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Bone DiseasesPhase 2NCT03571191

Denosumab Treatment for Fibrous Dysplasia

A Phase 2 study testing Denosumab in people with Bone Diseases and Pain, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Objectives: The primary objective of this study is to evaluate the effect of denosumab on bone turnover in individuals with fibrous dysplasia (FD). Secondary objectives are to determine the effect of denosumab on bone pain, FD lesion intensity as revealed in 18F-sodium fluoride PET/CT bone scan, and to determine the… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bone Diseases, Pain
What is being tested?
Denosumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
13 Jun 2019to 15 Mar 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age > or equal to 18 years
  • Skeletal maturity with fusion of epiphyses documented radiographically
  • Concomitant enrollment in the companion Screening and Natural History protocol 98-D-0145
  • Confirmed diagnosis of Fibrous Dysplasia
  • Self-reported FD-related bone pain at a site of FD, present for at least 3 months
  • Ability to understand and provide informed consent
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  • Willing and able to complete the protocol scheduled assessments and medication regimen
  • Willing and able to take calcium and vitamin D supplements provided by NIH
  • Women of child bearing potential must use two forms of acceptable contraception: hormonal contraception (birth control pills, injected hormones or vaginal ring); intrauterine device and/or barrier methods (condom or diaphragm) used with spermicide. Surgical sterilization (hysterectomy, tubal ligation, or vasectomy in a partner) is considered one form of contraception therefore only one other form of contraception will be required in these subjects. Verbal confirmation will be obtained at screening that two forms of acceptable contraception are being used, and that the subjects agree to use the two forms of contraception from the time they sign study consent through five months after study completion (19 months total).
  • Serum calcium or albumin-adjusted serum calcium within the normal range for the NIH laboratory.

Who cannot join

  • Administration of denosumab within the previous year
  • Use of bisphosphonates within one year prior to first day of the denosumab administration (Day 0). Examples of bisphosphonates include: pamidronate (Aredia), Alendronate (Fosamax) and Zoledronate (Zomata).
  • Prior history, or current evidence, of osteomyelitis/osteonecrosis of the jaw or presence of an active dental or jaw condition which requires oral surgery
  • Planned invasive dental procedure for the course of the study
  • Presence of non-healed dental or oral surgery
  • Orthopedic procedure performed less than 12-weeks prior to first day of the denosumab administration (Day 0)
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  • Acute fracture less than 12-weeks prior to first day of the denosumab administration (Day 0)
  • 25-hydroxyvitamin D level than 30 ng/mL (patients will be eligible for re-screening after a repletion period lasting no longer than 6 months)
  • Untreated or inadequately treated hypophosphatemia, defined as serum phosphate levels below the NIH normal range (patients will be eligible for re-screening after initiation or optimization of phosphorus replacement no longer than 6 months)
  • Subject is pregnant or breast feeding, or planning to become pregnant or breastfeed while on study and through 5 months after completion of treatment
  • Use of another investigational agent within the last 3 months prior to the first day of the denosumab administration (Day 0)
  • Subject has known sensitivity to any of the products to be administered during the study (e.g. polyketide antibiotics, mammalian derived products, calcium, or vitamin D)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: An Open Label Pilot Study of Denosumab Treatment for Fibrous Dysplasia

Objectives:

The primary objective of this study is to evaluate the effect of denosumab on bone turnover in individuals with fibrous dysplasia (FD). Secondary objectives are to determine the effect of denosumab on bone pain, FD lesion intensity as revealed in 18F-sodium fluoride PET/CT bone scan, and to determine the effect of denosumab discontinuation on bone turnover re-bound after discontinuation.

Read more

Study Population:

Up to 14 adult subjects with FD may be enrolled to ensure complete study data on 9 subjects.

Design:

This study is a single center, open label pilot study of once-monthly dosing of denosumab. Subjects will be treated for 6 months, after which they will be followed by an 8-month observation period. A final visit will occur 21 months after denosumab discontinuation. Dosing will be adopted from studies in adults on treatment for giant cell tumors, with denosumab administered at 120 mg per dose every 4 weeks, with loading doses on days 7 and 14 of month 1.

Outcome Measures:

Primary:

Assessment of the effects of denosumab on:

  1. Markers of bone turnover:

Beta-crosslaps C-telopeptides (bone resorption marker)

Procollagen-1-propeptide (bone formation marker)

Secondary:

Assessment of the effects of denosumab on:

  1. Bone histomorphometric indices: Mineralized perimeter Bone formation rate Cortical width Cortical area Osteoid width Osteoid perimeter Mineral apposition rate
  2. Surrogate markers of a direct therapeutic effect of denosumab on FD lesions: Semi-quantitative changes in RANKL, Ki67 (marker of cell proliferation), p16 (marker of cell senescence), and/or apoptosis index before and after treatment, as assessed by immunohistochemistry Changes in sentinel lesion intensity, measured quantitatively by uptake on 18Fsodium fluoride PET/CT bone scan.
  3. FD-related bone pain assessed by the Brief Pain Inventory (Short Form) , a validated self-reporting tool for assessment of pain.

Exploratory Endpoints:

  1. Effect of denosumab initiation and discontinuation on Serum calcium, phosphorus and parathyroid hormone Serum RANKL and osteoprotegerin (OPG), and RANKL/OPG levels
  2. Effect of denosumab discontinuation, as measured by the following outcomes: Biochemical markers of bone metabolism: beta-crosslaps C-telopeptides, procollagen-1 propeptide, bone specific alkaline phosphatase, osteocalcin, NTX-telopeptides
  3. Effect measured by change in other outcome measures, such as:

Bone density assessed by DXA

Physical Medicine and Rehabilitation evaluation

Read the detailed description

Objectives:

The primary objective of this study is to evaluate the effect of denosumab on bone turnover in individuals with fibrous dysplasia (FD). Secondary objectives are to determine the effect of denosumab on bone pain, FD lesion intensity as revealed in 18F-sodium fluoride PET/CT bone scan, and to determine the effect of denosumab discontinuation on bone turnover re-bound after discontinuation.

Study Population:

Up to 14 adult subjects with FD may be enrolled to ensure complete study data on 9 subjects.

Design:

This study is a single center, open label pilot study of once-monthly dosing of denosumab. Subjects will be treated for 6 months, after which they will be followed by an 8-month observation period. A final visit will occur 21 months after denosumab discontinuation. Dosing will be adopted from studies in adults on treatment for giant cell tumors, with denosumab administered at 120 mg per dose every 4 weeks, with loading doses on days 7 and 14 of month 1.

Outcome Measures:

Primary:

Assessment of the effects of denosumab on:

  1. Markers of bone turnover:
  • Beta-crosslaps C-telopeptides (bone resorption marker)
  • Procollagen-1-propeptide (bone formation marker)

Secondary:

Assessment of the effects of denosumab on:

  1. Bone histomorphometric indices:
  • Mineralized perimeter
  • Bone formation rate
  • Cortical width
  • Cortical area
  • Osteoid width
  • Osteoid perimeter
  • Mineral apposition rate
  1. Surrogate markers of a direct therapeutic effect of denosumab on FD lesions:
  • Semi-quantitative changes in RANKL, Ki67 (marker of cell proliferation), p16 (marker of cell senescence), and/or apoptosis index before and after treatment, as assessed by immunohistochemistry
  • Changes in sentinel lesion intensity, measured quantitatively by uptake on 18Fsodium fluoride PET/CT bone scan.
  1. FD-related bone pain assessed by the Brief Pain Inventory (Short Form), a validated self-reporting tool for assessment of pain.

Exploratory Endpoints:

  1. Effect of denosumab initiation and discontinuation on
  • Serum calcium, phosphorus and parathyroid hormone
  • Serum RANKL and osteoprotegerin (OPG), and RANKL/OPG levels
  1. Effect of denosumab discontinuation, as measured by the following outcomes: -Biochemical markers of bone metabolism: beta-crosslaps C-telopeptides, procollagen-1 propeptide, bone specific alkaline phosphatase, osteocalcin, NTX-telopeptides
  2. Effect measured by change in other outcome measures, such as:
  • Bone density assessed by DXA
  • Physical Medicine and Rehabilitation evaluation
Conditions
Bone Diseases, Pain
Being tested
Denosumab
Keywords
Bone Diseases, Fibrous Dysplasia (FD), Bone Turnover
Medical subject headings
Bone Diseases, Pain, Fibrous Dysplasia of Bone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DenosumabDrug

    Denosumab will be administered at 120 mg per dose every 4 weeks for six months, with loading doses on days 8 and 15 of month 1.

Study groups in NCT03571191
Study groupRoleWhat they receive
1ExperimentalDenosumab will be administered at 120 mg per dose every 4 weeks for six months, with loading doses on days 8 and 15 of month 1.
Receives: Drug: Denosumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary:1. Assessment of markers of bone turnover: Beta-crosslaps, C-telopeptides (bone resorption marker,Procollagen-1-propeptide (bone formation marker)

    Assessment of the effects of denosumab on: 1. Markers of bone turnover: Beta-crosslaps C-telopeptides (bone resorption marker) \& Procollagen-1-propeptide (bone formation marker)

    Measured: every 3 months

Secondary outcomes (6)

  1. Secondary outcome #1- Bone histomorphometric indices: (SqrRoot) Mineralized perimeter, (SqrRoot) Bone formation rate (SqrRoot) Cortical width (SqrRoot) Cortical area (SqrRoot) Osteoid width...

    Measured: 2 time points

  2. Secondary endpoint #3 - Pain assessments utilizing the Brief Pain Inventory scores

    Measured: 2 time points

  3. Secondary Endpoint #2 - Surrogate markers of a direct therapeutic effect of denosumab on FD lesions:-Semi-quantitative changes in RANKL, Ki67 (marker of cell proliferation), p16 (marker od cell senescence), and/or apoptosis index-Sen...

    Measured: 2-4 timepoints

  4. Exploratory endpoint #3 - Effect measured by change in other outcome measures(SqrRoot) Bone density assessed by DXA(SqrRoot) Physical Medicine and Rehabilitation evaluation

    Measured: Q 3 mths/Q 6 mths

  5. Exploratory endpoint #2 - Denosumab discontinuation effect on:(SqrRoot) Biochemical markers of bone metabolism: beta-crosslaps C-telopeptides, procollagen-1 propeptide, bone specific alkaline phosphatase, osteocalcin, NTX-telopeptides

    Measured: every 3 months

  6. Exploratory Endpoint # 1. Effect of denosumab initiation and discontinuation on(SqrRoot) Serum calcium, phosphorus and parathyroid hormone (SqrRoot) Serum circulating RANKL and osteoprotegerin (OPG), and RANKL/OPG level...

    Measured: up to12 timepoints

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2018
  2. Study start13 Jun 2019
  3. Primary completion17 Nov 2021
  4. Study completion15 Mar 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03571191
Sponsor's protocol ID
180114
Other IDs
18-D-0114
Status last verified
15 Feb 2022
First submitted
26 Jun 2018
Last updated
18 Feb 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Michel Z, MacDonald V, Arif A, Elbashir II, Freeman J, Gun ZH, Osamor C, Taylor J, Collins MT, Roszko KL, de Castro LF, Kram V, Boyce AM. Galphas variant detection discerns skeletal cell types involved in fibrous dysplasia pathogenesis. Bone. 2026 Apr;205:117792. doi: 10.1016/j.bone.2026.117792. Epub 2026 Jan 12.

    PubMed 41534675

  • de Castro LF, Whitlock JM, Michel Z, Pan K, Taylor J, Szymczuk V, Boyce B, Martin D, Kram V, Galisteo R, Melikov K, Chernomordik LV, Collins MT, Boyce AM. RANKL inhibition reduces lesional cellularity and Galphas variant expression and enables osteogenic maturation in fibrous dysplasia. Bone Res. 2024 Feb 20;12(1):10. doi: 10.1038/s41413-023-00311-7.

    PubMed 38378678

  • de Castro LF, Michel Z, Pan K, Taylor J, Szymczuk V, Paravastu S, Saboury B, Papadakis GZ, Li X, Milligan K, Boyce B, Paul SM, Collins MT, Boyce AM. Safety and Efficacy of Denosumab for Fibrous Dysplasia of Bone. N Engl J Med. 2023 Feb 23;388(8):766-768. doi: 10.1056/NEJMc2214862. No abstract available.

    PubMed 36812441

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Denosumab in people with Bone Diseases and Pain, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary:1. Assessment of markers of bone turnover: Beta-crosslaps, C-telopeptides (bone resorption marker,Procollagen-1-propeptide (bone formation marker) (time frame: every 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03571191, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2022.

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