SARS-CoV-2 InfectionPhase 1NCT05541861
Safety and Effects of an Investigational COVID-19 Vaccine as Booster in Healthy People
A Phase 1 study testing BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg, BNT162b4 5 mcg and BNT162b4 10 mcg in people with SARS-CoV-2 Infection and COVID-19, run by BioNTech SE at 17 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- SARS-CoV-2 Infection, COVID-19
- What is being tested?
- BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg, BNT162b4 5 mcg and BNT162b4 10 mcg
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 383 participants
- Where
- 17 sitesUnited States
- Study dates
- 8 Nov 2022to 22 Nov 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants were eligible to receive Dose 2 if all of the following criteria (in addition to inclusion criteria above) apply:
- Had given informed consent by signing and dating the ICF reflecting the respective protocol version before administration of Dose 2.
- Had enrolled in a dose cohort and received Dose 1 of BNT162b4 + BNT162b2 Bivalent (original/Omicron BA.4/BA.5) in this trial.
- Were healthy in the opinion of the investigator based on a brief (symptom-directed) physical examination.
- Exclusion Criteria (applicable to all dose groups unless specified otherwise):
- Breastfeeding or intending to become pregnant starting with Visit 0 until 28 days after receiving the last dose of trial IMP or intending to father children starting with Visit 0 until 28 days after receiving the last trial IMP dose.
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- History of any severe adverse reactions to vaccines or to vaccine components and including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a participant who had an anaphylactic adverse reaction to pertussis vaccine as a child).
- Current or history of the following medical conditions:
- Uncontrolled or moderate or severe respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease); symptoms of asthma severity as defined in the most recent US National Heart, Lung, and Blood Institute asthma management guidelines.
- Diabetes mellitus type 1 or type 2, or new onset of Diabetes mellitus type 1 or 2 from the administration of Dose 1, including cases controlled with diet alone (Not excluded: history of isolated gestational diabetes).
- Hypertension:
- If a person had been found to have elevated blood pressure or hypertension during screening or previously, excluded for blood pressure that is not well controlled. Well controlled blood pressure was defined as consistently <=140 mm Hg systolic and <= 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤150 mm Hg systolic and ≤90 mm Hg diastolic at Visit 0.
- If a person did not have a history of elevated blood pressure or hypertension previously or during screening, also excluded for systolic blood pressure ≥150 mm Hg at Visit 0 or diastolic blood pressure ≥100 mm Hg at Visit 0. Exclusion pertaining to Dose 2 (all cohorts): Participants who had new onset of worsening hypertension since enrollment, that, in the opinion of the investigator would constitute an increased risk to the individual's participation in Dose 2 would not receive Dose 2.
- Any current or history of cardiovascular diseases such as myocarditis, pericarditis, myocardial infarction, symptomatic congestive heart failure, cardiomyopathy or clinically significant arrhythmias. Exclusion pertaining to Dose 2 (all cohorts): Participants who had new onset of cardiovascular disease since enrollment, that, in the opinion of the investigator would constitute an increased risk to the individual's participation in Dose 2 would not receive Dose 2.
- A diagnosed bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions). Exclusion pertaining to Dose 2 (all cohorts): Participants who had new onset of a bleeding disorder since enrollment, that, in the opinion of the investigator, would constitute an increased risk to the individual's participation in Dose 2 would not receive Dose 2.
- Seizure disorders: History of seizure(s) within the past 3 years. Also excluded if participant had used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
- Screening 12-lead ECG that was consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of the trial results. Exclusion pertaining to Dose 2 (all cohorts): Only symptomatic participants or whose clinical picture, in the opinion of the investigator, warrant ECG will have a repeat 12-lead ECG prior to Dose 2.
- Note: ECG changes including but not limited to: paroxysmal or sustained atrial or ventricular arrhythmias, atrioventricular block (grade 2-3) or bundle branch block, diffuse ST-segment elevation or PR-segment inversion, QTcF interval (QT interval corrected by the Fridericia formula) >450 ms in men and >460 ms in women, changes supporting myocardial infarction and/or myocardial ischemia. Exclusion pertaining to Dose 2 (all cohorts): Subjects who had a repeat ECG prior to Dose 2 and had a change or new onset that, in the opinion of the investigator, will not receive Dose 2.
- Current or history of major psychiatric illness, including but not limited to bipolar disorder, major depressive disorder, schizophrenia, autism, and attention deficit-hyperactivity disorder that could interfere with participation and follow-up as required by the trial protocol. Exclusion pertaining to Dose 2 (Cohorts 1-4): Participants who had a change or new onset psychiatric illness.
- Current or history of the following diseases associated with immune dysregulation:
- Primary immunodeficiencies.
- History of solid organ or bone marrow transplantation.
- Asplenia: any condition resulting in the absence of a functional spleen.
- Currently existing or history of autoimmune disease including and not limited to thyroid autoimmune disease, multiple sclerosis, or psoriasis. Exclusion pertaining to Dose 2 (Cohorts 1-4): Participants who had a change or new onset immunodeficiency.
- Received any non-trial IMP within 28 days before Visit 0 or Visit 7 (Cohorts 1-4) and (Cohort 5) within 28 days before Dose 1 and Dose 2 (except seasonal influenza vaccine, which should be given at least 14 days before or after any administration of IMP).
- Received or planned treatment throughout the entire trial with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are administered for >=14 days at a dose of >=20 mg/day of prednisone or equivalent), e.g., for cancer or an autoimmune disease, or planned receipt throughout this trial. Inhaled/nebulized (except high doses as per exclusion criteria above), intraarticular, intrabursal, or topical (skin or eyes) corticosteroids were permitted.
- Blood/plasma products and/or immunoglobulin containing therapy (including monoclonal antibodies) received:
- Cohorts 1-4: within 120 days before Visit 1 or Visit 7 or administration was planned starting at Visit 0 or prior to Visit 7 until 120 days after the last IMP administration in this trial.
- Cohort 5: within 120 days before dosing and prior to Dose 2 or administration is planned starting at Visit 0 or prior to Dose 2 until 90 days after the last IMP administration in this trial.
- Exclusion pertaining to Dose 2 (Cohorts 1-4): if 28 days after the participant's last IMP dose had passed before they consent to continue Dose 2, blood/plasma products and/or immunoglobulin containing therapy (including monoclonal antibodies) received within 120 days before Dose 2 of IMP (Visit 7) continuously until 120 days after receiving Dose 2 of IMP.
- Received allergy treatment with antigen injections within 28 days before Visit 1 or Visit 7 (Cohorts 1-4) and within 28 days before dosing (Cohort 5) or where allergy treatment with antigen injections were scheduled within 14 days after any visit with IMP administration in this trial.
- Participants with a history of SARS-CoV-2 infection (symptomatic or asymptomatic) <60 days prior to randomization.
- Have received any non-RNA or unauthorized COVID-19 vaccine, aside from Dose 1 of the current trial.
- Any existing condition which may affect IMP administration and/or assessment of local reactions assessment at the injection site, e.g., tattoos, severe scars, etc.
- Were vulnerable individuals as per International Council for Harmonisation (ICH) E6 definition, i.e., are individuals whose willingness to participate in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
- Any screening hematology and/or blood chemistry laboratory value that meets the definition of a Grade >=1 abnormality at Visit 0, or an abnormal C-reactive protein (identified by any method) or troponin I value.
- Note: Participants with any stable Grade 1 abnormalities (according to the toxicity grading scale) may be considered eligible at the discretion of the investigator. Gilberts disease, in and of itself, is not considered exclusionary. Exclusion pertaining to Dose 2: Only symptomatic participants or whose clinical picture, in the opinion of the investigator, warrant laboratory investigation, would have a repeat lab(s) prior to Dose 2.
- History of alcohol abuse or drug addiction within 1 year before Visit 0, or a history (within the past 5 years) of substance abuse or known medical, psychological, or social conditions which, in the opinion of the investigator, could compromise their wellbeing if they participate as participants in the trial, or that could prevent, limit, or confound the protocol-specified assessments.
Who cannot join
None listed.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Great Lakes Clinical Trials LLC - Andersonville
Chicago, Illinois, 60640
CTI Clinical Research Center
Cincinnati, Ohio, 45212
Cenexel RCA (Research Centers of America)
Hollywood, Florida, 33024
Alliance for Multispecialty Research, LLC (Kansas)
Kansas City, Missouri, 64114
Alliance for Multispecialty Research, LLC
Knoxville, Tennessee, 37909
Johnson County Clin-Trials, Inc. (JCCT)
Lenexa, Kansas, 66219
University of Kentucky Center for Clinical and Translational Science (outpatient clinic)
Lexington, Kentucky, 40536
Research Institute of South Florida, Inc.
Miami, Florida, 33173
Clinical Research Consulting, LLC
Milford, Connecticut, 06460
Hoag Hospital
Newport Beach, California, 92663
Finger Lakes Clinical Research
Rochester, New York, 14618
Clinical Trials of Texas, LLC / Flourish Research
San Antonio, Texas, 78229
Endeavor Clinical Trials, LLC
San Antonio, Texas, 78229
California Research Foundation
San Diego, California, 92123
Alliance for Multispecialty Research, LLC
Tempe, Arizona, 85281
DM Clinical Research
Tomball, Texas, 77375
Diablo Clinical Research, Inc.
Walnut Creek, California, 94598
About this study
Official title: An Exploratory Phase I, Randomized, Observer-blind, Active-controlled, Dose-escalation Trial Evaluating the Safety, Tolerability, and Immunogenicity of an Investigational RNA-based SARS-CoV-2 Vaccine in COVID-19 Vaccine Experienced Healthy Adults
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.
Read more
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.
- Conditions
- SARS-CoV-2 Infection, COVID-19
- Being tested
- BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg, BNT162b4 5 mcg, BNT162b4 10 mcg, BNT162b4 15 mcg, BNT162b4 30 mcg
- Keywords
- Ribonucleic acid (RNA) vaccine, Vaccine, Active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcgBiological
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
BNT162b4 5 mcgBiological
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
BNT162b4 10 mcgBiological
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
BNT162b4 15 mcgBiological
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
BNT162b4 30 mcgBiological
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
BNT162b2 Monovalent (OMI XBB.1.5) 30 mcgBiological
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: BNT162b2 Bivalent 30 mcg + BNT162b4 5 mcg (Aged 18-55 Years) | Experimental | Participants aged 18-55 years received an intramuscular injection of BNT162b2 Bivalent 30 mcg along with BNT162b4 5 mcg at Day 1. Receives: Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg; Biological: BNT162b4 5 mcg |
| Cohort 2: BNT162b2 Bivalent 30 mcg + BNT162b4 10 mcg (Aged 18-55 Years) | Experimental | Participants aged 18-55 years received an intramuscular injection of BNT162b2 Bivalent 30 mcg along with BNT162b4 10 mcg at Day 1. Participants who consented to receive a second dose of the study drugs received BNT162b2 Bivalent 30 mcg along with BNT162b4 10 mcg again as Dose 2 at 6 to 7 months after Dose 1. Receives: Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg; Biological: BNT162b4 10 mcg |
| Cohort 3a: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 15 mcg (Aged 18-55 Years) | Experimental | Participants aged 18-55 years received a dose of BNT162b2 Bivalent 30 mcg (Omicron BA.4/BA.5) along with BNT162b4 15 mcg at Day 1, Participants who consented to receive a second dose of the study drugs received BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg along with BNT162b4 15 mcg again as Dose 2 at 6 to 7 months after Dose 1. Receives: Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg; Biological: BNT162b4 15 mcg; Biological: BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg |
| Cohort 3b: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 15 mcg (Aged >55 Years) | Experimental | Participants aged >55 years received a dose of BNT162b2 Bivalent 30 mcg (Omicron BA.4/BA.5) along with BNT162b4 15 mcg at Day 1. Participants who consented to receive a second dose of the study drugs received BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg along with BNT162b4 15 mcg again as Dose 2 at 6 to 7 months after Dose 1. Receives: Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg; Biological: BNT162b4 15 mcg; Biological: BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg |
| Cohort 4a: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 30 mcg (Aged 18-55 Years) | Experimental | Participants aged 18-55 years received a dose of BNT162b2 Bivalent 30 mcg (Omicron BA.4/BA.5) along with BNT162b4 30 mcg at Day 1. Participants who consented to receive a second dose of the study drugs received BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg along with BNT162b4 30 mcg again as Dose 2 at 6 to 7 months after Dose 1. Receives: Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg; Biological: BNT162b4 30 mcg; Biological: BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg |
| Cohort 4b: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 30 mcg (Aged >55 Years) | Experimental | Participants aged >55 years received a dose of BNT162b2 Bivalent 30 mcg (Omicron BA.4/BA.5) along with BNT162b4 30 mcg at Day 1. Participants who consented to receive a second dose of the study drugs received BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg along with BNT162b4 30 mcg again as Dose 2 at 6 to 7 months after Dose 1. Receives: Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg; Biological: BNT162b4 30 mcg; Biological: BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg |
| Comparator A: BNT162b2 Bivalent 30 mcg (Aged 18-55 Years) | Active comparator | Participants aged 18-55 years received one intramuscular injection of BNT162b2 30 mcg at Day 1. Receives: Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg |
| Comparator B: BNT162b2 Bivalent 30 mcg (Aged >55 Years) | Active comparator | Participants aged >55 years received one intramuscular injection of BNT162b2 30 mcg at Day 1. Receives: Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg |
| Cohort 5: BNT162b4 30 mcg (Aged 18-55 Years) | Experimental | Participants aged 18-55 years received two intramuscular injections of BNT162b4 30 mcg at Day 1 and 2 months post-Dose 1, respectively. Receives: Biological: BNT162b4 30 mcg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Solicited Local Reactions- Post Dose 1
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) and pre-listed (that is, solicited) in the e-diary. Solicited local reactions included: pain, erythema/redness, and induration/swelling.
Measured: Up to 7 days post-dose1
Number of Participants With Solicited Local Reactions- Post Dose 2
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) and pre-listed (that is, solicited) in the e-diary. Solicited local reactions included: pain, erythema/redness, and induration/swelling. Data for this outcome measure was not collected and analyzed for Cohort 1, and Comparator Cohorts A and B, as these Cohorts did not receive Dose 2 of the study drugs.
Measured: Up to 7 days post-dose 2
Number of Participants With Solicited Systemic Events- Post Dose 1
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the e-diary. Solicited systemic reactions included: vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, and fever.
Measured: Up to 7 days post-dose 1
Number of Participants With Solicited Systemic Events- Post Dose 2
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the e-diary. Solicited systemic reactions included: vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, and fever.
Measured: Up to 7 days post-dose 2
Number of Participants With Adverse Events (AEs)-Post Dose 1
An AE was defined as any untoward medical occurrence in a participant administered with a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment.
Measured: Up to 28 days post-dose 1
Number of Participants With Adverse Events (AEs)-Post Dose 2
An AE was defined as any untoward medical occurrence in a participant administered with a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment.
Measured: Up to 28 days post-dose 2
Number of Participants With Serious Adverse Events (SAEs)-Post Dose 1
An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death and was life-threatening. It also included any event requiring hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, caused a congenital anomaly or birth defect, or any other event determined as SAE as per medical or scientific judgment.
Measured: Up to 6 to 7 months post-dose 1 for Cohorts 1 to 4 and Comparator Cohorts; and up to 2 months post-dose 1 for Cohort 5
Number of Participants With Serious Adverse Events (SAEs)-Post Dose 2
An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death and was life-threatening. It also included any event requiring hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, caused a congenital anomaly or birth defect, or any other event determined as SAE as per medical or scientific judgment.
Measured: Up to 6 to 7 months post-dose 2 for Cohorts 2 to 4; and up to 3 months post-dose 2 for Cohort 5
Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters-Post Dose 1
Participants with hematological abnormalities for basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils and platelets were analyzed and only clinically significant abnormal data was reported in the outcome measure.
Measured: At Day 3 post-Dose 1; at Day 7 post-dose 1
Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters-Post Dose 2
Participants with hematological abnormalities for basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils and platelets were analyzed and only clinically significant abnormal data was reported in the outcome measure.
Measured: At Day 7 post-dose 2
Number of Participants With Clinically Significant Laboratory Abnormalities: Clinical Chemistry-Post Dose 1
Participants with laboratory abnormalities (clinical chemistry) for alanine aminotransferase, albumin, alkaline phosphatase, amylase, aspartate aminotransferase, C-reactive protein, creatinine, direct bilirubin, gamma glutamyl transferase, glucose, high sensitivity C reactive protein, indirect bilirubin, lipase, total bilirubin, troponin I type 3 and urea nitrogen were analyzed and only abnormal clinically significant data was reported in the outcome measure.
Measured: At Day 3 post-Dose 1; at Day 7 post-dose 1
Number of Participants With Clinically Significant Laboratory Abnormalities: Clinical Chemistry-Post Dose 2
Participants with laboratory abnormalities (clinical chemistry) for alanine aminotransferase, albumin, alkaline phosphatase, amylase, aspartate aminotransferase, C-reactive protein, creatinine, direct bilirubin, gamma glutamyl transferase, glucose, high sensitivity C reactive protein, indirect bilirubin, lipase, total bilirubin, troponin I type 3 and urea nitrogen were analyzed and only clinically significant abnormal data was reported in the outcome measure.
Measured: At Day 7 post-dose 2
Number of Participants With Clinically Significant New Electrocardiogram (ECG) Abnormalities -Post Dose 1
Participants with only clinically significant new ECG abnormalities were reported in the outcome measure.
Measured: At Day 3 post-Dose 1; at Day 7 post-dose 1
Number of Participants With Clinically Significant New ECG Abnormalities -Post Dose 2
Participants with only clinically significant new ECG abnormalities were reported in the outcome measure.
Measured: At Day 7 post-dose 2
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade 0 to Worst Grade >=3: Post-dose 1
The intensity of AEs and laboratory parameters was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants with shift change from Baseline Grade 0 to Worst Grade >=3 were reported in the outcome measure.
Measured: At Day 3 post-dose 1; at Day 7 post-dose 1
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade 0 to Worst Grade >=3: Post Dose 2
The intensity of AEs and laboratory parameters was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants with shift change from Baseline Grade 0 to Worst Grade >=3 were reported in the outcome measure.
Measured: At Day 7 post-dose 2
Number of Participants With Shift of Laboratory Parameters (Clinical Chemistry) From Baseline Grade 0 to Worst Grade >=3: Post Dose 1
The intensity of AEs and laboratory parameters was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants with shift change from Baseline Grade 0 to Worst Grade >=3 were reported in the outcome measure.
Measured: At Day 3 post-dose 1; at Day 7 post-dose 1
Number of Participants With Shift of Laboratory Parameters (Clinical Chemistry) From Baseline Grade 0 to Worst Grade >=3: Post-dose 2
The intensity of AEs and laboratory parameters was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants with shift change from Baseline Grade 0 to Worst Grade >=3 were reported in the outcome measure.
Measured: At Day 7 post-dose 2
Secondary outcomes (15)
Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Ancestral Strain-Post Dose 1
GMTs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody ancestral strain were measured by valid assay method. Data for this outcome measure was not planned to be collected and analyzed for Cohort 5.
Measured: At Pre-dose and Day 28 post dose-1
Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Ancestral Strain-Post Dose 2
GMTs for SARS-CoV-2 neutralizing antibody ancestral strain were measured by valid assay method. Data for this outcome measure was not planned to be collected and analyzed for Cohort 5.
Measured: At Pre-dose 2 and Day 28 post-dose 2
Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Omicron Strains (SARS-CoV-2 Omicron BA.4/BA.5)- Post Dose 1
GMTs for SARS-CoV-2 Omicron BA.4/BA.5 strain were measured by valid assay method.
Measured: At Pre-dose and Day 28 post-dose 1
Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Omicron Strains (SARS-CoV-2 Omicron BA.4/BA.5)- Post Dose 2
GMTs for SARS-CoV-2 Omicron BA.4/BA.5 strain were measured by valid assay method. Data for this outcome measure was not planned to be collected and analyzed for Cohort 5.
Measured: At Pre-dose 2 and Day 28 post-dose 2
Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Omicron Strains (SARS-CoV-2 Omicron XBB1.5)- Post Dose 2
GMTs for SARS-CoV-2 Omicron XBB1.5 strain were measured by valid assay method.
Measured: At Pre-dose 2 and Day 28 post-dose 2
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Ancestral Strain-Post Dose 1
GMFRs are defined as ratios of the results after vaccination (that is 28 days post-dose 1) to the results before vaccination (that is pre-dose 1).
Measured: From pre-dose 1 to 28 days post-dose 1
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Ancestral Strain-Post Dose 2
GMFRs are defined as ratios of the results after vaccination (that is 28 days post-dose 2) to the results before vaccination (that is pre-dose 2). Data for this outcome measure was not planned to be collected and analyzed for Cohorts 1, 5 and Comparator Cohorts A and B.
Measured: From pre-dose 2 to 28 days post-dose 2
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Omicron Strain (OMI BA.4/BA.5)-Post Dose 1
GMFRs are defined as ratios of the results after vaccination (that is 28 days post-dose 1) to the results before vaccination (that is pre-dose 1).
Measured: From pre-dose 1 to 28 days post-dose 1
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Omicron Strain (OMI BA.4/BA.5)-Post Dose 2
GMFRs are defined as ratios of the results after vaccination (that is 28 days post-dose 2) to the results before vaccination (that is pre-dose 2).
Measured: From pre-dose 2 to 28 days post-dose 2
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Omicron Strain (Omicron XBB1.5)-Post Dose 2
GMFRs are defined as ratios of the results after vaccination (that is 28 days post-dose 2) to the results before vaccination (that is pre-dose 2).
Measured: From Pre-dose 2 to Day 28 post-dose 2
Percentage of Participants With Seroresponse to SARS-CoV-2 Ancestral Strain-Post Dose 1
Seroresponse was defined as achieving >=4-fold rise from baseline (that is, pre-dose).
Measured: At Day 28 post-dose 1
Percentage of Participants With Seroresponse to SARS-CoV-2 Ancestral Strain-Post Dose 2
Seroresponse was defined as achieving >=4-fold rise from baseline (that is, pre-dose).
Measured: At Day 28 post-dose 2
Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strains (OMI BA.4/BA.5)- Post Dose 1
Seroresponse was defined as achieving >=4-fold rise from baseline (that is, pre-dose).
Measured: At Day 28 post-dose 1
Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strains (OMI BA.4/BA.5)- Post Dose 2
Seroresponse was defined as achieving >=4-fold rise from baseline (that is, pre-dose).
Measured: At Day 28 post-dose 2
Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strains (SARS-CoV-2 Omicron XBB1.5)- Post Dose 2
Seroresponse was defined as achieving >=4-fold rise from baseline (that is, pre-dose).
Measured: At Day 28 post-dose 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2022
- Study start8 Nov 2022
- Primary completion22 Nov 2024
- Study completion22 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SARS-CoV-2 InfectionStudies of the same condition, open and under way.
- More trials run by BioNTech SEThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 383 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioNTech SE
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- BioNTech Responsible Person, Study director, BioNTech SE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05541861
- Sponsor's protocol ID
- BNT162-21
- Status last verified
- Dec 2025
- First submitted
- 14 Sep 2022
- Last updated
- 13 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Arieta CM, Xie YJ, Rothenberg DA, Diao H, Harjanto D, Meda S, Marquart K, Koenitzer B, Sciuto TE, Lobo A, Zuiani A, Krumm SA, Cadima Couto CI, Hein S, Heinen AP, Ziegenhals T, Liu-Lupo Y, Vogel AB, Srouji JR, Fesser S, Thanki K, Walzer K, Addona TA, Tureci O, Sahin U, Gaynor RB, Poran A. The T-cell-directed vaccine BNT162b4 encoding conserved non-spike antigens protects animals from severe SARS-CoV-2 infection. Cell. 2023 May 25;186(11):2392-2409.e21. doi: 10.1016/j.cell.2023.04.007. Epub 2023 Apr 13.
PubMed 37164012Wang CY, Peng WJ, Kuo BS, Ho YH, Wang MS, Yang YT, Chang PY, Shen YH, Hwang KP. Toward a pan-SARS-CoV-2 vaccine targeting conserved epitopes on spike and non-spike proteins for potent, broad and durable immune responses. PLoS Pathog. 2023 Apr 20;19(4):e1010870. doi: 10.1371/journal.ppat.1010870. eCollection 2023 Apr.
PubMed 37079651
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Phase I, Randomized, Observer-blind, Active-controlled, Dose-escalation Trial Evaluating the Safety, Tolerability, and Immunogenicity of an Investigational RNA-based SARS-CoV-2 Vaccine in COVID-19 Vaccine Experienced Healthy Adults
- ClinicalTrials.gov ID
- NCT05541861
- Acronym / sponsor ID
- BNT162-21
- Conditions
- SARS-CoV-2 Infection, COVID-19
- Keywords
- Ribonucleic acid (RNA) vaccine, Vaccine, Active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 383 participants (actual)
- Lead sponsor
- BioNTech SEIndustry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Study start
- 8 Nov 2022 (actual)
- Primary completion
- 22 Nov 2024 (actual)
- Study completion
- 22 Nov 2024 (actual)
- First posted
- 15 Sep 2022 (actual)
- Results
- Posted 13 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: BNT162b2 Bivalent 30 mcg + BNT162b4 5 mcg (Aged 18-55 Years) | Experimental | Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg, Biological: BNT162b4 5 mcgParticipants aged 18-55 years received an intramuscular injection of BNT162b2 Bivalent 30 mcg along with BNT162b4 5 mcg at Day 1. |
| Cohort 2: BNT162b2 Bivalent 30 mcg + BNT162b4 10 mcg (Aged 18-55 Years) | Experimental | Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg, Biological: BNT162b4 10 mcgParticipants aged 18-55 years received an intramuscular injection of BNT162b2 Bivalent 30 mcg along with BNT162b4 10 mcg at Day 1. Participants who consented to receive a second dose of the study drugs received BNT162b2 Bivalent 30 mcg along with BNT162b4 10 mcg again as Dose 2 at 6 to 7 months after Dose 1. |
| Cohort 3a: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 15 mcg (Aged 18-55 Years) | Experimental | Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg, Biological: BNT162b4 15 mcg, Biological: BNT162b2 Monovalent (OMI XBB.1.5) 30 mcgParticipants aged 18-55 years received a dose of BNT162b2 Bivalent 30 mcg (Omicron BA.4/BA.5) along with BNT162b4 15 mcg at Day 1, Participants who consented to receive a second dose of the study drugs received BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg along with BNT162b4 15 mcg again as Dose 2 at 6 to 7 months after Dose 1. |
| Cohort 3b: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 15 mcg (Aged >55 Years) | Experimental | Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg, Biological: BNT162b4 15 mcg, Biological: BNT162b2 Monovalent (OMI XBB.1.5) 30 mcgParticipants aged >55 years received a dose of BNT162b2 Bivalent 30 mcg (Omicron BA.4/BA.5) along with BNT162b4 15 mcg at Day 1. Participants who consented to receive a second dose of the study drugs received BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg along with BNT162b4 15 mcg again as Dose 2 at 6 to 7 months after Dose 1. |
| Cohort 4a: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 30 mcg (Aged 18-55 Years) | Experimental | Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg, Biological: BNT162b4 30 mcg, Biological: BNT162b2 Monovalent (OMI XBB.1.5) 30 mcgParticipants aged 18-55 years received a dose of BNT162b2 Bivalent 30 mcg (Omicron BA.4/BA.5) along with BNT162b4 30 mcg at Day 1. Participants who consented to receive a second dose of the study drugs received BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg along with BNT162b4 30 mcg again as Dose 2 at 6 to 7 months after Dose 1. |
| Cohort 4b: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 30 mcg (Aged >55 Years) | Experimental | Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg, Biological: BNT162b4 30 mcg, Biological: BNT162b2 Monovalent (OMI XBB.1.5) 30 mcgParticipants aged >55 years received a dose of BNT162b2 Bivalent 30 mcg (Omicron BA.4/BA.5) along with BNT162b4 30 mcg at Day 1. Participants who consented to receive a second dose of the study drugs received BNT162b2 Monovalent (OMI XBB.1.5) 30 mcg along with BNT162b4 30 mcg again as Dose 2 at 6 to 7 months after Dose 1. |
| Comparator A: BNT162b2 Bivalent 30 mcg (Aged 18-55 Years) | Active comparator | Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcgParticipants aged 18-55 years received one intramuscular injection of BNT162b2 30 mcg at Day 1. |
| Comparator B: BNT162b2 Bivalent 30 mcg (Aged >55 Years) | Active comparator | Biological: BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcgParticipants aged >55 years received one intramuscular injection of BNT162b2 30 mcg at Day 1. |
| Cohort 5: BNT162b4 30 mcg (Aged 18-55 Years) | Experimental | Biological: BNT162b4 30 mcgParticipants aged 18-55 years received two intramuscular injections of BNT162b4 30 mcg at Day 1 and 2 months post-Dose 1, respectively. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (38 listed)
- Participants were eligible to receive Dose 2 if all of the following criteria (in addition to inclusion criteria above) apply:
- Had given informed consent by signing and dating the ICF reflecting the respective protocol version before administration of Dose 2.
- Had enrolled in a dose cohort and received Dose 1 of BNT162b4 + BNT162b2 Bivalent (original/Omicron BA.4/BA.5) in this trial.
- Were healthy in the opinion of the investigator based on a brief (symptom-directed) physical examination.
- Breastfeeding or intending to become pregnant starting with Visit 0 until 28 days after receiving the last dose of trial IMP or intending to father children starting with Visit 0 until 28 days after receiving the last trial IMP dose.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcgAnti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection. | Biological | Cohort 1: BNT162b2 Bivalent 30 mcg + BNT162b4 5 mcg (Aged 18-55 Years), Cohort 2: BNT162b2 Bivalent 30 mcg + BNT162b4 10 mcg (Aged 18-55 Years), Cohort 3a: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 15 mcg (Aged 18-55 Years), Cohort 3b: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 15 mcg (Aged >55 Years), Cohort 4a: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 30 mcg (Aged 18-55 Years), Cohort 4b: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 30 mcg (Aged >55 Years), Comparator A: BNT162b2 Bivalent 30 mcg (Aged 18-55 Years), Comparator B: BNT162b2 Bivalent 30 mcg (Aged >55 Years) |
| BNT162b4 5 mcgAnti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection. | Biological | Cohort 1: BNT162b2 Bivalent 30 mcg + BNT162b4 5 mcg (Aged 18-55 Years) |
| BNT162b4 10 mcgAnti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection. | Biological | Cohort 2: BNT162b2 Bivalent 30 mcg + BNT162b4 10 mcg (Aged 18-55 Years) |
| BNT162b4 15 mcgAnti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection. | Biological | Cohort 3a: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 15 mcg (Aged 18-55 Years), Cohort 3b: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 15 mcg (Aged >55 Years) |
| BNT162b4 30 mcgAnti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection. | Biological | Cohort 4a: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 30 mcg (Aged 18-55 Years), Cohort 4b: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 30 mcg (Aged >55 Years), Cohort 5: BNT162b4 30 mcg (Aged 18-55 Years) |
| BNT162b2 Monovalent (OMI XBB.1.5) 30 mcgAnti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection. | Biological | Cohort 3a: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 15 mcg (Aged 18-55 Years), Cohort 3b: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 15 mcg (Aged >55 Years), Cohort 4a: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 30 mcg (Aged 18-55 Years), Cohort 4b: BNT162b2 Bivalent/Monovalent 30 mcg + BNT162b4 30 mcg (Aged >55 Years) |
Primary outcome
Number of Participants With Solicited Local Reactions- Post Dose 1
Time frame: Up to 7 days post-dose1
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) and pre-listed (that is, solicited) in the e-diary. Solicited local reactions included: pain, erythema/redness, and induration/swelling.
Number of Participants With Solicited Local Reactions- Post Dose 2
Time frame: Up to 7 days post-dose 2
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) and pre-listed (that is, solicited) in the e-diary. Solicited local reactions included: pain, erythema/redness, and induration/swelling. Data for this outcome measure was not collected and analyzed for Cohort 1, and Comparator Cohorts A and B, as these Cohorts did not receive Dose 2 of the study drugs.
Number of Participants With Solicited Systemic Events- Post Dose 1
Time frame: Up to 7 days post-dose 1
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the e-diary. Solicited systemic reactions included: vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, and fever.
Number of Participants With Solicited Systemic Events- Post Dose 2
Time frame: Up to 7 days post-dose 2
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the e-diary. Solicited systemic reactions included: vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, and fever.
Number of Participants With Adverse Events (AEs)-Post Dose 1
Time frame: Up to 28 days post-dose 1
An AE was defined as any untoward medical occurrence in a participant administered with a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment.
Number of Participants With Adverse Events (AEs)-Post Dose 2
Time frame: Up to 28 days post-dose 2
An AE was defined as any untoward medical occurrence in a participant administered with a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment.
Number of Participants With Serious Adverse Events (SAEs)-Post Dose 1
Time frame: Up to 6 to 7 months post-dose 1 for Cohorts 1 to 4 and Comparator Cohorts; and up to 2 months post-dose 1 for Cohort 5
An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death and was life-threatening. It also included any event requiring hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, caused a congenital anomaly or birth defect, or any other event determined as SAE as per medical or scientific judgment.
Number of Participants With Serious Adverse Events (SAEs)-Post Dose 2
Time frame: Up to 6 to 7 months post-dose 2 for Cohorts 2 to 4; and up to 3 months post-dose 2 for Cohort 5
An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death and was life-threatening. It also included any event requiring hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, caused a congenital anomaly or birth defect, or any other event determined as SAE as per medical or scientific judgment.
Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters-Post Dose 1
Time frame: At Day 3 post-Dose 1; at Day 7 post-dose 1
Participants with hematological abnormalities for basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils and platelets were analyzed and only clinically significant abnormal data was reported in the outcome measure.
Number of Participants With Clinically Significant Laboratory Abnormalities: Hematological Parameters-Post Dose 2
Time frame: At Day 7 post-dose 2
Participants with hematological abnormalities for basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils and platelets were analyzed and only clinically significant abnormal data was reported in the outcome measure.
Number of Participants With Clinically Significant Laboratory Abnormalities: Clinical Chemistry-Post Dose 1
Time frame: At Day 3 post-Dose 1; at Day 7 post-dose 1
Participants with laboratory abnormalities (clinical chemistry) for alanine aminotransferase, albumin, alkaline phosphatase, amylase, aspartate aminotransferase, C-reactive protein, creatinine, direct bilirubin, gamma glutamyl transferase, glucose, high sensitivity C reactive protein, indirect bilirubin, lipase, total bilirubin, troponin I type 3 and urea nitrogen were analyzed and only abnormal clinically significant data was reported in the outcome measure.
Number of Participants With Clinically Significant Laboratory Abnormalities: Clinical Chemistry-Post Dose 2
Time frame: At Day 7 post-dose 2
Participants with laboratory abnormalities (clinical chemistry) for alanine aminotransferase, albumin, alkaline phosphatase, amylase, aspartate aminotransferase, C-reactive protein, creatinine, direct bilirubin, gamma glutamyl transferase, glucose, high sensitivity C reactive protein, indirect bilirubin, lipase, total bilirubin, troponin I type 3 and urea nitrogen were analyzed and only clinically significant abnormal data was reported in the outcome measure.
Number of Participants With Clinically Significant New Electrocardiogram (ECG) Abnormalities -Post Dose 1
Time frame: At Day 3 post-Dose 1; at Day 7 post-dose 1
Participants with only clinically significant new ECG abnormalities were reported in the outcome measure.
Number of Participants With Clinically Significant New ECG Abnormalities -Post Dose 2
Time frame: At Day 7 post-dose 2
Participants with only clinically significant new ECG abnormalities were reported in the outcome measure.
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade 0 to Worst Grade >=3: Post-dose 1
Time frame: At Day 3 post-dose 1; at Day 7 post-dose 1
The intensity of AEs and laboratory parameters was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants with shift change from Baseline Grade 0 to Worst Grade >=3 were reported in the outcome measure.
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade 0 to Worst Grade >=3: Post Dose 2
Time frame: At Day 7 post-dose 2
The intensity of AEs and laboratory parameters was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants with shift change from Baseline Grade 0 to Worst Grade >=3 were reported in the outcome measure.
Number of Participants With Shift of Laboratory Parameters (Clinical Chemistry) From Baseline Grade 0 to Worst Grade >=3: Post Dose 1
Time frame: At Day 3 post-dose 1; at Day 7 post-dose 1
The intensity of AEs and laboratory parameters was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants with shift change from Baseline Grade 0 to Worst Grade >=3 were reported in the outcome measure.
Number of Participants With Shift of Laboratory Parameters (Clinical Chemistry) From Baseline Grade 0 to Worst Grade >=3: Post-dose 2
Time frame: At Day 7 post-dose 2
The intensity of AEs and laboratory parameters was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants with shift change from Baseline Grade 0 to Worst Grade >=3 were reported in the outcome measure.
15 secondary outcomes
Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Ancestral Strain-Post Dose 1
Time frame: At Pre-dose and Day 28 post dose-1
Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Ancestral Strain-Post Dose 2
Time frame: At Pre-dose 2 and Day 28 post-dose 2
Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Omicron Strains (SARS-CoV-2 Omicron BA.4/BA.5)- Post Dose 1
Time frame: At Pre-dose and Day 28 post-dose 1
Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Omicron Strains (SARS-CoV-2 Omicron BA.4/BA.5)- Post Dose 2
Time frame: At Pre-dose 2 and Day 28 post-dose 2
Geometric Mean Titers (GMTs) for SARS-CoV-2 Neutralizing Antibody Omicron Strains (SARS-CoV-2 Omicron XBB1.5)- Post Dose 2
Time frame: At Pre-dose 2 and Day 28 post-dose 2
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Ancestral Strain-Post Dose 1
Time frame: From pre-dose 1 to 28 days post-dose 1
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Ancestral Strain-Post Dose 2
Time frame: From pre-dose 2 to 28 days post-dose 2
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Omicron Strain (OMI BA.4/BA.5)-Post Dose 1
Time frame: From pre-dose 1 to 28 days post-dose 1
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Omicron Strain (OMI BA.4/BA.5)-Post Dose 2
Time frame: From pre-dose 2 to 28 days post-dose 2
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 Omicron Strain (Omicron XBB1.5)-Post Dose 2
Time frame: From Pre-dose 2 to Day 28 post-dose 2
Percentage of Participants With Seroresponse to SARS-CoV-2 Ancestral Strain-Post Dose 1
Time frame: At Day 28 post-dose 1
Percentage of Participants With Seroresponse to SARS-CoV-2 Ancestral Strain-Post Dose 2
Time frame: At Day 28 post-dose 2
Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strains (OMI BA.4/BA.5)- Post Dose 1
Time frame: At Day 28 post-dose 1
Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strains (OMI BA.4/BA.5)- Post Dose 2
Time frame: At Day 28 post-dose 2
Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strains (SARS-CoV-2 Omicron XBB1.5)- Post Dose 2
Time frame: At Day 28 post-dose 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37164012Arieta CM, Xie YJ, Rothenberg DA, Diao H, Harjanto D, Meda S, Marquart K, Koenitzer B, Sciuto TE, Lobo A, Zuiani A, Krumm SA, Cadima Couto CI, Hein S, Heinen AP, Ziegenhals T, Liu-Lupo Y, Vogel AB, Srouji JR, Fesser S, Thanki K, Walzer K, Addona TA, Tureci O, Sahin U, Gaynor RB, Poran A. The T-cell-directed vaccine BNT162b4 encoding conserved non-spike antigens protects animals from severe SARS-CoV-2 infection. Cell. 2023 May 25;186(11):2392-2409.e21. doi: 10.1016/j.cell.2023.04.007. Epub 2023 Apr 13.
- Derived from this study: PubMed 37079651Wang CY, Peng WJ, Kuo BS, Ho YH, Wang MS, Yang YT, Chang PY, Shen YH, Hwang KP. Toward a pan-SARS-CoV-2 vaccine targeting conserved epitopes on spike and non-spike proteins for potent, broad and durable immune responses. PLoS Pathog. 2023 Apr 20;19(4):e1010870. doi: 10.1371/journal.ppat.1010870. eCollection 2023 Apr.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
BioNTech Responsible Person study director
BioNTech SE
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BNT162b2 Bivalent (original/Omicron BA.4/BA.5) 30 mcg, BNT162b4 5 mcg and BNT162b4 10 mcg in people with SARS-CoV-2 Infection and COVID-19, run by BioNTech SE at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 38 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Solicited Local Reactions- Post Dose 1 (time frame: Up to 7 days post-dose1). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05541861, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2026.