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.
Conditions
Interventions
Trade Name: Prolia
Product Name: Denusomab
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DENOSUMAB
CAS Number: 615258-40-7
Other descriptive name: DENOSUMAB
Concentration unit: g/l
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 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) ;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 ;Timepoint(s) of evaluation of this end point: Baseline Study week 0 and Study week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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) ;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 | — |
Countries
Germany
Contacts
Public ContactKlinisches Studienzentrum Pädiatrie
Children's Hospital of the University of Cologne
Outcome results
None listed