PMID- 36846967
OWN - NLM
STAT- MEDLINE
DCOM- 20240123
LR  - 20240123
IS  - 2052-1707 (Electronic)
IS  - 2052-1707 (Linking)
VI  - 11
IP  - 2
DP  - 2023 Apr
TI  - Safety, tolerability, and pharmacokinetics of a single ascending subcutaneous 
      dose of GSK3772847 in healthy participants.
PG  - e01054
LID - 10.1002/prp2.1054 [doi]
LID - e01054
AB  - The aim of this study was to evaluate the safety, tolerability, pharmacokinetics 
      (PK), and pharmacodynamics (PD) of GSK3772847, compared with placebo administered 
      subcutaneously (SC) in healthy participants, including cohorts of Japanese and 
      Chinese participants. This was a single-center, randomized, placebo-controlled, 
      double-blind, single ascending dose study. Following a screening period of up to 
      28 days, eligible participants were assigned to one of four cohorts receiving a 
      single dose of GSK3772847 70 mg (cohort 1) or 140 mg (cohorts 2, 3, and 4) or 
      placebo SC. In cohorts 1 and 2, participants were randomly assigned to one of 
      three injection sites (upper arm, abdomen, or thigh), while cohorts 3 and 4 
      included Japanese and Chinese participants, respectively, assigned to receive 
      GSK3772847 or placebo SC (upper arm). Participants attended follow-up visits on 
      Days 9, 15, 29, 43, 57, 71, and 85 before final analysis. GSK3772847 was 
      generally well tolerated. Most adverse events (AEs) were mild, resolved without 
      treatment and were considered not related to study treatment by the investigator. 
      There were no serious AEs or deaths during the study. The PK and PD were dose 
      dependent, with negligible differences across injection sites or ethnicities. 
      Target engagement was demonstrated by reduced free soluble interleukin 33 
      (sIL-33) concentrations and substantially increased total sIL-33 concentrations 
      compared with baseline. Subcutaneously administered GSK3772847 was well tolerated 
      in healthy participants, including cohorts of Japanese and Chinese participants, 
      and shows consistent PK and PD across injection sites and ethnicities.
CI  - (c) 2023 GSK. Pharmacology Research & Perspectives published by British 
      Pharmacological Society and American Society for Pharmacology and Experimental 
      Therapeutics and John Wiley & Sons Ltd.
FAU - Pefani, Eleni
AU  - Pefani E
AD  - GSK Medicines Research Centre, Stevenage, Hertfordshire, UK.
FAU - Stone, Sally
AU  - Stone S
AD  - GSK, Brentford, Middlesex, UK.
FAU - Zhu, Chang-Qing
AU  - Zhu CQ
AD  - GSK, Brentford, Middlesex, UK.
FAU - Nunn, Carol
AU  - Nunn C
AD  - GSK RD Respiratory R&D, Brentford, Middlesex, UK.
FAU - Fairman, David
AU  - Fairman D
AUID- ORCID: 0000-0002-7756-0212
AD  - GSK Medicines Research Centre, Stevenage, Hertfordshire, UK.
LA  - eng
GR  - 209635/GlaxoSmithKline/
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Pharmacol Res Perspect
JT  - Pharmacology research & perspectives
JID - 101626369
RN  - 26C72EGQ3G (melrilimab)
SB  - IM
MH  - Humans
MH  - Double-Blind Method
MH  - *Healthy Volunteers
PMC - PMC9969340
OTO - NOTNLM
OT  - Phase 1
OT  - asthma
OT  - monoclonal antibodies
OT  - pharmacodynamics
OT  - pharmacokinetics
COIS- EP, SS, DF, CQZ, and CN are employees of GSK and hold stocks/shares.
EDAT- 2023/02/28 06:00
MHDA- 2023/03/03 06:00
PMCR- 2023/02/27
CRDT- 2023/02/27 06:27
PHST- 2022/11/24 00:00 [revised]
PHST- 2022/07/26 00:00 [received]
PHST- 2022/12/06 00:00 [accepted]
PHST- 2023/02/27 06:27 [entrez]
PHST- 2023/02/28 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2023/02/27 00:00 [pmc-release]
AID - PRP21054 [pii]
AID - 10.1002/prp2.1054 [doi]
PST - ppublish
SO  - Pharmacol Res Perspect. 2023 Apr;11(2):e01054. doi: 10.1002/prp2.1054.