Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants

Journal
Clinical Infectious Diseases
ISSN
1058-4838
1537-6591
Date Issued
2020
Author(s)
Eric A F Simões
Eduardo Forleo-Neto
Gregory P Geba
Mohamed Kamal
Feng Yang
Helen Cicirello
Matthew R Houghton
Ronald Rideman
Qiong Zhao
Sarah L Benvin
Alicia Hawes
Erin D Fuller
Elzbieta Wloga
Jose M Novoa Pizarro
Flor M Munoz
Scott A Rush
Jason S McLellan
Leah Lipsich
Neil Stahl
George D Yancopoulos
David M Weinreich
Christos A Kyratsous
Sumathi Sivapalasingam
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85122546142
DOI
URL
Abstract
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>Respiratory syncytial virus (RSV) is a major cause of childhood medically attended respiratory infection (MARI).</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods</jats:title>
<jats:p>We conducted a randomized, double-blind, placebo-controlled phase 3 trial in 1154 preterm infants of 1 or 2 doses of suptavumab, a human monoclonal antibody that can bind and block a conserved epitope on RSV A and B subtypes, for the prevention of RSV MARI. The primary endpoint was proportion of subjects with RSV-confirmed hospitalizations or outpatient lower respiratory tract infection (LRTI).</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>There were no significant differences between primary endpoint rates (8.1%, placebo; 7.7%, 1-dose; 9.3%, 2-dose). Suptavumab prevented RSV A infections (relative risks, .38; 95% confidence interval [CI], .14–1.05 in the 1-dose group and .39 [95% CI, .14–1.07] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .0499), while increasing the rate of RSV B infections (relative risk 1.36 [95% CI, .73–2.56] in the 1-dose group and 1.69 [95% CI, .92–3.08] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .12). Sequenced RSV isolates demonstrated no suptavumab epitope changes in RSV A isolates, while all RSV B isolates had 2–amino acid substitution in the suptavumab epitope that led to loss of neutralization activity. Treatment emergent adverse events were balanced across treatment groups.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Suptavumab did not reduce overall RSV hospitalizations or outpatient LRTI because of a newly circulating mutant strain of RSV B. Genetic variation in circulating RSV strains will continue to challenge prevention efforts.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Clinical Trials Registration</jats:title>
<jats:p>NCT02325791.</jats:p>
</jats:sec>
Subjects
efficacy

; 

infants

; 

respiratory syncytial virus

; 

safety

; 

antibodies, monoclonal

; 

antiviral agents

; 

humans

; 

infant

; 

infant, newborn

; 

infant, premature

; 

respiratory syncytial virus infections

; 

respiratory syncytial virus, human

; 

epitope

; 

placebo

; 

suptavumab

; 

virus antigen

; 

antivirus agent

; 

monoclonal antibody

; 

amino acid substitution

; 

article

; 

bronchiolitis

; 

bronchitis

; 

child hospitalization

; 

conjunctivitis

; 

constipation

; 

controlled study

; 

coughing

; 

cumulative incidence

; 

diarrhea

; 

disease severity

; 

double blind procedure

; 

drug dose comparison

; 

drug dose regimen

; 

drug fatality

; 

drug half life

; 

drug hypersensitivity

; 

drug safety

; 

drug withdrawal

; 

ec99

; 

effective concentration

; 

female

; 

fever

; 

follow up

; 

gastroesophageal reflux

; 

hospitalization

; 

human

; 

human respiratory syncytial virus

; 

human respiratory syncytial virus a

; 

human respiratory syncytial virus b

; 

immunogenicity

; 

immunoprophylaxis

; 

in vitro study

; 

infant

; 

infection prevention

; 

limit of quantitation

; 

lower respiratory tract infection

; 

major clinical study

; 

male

; 

maximum concentration

; 

monoclonal antibody therapy

; 

nonhuman

; 

nose obstruction

; 

nose smear

; 

phase 3 clinical trial

; 

prematurity

; 

randomized controlled trial

; 

respiratory syncytial virus infection

; 

rhinitis

; 

rhinopharyngitis

; 

rna sequencing

; 

surface plasmon resonance

; 

upper respiratory tract infection

; 

viral respiratory tract infection

; 

virus neutralization

; 

clinical trial

; 

human respiratory syncytial virus

; 

newborn

; 

prematurity

; 

respiratory syncytial virus infection