E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of HBeAg positive chronic hepatitis B (CHB) in children. |
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E.1.1.1 | Medical condition in easily understood language |
HBeAg positive immunoactive Chronic (long-term) HepatitisB.Presence of HBeAg indicates an early stage of disease.Immunoactive disease means the liver has started to become damaged by the infection. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052552 |
E.1.2 | Term | Hepatitis B virus |
E.1.2 | System Organ Class | 100000004848 |
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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 HBeAg seroconversion (loss of HBeAg and presence of anti-HBe) between a group treated with PEG-IFN monotherapy and an untreated control group.
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E.2.2 | Secondary objectives of the trial |
To examine the short and longer term effects on various efficacy and safety measures between a group treated with PEG-IFN monotherapy and an untreated control group, and to evaluate pharmacokinetics (PK) in PEG-IFN treated subjects. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
For consenting/assenting subjects in the site specific liver elasticity sub-study, liver elastography will be performed at baseline, at the end of treatment/observation period, follow-up week 24 and follow-up year 2.
For consenting/assenting subjects in the site specific PK sub-study, additional visits will also be required for PK blood sampling. When adequate PK data have been collected over the first 24 weeks for at least 15 PEG-IFN treated subjects, ideally with
representation from all BSA categories, exposure will be analyzed and if necessary an adjustment will be made to the dosing regimen. Once PK data up to week 24/switch week 24 is available for at least 5 to 10 subjects in each BSA category, subject PK
sampling will be stopped. However, the sub-study may be stopped even if data from a minimum of 5 subjects in each BSA category are not obtained in the case of excessively long recruitment times.
For subjects with advanced fibrosis, a liver bipsy needs to be performed within 9 months prior to baseline. |
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E.3 | Principal inclusion criteria |
Children aged 3 to <18 years of age with CHB, HBeAg+ve, HBsAg+ve, detectable HBV DNA (>10,000 copies/mL [>2,000 IU/ml]) by PCR and ALT >ULN but ≤10 x ULN (using the local sites' reference range). Liver biopsy needs to have been conducted within the previous 2 years. |
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E.4 | Principal exclusion criteria |
Subjects co-infected with HCV, HDV, HIV, or who have received therapy for hepatitis B in the prior 6 months, or have cirrhosis, or who have de-compensated liver disease will be excluded. |
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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). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the 24 week post-end of-treatment/principal observation period. |
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E.5.2 | Secondary end point(s) |
• Loss of HBeAg, HBsAg seroconversion (loss of HBsAg and presence of anti-HBs), loss of HBsAg, quantitative serum ALT, proportion of normal ALT, quantitative HBV DNA, suppression of HBV DNA <100,000 copies/mL (<20,000 IU/mL), <10,000 copies/mL (<2,000 IU/mL), undetectable and change from baseline, combined endpoint of HBeAg seroconversion and HBV DNA <100,000 copies/mL (<20,000 IU/mL), and combined endpoint of HBeAg seroconversion and HBV DNA <10,000 copies/mL (<2,000 IU/mL).
• Persistence HBeAg seroconversion (loss of HBeAg and presence of anti-HBe).
• Descriptive change in liver elasticity (in liver elasticity sub-study subjects).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• At the end of treatment/principal observation period, at 24 weeks
after end of treatment/principal observation period, and at 1, 2, 3, 4 and 5 years after end of treatment/principal observation period.
• At the end of treatment/principal observation period, and at 1, 2, 3, 4 and 5 years after end of treatment/principal observation period.
• At end of treatment/principal observation period, and at 24 weeks and 2 years after end of treatment/principal observation period. |
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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 | No |
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) | 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 | 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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | No |
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 |
Australia |
Belgium |
Bulgaria |
China |
Germany |
Israel |
Italy |
Poland |
Russian Federation |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The primary endpoint will be assessed 24 weeks after the end of treatment/principal observation period, with a further 4.5 years of extended long-term follow-up. The end of study is Last Subject Last Visit. |
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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 | 9 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |