Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab

Study Overview
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Brief Summary
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Pilot study to assess the efficacy of a therapy with the RANKL-antibody denosumab in children 5-10 years of age with mutation in COL1A1 or COL1A2 leading to Osteogenesis imperfecta. Efficacy will be assessed by DXA measurements at the lumbar spine of the areal bone mineral density (BMD) which is the most frequently used parameter in trials investigating osteoporosis. The hypothesis of the study is: Osteoclastic activity which is increased in OI could be reduced by inhibition of osteoclast maturation. Denosumab inhibits maturation of the osteoclasts by inhibiting RANKL. BMD could be increased during a 36 week treatment course with denosumab measured after 48 weeks.

Official Title
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TRANSLATIONAL THERAPY IN PATIENTS WITH OSTEOGENESIS IMPERFECTA - A PILOT TRIAL ON TREATMENT WITH THE RANKL-ANTIBODY DENOSUMAB

Conditions
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Osteogenesis Imperfecta

Intervention / Treatment
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* Drug: Denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female subjects between 5 years and 10 years of age with molecular proven Osteogenesis imperfecta (COL1A1/A2 mutation) Subjects must have been treated for a minimum of 2 years with bisphosphonates prior to study entry Exclusion Criteria: Hypocalcemia (<1.03 mmol/l ionized 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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab subcutaneously<br> | Drug: Denosumab<br>* Denosumab will be given subcutaneously in a dosage of 1mg/kg body weight every 12 weeks. 4 interventions are planned until trial week 36. There is no control group planned.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of bone mineral density (BMD [g/cm2]) in lumbar spine after 36 weeks of treatment with denosumab. Changes will be calculated between baseline and study week 48. |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease of osteoclastic activity measured by urinary deoxypyridinoline (DPD). |  | 14 days (DPD) | 
| Parathormone in study week 12, 24, 36 and 48 compared to baseline. | Descriptive statistical analysis | 12 weeks | 
| N-Telopeptides in study week 12, 24, 36 and 48 compared to baseline. | descriptive statistical analysis | 12 weeks | 
| Osteocalcin in study week 12, 24, 36 and 48. | descriptive statistical analysis | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteogenesis imperfecta, COL1A1/A2, Denosumab, Bisphosphonates, Children, Areal bone mineral density