DEnosumab for the treatment of FIbrous Dysplasia/McCune-Albright Syndrome in adults (DeFiD): a randomized double-blind placebo-controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leids Universitair Medisch Centrum (LUMC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

13 Jun 2023 → ongoing

Decision date (initial)

2024-04-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-511090-30-00

EudraCT number

2022-002611-29

ClinicalTrials.gov

NCT05966064

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the effect of Denosumab on pain, assessed by the difference in maximum pain scores after 6 months (2 injections)

Secondary objectives 6

1. Evaluation of Denosumab effect on Quality of life, physical activity
2. Evaluation of possible neuropathic component of the reported pain
3. Evaluation of analgesics use
4. Evaluation of changes in mobility
5. Evaluation of Denosumab effect on Fibrous dysplasia lesion size and activity
6. Evaluation of Denosumab effect on bone density

Conditions and MedDRA coding

Fibrous dysplasia/McCune-Albright syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Being symptomatic with an established diagnosis of FD/MAS and closed growth plates (>18 years)
2. Pain in the region of an Fibrous dysplasia localization, not responding to adequate pain treatment and without mechanical component e.g. impending fracture
3. Pain score from Fibrous dysplasia lesion for maximum or average pain on VAS ≥ 4
4. Increased lesional activity defined as increased bone turnover markers (ALP, P1NP or CTX) or increased activity on Na18F-PET/CT or bone scintigraphy in at least one lesion
5. Normal levels of calcium, parathyroid hormone and vitamin D (supplementation is allowed)
6. Treated hypophosphatemia (defined as >0.7 at two separate measures)
7. Good dental health (last check within the last 12 months

Exclusion criteria 9

1. Active pregnancy wish, pregnancy or nursing
2. Pain not related to Fibrous dysplasia
3. Uncontrolled endocrine disease
4. Untreated vitamin D deficiency, hypocalcemia or hypophosphatemia
5. Previous use of bisphosphonates or Dmab < 6 months before inclusion (‘6 months wash out’)
6. Previously reported severe side effects on Denosumab
7. Inability to fulfil study requirements
8. Poor untreated dental health without intention to get treatment
9. Treatment with other bone influencing drugs, such as high doses corticosteroids

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The effect of Denosumab on pain, assessed by the difference in maximum pain score after 6 months (2 injections) by Brief Pain Inventory

Secondary endpoints 12

1. To evaluate the effect of Denosumab on average pain scores after 3, 6 months of treatment and in case of open label treatment after 9 and 12 months
2. To evaluate the number of patients with 50% reduction of maximal pain (BPI) after 3, 6 months of treatment and in case of open label treatment after 9 and 12 months
3. To evaluate the effect of Denosumab on quality of life, assessed with questionaries (SF-36) at baseline, 3 months and after 6 months and in case of open label treatment after 9 and 12 months
4. To evaluate the effect of Denosumab on average weekly pain assessed through a pain diary with VAS score
5. To investigate the effect of Denosumab on Physical activity assessment (Health Assessment Questionnaire – Disability Index and screenshot of pedometer of activity during the last week on smartphone) measured at baseline, 3 months and 6 months, and in case of open label treatment after 9 and 12 months
6. To evaluate the prevalence of possible neuropathic component of the reported pain through Pain Detect questionnaire at baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
7. To investigate the number of analgesics, use and dosage used at baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months
8. To assess the effect of Denosumab on disease activity through laboratory measurements of bone markers at baseline, 3 months and 6 months, and in case of open label treatment after 9 and 12 months
9. To assess the effect of Denosumab on lesions activity and lesions size through bone scans at baseline and after 6 months, and in the case of open label treatment after 12 months
10. To assess disease quantification by nuclear imaging before and after treatment (Skeletal Burden Score (SBS)
11. To assess bone density and the presence of vertebral fractures (Dual-energy X-ray absorptiometry (DXA) + Vertebral Fractures Assessment (VFA) at baseline and after 12 months
12. To assess potential side effects in the form of Atypical femoral fractures by performing and extended DXA after 12 months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leids Universitair Medisch Centrum (LUMC)

Sponsor organisation

Leids Universitair Medisch Centrum (LUMC)

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

Natasha Appelman-Dijkstra

Public contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

Natasha Appelman-Dijkstra

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications