E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis B crónica
Chronic hepatitis B |
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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 |
• Comparar la eficacia y la seguridad antivírales y la tolerabilidad de 300 mg una vez al día de tenofovir DF con las de un placebo una vez al día en adolescentes (de 12-17 años de edad) con infección por hepatitis B crónica
• To compare the antiviral efficacy, safety and tolerability of tenofovir DF 300 mg once daily versus placebo once daily in adolescents (aged 12–17 years) with chronic hepatitis B infection |
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E.2.2 | Secondary objectives of the trial |
• Evaluar las respuestas bioquímica y serológica al tenofovir DF y al placebo en adolescentes con infección por hepatitis B crónica • Evaluar la incidencia de mutaciones que confieren resistencia al fármaco
• To evaluate the biochemical and serological responses to tenofovir DF versus placebo in adolescents with chronic hepatitis B infection • To evaluate the incidence of drug resistance mutations
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female • 12 through 17 years of age, inclusive (consent of parent/legal guardian required) • Documented chronic HBV infection, defined as positive serum HBsAg ≥ 6 months • HBeAg positive • Weight ≥ 35 kg • Able to swallow oral tablets • HBV DNA ≥10^5 copies/mL (PCR method) • ALT ≥ 2 × ULN at screening, OR any history of ALT ≥ 2 × ULN over the past ≤ 24 months • Willing and able to provide written informed consent/assent (child and parent/legal guardian) • Negative serum β HCG pregnancy test (for post-menarchal females only) • Estimated glomerular filtration rate (creatinine clearance) ≥ 80 mL/min/1.73m2 • Adequate hematologic function (absolute neutrophil count ≥ 1,500/mm3; hemoglobin ≥ 10.0 g/dL) • No prior tenofovir DF therapy (subjects may have received prior interferon or oral anti-HBV nucleoside/nucleotide therapy; subjects must have discontinued interferon therapy ≥ 6 months prior to screening; subjects experienced on anti-HBV nucleoside/nucleotide therapy must have discontinued therapy ≥ 16 weeks prior to screening to avoid flare if randomized to the placebo arm)
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E.4 | Principal exclusion criteria |
• Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study. • Sexually-active males and females of reproductive potential who are not willing to use an effective method of contraception during the study. For males, condoms should be used and for females, a barrier contraception method should be used in combination with one other form of contraception. • Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN, PT > 1.2 x ULN, platelets < 150,000/mm3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy, variceal hemorrhage). • Receipt of interferon (pegylated or not) therapy within 6 months of the Screening Visit • Receipt of anti-HBV nucleoside/nucleotide therapy within 16 weeks of the Screening Visit • α-fetoprotein > 50 ng/mL • Evidence of hepatocellular carcinoma (HCC) • Co infection with HIV, HCV, or HDV • History of significant renal disease (e.g., nephrotic syndrome, renal dysgenesis, polycystic kidney disease, congenital nephrosis, acute tubular necrosis, other renal disease) • History of significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses, multiple bone fractures) • Significant cardiovascular, pulmonary or neurological disease • Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications • History of solid organ or bone marrow transplantation • Ongoing therapy with any of the following: - Nephrotoxic agents - Chronic daily non-steroidal anti-inflammatory drug therapy Administration of any of the above medications must be discontinued at least 30 days prior to the Baseline Visit and for the duration of the study period. • Known hypersensitivity to the study drugs, the metabolites or formulation excipients • Any other condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is a composite endpoint of HBV DNA < 400 copies/mL and ALT normal at Week 72.
For the HBV DNA component, a “persistent virologic response” approach to handling missing data will be employed; the details of this convention will be included in a separate statistical analysis plan. The primary safety endpoint is cumulative incidence of at least a 6% decrease from baseline in bone mineral density of the spine through Week 72.
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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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 | 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 end of study is defined when each subject reaches Week 192. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |