X-linked hypophosphatemia (XLH) rare genetic disorder due by inactivating mutations in the PHEX gene leading to increased levels in FGF-23. Elevated FGF-23 reduces renal phosphate reabsorbtion and and limits 1-alpha hydroxylase driven Vitamin D activation, eventually leading to phosphate wasting, defective bone mineralization and additional health issues. Burosumab is a recombinant fully human IgG1 monoclonal antibody developed to treat XLH by binding FGF23, thereby restoring normal phosphate homeostasis. BUR03 is a Phase 3b open-label, single-arm, single-center study to confirm the efficacy and safety of Burosumab treatment in adult (age ≥18 years) XLH patients without upper age limit and irrespective of baseline pain level and to further evaluate the efficacy in this cohort and the assocaited effect of treatment on physical functioning, mobility and activity. The study aims at enrolling and treating 34 subjects with a confirmed diagnosis of XLH with q4w s.c. injection of Burosumab 1mg/kg body weight over 48 weeks. Primary objective is to attiain normal serum phosphorus levels, secondary objectives include key parameters of physical function and activity, mobility and mineral homeostasis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Q4w, 1mg/kg Body weight, s.c.
Clinical Trial Unit, Orthopedic Department, Wuerzburg University
Würzburg, Germany
Effect of Burosumab treatment on attaining serum phosphorus levels within the normal range in adults with XLH
Proportion of subjects attaining a serum phosphorus concentration within the normal range
Time frame: 48 weeks
Change in chari rise test completion time
Change in chair rise test completion time from baseline to end of study visit
Time frame: 48 weeks
Change in 6-Minute-Walk test
Change in 6-Minute-Walk test distance from baseline to end of study visit
Time frame: 48 weeks
Change in timed up-and down stairs completion time
Change in timed up-and down stairs completion time from baseline to end of study visit
Time frame: 48 weeks
Normalization of TmP/GFR
Normalization of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR), proportion of subjects achieving normal values
Time frame: 48 weeks
Activity tracking
Activity tracking using 'Actibelt', to delineate total hours of physical activity per week
Time frame: 48 weeks
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