PMID- 38376227
OWN - NLM
STAT- MEDLINE
DCOM- 20240404
LR  - 20240405
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 68
IP  - 4
DP  - 2024 Apr 3
TI  - A phase 1 study in healthy volunteers to investigate the safety, tolerability, 
      and pharmacokinetics of VIR-2482: a monoclonal antibody for the prevention of 
      severe influenza A illness.
PG  - e0127323
LID - 10.1128/aac.01273-23 [doi]
LID - e01273-23
AB  - The objective of this study was to evaluate the safety, tolerability, 
      pharmacokinetics (PK), and immunogenicity of VIR-2482 in healthy adult subjects. 
      A phase 1, first-in-human, randomized, double-blind, placebo-controlled 
      dose-escalation study was conducted. One hundred participants were allocated to 
      four cohorts (60 mg, 300 mg, 1,200 mg, and 1,800 mg). In each cohort, 
      participants were randomized in a 4:1 ratio (active:placebo) to receive either 
      VIR-2482 or volume-matched placebo by gluteal intramuscular injection. 
      Participants remained at the investigative site under observation for 48 h, and 
      adverse events (AEs) were collected for 56 days. PK and immunogenicity were 
      measured up to 52 weeks post-dose. VIR-2482 was well tolerated at all doses 
      studied. The overall incidence of AEs was comparable between VIR-2482 (68.8%) and 
      placebo (85.0%). Nineteen VIR-2482 (23.8%) and six placebo (30.0%) recipients had 
      Grade 1 or 2 AEs that were considered to be related to the study intervention. 
      There were no treatment-related serious AEs. Injection-site reactions (ISRs) were 
      reported in six (7.5%) VIR-2482 recipients, while no such reactions were reported 
      among the placebo recipients. All ISRs were Grade 1, and there was no 
      relationship with the dose. Median VIR-2482 serum elimination half-life ranged 
      from 56.7 to 70.6 days across cohorts. The serum area under the curve and C(max) 
      were dose-proportional. Nasopharyngeal VIR-2482 concentrations were approximately 
      2%-5% of serum levels and were less than dose-proportional. The incidence of 
      immunogenicity across all cohorts was 1.3%. Overall, the safety, tolerability, 
      and pharmacokinetic profile of VIR-2482 at doses up to 1,800 mg supported its 
      further investigation as a long-acting antibody for the prevention of influenza A 
      illness. This study has been registered at ClinicalTrials.gov under identifier 
      NCT04033406.
FAU - Plotnik, David
AU  - Plotnik D
AUID- ORCID: 0000-0003-0688-8613
AD  - Vir Biotechnology, San Francisco, California, USA.
FAU - Sager, Jennifer E
AU  - Sager JE
AD  - Vir Biotechnology, San Francisco, California, USA.
FAU - Aryal, Madhukar
AU  - Aryal M
AD  - Vir Biotechnology, San Francisco, California, USA.
FAU - Fanget, Marie C
AU  - Fanget MC
AD  - Vir Biotechnology, San Francisco, California, USA.
FAU - Peter, Alessia
AU  - Peter A
AD  - Humabs BioMed, SA, Vir Biotechnology, Bellinzona, Switzerland.
FAU - Schmid, Michael A
AU  - Schmid MA
AD  - Humabs BioMed, SA, Vir Biotechnology, Bellinzona, Switzerland.
FAU - Cebrik, Deborah
AU  - Cebrik D
AD  - Vir Biotechnology, San Francisco, California, USA.
FAU - Mogalian, Erik
AU  - Mogalian E
AD  - Vir Biotechnology, San Francisco, California, USA.
FAU - Boundy, Keith
AU  - Boundy K
AD  - Vir Biotechnology, San Francisco, California, USA.
FAU - Yeh, Wendy W
AU  - Yeh WW
AD  - Vir Biotechnology, San Francisco, California, USA.
FAU - Griffin, Paul
AU  - Griffin P
AD  - Mater Health and University of Queensland, Queensland, Australia.
FAU - Reyes, Maribel
AU  - Reyes M
AD  - Vir Biotechnology, San Francisco, California, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT04033406
GR  - Vir Biotechnology Inc. (Vir)/
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20240220
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antibodies, Monoclonal)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Antibodies, Monoclonal/adverse effects
MH  - *Influenza, Human/drug therapy/prevention & control
MH  - Healthy Volunteers
MH  - Double-Blind Method
PMC - PMC10988998
OTO - NOTNLM
OT  - VIR-2482
OT  - human immunoglobulin G1
OT  - influenza
OT  - monoclonal antibodies
OT  - prophylaxis
COIS- The following authors are Vir employees and stockholders: D.P., J.E.S., M.A., 
      M.C.F., A.P., M.A.S., D.C., E.M., K.B., W.W.Y., and M.R. P.G. has no financial 
      disclosures to report.
EDAT- 2024/02/20 12:51
MHDA- 2024/04/04 06:44
PMCR- 2024/02/20
CRDT- 2024/02/20 09:14
PHST- 2024/04/04 06:44 [medline]
PHST- 2024/02/20 12:51 [pubmed]
PHST- 2024/02/20 09:14 [entrez]
PHST- 2024/02/20 00:00 [pmc-release]
AID - 01273-23 [pii]
AID - aac.01273-23 [pii]
AID - 10.1128/aac.01273-23 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2024 Apr 3;68(4):e0127323. doi: 
      10.1128/aac.01273-23. Epub 2024 Feb 20.