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Bivalent BNT162b2 3 microgram dose

Phase 3

SARS-CoV-2 Virus | Monoclonal antibody | Infectious Disease |BioNTech SE|Last Updated: Aug 6, 2026

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Trial Design

CONTROLLEDDMC
Total Trials1
Total Enrollment4,338

FDA Designations

No designations recorded

Clinical trial landscape

Bivalent BNT162b2 3 microgram dose · 1 trial · 3 indications

Phase 3 1
NCT05543616A Study to Learn About Variant-Adapted COVID-19 RNA Vaccine Candidate(s) in Healthy ChildrenSARS-CoV-2 Virus
COMPLETED4,338 Analytics
PHASE3COMPLETED
A Study to Learn About Variant-Adapted COVID-19 RNA Vaccine Candidate(s) in Healthy Children
SARS-CoV-2 VirusUnlock trial analytics

Study Endpoints

Primary Endpoints

Substudy A (SSA) - Ph 1 dose finding, percentage of participants reporting local reactions
for up to 7 days following Dose 1, Dose 2, Dose 3 and Dose 4

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

SSA - Ph 1 dose finding, percentage of participants reporting systemic events
for up to 7 days following Dose 1, Dose 2, Dose 3 and Dose 4

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

SSA - Ph 1 dose finding, percentage of participants reporting adverse events
from Dose 1 to 1 month after Dose 3 and from Dose 4 to 1 month after Dose 4

as elicited by investigational site staff

SSA - Ph 1 dose finding, percentage of participants reporting serious adverse events
from Dose 1 to 6 months after the last dose

as elicited by investigational site staff

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

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

SSA - Ph 2/3, percentage of participants reporting systemic events
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)

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

SSA - Ph 2/3, percentage of participants reporting adverse events
from Dose 1 to 1 month after the last dose

as elicited by investigational site staff

SSA - Ph 2/3, percentage of participants reporting serious adverse events
from Dose 1 to 6 months after the last dose

as elicited by investigational site staff

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
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

As measured at the central laboratory

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
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

As measured at the central laboratory

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
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

As measured at the central laboratory

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
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

As measured at the central laboratory

Substudy B (SSB) - percentage of participants reporting local reactions
for up to 7 days following Dose 1 (for Groups 1, 2 and 3) and Dose 2 (for Group 1)

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

SSB - percentage of participants reporting systemic events
for up to 7 days following Dose 1 (for Groups 1, 2 and 3) and Dose 2 (for Group 1)

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

SSB - percentage of participants reporting adverse events
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)

as elicited by investigational site staff

SSB - percentage of participants reporting serious adverse events
from Dose 1 to 6 months after the last dose

as elicited by investigational site staff

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
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

As measured at the central laboratory

SSB - noninferiority with respect to seroresponse rate to the Omicron BA.4/BA.5 strain in participants ≥6 months to <5 years of age
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

As measured at the central laboratory

Substudy C (SSC) - Ph 1 dose finding, percentage of participants reporting local reactions
for up to 7 days following Dose 1

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

SSC - Ph 1 dose finding, percentage of participants reporting systemic events
for up to 7 days following Dose 1

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

SSC - Ph 1 dose finding, percentage of participants reporting adverse events
1 month after Dose 1

as elicited by investigational site staff

SSC - Ph 1 dose finding, percentage of participants reporting serious adverse events
6 months after Dose 1

as elicited by investigational site staff

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
At baseline (before Dose 1) and 1 month after Dose 1

As measured at the central laboratory

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
At baseline (before Dose 1) and 1 month after Dose 1

As measured at the central laboratory

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
At baseline (before Dose 1) and 1 month after Dose 1

As measured at the central laboratory

Substudy D (SSD) - percentage of participants reporting local reactions
for up to 7 days following Dose 1

pain at the injection site, redness, and swelling as self-reported on electronic diaries

SSD - percentage of participants reporting systemic events
for up to 7 days following Dose 1

fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries

SSD - percentage of participants reporting adverse events
1 month after Dose 1

as elicited by investigational site staff

SSD - percentage of participants reporting serious adverse events
6 months after Dose 1

as elicited by investigational site staff

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
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

As measured at the central laboratory

SSD - difference in percentages of participants with seroresponse to the Omicron BA.4/BA.5 strain in participants ≥5 to <12 years of age
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

As measured at the central laboratory

Substudy E (SSE) - percentage of participants reporting local reactions
for up to 7 days following Dose 1

pain at the injection site, redness, and swelling as self-reported on electronic diaries

SSE - percentage of participants reporting systemic events
for up to 7 days following Dose 1

fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries

SSE - percentage of participants reporting adverse events
from Dose 1 to 1 month after Dose 1

as elicited by investigational site staff

SSE - percentage of participants reporting serious adverse events
from Dose 1 to 6 months after Dose 1

as elicited by investigational site staff

SSE - Ratio of the geometric mean of SARS-CoV-2 Omicron XBB.1.5-neutralizing titers
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

As measured at the central laboratory

SSE - difference in percentage of participants with seroresponse to Omicron XBB.1.5
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

As measured at the central laboratory

Secondary Endpoints

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
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
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
At baseline (before Dose 1), 1 month after Dose 2, and 1 month after Dose 3
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposePREVENTION

Treatment Arms

ArmTypeDescription
3 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1)EXPERIMENTALInjection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3
6 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1)EXPERIMENTALInjection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3
10 microgram dose, 6 Months to <2 Years (Substudy A, Phase 1)EXPERIMENTALInjection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3
10 microgram dose, 6 Months to <2 Years (Substudy A, Phase 2/3, Group 1) - 0/8 week scheduleEXPERIMENTALInjection in the muscle at 0- and 8-weeks
10 microgram dose, 6 Months to <2 Years (Substudy A, Phase 2/3, Group 2) - 0/8 week scheduleEXPERIMENTALInjection in the muscle at 0- and 8-weeks
3 microgram dose, 6 Months to <4 Years 6 Months (Substudy B, Group 1)EXPERIMENTALInjection in the muscle, 2 doses 2 months apart
3 microgram dose, 6 Months to <5 Years (Substudy B, Group 2)EXPERIMENTALInjection in the muscle, 1 dose
3 microgram dose, 6 Months to <5 Years (Substudy B, Group 3)EXPERIMENTALInjection in the muscle, 1 dose
6 microgram dose, 6 Months to <2 Years (Substudy C, Phase 1)EXPERIMENTALInjection in the muscle, 1 dose
10 microgram dose, 6 Months to <2 Years (Substudy C, Phase 1)EXPERIMENTALInjection in the muscle, 1 dose
10 microgram dose, 5 to <12 Years (Substudy D, Group 1)EXPERIMENTALInjection in the muscle, 1 dose
10 microgram dose, 5 to <12 Years (Substudy D, Group 2)EXPERIMENTALInjection in the muscle, 1 dose
10 microgram dose, 5 to <12 Years (Substudy D, Group 3)EXPERIMENTALInjection in the muscle, 1 dose
3 microgram dose, 2 Years to <4 years 3 months (Substudy A, Phase 1)EXPERIMENTALInjection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3
6 microgram dose, 2 Years to <4 years 3 months (Substudy A, Phase 1)EXPERIMENTALInjection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3
10 microgram dose, 2 Years to <4 years 3 months (Substudy A, Phase 1)EXPERIMENTALInjection in the muscle at 0-, 3-, and 11-weeks and approximately 6-months post-Dose 3
6 microgram dose, 2 Years to <5 Years (Substudy C, Phase 1)EXPERIMENTALInjection in the muscle, 1 dose
10 microgram dose, 2 Years to <5 Years (Substudy C, Phase 1)EXPERIMENTALInjection in the muscle, 1 dose
3 microgram dose, 6 Months to <2 Years (Substudy A, Phase 2/3, Group 3) - 0/3/11 week scheduleEXPERIMENTALInjection in the muscle at 0-, 3-, and 11-weeks
10 microgram dose, 2 to <5 Years (Substudy A, Phase 2/3, Group 4) - Single doseEXPERIMENTALInjection in the muscle, 1 dose
10 microgram dose, 2 to <5 Years (Substudy A, Phase 2/3, Group 5) - Single doseEXPERIMENTALInjection in the muscle, 1 dose
10 microgram dose, 5 Years to <12 Years (Substudy E, Group 2)EXPERIMENTALInjection in the muscle, 1 dose
10 microgram dose, 6 months to <2 years (Substudy A Phase 2/3, Group 6) - 0/8 week scheduleEXPERIMENTALInjection in the muscle at 0- and 8-weeks

Interventions

NameTypeDescription
Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram doseBIOLOGICALInjection in the muscle
Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram doseBIOLOGICALInjection in the muscle
Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram doseBIOLOGICALInjection in the muscle
Variant-adapted BNT162b2 (Omicron XBB.1.5) 3 microgram doseBIOLOGICALInjection in the muscle
Variant-adapted BNT162b2 (Omicron XBB.1.5) 6 microgram doseBIOLOGICALInjection in the muscle
Variant-adapted BNT162b2 (Omicron XBB.1.5) 10 microgram doseBIOLOGICALinjection in the muscle
Variant-adapted BNT162b2 (Omicron KP.2) 10 microgram doseBIOLOGICALInjection in the muscle
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Eligibility Criteria

Age Range6 Months to 11 Years
SexALL
Healthy VolunteersYes
Study Sites96

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: * Previo...

Countries:United StatesBrazilMexicoPuerto RicoSouth Africa
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Recent Changes (Last 90 Days)

MEDIUMSep 6, 2026NCT05543616TRIAL_REMOVED: changed
MEDIUMSep 6, 2026NCT05543616TRIAL_REMOVED: changed
MEDIUMSep 6, 2026NCT05543616TRIAL_REMOVED: changed
HIGHAug 6, 2026NCT05543616Status: ACTIVE_NOT_RECRUITING → COMPLETED
HIGHAug 6, 2026NCT05543616Status: ACTIVE_NOT_RECRUITING → COMPLETED