A randomized study to evaluate safety and immunogenicity of the BNT162b2 COVID-19 vaccine in healthy Japanese adults

Abstract

We report interim safety and immunogenicity findings from an ongoing phase 1/2 study of BNT162b2 in healthy Japanese adults. Participants were randomized 3:1 to receive 2 intramuscular injections of 30 μg BNT162b2 or placebo 21 days apart. Overall, 160 individuals were randomized: 119 received BNT162b2, and 41 received placebo. Participants were stratified by age: 20-64 years (n = 130) and 65-85 years (n = 30). More than 97% of BNT162b2 recipients received 2 doses. Local reactions and systemic events were generally transient and mild to moderate. Severe adverse events were uncommon; there were no serious adverse events. One month after dose 2, SARS-CoV-2 50% serum neutralizing geometric mean titers were 571 and 366, and geometric mean fold rises were 55.8 and 36.6, in the younger and older age groups, respectively. In summary, BNT162b2 has an acceptable safety profile and produces a robust immune response, regardless of age, in Japanese adults. (ClinicalTrials.gov, NCT04588480).

Conflict of interest statement

J.B., M.Y., M.A., O.K., I.S., P.D., W.G. and S.L. are employees of Pfizer Inc and may hold stock or stock options. E.L., Ӧ.T. and U.Ş. are employees of BioNTech Inc and may hold stock or stock options. M.H. and Y.O. have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1. Study flow diagram.

Includes all screened and randomized participants. Participants who received dose 1 but not dose 2 continued to be evaluated for safety and immunogenicity.

Fig. 2. Local reactions and systemic events reported within 7 days after administration of BNT162b2 or placebo in participants 20–64 years of age and 65–85 years of age.

A, B Local reactions after doses 1 and 2, respectively. C, D Systemic events after doses 1 and 2, respectively. Results are for the safety population (20–64 years of age: n = 97 for BNT162b2, and n = 33 for placebo; 65–85 years of age: n = 22 for BNT162b2, and n = 8 for placebo). Pain at injection site was graded as mild (does not interfere with activity), moderate (interferes with activity), severe (prevents daily activity), or grade 4 (led to emergency department visit or hospitalization). Redness and swelling were graded as mild (>2.0–5.0 cm in diameter), moderate (>5.0–10.0 cm in diameter), severe (>10.0 cm in diameter), or grade 4 (necrosis or exfoliative dermatitis for redness and necrosis for swelling). Fever categories are shown in the key. Fatigue, headache, chills, and new or worsened muscle or joint pain were graded as mild (does not interfere with activity), moderate (some interference with activity), or severe (prevents daily activity). Vomiting was graded as mild (1–2 times in 24 h), moderate (>2 times in 24 h), or severe (requires intravenous hydration), and diarrhea as mild (2–3 loose stools in 24 h), moderate (4–5 loose stools in 24 h) or severe (≥6 loose stools in 24 h). Grade 4 for all systemic events indicated an emergency department visit or hospitalization. No participant experienced a grade 4 local reaction or systemic event. Data are presented as percentages with associated 95% CIs shown as error bars for the percentage of participants experiencing any reaction.

Fig. 3. Geometric mean titers and geometric mean fold rises of SARS-CoV-2 50% neutralizing titers for participants by age group and overall.

Results are for the evaluable immunogenicity population. Data are presented as geometric mean values with associated 95% CIs shown as error bars. Dots represent individual 50% neutralizing titers; individual dots correspond with discrete visits for each time point and may be superimposed. Numbers within bars are the geometric means. n = Number of participants with valid and determinate assay results. GMTs, GMFRs, and two-sided 95% CIs were calculated by exponentiation of the mean logarithm of the titers or fold rises and the corresponding CIs (based on the Student t distribution). GMFRs are from before dose 1 to 1 month after dose 2. Assay results below the LLOQ (20, dashed line) were set to 0.5 × LLOQ. CI confidence interval, GMFR geometric mean fold rise, GMT geometric mean titer, NT50 50% neutralizing titer, LLOQ lower limit of quantitation, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2. In the placebo group, n = 41 except before dose 2, when n = 40.