PMID- 35106315
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220430
IS  - 2328-8957 (Print)
IS  - 2328-8957 (Electronic)
IS  - 2328-8957 (Linking)
VI  - 9
IP  - 2
DP  - 2022 Feb
TI  - A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of the Monoclonal 
      Antibody MHAA4549A in Patients With Acute Uncomplicated Influenza A Infection.
PG  - ofab630
LID - 10.1093/ofid/ofab630 [doi]
LID - ofab630
AB  - BACKGROUND: MHAA4549A, a human monoclonal antibody targeting the influenza A 
      hemagglutinin stalk, neutralizes influenza A virus in animal and human volunteer 
      challenge studies. We investigated the safety and tolerability, efficacy, and 
      pharmacokinetics of MHAA4549A in outpatients with acute, uncomplicated influenza 
      A infection. METHODS: This was a phase 2, randomized, double-blind, 
      placebo-controlled trial of single intravenous (IV) doses of 3600 mg or 8400 mg 
      of MHAA4549A or IV placebo in adult outpatients testing positive for influenza A. 
      Patients were enrolled across 35 sites in 6 countries. Randomization and dosing 
      occurred within </=72 hours of symptom onset; the study duration was 14 weeks. The 
      primary end point was the nature and frequency of adverse events (AEs). Secondary 
      end points included median time to alleviation of all influenza symptoms, effects 
      on nasopharyngeal viral load and duration of viral shedding, and MHAA4549A serum 
      pharmacokinetics. RESULTS: Of 125 randomized patients, 124 received study 
      treatment, with 99 confirmed positive for influenza A by central testing. The 
      frequency of AEs between the MHAA4549A and placebo groups was similar; nausea was 
      most common (8 patients; 6.5%). MHAA4549A serum exposure was confirmed in all 
      MHAA4549A-treated patients and was dose-proportional. No hospitalizations or 
      deaths occurred. Between the MHAA4549A and placebo groups, no statistically 
      significant differences occurred in the median time to alleviation of all 
      symptoms, nasopharyngeal viral load, or duration of viral shedding. CONCLUSIONS: 
      While MHAA4549A was safe and well tolerated with confirmed exposure, the antibody 
      did not improve clinical outcomes in patients with acute uncomplicated influenza 
      A infection.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of 
      Infectious Diseases Society of America.
FAU - Lim, Jeremy J
AU  - Lim JJ
AD  - Early Clinical Development, Genentech, Inc., South San Francisco, California, 
      USA.
FAU - Dar, Sadia
AU  - Dar S
AD  - Clinical Research Solutions, LLC, Smryna, Tennessee, USA.
FAU - Venter, Dirk
AU  - Venter D
AD  - Henderson Medical Centre, Auckland, New Zealand.
FAU - Horcajada, Juan P
AU  - Horcajada JP
AD  - Department of Infectious Diseases, Hospital del Mar, Institut Hospital del Mar 
      d'Investigacions Mediques, Universitat Autonoma, Universitat Pompeu Fabra, 
      Barcelona, Spain.
FAU - Kulkarni, Priya
AU  - Kulkarni P
AD  - Early Clinical Development, Genentech, Inc., South San Francisco, California, 
      USA.
FAU - Nguyen, Allen
AU  - Nguyen A
AD  - Early Clinical Development, Genentech, Inc., South San Francisco, California, 
      USA.
FAU - McBride, Jacqueline M
AU  - McBride JM
AD  - Early Clinical Development, Genentech, Inc., South San Francisco, California, 
      USA.
FAU - Deng, Rong
AU  - Deng R
AD  - Early Clinical Development, Genentech, Inc., South San Francisco, California, 
      USA.
FAU - Galanter, Joshua
AU  - Galanter J
AD  - Early Clinical Development, Genentech, Inc., South San Francisco, California, 
      USA.
FAU - Chu, Tom
AU  - Chu T
AD  - Early Clinical Development, Genentech, Inc., South San Francisco, California, 
      USA.
FAU - Newton, Elizabeth M
AU  - Newton EM
AD  - Early Clinical Development, Genentech, Inc., South San Francisco, California, 
      USA.
FAU - Tavel, Jorge A
AU  - Tavel JA
AD  - Early Clinical Development, Genentech, Inc., South San Francisco, California, 
      USA.
FAU - Peck, Melicent C
AU  - Peck MC
AD  - Early Clinical Development, Genentech, Inc., South San Francisco, California, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20211210
PL  - United States
TA  - Open Forum Infect Dis
JT  - Open forum infectious diseases
JID - 101637045
PMC - PMC8801227
OTO - NOTNLM
OT  - MHAA4549A
OT  - antiviral agents
OT  - influenza A virus
OT  - monoclonal antibody
EDAT- 2022/02/03 06:00
MHDA- 2022/02/03 06:01
PMCR- 2021/12/10
CRDT- 2022/02/02 05:35
PHST- 2021/08/16 00:00 [received]
PHST- 2021/12/09 00:00 [accepted]
PHST- 2022/02/02 05:35 [entrez]
PHST- 2022/02/03 06:00 [pubmed]
PHST- 2022/02/03 06:01 [medline]
PHST- 2021/12/10 00:00 [pmc-release]
AID - ofab630 [pii]
AID - 10.1093/ofid/ofab630 [doi]
PST - epublish
SO  - Open Forum Infect Dis. 2021 Dec 10;9(2):ofab630. doi: 10.1093/ofid/ofab630. 
      eCollection 2022 Feb.