E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Long term infection with the hepatitis B virus |
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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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008910 |
E.1.2 | Term | Chronic hepatitis B |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 investigate the efficacy of adefovir dipivoxil for the treatment of chronic hepatitis B in children and adolescents (age 2 to < 18) compared to placebo following 48 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
- To investigate the safety of adefovir dipivoxil for the treatment of chronic hepatitis B in children and adolescents (age 2 to < 18) compared to placebo following 48 weeks of treatment.
- To evaluate the proportion of children and adolescents who experience HBeAg and HBsAg seroconversion following 48 weeks of treatment with adefovir dipivoxil or placebo.
- To evaluate the development of conserved-site mutations associated with resistance to adefovir dipivoxil.
- To evaluate the safety (including assessment of growth and renal function) and efficacy of adefovir dipivoxil in children and adolescents for up to 5 years. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients aged 2 to < 18 years.
- Females of childbearing potential must have a negative serum pregnancy test at screening. Females of childbearing potential who are using effective methods of contraception and will agree to continue to do so from 30 days prior to randomization, throughout study medication dosing and for 30 days after the last dose of study medication will be able to participate.
-Documented chronic hepatitis B (positive HBsAg present for ≥ 6 months prior to randomization). HBsAg must be positive at the initial screening visit (i.e., within 4 weeks of first dose) before patients can be enrolled into the study.
- Documented positive HBeAg at screening.
- Serum HBV DNA ≥ 1 × 105 copies/mL (PCR assay) at either the initial or confirmatory screening visits. |
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E.4 | Principal exclusion criteria |
- Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol. This would include any active clinically significant renal, cardiac, pulmonary, vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, or malignancy.
- Received immunoglobulins or other immune- or cytokine-based therapies with possible activity against hepatitis B disease within 6 months prior to the initial screening visit.
- Received interferon therapy within 6 months prior to the initial screening visit.
- Received lamivudine therapy within 6 months prior to the initial screening visit.
- Received previous treatment with antiviral agents demonstrating anti-HBV activity other than interferon or lamivudine within 6 months prior to the initial screening visit (e.g., famciclovir, lobucavir, ganciclovir, emtricitabine, amdoxovir, clevudine, entecavir, or others). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint
- Serum HBV DNA < 1000 copies/mL (PCR based assay) and normal ALT |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoint
- Serum HBV DNA < 1000 copies/mL (PCR based assay) and normal ALT at Weeks 96,
144, 192, and 240.
- Change from baseline in serum HBV DNA.
- Change from baseline in ALT. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At Weeks 48, 96, 144, 192, and 240 unless
otherwise stated. |
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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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA 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.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |