Study of Denosumab for Prevention of Skeletal Disease Progression in Children With Fibrous Dysplasia

Phase 2

Active, not recruiting

• Conditions: Fibrous Dysplasia
• Interventions: Drug: denosumab

• Registration Number: NCT05419050
• Lead Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)

Brief Summary

Background:

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.

Objective:

To test a study drug (denosumab) in children with FD.

Eligibility:

Children aged 4 to 14 years with FD and who are also enrolled in the Screening and Natural History protocol (98-D-0145).

Design:

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.

Detailed Description

Study Description:

This will be a phase 2, open label, single arm study of denosumab treatment to prevent fibrous dysplasia (FD) lesion progression in children.

Objectives:

Primary Objective:

Evaluate the effect of denosumab on FD lesion progression in children.

Secondary Objectives:

* 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.

Endpoints:

Primary Endpoint:

Change in Skeletal Burden Score from baseline to 48 weeks

Secondary Endpoints:

* 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 Timeline

• Study First Submitted: 2022-06-11
• Study First Submitted QC: 2022-06-14
• Study First Posted: 2022-06-15
• Study Start: 2022-10-12
• Status Verified: 2025-02-21
• Last Update Submitted: 2025-02-22
• Last Update Posted: 2025-02-25
• Primary Completion: 2026-01-09
• Study Completion: 2026-01-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment	denosumab	treatment arm

Primary Outcome Measures

Name	Time	Method
Change in Skeletal Burden Score	48 weeks	Skeletal Burden Score is a validated measure for quantifying FD disease burden shown to correlate with skeletal outcomes

Secondary Outcome Measures

Name	Time	Method
Change in functional parameters: - Muscle strength - Range-of-motion - Walking speed (6-minute walk)	48 weeks	Outcome measures that reflect activities of daily living
Change in patient-reported outcome scales: - SF10 - Brief Pain Inventory - Brief Fatigue Inventory	48 weeks	Outcome measures to determine pain and quality of life
Adverse events	76 weeks	Safety endpoints for expected and unexpected adverse events
Change in 18F-NaF PET/CT total lesion activity from baseline to 48 weeks	48 weeks	reflect underlying lesion activity and correlate with skeletal outcomes
Change in 18F-NaF PET/CT sentinel lesion intensity (SUVmax)	48 weeks	reflect underlying lesion activity and 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	48 weeks	reflect underlying bone turnover, and correlate with skeletal outcomes

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States