PMID- 30150460
OWN - NLM
STAT- MEDLINE
DCOM- 20191010
LR  - 20191010
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 62
IP  - 11
DP  - 2018 Nov
TI  - Evaluation of MEDI8852, an Anti-Influenza A Monoclonal Antibody, in Treating 
      Acute Uncomplicated Influenza.
LID - 10.1128/AAC.00694-18 [doi]
LID - e00694-18
AB  - We evaluated MEDI8852, a human IgG1 monoclonal antibody that binds a highly 
      conserved influenza A hemagglutinin stalk epitope, in outpatients with 
      uncomplicated influenza A infection. A total of 126 subjects aged 18 to 65 years 
      were enrolled during the 2015 to 2016 Northern and 2016 Southern Hemisphere 
      seasons. Subjects with symptom onset </=5 days before dosing were randomized to 
      four cohorts: 750 mg (cohort 1) or 3,000 mg (cohort 2) MEDI8852 (single 
      intravenous infusion) plus 75 mg oseltamivir, placebo plus 75 mg oseltamivir 
      (cohort 3), and 3,000 mg MEDI8852 alone (cohort 4). Subjects were monitored 
      through day 10 for solicited influenza symptoms, day 28 for adverse events (AEs), 
      and day 101 for serious AEs and AEs of special interest. Nasopharyngeal samples 
      were collected through day 7 for confirmation of influenza A infection, viral 
      shedding, and oseltamivir and MEDI8852 susceptibility. Slightly more AEs were 
      reported in subjects receiving MEDI8852 (cohorts 1, 2, and 4 combined: 39/93, 
      41.9%) than oseltamivir only (cohort 3: 10/32, 31.3%). Most AEs were mild or 
      moderate. The most common AE was bronchitis (11/93, 11.8%; 1/32, 3.1%). The 
      median (range) decrease in viral shedding (log(10) virus genome copies/ml) was 
      similar between the two groups (-3.58 [-6.2. 0.5]; -3.43 [-5.9, 0.9]). Genotypic 
      analyses found a limited number of hemagglutinin and neuraminidase amino acid 
      changes between viruses isolated before and after therapy; however, none appeared 
      within a known oseltamivir-resistant site or MEDI8852-binding region. The safety 
      profile of MEDI8852 supports its continued development for treatment of patients 
      hospitalized with influenza A infection. (This study has been registered at 
      ClinicalTrials.gov under identifier NCT02603952.).
CI  - Copyright (c) 2018 American Society for Microbiology.
FAU - Ali, S Omar
AU  - Ali SO
AUID- ORCID: 0000-0003-3131-3299
AD  - MedImmune, Gaithersburg, Maryland, USA alisy@medimmune.com.
FAU - Takas, Therese
AU  - Takas T
AD  - MedImmune, Gaithersburg, Maryland, USA.
FAU - Nyborg, Andrew
AU  - Nyborg A
AD  - MedImmune, Gaithersburg, Maryland, USA.
FAU - Shoemaker, Kathryn
AU  - Shoemaker K
AD  - MedImmune, Gaithersburg, Maryland, USA.
FAU - Kallewaard, Nicole L
AU  - Kallewaard NL
AD  - MedImmune, Gaithersburg, Maryland, USA.
FAU - Chiong, Rafael
AU  - Chiong R
AD  - Kendall South Medical Center, Miami, Florida, USA.
FAU - Dubovsky, Filip
AU  - Dubovsky F
AD  - MedImmune, Gaithersburg, Maryland, USA.
FAU - Mallory, Raburn M
AU  - Mallory RM
AD  - MedImmune, Gaithersburg, Maryland, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02603952
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20181024
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antiviral Agents)
RN  - 0 (Hemagglutinins)
RN  - 20O93L6F9H (Oseltamivir)
RN  - EC 3.2.1.18 (Neuraminidase)
RN  - OZS4TXB9VO (MEDI8852)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antiviral Agents/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Hemagglutinins/metabolism
MH  - Humans
MH  - Influenza A virus/*drug effects
MH  - Influenza, Human/*drug therapy/metabolism
MH  - Male
MH  - Middle Aged
MH  - Neuraminidase/metabolism
MH  - Oseltamivir/therapeutic use
MH  - Virus Shedding/drug effects
MH  - Young Adult
PMC - PMC6201130
OTO - NOTNLM
OT  - influenza
OT  - monoclonal antibody
OT  - safety
OT  - treatment
EDAT- 2018/08/29 06:00
MHDA- 2019/10/11 06:00
PMCR- 2019/04/24
CRDT- 2018/08/29 06:00
PHST- 2018/05/14 00:00 [received]
PHST- 2018/08/17 00:00 [accepted]
PHST- 2018/08/29 06:00 [pubmed]
PHST- 2019/10/11 06:00 [medline]
PHST- 2018/08/29 06:00 [entrez]
PHST- 2019/04/24 00:00 [pmc-release]
AID - AAC.00694-18 [pii]
AID - 00694-18 [pii]
AID - 10.1128/AAC.00694-18 [doi]
PST - epublish
SO  - Antimicrob Agents Chemother. 2018 Oct 24;62(11):e00694-18. doi: 
      10.1128/AAC.00694-18. Print 2018 Nov.