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Safety and Immunogenicity of RNA-based Vaccines Against SARS-CoV-2 Variants in Healthy Participants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05004181
Recruitment Status : Recruiting
First Posted : August 13, 2021
Last Update Posted : September 21, 2022
Sponsor:
Information provided by (Responsible Party):
BioNTech SE

Brief Summary:
This trial consists of three parts, Part A, Part B, and Part C, and will evaluate the safety and immunogenicity of a third booster injection of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), and the safety and immunogenicity of a third booster injection of the monovalent vaccine BNT162b2 (B.1.617.2) or BNT162b2 (B.1.1.7), in participants who have received two doses of the parent vaccine BNT162b2 at 30 µg, at least 6 months after the second dose of BNT162b2. It will also evaluate the safety and immunogenicity of a three-dose regimen of BNT162b2 (B.1.1.7 + B.1.617.2) in participants who have not received prior Coronavirus Disease 2019 (COVID-19) vaccination. In addition, the safety and immunogenicity of BNT162b2 (B.1.1.529) or BNT162b2 given as a third or fourth vaccine dose to RNA COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection will be evaluated and contrasted with the natural immune response reached after infection with the SARS-CoV-2 Omicron variant.

Condition or disease Intervention/treatment Phase
SARS-CoV2 Infection COVID-19 SARS-CoV-2 Acute Respiratory Disease SARS (Disease) Biological: BNT162b2 Biological: BNT162b2 (B.1.1.7 + B.1.617.2) Biological: BNT162b2 (B.1.1.7) Biological: BNT162b2 (B.1.617.2) Biological: BNT162b2 (B.1.1.529) Other: Observational Phase 2

Detailed Description:
Trial participants in Part A will be assigned to one of 6 cohorts (Cohort 1-6). Trial participants in Part B will be assigned to one of 3 cohorts (Cohort 1, 4, and 6). Trial participants in Part C will be randomized in a 2:2:1 ratio into 3 cohorts (Cohort 7-9).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1470 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase II Trial to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Monovalent and Multivalent RNA-based Vaccines in Healthy Subjects
Actual Study Start Date : August 25, 2021
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
Experimental: Part A - Cohort 1: 18 to 55 years of age
Participants will receive 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
Intramuscular (IM)

Experimental: Part A - Cohort 2: 18 to 55 years of age
Participants will receive 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
Intramuscular (IM)

Experimental: Part A - Cohort 3: 18 to 55 years of age
Participants will receive 1 dose of BNT162b2 (B.1.1.7) of 30 µg.
Biological: BNT162b2 (B.1.1.7)
Intramuscular (IM)

Experimental: Part A - Cohort 4: 18 to 55 years of age
Participants will receive 1 dose of BNT162b2 (B.1.617.2) of 30 µg.
Biological: BNT162b2 (B.1.617.2)
Intramuscular (IM)

Experimental: Part A - Cohort 5: 18 to 55 years of age
Participants will receive 1 dose of BNT162b2 of 30 µg.
Biological: BNT162b2
Intramuscular (IM)

Experimental: Part A - Cohort 6: 18 to 55 years of age
Participants will receive 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
Intramuscular (IM)

Experimental: Part B - Cohort 1: 18 to 85 years of age
Participants will receive 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
Intramuscular (IM)

Experimental: Part B - Cohort 4: 18 to 85 years of age
Participants will receive 1 dose of BNT162b2 (B.1.617.2) of 30 µg.
Biological: BNT162b2 (B.1.617.2)
Intramuscular (IM)

Experimental: Part B - Cohort 6: 18 to 85 years of age
Participants will receive 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.
Biological: BNT162b2 (B.1.1.7 + B.1.617.2)
Intramuscular (IM)

Experimental: Part C - Cohort 7: 18 to 85 years of age
Participants will receive 1 dose of BNT162b2 (B.1.1.529) of 30 µg.
Biological: BNT162b2 (B.1.1.529)
Intramuscular (IM)

Experimental: Part C - Cohort 8: 18 to 85 years of age
Participants will receive 1 dose of BNT162b2 of 30 µg.
Biological: BNT162b2
Intramuscular (IM)

Part C - Cohort 9: 18 to 85 years of age
Participants will receive no vaccination within 3 months after Visit 1.
Other: Observational
No vaccination within 3 months after Visit 1.




Primary Outcome Measures :
  1. All parts - Percentage of participants reporting local reactions at the injection site [ Time Frame: up to 7 days after each dose ]
    Local reactions (pain, tenderness, erythema/redness, induration/swelling).

  2. All parts - Percentage of participants reporting systemic events [ Time Frame: up to 7 days after each dose ]
    Systemic events (fever, fatigue, headache, chills, vomiting, nausea, diarrhea, new or worsened muscle pain, and new or worsened joint pain).

  3. Part A and C - Percentage of participants reporting adverse events (AEs) [ Time Frame: Dose 1 up to 1 month after the last dose ]
  4. All parts - Percentage of participants reporting serious adverse events (SAEs) [ Time Frame: Dose 1 up to 6 months after the last dose ]
  5. Part B - Percentage of participants reporting adverse events (AEs) [ Time Frame: Dose 1 up to 1 month after each dose ]
  6. Part B - Geometric mean ratio (GMR) of B.1.1.7 [ Time Frame: 1 month ]
    GMR of B.1.1.7 neutralizing titers (NT) 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial.

  7. Part B - GMR of B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
  8. Part B - GMR of B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
  9. Part B - The difference in Seroresponse (SR) to B.1.1.7 [ Time Frame: 1 month ]
    The difference in SR to B.1.1.7 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial.

  10. Part B - The difference in SR to B.1.617.2 [ Time Frame: 1 month ]
    The difference in SR to B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial.

  11. Part B - The difference in SR to B.1.617.2 NT 1 month after 1 dose of BNT162b2 (B.1.617.2) on BNT162b2-experienced participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
  12. Part B - GMR of B.1.1.7 NT 1 month after 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
  13. Part B - GMR of B.1.617.2 NT 1 month after 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
  14. Part B - The difference in SR to B.1.1.7 NT 1 month after 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02 / C4591001 trial [ Time Frame: 1 month ]
  15. Part B - The difference in SR to B.1.617.2 NT 1 month after 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) on BNT162b2-naïve participants to the reference strain NT 1 month after 2 doses of BNT162b2 in participants from the Phase III BNT162-02/C4591001 trial [ Time Frame: 1 month ]
  16. Part C - GMR of B.1.1.529 NT 1 month after one dose of BNT162b2 (B.1.1.529) in RNA-based COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection to those at 1 month after one dose of BNT162b2 for Cohorts 7 and 8. [ Time Frame: 1 month ]
  17. Part C - The difference in SR of B.1.1.529 NT 1 month after one dose of BNT162b2 (B.1.1.529) in RNA-based COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection to those at 1 month after one dose of BNT162b2 for Cohorts 7 and 8. [ Time Frame: 1 month ]

Secondary Outcome Measures :
  1. Part A - Geometric mean titer (GMT) [ Time Frame: Day 1 up to Day 421 ]
    For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and variant(s) of concern (VOC) specific NT.

  2. Part A - Geometric mean fold rises (GMFR) from before vaccination to each subsequent time point after vaccination [ Time Frame: Day 1 to Day 421 ]
    For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT.

  3. Part A - SR in terms of NT at each post vaccination time point [ Time Frame: Day 1 to Day 421 ]
    For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT.

  4. Part B - GMT - B.1.1.7 + B.1.617.2 vs BNT162b2 [ Time Frame: Day 1 to Day 360 ]

    VOC and reference strain-specific NTs in participants from the BNT162-17 trial and reference strain NTs in participants from the Phase III BNT162-02 / C4591001 trial (BNT162b2-experienced participants).

    GMTs and SRs of reference strain NT 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) and dose 2 of BNT162b2.


  5. Part B - GMT - B.1.617.2 vs BNT162b2 [ Time Frame: Day 1 to Day 360 ]

    VOC and reference strain-specific NTs in participants from the BNT162-17 trial and reference strain NTs in participants from the Phase III BNT162-02 / C4591001 trial (BNT162b2-experienced participants).

    GMTs and SRs of reference strain NT 1 month after 1 dose of BNT162b2 (B.1.617.2) and dose 2 of BNT162b2.


  6. Part B - GMT - B.1.1.7 + B.1.617.2 to the reference strain [ Time Frame: Day 1 to Day 386 ]

    VOC and reference strain NTs in participants from the BNT162-17 trial and reference strain NTs in participants from the Phase III BNT162-02 / C4591001 trial (BNT162b2-naïve participants).

    GMTs and SRs of VOCs and reference strain NT 1 month after dose 2 and dose 3 of BNT162b2 (B.1.1.7 + B.1.617.2).


  7. Part C - GMT - B.1.1.529 or BNT162b2 or a post SARS-CoV-2 infection [ Time Frame: Day 1 to Day 360 ]
    VOC NT in RNA-based COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection at baseline and 7 days, 1 month, and 3 months after the trial start for Cohorts 7, 8, and 9, and 6 and 12 months after the trial start for Cohorts 7 and 8.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Have given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
  • Volunteers who at the time of consent are:
  • Part A: 18 to 55 years old.
  • Part B and Part C: 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 85 years old).
  • For Cohorts 1 to 5: In Part A, who have received BNT162b2 vaccine (30 µg, two-dose regimen) in either a clinical trial or as part of the governmental vaccination programs at least 6 months before Visit 0. Participants who are currently enrolled in the Phase III BNT162-02 / C4591001 trial, have already been unblinded, and have previously received two doses of BNT162b2 at least 6 months earlier can be included (for Cohorts 1 and 4 in Part B, prior enrollment and dosing in the BNT162-02 / C4591001 trial is mandatory). At enrollment into Part B of this trial, their participation in the BNT162-02 / C4591001 trial will be terminated. Participants should have not experienced COVID-19 based on medical history.
  • For Cohort 6: Are COVID-19 vaccine-naïve and have not experienced COVID-19 based on their medical history.
  • Are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other trial procedures.
  • Are overall healthy at Visit 0 in the clinical judgment of the investigator based on the medical history, clinical assessment (including physical examination, vital signs, blood and urine clinical laboratory tests, 12-lead electrocardiogram (ECG), and oral swab for Nucleic Acid Amplification-based Test (NAAT)-based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing).
  • Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 12 weeks before Visit 0, can be included.
  • Note: Volunteers who had hepatitis C (HCV) infection, but have completed curative treatment based on the medical history can be included. Volunteers who had or have hepatitis B (HBV) or human immunodeficiency virus (HIV) based on the medical history cannot be included.
  • Agree not to enroll in another trial of an Investigational Medicinal Product (IMP), starting after Visit 0 and continuously until the last planned visit in this trial.
  • Women of childbearing potential (WOCBP) must test negative in a urine beta-human chorionic gonadotropin (β-HCG) test at Visits 0 and 1.
  • WOCBP must agree to practice a highly effective form of contraception starting at Visit 0 and continuously until 28 days after their last IMP administration in this trial.
  • WOCBP must confirm that they practiced an acceptable form of contraception for the 14 days prior to Visit 0.
  • WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.
  • Men who are sexually active with a WOCBP and have not had a vasectomy must agree to use a highly effective form of contraception with their female partner of childbearing potential starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.
  • Men must be willing to refrain from sperm donation, starting after Visit 0 and continuously until 28 days after their last vaccination.
  • For Part C, Cohorts 7, 8, and 9: have received two or three documented doses of any authorized COVID-19 RNA-based vaccine (e.g., BNT162b2 [Comirnaty] or the Moderna vaccine [Spikevax]) prior to being diagnosed with SARS-CoV-2 infection from January 2022 onwards (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections).
  • Note: The interval between the last COVID-19 RNA-based vaccine administered and randomization should be >4 months. The latest prior diagnosed SARS-CoV-2 infection should be at least 2 months before randomization. The latest SARS-CoV-2 infection should be documented with a result from a NAAT (as a preferable option). In case no historic NAAT result is available proving prior SARS-CoV-2 infection, the local positive result of SARS-CoV-2 N-binding antibodies done at screening will be sufficient.

Exclusion Criteria:

  • Any existing condition which may affect vaccine injection and/or assessment of local reactions assessment, e.g., tattoos, severe scars, etc.
  • Any bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that, in the investigator's judgment, make the participant inappropriate for the trial.
  • Any current febrile illness (body temperature ≥38.0°C/≥100.4°F) or other acute illness within 48 h prior to Day 1/IMP injection in this trial.
  • Any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias.
  • History of COVID-19 and/or clinical (based on COVID-19 symptoms/signs alone, if a SARS CoV 2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS CoV 2 NAAT result) evidence of prior infection with SARS CoV 2 at screening (Visit 0).
  • Note: not applicable for Part C.
  • History of Guillain-Barré syndrome.
  • Known or suspected immunodeficiency.
  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the trial IMPs.
  • History or known allergy, hypersensitivity, or intolerance to the trial IMP including any excipients of the IMPs in this trial.
  • Have received any SARS CoV 2 vaccination other than BNT162b2 (30 µg BNT162b2 given as a course of two doses approximately 21 days apart).
  • Note: not applicable for Part C.
  • Have received a live or live attenuated vaccine within 28 days prior to Day 1/IMP injection.
  • Have received any other vaccines within 14 days before or after any IMP injection, e.g., influenza, tetanus, pneumococcal, hepatitis A or B. When possible standard or care vaccinations should be planned with the trial IMP administrations in mind.
  • Individuals who receive treatment 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, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
  • Receipt of blood/plasma products or immunoglobulin, from 60 days before IMP administration or planned receipt throughout this trial.
  • Participation in other trials involving IMP within 28 days or 5 half-lives (whichever is longer) prior to Visit 1 and/or during trial participation, besides participation in trials with BNT162b2.
  • Are pregnant or breastfeeding or are planning pregnancy within 28 days after last IMP treatment.
  • Are vulnerable individuals as per International Conference on 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.
  • For Part C, Cohorts 7, 8, and 9: Vaccination with other non-RNA or unauthorized COVID-19 vaccines.
  • For Part C, Cohorts 7, 8, and 9: Vaccination with any COVID-19 vaccine after SARS-CoV-2 infection from January 2022 onwards (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05004181


Contacts
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Contact: BioNTech clinical trials patient information +49 6131 9084 ext 0 patients@biontech.de

Locations
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Sponsors and Collaborators
BioNTech SE
Investigators
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Study Director: BioNTech Responsible Person BioNTech SE
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Responsible Party: BioNTech SE
ClinicalTrials.gov Identifier: NCT05004181    
Other Study ID Numbers: BNT162-17
2021-003458-22 ( EudraCT Number )
First Posted: August 13, 2021    Key Record Dates
Last Update Posted: September 21, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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COVID-19
Respiration Disorders
Respiratory Tract Diseases
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases