DEnosumab for the Treatment of FIbrous Dysplasia/McCune-Albright Syndrome in Adults (DeFiD) - Clinical Trial for Fibrous Dysplasia | NCT05966064

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Primary Purpose

Status

Recruiting

Phase

Phase 4

Locations

Netherlands

Study Type

Interventional

Intervention

Denosumab 120 Mg/1.7 Ml Inj

Placebo

About this trial

This is an interventional treatment trial for Fibrous Dysplasia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Leiden University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Denosumab

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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)

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)

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)

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)

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.

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)

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)

To investigate the number of analgesics used for pain

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

To investigate the frequency use of analgesics for pain

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

To investigate the dosage of analgesics used for pain

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

Denosumab effect on serum bone markers

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)

Denosumab effect on serum markers

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

Denosumab effect on lesion size

Na18F-PET/CT scan- measurement of lesion size

Denosumab effect on lesion activity

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

disease quantification (Skeletal Burden Score (SBS)

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

Denosumab effect on bone density

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)

Denosumab effect on vertebral fractures

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

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

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

Full Information

NCT ID

NCT05966064

First Posted

June 19, 2023

Last Updated

July 20, 2023

Sponsor

Natasha Appelman-Dijkstra

1. Study Identification

Unique Protocol Identification Number

NCT05966064

Brief Title

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

Acronym

DeFiD

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 13, 2023 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Natasha Appelman-Dijkstra

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Product Manufactured in and Exported from the U.S.

No

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fibrous Dysplasia, McCune Albright Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

82 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Denosumab

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Denosumab 120 Mg/1.7 Ml Inj

Other Intervention Name(s)

Xgeva

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

placebo randomized at baseline and after 3 months

Primary Outcome Measure Information:

Title

Denosumab effect on maximal pain score

Description

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 Outcome Measure Information:

Title

Denosumab effect on average pain scores

Description

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

Title

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

Description

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

Title

Denosumab effect on quality of life

Description

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

Title

Denosumab effect on average weekly pain score

Description

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

Title

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

Description

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

Title

Denosumab effect on Physical activity assessment assessed through screenshot of pedometer

Description

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

Title

Evaluation of prevalence of possible neuropathic component of the reported pain

Description

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)

Time Frame