This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals. The study consists of 2 parts: Phase 1: to identify preferred vaccine candidate(s) and dose level(s); Phase 2/3: an expanded cohort and efficacy part. The study will evaluate the safety, tolerability, and immunogenicity of 3 different SARS-CoV-2 RNA vaccine candidates against COVID-19 and the efficacy of 1 candidate: - As a 2-dose (separated by 21 days) schedule; - At various different dose levels in Phase 1; - As a booster; - In 3 age groups (Phase 1: 18 to 55 years of age, 65 to 85 years of age; Phase 2/3: ≥12 years of age [stratified as 12-15, 16-55 or >55 years of age]). The candidate selected for efficacy evaluation in Phase 2/3 is BNT162b2 at a dose of 30 µg. Participants who originally received placebo will be offered the opportunity to receive BNT162b2 at defined points as part of the study. In order to describe the boostability of BNT162, and potential heterologous protection against emerging SARS-CoV-2 VOCs, an additional dose of BNT162b2 at 30 µg will be given to Phase 1 participants approximately 6 to 12 months after their second dose of BNT162b1 or BNT162b2. This will provide an early assessment of the safety of a third dose of BNT162, as well as its immunogenicity. The assessment of boostability will be further expanded in a subset of Phase 3 participants at selected sites in the US who will receive a third dose of BNT162b2 at 30 µg or a third and potentially a fourth dose of prototype BNT162b2VOC at 30 µg (BNT162b2s01, based upon the South African variant and hereafter referred to as BNT162b2SA). A further subset of Phase 3 participants will receive a third, lower, dose of BNT162b2 at 5 or 10 µg. To further describe potential homologous and heterologous protection against emerging SARS-CoV-2 VOCs, a new cohort of participants will be enrolled who are COVID-19 vaccine-naïve (ie, BNT162b2-naïve) and have not experienced COVID-19. They will receive BNT162b2SA given as a 2-dose series, separated by 21 days. To reflect current and anticipated recommendations for COVID 19 vaccine boosters, participants in C4591001 who meet specified recommendations and have not already received one, will be offered a third dose of BNT162b2 after their second dose of BNT162.
Biological: BNT162b1
Intramuscular injection
Biological: BNT162b2
Intramuscular injection
Other: Placebo
Intramuscular injection
Biological: BNT162b2SA
Intramuscular injection
Inclusion Criteria:
• Male or female participants between the ages of 18 and 55 years, inclusive, 65 and 85
years, inclusive, or ≥12 years, inclusive, at randomization (dependent upon study phase).
For the boostability and protection-against-VOCs subset: Existing participants enrolled to
receive a third dose of BNT162b2 at 30 µg or BNT162b2SA; male or female participants
between the ages of 18 and 55 years, inclusive, at rerandomization.
Newly enrolled participants enrolled to receive 2 doses of BNT162b2SA; male or female
participants between the ages of 18 and 55 years, inclusive, at enrollment.
Existing participants enrolled to receive a third dose of BNT162b2 at 5 or 10 µg; male or
female participants ≥18 years at rerandomization.
Note that participants <18 years of age cannot be enrolled in the EU.
- Participants who are willing and able to comply with all scheduled visits, vaccination
plan, laboratory tests, lifestyle considerations, and other study procedures.
- Healthy participants who are determined by medical history, physical examination, and
clinical judgment of the investigator to be eligible for inclusion in the study.
- Participants who, in the judgment of the investigator, are at risk for acquiring
COVID-19.
- Boostability and protection-against-VOCs existing participant subset only:
Participants who provided a serum sample at Visit 3, with Visit 3 occurring within the
protocol-specified window.
- Capable of giving personal signed informed consent
Exclusion Criteria:
- Other medical or psychiatric condition including recent (within the past year) or
active suicidal ideation/behavior or laboratory abnormality that may increase the risk
of study participation or, in the investigator's judgment, make the participant
inappropriate for the study.
- Phases 1 and 2 only: Known infection with human immunodeficiency virus (HIV),
hepatitis C virus (HCV), or hepatitis B virus (HBV).
- History of severe adverse reaction associated with a vaccine and/or severe allergic
reaction (eg, anaphylaxis) to any component of the study intervention(s).
- Receipt of medications intended to prevent COVID 19.
- Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result
was not available) or microbiological (based on COVID-19 symptoms/signs and a positive
SARS-CoV-2 NAAT result) diagnosis of COVID 19
- Phase 1 only: Individuals at high risk for severe COVID-19, including those with any
of the following risk factors:
- Hypertension
- Diabetes mellitus
- Chronic pulmonary disease
- Asthma
- Current vaping or smoking
- History of chronic smoking within the prior year
- BMI >30 kg/m2
- Anticipating the need for immunosuppressive treatment within the next 6 months
- Phase 1 only: Individuals currently working in occupations with high risk of exposure
to SARS-CoV-2 (eg, healthcare worker, emergency response personnel).
- Immunocompromised individuals with known or suspected immunodeficiency, as determined
by history and/or laboratory/physical examination.
- Phase 1 only: Individuals with a history of autoimmune disease or an active autoimmune
disease requiring therapeutic intervention.
- Bleeding diathesis or condition associated with prolonged bleeding that would, in the
opinion of the investigator, contraindicate intramuscular injection.
- Women who are pregnant or breastfeeding.
- Previous vaccination with any coronavirus vaccine.
- Individuals who receive treatment with immunosuppressive therapy, including cytotoxic
agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or
planned receipt throughout the study.
- Phase 1 only: Regular receipt of inhaled/nebulized corticosteroids.
- Receipt of blood/plasma products or immunoglobulin, from 60 days before study
intervention administration or planned receipt throughout the study.
- Participation in other studies involving study intervention within 28 days prior to
study entry through and including 6 months after the last dose of study intervention,
with the exception of non-Pfizer interventional studies for prevention of COVID 19,
which are prohibited throughout study participation.
- Previous participation in other studies involving study intervention containing lipid
nanoparticles.
- Phase 1 only: Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at
the screening visit.
- Phase 1 only: Any screening hematology and/or blood chemistry laboratory value that
meets the definition of a ≥ Grade 1 abnormality.
- Phase 1 only: Positive test for HIV, hepatitis B surface antigen (HBsAg), hepatitis B
core antibodies (HBc Abs), or hepatitis C virus antibodies (HCV Abs) at the screening
visit.
- Phase 1 only: SARS-CoV-2 NAAT-positive nasal swab within 24 hours before receipt of
study intervention.
- Investigator site staff or Pfizer employees directly involved in the conduct of the
study, site staff otherwise supervised by the investigator, and their respective
family members.
North Alabama Research Center, LLC
Athens, Alabama, United States
Birmingham Clinical Research Unit
Birmingham, Alabama, United States
Medical Affiliated Research Center
Huntsville, Alabama, United States
Optimal Research, LLC
Huntsville, Alabama, United States
Alliance for Multispecialty Research, LLC
Mobile, Alabama, United States
Chinle Comprehensive Health Care Facility
Chinle, Arizona, United States
Johns Hopkins Center for American Indian Health
Chinle, Arizona, United States
The Pain Center of Arizona
Phoenix, Arizona, United States
HOPE Research Institute
Phoenix, Arizona, United States
Alliance for Multispecialty Research, LLC
Tempe, Arizona, United States
Whiteriver Indian Hospital
Whiteriver, Arizona, United States
Anaheim Clinical Trials, LLC
Anaheim, California, United States
Collaborative Neuroscience Research, LLC
Long Beach, California, United States
Long Beach Clinical Trials Services Inc.
Long Beach, California, United States
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, United States
National Research Institute
Los Angeles, California, United States
Velocity Clinical Research, North Hollywood
North Hollywood, California, United States
Paradigm Clinical Research Center
Redding, California, United States
Kaiser Permanente Sacramento
Sacramento, California, United States
Clinical and Translational Science Center (CTSC) Clinical Research Center (CCRC)
Sacramento, California, United States
UC Davis Medical Center
Sacramento, California, United States
California Research Foundation
San Diego, California, United States
Kaiser Permanente Santa Clara
Santa Clara, California, United States
Bayview Research Group
Valley Village, California, United States
Diablo Clinical Research, Inc.
Walnut Creek, California, United States
Lynn Institute of Denver
Aurora, Colorado, United States
Clinical Research Consulting, LLC
Milford, Connecticut, United States
Yale Center for Clinical Investigations (CSRU)
New Haven, Connecticut, United States
Alliance for Multispecialty Research
Coral Gables, Florida, United States
DeLand Clinical Research Unit
DeLand, Florida, United States
Fleming Island Center for Clinical Research
Fleming Island, Florida, United States
Indago Research & Health Center, Inc
Hialeah, Florida, United States
Research Centers of America
Hollywood, Florida, United States
Jacksonville Center for Clinical Research
Jacksonville, Florida, United States
Clinical Neuroscience Solutions, Inc.
Jacksonville, Florida, United States
Acevedo Clinical Research Associates
Miami, Florida, United States
Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
Orlando, Florida, United States
Atlanta Center for Medical Research
Atlanta, Georgia, United States
IACT Health
Columbus, Georgia, United States
Meridian Clinical Research, LLC
Savannah, Georgia, United States
Clinical Research Atlanta
Stockbridge, Georgia, United States
East-West Medical Research Institute
Honolulu, Hawaii, United States
Solaris Clinical Research
Meridian, Idaho, United States
Optimal Research
Peoria, Illinois, United States
University of Iowa Hospitals & Clinics Investigational Drug Servces
Iowa City, Iowa, United States
University of Iowa Hospitals & Clinics
Iowa City, Iowa, United States
Meridian Clinical Research, LLC
Sioux City, Iowa, United States
Alliance for Multispecialty Research, LLC
Newton, Kansas, United States
Alliance for Multispecialty Research, LLC
Wichita, Kansas, United States
Kentucky Pediatric/ Adult Research
Bardstown, Kentucky, United States
Benchmark Research
Metairie, Louisiana, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, United States
LSU Health Sciences Center at Shreveport Clinical Trials Office
Shreveport, Louisiana, United States
LSUHSC-Shreveport
Shreveport, Louisiana, United States
Pharmaron CPC, Inc.
Baltimore, Maryland, United States
University of Maryland Medical Center Investigational Drug Service Pharmacy
Baltimore, Maryland, United States
University of Maryland, Baltimore, Health Sciences Research Facility III
Baltimore, Maryland, United States
University of Maryland, Center for Vaccine Development and Global Health
Baltimore, Maryland, United States
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States
Boston Medical Center
Boston, Massachusetts, United States
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, United States
Michigan Center for Medical Research
Farmington Hills, Michigan, United States
MedPharmics, LLC
Gulfport, Mississippi, United States
Clinical Research Professionals
Chesterfield, Missouri, United States
Sundance Clinical Research, LLC
Saint Louis, Missouri, United States
Bozeman Health Deaconess Hospital dba Bozeman Health Clinical Research
Bozeman, Montana, United States
Bozeman Health Deaconess Hospital
Bozeman, Montana, United States
Methodist Physicians Clinic / CCT Research
Fremont, Nebraska, United States
Meridian Clinical Research, LLC
Norfolk, Nebraska, United States
Quality Clinical Research, Inc.
Omaha, Nebraska, United States
Meridian Clinical Research, LLC
Omaha, Nebraska, United States
Wake Research-Clinical Research Center of Nevada, LLC
Las Vegas, Nevada, United States
Amici Clinical Research
Raritan, New Jersey, United States
South Jersey Infectious Disease
Somers Point, New Jersey, United States
Johns Hopkins Center for American Indian Health
Gallup, New Mexico, United States
Johns Hopkins Center for American Indian Health
Shiprock, New Mexico, United States
Meridian Clinical Research, LLC
Binghamton, New York, United States
Meridian Clinical Research LLC
Endwell, New York, United States
NYU Langone Health
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Rochester Clinical Research, Inc.
Rochester, New York, United States
University of Rochester Medical Center- Kari Steinmetz
Rochester, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
SUNY Upstate Medical University Global Health Research Unit
Syracuse, New York, United States
Meridian Clinical Research LLC
Vestal, New York, United States
PMG Research of Raleigh, LLC d/b/a PMG Research of Cary
Cary, North Carolina, United States
PMG Research of Charlotte LLC
Charlotte, North Carolina, United States
Accessioning Unit and Repository
Durham, North Carolina, United States
Duke Vaccine and Trials Unit
Durham, North Carolina, United States
Clinical Research Pickett Road
Durham, North Carolina, United States
Duke Investigational Drug Service Pharmacy
Durham, North Carolina, United States
PharmQuest
Greensboro, North Carolina, United States
PMG Research of Hickory, LLC
Hickory, North Carolina, United States
PMG Research of Raleigh, LLC
Raleigh, North Carolina, United States
M3 Wake Research, Inc.
Raleigh, North Carolina, United States
PMG Research of Salisbury, LLC
Salisbury, North Carolina, United States
PMG Research of Wilmington, LLC
Wilmington, North Carolina, United States
PMG Research of Winston-Salem, LLC
Winston-Salem, North Carolina, United States
Lillestol Research Llc
Fargo, North Dakota, United States
Meridian Clinical Research, LLC
Cincinnati, Ohio, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Meridian Clinical Research LLC
Cincinnati, Ohio, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
VA Northeast Ohio Healthcare System
Cleveland, Ohio, United States
Velocity Clinical Research, Inc.
Cleveland, Ohio, United States
Aventiv Research Inc.
Columbus, Ohio, United States
Dayton Clinical Research
Dayton, Ohio, United States
Dayton Clinical Research
Dayton, Ohio, United States
PriMED Clinical Research
Dayton, Ohio, United States
Senders Pediatrics
South Euclid, Ohio, United States
Lynn Institute of Norman
Norman, Oklahoma, United States
Kaiser Permanente Northwest-Center for Health Research
Portland, Oregon, United States
Lehigh Valley Health Network/Network Office of Research and Innovation
Allentown, Pennsylvania, United States
Velocity Clinical Research, Providence
East Greenwich, Rhode Island, United States
Main Street Physician's Care
Little River, South Carolina, United States
Main Street Physician's Care
Loris, South Carolina, United States
Holston Medical Group
Bristol, Tennessee, United States
Holston Medical Group
Kingsport, Tennessee, United States
Alliance for Multispecialty Research, LLC
Knoxville, Tennessee, United States
Alliance for Multispecialty Research, LLC
Knoxville, Tennessee, United States
Clinical Neuroscience Solutions, Inc.
Memphis, Tennessee, United States
Clinical Research Associates, Inc.
Nashville, Tennessee, United States
Trinity Clinical Research
Tullahoma, Tennessee, United States
Benchmark Research
Austin, Texas, United States
ARC Clinical Research at Four Points
Austin, Texas, United States
Tekton Research, Inc.
Austin, Texas, United States
Tekton Research
Austin, Texas, United States
North Texas Infectious Diseases Consultants, P.A.
Dallas, Texas, United States
Ventavia Research Group, LLC
Fort Worth, Texas, United States
Benchmark Research
Fort Worth, Texas, United States
Texas Health Resources
Fort Worth, Texas, United States
University of Texas Medical Branch
Galveston, Texas, United States
Ventavia Research Group, LLC
Houston, Texas, United States
Texas Center for Drug Development, Inc.
Houston, Texas, United States
Ventavia Research Group, LLC
Keller, Texas, United States
SMS Clinical Research, LLC
Mesquite, Texas, United States
LinQ Research, LLC
Pearland, Texas, United States
Benchmark Research.
San Angelo, Texas, United States
Clinical Trials of Texas, Inc.
San Antonio, Texas, United States
Diagnostics Research Group
San Antonio, Texas, United States
Martin Diagnostic Clinic
Tomball, Texas, United States
J. Lewis Research, Inc. / Foothill Family Clinic
Salt Lake City, Utah, United States
J. Lewis Research, Inc. / Foothill Family Clinic South
Salt Lake City, Utah, United States
Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
Annandale, Virginia, United States
Virginia Research Center LLC
Midlothian, Virginia, United States
Benaroya Research Institute at Virginia Mason
Seattle, Washington, United States
Wenatchee Valley Hospital
Wenatchee, Washington, United States
Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich
Caba, Argentina
Hospital Santo Antonio/ Associacao Obras Sociais Irma Dulce
Salvador, Bahia, Brazil
CEPIC - Centro Paulista de Investigacao Clinica e Servicos Medicos Ltda (Casa Branca)
Sao Paulo, Brazil
CRS Clinical Research Services Berlin GmbH
Berlin, Germany
Medizentrum Essen Borbeck
Essen, Germany
IKF Pneumologie GmbH & Co KG
Frankfurt am Main, Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany
CRS Clinical Research Services Mannheim GmbH
Mannheim, Germany
Studienzentrum Brinkum Dr. Lars Pohlmeier und Torsten Drescher
Stuhr, Germany
Newtown Clinical Research Centre
Johannesburg, Gauteng, South Africa
Jongaie Research
Pretoria, Gauteng, South Africa
Limpopo Clinical Research Initiative
Thabazimbi, Limpopo, South Africa
Tiervlei Trial Centre, Basement Level, Karl Bremer Hospital
Cape Town, Western CAPE, South Africa
Ankara Universitesi Tip Fakultesi, Ibni Sina Hastanesi
Ankara, Turkey
Hacettepe Universitesi Tip Fakultesi
Ankara, Turkey
Istanbul Yedikule Gogus Hastaliklari ve Gogus Cerrahisi Egitim Arastirma Hastanesi
Istanbul, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi
Istanbul, Turkey
Istanbul Universitesi-Cerrahpasa, Cerrahpasa Tip Fakultesi
Istanbul, Turkey
Medipol Mega Universite Hastanesi
Istanbul, Turkey
Acibadem Atakent Hastanesi
Istanbul, Turkey
Kocaeli Universitesi Tip Fakultesi
Kocaeli, Turkey
Sakarya Universitesi Egitim ve Arastirma Hastanesi
Sakarya, Turkey
Pfizer CT.gov Call Center, Study Director
Pfizer