9 Participants Needed

Denosumab for Fibrous Dysplasia

Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)
Must be taking: Calcium, Vitamin D
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This trial is testing denosumab, a drug that helps strengthen bones, in adults with fibrous dysplasia, a condition where bones grow abnormally. Denosumab works by stopping the cells that break down bone tissue, aiming to reduce bone pain and improve bone strength.

Will I have to stop taking my current medications?

The trial requires that you have not used bisphosphonates (a type of medication for bone conditions) within one year before starting the study. Other current medications are not specifically mentioned, so it's best to discuss your medications with the study team.

What data supports the effectiveness of the drug Denosumab for treating fibrous dysplasia?

Denosumab has shown promise in reducing pain and the size of bone lesions in patients with fibrous dysplasia, as seen in case reports where patients experienced improvements that were not achieved with previous treatments. Additionally, Denosumab is effective in other bone-related conditions, like osteoporosis, by targeting a protein involved in bone breakdown, which may explain its potential benefits in fibrous dysplasia.12345

Is Denosumab generally safe for use in humans?

Denosumab, also known as Prolia or Xgeva, is a biologic treatment that has been monitored for safety in various conditions, including rheumatoid arthritis. Safety data from registers in Europe and the UK show that biologic treatments can have adverse effects, such as infections and cardiovascular events, which are closely monitored to ensure patient safety.678910

How is the drug denosumab unique for treating fibrous dysplasia?

Denosumab is unique because it is a monoclonal antibody that targets RANKL, a protein involved in bone resorption, which is different from traditional treatments like bisphosphonates. It is administered as a subcutaneous injection, offering an alternative route and mechanism for managing bone-related conditions.511121314

Research Team

AM

Alison M Boyce, M.D.

Principal Investigator

National Institute of Dental and Craniofacial Research (NIDCR)

Eligibility Criteria

Adults over 18 with confirmed fibrous dysplasia and chronic bone pain, who have reached skeletal maturity. They must not have used denosumab or bisphosphonates in the past year, be willing to take supplements, use two forms of contraception if applicable, and cannot be pregnant or planning pregnancy within five months post-study.

Inclusion Criteria

I have had bone pain for at least 3 months in an area affected by FD.
I am 18 years old or older.
I use two reliable birth control methods if I can have children.
See 8 more

Exclusion Criteria

I have received denosumab in the last year.
I have had jawbone infections or conditions needing oral surgery.
I have had a bone fracture within the last 3 months.
See 9 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive denosumab at 120 mg per dose every 4 weeks for six months, with loading doses on days 7 and 14 of month 1

6 months

Observation

Participants are followed for an 8-month observation period after treatment

8 months

Follow-up

A final visit occurs 21 months after denosumab discontinuation to monitor long-term effects

21 months post-treatment

Treatment Details

Interventions

  • Denosumab
Trial OverviewThe trial tests Denosumab's effects on bone turnover in fibrous dysplasia patients. It involves monthly doses for six months followed by an eight-month observation period. The study measures changes in bone markers, lesion intensity via PET/CT scans, and FD-related pain levels.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: 1Experimental Treatment1 Intervention
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.

Denosumab is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Prolia for:
  • Osteoporosis in postmenopausal women
  • Bone loss associated with hormone ablation therapy for prostate cancer
  • Bone loss associated with hormone ablation therapy for breast cancer
🇺🇸
Approved in United States as Prolia for:
  • Treatment of postmenopausal women with osteoporosis at high risk for fracture
  • Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
  • Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer
🇨🇦
Approved in Canada as Prolia for:
  • Treatment of osteoporosis in postmenopausal women at high risk for fracture
  • Treatment to increase bone mass in men with osteoporosis at high risk for fracture
🇯🇵
Approved in Japan as Prolia for:
  • Treatment of osteoporosis in postmenopausal women
  • Treatment of bone loss associated with hormone ablation therapy for prostate cancer

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Institute of Dental and Craniofacial Research (NIDCR)

Lead Sponsor

Trials
312
Recruited
853,000+

Findings from Research

Denosumab, a monoclonal antibody targeting RANKL, showed significant efficacy in reducing pain and tumor growth in a 9-year-old boy with severe fibrous dysplasia over 7 months of treatment, indicating its potential as a therapeutic option for this condition.
While denosumab effectively suppressed bone turnover markers and reduced disease symptoms, it also caused notable disturbances in mineral metabolism, including hypophosphatemia and secondary hyperparathyroidism, highlighting the need for careful monitoring during treatment.
Denosumab treatment for fibrous dysplasia.Boyce, AM., Chong, WH., Yao, J., et al.[2021]
Denosumab therapy led to a decrease in the size and activity of fibrous dysplasia lesions in two patients, along with reduced pain and bone turnover markers, which was not achieved with previous bisphosphonate treatments.
These cases suggest that denosumab could be a promising alternative for patients who do not respond to bisphosphonates, and it may also serve as neoadjuvant therapy to enhance surgical outcomes in severe cases.
Regression of fibrous dysplasia in response to denosumab therapy: A report of two cases.Meier, ME., van der Bruggen, W., van de Sande, MAJ., et al.[2021]
Denosumab was administered to two patients with fibrous dysplasia (FD) who had previously been treated with bisphosphonates, but neither patient experienced improvement in bone pain after treatment with denosumab.
Despite the lack of pain relief in these cases, literature suggests that denosumab may reduce bone turnover markers and has shown promise in improving bone pain for other patients with FD, indicating the need for further research on its efficacy and optimal treatment protocols.
Denosumab Use in Adults With Fibrous Dysplasia: Case Reports and Review of the Literature.Hung, C., Shibli-Rahhal, A.[2022]

References

Denosumab treatment for fibrous dysplasia. [2021]
Regression of fibrous dysplasia in response to denosumab therapy: A report of two cases. [2021]
Denosumab Use in Adults With Fibrous Dysplasia: Case Reports and Review of the Literature. [2022]
Clinical value of RANKL, OPG, IL-6 and sclerostin as biomarkers for fibrous dysplasia/McCune-Albright syndrome. [2023]
Denosumab: a case of MRONJ with resolution. [2018]
Routine database registration of biological therapy increases the reporting of adverse events twentyfold in clinical practice. First results from the Danish Database (DANBIO). [2019]
Safety of Biologics Approved for the Treatment of Rheumatoid Arthritis and Other Autoimmune Diseases: A Disproportionality Analysis from the FDA Adverse Event Reporting System (FAERS). [2019]
Cysteamine: Ehlers-Danlos syndrome. [2013]
European biologicals registers: methodology, selected results and perspectives. [2013]
The British Society for Rheumatology biologics register. [2018]
Denosumab, an Alternative to Bisphosphonates but also Associated with Osteonecrosis of the Jaw--What is the Risk?. [2018]
Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. [2021]
Quantitative pharmacology of denosumab in patients with bone metastases from solid tumors. [2015]
Interstitial Lung Disease in a Patient Treated with Denosumab. [2022]