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Principal Investigator: Margaret Juliana McElrath
Organization: FRED HUTCHINSON CANCER RESEARCH CENTER
Fiscal Year: 2020
Award: $6,554,653
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 coronavirus><2019-nCoV><21+ years old><Abdominal Typhus><Address><Adenoviridae><Adenoviruses><Adult><Adult Human><Age-Years><Antibody Response><Antigens><Assay><Binding><Bioassay><Biologic Assays><Biological Assay><Biometrics><Biometry><Biostatistics><Blood Serum><COVID-19><COVID-19 epidemic><COVID-19 pandemic><COVID-19 vaccine><COVID19><COVID19 epidemic><COVID19 pandemic><COVID19 vaccine><Cell Surface Glycoproteins><Cellular Assay><Cellular Immune Function><Chimp><Chimpanzee><Clinical><Clinical Trials><Clinical Trials Network><Cohort Studies><Communicable Diseases><Concurrent Studies><Constitution><Country><Data Analytics><Development><Diagnosis><Disease><Disease Outbreaks><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><Outbreaks><Paludism><Pan Genus><Pan Species><Participant><Pb element><Persons><Phase><Physicians><Placebos><Plasmodium Infections><Population><Preparation><Prevent infection><Prevention><Preventive><Proteins><Protocol><Protocols documentation><Quality Control><Randomized><Randomized Clinical Trials><Recombinants><Research Methodology><Research Methods><Risk><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Safety><Sampling><Scientist><Serologic><Serological><Serum><Severe acute respiratory syndrome coronavirus 2><Severities><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 epidemic><coronavirus disease 2019 pandemic><coronavirus disease 2019 vaccine><design><designing><developmental><efficacy study><efficacy testing><efficacy trial><eighteen year old><eighteen years of age><experience><heavy metal Pb><heavy metal lead><high risk><host response><human immunodeficiency virus vaccine><immune function><immunogen><immunogenicity><immunoresponse><improved><interventional strategy><monoclonal antibody drugs><mortality><neutralizing antibody><operation><plasmid vaccine><prevent><preventing><programs><quality assurance><racial and ethnic><racial diversity><racially diverse><randomisation><randomization><randomly assigned><recruit><response><screening><sham therapy><therapeutic mAbs><vaccination study><vaccination trial><vaccine study><vaccine trial><vector vaccine>