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

BioNTech

Status and phase: Enrolling; Phase 3; Phase 2

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

Treatments: Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram dose; Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 6 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 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) 10 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT05543616

C4591048

2023-503736-40 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 3,692 estimated patients

Sex: All

Ages: 6 months to 11 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

3,692 participants in 23 patient groups

3 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1)

Experimental group

Description:

Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3

Treatment:

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram dose

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose

6 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1)

Experimental group

Description:

Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 6 microgram dose

10 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1)

Experimental group

Description:

Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose

Selected dose, 6 Months to <2 Years (Substudy A, Phase 2/3, Group 1) - 0/8 week schedule

Experimental group

Description:

Injection in the muscle at 0- and 8-weeks

Treatment:

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) Substudy A Ph 2/3 Selected Dose

Selected dose, 6 Months to <2 Years (Substudy A, Phase 2/3, Group 2) - 0/8 week schedule

Experimental group

Description:

Injection in the muscle at 0- and 8-weeks

Treatment:

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) Substudy A Ph 2/3 Selected Dose

3 microgram dose, 6 Months to <4 Years 6 Months (Substudy B, Group 1)

Experimental group

Description:

Injection in the muscle, 2 doses 2 months apart

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose

3 microgram dose, 6 Months to <5 Years (Substudy B, Group 2)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose

3 microgram dose, 6 Months to <5 Years (Substudy B, Group 3)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose

6 microgram dose, 6 Months to <2 Years (Substudy C, Phase 1)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose

10 microgram dose, 6 Months to <2 Years (Substudy C, Phase 1)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose

10 microgram dose, 5 to <12 Years (Substudy D, Group 1)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose

10 microgram dose, 5 to <12 Years (Substudy D, Group 2)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose

10 microgram dose, 5 to <12 Years (Substudy D, Group 3)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose

3 microgram dose, 2 Years to <4 years 3 months (Substudy A, Phase 1)

Experimental group

Description:

Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3

Treatment:

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram dose

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose

6 microgram dose, 2 Years to <4 years 3 months (Substudy A, Phase 1)

Experimental group

Description:

Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 6 microgram dose

10 microgram dose, 2 Years to <4 years 3 months (Substudy A, Phase 1)

Experimental group

Description:

Injection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose

6 microgram dose, 2 Years to <5 Years (Substudy C, Phase 1)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose

10 microgram dose, 2 Years to <5 Years (Substudy C, Phase 1)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose

3 microgram dose, 6 Months to <2 Years (Substudy A, Phase 2/3, Group 3) - 0/3/11 week schedule

Experimental group

Description:

Injection in the muscle at 0-, 3-, and 11-weeks

Treatment:

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram dose

Selected dose, 2 to <5 Years (Substudy A, Phase 2/3, Group 4) - Single dose

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) Substudy A Ph 2/3 Selected Dose

Selected dose, 2 to <5 Years (Substudy A, Phase 2/3, Group 5) - Single dose

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) Substudy A Ph 2/3 Selected Dose

3 microgram dose, 2 Years to <5 Years (Substudy E, Group 1)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram dose

10 microgram dose, 5 Years to <12 Years (Substudy E, Group 2)

Experimental group

Description:

Injection in the muscle, 1 dose

Treatment:

Biological: Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram dose