E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Chronic hepatitis C (CHC) genotype 2 or 3 infection with previous response relapse | |
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 evaluate the efficacy of pegylated interferon alfa-2a 40 kD (PEGASYS®) combination therapy with ribavirin (Copegus®) given for 24 or 48 weeks in patients with chronic hepatitis C (CHC) virus infection genotype 2 or 3 who responded during (i.e. had HCV-RNA < 50 IU/mL at the end of previous therapy), but relapsed after (i.e. had detectable HCV-RNA after the end of prior treatment) previous therapy with pegylated interferon and ribavirin given for at least 12 weeks and at most 24 weeks. | |
E.2.2 | Secondary objectives of the trial | To prospectively evaluate: •the predictive value of monitoring of viral load at screening visit, day 0, 6, 13 og 27, week 8, 12 og 24, for determining which patients will obtain a sustained virological response (SVR) when treated with combination therapy given for 24 or 48 weeks. •the association between non-invasive fibrosis indexes, e.g. APRI and GUCI, and the therapeutic efficacy of therapy. •the association between pretreatment blood, serum, and plasma factors and the therapeutic efficacy of therapy . •adherence to therapy •the association between trough ribavirin concentration day 13, 27, week 8, 12, and 24 and (week 48 group A + B) the therapeutic efficacy of therapy. •the association between BMI/waist measurement and the therapeutic efficacy of therapy. •the association between cirrhosis, bridging fibrosis,significant fibrosis, grade of inflammation, and steatosis grade in the available liver biopsies, and the therapeutic efficacy of therapy. | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | •Male and female patients ≥ 18 years of age •Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test •Serum HCV-RNA ≥ 15 IU/mL. •HCV genotype 2 or/and 3 infection confirmed within the past 6 months preceding the initiation of test drug dosing. The HCV genotype must have been reconfirmed after the termination of the previous treatment period. •Previous relapse (i.e. HCV-RNA < 50 IU/mL at end of previous therapy) after one treatment period with pegylated interferon alfa-2a or alfa-2b combination therapy with ribavirin for at least 12 weeks and at most 24 weeks. •A minimum of 24 weeks must have elapsed since the last dose of pegylated interferon or ribavirin in the previous treatment period before the patients can be included in this study. •Compensated liver disease (Child-Pugh Grade A clinical classification) •Patients with suspected cirrhosis or transition to cirrhosis must have an abdominal ultrasound, CT scan, or MRI scan without evidence of hepatocellular carcinoma and a serum AFP < 100 ng/mL within 2 months of randomization •Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug •All fertile males and females receiving ribavirin must be using effective contraception during treatment and during the 6 months after treatment end •Having a liver biopsy obtained within 5 years of this study is encouraged, but optional in accordance with local treatment traditions. | |
E.4 | Principal exclusion criteria | •Women with ongoing pregnancy or breast feeding •Previous non-response during treatment (as defined as having detectable HCV RNA ≥ 50 IU/ml at the end of previous treatment) with pegylated interferon alfa-2a or alfa-2b combination therapy with ribavirin for at least 12 weeks and at most 24 weeks. •Less than 24 weeks have elapsed since the last dose of pegylated interferon or ribavirin in the previous treatment period prior to inclusion in this study. •Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤ 6 months prior to the first dose of study drug •Any investigational drug ≤ 6 weeks prior to the first dose of study drug. •HCV genotype 1, 4, 5 or 6 infection. •Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, anti-HIV Ab •Evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures) •History or other evidence of decompensated liver disease •Neutrophil count < 1500 cells/mm3 or platelet count < 75,000 cells/mm3 at screening •Serum creatinine level > 2 mg/dl (> 124 µmol/L) or creatinine clearance < 50 ml/minute at screening •Severe psychiatric disease, especially depression, as judged by the treating physician. •History of a severe seizure disorder or current anticonvulsant use •History of immunologically mediated disease, severe chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation 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 •Thyroid dysfunction not adequately controlled (TSH and T4 levels out of normal range) •Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration) or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension •Evidence of drug abuse (including excessive alcohol consumption) in accordance with local therapeutic traditions. (Patients receiving Methadone or Subutex therapy may be included in this study.) •Inability or unwillingness to provide informed consent or abide by the requirements of the study •Male partners of women who are pregnant •Hemoglobin < 11.3 g/dL (< 7.0 mmol/L) in women or < 12.9 g/dL (< 8.0 mmol/L) in men at screening. •Any patient with an increased baseline risk for anemia (e.g. thalassemia, spherocytosis, etc) or for whom anemia would be medically problematic •Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin therapy) would not be well-tolerated •Evidence of IVDU since end of previous treatment period with peg-interferon and ribavirin | |
E.5 End points |
E.5.1 | Primary end point(s) | •SVR rate defined as percentage of patients with non-detectable HCV-RNA 24 weeks after completion of the 24 or 48 week treatment period | |
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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
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 | Last visit of last subject, i.e. 6 month after end of treatment | |
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 | 6 |
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 | 6 |