A Trial Investigating the Safety and Effects of Four BNT162 Vaccines Against COVID-19 in Healthy and Immunocompromised Adults

NCT04380701 | Completed Phase 1 Results

• 3 other identifiers: BNT162-012020-001038-36U1111-1249-4220
• Study Type: interventional
• Target: 512
• Locations: 1 country
• Sites: 5

Brief Summary

Originally, the study was planned to include two parts, i.e., Part A and Part B, however Part B was cancelled due to changes in the overall clinical development plan. The objectives originally described for Part B have been implemented in the ongoing development via a pivotal Phase I/II/III trial BNT162-02/C4591001 (ClinicalTrials.gov NCT: 04368728). The conducted Part A was a dose-finding part to investigate the optimal dose of four different vaccines (BNT162a1, BNT162b1, BNT162b2, and BNT162c2), allowing dose adjustments upwards and downwards in younger participants. Doses tested in older participants and expansion cohorts were chosen based on acceptability of dosing in younger participants. The vaccines BNT162a1, BNT162b1, BNT162b2, and BNT162c2 were administered using a Prime/Boost (P/B) regimen with two doses given \~21 days apart. The vaccine BNT162c2 was also administered using a Single dose (SD) regimen. Four additional expansion cohorts (cohorts 11, 12, 13, and 14) aged from 18 to 85 years received BNT162b2 using a P/B regimen only. In cohort 11, participants received BNT162b2 using one 3 μg prime dose (Dose 1) and one 30 μg boost dose (Dose 2) of BNT162b2. Participants in cohorts 12, 13, and 14 received two doses of BNT162b2 30 µg, each.

Conditions

Infections, Respiratory; Virus Diseases; Infection Viral; Vaccine Adverse Reaction; RNA Virus Infections; Protection Against COVID-19 and Infections With SARS CoV 2

Keywords

SARS-CoV-2; Severe Acute Respiratory Syndrome (SARS); Coronavirus Disease 2019; COVID-2019; Virus Diseases

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Solicited Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling) Recorded up to 7 Days After Each IMP Dose.

  Solicited local reactions at the injection site (pain, tenderness, erythema/redness, and induration/swelling) were monitored and graded using criteria based on the guidance given in US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials". The reporting of local reactions was based on the participant's assessments via daily solicited reports in the participant diaries.

  From Day 1 to Day 8 for Dose 1 (Prime Immunization) and from Day 22 to Day 29 for Dose 2 (Boost Immunization)

• Number of Participants With Solicited Systemic Reactions (Nausea, Vomiting, Diarrhea, Headache, Fatigue, Myalgia, Arthralgia, Chills, Loss of Appetite, Malaise, and Fever) Recorded up to 7 Days After Each IMP Dose.

  Solicited systemic reactions (nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever) were monitored and graded using criteria based on the guidance given in US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials". The reporting of systemic reactions was based on the participant's assessments via daily solicited reports in the participant diaries.

  From Day 1 to Day 8 for Dose 1 (Prime Immunization) and from Day 22 to Day 29 for Dose 2 (Boost Immunization)

• The Percentage of Participants With at Least 1 Unsolicited Treatment Emergent Adverse Event (TEAE) Occurring After Dose 1 (Prime Immunization) up to Dose 2 (Boost Immunization) or 28 Days After Dose 1.

  TEAEs without AEs based on solicited reporting via diaries, were analyzed by vaccine, age group, dose level, and for each IMP dose. The percentage of participants reporting at least one TEAE was summarized by adverse event types (any TEAE and any grade \>=3 TEAE) using the Safety Set.

  28 days following Dose 1 or up to Dose 2 (whichever was first)

• The Percentage of Participants With at Least 1 Unsolicited TEAE Occurring After Dose 1 up to 28 Days After Dose 2 (Boost Immunization) or After Dose 1 (Prime Immunization) (if no Dose 2)

  TEAEs, without AEs based on solicited reporting via diaries, were analyzed by vaccine, age group, dose level, and for each IMP dose. The percentage of participants reporting at least one TEAE was summarized by adverse event types (any TEAE and any grade \>=3 TEAE) using the Safety Set.

  28 days following Dose 2 or Dose 1 (if no Dose 2 was given)

Secondary Outcomes (9)

• Functional Antibody Responses (Titers) for BNT162a1, BNT162b1, BNT162b2 (Younger and Older Dose Ranging Cohorts), and BNT162c2 (P/B)

  up to 183 days following Dose 1

• Fold Increase in Functional Antibody Titers as Compared to Baseline for BNT162a1, BNT162b1, BNT162b2 (Younger and Older Dose Ranging Cohorts), and BNT162c2 (P/B)

  up to 183 days following Dose 1

• Number of Participants With Seroconversion Defined as a Minimum of 4-fold Increase of Functional Antibody Titers as Compared to Baseline for BNT162a1, BNT162b1, BNT162b2 (Younger and Older Dose Ranging Cohorts), and BNT162c2 (P/B)

  up to 183 days following Dose 1

• Functional Antibody Responses (Titers) for BNT162c2 (SD)

  up to 183 days following Dose 1

• Fold Increase in Functional Antibody Titers as Compared to Baseline for BNT162c2 (SD)

  up to 183 days following Dose 1

Study Arms (9)

BNT162a1 (P/B) - Part A 18-55 years of age

EXPERIMENTAL

Escalating dose levels

Biological: BNT162a1

BNT162b1 (P/B) - Part A 18-55 years of age

EXPERIMENTAL

Escalating dose levels

Biological: BNT162b1

BNT162b2 (P/B) - Part A 18-55 years of age

EXPERIMENTAL

Escalating dose levels

Biological: BNT162b2

BNT162c2 (P/B) - Part A 18-55 years of age

EXPERIMENTAL

Escalating dose levels

Biological: BNT162c2

BNT162c2 (prime only) - Part A 18-55 years of age

EXPERIMENTAL

Single dose

Biological: BNT162c2

BNT162b1 (P/B) - Part A 56-85 years of age

EXPERIMENTAL

Escalating dose levels

Biological: BNT162b1

BNT162b2 (P/B) - Part A 56-85 years of age

EXPERIMENTAL

Escalating dose levels

Biological: BNT162b2

BNT162b2 (P/B) - Part A 18-85 years of age (Expansion cohorts 11 to 13)

EXPERIMENTAL

Fixed doses used; cohort 11: alternative posology dose group expansion cohort; cohort 12: adaptive immune response dose group expansion cohort; cohort 13: immunocompromised (IC) participants expansion cohort

Biological: BNT162b2

BNT162b2 (P/B) - Part A 18-85 years of age (Expansion cohort 14)

EXPERIMENTAL

fixed doses used; B-cell immune response dose group expansion cohort

Biological: BNT162b2

Interventions

BNT162a1 BIOLOGICAL

Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.

BNT162a1 (P/B) - Part A 18-55 years of age

BNT162b1 BIOLOGICAL

Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.

BNT162b1 (P/B) - Part A 18-55 years of age; BNT162b1 (P/B) - Part A 56-85 years of age

BNT162b2 BIOLOGICAL

Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.

BNT162b2 (P/B) - Part A 18-55 years of age; BNT162b2 (P/B) - Part A 18-85 years of age (Expansion cohort 14); BNT162b2 (P/B) - Part A 18-85 years of age (Expansion cohorts 11 to 13); BNT162b2 (P/B) - Part A 56-85 years of age

BNT162c2 BIOLOGICAL

Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.

BNT162c2 (P/B) - Part A 18-55 years of age; BNT162c2 (prime only) - Part A 18-55 years of age

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
• They must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions (e.g., to practice social distancing and to follow good practices to reduce their chances of being infected or spreading COVID-19), and other requirements of the trial.
• They must be able to understand and follow trial-related instructions.
• For younger adult cohorts, volunteers must be aged 18 to 55 years, have a body mass index (BMI) over 19 kg/m\^2 and under 30 kg/m\^2, and weigh at least 50 kg at Visit 0. OR For older adult cohorts, volunteers must be aged 56 to 85 years, have a BMI over 19 kg/m\^2 and under 30 kg/m\^2, and weigh at least 50 kg at Visit 0. OR For the immunocompromised adult cohort (Cohort 13), volunteers must be aged 18 to 85 years, have a BMI over 19 kg/m\^2 and under 30 kg/m\^2, and weigh at least 50 kg at Visit 0.
• They must be healthy, in the clinical judgment of the investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs (systolic/diastolic blood pressure, pulse rate, body temperature, respiratory rate), and clinical laboratory tests (blood chemistry, hematology, and urine chemistry) at Visit 0. Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. OR For the immunocompromised cohort (Cohort 13); volunteers who have previously received solid organ transplant, or peripheral blood stem cell transplantation ≥6 months after transplantation, or individuals with human immunodeficiency virus (HIV) infection with a CD4+ T-cell count of ≥200 x 10\^6 /L at Visit 0. Individuals with lower T-cell counts will be excluded from the trial on the basis that this represents a significant medical complication. In the clinical judgment of the investigator, volunteers must be immunocompromised but otherwise healthy. After consultation with the Medical Monitor, this may include individuals receiving immunosuppressant therapy due to another confounding disease at least 2 weeks prior to enrollment and/or at least 6 weeks following immunization with BNT162b2, and/or individuals with immunosuppressive treatment of an autoimmune disease if the disease is stable.
• Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin urine test at Visit 0 and Visit 1. Women that are postmenopausal or permanently sterilized will be considered as not having reproductive potential.
• WOCBP must agree to practice a highly effective form of contraception during the trial, starting after Visit 0 and continuously until 60 days after receiving the last immunization. WOCBP must agree to require their male partners to use condoms during sexual contact (unless male partners are sterilized or infertile).
• WOCBP must confirm that they practice at least one highly effective 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 during trial, starting after Visit 0 and continuously until 60 days after receiving the last immunization.
• Men who are sexually active with a WOCBP and have not had a vasectomy must agree to practice a highly effective form of contraception with their female partner of childbearing potential during the trial, starting after Visit 0 and continuously until 60 days after receiving the last immunization.
• Men must be willing to refrain from sperm donation, starting after Visit 0 and continuously until 60 days after receiving the last immunization.
• They must have confirmation of their health insurance coverage prior to Visit 0.
• They must agree to not be vaccinated during the trial, starting after Visit 0 and continuously until 28 days after receiving the last immunization.

You may not qualify if:

• Have had any acute illness, as determined by the investigator, with or without fever, within 72 hours prior to the first immunization. An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the investigator, the residual symptoms will not compromise their well-being if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments.
• Are breastfeeding on the day of Visit 0 or who plan to breastfeed during the trial, starting after Visit 0 and continuously until at least 90 days after receiving the last immunization.
• Have a known allergy, hypersensitivity, or intolerance to the planned investigational medicinal product (IMP) including any excipients of the IMP.
• Had any medical condition or any major surgery (e.g., requiring general anesthesia) within the past 5 years which, in the opinion of the investigator, could compromise their well-being if they participate as trial subjects in the trial, or that could prevent, limit, or confound the protocol-specified assessments.
• Have any surgery planned during the trial, starting after Visit 0 and continuously until at least 90 days after receiving the last immunization.
• Had any chronic use (more than 21 continuous days) of any systemic medications, including immunosuppressant's or other immune-modifying drugs (except for Cohort 13), within the 6 months prior to Visit 0 unless in the opinion of the investigator, the medication would not prevent, limit, or confound the protocol-specified assessments or could compromise subject safety. Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included.
• Had any vaccination within the 28 days prior to Visit 0.
• Had administration of any immunoglobulins and/or any blood products within the 3 months prior to Visit 0.
• Had administration of another investigational medicinal product including vaccines within 60 days or 5 half-lives (whichever is longer), prior to Visit 0.
• Have a known history of active or ongoing hepatitis B or hepatitis C infection; or except for Cohort 13: HIV-1 or HIV-2 infection within the 30 days prior to Visit 0.
• Have a positive polymerase chain reaction (PCR)-based test for SARS-CoV-2 within the 30 days prior to Visit 1.
• Have a positive drugs of abuse (for amphetamines, benzodiazepines, barbiturates, cocaine, cannabinoids, opiates, methadone, methamphetamines, phencyclidine, and tricyclic antidepressants) result at Visit 0 or Visit 1.
• Have a positive breath alcohol test at Visit 0 or Visit 1.
• Previously participated in an investigational trial involving lipid nanoparticles.
• Have any affiliation with the trial site (e.g., are close relative of the investigator or dependent person, such as an employee or student of the trial site).

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (5)

Contract Research Organization

Berlin, Germany

Location

Universitäts Klinikum

Frankfurt am Main, Germany

Location

Universitäts Klinikum

Heidelberg, Germany

Location

Contract Research Organization

Kiel, Germany

Location

Contract Research Organization

Mannheim, Germany

Location

Related Publications (10)

• Muik A, Wallisch AK, Sanger B, Swanson KA, Muhl J, Chen W, Cai H, Maurus D, Sarkar R, Tureci O, Dormitzer PR, Sahin U. Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera. Science. 2021 Mar 12;371(6534):1152-1153. doi: 10.1126/science.abg6105. Epub 2021 Jan 29.

  PMID: 33514629 BACKGROUND

• Sahin U, Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, Baum A, Pascal K, Quandt J, Maurus D, Brachtendorf S, Lorks V, Sikorski J, Hilker R, Becker D, Eller AK, Grutzner J, Boesler C, Rosenbaum C, Kuhnle MC, Luxemburger U, Kemmer-Bruck A, Langer D, Bexon M, Bolte S, Kariko K, Palanche T, Fischer B, Schultz A, Shi PY, Fontes-Garfias C, Perez JL, Swanson KA, Loschko J, Scully IL, Cutler M, Kalina W, Kyratsous CA, Cooper D, Dormitzer PR, Jansen KU, Tureci O. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature. 2020 Oct;586(7830):594-599. doi: 10.1038/s41586-020-2814-7. Epub 2020 Sep 30.

  PMID: 32998157 BACKGROUND

• Sahin U, Muik A, Vogler I, Derhovanessian E, Kranz LM, Vormehr M, Quandt J, Bidmon N, Ulges A, Baum A, Pascal KE, Maurus D, Brachtendorf S, Lorks V, Sikorski J, Koch P, Hilker R, Becker D, Eller AK, Grutzner J, Tonigold M, Boesler C, Rosenbaum C, Heesen L, Kuhnle MC, Poran A, Dong JZ, Luxemburger U, Kemmer-Bruck A, Langer D, Bexon M, Bolte S, Palanche T, Schultz A, Baumann S, Mahiny AJ, Boros G, Reinholz J, Szabo GT, Kariko K, Shi PY, Fontes-Garfias C, Perez JL, Cutler M, Cooper D, Kyratsous CA, Dormitzer PR, Jansen KU, Tureci O. BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans. Nature. 2021 Jul;595(7868):572-577. doi: 10.1038/s41586-021-03653-6. Epub 2021 May 27.

  PMID: 34044428 BACKGROUND

• Vogel AB, Kanevsky I, Che Y, Swanson KA, Muik A, Vormehr M, Kranz LM, Walzer KC, Hein S, Guler A, Loschko J, Maddur MS, Ota-Setlik A, Tompkins K, Cole J, Lui BG, Ziegenhals T, Plaschke A, Eisel D, Dany SC, Fesser S, Erbar S, Bates F, Schneider D, Jesionek B, Sanger B, Wallisch AK, Feuchter Y, Junginger H, Krumm SA, Heinen AP, Adams-Quack P, Schlereth J, Schille S, Kroner C, de la Caridad Guimil Garcia R, Hiller T, Fischer L, Sellers RS, Choudhary S, Gonzalez O, Vascotto F, Gutman MR, Fontenot JA, Hall-Ursone S, Brasky K, Griffor MC, Han S, Su AAH, Lees JA, Nedoma NL, Mashalidis EH, Sahasrabudhe PV, Tan CY, Pavliakova D, Singh G, Fontes-Garfias C, Pride M, Scully IL, Ciolino T, Obregon J, Gazi M, Carrion R Jr, Alfson KJ, Kalina WV, Kaushal D, Shi PY, Klamp T, Rosenbaum C, Kuhn AN, Tureci O, Dormitzer PR, Jansen KU, Sahin U. BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature. 2021 Apr;592(7853):283-289. doi: 10.1038/s41586-021-03275-y. Epub 2021 Feb 1.

  PMID: 33524990 BACKGROUND

• Ji RR, Qu Y, Zhu H, Yang Y, Vogel AB, Sahin U, Qin C, Hui A. BNT162b2 Vaccine Encoding the SARS-CoV-2 P2 S Protects Transgenic hACE2 Mice against COVID-19. Vaccines (Basel). 2021 Apr 1;9(4):324. doi: 10.3390/vaccines9040324.

  PMID: 33915773 BACKGROUND

• Li J, Hui A, Zhang X, Yang Y, Tang R, Ye H, Ji R, Lin M, Zhu Z, Tureci O, Lagkadinou E, Jia S, Pan H, Peng F, Ma Z, Wu Z, Guo X, Shi Y, Muik A, Sahin U, Zhu L, Zhu F. Safety and immunogenicity of the SARS-CoV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomized, placebo-controlled, double-blind phase 1 study. Nat Med. 2021 Jun;27(6):1062-1070. doi: 10.1038/s41591-021-01330-9. Epub 2021 Apr 22.

  PMID: 33888900 BACKGROUND

• Muik A, Lui BG, Wallisch AK, Bacher M, Muhl J, Reinholz J, Ozhelvaci O, Beckmann N, Guimil Garcia RC, Poran A, Shpyro S, Finlayson A, Cai H, Yang Q, Swanson KA, Tureci O, Sahin U. Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine-elicited human sera. Science. 2022 Feb 11;375(6581):678-680. doi: 10.1126/science.abn7591. Epub 2022 Jan 18.

  PMID: 35040667 BACKGROUND

• Quandt J, Muik A, Salisch N, Lui BG, Lutz S, Kruger K, Wallisch AK, Adams-Quack P, Bacher M, Finlayson A, Ozhelvaci O, Vogler I, Grikscheit K, Hoehl S, Goetsch U, Ciesek S, Tureci O, Sahin U. Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes. Sci Immunol. 2022 Sep 16;7(75):eabq2427. doi: 10.1126/sciimmunol.abq2427. Epub 2022 Sep 16.

  PMID: 35653438 BACKGROUND

• Pather S, Charpentier N, van den Ouweland F, Rizzi R, Finlayson A, Salisch N, Muik A, Lindemann C, Khanim R, Abduljawad S, Smith ER, Gurwith M, Chen RT; Benefit-Risk Assessment of VAccines by TechnolOgy Working Group (BRAVATO; ex-V3SWG). A Brighton Collaboration standardized template with key considerations for a benefit-risk assessment for the Comirnaty COVID-19 mRNA vaccine. Vaccine. 2024 Sep 17;42(22):126165. doi: 10.1016/j.vaccine.2024.126165. Epub 2024 Aug 27.

  PMID: 39197299 DERIVED

• Muik A, Lui BG, Bacher M, Wallisch AK, Toker A, Finlayson A, Kruger K, Ozhelvaci O, Grikscheit K, Hoehl S, Ciesek S, Tureci O, Sahin U. Omicron BA.2 breakthrough infection enhances cross-neutralization of BA.2.12.1 and BA.4/BA.5. Sci Immunol. 2022 Nov 25;7(77):eade2283. doi: 10.1126/sciimmunol.ade2283. Epub 2022 Nov 18.

  PMID: 36125366 DERIVED

MeSH Terms

Conditions

Respiratory Tract Infections; Virus Diseases; RNA Virus Infections; Severe Acute Respiratory Syndrome; COVID-19

Interventions

BNT162 Vaccine

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pneumonia, Viral; Pneumonia; Lung Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Results Point of Contact

• Title: BioNTech clinical trials patient information
• Organization: BioNTech SE

patients@biontech.de

+49 6131 9084

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 8, 2020
• Study Start: April 23, 2020
• Primary Completion: June 30, 2021
• Study Completion: April 13, 2022
• Last Updated: July 12, 2024
• Results First Posted: July 12, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5)