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

Primary Purpose

Fibrous Dysplasia

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

denosumab

About this trial

This is an interventional treatment trial for Fibrous Dysplasia focused on measuring McCune-Albright Syndrome

Eligibility Criteria

4 Years - 14 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

treatment

Arm Description

treatment arm

Outcomes

Primary Outcome Measures

Change in Skeletal Burden Score

Skeletal Burden Score is a validated measure for quantifying FD disease burden shown to correlate with skeletal outcomes

Secondary Outcome Measures

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

reflect underlying bone turnover, and correlate with skeletal outcomes

Adverse events

Safety endpoints for expected and unexpected adverse events

Change in functional parameters: - Muscle strength - Range-of-motion - Walking speed (6-minute walk)

Outcome measures that reflect activities of daily living

Change in 18F-NaF PET/CT total lesion activity from baseline to 48 weeks

reflect underlying lesion activity and correlate with skeletal outcomes

Change in patient-reported outcome scales: - SF10 - Brief Pain Inventory - Brief Fatigue Inventory

Outcome measures to determine pain and quality of life

Change in 18F-NaF PET/CT sentinel lesion intensity (SUVmax)

reflect underlying lesion activity and correlate with skeletal outcomes

Full Information

NCT ID

NCT05419050

First Posted

June 11, 2022

Last Updated

October 11, 2023

Sponsor

National Institute of Dental and Craniofacial Research (NIDCR)

1. Study Identification

Unique Protocol Identification Number

NCT05419050

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 10, 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 12, 2022 (Actual)

Primary Completion Date

December 31, 2026 (Anticipated)

Study Completion Date

December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Dental and Craniofacial Research (NIDCR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fibrous Dysplasia

Keywords

McCune-Albright Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

treatment

Arm Type

Experimental

Arm Description

treatment arm

Intervention Type

Drug

Intervention Name(s)

denosumab

Intervention Description

monoclonal antibody to receptor activator of nuclear kappa-B ligand (RANKL), a protein involved in regulating osteoclastogenesis

Primary Outcome Measure Information:

Title

Change in Skeletal Burden Score

Description

Skeletal Burden Score is a validated measure for quantifying FD disease burden shown to correlate with skeletal outcomes

Time Frame

48 weeks

Secondary Outcome Measure Information:

Title

Description

reflect underlying bone turnover, and correlate with skeletal outcomes

Time Frame

48 weeks

Title

Adverse events

Description

Safety endpoints for expected and unexpected adverse events

Time Frame

76 weeks

Title

Change in functional parameters: - Muscle strength - Range-of-motion - Walking speed (6-minute walk)

Description

Outcome measures that reflect activities of daily living

Time Frame

48 weeks

Title

Change in 18F-NaF PET/CT total lesion activity from baseline to 48 weeks

Description

reflect underlying lesion activity and correlate with skeletal outcomes

Time Frame

48 weeks

Title

Change in patient-reported outcome scales: - SF10 - Brief Pain Inventory - Brief Fatigue Inventory

Description

Outcome measures to determine pain and quality of life

Time Frame

48 weeks

Title

Change in 18F-NaF PET/CT sentinel lesion intensity (SUVmax)

Description

reflect underlying lesion activity and correlate with skeletal outcomes

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Years

Maximum Age & Unit of Time

14 Years

Accepts Healthy Volunteers

Eligibility 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Alison M Boyce, M.D.

Phone

(301) 827-4802

alison.boyce@nih.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alison M Boyce, M.D.

Organizational Affiliation

National Institute of Dental and Craniofacial Research (NIDCR)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Phone

800-411-1222

Ext

TTY dial 711

ccopr@nih.gov

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

.all IPD that underlie results in a publication

IPD Sharing Time Frame

starting 6 months after publication

IPD Sharing Access Criteria

Data will be shared on reasonable request to the PI

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_000780-D.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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