PMID- 35506164
OWN - NLM
STAT- MEDLINE
DCOM- 20220718
LR  - 20221014
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 15
IP  - 7
DP  - 2022 Jul
TI  - A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of 
      respiratory syncytial virus neutralizing monoclonal antibody MK-1654 in healthy 
      Japanese adults.
PG  - 1753-1763
LID - 10.1111/cts.13290 [doi]
AB  - Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract 
      infection among all infants worldwide and remains a significant cause of 
      morbidity and mortality. To address this unmet medical need, MK-1654, a half-life 
      extended RSV neutralizing monoclonal antibody, is in clinical development for the 
      prevention of RSV disease in infants. This was a phase I, randomized, 
      placebo-controlled, single-site, double-blind trial of MK-1654 in 44 healthy 
      Japanese adults. The safety, tolerability, pharmacokinetics, antidrug antibodies 
      (ADAs), and serum neutralizing antibody (SNA) titers against RSV were evaluated 
      for 1 year after a single intramuscular (i.m.) or intravenous (i.v.) dose of 
      MK-1654 or placebo in five groups (100 mg i.m., 300 mg i.m., 300 mg i.v., 1000 mg 
      i.v., or placebo). MK-1654 was generally well-tolerated in Japanese adults. There 
      were no serious drug-related adverse events (AEs) reported in any MK-1654 
      recipient and no discontinuations due to any AEs in the study. The half-life of 
      MK-1654 ranged from 76 to 91 days across dosing groups. Estimated bioavailability 
      was 86% for 100 mg i.m. and 77% for 300 mg i.m. One participant out of 33 (3.0%) 
      developed detectable ADA with no apparent associated AEs. The RSV SNA titers 
      increased in a dose-dependent manner among participants who received MK-1654. 
      These data support the development of MK-1654 for use in Japanese infants.
CI  - (c) 2022 Merck Sharp & Dohme LLC. Clinical and Translational Science published by 
      Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Orito, Yuji
AU  - Orito Y
AD  - MSD K.K., Tokyo, Japan.
FAU - Otani, Naoyuki
AU  - Otani N
AD  - Oita University, Oita, Japan.
FAU - Matsumoto, Yuki
AU  - Matsumoto Y
AD  - MSD K.K., Tokyo, Japan.
FAU - Fujimoto, Katsukuni
AU  - Fujimoto K
AD  - MSD K.K., Tokyo, Japan.
FAU - Oshima, Nobuyuki
AU  - Oshima N
AD  - MSD K.K., Tokyo, Japan.
FAU - Maas, Brian M
AU  - Maas BM
AD  - Merck and Co., Inc., Rahway, New Jersey, USA.
FAU - Caro, Luzelena
AU  - Caro L
AD  - Merck and Co., Inc., Rahway, New Jersey, USA.
FAU - Aliprantis, Antonios O
AU  - Aliprantis AO
AD  - Merck and Co., Inc., Rahway, New Jersey, USA.
AD  - Flagship Pioneering, Boston, Massachusetts, USA.
FAU - Cox, Kara S
AU  - Cox KS
AD  - Merck and Co., Inc., Rahway, New Jersey, USA.
FAU - Tokumaru, Osamu
AU  - Tokumaru O
AD  - Oita University, Oita, Japan.
FAU - Kodama, Masaaki
AU  - Kodama M
AD  - Oita University, Oita, Japan.
FAU - Kudo, Hideo
AU  - Kudo H
AD  - Oita University, Oita, Japan.
FAU - Imai, Hiromitsu
AU  - Imai H
AUID- ORCID: 0000-0001-7805-1180
AD  - Oita University, Oita, Japan.
FAU - Uemura, Naoto
AU  - Uemura N
AD  - Oita University, Oita, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20220517
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Humans
MH  - Infant
MH  - Japan
MH  - *Respiratory Syncytial Virus Infections/drug therapy/prevention & control
MH  - *Respiratory Syncytial Virus, Human
PMC - PMC9283748
COIS- Y.O., Y.M., K.F., N.O., B.M.M., L.C., and A.O.A. are employees (or were at the 
      time of the study) of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., 
      Rahway, NJ, USA, and may hold stock in Merck & Co., Inc., Rahway, NJ, USA. K.S.C. 
      is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., 
      Rahway, NJ, USA, may hold stock in Merck & Co., Inc., Rahway, NJ, USA, and is 
      named on an issued patent related to the discovery of the RSV antibody. N.U. 
      reports payments as a Primary Investigator for the study, is a paid consultant to 
      MSD K.K. for general clinical pharmacology matters at the time of the conduct 
      study, and holds stock in Merck & Co., Inc., Rahway, NJ, USA. All other authors 
      declared no competing interest for this work. As an Associate Editor for Clinical 
      & Translational Science, Naoto Uemara was not involved in the review or decision 
      process for this paper.
EDAT- 2022/05/05 06:00
MHDA- 2022/07/19 06:00
PMCR- 2022/07/01
CRDT- 2022/05/04 02:33
PHST- 2022/03/31 00:00 [revised]
PHST- 2021/12/06 00:00 [received]
PHST- 2022/04/14 00:00 [accepted]
PHST- 2022/05/05 06:00 [pubmed]
PHST- 2022/07/19 06:00 [medline]
PHST- 2022/05/04 02:33 [entrez]
PHST- 2022/07/01 00:00 [pmc-release]
AID - CTS13290 [pii]
AID - 10.1111/cts.13290 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2022 Jul;15(7):1753-1763. doi: 10.1111/cts.13290. Epub 2022 May 
      17.