PMID- 30828689
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2473-4039 (Electronic)
IS  - 2473-4039 (Linking)
VI  - 3
IP  - 2
DP  - 2019 Feb
TI  - First-in-Asian Phase I Study of the Anti-Fibroblast Growth Factor 23 Monoclonal 
      Antibody, Burosumab: Safety and Pharmacodynamics in Adults With X-linked 
      Hypophosphatemia.
PG  - e10074
LID - 10.1002/jbm4.10074 [doi]
LID - e10074
AB  - 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](2)D(3) 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 (AUC(0-t)) values calculated using the change from baseline 
      values of serum phosphorus, serum 1,25(OH)(2)D(3), and TmP/GFR were correlated 
      with the AUC(0-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.
CI  - (c) 2018 The Authors published by Wiley Periodicals, Inc. on behalf of American 
      Society for Bone and Mineral Research.
FAU - Cheong, Hae Il
AU  - Cheong HI
AD  - Department of Pediatrics Seoul National University Children's Hospital Seoul 
      Republic of Korea.
FAU - Yoo, Han-Wook
AU  - Yoo HW
AD  - Department of Pediatrics Asan Medical Center Seoul Republic of Korea.
FAU - Adachi, Masanori
AU  - Adachi M
AD  - Department of Endocrinology and Metabolism Kanagawa Children's Medical Center 
      Kanagawa Japan.
FAU - Tanaka, Hiroyuki
AU  - Tanaka H
AD  - Department of Pediatrics Okayama Saiseikai General Hospital Okayama Japan.
FAU - Fujiwara, Ikuma
AU  - Fujiwara I
AD  - Department of Pediatric Endocrinology and Environmental Medicine Tohoku 
      University Graduate School of Medicine Miyagi Japan.
FAU - Hasegawa, Yukihiro
AU  - Hasegawa Y
AD  - Division of Endocrinology and Metabolism Tokyo Metropolitan Children's Medical 
      Center Tokyo Japan.
FAU - Harada, Daisuke
AU  - Harada D
AD  - Department of Pediatrics Osaka Hospital Japan Community Healthcare Organization 
      (JCHO) Osaka Japan.
FAU - Sugimoto, Maiko
AU  - Sugimoto M
AD  - Kyowa Hakko Kirin Co. Ltd Tokyo Japan.
FAU - Okada, Yosuke
AU  - Okada Y
AD  - Kyowa Hakko Kirin Co. Ltd Tokyo Japan.
FAU - Kato, Masaki
AU  - Kato M
AD  - Kyowa Hakko Kirin Co. Ltd Tokyo Japan.
FAU - Shimazaki, Ryutaro
AU  - Shimazaki R
AD  - Kyowa Hakko Kirin Co. Ltd Tokyo Japan.
FAU - Ozono, Keiichi
AU  - Ozono K
AD  - Department of Pediatrics Osaka University Graduate School of Medicine Osaka 
      Japan.
FAU - Seino, Yoshiki
AU  - Seino Y
AD  - Department of Pediatrics Osaka Hospital Japan Community Healthcare Organization 
      (JCHO) Osaka Japan.
LA  - eng
PT  - Journal Article
DEP - 20180914
PL  - England
TA  - JBMR Plus
JT  - JBMR plus
JID - 101707013
PMC - PMC6383703
OTO - NOTNLM
OT  - CELL/TISSUE SIGNALING-ENDOCRINE PATHWAYS
OT  - CLINICAL TRIALS
OT  - DISEASES AND DISORDERS OF/RELATED TO BONE
OT  - DISORDERS OF CALCIUM/PHOSPHATE, OTHER
OT  - OSTEOMALACIA AND RICKETS
OT  - PTH/VIT D/FGF2
EDAT- 2019/03/05 06:00
MHDA- 2019/03/05 06:01
PMCR- 2018/09/14
CRDT- 2019/03/05 06:00
PHST- 2018/05/31 00:00 [received]
PHST- 2018/08/03 00:00 [revised]
PHST- 2018/08/05 00:00 [accepted]
PHST- 2019/03/05 06:00 [entrez]
PHST- 2019/03/05 06:00 [pubmed]
PHST- 2019/03/05 06:01 [medline]
PHST- 2018/09/14 00:00 [pmc-release]
AID - JBM410074 [pii]
AID - 10.1002/jbm4.10074 [doi]
PST - epublish
SO  - JBMR Plus. 2018 Sep 14;3(2):e10074. doi: 10.1002/jbm4.10074. eCollection 2019 
      Feb.