Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab (OI-AK)
Primary Purpose
Osteogenesis Imperfecta
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Denosumab
Sponsored by
About this trial
This is an interventional treatment trial for Osteogenesis Imperfecta focused on measuring Osteogenesis imperfecta, COL1A1/A2, Denosumab, Bisphosphonates, Children, Areal bone mineral density
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.
Sites / Locations
- University Cologne, Childrens Hospital, Cologne, Germany
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Denosumab subcutaneously
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Decrease of osteoclastic activity measured by urinary deoxypyridinoline (DPD).
Parathormone in study week 12, 24, 36 and 48 compared to baseline.
Descriptive statistical analysis
N-Telopeptides in study week 12, 24, 36 and 48 compared to baseline.
descriptive statistical analysis
Osteocalcin in study week 12, 24, 36 and 48.
descriptive statistical analysis
Full Information
NCT ID
NCT01799798
First Posted
February 14, 2013
Last Updated
January 26, 2015
Sponsor
University of Cologne
1. Study Identification
Unique Protocol Identification Number
NCT01799798
Brief Title
Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
Acronym
OI-AK
Official Title
TRANSLATIONAL THERAPY IN PATIENTS WITH OSTEOGENESIS IMPERFECTA - A PILOT TRIAL ON TREATMENT WITH THE RANKL-ANTIBODY DENOSUMAB
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cologne
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteogenesis Imperfecta
Keywords
Osteogenesis imperfecta, COL1A1/A2, Denosumab, Bisphosphonates, Children, Areal bone mineral density
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Denosumab subcutaneously
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Denosumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Decrease of osteoclastic activity measured by urinary deoxypyridinoline (DPD).
Time Frame
14 days (DPD)
Title
Parathormone in study week 12, 24, 36 and 48 compared to baseline.
Description
Descriptive statistical analysis
Time Frame
12 weeks
Title
N-Telopeptides in study week 12, 24, 36 and 48 compared to baseline.
Description
descriptive statistical analysis
Time Frame
12 weeks
Title
Osteocalcin in study week 12, 24, 36 and 48.
Description
descriptive statistical analysis
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joerg Oliver Semler, MD
Organizational Affiliation
University Cologne, Childrens Hospital, Cologne, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Cologne, Childrens Hospital, Cologne, Germany
City
Cologne
State/Province
NRW
ZIP/Postal Code
50924
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
22947550
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.
Results Reference
background
Learn more about this trial
Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
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