Study of Denosumab for Prevention of Skeletal Disease Progression in Children With Fibrous Dysplasia
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|ClinicalTrials.gov Identifier: NCT05419050|
Recruitment Status : Recruiting
First Posted : June 15, 2022
Last Update Posted : October 18, 2022
Fibrous dysplasia (FD) is a disease that affects the bones. It causes bone lesions that can become weak and lead to fractures, deformity, and nerve injuries. FD bone lesions begin to develop soon after birth and grow during childhood. The lesions stop growing in adults but can still cause disability. Researchers want to find ways to stop the growth of FD bone lesions.
To test a study drug (denosumab) in children with FD.
Children aged 4 to 14 years with FD and who are also enrolled in the Screening and Natural History protocol (98-D-0145).
Participants will have a screening visit at the NIH clinic or by telehealth. Their medical history will be reviewed.
Participants will stay overnight in the hospital 4 times in 76 weeks. Each stay will last 5 to 7 nights.
Participants will also visit a local lab for blood and urine tests every 4 weeks during the study.
Participants will receive denosumab once every 4 weeks for 48 weeks. The medication is given as a shot injected under the skin using a small needle. Some injections may be performed at home by a caregiver. The caregiver will receive training for this procedure.
Participants will undergo many tests that may be repeated throughout the study. They will have a dental exam. They will have tests of their strength and ability to move freely. They will have x-rays and other scans to get pictures of their bones.
Participants will be given another medicine that is administered through a needle in the arm over 30 minutes.
|Condition or disease||Intervention/treatment||Phase|
|Fibrous Dysplasia||Drug: denosumab||Phase 2|
This will be a phase 2, open label, single arm study of denosumab treatment to prevent fibrous dysplasia (FD) lesion progression in children.
Evaluate the effect of denosumab on FD lesion progression in children.
- Evaluate the effects of denosumab on FD lesion activity.
- Evaluate the effect of denosumab on strength and mobility.
- Evaluate the effect of denosumab on pain and quality of life.
- Evaluate the safety and tolerability of denosumab in children with FD.
Change in Skeletal Burden Score from baseline to 48 weeks
- Percent change in serum bone turnover markers from baseline to 48 weeks: Procollagen 1 Intact N-Terminal Propeptide (P1NP, formation marker), C- telopeptides (CTX, resorption marker), osteocalcin, and bone-specific alkaline phosphatase
- Change in 18F-NaF PET/CT total lesion activity from baseline to 48 weeks
- Change in 18F-NaF PET/CT sentinel lesion intensity (SUVmax) from baseline to 48 weeks
- Change in functional parameters from baseline to 48 weeks, including muscle strength, range-of-motion, and walking speed
- Change in patient-reported outcome scales evaluating pain and quality of life from baseline to 48 weeks, including PROMIS Pediatric measures of Pain Intensity, Pain Interference, Mobility, and Fatigue.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Denosumab for Prevention of Skeletal Disease Progression in Children With Fibrous Dysplasia|
|Actual Study Start Date :||October 12, 2022|
|Estimated Primary Completion Date :||December 1, 2023|
|Estimated Study Completion Date :||June 1, 2024|
monoclonal antibody to receptor activator of nuclear kappa-B ligand (RANKL), a protein involved in regulating osteoclastogenesis
- Change in Skeletal Burden Score [ Time Frame: 48 weeks ]Skeletal Burden Score is a validated measure for quantifying FD disease burden shown to correlate with skeletal outcomes
- Percent change in serum bone turnover markers from baseline to 48 weeks: procollagen 1 propeptide (P1NP, formation marker), beta crosslaps telopeptides (CTX, resorption marker), osteocalcin, and bone-specific alkaline phosphatase [ Time Frame: 48 weeks ]reflect underlying bone turnover, and correlate with skeletal outcomes
- Adverse events [ Time Frame: 76 weeks ]Safety endpoints for expected and unexpected adverse events
- Change in functional parameters: - Muscle strength - Range-of-motion - Walking speed (6-minute walk) [ Time Frame: 48 weeks ]Outcome measures that reflect activities of daily living
- Change in 18F-NaF PET/CT total lesion activity from baseline to 48 weeks [ Time Frame: 48 weeks ]reflect underlying lesion activity and correlate with skeletal outcomes
- Change in patient-reported outcome scales: - SF10 - Brief Pain Inventory - Brief Fatigue Inventory [ Time Frame: 48 weeks ]Outcome measures to determine pain and quality of life
- Change in 18F-NaF PET/CT sentinel lesion intensity (SUVmax) [ Time Frame: 48 weeks ]reflect underlying lesion activity and correlate with skeletal outcomes
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05419050
|Contact: Alison M Boyce, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY dial 711 email@example.com|
|Principal Investigator:||Alison M Boyce, M.D.||National Institute of Dental and Craniofacial Research (NIDCR)|