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

NCT ID: NCT01799798

Last Updated: 2015-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2015-01-31

Brief 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.

Conditions

Osteogenesis Imperfecta

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Denosumab subcutaneously

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cologne

OTHER

Sponsor Role: lead

Responsible Party

Dr. med. Joerg Oliver Semler

Head of the outpatient center for sceletal dysplasias

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joerg Oliver Semler, MD

Role: PRINCIPAL_INVESTIGATOR

University Cologne, Childrens Hospital, Cologne, Germany

Locations

University Cologne, Childrens Hospital, Cologne, Germany

Cologne, North Rhine-Westphalia, Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 22947550 (View on PubMed)

Other Identifiers

Uni-Koeln-1574

Identifier Type: -

Identifier Source: org_study_id