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

Phase 4RecruitingNCT05966064

Natasha Appelman-Dijkstra82 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Fibrous Dysplasia

Outcomes

Primary Outcomes

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)

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

Secondary Outcomes

Denosumab effect on average pain scores

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

Time frame: 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)

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)

Time frame: 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

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

Time frame: 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

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

Time frame: 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

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.

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

Denosumab effect on Physical activity assessment assessed through screenshot of pedometer

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)

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

Evaluation of prevalence of possible neuropathic component of the reported pain

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)