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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Dr. med. Joerg Oliver Semler, University of Cologne
ClinicalTrials.gov Identifier:
NCT01799798
First received: February 14, 2013
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Osteogenesis Imperfecta
Drug: Denosumab
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Cologne:

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. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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


Estimated Enrollment: 10
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)
Arms Assigned Interventions
Experimental: Denosumab subcutaneously 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.

  Eligibility

Ages Eligible for Study:   5 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01799798

Locations
Germany
University Cologne, Childrens Hospital, Cologne, Germany
Cologne, NRW, Germany, 50924
Sponsors and Collaborators
University of Cologne
Investigators
Principal Investigator: Joerg Oliver Semler, MD University Cologne, Childrens Hospital, Cologne, Germany
  More Information

Additional Information:
Publications:
Responsible Party: Dr. med. Joerg Oliver Semler, Head of the outpatient center for sceletal dysplasias, University of Cologne
ClinicalTrials.gov Identifier: NCT01799798     History of Changes
Other Study ID Numbers: Uni-Koeln-1574
Study First Received: February 14, 2013
Last Updated: March 6, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by University of Cologne:
Osteogenesis imperfecta
COL1A1/A2
Denosumab
Bisphosphonates
Children
Areal bone mineral density

Additional relevant MeSH terms:
Osteogenesis Imperfecta
Bone Diseases
Bone Diseases, Developmental
Collagen Diseases
Connective Tissue Diseases
Genetic Diseases, Inborn
Musculoskeletal Diseases
Osteochondrodysplasias

ClinicalTrials.gov processed this record on October 29, 2014