NCT01799798

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2013

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

February 14, 2013

Completed
13 days until next milestone

First Posted

Study publicly available on registry

February 27, 2013

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2015

Completed
Last Updated

January 27, 2015

Status Verified

January 1, 2015

Enrollment Period

1.9 years

First QC Date

February 14, 2013

Last Update Submit

January 26, 2015

Conditions

Osteogenesis Imperfecta

Keywords

Osteogenesis imperfectaCOL1A1/A2DenosumabBisphosphonatesChildrenAreal bone mineral density

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (4)

  • Decrease of osteoclastic activity measured by urinary deoxypyridinoline (DPD).

    14 days (DPD)

  • Parathormone in study week 12, 24, 36 and 48 compared to baseline.

    12 weeks

  • N-Telopeptides in study week 12, 24, 36 and 48 compared to baseline.

    12 weeks

  • Osteocalcin in study week 12, 24, 36 and 48.

    12 weeks

Study Arms (1)

Denosumab subcutaneously

EXPERIMENTAL
Drug: Denosumab

Interventions

DenosumabDRUG

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.

Denosumab subcutaneously

Eligibility Criteria

Age5 Years - 11 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Cologne, Childrens Hospital, Cologne, Germany

Cologne, North Rhine-Westphalia, 50924, Germany

Location

Related 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.

    PMID: 22947550BACKGROUND

MeSH Terms

Conditions

Osteogenesis Imperfecta

Interventions

Denosumab

Condition Hierarchy (Ancestors)

OsteochondrodysplasiasBone Diseases, DevelopmentalBone DiseasesMusculoskeletal DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesCollagen DiseasesConnective Tissue DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Joerg Oliver Semler, MD

    University Cologne, Childrens Hospital, Cologne, Germany

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Head of the outpatient center for sceletal dysplasias

Study Record Dates

First Submitted

February 14, 2013

First Posted

February 27, 2013

Study Start

February 1, 2013

Primary Completion

January 1, 2015

Study Completion

January 1, 2015

Last Updated

January 27, 2015

Record last verified: 2015-01

Locations

DE(1)