ew therapeutic approach in OI with the antibody Denosumab

Conditions: 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.
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2012-002887-29-DE

Lead Sponsor: niversity of Cologne

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

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

Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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).;Secondary Objective: •Decrease of osteoclastic activity measured by <br> Deoxypyridinolin (DPD) and changes of bone metabolism <br> (Parathormone, N-Telopeptides, Osteocalcin).<br>•Mobility of patients (Gross motor function measurement <br> score)<br>•Skeletal pain (visual pain scale)<br>•Changes of bone mineral density of the whole body<br>•Morphometry of spine (Severity Score of the spine) <br>;Primary end point(s): Primary efficacy endpoint: <br>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 ;Timepoint(s) of evaluation of this end point: Baseline Study week 0 and Study week 48

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Key secondary endpoint(s): <br>•Decrease of osteoclastic activity measured by Deoxypyridinolin (DPD) and changes of bone metabolism (Parathormone, N-Telopeptides, Osteocalcin).<br>•Mobility of patients (Gross motor function measurement score)<br>•Skeletal pain (visual pain scale)<br>•Changes of bone mineral density of the whole body<br>•Morphometry of spine (Severity Score of the spine) <br>;Timepoint(s) of evaluation of this end point: Key secondary endpoint(s): <br>•Decrease of osteoclastic activity measured by Deoxypyridinolin (DPD) and changes of bone metabolism (Parathormone, N-Telopeptides, Osteocalcin).<br>Study week -12, 0, 12, 24, 36, 48.<br>•Mobility of patients (Gross motor function measurement score)<br>Study week 0, 24 and 48<br>•Skeletal pain (visual pain scale)<br>Study week -12, 0, 12, 24, 36, 48.<br>•Changes of bone mineral density of the whole body study week 0 and 48<br>•Morphometry of spine (Severity Score of the spine)<br>Study week 0 and 48<br>