Document text
Principal Investigator: Dan H. Barouch
Organization: FRED HUTCHINSON CANCER CENTER
Fiscal Year: 2023
Award: $2,683,830
Funding agency: National Institute of Allergy and Infectious Diseases
FOA: PA-20-272: Administrative Supplements to Existing NIH Grants and Cooperative Agreements
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 implementation of the COVID-19 vaccine efficacy trial entitled “A
parallel-group, Phase III, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety,
and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (monovalent and bivalent)
for prevention against COVID-19 in adults 18 years of age 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 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, multi-stage, modified double-blind, placebo-controlled, multi-armed study will test the efficacy,
safety and immunogenicity of Sanofi-Pasteur SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant,
monovalent D614 (monovalent vaccine) & SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent
D614/B.1.351 (bivalent vaccine), to modify COVID-19 disease in adults 18 years of age and older. 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 assess the clinical efficacy of the investigational CoV2 preS dTM recombinant
protein adjuvanted with AS03 – both monovalent and bivalent (“study vaccines”) in naïve adults for the prevention
of symptomatic COVID-19 occurring > 14 days after the second injection; to assess the safety of the study
vaccines compared to placebo throughout the study; to assess, in participants who are SARS-CoV-2 naïve, the
clinical efficacy of the CoV2 preS dTM-AS03 vaccines for prevention of the following occurring > 14 days after
the second injection: prevention of SARS-CoV-2 infection, prevention of severe COVID-19; to describe the
frequency & spectrum of disease in episodes of symptomatic COVID-19 in SARS-CoV-2 non-naïve adults in
each study group.
This efficacy trial will tell us much about the ability of two recombinant vaccines, targeting two of the most
common SARS-CoV-2 variants, to induce strong adaptive protective responses. After the Novavax vaccine, this
is the second large scale recombinant protein vaccine to be tested for efficacy and it is the first trial to use a
bivalent vaccine including the B.1.351 variant of concern. If successful, this will be an important vaccine that can
be scaled up rapidly and deployed throughout the world. The results of this trial will be used to assess registration
of this vaccine product and will also provide crucial information to inform future generations of COVID-19
vaccines.
Terms: <18 year old><18 years of age><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><21+ years old><Address><Adjuvant><Administrative Supplement><Adult><Adult Human><Assay><Award><B.1.351><Bioassay><Biologic Assays><Biological Assay><Biometrics><Biometry><Biostatistics><COVID crisis><COVID disease severity><COVID epidemic><COVID pandemic><COVID severity><COVID-19><COVID-19 Prevention Network><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 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19><COVID19 crisis><COVID19 disease severity><COVID19 epidemic><COVID19 global health 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of Health><Parents><Participant><Pb element><Persons><Phase><Physicians><Placebo Control><Placebos><Population><Prevention><Protocol><Protocols documentation><Qualifying><Recombinant Proteins><Recombinant Vaccines><Risk><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 B.1.351><SARS-CoV-2 beta><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 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><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><Scientist><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 coronavirus 2><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 vaccine><Severe acute respiratory syndrome related corona virus 2><Sham Treatment><Site><South Africa strain><South Africa variant><South African strain><South African variant><U-Series Cooperative Agreements><United States><United States National Institutes of Health><Vaccines><Wuhan coronavirus><adulthood><age 18 years><clinical efficacy><clinical trial recruitment><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 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 network><coronavirus disease 2019 public health crisis><coronavirus disease 2019 screening><coronavirus disease 2019 severity><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><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 vaccine><coronavirus disease-19 virus><coronavirus infectious disease-19><determine efficacy><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><efficacy testing><efficacy trial><eighteen year old><eighteen years of age><evaluate efficacy><examine efficacy><experience><hCoV19><heavy metal Pb><heavy metal lead><high risk group><high risk individual><high risk people><high risk population><host response><human immunodeficiency virus vaccine><immune system response><immunogenicity><immunoresponse><infected with COVID-19><infected with 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coronavirus><vaccine study><vaccine trial><variants of concern>