- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05966064
DEnosumab for the Treatment of FIbrous Dysplasia/McCune-Albright Syndrome in Adults (DeFiD) (DeFiD)
DEnosumab for the Treatment of FIbrous Dysplasia/McCune-Albright Syndrome in Adults (DeFiD): a Randomized Double-blind Placebo-controlled Trial
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Natasha Appelman-Dijkstra, MD, PhD
- Phone Number: +31 625301410
- Email: n.m.appelman-dijkstra@lumc.nl
Study Locations
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-
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Leiden, Netherlands
- Recruiting
- Leiden University Medical Center
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Contact:
- Natasha Appelman-Dijkstra, MD, PhD
- Phone Number: +31 625301410
- Email: n.m.appelman-dijkstra@lumc.nl
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Principal Investigator:
- Natasha Appelman-Dijkstra
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Denosumab
Denosumab randomized at baseline and 3 months in a double-blinded fashion and in case of open label at 6 and 9 months
|
Denosumab randomized at baseline and after 3 months at 6 and 9 months in case of open label
Other Names:
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Placebo Comparator: Placebo
Placebo randomized at baseline and 3 months in a double-blinded fashion.
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placebo randomized at baseline and after 3 months
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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at baseline, 3 months and after 6 months and in case of open label treatment after 9 and 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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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)
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)
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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
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)
|
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
Time Frame: every week from baseline, through study completion, an average of 1 year
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Evaluation of Denosumab effect on average weekly pain score assessed through a pain diary with VAS score (scale 0 to 10)
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every week from baseline, through study completion, an average of 1 year
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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.
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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
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)
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baseline, 3 months and 6 months, and in case of open label treatment after 9 and 12 months
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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
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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)
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baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
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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
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number of used analgesics for pain : unit of measure: number
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baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
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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
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the frequency use of analgesics for pain (daily, multiple times per day, multiple times per week, monthly, when necessary)
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baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
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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
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dosage of analgesics used for pain (unit of measure: mg)
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baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
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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)
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baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
|
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
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effect of Denosumab on serum calcium(mmol/L), fosfate (mmol/L), PTH (pmol/L)
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baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
|
Denosumab effect on lesion size
Time Frame: baseline and after 6 months, and in the case of open label treatment after 12 months
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Na18F-PET/CT scan- measurement of lesion size
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baseline and after 6 months, and in the case of open label treatment after 12 months
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Denosumab effect on lesion activity
Time Frame: baseline and after 6 months, and in the case of open label treatment after 12 months
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Na18F-PET/CT scan- ,measurement of Na18F uptake
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baseline and after 6 months, and in the case of open label treatment after 12 months
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disease quantification (Skeletal Burden Score (SBS)
Time Frame: at baseline, 6 months and after 12 months
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nuclear imaging ((Skeletal Burden Score (SBS): scale 0 to 75, higher scores meaning increased disease activity
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at baseline, 6 months and after 12 months
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Denosumab effect on bone density
Time Frame: baseline and after 12 months
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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)
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baseline and after 12 months
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Denosumab effect on vertebral fractures
Time Frame: baseline and after 12 months
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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
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baseline and after 12 months
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To assess potential side effects in the form of Atypical femoral fractures
Time Frame: after 12 months
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Dual-energy X-ray absorptiometry (DXA) femur extended
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after 12 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Natasha Appelman-Dijsktra, MD, PhD, Leiden University Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2022-501705-12-00
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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