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NCT Number: NCT05966064

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

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.

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Key information

Conditions

Fibrous Dysplasia Bone Diseases Bone Diseases, Developmental Fibrous Dysplasia of Bone Fibrous Dysplasia, Polyostotic McCune Albright Syndrome Musculoskeletal Diseases Osteochondrodysplasias

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Leiden University Medical Center

Leiden, Netherlands

Location status: Recruiting

Location contact

Natasha Appelman-Dijkstra

PRINCIPAL_INVESTIGATOR

Natasha Appelman-Dijkstra, MD, PhD

CONTACT

[email protected]

+31 625301410

About this study

Eligible patients will be randomized to treatment with either subcutaneous Dmab 120mg or placebo at baseline and 3 months in a blinded fashion. At 6 months, after 2 injections, patients with pain score <4 will exit the study to discontinue study medication and proceed in usual care, while patients with pain score ≥4 or lesional growth will be offered Dmab 120 mg at 6 and 9 months in an open-label design.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

Exclusion criteria

  • Active pregnancy wish, pregnancy or nursing
  • Pain not related to FD
  • Uncontrolled endocrine disease
  • Untreated vitamin D deficiency, hypocalcemia or hypophosphatemia
  • Previous use of bisphosphonates or Dmab < 6 months before inclusion ('6 months wash out')
  • 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

Treatment and study plan

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

Other names: Xgeva

Placebo

Drug

placebo randomized at baseline and after 3 months

Primary outcomes

  1. Denosumab effect on maximal pain score

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

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

Secondary outcomes

  1. Denosumab effect on average pain scores

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

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

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

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

    Evaluation of the number of patients with 50% reduction of maximal pain score changes after treatment, asseses by Brief Pain Inventory (scale 0 to 10; 0-no pain, 10 worst pain)

  3. Denosumab effect on quality of life

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

    Evaluation of Denosumab effect on quality of life, assessed with validated questionnaire SF-36 (scale 0-100, higher scores indicate better health status)

  4. Denosumab effect on average weekly pain score

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

    Evaluation of Denosumab effect on average weekly pain score assessed through a pain diary with VAS score (scale 0 to 10)

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

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

    Evaluation of Denosumab effect on on Physical activity assessment (Health Assessment Questionnaire - Disability Index: Health state index scores generally range from less than 0 (where 0 is a health state equivalent to death; negative values are valued as worse than death) to 1 (perfect health), with higher scores indicating higher health utility, though health state preferences can differ between countries.

  6. Denosumab effect on Physical activity assessment assessed through screenshot of pedometer

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

    Evaluation of Denosumab effect on on Physical activity assessment ( screenshot of pedometer of activity during the last week on smartphone, unit measure: number of steps during the last week)

  7. Evaluation of prevalence of possible neuropathic component of the reported pain

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

    to evaluate the prevalence of possible neuropathic component of the reported pain through Pain Detect questionnaire (It is scored from 0 to 38, with total scores of less than 12 considered to represent nociceptive pain, 13-18 possible NeP, and >19 representing >90% likelihood of Neuropathic pain)

  8. To investigate the number of analgesics used for pain

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

    number of used analgesics for pain : unit of measure: number

  9. To investigate the frequency use of analgesics for pain

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

    the frequency use of analgesics for pain (daily, multiple times per day, multiple times per week, monthly, when necessary)

  10. To investigate the dosage of analgesics used for pain

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

    dosage of analgesics used for pain (unit of measure: mg)

  11. Denosumab effect on serum bone markers

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

    effect of denosumab on bone serum markers (alkaline phosphatase (measure unit: U/L), P1NP -Procollagen-1-propeptide (measure unit: ng/ml), Beta-crosslaps (measure unit: ug/L)

  12. Denosumab effect on serum markers

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

    effect of Denosumab on serum calcium(mmol/L), fosfate (mmol/L), PTH (pmol/L)

  13. Denosumab effect on lesion size

    Time frame: baseline and after 6 months, and in the case of open label treatment after 12 months

    Na18F-PET/CT scan- measurement of lesion size

  14. Denosumab effect on lesion activity

    Time frame: baseline and after 6 months, and in the case of open label treatment after 12 months

    Na18F-PET/CT scan- ,measurement of Na18F uptake

  15. disease quantification (Skeletal Burden Score (SBS)

    Time frame: at baseline, 6 months and after 12 months

    nuclear imaging ((Skeletal Burden Score (SBS): scale 0 to 75, higher scores meaning increased disease activity

  16. Denosumab effect on bone density

    Time frame: baseline and after 12 months

    Dual-energy X-ray absorptiometry (DXA) - bone density measurement ( T-score of -1.0 or above = normal bone density T-score between -1.0 and -2.5 = low bone density, or osteopenia; T-score of -2.5 or lower = osteoporosis)

  17. Denosumab effect on vertebral fractures

    Time frame: baseline and after 12 months

    Dual-energy X-ray absorptiometry (DXA) - assement of presence of Vertebral Fractures through Vertebral Fractures Assessment (VFA) and changes from baseline until 12 months after

  18. To assess potential side effects in the form of Atypical femoral fractures

    Time frame: after 12 months

    Dual-energy X-ray absorptiometry (DXA) femur extended

Study contacts

Contact information is provided by the study sponsor or research team.

Natasha Appelman-Dijkstra, MD, PhD

CONTACT

[email protected]

+31 625301410

Sponsors and collaborators

Lead sponsor

Natasha Appelman-Dijkstra

Other

Registry information

Official study title

DEnosumab for the Treatment of FIbrous Dysplasia/McCune-Albright Syndrome in Adults (DeFiD): a Randomized Double-blind Placebo-controlled Trial

Acronym: DeFiD

Important dates

Study start
2023
Primary completion
2027
Study completion
2028
First posted
Jul 28, 2023
Registry last updated
Jan 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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