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Principal Investigator: Dan H. Barouch
Organization: FRED HUTCHINSON CANCER CENTER
Fiscal Year: 2022
Award: $293,963
Funding agency: National Institute of Allergy and Infectious Diseases
Project Abstract
Efforts to control the pandemic have resulted in widespread shelter-in-place orders. Transmission of SARS-
CoV-2 occurs primarily through person-to-person contact and respiratory droplet transmission (Lai,2020).
Household contacts of a person infected with SARS-CoV-2 are at a high risk for acquiring infection, with
transmission rates ranging from approximately 10% to 15%. The majority of individuals who acquire infection
from household contacts develop symptoms of COVID-19(Burke,2020) (Jing, 2020), (Bi,2020) (Li,2020b).
Prophylaxis is urgently needed to reduce transmission rates and/or reduce the occurrence of symptomatic
disease.
Ideally, prophylaxis would need to be given as soon as possible after a known exposure, as the duration of
time between symptomatic infection in the source individual and the development of symptoms in newly
infected individual is thought to be approximately 5 days, with a possible range of 2 to14 days(Lauer,2020)
(Li,2020a). Animal models suggest that SARS-CoV-2 RT-PCR in nasopharyngeal (NP) samples become
positive within a few days after infection (Rockx,2020). An ideal agent for prophylaxis should be fast acting and
highly effective and should protect against multiple viral variants. A monoclonal antibody (mAb) combination
therapy, with two different monoclonal antibodies that bind distinct regions of the portion of the SARS-CoV-2
spike(S) protein that bind to and facilitate entry into host cells, has been developed in order to achieve these
goals.
A mAb combination against SARS-CoV-2 for post-exposure prophylaxis that can either prevent the
development of disease or reduce viral acquisition or shedding could be key to reducing transmission of the
virus and limiting symptoms and adverse outcomes following infection.
Currently, however, there is no approved prophylaxis for COVID-19 nor for patients that are infected with
SARS-CoV-2 but are asymptomatic. Given the speed at which this outbreak has spread and how it has
impacted almost every community globally, there is an urgent need to develop safe and efficacious
interventions to slow the spread of the SARS-CoV-2 virus and decrease adverse outcomes associated with
symptomatic disease.
This is a pivotal phase 3 randomized, double-blind, placebo-controlled study in adults with household contact
exposure to individuals with SARS-CoV-2 infection in geographic areas with an active COVID-19 outbreak.
This study is designed to assess the efficacy and safety of co-administered REGN10933+REGN10987
combination therapy (“REGN10933+REGN10987”) to reduce the proportion of SARS-CoV-2 infections and
prevent the development of COVID-19 disease (symptomatic SARS-CoV2 infection), after household exposure
to individuals with SARS-CoV-2 infection. Safety, tolerability, pharmacokinetics (PK), and immunogenicity of
REGN10933+REGN10987 will also be evaluated.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><21+ years old><Adult><Adult Human><Animal Model><Animal Models and Related Studies><Antibodies><Binding><Binding Proteins><COVID infected patient><COVID patient><COVID positive patient><COVID-19><COVID-19 Prevention Network><COVID-19 S protein><COVID-19 infected patient><COVID-19 infection><COVID-19 outbreak><COVID-19 patient><COVID-19 positive patient><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 virus><COVID19><COVID19 S protein><COVID19 infection><COVID19 outbreak><COVID19 patient><COVID19 positive patient><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 virus><CV-19><CV19><Cell Body><Cells><Clinical Treatment Moab><CoV-2><CoV2><CoVPN><Combined Modality Therapy><Communities><Development><Disease><Disease Outbreaks><Disorder><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Drug Kinetics><Exposure to><Geographic Area><Geographic Locations><Geographic Region><Geographical Location><Goals><Household><Individual><Infection><Investigation><Ligand Binding Protein><Ligand Binding Protein Gene><Molecular Interaction><Monoclonal Antibodies><Multimodal Therapy><Multimodal Treatment><Outbreaks><Persons><Pharmacokinetics><Phase><Prophylactic treatment><Prophylaxis><Protein Binding><RT-PCR><RTPCR><Randomized><Reverse Transcriptase Polymerase Chain Reaction><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 outbreak><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 infection><SARS-CoV2 outbreak><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Safety><Sampling><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 outbreak><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome related corona virus 2><Shelter facility><Source><Speed><Symptoms><Time><Transmission><Variant><Variation><Viral><Virus><Wuhan coronavirus><adulthood><adverse consequence><adverse outcome><bound protein><combination therapy><combined modality treatment><combined treatment><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 outbreak><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 prevention network><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 outbreak><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><design><designing><developmental><efficacious intervention><geographic site><hCoV19><high risk><immunogenicity><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><mAbs><model of animal><model organism><multi-modal therapy><multi-modal treatment><nCoV2><pandemic><pandemic disease><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><placebo controlled study><prevent><preventing><randomisation><randomization><randomly assigned><respiratory><reverse transcriptase PCR><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><shelter><shelter-housing><transmission process><viral transmission><virus transmission>