Ignite Creation Date:
2024-05-06 @ 1:04 PM
Last Modification Date:
2024-10-26 @ 1:08 PM
Study NCT ID:
NCT03920072
Status:
COMPLETED
Last Update Posted:
2022-05-20
First Post:
2018-10-29
Brief Title:
Study of the Anti-FGF23 Antibody Burosumab in Adults With XLH
Sponsor:
Kyowa Kirin Pharmaceutical Development Ltd
Organization:
Kyowa Kirin Pharmaceutical Development Ltd
Study Overview
Official Title:
A Phase 3b Open-label Study of the Anti-FGF23 Antibody Burosumab KRN23 in Adult Patients With X-linked Hypophosphatemia XLH
Status:
COMPLETED
Status Verified Date:
2022-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
Detailed Description:
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 125OH2D 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 FGFR1Klotho 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 TmPGFR from the kidney and increases the production of 125OH2D 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
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 125OH2D 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 FGFR1Klotho 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 TmPGFR from the kidney and increases the production of 125OH2D 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None