Phase 1
N=383
Safety and Effects of an Investigational COVID-19 Vaccine as Booster in Healthy People
SARS-CoV-2 Infection · COVID-19
Bottom Line
View on ClinicalTrials.gov: NCT05541861 ↗Enrolled (actual)
383
Serious AEs
1.8%
Results posted
Jan 2026
Primary outcome: Primary: Number of Participants With Solicited Local Reactions- Post Dose 1 — 30; 30; 29; 30 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg (Biological); BNT162b4 5 mcg (Biological); BNT162b4 10 mcg (Biological); BNT162b4 15 mcg (Biological); BNT162b4 30 mcg (Biological); BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- BioNTech SE
- Primary completion
- Nov 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Solicited Local Reactions- Post Dose 1 |
30; 30; 29; 30; 41; 33 | — |
| PRIMARY Number of Participants With Solicited Local Reactions- Post Dose 2 |
23; 18; 23; 29; 24; 11 | — |
| PRIMARY Number of Participants With Solicited Systemic Events- Post Dose 1 |
1; 0; 0; 2; 0; 0 | — |
| PRIMARY Number of Participants With Solicited Systemic Events- Post Dose 2 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Adverse Events (AEs)-Post Dose 1 |
11; 4; 8; 6; 8; 5 | — |
| PRIMARY Number of Participants With Adverse Events (AEs)-Post Dose 2 |
3; 9; 3; 5; 2; 2 | — |
| PRIMARY Number of Participants With Serious Adverse Events (SAEs)-Post Dose 1 |
0; 0; 1; 1; 0; 0 | — |
| PRIMARY Number of Participants With Serious Adverse Events (SAEs)-Post Dose 2 |
1; 0; 1; 1; 1; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters-Post Dose 1 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters-Post Dose 2 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Laboratory Abnormalities: Clinical Chemistry-Post Dose 1 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Laboratory Abnormalities: Clinical Chemistry-Post Dose 2 |
0; 0; 0; 1; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant New Electrocardiogram (ECG) Abnormalities -Post Dose 1 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant New ECG Abnormalities -Post Dose 2 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade 0 to Worst Grade >=3: Post-dose 1 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade 0 to Worst Grade >=3: Post Dose 2 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Shift of Laboratory Parameters (Clinical Chemistry) From Baseline Grade 0 to Worst Grade >=3: Post Dose 1 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Shift of Laboratory Parameters (Clinical Chemistry) From Baseline Grade 0 to Worst Grade >=3: Post-dose 2 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Ancestral Strain-Post Dose 1 |
3310.0; 4561.4; 3031.5; 6245.1; 3052.9; 2267.0 | — |
| SECONDARY Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Ancestral Strain-Post Dose 2 |
5940.9; 5717.3; 3559.2; 5751.4; 3862.0; 3551.6 | — |
| SECONDARY Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Omicron Strains (SARS-CoV-2 Omicron BA.4/BA.5)- Post Dose 1 |
881.7; 1475.9; 1125.3; 1948.8; 1067.2; 625.2 | — |
| SECONDARY Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Omicron Strains (SARS-CoV-2 Omicron BA.4/BA.5)- Post Dose 2 |
2597.0; 2502.1; 1750.6; 2089.7; 2179.6; 1663.4 | — |
| SECONDARY Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Omicron Strains (SARS-CoV-2 Omicron XBB1.5)- Post Dose 2 |
353.3; 356.8; 608.2; 335.2; 2493.1; 3325.2 | — |
| SECONDARY Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Ancestral Strain-Post Dose 1 |
3.4; 2.9; 3.3; 2.3; 3.4; 4.2 | — |
| SECONDARY Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Ancestral Strain-Post Dose 2 |
2.2; 2.0; 2.1; 2.6; 2.8 | — |
| SECONDARY Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Omicron Strain (OMI BA.4/BA.5)-Post Dose 1 |
5.4; 4.5; 4.4; 3.1; 5.8; 5.9 | — |
| SECONDARY Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Omicron Strain (OMI BA.4/BA.5)-Post Dose 2 |
4.4 | — |
| SECONDARY Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Omicron Strain (Omicron XBB1.5)-Post Dose 2 |
5.6; 7.8; 4.9; 6.5 | — |
| SECONDARY Percentage of Participants With Seroresponse to SARS-CoV-2 Ancestral Strain-Post Dose 1 |
32.5; 30.8; 35.7; 20.0; 38.5; 43.9 | — |
| SECONDARY Percentage of Participants With Seroresponse to SARS-CoV-2 Ancestral Strain-Post Dose 2 |
24.0; 16.0; 32.1; 23.1; 27.3 | — |
| SECONDARY Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strains (OMI BA.4/BA.5)- Post Dose 1 |
52.5; 46.2; 47.6; 30.0; 59.0; 61.0 | — |
| SECONDARY Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strains (OMI BA.4/BA.5)- Post Dose 2 |
44.0 | — |
| SECONDARY Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strains (SARS-CoV-2 Omicron XBB1.5)- Post Dose 2 |
64.0; 77.8; 50.0; 72.7 | — |
Summary
This was an exploratory Phase I, randomized, observer-blind, active-controlled, dose-escalation trial to evaluate four dose levels (DLs) of BNT162b4 given in combination with BNT162b2 Bivalent (original/Omicron BA.4/BA.5) to select a safe and tolerable dose and to evaluate BNT162b4 + BNT162b2 Bivalent (original/Omicron BA.4/BA.5) when given as Dose 1 and Dose 2 (booster) in Cohorts 1 and 2 and BNT162b4 + BNT162b2 Monovalent (OMI XBB.1.5) when given as Dose 2 (booster) in Cohorts 3a, 3b, 4a, and 4b, and 30 microgram (mcg) BNT162b4 when given alone as Dose 1 and Dose 2 in Cohort 5.
The trial used a staggered dosing process schema, i.e., enrollment into the next higher dose level was done sequentially and subject to safety data from the previous dose levels, with sentinel participants in Cohorts 1, 2, 3a, and 4a. Cohort 3b investigating the same dose level as cohort 3a but in participants aged >55 years was opened after safety data for participants aged 18-55 years in Cohort 3a had been reviewed. Enrollment into Cohorts 4a and 4b was opened after safety data for Cohort 3a and 3b had been reviewed. Cohort 5 participants were not randomized and received two doses of BNT162b4 alone after which a safety review was performed after all participants received Dose 2 in this cohort.
BNT162b4 plus BNT162b2 Bivalent (original/Omicron BA.4/BA.5)/Monovalent (OMI XBB.1.5) was co-administered (as a single injection).
BNT162b4 alone was administered as a single injection.
Eligibility Criteria
Inclusion Criteria (applicable to all dose groups unless specified otherwise):
- Had given informed consent by signing and dating the informed consent form (ICF) before initiation of any trial-specific procedures.
- Were willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions, e.g., to follow good practices to reduce their chances of being infected or spreading COVID-19, and other requirements of the trial. This included that they were able to understand and follow trial-related instructions.
- Were aged 18 years and older at randomization (Cohorts 1-4) or 18 to 55 years (Cohort 5), had a body mass index over 18.5 kg/m^2 and under 35 kg/m^2 (Cohorts 1-4) and under 30 kg/m^2 (Cohort 5), and weighed at least 50 kg at Visit 0.
- Were healthy, in the clinical judgment of the investigator based on participant-reported medical history data, and physical examination, 12-lead ECG, vital signs, and clinical laboratory test outcomes at Visit 0.
- Note: Healthy participants with pre-existing stable disease (e.g., obesity), defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 84 days before Visit 0, could be included.
- Agreed not to enroll in another trial with an IMP starting from Visit 0 and until 168 days (Cohorts 1-4) and 90 days (Cohort 5) after receiving the last IMP dose. Inclusion criteria pertaining to Dose 2 (Cohorts 1-4 only): If 168 days after the participant's first IMP dose had passed before they consented to Dose 2, they should have agreed to not enroll in another trial from the time of consent to Dose 2 until 168 days after receiving Dose 2 of the IMP.
- Agreed not to be vaccinated with:
- Non-trial vaccines (except COVID-19 vaccines, as per next sub-bullet) starting 28 days prior to the Dose 1 and until 28 days after receiving of the last IMP dose. Seasonal influenza vaccine is allowed; however, it should be given at least 14 days before or after any administration of IMP. Inclusion criteria pertaining to Dose 2 (Cohorts 1-4 only): If 28 days after the participant's first IMP dose had passed before they consented to continue Dose 2, they should not have been vaccinated with non-trial vaccines starting from the time of consent to Dose 2 and until 168 days after receiving the Dose 2 of the IMP.
- Non-trial COVID-19 vaccines starting at least 90 days prior to the Visit 1 and until completion of the participant's last trial visit (Cohorts 1-4) and until 28 days post-Dose 2 (Cohort 5 only).
- Had been vaccinated with at least three doses of an RNA-based COVID-19 vaccine authorized in the United States (US) before Visit 0. The last COVID-19 RNA vaccine dose must have been administered at least 90 days before Visit 1.
- Note: Documented confirmation of prior COVID-19 vaccine receipt must be obtained prior to randomization (Cohorts 1-4) or prior to Visit 1 (Cohort 5 only).
- Had negative human immunodeficiency virus (HIV) -1 and HIV-2 test results at Visit 0.
- Had negative Hepatitis B surface antigen test results at Visit 0.
- Had negative anti-Hepatitis C virus (HCV) antibodies, or negative HCV polymerase chain reaction test results if the anti-HCV was positive at Visit 0.
- Participants of childbearing potential (POCBP) that had a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test result at Visit 0 and negative urine pregnancy test results prior to receiving Dose 1, additionally for Cohort 5 only, a negative urine pregnancy test result prior to receiving Dose 2. Participants born female that were postmenopausal or permanently sterilized (verified by medical records) were not considered POCBP. Inclusion criteria pertaining to Dose 2 (Cohorts 1-4 only): POCBP that had a negative urine pregnancy test results prior to receiving Dose 2.
- POCBP who agreed to practice a highly effective form of contraception and required their male sexual partners to use condoms with a spermicidal agent, star
Data sourced from ClinicalTrials.gov (NCT05541861). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.