Burosumab for Fibroblast Growth Factor-23 Mediated Hypophosphatemia in Fibrous Dysplasia

Background: Fibrous dysplasia (FD) is a disorder that affects bone growth. Affected bone tissue is weakened, and people with FD are prone to deformities, fractures, and other problems. People with FD may also have low blood phosphate levels. This can make bones even weaker. Better treatments are needed. Objective: To test a study drug (burosumab) in people with FD who have low blood phosphate levels. Eligibility: People aged 1 year or older who have FD and low blood phosphate levels. Design: Participants will visit the NIH 3 times in 48 weeks. Each visit will last 5 to 7 days. Participants will self-inject burosumab under the skin in their belly, upper arm, or thigh. They (or a caregiver) will do this at home 1 or 2 times a month. They will be trained in person on how to inject the drug. Home injections will be guided via telehealth. During NIH visits, participants will have a physical exam with blood and urine tests. They will have x-rays of different parts of their body. They will have a radioactive tracer injected into their vein; then they will have a bone scan. They will have tests to assess their strength, walking, and movement. They will complete questionnaires about their pain, mobility, and fatigue levels. Adult participants may have bone biopsies. These will be done under anesthesia with sedation. Small samples of FD-affected bone will be removed for study. Between NIH visits, participants will go to a local laboratory for blood and urine tests. Child participants will have an additional follow-up visit 2 weeks after the final NIH visit.

Study Description: This will be a phase 2, open-label, single-arm study to evaluate the safety and efficacy of burosumab to normalize serum phosphate levels in subjects with fibrous dysplasia (FD) and fibroblast growth factor 23 (FGF23)-mediated hypophosphatemia. Objectives: Primary Objective: -Evaluate the efficacy of burosumab to normalize serum phosphate levels in subjects with FD and FGF23-mediated hypophosphatemia at 48 weeks. Secondary Objectives: * Evaluate the efficacy of burosumab to normalize serum phosphate levels in subjects with FD and FGF23-mediated hypophosphatemia at 24 weeks. * Evaluate the safety and tolerability of burosumab in patients with FD. * Evaluate the effect of burosumab on increasing serum phosphate and additional mineral markers. * Evaluate the impact of burosumab on FD lesion activity. * Evaluate the effect of burosumab on functional parameters. * Evaluate the effect of burosumab on pain and health-related quality of life. Endpoints: Primary Endpoint: -The proportion of subjects achieving serum phosphate levels within the target range (Z-score -1 to +2) at Week 48. Secondary Endpoints: * Proportion of subjects achieving serum phosphate levels within the target range (Z-score -1 to +2) at Week 24. * Adverse events and clinical safety laboratory tests for up to 4 weeks after the final burosumab dose (48 weeks for adult subjects, 50 weeks for pediatric subjects). * Change and percent change from baseline to post-baseline visits in serum phosphate, serum 1,25(OH)2D, ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR). * Change in FD lesion activity using Fluorine-18 Sodium Fluoride Positron Emission Tomography/Computed Tomography (18F-NaF PET/CT) total lesion activity from baseline to 48 weeks * Change and percent change in serum bone turnover markers, including procollagen 1 N-terminal propeptide (P1NP), beta crosslaps C-telopeptides (CTX), osteocalcin, and bone-specific alkaline phosphatase from baseline to 48 weeks. * Change in FD lesion histology and cell proliferation as assessed by minimally invasive bone biopsies from baseline to 48 weeks (adults with capacity to consent only) from baseline to 48 weeks * Skeletal changes assessed on skeletal survey at baseline and 48 weeks * Change from baseline to 48 weeks in: * Muscle strength * Range-of-motion * Walking speed (9-minute walk) Change from baseline to 48 weeks in patient reported outcomes measures: * Short Form Health Survey 36 (SF-36): adults * Short Form Health Survey 10 (SF-10): children * Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity: Pediatric and Parent Proxy version 1.0, Adult version 2.0 * PROMIS Pain Interference: Pediatric and Parent Proxy v 2.0, Adult v 1.1 * PROMIS Mobility: Pediatric and Parent Proxy version 2.0, Adult Mobility Lower Extremity v 1.0 * PROMIS Fatigue: Pediatric and Parent Proxy v 2.0, Adult FACIT 13a v1.0 * Activities of Daily Living Questions: adults and children