Denosumab for Fibrous dysplasia | McCune-Albright syndrome

Inclusion criteria

• {"criterion_text":"- Being symptomatic with an established diagnosis of FD/MAS and closed growth plates (>18 years)\n- Pain in the region of an Fibrous dysplasia localization, not responding to adequate pain treatment and without mechanical component e.g. impending fracture\n- Pain score from Fibrous dysplasia lesion for maximum or average pain on VAS ≥ 4\n- 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\n- Normal levels of calcium, parathyroid hormone and vitamin D (supplementation is allowed)\n- Treated hypophosphatemia (defined as >0.7 at two separate measures)\n- Good dental health (last check within the last 12 months"}

Exclusion criteria

• {"criterion_text":"- Active pregnancy wish, pregnancy or nursing\n- Pain not related to Fibrous dysplasia\n- Uncontrolled endocrine disease\n- Untreated vitamin D deficiency, hypocalcemia or hypophosphatemia\n- Previous use of bisphosphonates or Dmab < 6 months before inclusion (‘6 months wash out’)\n- Previously reported severe side effects on Denosumab\n- Inability to fulfil study requirements\n- Poor untreated dental health without intention to get treatment\n- Treatment with other bone influencing drugs, such as high doses corticosteroids"}

Primary endpoints

• {"endpoint_text":"- The effect of Denosumab on pain, assessed by the difference in maximum pain score after 6 months (2 injections) by Brief Pain Inventory","definition_or_measurement_approach":"Measured by Brief Pain Inventory (BPI); difference in maximum pain score after 6 months (2 injections)."}

Secondary endpoints

• {"endpoint_text":"- 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\n- 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\n- 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\n- To evaluate the effect of Denosumab on average weekly pain assessed through a pain diary with VAS score\n- 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\n- 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\n- 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\n- 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\n- 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\n- To assess disease quantification by nuclear imaging before and after treatment (Skeletal Burden Score (SBS)\n- 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\n- To assess potential side effects in the form of Atypical femoral fractures by performing and extended DXA after 12 months","definition_or_measurement_approach":"Endpoints measured using: BPI for average pain and % responders at 3, 6 (and 9, 12 months if open-label); SF-36 for quality of life at baseline, 3, 6 (and 9, 12 months); pain diary with VAS for weekly pain; HAQ-DI and smartphone pedometer screenshot for physical activity; Pain Detect questionnaire for neuropathic pain; medication review for analgesic use; laboratory bone markers (ALP, P1NP, CTX) for disease activity; Na[18F]-PET/CT or bone scintigraphy and Skeletal Burden Score (SBS) for lesion activity/size; DXA + VFA and extended DXA for bone density, vertebral fractures and atypical femoral fractures."}

Netherlands

Earliest CTIS Part Ii Submission Date

26-03-2024

Latest Decision Or Authorization Date

02-04-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

82

Primary sponsor

Full Name

Leids Universitair Medisch Centrum (LUMC)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands