A Phase 2 Study of Denosumab for Prevention of Skeletal Disease Progression in Children With Fibrous Dysplasia

• Status: Not yet recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)
• Treatments: Denosumab

Criteria

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Confirmed diagnosis of fibrous dysplasia

• Age 4 to 14 years

• Concurrent enrollment in the companion Screening and Natural History protocol 98 D 0145

• Provision of signed and dated informed consent form

• Stated willingness of guardian/Legally Authorized Representative (LAR) to comply with all study procedures and availability for the duration of the study

• Ability of guardian/LAR to understand and the willingness to sign a written informed consent document

• For females of reproductive potential: agreement to use highly effective contraception for during study participation. Highly effective contraception methods include:

• Total abstinence. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

• Combination of the following (a+b or a+c, or b+c):

• Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception

• Placement of an intrauterine device (IUD) or intrauterine system (IUS)

• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner

• Minimum body weight of 12 kilograms

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Pregnancy or lactation

• Known allergic reactions to denosumab

• Prior history, or current evidence, of osteomyelitis/osteonecrosis of the jaw

• Planned invasive dental procedure for the course of the study

• Presence of non-healed dental or oral surgery

• Orthopedic procedure performed less than 6-weeks prior to first day of the denosumab administration (Day 0)

• Acute fracture less than 6-weeks prior to first day of the denosumab administration (Day 0)

• Serum calcium or albumin-adjusted serum calcium below the normal range for the NIH laboratory (patients will be eligible for re-screening after a repletion period lasting up to 6 months)

• 25-hydroxyvitamin D level than 20 ng/mL (patients will be eligible for re screening after a repletion period lasting up to 6 months)

• Untreated or inadequately treated hypophosphatemia as determined by the principal investigator (patients will be eligible for re-screening after initiation or optimization of phosphorus replacement no longer than 6 months)

• Inability to comply with a non-sedated 18F-NaF PET/CT (subjects will be eligible for re- screening after 6 months)

• Use of another investigational agent within the last 3 months prior to the first day of the denosumab administration (Day 0)

• Have any condition which in the opinion of the PI could present a concern for subject safety or difficulty with data interpretation.