Study Name

Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

Design

Ongoing, randomized, placebo-controlled, observer-blinded, dose-escalation trial

Objective

To evaluate safety and immunogenicity of the 10-μg, 20-μg, and 30-μg dose levels of BNT162b1 and BNT162b2 in adults 18 to 55 years of age and adults 65 to 85 years of age

Methods

Inclusion criteria were healthy adults 18 to 55 years of age or 65 to 85 years of age. Exclusion criteria were known infection with human immunodeficiency virus, hepatitis B or C virus, an immunocompromised condition, history of autoimmune disease, or previous diagnosis of COVID-19.

Patients were randomly assigned to groups according to vaccine candidate, dose level, and age range.

Groups of participants 18 to 55 years of age and 65 to 85 years of age were to receive doses of 10 μg, 20 μg, or 30 μg of BNT162b1 or BNT162b2 (or placebo) on a two-dose schedule.

One group of participants 18 to 55 years of age was assigned to receive 100-μg doses of BNT162b1 or placebo. 

All the participants were assigned to receive two 0.5-ml injections of active vaccine or placebo into the deltoid, administered 21 days apart.

The first five participants in each new dose level or age group were observed for four hours after the injection to identify immediate adverse events. All the other participants were observed for 30 minutes.

Immunogenicity assessments were conducted before the administration of vaccine or placebo, at 7 days and 21 days after the first dose, and at 7 days (i.e., day 28) and 14 days (i.e., day 35) after the second dose.

Study Groups/Patients

A total of 195 participants were randomly assigned to 13 groups comprising 15 participants each; in each group, 12 participants received vaccine and 3 received placebo.

Outcome Measures

The primary end points were local and systemic reactions as a response to the vaccine, and immunogenicity of both candidates:

Local reactions for adults aged 18-55 years of age after both doses of each candidate

Local reactions for adults aged 65-85 years of age after both doses of each candidate

Systemic reactions for adults aged 18-55 years of age after both doses of each candidate

Systemic reactions for adults aged 65-85 years of age after both doses of each candidate

Immuogenicity - 50% neutralizing geometric mean titers (GMTs) for the two vaccine candidates for both adult groups

Results

Local Reactions:

Participants 18-55 years of age:

Participants 65-85 years of age:

Systemic Reactions:

Participants 18-55 years of age:

Participants 65-85 years of age:

Immunogenicity:

The 50% neutralizing geometric mean titers (GMTs) for the two vaccine candidates at the 30-μg dose level on day 28 or day 35 ranged from 1.7 to 4.6 times the GMT of the convalescent serum panel among participants 18 to 55 years of age and from 1.1 to 2.2 times the GMT of the convalescent serum panel among those 65 to 85 years of age.

Study Author Conclusions

The safety and immunogenicity data support the selection of BNT162b2 for advancement to phase 2–3 safety and efficacy evaluation.

InpharmD Researcher Critique

Preliminary data suggest progression to next phases with vaccine candidate BNT162b2. There is uncertainty since cellular immunity to COVID-19 has not been fully established. Additionally, the human convalescent serum panels are not standardized among laboratories, and each represents a unique distribution of donor characteristics and times of collection.