Document text
Principal Investigator: Dan H. Barouch
Organization: FRED HUTCHINSON CANCER CENTER
Fiscal Year: 2022
Award: $3,879,990
Funding agency: National Institute of Allergy and Infectious Diseases
NOSI: NOT-AI-20-034
FOA: PA-20-135 – Emergency Competitive Revision to Existing NIH Awards
Activity Code/Award: UM1/A1068614-15 (parent award)
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Project Abstract
This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines
Leadership Operations Center (LOC) for continuing implementation of the first COVID-19 vaccine efficacy trial
“A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy,
Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 (Moderna) Vaccine in Adults Aged 18 Years and
Older.”
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 HVTN has joined 4 other National Institute of
Health (NIH) clinical trial networks to form the CoVPN, an enhanced network dedicated to developing globally
effective vaccines for SARS-CoV-2. Due to its extensive experience implementing HIV vaccine trials, the HIV
Vaccine Trials Network (HVTN) LOC was selected to as the CoVPN vaccine LOC.
This trial, a phase 3, placebo-controlled, double-blinded study will test the efficacy of mRNA-1273 SARS-CoV-
2, a lipid co-formulated messenger ribonucleic acid (mRNA) vaccine encoding the SARS-CoV-2 spike protein
(S), to modify COVID-19 disease in adults 18 year of age and older. Participants will be recruited from clinical
trial sites across the US, using data analytics to target high risk individuals with a diverse racial and ethnic
profile. In addition, the CoVPN will use accessory community-based sites, staffed by clinical teams from the
home sites and employ mobile clinics to enroll individuals in new high risk settings (e.g., meat packing plants).
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 validated assays for diagnosis and immune monitoring.
Specific aims of this study are to demonstrate efficacy of mRNA-1273 SARS-CoV-2 to prevent COVID-19, to
evaluate the safety and reactogenicity of 2 injections given 28 days apart, the assess the ability to prevent
infection with SARS-CoV-2, the assess the ability to modify COVID-19 infection, to evaluate viral infection
kinetics, and to evaluate the vaccine induced immune response. A booster injection (3rd dose) will be offered to
participants at least 6 months after the last dose of the primary series. This efficacy trial will tell us much about
the adaptive immune response in persons who receive three doses of an mRNA SARS-CoV-2 S protein-based
vaccine and about their ability to modify the disease course of COVID-19 against current circulating strains. In
addition, It will improve our understanding of the dynamics and duration of these responses. Lastly, the results
of this trial will enable assessment for rare side effects, such as cardiomyopathy, that wouldn’t otherwise be
detected in smaller clinical trials.
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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><Cardiomyopathies><Clinic><Clinical><Clinical Trials><Clinical Trials Network><CoV-2><CoV2><CoVPN><Code><Coding System><Communities><Data Analytics><Diagnosis><Disease><Disorder><Dose><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Emergencies><Emergency Situation><End Point Assay><Endpoint Assays><Enrollment><Goals><HIV Vaccine Trials Network><HIV vaccine><HIV/AIDS Vaccines><HVTN><Health><Home><Hospital Admission><Hospitalization><Immune Monitoring><Immune response><Immunity><Immunologic Monitoring><Immunological Monitoring><Immunological response><Immunomonitoring><Individual><Infection prevention><Injections><Kinetics><Laboratories><Lead><Leadership><Lipids><Meat><Monitor><Myocardial Diseases><Myocardial Disorder><Myocardiopathies><NIH><National Institutes of Health><Non-Polyadenylated RNA><Parents><Participant><Pb element><Persons><Phase><Placebo Control><Plants><Population><Prevent infection><Protocol><Protocols documentation><RNA><RNA Gene Products><Randomized><Ribonucleic Acid><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 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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><Site><United States National Institutes of Health><Vaccines><Viral Diseases><Virus Diseases><Wuhan coronavirus><adaptive immune response><adulthood><age 18 years><base><blind><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><efficacy analysis><efficacy assessment><efficacy evaluation><efficacy examination><efficacy 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