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

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05543616
• Other study ID #: C4591048
• Secondary ID: 2023-503736-40
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 23, 2022
• Est. completion date: August 11, 2025

Study information

• Verified date: May 2024
• Source: BioNTech SE
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 2 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3692
• Est. completion date: August 11, 2025
• Est. primary completion date: August 11, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 11 Years

Eligibility

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 =2 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.

Related Conditions & MeSH terms

• Coronavirus Infections
• COVID-19
• Severe Acute Respiratory Syndrome
• Severe Acute Respiratory Syndrome Coronavirus 2

Intervention

Biological:
• Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose
Injection in the muscle
• Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose
Injection in the muscle
• Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose
Injection in the muscle
• Variant-adapted BNT162b2 (Omicron XBB.1.5) Substudy A Ph 2/3 Selected Dose
Injection in the muscle
• Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram dose
Injection in the muscle
• Variant-adapted BNT162b2 (Omicron XBB.1.5) 6 microgram dose
Injection in the muscle
• Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose
injection in the muscle

Locations

Country	Name	City	State
Brazil	Consultoria em Controle de Infecção Hospitalar	Belo Horizonte	Minas Gerais
Brazil	Centro Médico São Francisco	Curitiba	Paraná
Brazil	Centro Médico São Francisco	Curitiba	Paraná
Brazil	Centro de Estudos e Pesquisa em Molestias Infecciosas - CPCLIN/RN	Natal	RIO Grande DO Norte
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	RIO Grande DO SUL
Brazil	Hospital de Clínicas de Porto Alegre - Escritório de Projetos e Parcerias Estratégicas	Porto Alegre	RIO Grande DO SUL
Brazil	Obras Sociais Irma Dulce	Salvador	Bahia
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto	SÃO Paulo
Brazil	CEPIC - Centro Paulista de Investigação Clínica	São Paulo
Puerto Rico	Clinical Research Puerto Rico	Guayama
Puerto Rico	University of Puerto Rico - Medical Sciences Campus	San Juan
South Africa	REIMED Reiger Park	Boksburg	Gauteng
South Africa	TREAD Research	Cape Town	Western CAPE
South Africa	Synergy Biomed Research Institute	East London	Eastern CAPE
South Africa	Newtown Clinical Research	Johannesburg	Gauteng
South Africa	University of Witwatersrand (WITS) - Vaccines and Infectious Diseases Analytics (VIDA)	Johannesburg	Gauteng
South Africa	Wits RHI	Johannesburg	Gauteng
South Africa	Wits VIDA Nkanyezi Research Unit	Johannesburg	Gauteng
South Africa	Perinatal HIV Research Unit (PHRU)	Klerksdorp	North-west
South Africa	Gole Biomed Research Centre	Polokwane	Limpopo
South Africa	Botho Ke Bontle Health Services	Pretoria	Gauteng
South Africa	Sandton Medical Research Centre	Sandton	Gauteng
United States	Advanced Research Center Inc.	Anaheim	California
United States	The Iowa Clinic, P.C.	Ankeny	Iowa
United States	Emory Children's Center	Atlanta	Georgia
United States	Emory Children's Center Illness Pod	Atlanta	Georgia
United States	Emory University Investigational Drug Service	Atlanta	Georgia
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Center for Immunization Research Inpatient Unit	Baltimore	Maryland
United States	Johns Hopkins Center for Immunization Outpatient Clinic	Baltimore	Maryland
United States	Meridian Clinical Research, LLC	Binghamton	New York
United States	UAB Child Health Research Unit (CHRU)	Birmingham	Alabama
United States	UAB Child Health Research Unit (CHRU)	Birmingham	Alabama
United States	Boston Medical Center	Boston	Massachusetts
United States	Boston medical Center (investigational Pharmacy Services, IP delivery)	Boston	Massachusetts
United States	Boston Medical Center Crosstown Building	Boston	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	SUNY Downstate Health Sciences University	Brooklyn	New York
United States	Coastal Pediatric Research	Charleston	South Carolina
United States	Coastal Pediatric Research	Charleston	South Carolina
United States	Atrium Health - Carolinas Medical Center	Charlotte	North Carolina
United States	Pediatric Research of Charlottesville, LLC	Charlottesville	Virginia
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Senders Pediatrics	Cleveland	Ohio
United States	Velocity Clinical Research, Cleveland	Cleveland	Ohio
United States	Centricity Research Columbus Ohio Multispecialty	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Cedar Health Research	Dallas	Texas
United States	Dayton Clinical Research	Dayton	Ohio
United States	PriMED Clinical Research	Dayton	Ohio
United States	Duke University - Main Hospital and Clinics	Durham	North Carolina
United States	Velocity Clinical Research, Providence	East Greenwich	Rhode Island
United States	Proactive Clinical Research, LLC	Edinburg	Texas
United States	Allegheny Health and Wellness Pavilion	Erie	Pennsylvania
United States	Northwest Arkansas Pediatric Clinic	Fayetteville	Arkansas
United States	ACRC TRIALS / Catalyst Physician Group / Frisco Medical Village	Frisco	Texas
United States	University of Texas Medical Branch	Galveston	Texas
United States	Tribe Clinical Research, LLC	Greenville	South Carolina
United States	Cyn3rgy Research	Gresham	Oregon
United States	Meridian Clinical Research, LLC	Hastings	Nebraska
United States	Indago Research & Health Center, Inc	Hialeah	Florida
United States	PediaClinic	Highlands Ranch	Colorado
United States	DM Clinical Research	Houston	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	Clinical Neuroscience Solutions, Inc. dba CNS Healthcare	Jacksonville	Florida
United States	Paradigm Clinical Research Centers, Inc	La Mesa	California
United States	Hoag Medical Group Foothill Ranch	Lake Forest	California
United States	Midwest Children's Health Research Institute	Lincoln	Nebraska
United States	Velocity Clinical Research, Lincoln	Lincoln	Nebraska
United States	Kaiser Permanente	Los Angeles	California
United States	Dr. Ruben Aleman and Associates	McAllen	Texas
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Acevedo Clinical Research Associates	Miami	Florida
United States	Bio-Medical Research LLC	Miami	Florida
United States	Virginia Research Center	Midlothian	Virginia
United States	Virginia Research Center	Midlothian	Virginia
United States	Saltzer Health	Nampa	Idaho
United States	Clinical Research Associates Inc	Nashville	Tennessee
United States	Rutgers Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Rutgers University	New Brunswick	New Jersey
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Yale University- Yale Center for Clinical Investigation	New Haven	Connecticut
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Alliance for Multispecialty Research, LLC	Newton	Kansas
United States	Kaiser Permanente Oakland	Oakland	California
United States	Kaiser Permanente Oakland	Oakland	California
United States	Children's Hospital & Medical Center	Omaha	Nebraska
United States	Accel Research Sites Network- Nona Pediatric Center	Orlando	Florida
United States	Clinical Neuroscience Solutions, Inc.	Orlando	Florida
United States	Clinical and Translational Research Unit (CTRU) & Spectrum Biobank	Palo Alto	California
United States	Center for Clinical Trials, LLC	Paramount	California
United States	SEC Clinical Research	Pensacola	Florida
United States	SEC Clinical Research	Pensacola	Florida
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	ACRC Trials (Administrative Site)	Plano	Texas
United States	SKY Integrative Medical Center/SKYCRNG	Ridgeland	Mississippi
United States	Rochester Clinical Research, LLC	Rochester	New York
United States	University of Rochester Medical Center	Rochester	New York
United States	Peninsula Research Associates	Rolling Hills Estates	California
United States	Kaiser Permanente Sacramento	Sacramento	California
United States	Kaiser Permanente Sacramento	Sacramento	California
United States	Paradigm Clinical Research, LLC	San Diego	California
United States	Kaiser Permanente Santa Clara	Santa Clara	California
United States	Kaiser Permanente Santa Clara	Santa Clara	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Seattle Children's- Building Cure	Seattle	Washington
United States	Louisiana State University Health Sciences Shreveport	Shreveport	Louisiana
United States	Asclepes Research Center - Spring Hill	Spring Hill	Florida
United States	Stanford University Medical Center	Stanford	California
United States	Coastal Pediatric Research	Summerville	South Carolina
United States	Coastal Pediatric Research	Summerville	South Carolina
United States	Alliance for Multispecialty Research, LLC	Syracuse	Utah
United States	PAS Research	Tampa	Florida
United States	PAS Research	Tampa	Florida
United States	Rophe Adult and Pediatric Medicine/SKYCRNG	Union City	Georgia
United States	Children's National Medical Center	Washington	District of Columbia
United States	Emerson Clinical Research Institute	Washington	District of Columbia
United States	Emerson Clinical Research Institute	Washington	District of Columbia
United States	Emerson Clinical Research Institute - Washington - Connecticut Avenue	Washington	District of Columbia
United States	Meridian Clinical Research, LLC	Washington	District of Columbia
United States	The Iowa Clinic	West Des Moines	Iowa
United States	The Iowa Clinic, P.C.	West Des Moines	Iowa
United States	Alliance for Multispecialty Research, LLC	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
BioNTech SE	Pfizer

Countries where clinical trial is conducted

United States,  Brazil,  Puerto Rico,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	SSA - Ph 2/3 selected dose, 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 5), Dose 2 (for Groups 1, 2, and 3), and Dose 3 (for Group 3)
Primary	SSA - Ph 2/3 selected dose, 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 5), Dose 2 (for Groups 1, 2, and 3), and Dose 3 (for Group 3)
Primary	SSA - Ph 2/3 selected dose, percentage of participants reporting adverse events	as elicited by investigational site staff	from Dose 1 to 1 month after the last dose
Primary	SSA - Ph 2/3 selected dose, percentage of participants reporting serious adverse events	as elicited by investigational site staff	from Dose 1 to 6 months after the last dose
Primary	SSA - Ph 2/3 selected dose, 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) at the selected dose (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
Primary	SSA - Ph 2/3 selected dose, 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) at the selected dose (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
Primary	SSA - Ph 2/3 selected dose, 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) at the selected dose 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
Primary	SSA - Ph 2/3 selected dose, 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) at the selected dose 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
Primary	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)
Primary	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)
Primary	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)
Primary	SSB - percentage of participants reporting serious adverse events	as elicited by investigational site staff	from Dose 1 to 6 months after the last dose
Primary	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
Primary	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
Primary	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
Primary	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
Primary	SSC - Ph 1 dose finding, percentage of participants reporting adverse events	as elicited by investigational site staff	1 month after Dose 1
Primary	SSC - Ph 1 dose finding, percentage of participants reporting serious adverse events	as elicited by investigational site staff	6 months after Dose 1
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	SSD - percentage of participants reporting adverse events	as elicited by investigational site staff	1 month after Dose 1
Primary	SSD - percentage of participants reporting serious adverse events	as elicited by investigational site staff	6 months after Dose 1
Primary	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
Primary	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
Primary	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
Primary	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
Primary	SSE - percentage of participants reporting adverse events	as elicited by investigational site staff	1 month after Dose 1
Primary	SSE - percentage of participants reporting serious adverse events	as elicited by investigational site staff	6 months after Dose 1
Primary	SSE - noninferiority with respect to ratio of the geometric mean of SARS-CoV-2 reference strain-neutralizing titers in participants =5 to <12 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 =5 to <12 years of age to 1 month after Dose 2 in Study C4591007 Phase 2/3 participants who received 2 doses of original BNT162b2 10 microgram
Primary	SSE - noninferiority with respect to seroresponse rate to the reference strain in participants =5 to <12 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 =5 to <12 years of age and at 1 month after Dose 2 in Study C4591007 Phase 2/3 participants who received 2 doses of original BNT162b2 10 microgram
Secondary	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
Secondary	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, 1 month after Dose 3, and 1 month after Dose 4
Secondary	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, 1 month after Dose 3, and 1 month after Dose 4
Secondary	SSA - Ph 2/3 selected dose, 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)
Secondary	SSA - Ph 2/3 selected dose, 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)
Secondary	SSA - Ph 2/3 selected dose, 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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	SSE - geometric mean titers elicited by BNT162b2 (Omicron XBB.1.5) given as a single dose in participants =2 to <12 years of age and by original BNT162b2 in Study C4591007 participants =2 to <12 years of age	As measured at the central laboratory	At baseline (before Dose 1), 1 month after Dose 1 for participants =2 to <12 years who received 1 dose BNT162b2 (Omi XBB.1.5), 1 month after Dose 3 for C4591007 participants =2 to <5 years, and 1 month after Dose 2 for C4591007 participants =5 to <12 yrs
Secondary	SSE - geometric mean fold rise elicited by BNT162b2 (Omicron XBB.1.5) given as a single dose in participants =2 to <12 years of age and by original BNT162b2 in Study C4591007 participants =2 to <12 years of age	As measured at the central laboratory	At baseline (before Dose 1), 1 month after Dose 1 for participants =2 to <12 years who received 1 dose BNT162b2 (Omi XBB.1.5), 1 month after Dose 3 for C4591007 participants =2 to <5 years, and 1 month after Dose 2 for C4591007 participants =5 to <12 yrs
Secondary	SSE - percentage of participants with seroresponse elicited by BNT162b2 (Omicron XBB.1.5) given as a single dose in participants =2 to <12 years of age and by original BNT162b2 in Study C4591007 participants =2 to <12 years of age	As measured at the central laboratory	At baseline (before Dose 1), 1 month after Dose 1 for participants =2 to <12 years who received 1 dose BNT162b2 (Omi XBB.1.5), 1 month after Dose 3 for C4591007 participants =2 to <5 years, and 1 month after Dose 2 for C4591007 participants =5 to <12 yrs

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