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Currently, you can access the following clinical trials being conducted worldwide:
Clinicaltrials.gov identifier NCT03920072
Recruitment Status Recruiting
First Posted April 18, 2019
Last update posted November 27, 2019
This is phase 3b open-label, international, multicenter study to continue to monitor the long-term safety and efficacy of burosumab in adult patients with XLH that participated in previous clinical trials with burosumab (UX023-CL303 / UX023-CL304).
XLH is a rare, genetic disorder that is serious, chronically debilitating and represents an unmet medical need. XLH is the most common inherited form of rickets and the most common inherited defect in renal tubular phosphate transport. XLH is transmitted as an X-linked dominant disorder. Mutations resulting in the loss of function of PHEX form the genetic basis for XLH. More than 300 different PHEX gene mutations have been identified in patients with XLH (PHEXdb); however, few definitive correlations have been observed between specific mutations and phenotypic severity. Patients with XLH have hypophosphatemia due to excessive serum FGF23 levels. FGF23 reduces serum phosphorus levels by two distinct mechanisms of action. The primary mechanism is to inhibit phosphate reabsorption in the proximal tubule of the kidney. The secondary mechanism is to decrease phosphate absorption by the small intestine through the inhibition of 1,25(OH)2D production in the kidney. Burosumab has the potential to block or reduce FGF23 action and improve phosphate homeostasis in XLH patients. Burosumab binds the amino-terminal domain of FGF23 that interacts with the FGF-binding portion of the combination FGFR1/Klotho receptor, preventing FGF23 from binding to and signaling from its receptor. Both intact and fragmented FGF23 polypeptides are immunoprecipitated with burosumab. By inhibiting FGF23, burosumab restores tubular reabsorption of phosphate (as measured by the ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate [TmP/GFR]) from the kidney and increases the production of 1,25(OH)2D that also enhances intestinal absorption of phosphate. The dual action on kidney reabsorption and intestinal absorption improves serum phosphorus levels, which is expected to improve bone mineralization and reduce the diverse bone and non-bone manifestations associated with hypophosphatemia in XLH patients.
|Other: Open label
All subjects will be administered subcutaneously burosumab every 4 weeks at the dosage defined in study UX023-CL303 or UX023-CL304 until December 2021 or when the drug becomes commercially available.
Burosumab is a sterile, clear, colourless and preservative free solution supplied in single-use 5ml vials containing 1mL of burosumab at a concentration of 30mg/mL
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, , Learn About Clinical Studies.-->
1. Subjects who provide written informed consent after the nature of the study has been
explained, and prior to any research-related procedures.
2. Subjects who participated in Study UX023-CL303 or UX023-CL304. Any subjects that did
not complete Study UX023-CL303 or UX023-CL304 may be included on a case-by-case basis.
Subjects' enrolment is not dependent on any response to Primary or Secondary endpoints
in studies UX023-CL303 or UX023-CL304.
3. Willing to provide access to prior medical records for the collection of historical
growth, biochemical and radiographic data, and disease history.
4. 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.
5. 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 two 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. If sexually active, male and female subjects must be willing to
use one highly effective method of contraception for the duration of the study.
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
2. Presence of a concurrent disease or condition that would interfere with study
participation or affect safety in the opinion of the investigator or Sponsor.
3. 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.
4. Subjects with major protocol deviations in Study UX023-CL303 or UX023-CL304 which in
the view of the investigator places the subject at high risk of poor treatment
compliance or of not completing the study.
5. Subjects who discontinued treatment from Study UX023-CL303 or UX023-CL304 due to
either a grade ≥3 treatment-related hypersensitivity reaction or a burosumab-related
hypersensitivity reaction reported as a SAE.
Contact: Development Division Project Management Department 609-919-1100 firstname.lastname@example.org
CHU de Bicetre
St. Vincent's University Hospital
Azienda ospedaliera universitaria Careggi
Western General Hospital
National Hospital for Neurology and Neurosurgery-University College London Hospitals NHS Foundation Trust
Nuffield Orthopaedic Centre - Oxford University Hospitals Nhs Trust
Northen General Hospital
Royal National Orthopaedic Hospital NHS Trust
Kyowa Kirin Pharmaceutical Development Ltd
Principal Investigator: Peter Kamenicky CHU de Bicêtre