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

Study Overview
=================
Brief 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.

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

Conditions
-----------------
SARS-CoV-2 Virus, Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19

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) Substudy A Ph 2/3 Selected 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


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 11 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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) | 
| 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) | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| SSE - percentage of participants reporting adverse events | as elicited by investigational site staff | 1 month after Dose 1 | 
| SSE - percentage of participants reporting serious adverse events | as elicited by investigational site staff | 6 months after Dose 1 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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) | 
| 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) | 
| 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) | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, Coronavirus, Vaccine, SARS-CoV-2, RNA Vaccine