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Principal Investigator: Margaret Juliana McElrath
Organization: FRED HUTCHINSON CANCER CENTER
Fiscal Year: 2022
Award: $531,957
Funding agency: National Institute of Allergy and Infectious Diseases
This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines
Leadership Operations Center (LOC) for implementation of the first COVID-19 vaccine efficacy trial “A Phase
III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy,
and Immunogenicity of AZD1222, A Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-
19.”
With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in
SARS-CoV-2 infected individuals. Addressing this gap, the National Institute of Health (NIH) led rapid
constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of
physician scientists at 64 United States (US) and 55 international clinical trial sites in 15 countries dedicated to
developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global
HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the
LOC for CoVPN vaccine trials.
This trial, a phase 3, placebo-controlled, double-blinded study will test the efficacy of AZD1222, a recombinant
replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 spike (S) surface glycoprotein, to
modify COVID-19 disease in adults 18 year of age and older. Participants will be recruited from up to 100
clinical trial sites across the US, using data analytics to target high risk individuals with a diverse racial and
ethnic profile.
Participants will receive symptomatic screening for SARS-CoV-2 infection, and if they become infected will be
monitored with frequent clinical check-ins and remote monitoring of vital signs. Infected individuals who
progress to moderate-severe COVID-19 will be referred for hospitalization. All trial endpoint assays will be
done at CoVPN laboratories, using qualified and validated assays for diagnosis and immune monitoring.
Specific aims of this study are to demonstrate efficacy of AZD1222 to prevent COVID-19, to evaluate the
safety, tolerability and reactogenicity of 2 injections given 4 weeks apart, to assess the ability to prevent
infection with SARS-CoV-2, to assess the ability to modify COVID-19 disease, to assess the ability to prevent
emergency room visits, and to evaluate the binding and neutralizing antibody responses. This efficacy trial will
tell us much about the adaptive immune response in persons who receive a SARS-CoV-2 S protein based
vaccine and about their ability to modify the disease course of COVID-19. In addition, it will improve our
understanding of the dynamics and duration of these responses and will inform rational design and testing of
preventive and therapeutic monoclonal antibody interventions. Lastly, the results of this trial will be used to
assess registration of this vaccine product as well as to modify future COVID-19 vaccine trials planned over the
next 12 months.
Terms: <18 year old><18 years of age><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV vaccine><21+ years old><AZD1222><Abdominal Typhus><Address><Adenoviridae><Adenoviruses><Adult><Adult Human><Age-Years><Antibody Response><Antigens><Assay><AstraZeneca COVID-19 vaccine><AstraZeneca coronavirus disease 2019 vaccine><Binding><Bioassay><Biologic Assays><Biological Assay><Biometrics><Biometry><Biostatistics><Blood Serum><COVID crisis><COVID disease severity><COVID epidemic><COVID pandemic><COVID severity><COVID-19><COVID-19 Prevention Network><COVID-19 S protein><COVID-19 crisis><COVID-19 disease severity><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection><COVID-19 outbreak><COVID-19 pandemic><COVID-19 prevention><COVID-19 public health crisis><COVID-19 screening><COVID-19 severity><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 vaccine><COVID-19 virus><COVID19><COVID19 S protein><COVID19 crisis><COVID19 disease severity><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 infection><COVID19 outbreak><COVID19 pandemic><COVID19 prevention><COVID19 public health crisis><COVID19 screening><COVID19 severity><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 vaccine><COVID19 virus><CV-19><CV19><Cell Surface Glycoproteins><Cellular Assay><Cellular Immune Function><Chimp><Chimpanzee><Clinical><Clinical Trials><Clinical Trials Network><CoV-2><CoV2><CoVPN><Cohort Studies><Communicable Diseases><Concurrent Studies><Constitution><Country><Data Analytics><Development><Diagnosis><Disease><Disorder><Dose><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><ED visit><ER visit><Emergency care visit><Emergency department visit><Emergency hospital visit><Emergency room visit><End Point Assay><Endpoint Assays><Enteric Fever><Eye><Eyeball><Future><Goals><HIV Vaccine Trials Network><HIV vaccine><HIV/AIDS Vaccines><HVTN><Health><Hospital Admission><Hospitalization><Immune><Immune Monitoring><Immune response><Immunes><Immunity><Immunologic Monitoring><Immunological Monitoring><Immunological response><Immunology><Immunomonitoring><Individual><Infection><Infection Control><Infection prevention><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Injections><International><Intervention><Intervention Strategies><Knowledge><Laboratories><Lead><Leadership><MAb Therapeutics><Malaria><Mediating><Membrane Glycoproteins><Molecular Interaction><Monitor><Morbidity><Morbidity - disease rate><Multi-center studies><Multicenter Studies><NIH><National Institutes of Health><Paludism><Pan Genus><Pan Species><Participant><Pb element><Persons><Phase><Physicians><Placebo Control><Placebos><Plasmodium Infections><Population><Preparation><Prevent infection><Prevention><Preventive><Protocol><Protocols documentation><Quality Control><Randomized><Randomized Clinical Trials><Recombinants><Research Methodology><Research Methods><Risk><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 disease severity><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 outbreak><SARS-CoV-2 pandemic><SARS-CoV-2 screening><SARS-CoV-2 severity><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 outbreak><SARS-CoV2 pandemic><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-CoV2 vaccine><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Safety><Sampling><Scientist><Serology test><Serum><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 CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV 2 vaccine><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 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 outbreak><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Sham Treatment><Site><Surface Glycoproteins><System><Testing><Therapeutic Monoclonal Antibodies><Typhoid><Typhoid Fever><United States><United States National Institutes of Health><Vaccines><Validation><Wuhan coronavirus><adaptive immune response><adulthood><age 18 years><base><cell assay><clinical trial analysis><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 crisis><coronavirus disease 2019 disease severity><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 outbreak><coronavirus disease 2019 pandemic><coronavirus disease 2019 prevention><coronavirus disease 2019 prevention network><coronavirus disease 2019 public health crisis><coronavirus disease 2019 screening><coronavirus disease 2019 severity><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease severity><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 outbreak><coronavirus disease-19 pandemic><coronavirus disease-19 prevention><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus infectious disease-19><design><designing><developmental><efficacy study><efficacy testing><efficacy trial><eighteen year old><eighteen years of age><ethnoracial><experience><hCoV19><heavy metal Pb><heavy metal lead><high risk><host response><human immunodeficiency virus vaccine><immune function><immune system response><immunogen><immunogenicity><immunoresponse><improved><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><interventional strategy><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><monoclonal antibody drugs><mortality><nCoV2><neutralizing antibody><operation><placebo controlled><plasmid vaccine><prevent><prevent COVID-19><prevent COVID19><prevent coronavirus disease 2019><preventing><programs><quality assurance><racial and ethnic><racial diversity><racially diverse><randomisation><randomization><randomly assigned><rational design><recruit><remote monitoring><response><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><serology assay><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 disease severity><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 screening><severe acute respiratory syndrome coronavirus 2 severity><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><sham therapy><symptomatic COVID-19><symptomatic COVID19><symptomatic coronavirus disease 2019><therapeutic mAbs><vaccination study><vaccination trial><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine for novel coronavirus><vaccine study><vaccine trial><vector vaccine>