Anti-FGF23 (Burosumab) in Adult Patients With XLH
Anti-FGF23 (Burosumab) in Adult Patients With XLH
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.
Inclusion Criteria:

 -  Male or female, aged ≥ 18 years, inclusive

 -  Diagnosis of X-linked Hypophosphatemia supported by classic clinical features of adult
 XLH (e.g. short statue or bowed legs, clinical symptoms as judged by the investigator)
 and at least one of the following at Screening visit:

 -  documented PHEX mutation in either the patient, or

 -  in a directly related family member with appropriate X-linked inheritance

 -  Increased serum levels of c-term FGF23 or iFGF23

 -  Biochemical findings consistent with XLH at Screening visit following overnight
 fasting:

 -  Serum phosphorus level or

 -  TmP/GFR below lab specific lower limit of normal (LLN)

 -  Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (using the Chronic Kidney
 Disease Epidemiology Collaboration equitation) or eGFR of 30 up to 60 mL/min at
 Screening visit with confirmation that the renal insufficiency is not due to
 nephrocalcinosis

 -  Subjects who provide written informed consent after the nature of the study has been
 explained, and prior to any research-related procedures.

 -  Participants must, in the opinion of the investigator, be willing and able to complete
 all aspects of the study, adhere to the study visit schedule and comply with the
 assessments.

 -  Females of child-bearing potential must have a negative urine pregnancy test at
 Screening and be willing to have additional pregnancy tests during the study. Females
 considered not to be of child-bearing potential include those who have been in
 menopause for at least 2 years prior to Screening, or have had tubal ligation at least
 one year prior to Screening, or have had a total hysterectomy or bilateral
 salpingo-oophorectomy.

 -  Female Participants of child-bearing potential who are sexually active must consent to
 use an effective method of contraception as determined by the site investigator (i.e.
 oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring,
 intrauterine devices, surgical hysterectomy, vasectomy, tubal ligation, or true
 abstinence) from the period following the signing of the informed consent through 12
 weeks after the last dose of study drug.

 Exclusion Criteria:

 -  Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the
 age-adjusted normal limits and deemed as clinically significant in the opinion of the
 investigator.

 -  Vitamin D deficiency (25OH D3 < 20ng/ml); if Vitamin D is low at screening,
 substitution is allowed and recompensation has to be confirmed before treatment start
 by normalized levels of Vitamin D (25OH D3 ≥ 20ng/ml)

 -  Serum intact parathyroid hormone (iPTH) >2.5-fold the upper limit of normal (ULN)

 -  Severe renal insufficiency with a Glomerular filtration rate (eGFR) <30 at screening

 -  Treatment with oral phosphate and / or active vitamin D analogues in addition to
 Burosumab treatment. (In order to ensure appropriate patient care and preclude any
 harm due to deficient supply, required supplementation with oral phosphate salts
 and/or active vitamin D analogues at screening can be continued during the run-in
 phase but has to be stopped before Baseline and Initiation of treatment with
 Burosumab.)

 -  Treatment with bisphosphates or Denosumab within the last 6 months

 -  Treatment with Teriparatide within the last 3 months

 -  Intake of calcimimetics within 30 days before screening

 -  Patients with known hypersensitivity to Burosumab and the active substances of any of
 the excipients of Burosumab

 -  Presence of a concurrent disease or condition that would interfere with study
 participation or affect safety in the opinion of the investigator

 -  Use of any investigational product other than Burosumab or investigational medical
 device within 30 days prior to screening, or requirement for any investigational agent
 prior to completion of all scheduled study assessments.