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

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.

Timeline

Start

2020-04-23

Primary completion

2021-06-30

Completion

2022-04-13

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications