PMID- 30402880
OWN - NLM
STAT- MEDLINE
DCOM- 20200109
LR  - 20200309
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Print)
IS  - 0009-9236 (Linking)
VI  - 105
IP  - 4
DP  - 2019 Apr
TI  - M281, an Anti-FcRn Antibody: Pharmacodynamics, Pharmacokinetics, and Safety 
      Across the Full Range of IgG Reduction in a First-in-Human Study.
PG  - 1031-1039
LID - 10.1002/cpt.1276 [doi]
AB  - M281 is a fully human, anti-neonatal Fc receptor (FcRn) antibody that inhibits 
      FcRn-mediated immunoglobulin G (IgG) recycling to decrease pathogenic IgG while 
      preserving IgG production. A randomized, double-blind, placebo-controlled, 
      first-in-human study with 50 normal healthy volunteers was designed to probe 
      safety and the physiological maximum for reduction of IgG. Intravenous infusion 
      of single ascending doses up to 60 mg/kg induced dose-dependent serum IgG 
      reductions, which were similar across all IgG subclasses. Multiple weekly doses 
      of 15 or 30 mg/kg achieved mean IgG reductions of  approximately 85% from baseline and 
      maintained IgG reductions >/=75% from baseline for up to 24 days. M281 was well 
      tolerated, with no serious or severe adverse events (AEs), few moderate AEs, and 
      a low incidence of infection-related AEs similar to placebo treatment. The 
      tolerability and consistency of M281 pharmacokinetics and pharmacodynamics 
      support further evaluation of M281 in diseases mediated by pathogenic IgG.
CI  - (c) 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley 
      Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Ling, Leona E
AU  - Ling LE
AD  - Momenta Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
FAU - Hillson, Jan L
AU  - Hillson JL
AD  - Momenta Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
FAU - Tiessen, Renger G
AU  - Tiessen RG
AD  - PRA Health Sciences, Groningen, The Netherlands.
FAU - Bosje, Tjerk
AU  - Bosje T
AD  - PRA Health Sciences, Groningen, The Netherlands.
FAU - van Iersel, Mattheus Paulus
AU  - van Iersel MP
AD  - PRA Health Sciences, Groningen, The Netherlands.
FAU - Nix, Darrell J
AU  - Nix DJ
AD  - Drug Development Consulting, North New Portland, Maine, USA.
FAU - Markowitz, Lynn
AU  - Markowitz L
AD  - Momenta Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
FAU - Cilfone, Nicholas A
AU  - Cilfone NA
AD  - Momenta Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
FAU - Duffner, Jay
AU  - Duffner J
AD  - Momenta Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
FAU - Streisand, James B
AU  - Streisand JB
AD  - Momenta Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
FAU - Manning, Anthony M
AU  - Manning AM
AD  - Momenta Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
FAU - Arroyo, Santiago
AU  - Arroyo S
AD  - Momenta Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20181204
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Antibodies)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Fc)
RN  - TW3XAW0RCY (Fc receptor, neonatal)
SB  - IM
MH  - Adult
MH  - Antibodies/adverse effects/*metabolism/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Healthy Volunteers
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Humans
MH  - Immunoglobulin G/*metabolism
MH  - Infusions, Intravenous/methods
MH  - Male
MH  - Receptors, Fc/*metabolism
MH  - Young Adult
PMC - PMC6587432
COIS- L.E.L., L.M., J.D., A.M.M., and S.A. are full-time employees of Momenta 
      Pharmaceuticals and may own stock or stock options. J.L.H. was an employee of 
      Momenta Pharmaceuticals when the study was designed and conducted and 
      subsequently a paid consultant of Momenta Pharmaceuticals and may own stock or 
      stock options of Momenta Pharmaceuticals. N.A.C. was a full-time employee of 
      Momenta Pharmaceuticals during the execution of the study and subsequently a paid 
      consultant of Momenta Pharmaceuticals, and owned stock, restricted stock, and 
      stock options in Momenta Pharmaceuticals during manuscript preparation. R.G.T., 
      T.B., and M.P.v.I. are full-time employees of PRA Health Sciences and may own 
      stock or stock options in PRA Health Sciences. D.J.N. was principal of Drug 
      Development Consulting, currently is a full-time employee of Certara Strategic 
      Consulting and is a paid consultant of Momenta Pharmaceuticals. J.B.S. is 
      principal at Streisand Biomedical Consulting and a paid consultant of Momenta 
      Pharmaceuticals.
EDAT- 2018/11/08 06:00
MHDA- 2020/01/10 06:00
PMCR- 2018/12/04
CRDT- 2018/11/08 06:00
PHST- 2018/08/17 00:00 [received]
PHST- 2018/10/19 00:00 [accepted]
PHST- 2018/11/08 06:00 [pubmed]
PHST- 2020/01/10 06:00 [medline]
PHST- 2018/11/08 06:00 [entrez]
PHST- 2018/12/04 00:00 [pmc-release]
AID - CPT1276 [pii]
AID - 10.1002/cpt.1276 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2019 Apr;105(4):1031-1039. doi: 10.1002/cpt.1276. Epub 2018 
      Dec 4.