E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008910 |
E.1.2 | Term | Chronic hepatitis B |
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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 and safety of PEG-IFN given for both varied duration, either 24 or 48 weeks and at different doses, 90 or 180mcg weekly doses in the treatment of HBeAg positive patients with chronic hepatitis B virus infection, 24 weeks after the end of therapy |
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E.2.2 | Secondary objectives of the trial |
To compare the influence of varied duration and dose on the secondary endpoints and in the event of equivocal findings to explore potential subsets of patients who might benefit from particular treatment regimens. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Age >= 18 years •Positive HBsAg for more than 6 months, positive HBeAg, detectable HBV DNA (patients must have > 500,000 copies/ml (100,000 IU/ml) as measured by PCR) and anti HBs negative •Elevated serum ALT > ULN but <= 10 x ULN as determined by two abnormal values taken >= 14 days apart during the six months before the first dose of study drug with at least one of the determinations obtained <= 35 days prior to the first dose. •A liver biopsy obtained within the past 2 years (and more than 6 months after the end of any previous therapy for hepatitis B) demonstrating liver disease consistent with chronic hepatitis B. Patients with cirrhosis or bridging fibrosis on liver biopsy must also have a liver imaging study to rule out hepatic carcinoma. •Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and for 3 months after treatment completion.
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E.4 | Principal exclusion criteria |
•Patients must not have received antiviral therapy for their chronic hepatitis B within the previous 6 months. Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded. Exception: patients who have had a limited (<= 7 day) course of acyclovir for herpetic lesions more than 1 month prior to the first administration of test drug are not excluded. •Positive test at screening for HAV IgM Ab, HCV-RNA or HCVAb, HDV Ab or HIV Ab. •Serum concentrations of ceruloplasmin or alfa1-antitrypsin consistent with an increased risk of metabolic liver disease. •Any evidence of decompensated liver disease (Childs B-C, Appendix 2) •History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures, thalassemia). •Women with ongoing pregnancy or who are breast feeding. •Neutrophil count < 1500 cells/mm3or platelet count < 90,000 cells/mm3. •Serum creatinine level > 1.5 times the upper limit of normal at screening. •Evidence of alcohol and/or drug abuse within one year of entry. •History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis, suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease. •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 other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease. •History or other evidence of chronic pulmonary disease associated with functional limitation. •History of severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases). •History of a severe seizure disorder or current anticonvulsant use. •Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is >= 20% within 2 years. Patients with a lesion suspicious for hepatic malignancy on a screening imaging study will only be eligible if the likelihood of carcinoma is <=10% following an appropriate evaluation. •History of having received any systemic anti-neoplastic (including radiation) or immunomodulatory treatment (including systemic corticosteroids) <= 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. •History of major organ transplantation with an existing functional graft •History of thyroid disease poorly controlled on prescribed medications. Patients with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded. •History or other evidence of severe retinopathy •Inability or unwillingness to provide informed consent or abide by the requirements of the study. •History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study. •Patients with a value of alpha-fetoprotein >100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months.
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E.5 End points |
E.5.1 | Primary end point(s) |
HBeAg seroconversion (loss of HBeAg and presence of anti-HBe) at the end of the initial 24 week treatment free 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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
standard dose and standard duration |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
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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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |