| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic hepatitis C, genotype 1 |
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| MedDRA Classification |
| 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 |
| To compare the efficacy, the safety and tolerability of two dose regimen of Multiferon® in combination with ribavirin in genotype 1 HCV infected subjects who have had an incomplete viral response or a relapse after a pegylated recombinant IFN α based therapy. |
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| E.2.2 | Secondary objectives of the trial |
| To identify the parameters from treatment history and disease characteristics that influence the final treatment outcome after second line treatment with Multiferon®, including the quality of the viral response to the first line PEG interferon treatment and the baseline disease characteristics before Multiferon® treatment. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Documentation of genotype 1 HCV infection (mixed genotype accepted) by licensed diagnostic tests (RIBA or HCV PCR, with genotyping assay).
Viral relapser or non-responder to a previous treatment with pegylated interferon and ribavirin of no less than 12 weeks, with an initial viral response characterized by a reduction of plasma HCV-RNA PCR from baseline by at least 1 log10 at any time during pegylated interferon treatment.
Ability and willingness to give written informed consent.
Male and female subjects, ages > 18 to 65 years, weight < 130 kg.
Chronic liver disease consistent with HCV infection on a liver biopsy in the previous 2 years. Judged by a local pathologist. Eligible subjects must have a total fibrosis score of > 0. Those subjects who have not had biopsies in the past 2 years will be required to have a biopsy prior to enrollment.
If hepatic cirrhosis is defined by liver biopsy (fibrosis score of 6) or by imaging study, then subjects must be no more than Child-Pugh class A and have a serum α-fetoprotein less than or equal to the ULN within 28 days prior to study entry.
Laboratory values that meet the following criteria within 28 days before study entry:
Absolute neutrophil count ≥ 1.0x109/L. Platelet count ≥70x109/L. Hemoglobin ≥100 g/L. Serum creatinine ≤150 μmol/L. Thyroid-stimulating hormone (TSH) values within the normal range of the local institution laboratory. ALT level < 10 time ULN.
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| E.4 | Principal exclusion criteria |
Previously treated with more than two courses of treatment with an IFN-α based regimen -including consensus IFN-α (i.e. a course of treatment is any treatment of more than 12 weeks of therapy).
Known HIV 1 or HIV 2 antibody positivity or Hepatitis B Surface Antigen (HBsAg) positivity at any time prior to entry.
Any past evidence of medical conditions associated with chronic liver disease other than HCV (e.g., genetic hemochromatosis, autoimmune hepatitis, alcoholic cirrhosis, toxin exposures).
Severe psychiatric disease, especially depression. Subjects with severe psychiatric disease, a previous suicidal attempt or hospitalization for a psychiatric episode within the previous 24 weeks.
History of hypersensitivity to ribavirin, IFN or other component of the study products.
History of uncontrolled seizure disorders.
Any past or current evidence of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
Evidence of chronic pulmonary disease associated with functional limitation (forced to stop periodically every few minutes or every 100 meters by dyspnea, or need for ambulatory oxygen supplementation).
Evidence of severe cardiac insufficiency (e.g., Patients with heart disease who are comfortable at rest but have symptoms with less than ordinary activity), myocardial infarction, or ventricular tachyarrhythmia requiring ongoing treatment or unstable angina within 24 weeks of entry.
Severe retinopathy due to diabetes, hypertension, or macular degeneration.
History of major organ transplantation with an existing functional graft.
History or other evidence of severe illness, malignancy or any other conditions that would make the subject, in the opinion of the investigator, unsuitable for the study, i.e., a history of a solid tumor or active bacterial infection, conditions that could potentially be exacerbated by the study drugs.
Any systemic antineoplastic or immunomodulatory treatment or radiation within 24 weeks of the study entry or the expectation that such treatment will be needed at any time during the study.
More than or equal to a 30-day use of supraphysiologic doses of corticosteroid (>10 mg of prednisone daily or equivalent) within the previous 90 days of study entry.
Active drug or alcohol abuse or dependence, which in the opinion of the investigator, would interfere with adherence to study requirements, or endanger the subject’s health while on the study. Subjects in methadone programs are eligible to participate.
Known hemoglobinopathy (e.g. thalassemia) or any other cause of or tendency to hemolysis.
Administration of investigational drug with potential activity against HCV within 6 weeks of study entry (e.g. IL-10, polymerase or protease inhibitor).
Presence of acute or active infection within 4 weeks of study entry.
Women who are pregnant or breast-feeding.
Women with a positive serum or urine pregnancy test within 28 days prior to study entry and at study entry.
All women of reproductive potential (defined for this study as sexually mature women who have not been postmenopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or have not undergone hysterectomy or oophorectomy) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL performed within 24 hours before initiating the protocol-specified medication(s).
Female study volunteers who are not of reproductive potential (who have been postmenopausal for at least 24 consecutive months or have undergone hysterectomy or oophorectomy) are eligible without requiring the use of contraception. Acceptable documentation of menopause, hysterectomy, and oophorectomy must be obtained.
All study patients (male or female) who will receive ribavirin must not participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) and, if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must use two reliable methods of contraception simultaneously while receiving protocol-specified medication(s), and for 6 months after stopping the medication(s).
Participation in another therapeutic trial.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
This is a proof-of-concept study to explore the efficacy and safety of Multiferon® in combination with ribavirin in the treatment of patients with chronic HCV infection. No confirmatory hypothesis is proposed. Descriptive statistics will be used to compare the effect of Multiferon® at low and high dose in combination with ribavirin to establish the appropriate parameters for future studies.
The primary efficacy parameters to evaluate the efficacy of Multiferon at high and low dose is the rate of viral response i.e. quantitative HCV-RNA PCR less than limit of detection of the assay at week 12, end of treatment and end of follow-up
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| 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 | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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 | 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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
|
| The study ends with last visit of the last subject. |
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| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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