Fibrous DysplasiaPhase 4DeFiDNCT05966064
DEnosumab for the Treatment of FIbrous Dysplasia/McCune-Albright Syndrome in Adults (DeFiD)
A Phase 4 study testing Denosumab 120 Mg/1.7 Ml Inj in people with Fibrous Dysplasia and McCune Albright Syndrome, run by Natasha Appelman-Dijkstra at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fibrous Dysplasia, McCune Albright Syndrome
- What is being tested?
- Denosumab 120 Mg/1.7 Ml Inj
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 1 siteNetherlands
- Study dates
- 13 Jun 2023to Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden
Natasha Appelman-Dijkstra, MD, PhD, +31 625301410, n.m.appelman-dijkstra@lumc.nl
Natasha Appelman-Dijkstra
About this study
Official title: 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.
Read the 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.
- Conditions
- Fibrous Dysplasia, McCune Albright Syndrome
- Being tested
- Denosumab 120 Mg/1.7 Ml Inj, Placebo
- Medical subject headings
- Fibrous Dysplasia of Bone, Fibrous Dysplasia, Polyostotic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Denosumab 120 Mg/1.7 Ml InjDrug
Also called Xgeva
Denosumab randomized at baseline and after 3 months at 6 and 9 months in case of open label
PlaceboDrug
placebo randomized at baseline and after 3 months
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Denosumab 120 Mg/1.7 Ml Inj |
| Placebo | Placebo comparator | Placebo randomized at baseline and 3 months in a double-blinded fashion. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Evaluation of average pain score changes after treatment, assessed by Brief Pain Inventory (scale 0 to 10; 0-no pain,10 worst pain)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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)
Measured: 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)
Measured: baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
To investigate the number of analgesics used for pain
number of used analgesics for pain : unit of measure: number
Measured: baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
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)
Measured: baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
To investigate the dosage of analgesics used for pain
dosage of analgesics used for pain (unit of measure: mg)
Measured: baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
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)
Measured: baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
Denosumab effect on serum markers
effect of Denosumab on serum calcium(mmol/L), fosfate (mmol/L), PTH (pmol/L)
Measured: baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
Denosumab effect on lesion size
Na18F-PET/CT scan- measurement of lesion size
Measured: baseline and after 6 months, and in the case of open label treatment after 12 months
Denosumab effect on lesion activity
Na18F-PET/CT scan- ,measurement of Na18F uptake
Measured: baseline and after 6 months, and in the case of open label treatment after 12 months
disease quantification (Skeletal Burden Score (SBS)
nuclear imaging ((Skeletal Burden Score (SBS): scale 0 to 75, higher scores meaning increased disease activity
Measured: at baseline, 6 months and after 12 months
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)
Measured: baseline and after 12 months
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
Measured: baseline and after 12 months
To assess potential side effects in the form of Atypical femoral fractures
Dual-energy X-ray absorptiometry (DXA) femur extended
Measured: after 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2023
- Study start13 Jun 2023
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fibrous DysplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 82 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Natasha Appelman-Dijkstra
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Natasha Appelman-Dijkstra, Leiden University Medical Center
- Investigators
- Natasha Appelman-Dijsktra, MD, PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05966064
- Sponsor's protocol ID
- 2022-501705-12-00
- Acronym
- DeFiD
- Status last verified
- Jan 2025
- First submitted
- 19 Jun 2023
- Last updated
- 29 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DEnosumab for the Treatment of FIbrous Dysplasia/McCune-Albright Syndrome in Adults (DeFiD): a Randomized Double-blind Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT05966064
- Acronym / sponsor ID
- DeFiD / 2022-501705-12-00
- Conditions
- Fibrous Dysplasia, McCune Albright Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 82 participants (estimated)
- Lead sponsor
- Natasha Appelman-DijkstraUniversity, hospital or other
- Study start
- 13 Jun 2023 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 28 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab | Active comparator | Drug: Denosumab 120 Mg/1.7 Ml InjDenosumab randomized at baseline and 3 months in a double-blinded fashion and in case of open label at 6 and 9 months |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo randomized at baseline and 3 months in a double-blinded fashion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (9 listed)
- 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')
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Denosumab 120 Mg/1.7 Ml InjAlso: XgevaDenosumab randomized at baseline and after 3 months at 6 and 9 months in case of open label | Drug | Denosumab |
| Placeboplacebo randomized at baseline and after 3 months | Drug | Placebo |
Primary outcome
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)
18 secondary outcomes
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
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
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
Denosumab effect on average weekly pain score
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
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
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
Time frame: baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
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
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
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
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
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
Denosumab effect on lesion size
Time frame: baseline and after 6 months, and in the case of open label treatment after 12 months
Denosumab effect on lesion activity
Time frame: baseline and after 6 months, and in the case of open label treatment after 12 months
disease quantification (Skeletal Burden Score (SBS)
Time frame: at baseline, 6 months and after 12 months
Denosumab effect on bone density
Time frame: baseline and after 12 months
Denosumab effect on vertebral fractures
Time frame: baseline and after 12 months
To assess potential side effects in the form of Atypical femoral fractures
Time frame: after 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Natasha Appelman-Dijsktra, MD, PhD principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Denosumab 120 Mg/1.7 Ml Inj in people with Fibrous Dysplasia and McCune Albright Syndrome, run by Natasha Appelman-Dijkstra at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Natasha Appelman-Dijkstra, MD, PhD (+31 625301410, n.m.appelman-dijkstra@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2025.