Safety and Effects of an Investigational COVID-19 Vaccine as Booster in Healthy People

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 (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.

Timeline

Start

2022-11-08

Primary completion

2024-11-22

Completion

2024-11-22

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.
• Wang 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.

Drugs

Indications