Safety and Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People
Study Details
Study Description
Brief Summary
This is an exploratory Phase I, randomized, observer-blind, active-controlled, dose escalation trial to evaluate three dose levels (DLs) of BNT162b4 given in combination with BNT162b5 Bivalent (or BNT162b2 Bivalent) to select a safe and tolerable dose. There will be three observer-blind cohorts (1, 2, 3), each with two arms. The trial will use a staggered dosing process schema with sentinel participants in all cohorts. BNT162b4 plus BNT162b5 Bivalent (or BNT162b2 Bivalent) will be administered concomitantly (as a single injection).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg + BNT162b4 5 µg
|
Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Biological: BNT162b4 5 µg
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
|
| Experimental: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg + BNT162b4 10 µg
|
Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Biological: BNT162b4 10 µg
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
|
| Experimental: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg + BNT162b4 15 µg
|
Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Biological: BNT162b4 15 µg
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
|
| Active Comparator: BNT162b5 Bivalent or BNT612b2 Bivalent 30 µg
|
Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
|
Outcome Measures
Primary Outcome Measures
- Frequency of solicited local reactions at the injection site (pain, erythema/redness, induration/swelling) recorded up to 7 days after each dose [Up to 7 days after each dose]
- Frequency of solicited systemic events (vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills and fever) recorded up to 7 d after each dose [Up to 7 days after each dose]
- Proportion of participants with at least one adverse event (AE) occurring up to 28 days after each dose [Up to 28 days after each dose]
- Proportion of participants with at least one serious adverse event (SAE) occurring up to 6 months after their last dose [Up to 6 months after last dose]
- Percentage of participants with abnormal hematology and chemistry laboratory values 3 days (sentinel group only) and 7 days after each dose [Up to 7 days after each dose]
In participants receiving at least one dose of trial vaccine, the percentage of participants receiving each dose of trial vaccine per DL cohort.
- Percentage of participants with grading shifts in hematology and chemistry laboratory assessments between baseline and 3 days (sentinel group only) and 7 days after each dose [Up to 7 days after each dose]
In participants receiving at least one dose of trial vaccine, the percentage of participants receiving each dose of trial vaccine per DL cohort.
- Percentage of participants receiving each dose of trial vaccine per DL cohort with new electrocardiogram (ECG) abnormalities 3 days (sentinel group only) and 7 days after each dose [Up to 7 days after each dose]
In participants receiving at least one dose trial vaccine, the percentage of participants receiving each dose of trial vaccine per DL cohort. ECG abnormalities will be included that are consistent with probable or possible myocarditis or pericarditis as defined in the protocol.
Secondary Outcome Measures
- Geometric mean titer (GMT) at each time point [From Day 1 until Day 180]
For participants receiving each dose of trial vaccine per DL cohort. SARS-CoV-2 ancestral strain neutralizing titers and SARS-CoV-2 Omicron neutralizing titers (viral strains matching the antigen encoded by BNT162b5).
- Percentages of participants with sero response at each timepoint after each investigational medicinal product (IMP) dose [From Day 1 until Day 180]
For participants receiving each dose of trial vaccine per DL cohort. SARS-CoV-2 ancestral strain neutralizing titers and SARS-CoV-2 Omicron neutralizing titers (viral strains matching the antigen encoded by BNT162b5).
- Geometric mean fold rises (GMFRs) from baseline (pre-Dose 1) to each subsequent timepoint [From Day 1 until Day 180]
For participants receiving each dose of trial vaccine per DL cohort. SARS-CoV-2 ancestral strain neutralizing titers and SARS-CoV-2 Omicron neutralizing titers (viral strains matching the antigen encoded by BNT162b5).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Have given informed consent by signing and dating the informed consent form (ICF) before initiation of any trial-specific procedures.
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Are 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 includes that they are able to understand and follow trial-related instructions.
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Are aged 18 to 55 years at randomization, have a body mass index over 18.5 kg/m2 and under 35 kg/m2, and weigh at least 50 kg at Visit 0.
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Are healthy, in the clinical judgment of the investigator based on volunteer-reported medical history data, and physical examination, 12-lead ECG, vital signs, and clinical laboratory test outcomes at Visit 0.
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Note: Healthy volunteers 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, can be included.
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Agree not to enroll in another trial with an IMP starting from Visit 0 and until 168 days after receiving the last IMP dose.
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Agree not to be vaccinated with:
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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.
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Non-trial COVID-19 vaccines until 180 days after receiving of the last IMP dose.
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Have 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 4 months before Visit 1.
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Note: Documented confirmation of prior COVID-19 vaccine receipt must be obtained prior to randomization.
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Have negative human immunodeficiency virus (HIV) -1 and -2 test results at Visit 0.
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Have negative Hepatitis B surface antigen (HBsAg) test results at Visit 0.
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Have negative anti-Hepatitis C virus (HCV) antibodies, or negative HCV polymerase chain reaction (PCR) test results if the anti-HCV is positive at Visit 0.
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Volunteers of childbearing potential (VOCBP) that have 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. Volunteers born female that are postmenopausal or permanently sterilized (verified by medical records) will not be considered VOBCP.
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VOCBP who agree to practice a highly effective form of contraception and to require their male sexual partners to use condoms with a spermicidal agent, starting at Visit 0 and continuously until 28 days after receiving the last IMP dose.
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VOCBP who agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial, starting at Visit 0 and continuously until 28 days after receiving the last IMP dose.
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Men who are sexually active with partners of childbearing potential and who have not had a verified vasectomy (documented in medical records) that agree to use condoms with a spermicidal agent and to practice a highly effective form of contraception with their sexual partners born female during the trial, starting at Visit 0 and continuously until 28 days after receiving the last IMP dose.
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Men who are willing to refrain from sperm donation, starting at Visit 0 and continuously until 28 days after receiving the last IMP dose.
Exclusion Criteria:
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Breastfeeding or intending to become pregnant starting with Visit 0 until 28 days after receiving last dose or 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 such as antibiotics or lipids, etc., and including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had an anaphylactic adverse reaction to pertussis vaccine as a child).
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Current or history of the following medical conditions:
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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 Asthma Education and Prevention Program Expert Panel report.
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Diabetes mellitus type 1 or type 2, including cases controlled with diet alone (Not excluded: history of isolated gestational diabetes).
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Hypertension:
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If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well controlled blood pressure is 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.
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If a person does not have a history of elevated blood pressure or hypertension previously or during screening, also exclude for systolic blood pressure ≥150 mm Hg at Visit 0 or diastolic blood pressure ≥100 mm Hg at Visit 0.
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Any current or history of cardiovascular diseases such as myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias.
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A diagnosed bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
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Seizure disorder: History of seizure(s) within past 3 years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
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Screening 12-lead ECG that is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of the trial results.
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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.
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The following diseases associated with immune dysregulation:
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Primary immunodeficiencies.
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History of solid organ or bone marrow transplantation.
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Asplenia: any condition resulting in the absence of a functional spleen.
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Currently existing or history of autoimmune disease including and not limited to thyroid autoimmune disease, multiple sclerosis, or psoriasis.
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Received any non-trial IMP within 28 days before Visit 0.
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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, intraarticular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
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Blood/plasma products and/or immunoglobulin containing therapy (including monoclonal antibodies) received within 120 days before Visit 1 or administration is planned starting at Visit 0 until 120 days after the last IMP administration in this trial.
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Received allergy treatment with antigen injections within 28 days before Visit 1 or where allergy treatment with antigen injections are scheduled within 14 days after any visit with IMP administration in this trial.
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Participants with a history of SARS-CoV-2 infection (symptomatic or asymptomatic) <60 days prior to randomization.
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Have received any non-RNA or unauthorized COVID-19 vaccine.
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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.
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Are vulnerable individuals as per International Council for Harmonisation (ICH) E6 definition, i.e., are individuals whose willingness to volunteer 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.
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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 or troponin I value.
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Note: With the exception of bilirubin, participants with any stable Grade 1 abnormalities (according to the toxicity grading scale) may be considered eligible at the discretion of the investigator.
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- BioNTech SE
- Pfizer
Investigators
- Study Director: BioNTech Responsible Person, BioNTech SE
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BNT162-21