E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pre-cirrhotic chronic hepatitis B virus (HBV) infection |
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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 gain an understanding of the cellular immune responses to HBV associated with standard Pegasys monotherapy versus Lamivudine priming of Pegasys [in two regimens] in HBeAg positive patients. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the relationship between early immunological and virological parameters with outcome of standard Pegasys monotherapy versus Lamivudine priming of Pegasys [in two regimens] in HBeAg positive chronic hepatitis B. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
To be eligible for this study, patients must have the following documented: 1. Age > 18 years 2. Positive HBsAg for more than 6 months, positive HBeAg, detectable HBV DNA (patients must have >100,000 iu/ml (>500,000 copies/ml) as measured by PCR) 3. Elevated serum ALT > 1.1 x ULN but < 10X ULN 4. A liver biopsy obtained within the past 18 months (and more than 6 months after the end of any previous therapy for hepatitis B) demonstrating liver disease consistent with pre-cirrhotic chronic hepatitis B. 5. Negative urine pregnancy test (for women of childbearing potential) documented within the 48-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 |
· Histological or clinical evidence of established cirrhosis · HIV co-infection (written consent will be taken for the HIV testing and counselling offered) · HCV or HDV co-infection · Renal impairment: serum creatinine >1.5 ULN · Neurological/psychiatric disorder · Severe cardiac or pulmonary disease · History or other evidence of severe retinopathy · Severe seizure disorder or current anti-convulsant use · Active or suspected cancer or a history of malignancy where the risk of recurrence is greater than 20% within 2 years. · Any other significant systemic disease, including thyroid disease · Unable to conform to study protocol due to alcohol use in excess of 20gms/day or drug abuse · Alcohol abuse [alcohol in excess of safe limits of 28 units/ week for men and 21 units/week for women] and/or intravenous drug abuse within 1 year of entry · A medical condition associated with chronic liver disease other than viral hepatitis · Neutrophil count <1,500 cells/ml or platelet count < 100,000 cells/ml · Albumin < lower limit of normal · Serum alphafetoprotein >2 x ULN · Anti-viral treatment with interferon alpha or nucleoside analogue within 18 months · Previous treatment with Lamivudine for > 12 months · Evidence of emergence of Lamivudine resistant HBV · Any research study within previous 3 months
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E.5 End points |
E.5.1 | Primary end point(s) |
· Serious or life-threatening adverse event · Subject is found to be in violation of the protocol exclusion criteria · Failure to comply with the dosing, evaluations or other requirements of the study · Request of the subject (subjects have the right to discontinue treatment at any time for any reason) · Subject becomes pregnant · The investigator feels that discontinuation is in the best interest of the subject
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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 | Yes |
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) | 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 |
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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.8.5 | 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 | 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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |