Pfizer

Va

ccinated with study intervention produced by manufacturing “Process 1” will be selected 
for this descriptive analysis.
Participants are expected to participate for up to a maximum of approximately 26 months. 
The duration of study follow-up may be shorter among participants enrolled in Phase 1 
dosing arms that are not evaluated in Phase 2/3. 
4.2. Scientific Rationale for Study Design
Additional surveillance for COVID-19 will be conducted as part of the study, given the 
potential risk of disease enhancement. If a participant experiences symptoms, as detailed in 
Section 8.13, a COVID-19 illness and subsequent convalescent visit will occur. As part of 
these visits, samples (nasal [midturbinate] swab and blood) will be taken for antigen and 
antibody assessment as well as recording of COVID-19–related clinical and laboratory 
information (including local diagnosis). 
Human reproductive safety data are not available for BNT162 RNA-based COVID-19 
vaccines, but there is no suspicion of human teratogenicity based on the intended mechanism 
of action of the compound. Therefore, the use of a highly effective method of contraception 
is required (see Appendix 4).
4.3. Justification for Dose
Because of the requirement for a rapid response to the newly emerged COVID-19 pandemic, 
sufficient data were not available to experimentally validate the dose selection and initial 
starting dose. Therefore, the original planned starting dose of 10 µg (for both BNT162b1 and 
BNT162b2) in this study was based on nonclinical experience with the same RNAs encoding 
other viral antigens (such as influenza and HIV antigens). The general safety and 
effectiveness of uRNA and modRNA platforms have been demonstrated in oncological 
clinical trials with different administration routes (NCT02410733, NCT03871348). Doses of 
up to 400 µg total uRNA have been administered IV as RNA lipoplex (RNA-LPX) and doses 
of up to 1000 µg total naked modRNA have been administered intratumorally, both without 
signs of unpredictable overstimulation of the immune system.
Based on nonclinical data of the RNA components, with other liposomes or in conjunction 
with the lipid nanoparticles as will be tested clinically in this study, it was expected that 
doses in the 1- to 5-µg range would be immunogenic and induce neutralizing antibodies;
however, it was anticipated that 3- to 10-fold higher doses would likely be required to elicit a 
stronger antibody response. Based on previous clinical and nonclinical experience, it was 
expected that doses of up to 100 µg would be well tolerated.
Update as part of protocol amendment 2: preliminary experience in this study and the 
BioNTech study conducted in Germany (BNT162-01) suggests that, for vaccine candidates 
based on the modRNA platform, a dose level between 30 µg and 100 µg warrants 
consideration. Therefore, a 50-µg dose level is formally included for BNT16