A Phase 3b Open-label Study of Burosumab (KRN23) in adults with XLH
Research type
Research Study
Full title
A Phase 3b Open-label Study of the Anti-FGF23 Antibody, Burosumab (KRN23) in Adult Patients with X-linked Hypophosphatemia (XLH)
IRAS ID
249697
Contact name
Robin Lachmann
Contact email
Sponsor organisation
Kyowa Kirin Pharmaceutical Development Ltd
Eudract number
2018-000202-37
Duration of Study in the UK
1 years, 2 months, 31 days
Research summary
X-linked hypophosphatemia (XLH) is a disorder of hypophosphataemia, renal phosphate wasting and defective bone mineralisation caused by inactivating mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). In the absence of functional PHEX, release of fibroblast growth factor 23 (FGF23) by osteocytes is greatly increased. Excess circulating FGF23 leads to decreased reabsorption of phosphate and reduced 1,25-dihydroxyvitamin D (1,25(OH)2D) production, resulting in decreased intestinal absorption of calcium and phosphate. XLH is a rare, genetic disorder that is serious, chronically debilitating and represents an unmet medical need. This genetic deficiency is estimated to occur in about 1:20,000 live births.
Adult patients with XLH have significant morbidity that increases with age. The current standard of care for XLH in children consists of oral phosphate and vitamin D (calcitriol) replacement, which is typically discontinued in adolescence once longitudinal bone growth is complete
Clinical studies to date have demonstrated that burosumab treatment blocks FGF23 action and leads to a sustained increase in serum phosphorus levels due to increased TmP/GFR. In conclusion, burosumab inhibits the effects of FGF23, restoring phosphate, vitamin D and bone metabolism homeostasis. By positively modulating serum phosphorus, it has been demonstrated at 24 weeks of the UX023 – CL303 that the improvement in phosphate balance was associated with increases in markers of bone formation and reabsorption, consistent with increased bone remodelling.
Approximately 40 subjects who completed either UX023-CL303 or UX023-CL304 will be enrolled.The objectives are to assess the efficacy and safety of burosumab administered via subcutaneous (SC) injections every 4 weeks and to allow subjects continued access to burosumab up until December 2019 or until commercially available.
Burosumab will be administered by a health care professional every 4 weeks at the subject’s home or local clinic and subjects will attend visits to the clinic every 12 weeks.REC name
East of Scotland Research Ethics Service REC 2
REC reference
18/ES/0136
Date of REC Opinion
13 Dec 2018
REC opinion
Further Information Favourable Opinion