Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Adults

This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy adults.

The study consists of 2 parts: Phase 1: to identify preferred vaccine candidate(s) and dose level(s); Phase 2/3: an expanded cohort and efficacy part.

The study will evaluate the safety, tolerability, and immunogenicity of 2 different SARS CoV 2 RNA vaccine candidates against COVID 19 and the efficacy of 1 candidate:

• As a 2-dose (separated by 21 days) schedule;
• At various different dose levels in Phase 1;
• In 3 age groups (Phase 1: 18 to 55 years of age, 65 to 85 years of age; Phase 2/3: 18 to 85 years of age [stratified as ?55 or >55 years of age]).

The candidate selected for evaluation in Phase 2/3 is BNT162b2 (mid-dose).

• SARS-CoV-2 Infection
• COVID-19

• Biological: BNT162b1
  Intramuscular injection
• Biological: BNT162b2
  Intramuscular injection
• Other: Placebo
  Intramuscular injection

• Experimental: Low dose, 18-55 years of age (2 doses)
  Interventions:

  • Biological: BNT162b1
  • Biological: BNT162b2
• Experimental: Low-mid dose, 18-55 years of age (2 doses)
  Interventions:

  • Biological: BNT162b1
  • Biological: BNT162b2
• Experimental: Mid dose, 18-55 years of age (2 doses)
  Interventions:

  • Biological: BNT162b1
  • Biological: BNT162b2
• Experimental: Low dose, 65-85 years of age (2 doses)
  Interventions:

  • Biological: BNT162b1
  • Biological: BNT162b2
• Experimental: Low-mid dose, 65-85 years of age (2 doses)
  Interventions:

  • Biological: BNT162b1
  • Biological: BNT162b2
• Experimental: Mid dose, 65-85 years of age (2 doses)
  Interventions:

  • Biological: BNT162b1
  • Biological: BNT162b2
• Experimental: Mid dose, 18-85 years of age (2 doses)
  Intervention: Biological: BNT162b2
• Placebo Comparator: Placebo, 18-55 years of age
  Intervention: Other: Placebo
• Placebo Comparator: Placebo, 65-85 years of age
  Intervention: Other: Placebo
• Placebo Comparator: Placebo, 18-85 years of age
  Intervention: Other: Placebo
• Experimental: High dose, 18-55 years of age (2 doses)
  Intervention: Biological: BNT162b1

Inclusion Criteria:

• Male or female participants between the ages of 18 and 55 years, inclusive, 65 and 85 years, inclusive, or 18 and 85 years, inclusive, at randomization (dependent upon study phase).
• Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
• Healthy participants who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study.
• Participants who, in the judgment of the investigator, are at risk for acquiring COVID-19.
• Capable of giving personal signed informed consent

Exclusion Criteria:

• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
• Receipt of medications intended to prevent COVID 19.
• Previous clinical or microbiological diagnosis of COVID 19.

• Phase 1 only: Individuals at high risk for severe COVID-19, including those with any of the following risk factors:

  • Hypertension
  • Diabetes mellitus
  • Chronic pulmonary disease
  • Asthma
  • Current vaping or smoking
  • History of chronic smoking within the prior year
  • BMI >30 kg/m2
  • Anticipating the need for immunosuppressive treatment within the next 6 months
• Phase 1 only: Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel).
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• Phase 1 only: Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention.
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• Women who are pregnant or breastfeeding.
• Previous vaccination with any coronavirus vaccine.
• Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
• Phase 1 only: Regular receipt of inhaled/nebulized corticosteroids.
• Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
• Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
• Previous participation in other studies involving study intervention containing lipid nanoparticles.
• Phase 1 only: Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at the screening visit.
• Phase 1 only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ? Grade 1 abnormality.
• Phase 1 only: Positive test for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (HBc Abs), or hepatitis C virus antibodies (HCV Abs) at the screening visit.
• Phase 1 only: SARS-CoV-2 NAAT-positive nasal swab within 24 hours before receipt of study intervention.
• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.