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

Osteogenesis Imperfecta Clinical Trial

— OI-AK  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01799798
• Other study ID #: Uni-Koeln-1574
• Status: Completed
• Phase: Phase 2
• First received: February 14, 2013
• Last updated: January 26, 2015
• Start date: February 2013
• Est. completion date: January 2015

Study information

• Verified date: January 2015
• Source: University of Cologne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 11 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Intervention

Drug:
• Denosumab
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.

Locations

Country	Name	City	State
Germany	University Cologne, Childrens Hospital, Cologne, Germany	Cologne	NRW

Sponsors (1)

Lead Sponsor	Collaborator
University of Cologne

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Semler O, Netzer C, Hoyer-Kuhn H, Becker J, Eysel P, Schoenau E. First use of the RANKL antibody denosumab in osteogenesis imperfecta type VI. J Musculoskelet Neuronal Interact. 2012 Sep;12(3):183-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Decrease of osteoclastic activity measured by urinary deoxypyridinoline (DPD).		14 days (DPD)	Yes
Secondary	Parathormone in study week 12, 24, 36 and 48 compared to baseline.	Descriptive statistical analysis	12 weeks	No
Secondary	N-Telopeptides in study week 12, 24, 36 and 48 compared to baseline.	descriptive statistical analysis	12 weeks	No
Secondary	Osteocalcin in study week 12, 24, 36 and 48.	descriptive statistical analysis	12 weeks	No

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