NCT03571191

Denosumab Treatment for Fibrous Dysplasia

Active, enrolled Phase 2 Last updated 18 February 2022

What this trial tests

Phase 2 trial testing Denosumab in Bone Diseases in 9 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

13 June 2019

Primary endpoint
17 November 2021

15 March 2030

Quick facts

Lead sponsor	National Institute of Dental and Craniofacial Research (NIDCR)
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	9
Start date	13 June 2019
Primary completion	17 November 2021
Estimated completion	15 March 2030
Sites	1 location across United States

Drugs / interventions tested

• Denosumab (DENOSUMAB) — full drug profile →

Conditions studied

• Bone Diseases — all drugs for Bone Diseases →
• Pain — all drugs for Pain →

Sponsor

National Institute of Dental and Craniofacial Research (NIDCR)

Who can join

18 and older, any sex, with Bone Diseases or Pain. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own 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
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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Bone Turnover Markers: Basic Biology to Clinical Applications.
   Schini M, Vilaca T, Gossiel F, Salam S, et al · · 2023 · cited 204× · PMID 36510335 · DOI 10.1210/endrev/bnac031
2. Fibrous Dysplasia/McCune-Albright Syndrome: A Rare, Mosaic Disease of Gα s Activation.
   Boyce AM, Collins MT. · · 2020 · cited 119× · PMID 31673695 · DOI 10.1210/endrev/bnz011
3. Safety and Efficacy of Denosumab for Fibrous Dysplasia of Bone.
   de Castro LF, Michel Z, Pan K, Taylor J, et al · · 2023 · cited 51× · PMID 36812441 · DOI 10.1056/nejmc2214862
4. Pain Phenotypes in Rare Musculoskeletal and Neuromuscular Diseases.
   Tucker-Bartley A, Lemme J, Gomez-Morad A, Shah N, et al · · 2021 · cited 30× · PMID 33581222 · DOI 10.1016/j.neubiorev.2021.02.009
5. Safety of therapy with and withdrawal from denosumab in fibrous dysplasia and McCune-Albright syndrome: an observational study.
   Meier ME, Clerkx SN, Winter EM, Pereira AM, et al · · 2021 · cited 29× · PMID 34076303 · DOI 10.1002/jbmr.4380
6. Denosumab for craniofacial fibrous dysplasia: duration of efficacy and post-treatment effects.
   Raborn LN, Burke AB, Ebb DH, Collins MT, et al · · 2021 · cited 29× · PMID 33772327 · DOI 10.1007/s00198-021-05895-6
7. Craniofacial Fibrous Dysplasia: Clinical and Therapeutic Implications.
   Szymczuk V, Taylor J, Boyce AM. · · 2023 · cited 23× · PMID 36849642 · DOI 10.1007/s11914-023-00779-6
8. Denosumab Treatment for Giant Cell Tumors, Aneurysmal Bone Cysts, and Fibrous Dysplasia-Risks and Benefits.
   Pan KS, Boyce AM. · · 2021 · cited 23× · PMID 33616817 · DOI 10.1007/s11914-021-00657-z