin
10. Positive evidence of HBsAg, HIV-antibodies in the screening phase
11. Immune suppressed patients
12. Treatment with systemic antineoplastic drugs or immunomodulators (including supraphysiological doses of steroids or radiation) within the last six months before the start of the study and throughout the whole study
13. Chronic hepatitis not caused by hepatitis virus C (such as haemochromatosis, autoimmune hepatitis, liver disease caused by metabolic disorder or alcohol)
14. Decompensated cirrhosis of the liver or liver disease Child-Pugh grade B or C or condition following decompensation
15. Signs of hepatocellular carcinoma within two months before the randomization because of the presence of cirrhosis or transition into cirrhosis
16. Ascites or history of oesophageal varices with bleeding
17. Haemoglobin of <13 g/dl for women or <14 g/dl for men in the screening phase
18. Patients with increased risk of anaemia (such as thalassaemia, spherocytosis, etc.) or patients for whom anaemia would signify a particular medical risk
19. Neutropenia <1,500/mcl or thrombocytopenia <90,000/mcll diagnosed in the screening phase
20. Serum creatinine >1.5 mg/dl in the screening phase
21. Patients with a history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study
22. History of severe psychiatric illness, particularly severe depression. Severe psychiatric illness is defined as any history of at least three months continuous antidepressive or antipsychotic treatment or any evidence of suicidal tendency or referral to hospital as a result of psychiatric illness
23. Epilepsy
24. Autoimmune disease such as chronic inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosis, sclerodema, severe psoriasis, rheumatoid arthritis, etc.
25. Disorders of thyroid gland function that could not be controlled with euthyroid medication
26. Insufficiently controlled diabetes mellitus (HbA1c >8,5%)
27. Clinically manifest gout.
28. Chronic pulmonary disease with functional limitation
29. Previous severe heart disease such as heart failure NYHA class III or IV, myocardial infarction within the last six months, ventricular tachycardia requiring treatment, unstable angina, cerebrovascular perfusion disorders or other significant cardiovascular disease.
30. Organ transplant, other than corneal transplant
31. Evidence of acute or presumed cancer during the last 5 years (with the exception of a adequate treated basiliom) or any other severe disease which in the opinion of the investigator represents a criterion for exclusion from the study.
32. Evidence of clinical relevant retinopathy such as CMV retinitis or macular degeneration or retinopathy caused by hypertension or diabetes.
33. Active consumption of drugs including excessive consumption of alcohol within the last year before the start of the study, with the exception of prescribed replacement therapy
34. Patients in states of agitation or confusion
35. Patients with a history of delirium or exogenous psychosis
36. Not prepared or incapable of giving informed consent in writing, failure to agree to legal requirements regarding data protection or to be prepared to participate in the trial or adhere to the conditions of the study
37. Any other clinical condition which in the opinion of the investigator could put the acceptance of the patient or his/her participation in or conclusion of the treatment in question. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective of this pilot trial is the evaluation and comparison of different HCV-RNA virus kinetic models with various hypotheses to the Ribavirin mechanism of effect, in order to estimate, with an optimized model, a possible advantage of preliminary treatment with Ribavirin on the virological response, even with a few number of patients. At first, model adjustments should be compared using the individual response effects regarding the level of infection (model 1), virus production (model 2) and/or the reduction rate of infected cells (model 3), if possible using variance analysis or the non-parametric Friedman test. |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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 | 5 |
| 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 | Information not present in EudraCT |
| 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
|
| End of trial is defined as last patient last visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
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