E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In this study we will evaluate the efficacy of Denosumab in children with Osteogenesis imperfecta. Subjects will be treated every 12 weeks over 36 weeks with Denosumab 1mg/kg body weight s.c.. Efficacy will be evaluated by DXA measurements of the spine for bone mineral density. |
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E.1.1.1 | Medical condition in easily understood language |
Efficacy of Denosumab in children with Osteogenesis imperfecta should be evaluated in this trial. |
Bei Kindern mit Glasknochen soll die Wirksamkeit von Denosumab (keine Veschlechertung der Knochendichte) bei Therapie über 36 Wochen nach 48 Wochen untersucht werden (Dosis 1mg/kgKG alle 3 Monate).
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Pilot study to assess the safety and efficacy of a therapy with the RANKL-antibody Denosumab in children 5-10 years of age with mutation in COL1A1 or COL1A2 leading to a defect in collagen production (Osteogenesis imperfecta). Efficacy will be assessed by DXA measurements at the lumbar spine (BMD). |
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E.2.2 | Secondary objectives of the trial |
• Decrease of osteoclastic activity measured by
Deoxypyridinolin (DPD) and changes of bone metabolism
(Parathormone, N-Telopeptides, Osteocalcin).
• Mobility of patients (Gross motor function measurement
score)
• Skeletal pain (visual pain scale)
• Changes of bone mineral density of the whole body
• Morphometry of spine (Severity Score of the spine)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female subjects between 5 years and 10 years of age with molecular proven Osteogenesis imperfecta type III/IV (COL1A1/1A2 mutation)
• Subjects must have been treated for a minimum of 2 years with Neridronate prior to study entry
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E.4 | Principal exclusion criteria |
• Hypocalcemia (<1.03 mmol/l ionisized Calcium)
• Subjects with reduced renal function (estimated GFR (Schwartz formula) <30ml/min/1.73m2)
• Any other abnormal finding such as physical examination or laboratory evaluation, in the opinion of the investigator that is indicative of a disease that would compromise the safety of the patient when getting Denosumab s.c.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint:
Changes of bone mineral density (BMD [g/cm2]) between study week 0 and 48 of the lumbar spine after 36 weeks of treatment with Denosumab |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline Study week 0 and Study week 48 |
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E.5.2 | Secondary end point(s) |
Key secondary endpoint(s):
• Decrease of osteoclastic activity measured by Deoxypyridinolin (DPD) and changes of bone metabolism (Parathormone, N-Telopeptides, Osteocalcin).
• Mobility of patients (Gross motor function measurement score)
• Skeletal pain (visual pain scale)
• Changes of bone mineral density of the whole body
• Morphometry of spine (Severity Score of the spine)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key secondary endpoint(s):
• Decrease of osteoclastic activity measured by Deoxypyridinolin (DPD) and changes of bone metabolism (Parathormone, N-Telopeptides, Osteocalcin).
Study week -12, 0, 12, 24, 36, 48.
• Mobility of patients (Gross motor function measurement score)
Study week 0, 24 and 48
• Skeletal pain (visual pain scale)
Study week -12, 0, 12, 24, 36, 48.
• Changes of bone mineral density of the whole body study week 0 and 48
• Morphometry of spine (Severity Score of the spine)
Study week 0 and 48
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | 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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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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Last visit of the last subject |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |