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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05419050
Recruitment Status : Recruiting
First Posted : June 15, 2022
Last Update Posted : October 18, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )

Tracking Information
First Submitted Date  ICMJE June 11, 2022
First Posted Date  ICMJE June 15, 2022
Last Update Posted Date October 18, 2022
Actual Study Start Date  ICMJE October 12, 2022
Estimated Primary Completion Date December 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2022)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2022)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Denosumab for Prevention of Skeletal Disease Progression in Children With Fibrous Dysplasia
Official Title  ICMJE A Phase 2 Study of Denosumab for Prevention of Skeletal Disease Progression in Children With Fibrous Dysplasia
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fibrous Dysplasia
Intervention  ICMJE Drug: denosumab
monoclonal antibody to receptor activator of nuclear kappa-B ligand (RANKL), a protein involved in regulating osteoclastogenesis
Study Arms  ICMJE Experimental: treatment
treatment arm
Intervention: Drug: denosumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 14, 2022)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2024
Estimated Primary Completion Date December 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 14 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alison M Boyce, M.D. (301) 827-4802 alison.boyce@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05419050
Other Study ID Numbers  ICMJE 10000780
000780-D
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: .all IPD that underlie results in a publication
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: starting 6 months after publication
Access Criteria: Data will be shared on reasonable request to the PI
Current Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE National Institute of Dental and Craniofacial Research (NIDCR)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alison M Boyce, M.D. National Institute of Dental and Craniofacial Research (NIDCR)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date October 5, 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP