Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab (OI-AK)
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||TRANSLATIONAL THERAPY IN PATIENTS WITH OSTEOGENESIS IMPERFECTA - A PILOT TRIAL ON TREATMENT WITH THE RANKL-ANTIBODY DENOSUMAB|
- 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. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
- Decrease of osteoclastic activity measured by urinary deoxypyridinoline (DPD). [ Time Frame: 14 days (DPD) ] [ Designated as safety issue: Yes ]
- Parathormone in study week 12, 24, 36 and 48 compared to baseline. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Descriptive statistical analysis
- N-Telopeptides in study week 12, 24, 36 and 48 compared to baseline. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]descriptive statistical analysis
- Osteocalcin in study week 12, 24, 36 and 48. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]descriptive statistical analysis
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
|Experimental: Denosumab subcutaneously||
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01799798
|University Cologne, Childrens Hospital, Cologne, Germany|
|Cologne, NRW, Germany, 50924|
|Principal Investigator:||Joerg Oliver Semler, MD||University Cologne, Childrens Hospital, Cologne, Germany|