Dataset Information

Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia.

ABSTRACT: X-linked hypophosphatemia (XLH) is characterized by lower extremity deformities that lead to bone and/or joint pain that result from decreased renal tubular reabsorption leading to hypophosphatemia caused by elevated levels of fibroblast growth factor 23 (FGF23). OBJECTIVE:Validate the use of SF-36v2 Health Survey (SF-36v2) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) to measure previously unstudied health-related quality of life (HRQoL) in XLH patients and determine the change in HRQoL before and after treatment with KRN23, a human monoclonal anti-FGF23 antibody. METHODS:Twenty-eight adult outpatients with XLH received up to four doses of KRN23 administered subcutaneously every 28 days. General HRQoL was measured with the SF-36v2 and condition-related HRQoL with the WOMAC at baseline and study endpoint as a secondary outcome of a Phase 1/2, open-label, multicenter, dose-escalation trial. RESULTS:Testing for scale discriminant validity and convergent-divergent validity supported the use of these scales in the assessment of HRQoL in XLH. Both instruments indicated impairment of physical function at baseline with all mean scores showing a trend to improved health at study endpoint compared to baseline. When corrected for multiple comparisons, the score for Role Limitations due to physical health on the SF-36v2 which measures the patient's perception of their own chronic functional impairments due to poor physical health remained significantly improved (P < 0.05), increasing to the mean score of US adults. For the WOMAC, Physical Functioning and Stiffness scores were significantly improved (P < 0.05). CONCLUSION:KRN23 administration was associated with significantly improved patient perception of their Physical Functioning and Stiffness due to their disease. This study demonstrates that the SF-36v2 and WOMAC are valid tools for assessing HRQoL in XLH.

SUBMITTER: Ruppe MD

PROVIDER: S-EPMC4926842 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia.

Ruppe Mary D MD Zhang Xiaoping X Imel Erik A EA Weber Thomas J TJ Klausner Mark A MA Ito Takahiro T Vergeire Maria M Humphrey Jeffrey S JS Glorieux Francis H FH Portale Anthony A AA Insogna Karl K Peacock Munro M Carpenter Thomas O TO

Bone reports 20160513

X-linked hypophosphatemia (XLH) is characterized by lower extremity deformities that lead to bone and/or joint pain that result from decreased renal tubular reabsorption leading to hypophosphatemia caused by elevated levels of fibroblast growth factor 23 (FGF23).<h4>Objective</h4>Validate the use of SF-36v2 Health Survey (SF-36v2) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) to measure previously unstudied health-related quality of life (HRQoL) in XLH patients and determine ...[more]

PMID: 28326356

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Project description:X-linked hypophosphatemia (XLH) is a disease caused by abnormally elevated FGF23 levels, which cause persistent hypophosphatemia accompanied by subsequent reduction in bone mineralization that presents as rickets or osteomalacia. Burosumab is a fully human monoclonal antibody targeting FGF23 that is under development for the treatment of FGF23-related hypophosphatemia including XLH. The safety, tolerability, and proof of concept of burosumab have been evaluated in patients with XLH in previous studies conducted in countries outside of Asia. The objective of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and expression of anti-drug antibodies in Japanese and Korean adults with XLH. This was a multicenter, sequential dose-escalation, open-label, single-dose study. This study began with cohort 1 (s.c. dose of burosumab 0.3?mg/kg), after which the dose was escalated sequentially in cohort 2 (s.c. dose of burosumab 0.6?mg/kg) and cohort 3 (s.c. dose of burosumab 1.0?mg/kg). The PK of burosumab were linear within the dose range of 0.3 to 1.0?mg/kg. The PD effects such as serum phosphorus concentration, serum 1,25[OH]2D3 concentration, and ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) were elevated after a single s.c. administration. The area under the receiver-operating characteristic curve from 0 to t (AUC0-t) values calculated using the change from baseline values of serum phosphorus, serum 1,25(OH)2D3, and TmP/GFR were correlated with the AUC0-t of burosumab. Furthermore, no serious adverse events (AEs), deaths, remarkable increase or decrease in the corrected calcium or intact PTH levels, or signs of nephrocalcinosis or its worsening were observed after treatment. Some AEs and drug-related AEs were observed; however, there were no clinically meaningful tendencies. The positive effects and acceptable safety profile seen in this study are encouraging for Japanese and Korean patients with XLH.

Dataset Information

Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia.

Publications

Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia.

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