A Study to Learn About Variant-Adapted COVID-19 RNA Vaccine Candidate(s) in Healthy Children

A MASTER PHASE 1/2/3 PROTOCOL TO INVESTIGATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF VARIANT-ADAPTED BNT162b2 RNA-BASED VACCINE CANDIDATE(S) IN HEALTHY CHILDREN

The purpose of this clinical trial is to learn about the safety, extent of the side effects, and immune responses of the study vaccine (called variant-adapted BNT162b2 RNA-based vaccine) in healthy children. The trial is divided into 5 individual studies or substudies based on age group and prior history of COVID-19 vaccinations. All participants in each of the 5 sub-studies will receive study vaccine as a shot depending on what group they are in.

• Substudy A design: Phase 1 includes participants 6 months through less than 4 years 3 months of age who have not received a previous coronavirus vaccination (COVID-19 vaccine naïve) and will receive 3 doses of study vaccine as their initial series, followed by a fourth dose of study vaccine. Phase 2/3 includes participants 6 months through less than 5 years of age who have not received a previous coronavirus vaccination (COVID-19 vaccine naive) and will receive 1, 2, or 3 doses of study vaccine, depending on what group they are in.
• Substudy B design: includes participants 6 months through less than 5 years of age who have either received 2 or 3 prior doses of BNT162b2 and will receive study vaccine as their third or fourth dose.
• Substudy C design: Phase 1 includes participants 6 months through less than 5 years of age who have received 3 prior doses of BNT162b2 and will receive study vaccine as their fourth dose.
• Substudy D design: includes participants 5 through less than12 years of age who have received 2 or 3 prior doses of BNT162b2 and will receive study vaccine as their third or fourth dose.
• Substudy E design: includes participants 5 through less than 12 years of age who have not received a previous coronavirus vaccination (COVID-19 vaccine naive) and will receive a single dose of study vaccine.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19; Severe Acute Respiratory Syndrome Coronavirus 2; SARS-CoV-2 Virus
• Intervention / Treatment: Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram dose; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 6 microgram dose; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose; Biological: Variant-adapted BNT162b2 (Omicron KP.2) 10 microgram dose

• Study Type: Interventional
• Enrollment (Estimated): 4292
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 04266-010
    • CEPIC - Centro Paulista de Investigacao Clinica
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41680-020
      • Obras Sociais Irma Dulce
  • Paraná
    • Curitiba, Paraná, Brazil, 80810-050
      • Centro Médico São Francisco
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, CEP: 59025-050
      • Centro de Estudos e Pesquisa em Molestias Infecciosas - CPCLIN/RN
  • São Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
• Mexico
  • Mexico City, Mexico, 06760
    • Caimed Investigacion En Salud S.A. de C.V.
  • Veracruz, Mexico, 91900
    • Sociedad de Metabolismo y Corazón S.C.
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64060
      • Christus - Latam Hub Center of Excellence and Innovation S.C.
• Puerto Rico
  • Guayama, Puerto Rico, 00784
    • Clinical Research Puerto Rico
  • San Juan, Puerto Rico, 00935
    • University of Puerto Rico - Medical Sciences Campus
• South Africa
  • Eastern Cape
    • East London, Eastern Cape, South Africa, 5201
      • Synergy Biomed Research Institute
  • Free State
    • Welkom, Free State, South Africa, 9460
      • Jaymed Research
  • Gauteng
    • Boksburg, Gauteng, South Africa, 1459
      • REIMED Reiger Park
    • Johannesburg, Gauteng, South Africa, 2113
      • Newtown Clinical Research
    • Johannesburg, Gauteng, South Africa, 2001
      • Wits RHI
    • Johannesburg, Gauteng, South Africa, 2013
      • University of Witwatersrand (WITS) - Vaccines and Infectious Diseases Analytics (VIDA)
    • Johannesburg, Gauteng, South Africa, 2093
      • Wits VIDA Nkanyezi Research Unit
    • Pretoria, Gauteng, South Africa, 0184
      • Botho ke Bontle Health Services
    • Sandton, Gauteng, South Africa, 2196
      • Sandton Medical Research Centre
  • Limpopo
    • Polokwane, Limpopo, South Africa, 0699
      • Gole Biomed Research Centre
  • Mpumalanga
    • Middelburg, Mpumalanga, South Africa, 1055
      • Merclinco
  • North West
    • Klerksdorp, North West, South Africa, 2571
      • Perinatal HIV Research Unit (PHRU)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7530
      • TREAD Research
    • Plettenberg Bay, Western Cape, South Africa, 6600
      • Tsitsikamma Clinical Research Initiative (TCRI)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • UAB Child Health Research Unit (CHRU)
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center Inc.
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • Paramount, California, United States, 90723
      • Center for Clinical Trials, LLC
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates
    • Sacramento, California, United States, 95815
      • Kaiser Permanente Sacramento
  • Colorado
    • Highlands Ranch, Colorado, United States, 80126
      • PediaClinic
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
    • New Haven, Connecticut, United States, 06519
      • Yale University- Yale Center for Clinical Investigation
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Medical Center
    • Washington D.C., District of Columbia, United States, 20016
      • Velocity Clinical Research, Washington DC
    • Washington D.C., District of Columbia, United States, 20009
      • Emerson Clinical Research Institute
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research Associates
    • Miami, Florida, United States, 33144
      • Bio-Medical Research LLC
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
    • Pensacola, Florida, United States, 32503
      • SEC Clinical Research
    • Tampa, Florida, United States, 33613
      • PAS Research
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
    • Atlanta, Georgia, United States, 30322
      • Emory Children's Center Illness POD
    • Union City, Georgia, United States, 30291
      • Rophe Adult and Pediatric Medicine/SKYCRNG
  • Iowa
    • Ankeny, Iowa, United States, 50023
      • The Iowa Clinic, P.C.
    • West Des Moines, Iowa, United States, 50266
      • The Iowa Clinic, P.C.
    • West Des Moines, Iowa, United States, 50266
      • The Iowa Clinic
  • Kansas
    • Newton, Kansas, United States, 67114
      • AMR Clinical
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty Research, LLC
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Louisiana State University Health Sciences Shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Center for Immunization Research Inpatient Unit
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Center for Immunization Outpatient Clinic
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02119
      • Boston Medical Center Crosstown Building
  • Mississippi
    • Ridgeland, Mississippi, United States, 39157
      • SKY Integrative Medical Center/SKYCRNG
  • Nebraska
    • Hastings, Nebraska, United States, 68901
      • Velocity Clinical Research, Hastings
    • Lincoln, Nebraska, United States, 68510
      • Velocity Clinical Research, Lincoln
    • Omaha, Nebraska, United States, 68114
      • Children's Hospital & Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Robert Wood Johnson Medical School
  • New York
    • Binghamton, New York, United States, 13905
      • Velocity Clinical Research, Binghamton
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Health Sciences University
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, LLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Atrium Health - Carolinas Medical Center
    • Durham, North Carolina, United States, 27703
      • Duke Vaccine and Trials Unit
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44122
      • Velocity Clinical Research, Cleveland
    • Cleveland, Ohio, United States, 44121
      • Senders Pediatrics
    • Columbus, Ohio, United States, 43213
      • Centricity Research Columbus Ohio Multispecialty
    • Dayton, Ohio, United States, 45409
      • Dayton Clinical Research
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Cyn3rgy Research
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16506
      • Allegheny Health and Wellness Pavilion
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Velocity Clinical Research, Providence
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research, LLC
    • Summerville, South Carolina, United States, 29486
      • Coastal Pediatric Research
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates Inc
  • Texas
    • Corpus Christi, Texas, United States, 78411
      • Driscoll Children's Hospital
    • Dallas, Texas, United States, 75251
      • Cedar Health Research
    • Edinburg, Texas, United States, 78539
      • Proactive Clinical Research, LLC
    • Frisco, Texas, United States, 75033
      • ACRC Trials
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • Houston, Texas, United States, 77065
      • DM Clinical Research- Cyfair
    • McAllen, Texas, United States, 78504
      • Dr. Ruben Aleman and Associates
    • Plano, Texas, United States, 75024
      • ACRC Trials (Administrative Site)
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • Pediatric Research of Charlottesville, LLC
    • Midlothian, Virginia, United States, 23114
      • Virginia Research Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
    • Seattle, Washington, United States, 98101
      • Seattle Children's- Building Cure

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 11 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Substudy A

Inclusion Criteria:

• Phase 1: Healthy male or female participants ≥6 months to <4 years 3 months of age, at the time of randomization.
• Phase 2/3: Healthy male or female participants ≥6 months to <5 years of age at the time of randomization/enrollment.

Exclusion Criteria:

• Previous or current diagnosis of multisystem inflammatory syndrome in children (MIS-C).
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination, or individuals who receive treatment with immunosuppressive therapy.
• Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus. Note: Stable type 1 diabetes and hypothyroidism are permitted.
• Any history of myocarditis or pericarditis.
• Previous vaccination with any COVID-19 vaccine.
• Receipt of systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids, eg, for cancer) or radiotherapy, within 60 days before enrollment through the conclusion of the study. Systemic corticosteroids (≥2 mg/kg of body weight or ≥20 mg/day of prednisone or equivalent for persons who weigh >10 kg) for ≥14 days is prohibited from 28 days prior to enrollment through 28 days after administration of study intervention.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies (except palivizumab), from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.

Substudy B

Inclusion Criteria:

- Healthy male or female participants = ≥6 months to <5 years of age, at the time of enrollment.

Exclusion Criteria:

• Previous or current diagnosis of MIS-C.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination, or individuals who receive treatment with immunosuppressive therapy.
• Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus.
• Prior receipt of any COVID 19 vaccine other than BNT162b2.
• Receipt of systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids, eg, for cancer) or radiotherapy, within 60 days before enrollment through the conclusion of the study. Systemic corticosteroids (≥2 mg/kg of body weight or ≥20 mg/day of prednisone or equivalent for persons who weigh >10 kg) for ≥14 days is prohibited from 28 days prior to enrollment through 28 days after administration of study intervention.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies (except palivizumab), from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.

Substudy C

Inclusion Criteria:

- Healthy male or female participants ≥6 months to <5 years of age, at the time of randomization/enrollment.

Exclusion Criteria:

• Previous or current diagnosis of MIS-C.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination, or individuals who receive treatment with immunosuppressive therapy.
• Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus.
• Prior receipt of any COVID 19 vaccine other than BNT162b2.
• Receipt of systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids, eg, for cancer) or radiotherapy, within 60 days before enrollment through the conclusion of the study. Systemic corticosteroids (≥2 mg/kg of body weight or ≥20 mg/day of prednisone or equivalent for persons who weigh >10 kg) for ≥14 days is prohibited from 28 days prior to enrollment through 28 days after administration of study intervention.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies (except palivizumab), from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.

Substudy D

Inclusion Criteria:

- Healthy male or female participants ≥5 years to <12 years of age, at the time of enrollment.

Exclusion Criteria:

• Previous or current diagnosis of MIS-C.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination, or individuals who receive treatment with immunosuppressive therapy.
• Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus.
• Female who is pregnant or breastfeeding.
• Prior receipt of any COVID 19 vaccine other than BNT162b2.
• Receipt of systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids, eg, for cancer) or radiotherapy, within 60 days before enrollment through the conclusion of the study. Systemic corticosteroids (≥2 mg/kg of body weight or ≥20 mg/day of prednisone or equivalent for persons who weigh >10 kg) for ≥14 days is prohibited from 28 days prior to enrollment through 28 days after administration of study intervention.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies (except palivizumab), from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.

Substudy E

Inclusion Criteria:

- Healthy male or female participants ≥5 years to <12 years of age, at the time of enrollment.

Exclusion Criteria:

• Previous or current diagnosis of MIS-C.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination, or individuals who receive treatment with immunosuppressive therapy.
• Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus.
• Any history of myocarditis or pericarditis.
• Female who is pregnant or breastfeeding.
• Previous vaccination with any COVID 19 vaccine.
• Receipt of systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids, eg, for cancer) or radiotherapy, within 60 days before enrollment through the conclusion of the study. Systemic corticosteroids (≥2 mg/kg of body weight or ≥20 mg/day of prednisone or equivalent for persons who weigh >10 kg) for ≥14 days is prohibited from 28 days prior to enrollment through 28 days after administration of study intervention.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies (except palivizumab), from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

23

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3 microgram dose, 6 Months to <4 Years 6 Months (Substudy B, Group 1); Injection in the muscle, 2 doses 2 months apart	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose; Injection in the muscle
Experimental: 3 microgram dose, 6 Months to <5 Years (Substudy B, Group 2); Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose; Injection in the muscle
Experimental: 3 microgram dose, 6 Months to <5 Years (Substudy B, Group 3); Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose; Injection in the muscle
Experimental: 10 microgram dose, 5 to <12 Years (Substudy D, Group 1); Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Injection in the muscle
Experimental: 10 microgram dose, 5 to <12 Years (Substudy D, Group 2); Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Injection in the muscle
Experimental: 10 microgram dose, 5 to <12 Years (Substudy D, Group 3); Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Injection in the muscle
Experimental: 6 microgram dose, 6 Months to <2 Years (Substudy C, Phase 1); Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose; Injection in the muscle
Experimental: 10 microgram dose, 6 Months to <2 Years (Substudy C, Phase 1); Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Injection in the muscle
Experimental: 6 microgram dose, 2 Years to <5 Years (Substudy C, Phase 1); Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose; Injection in the muscle
Experimental: 10 microgram dose, 2 Years to <5 Years (Substudy C, Phase 1); Injection in the muscle, 1 dose	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Injection in the muscle
Experimental: 3 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1); Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose; Injection in the muscle; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram dose; Injection in the muscle
Experimental: 6 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1); Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose; Injection in the muscle; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 6 microgram dose; Injection in the muscle
Experimental: 10 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1); Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Injection in the muscle; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose; injection in the muscle
Experimental: 3 microgram dose, 2 Years to <4 years 3 months (Substudy A, Phase 1); Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose; Injection in the muscle; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram dose; Injection in the muscle
Experimental: 6 microgram dose, 2 Years to <4 years 3 months (Substudy A, Phase 1); Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose; Injection in the muscle; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 6 microgram dose; Injection in the muscle; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose; injection in the muscle
Experimental: 10 microgram dose, 2 Years to <4 years 3 months (Substudy A, Phase 1); Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3	Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Injection in the muscle
Experimental: 3 microgram dose, 6 Months to <2 Years (Substudy A, Phase 2/3, Group 3) - 0/3/11 week schedule; Injection in the muscle at 0-, 3-, and 11-weeks	Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram dose; Injection in the muscle
Experimental: 10 microgram dose, 5 Years to <12 Years (Substudy E, Group 2); Injection in the muscle, 1 dose	Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose; injection in the muscle
Experimental: 10 microgram dose, 6 Months to <2 Years (Substudy A, Phase 2/3, Group 1) - 0/8 week schedule; Injection in the muscle at 0- and 8-weeks	Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose; injection in the muscle
Experimental: 10 microgram dose, 6 Months to <2 Years (Substudy A, Phase 2/3, Group 2) - 0/8 week schedule; Injection in the muscle at 0- and 8-weeks	Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose; injection in the muscle
Experimental: 10 microgram dose, 2 to <5 Years (Substudy A, Phase 2/3, Group 4) - Single dose; Injection in the muscle, 1 dose	Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose; injection in the muscle
Experimental: 10 microgram dose, 2 to <5 Years (Substudy A, Phase 2/3, Group 5) - Single dose; Injection in the muscle, 1 dose	Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose; injection in the muscle
Experimental: 10 microgram dose, 6 months to <2 years (Substudy A Phase 2/3, Group 6) - 0/8 week schedule; Injection in the muscle at 0- and 8-weeks	Biological: Variant-adapted BNT162b2 (Omicron KP.2) 10 microgram dose; Injection in the muscle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SSA - Ph 1 dose finding, percentage of participants reporting adverse events	as elicited by investigational site staff	from Dose 1 to 1 month after Dose 3 and from Dose 4 to 1 month after Dose 4
SSA - Ph 1 dose finding, percentage of participants reporting serious adverse events	as elicited by investigational site staff	from Dose 1 to 6 months after the last dose
Substudy B (SSB) - percentage of participants reporting local reactions	Participants ≥6 months to <2 years of age: tenderness at the injection site, redness, and swelling as self-reported on electronic diaries Participants ≥2 to <5 years of age: pain at the injection site, redness, and swelling as self-reported on electronic diaries	for up to 7 days following Dose 1 (for Groups 1, 2 and 3) and Dose 2 (for Group 1)
SSB - percentage of participants reporting systemic events	Participants ≥6 months to <2 years of age: fever, decreased appetite, drowsiness, and irritability as self-reported on electronic diaries Participants ≥2 to <5 years of age: fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries	for up to 7 days following Dose 1 (for Groups 1, 2 and 3) and Dose 2 (for Group 1)
SSB - percentage of participants reporting adverse events	as elicited by investigational site staff	from the first study vaccination to 1 month after the first study vaccination (for Groups 1, 2, and 3), and from the second study vaccination to 1 month after the second study vaccination (for Group 1 only)
SSB - percentage of participants reporting serious adverse events	as elicited by investigational site staff	from Dose 1 to 6 months after the last dose
Substudy C (SSC) - Ph 1 dose finding, percentage of participants reporting local reactions	Participants ≥6 months to <2 years of age: tenderness at the injection site, redness, and swelling as self-reported on electronic diaries Participants ≥2 to <5 years of age: pain at the injection site, redness, and swelling as self-reported on electronic diaries	for up to 7 days following Dose 1
SSC - Ph 1 dose finding, percentage of participants reporting systemic events	Participants ≥6 months to <2 years of age: fever, decreased appetite, drowsiness, and irritability as self-reported on electronic diaries Participants ≥2 to <5 years of age: fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries	for up to 7 days following Dose 1
SSC - Ph 1 dose finding, percentage of participants reporting adverse events	as elicited by investigational site staff	1 month after Dose 1
SSC - Ph 1 dose finding, percentage of participants reporting serious adverse events	as elicited by investigational site staff	6 months after Dose 1
SSC - Ph 1 dose finding - geometric mean titers elicited by prophylactic bivalent BNT162b2 at each dose level given as a fourth dose in participants ≥6 months to <5 years of age	As measured at the central laboratory	At baseline (before Dose 1) and 1 month after Dose 1
SSC - Ph 1 dose finding - geometric mean fold rise elicited by prophylactic bivalent BNT162b2 at each dose level given as a fourth dose in participants ≥6 months to <5 years of age	As measured at the central laboratory	At baseline (before Dose 1) and 1 month after Dose 1
SSC - Ph 1 dose finding - percentage of participants with seroresponse elicited by prophylactic bivalent BNT162b2 at each dose level given as a fourth dose in participants ≥6 months to <5 years of age	As measured at the central laboratory	At baseline (before Dose 1) and 1 month after Dose 1
Substudy D (SSD) - percentage of participants reporting local reactions	pain at the injection site, redness, and swelling as self-reported on electronic diaries	for up to 7 days following Dose 1
SSD - percentage of participants reporting systemic events	fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries	for up to 7 days following Dose 1
SSD - percentage of participants reporting adverse events	as elicited by investigational site staff	1 month after Dose 1
SSD - percentage of participants reporting serious adverse events	as elicited by investigational site staff	6 months after Dose 1
Substudy A (SSA) - Ph 1 dose finding, percentage of participants reporting local reactions	Participants ≥6 months to <2 years of age: tenderness at the injection site, redness, and swelling as self-reported on electronic diaries Participants ≥2 to <5 years of age: pain at the injection site, redness, and swelling as self-reported on electronic diaries	for up to 7 days following Dose 1, Dose 2, Dose 3 and Dose 4
SSA - Ph 1 dose finding, percentage of participants reporting systemic events	Participants ≥6 months to <2 years of age: fever, decreased appetite, drowsiness, and irritability as self-reported on electronic diaries Participants ≥2 to <5 years of age: fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries	for up to 7 days following Dose 1, Dose 2, Dose 3 and Dose 4
SSD - difference in percentages of participants with seroresponse to the Omicron BA.4/BA.5 strain in participants ≥5 to <12 years of age	As measured at the central laboratory	at 1 month after bivalent BNT162b2 as a fourth dose for participants who received 3 prior doses of BNT162b2 10 µg and at 1 month after a third dose of BNT162b2 10 µg for Study C4591007 Phase 2/3 participants who received 3 doses of BNT162b2 10 µg
SSB - superiority with respect to ratio of the geometric mean of SARS-CoV-2 Omicron BA.4/BA.5-neutralizing titers in participants ≥6 months to <5 years of age	As measured at the central laboratory	at 1 month after Dose 4 for Group 2 participants who received 3 prior doses of BNT162b2 3 µg and a fourth dose of bivalent BNT162b2 to 1 month after Dose 3 in Study C4591007 participants ≥6 months to <5 years of age who received 3 doses of BNT162b2 3 µg
SSB - noninferiority with respect to seroresponse rate to the Omicron BA.4/BA.5 strain in participants ≥6 months to <5 years of age	As measured at the central laboratory	at 1 month after Dose 4 for Group 2 participants who received 3 prior doses of BNT162b2 3 µg and a fourth dose of bivalent BNT162b2 to 1 month after Dose 3 in Study C4591007 participants ≥6 months to <5 years of age who received 3 doses of BNT162b2 3 µg
SSD - the ratio of the geometric mean of SARS-CoV-2 Omicron BA.4/BA.5-neutralizing titers in participants ≥5 to <12 years of age	As measured at the central laboratory	at 1 month after Dose 4 for participants who received 3 prior doses of BNT162b2 10 μg and a fourth dose of bivalent BNT162b2 to those at 1 month after Dose 3 for Study C4591007 Phase 2/3 participants who received 3 doses of BNT162b2 10 μg
Substudy E (SSE) - percentage of participants reporting local reactions	pain at the injection site, redness, and swelling as self-reported on electronic diaries	for up to 7 days following Dose 1
SSE - percentage of participants reporting systemic events	fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries	for up to 7 days following Dose 1
SSA - Ph 2/3, percentage of participants reporting local reactions	Participants ≥6 months to <2 years of age: tenderness at the injection site, redness, and swelling as self-reported on electronic diaries Participants ≥2 to <5 years of age: pain at the injection site, redness, and swelling as self-reported on electronic diaries	for up to 7 days following Dose 1 (for Groups 1 through 6), Dose 2 (for Groups 1, 2, 3, and 6), and Dose 3 (for Group 3)
SSA - Ph 2/3, percentage of participants reporting systemic events	Participants ≥6 months to <2 years of age: fever, decreased appetite, drowsiness, and irritability as self-reported on electronic diaries Participants ≥2 to <5 years of age: fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries	for up to 7 days following Dose 1 (for Groups 1 through 6), Dose 2 (for Groups 1, 2, 3, and 6), and Dose 3 (for Group 3)
SSA - Ph 2/3, percentage of participants reporting adverse events	as elicited by investigational site staff	from Dose 1 to 1 month after the last dose
SSA - Ph 2/3, percentage of participants reporting serious adverse events	as elicited by investigational site staff	from Dose 1 to 6 months after the last dose
SSA - Ph 2/3, noninferiority with respect to ratio of the geometric mean of SARS-CoV-2 Omicron XBB.1.5-neutralizing titers in participants ≥6 months to <2 years of age	As measured at the central laboratory	At 1 month after 2 doses of BNT162b2 (Omicron XBB.1.5) 10 microgram (on a 0- and 8-week schedule) to 1 month after 3 doses (on a 0-, 3-, and 11-week schedule) of BNT162b2 (Omicron XBB.1.5) 3 microgram
SSA - Ph 2/3, noninferiority with respect to seroresponse rate to the Omicron XBB.1.5 strain titers in participants ≥6 months to <2 years of age	As measured at the central laboratory	At 1 month after 2 doses of BNT162b2 (Omicron XBB.1.5) 10 microgram (on a 0- and 8-week schedule) and at 1 month after 3 doses (on a 0-, 3-, and 11-week schedule) of BNT162b2 (Omicron XBB.1.5) 3 microgram
SSA - Ph 2/3, noninferiority with respect to ratio of the geometric mean of SARS-CoV-2 Omicron XBB.1.5-neutralizing titers in participants ≥2 to <5 years of age	As measured at the central laboratory	At 1 month after 1 dose of BNT162b2 (Omicron XBB.1.5) 10 microgram in participants ≥2 to <5 years of age to 1 month after 3 doses (on a 0/3/11-week schedule) of BNT162b2 (Omicron XBB.1.5) 3 microgram in participants ≥6 months to <2 years of age
SSA - Ph 2/3, noninferiority with respect to seroresponse rate to the Omicron XBB.1.5 strain in participants ≥2 to <5 years of age	As measured at the central laboratory	At 1 month after 1 dose of BNT162b2 (Omicron XBB.1.5) 10 microgram in participants ≥2 to <5 years of age and at 1 month after 3 doses (0/3/11-week schedule) of BNT162b2 (Omicron XBB.1.5) 3 microgram in participants ≥6 months to <2 years of age
SSE - percentage of participants reporting adverse events	as elicited by investigational site staff	from Dose 1 to 1 month after Dose 1
SSE - percentage of participants reporting serious adverse events	as elicited by investigational site staff	from Dose 1 to 6 months after Dose 1
SSE - Ratio of the geometric mean of SARS-CoV-2 Omicron XBB.1.5-neutralizing titers	As measured at the central laboratory	At 1 month after 1 dose of BNT162b2 (Omi XBB.1.5) 10 microgram in participants ≥5 to 12 years of age to 1 month after 1 dose of BNT162b2 (Omi XBB.1.5) 30 microgram in participants ≥12 years of age from study C4591054 Substudy A
SSE - difference in percentage of participants with seroresponse to Omicron XBB.1.5	As measured at the central laboratory	At 1 month after 1 dose of BNT162b2 (Omi XBB.1.5) 10 microgram in participants ≥5 to 12 years of age and 1 month after 1 dose of BNT162b2 (Omi XBB.1.5) 30 microgram in participants ≥12 years of age from study C4591054 Substudy A

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SSB - geometric mean titers elicited by bivalent BNT162b2 given as third and/or fourth dose in participants ≥6 months <5 years of age	As measured at the central laboratory	Group 1: At baseline (before Dose 1), 1 month after Dose 1 and 1 month after Dose 2; Groups 2 and 3: At baseline (before Dose 1) and 1 month after Dose 1
SSB - geometric mean fold rise elicited by bivalent BNT162b2 given as third and/or fourth dose in participants ≥6 months <5 years of age	As measured at the central laboratory	Group 1: At baseline (before Dose 1), 1 month after Dose 1 and 1 month after Dose 2; Groups 2 and 3: At baseline (before Dose 1) and 1 month after Dose 1
SSB - percentages of participants with seroresponse elicited by bivalent BNT162b2 given as third and/or fourth dose in participants ≥6 months <5 years of age	As measured at the central laboratory	Group 1: At baseline (before Dose 1), 1 month after Dose 1 and 1 month after Dose 2; Groups 2 and 3: At baseline (before Dose 1) and 1 month after Dose 1
SSA - Ph 1 dose finding, geometric mean titers elicited by prophylactic variant-adapted BNT162b2 at each dose level and variant vaccine type (if applicable) in COVID-19 vaccine-naïve participants ≥6 months to <5 years of age	As measured at the central laboratory	At baseline (before Dose 1), 1 month after Dose 2, 1 month after Dose 3, and 1 month after Dose 4
SSB - noninferiority with respect to ratio of the geometric mean of SARS-CoV-2 reference strain-neutralizing titers in participants ≥6 months to <5 years of age	As measured at the central laboratory	at 1 month after Dose 4 for participants who received 3 prior doses of BNT162b2 3 µg and a fourth dose of bivalent BNT162b2 to Study C4591007 participants ≥6 months to <5 years of age who received 3 doses of BNT162b2 3 µg
SSB - noninferiority with respect to seroresponse rate to the reference strain in participants ≥6 months to <5 years of age	As measured at the central laboratory	at 1 month after Dose 4 for participants who received 3 prior doses of BNT162b2 3 µg and a fourth dose of bivalent BNT162b2 to Study C4591007 participants ≥6 months to <5 years of age who received 3 doses of BNT162b2 3 µg
SSD - geometric mean titers elicited by bivalent BNT162b2 given as a fourth dose in participants ≥5 to <12 years of age	As measured at the central laboratory	At baseline (before Dose 1) and 1 month after Dose 1
SSD - geometric mean fold rise elicited by bivalent BNT162b2 given as a fourth dose in participants ≥5 to <12 years of age	As measured at the central laboratory	At baseline (before Dose 1) and 1 month after Dose 1
SSD - percentages of participants with seroresponse elicited by bivalent BNT162b2 given as a fourth dose in participants ≥5 to <12 years of age	As measured at the central laboratory	At baseline (before Dose 1) and 1 month after Dose 1
SSA - Ph 1 dose finding, geometric mean fold rise elicited by prophylactic variant-adapted BNT162b2 at each dose level and variant vaccine type (if applicable) in COVID-19 vaccine-naïve participants ≥6 months to <5 years of age	As measured at the central laboratory	At baseline (before Dose 1), 1 month after Dose 2, and 1 month after Dose 3
SSA - Ph 1 dose finding, percentage of participants with seroresponse elicited by prophylactic variant-adapted BNT162b2 at each dose level and variant-adapted vaccine type in COVID-19 vaccine-naïve participants ≥6 months to <5 years of age	As measured at the central laboratory	At baseline (before Dose 1), 1 month after Dose 2, and 1 month after Dose 3
SSA - Ph 2/3, geometric mean titers elicited by variant-adapted BNT162b2 (Omicron XBB.1.5) in COVID-19 vaccine-naive participants ≥6 months to <5 years of age	As measured at the central laboratory	At baseline (before Dose 1), 1 month after Dose 1 (Groups 2 and 4), 1 month after Dose 2 (Group 1), and 1 month after Dose 3 (Group 3)
SSA - Ph 2/3, geometric mean fold rise elicited by variant-adapted BNT162b2 (Omicron XBB.1.5) in COVID-19 vaccine naive participants ≥6 months to <5 years of age	As measured at the central laboratory	At baseline (before Dose 1), 1 month after Dose 1 (Groups 2 and 4), 1 month after Dose 2 (Group 1), and 1 month after Dose 3 (Group 3)
SSA - Ph 2/3, percentages of participants with seroresponse elicited by variant-adapted BNT162b2 (Omicron XBB.1.5) in COVID-19 vaccine-naive participants ≥6 months to <5 years of age	As measured at the central laboratory	At baseline (before Dose 1), 1 month after Dose 1 (Groups 2 and 4), 1 month after Dose 2 (Group 1), and 1 month after Dose 3 (Group 3)
SSE - geometric mean titers elicited by BNT162b2 (Omicron XBB.1.5) given as a single 10 microgram dose in participants ≥5 to <12 years of age and as a single 30 microgram dose in Study C4591054 Substudy A participants ≥12 years of age	As measured at the central laboratory	At baseline (before Dose 1) and 1 month after Dose 1
SSE - geometric mean fold rise elicited by BNT162b2 (Omicron XBB.1.5) given as a single 10 microgram dose in participants ≥5 to <12 years of age and as a single 30 microgram dose in Study C4591054 Substudy A participants ≥12 years of age	As measured at the central laboratory	At baseline (before Dose 1) and 1 month after Dose 1
SSE - percentage of participants with seroresponse elicited by BNT162b2 (Omicron XBB.1.5) given as a single 10 microgram dose in participants ≥5 to <12 years of age and as a single 30 mcg dose in Study C4591054 Substudy A participants ≥12 years of age	As measured at the central laboratory	At baseline (before Dose 1) and 1 month after Dose 1

Collaborators and Investigators

• Sponsor: BioNTech SE
• Collaborators: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2022
• Primary Completion (Estimated): July 23, 2026
• Study Completion (Estimated): July 23, 2026

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Vaccine; Coronavirus; COVID-19; RNA Vaccine
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronaviridae Infections; Nidovirales Infections; COVID-19; Coronavirus Infections
• Other Study ID Numbers: C4591048; 2024-000001-33 (EudraCT Number); 2023-503736-40-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No