Clinical trial NCT01799798: Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
Official title: TRANSLATIONAL THERAPY IN PATIENTS WITH OSTEOGENESIS IMPERFECTA - A PILOT TRIAL ON TREATMENT WITH THE RANKL-ANTIBODY DENOSUMAB
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteogenesis Imperfecta
Keywords: Osteogenesis imperfecta
COL1A1/A2
Denosumab
Bisphosphonates
Children
Areal bone mineral density
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2013-02-27
Enrollment: 10
Sex: ALL
Minimum age (years): 5
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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.
timeFrame: 48 weeks
Secondary outcomes:
measure: Decrease of osteoclastic activity measured by urinary deoxypyridinoline (DPD).
timeFrame: 14 days (DPD)
measure: Parathormone in study week 12, 24, 36 and 48 compared to baseline.
timeFrame: 12 weeks
measure: N-Telopeptides in study week 12, 24, 36 and 48 compared to baseline.
timeFrame: 12 weeks
measure: Osteocalcin in study week 12, 24, 36 and 48.
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: University Cologne, Childrens Hospital, Cologne, Germany
state: NRW
Study officials:
affiliation: University Cologne, Childrens Hospital, Cologne, Germany
name: Joerg Oliver Semler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.