NCT05543616 - A Study to Learn About Variant-Adapted COVID-19 RNA Vaccine Candidate(s) in Healthy Children | Crick

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 11 YearsHealthy volunteers:

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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.

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: from Dose 1 to 6 months after the last dose

SSA - Ph 2/3, percentage of participants reporting local reactions

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Substudy B (SSB) - percentage of participants reporting local reactions

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Substudy C (SSC) - Ph 1 dose finding, percentage of participants reporting local reactions

Time frame: for up to 7 days following Dose 1

SSC - Ph 1 dose finding, percentage of participants reporting systemic events

Time frame: 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

Time frame: 1 month after Dose 1

SSC - Ph 1 dose finding, percentage of participants reporting serious adverse events

as elicited by investigational site staff

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: for up to 7 days following Dose 1

SSD - percentage of participants reporting adverse events

as elicited by investigational site staff

Time frame: 1 month after Dose 1

SSD - percentage of participants reporting serious adverse events

as elicited by investigational site staff

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: for up to 7 days following Dose 1

SSE - percentage of participants reporting adverse events

as elicited by investigational site staff

Time frame: from Dose 1 to 1 month after Dose 1

SSE - percentage of participants reporting serious adverse events

as elicited by investigational site staff

Time frame: 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

Time frame: 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

Time frame: 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 Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

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

Overview

Conditions

Interventions

Eligibility

Locations (96)

Outcomes

Primary Outcomes

Secondary Outcomes