X-linked hypophosphatemia (XLH) is a disorder of renal phosphate wasting, and the most common heritable form of rickets. In XLH patients, high circulating levels of fibroblast growth factor 23 (FGF23) impair normal phosphate reabsorption in the kidney. Low serum phosphorus levels result in hypomineralization of bone and associated abnormalities including rickets, bowing of the legs, and short stature. MedDRA version: 20.0 Level: LLT Classification code 10077957 Term: X-linked hypophosphatemia S
Conditions
Interventions
Trade Name: Crysvita
Product Name: Crysvita
Pharmaceutical Form: Solution for injection
INN or Proposed INN: BUROSUMAB
CAS Number: 1610833-03-8
Concentration unit: mg/ml milligram(s)/millilitre
Concen
Sponsors
Julius-Maximilian University of Würzburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female, aged = 18 years, inclusive 2) 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: a) documented PHEX mutation in either the patient, or in a directly related family member with appropriate X-linked inheritance b) Increased serum levels of c-term FGF23 or iFGF23 3) Biochemical findings consistent with XLH at Screening visit following overnight fasting: a) Serum phosphorus level or b) TmP/GFR below lab specific lower limit of normal (LLN) 4) 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 5) Subjects who provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures. 6) 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. 7) 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. 8) 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1) 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. 2) Vitamin D deficiency (25OH D3 2.5-fold the upper limit of normal (ULN) 4) Severe renal insufficiency with a Glomerular filtration rate (eGFR) <30 at screening 5) 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.) 6) Treatment with bisphosphates or Denosumab within the last 6 months 7) Treatment with Teriparatide within the last 3 months 8) Intake of calcimimetics within 30 days before screening 9) Patients with known hypersensitivity to Burosumab and the active substances of any of the excipients of Burosumab 10) Presence of a concurrent disease or condition that would interfere with study participation or affect safety in the opinion of the investigator 11) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To confirm the efficacy of Burosumab treatment in terms normalizing phosphorous metabolisms in adults with XLH irrespective of baseline pain level.;Secondary Objective: To evaluate the effect of Burosumab treatment on mobility, daily activity and physical functioning as well as the outcome of the quality of life (QoL). Establish the safety and tolerability profile of Burosumab in the treatment of adults with XLH including adverse events (AEs), ectopic mineralization risk, immunogenicity, and cardiovascular effects.;Primary end point(s): The primary endpoint is the achievement of mean serum phosphorus levels defined as the proportion of subjects attaining a serum phosphorus concentration within the normal range. The individual value for this endpoint is calculated based on the average of a subject's individual values at the midpoint of the representative q4w dosing intervals (week 10, 22, 34 and 50) i.e., two weeks after IMP administration.;Timepoint(s) of evaluation of this end point: Week 12, 22, 34 and 50 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Laboratory parameters of phosphorus and calcium homeostasis (TmP/GFR) • Changes from baseline regarding 6-Minute-Walk Test • Changes from baseline in Chair rise Test completion time • Changes from baseline in Timed-up and down stair Test completion time • Activity tracking using ‘Actibelt®’, including data on average gait speed per day, number of steps per day, total walking distance, and total hours of physical activity measured before treatment initiation and four times during treatment for at least seven consecutive days. ;Timepoint(s) of evaluation of this end point: Week 50 | — |
Countries
Germany
Contacts
Public ContactCoordinating Investigator
Julius-Maximilian University of Würzburg
Outcome results
None listed