Document text
Principal Investigator: Peter B. Gilbert
Organization: FRED HUTCHINSON CANCER CENTER
Fiscal Year: 2022
Award: $234,860
Funding agency: National Institute of Allergy and Infectious Diseases
Project Abstract
This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership
Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial entitled “A Phase 3,
Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Safety and
Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS)
with Matrix-M™ Adjuvant in Adult Participants ≥ 18 years.”
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 Institutes 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 145 United States (US) and 71 international clinical trial sites in 17 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 Phase 3, placebo-controlled, observer-blinded study will test the efficacy, safety and immunogenicity of a
SARS CoV-2 rS, a nanoparticle vaccine administered with Matrix-M adjuvant administered in two doses 21 days
apart, to modify COVID-19 disease in adults 18 years of age and older. Participants who receive placebo during
original randomization will receive vaccine at unblinding. All participants will be offered a 3rd booster dose no
than 8 months after completing the original regimen. Participants will be recruited from clinical trial sites across
the US and globally 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 using
qualified and validated assays for diagnosis and immune monitoring.
Specific aims of this study are to demonstrate efficacy of SARS-CoV-2 rS vaccine to prevent SARS-CoV-2
infection and COVID-19 disease; to evaluate its effect across race, ethnicity, high-risk vs. low-risk demographic
groups; to evaluate binding and neutralizing antibody responses; to evaluate the durability of immune responses;
to assess the vaccine safety; to assess all-cause mortality in the two groups; and to perform health economics
and outcomes research (HEOR). This efficacy trial will tell us much about the adaptive immune response in
persons who receive a SARS-CoV-2 rS nanoparticle-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 immune
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.
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><Abdominal Typhus><Address><Adjuvant><Adult><Adult Human><Antibodies><Antibody Response><Assay><Binding><Bioassay><Biologic Assays><Biological Assay><Biometrics><Biometry><Biostatistics><Blinded><COVID crisis><COVID disease severity><COVID epidemic><COVID pandemic><COVID severity><COVID-19><COVID-19 Prevention Network><COVID-19 S protein><COVID-19 antibody><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 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 public health crisis><COVID19 screening><COVID19 severity><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 vaccine><COVID19 virus><CV-19><CV19><Cell Body><Cells><Cellular Assay><Cellular Immune Function><Characteristics><Clinical><Clinical Trials><Clinical Trials Network><CoV-2><CoV2><CoVPN><Cohort Studies><Communicable Diseases><Concurrent Studies><Constitution><Coronaviridae><Coronavirus><Country><Data Analytics><Development><Diabetes Mellitus><Diagnosis><Disease><Disorder><Dose><End Point Assay><Endpoint Assays><Enteric Fever><Ethnic Origin><Ethnicity><Eye><Eyeball><Follow-Up Studies><Followup Studies><Future><Goals><HIV Vaccine Trials Network><HIV vaccine><HIV/AIDS Vaccines><HVTN><Health><Hospital Admission><Hospitalization><Hypertension><Immune><Immune Monitoring><Immune response><Immunes><Immunity><Immunologic Monitoring><Immunological Monitoring><Immunological response><Immunology><Immunomonitoring><Individual><Infection Control><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><International><Intervention><Intervention Strategies><Knowledge><Laboratories><Lead><Leadership><MAb Therapeutics><Malaria><Mediating><Molecular Interaction><Monitor><Morbidity><Morbidity - disease rate><NIH><National Institutes of Health><Novavax COVID-19 vaccine><Novavax S protein vaccine><Novavax coronavirus disease 2019 vaccine><Obesity><Outcomes Research><Paludism><Participant><Pb element><Persons><Phase><Physicians><Placebo Control><Placebos><Plasmodium Infections><Population><Preparation><Prevention><Preventive><Proteins><Protocol><Protocols documentation><Quality Control><RS protein><Race><Racial Group><Racial Stocks><Randomized><Randomized Clinical Trials><Recombinants><Regimen><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 antibody><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 rS><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 antibody><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><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><Severity of illness><Sham Treatment><Site><System><Testing><Therapeutic Monoclonal Antibodies><Typhoid><Typhoid Fever><United States><United States National Institutes of Health><Vaccination><Vaccines><Validation><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Virus><Wuhan coronavirus><adaptive immune response><adiposity><adulthood><age 18 years><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><base><booster dose><booster shot><booster vaccine><cell assay><clinical trial analysis><corona virus><corona virus disease 2019><corona virus disease 2019 epidemic><corona 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