DEnosumab for the Treatment of FIbrous Dysplasia/McCune-Albright Syndrome in Adults (DeFiD)

NCT05966064 | Recruiting Phase 4 DMC

• 1 other identifier: 2022-501705-12-00
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

Fibrous Dysplasia/McCune-Albright syndrome (FD/MAS) is a rare disease, consisting of the replacement of normal bone tissue with fibrous tissue. FD lesions may be isolated in one or more bones or may be associated with endocrinopathies in McCune-Albright syndrome. Bone lesions constitute of weak bone tissue, leading to higher risk of fractures, pain and decreased quality of life. There is no cure for FD lesions and current therapies failed to soothe patients' complaints or to display any effect on progression of the lesions on imaging. However, the RANKL-inhibitor Denosumab demonstrated encouraging results in mouse models and in off-label clinical use, leading to clinical, biochemical and radiographical improvements. Study's aim is to investigate whether 3-monthly Denosumab will improve the clinical, radiological and biochemical manifestations of FD bone lesions.

Conditions

Fibrous Dysplasia; McCune Albright Syndrome

Outcome Measures

Primary Outcomes (1)

• Denosumab effect on maximal pain score

  Evaluation of maximal pain score changes after treatment, assessed by Brief Pain Inventory (scale 0 to 10; 0-no pain, 10 worst pain)

  at baseline, 3 months and after 6 months and in case of open label treatment after 9 and 12 months

Secondary Outcomes (18)

• Denosumab effect on average pain scores

  at baseline, 3 months and after 6 months and in case of open label treatment after 9 and 12 months

• To evaluate the number of patients with 50% reduction of maximal pain (BPI)

  at baseline, 3 months and after 6 months and in case of open label treatment after 9 and 12 months

• Denosumab effect on quality of life

  at baseline, 3 months and after 6 months and in case of open label treatment after 9 and 12 months

• Denosumab effect on average weekly pain score

  every week from baseline, through study completion, an average of 1 year

• Denosumab effect on Physical activity assessment assessed through Health Assessment Questionnaire - Disability Index

  baseline, 3 months and 6 months, and in case of open label treatment after 9 and 12 months

Study Arms (2)

Denosumab

ACTIVE COMPARATOR

Denosumab randomized at baseline and 3 months in a double-blinded fashion and in case of open label at 6 and 9 months

Drug: Denosumab 120 Mg/1.7 Ml Inj

Placebo

PLACEBO COMPARATOR

Placebo randomized at baseline and 3 months in a double-blinded fashion.

Drug: Placebo

Interventions

Denosumab 120 Mg/1.7 Ml Inj DRUG

Denosumab randomized at baseline and after 3 months at 6 and 9 months in case of open label

Also known as: Xgeva

Denosumab

Placebo DRUG

placebo randomized at baseline and after 3 months

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic patients with established diagnosis of FD/MAS and closed growth plates(\>18 years)
• Pain in the region of an FD localization, not responding to adequate pain treatment and without mechanical component e.g. impending fracture
• Pain score from FD lesion for maximum or average pain on VAS ≥ 4
• Increased lesional activity defined as increased bone turnover markers (ALP, P1NP or CTX) or increased activity on Na\[18F\]-PET/CT or bone scintigraphy in at least one lesion
• Normal levels of calcium, parathyroid hormone and vitamin D (supplementation is allowed)
• Treated hypophosphatemia (defined as \>0.7 at two separate measures)
• good dental health (last check within the last 12 months)

You may not qualify if:

• Active pregnancy wish, pregnancy or nursing
• Pain not related to FD
• Uncontrolled endocrine disease
• Untreated vitamin D deficiency, hypocalcemia or hypophosphatemia
• Previously reported severe side effects on Dmab
• Inability to fulfil study requirements
• Poor untreated dental health without intention to get treatment
• Treatment with other bone influencing drugs, such as high doses corticosteroids

Sponsors & Collaborators

• Natasha Appelman-Dijkstra: lead

Study Sites (1)

Leiden University Medical Center

Leiden, Netherlands

RECRUITING

MeSH Terms

Conditions

Fibrous Dysplasia of Bone; Fibrous Dysplasia, Polyostotic

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Natasha Appelman-Dijsktra, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natasha Appelman-Dijkstra, MD, PhD

CONTACT

+31 625301410; n.m.appelman-dijkstra@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator, Internist-Endocrinologist, MD, PhD

Study Record Dates

• First Submitted: June 19, 2023
• First Posted: July 28, 2023
• Study Start: June 13, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 29, 2025

Record last verified: 2025-01

Locations

NL (1)