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

• Percentage of participants in Phase 1 reporting local reactions [ Time Frame: For 7 days after dose 1 and dose 2 ]
  Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
• Percentage of participants in Phase 1 reporting systemic events [ Time Frame: For 7 days after dose 1 and dose 2 ]
  Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
• Percentage of participants in Phase 1 reporting adverse events [ Time Frame: From dose 1 through 1 month after the last dose ]
  As elicited by investigational site staff
• Percentage of participants in Phase 1 reporting serious adverse events [ Time Frame: From dose 1 through 6 months after the last dose ]
  As elicited by investigational site staff
• Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values [ Time Frame: 1 day after dose 1 ]
  As measured at the central laboratory
• Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values [ Time Frame: 7 days after dose 1 ]
  As measured at the central laboratory
• Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values [ Time Frame: 7 days after dose 2 ]
  As measured at the central laboratory
• Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between baseline and 1 day after dose 1 ]
  As measured at the central laboratory
• Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between baseline and 7 days after dose 1 ]
  As measured at the central laboratory
• Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between before dose 2 and 7 days after dose 2 ]
  As measured at the central laboratory
• In the first 360 participants randomized into Phase 2/3, percentage of participants reporting local reactions [ Time Frame: For 7 days after dose 1 and dose 2 ]
  Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
• In the first 360 participants randomized into Phase 2/3, percentage of participants reporting systemic events [ Time Frame: For 7 days after dose 1 and dose 2 ]
  Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
• In the first 360 participants randomized into Phase 2/3, percentage of participants reporting adverse events [ Time Frame: From dose 1 through 1 month after the last dose ]
  As elicited by investigational site staff
• In the first 360 participants randomized into Phase 2/3, percentage of participants reporting serious adverse events [ Time Frame: From dose 1 through 6 months after the last dose ]
  As elicited by investigational site staff
• In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting local reactions [ Time Frame: For 7 days after dose 1 and dose 2 ]
  Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
• In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting systemic events [ Time Frame: For 7 days after dose 1 and dose 2 ]
  Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
• Percentage of participants in Phase 2/3 reporting adverse events [ Time Frame: From dose 1 through 1 month after the last dose ]
  As elicited by investigational site staff
• Percentage of participants in Phase 2/3 reporting serious adverse events [ Time Frame: From dose 1 through 6 months after the last dose ]
  As elicited by investigational site staff
• Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination [ Time Frame: From 7 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination [ Time Frame: From 7 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Percentage of participants 12-15 years of age in Phase 3 reporting adverse events [ Time Frame: From dose 1 through 1 month after the last dose ]
  As elicited by investigational site staff
• Percentage of participants 12-15 years of age in Phase 3 reporting adverse events [ Time Frame: From dose 1 through 6 months after the last dose ]
  As elicited by investigational site staff
• In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting local reactions [ Time Frame: For 7 days after dose 1 and dose 2 ]
  Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
• In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting systemic events [ Time Frame: For 7 days after dose 1 and dose 2 ]
  Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

• Percentage of participants reporting local reactions [ Time Frame: For 7 days after dose 1 and dose 2 ]
  Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
• Percentage of participants reporting systemic events [ Time Frame: For 7 days after dose 1 and dose 2 ]
  Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
• Percentage of participants reporting adverse events [ Time Frame: From dose 1 through 1 month after the last dose ]
  As elicited by investigational site staff
• Percentage of participants reporting serious adverse events [ Time Frame: From dose 1 through 6 months after the last dose ]
  As elicited by investigational site staff
• Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values [ Time Frame: 1 day after dose 1 ]
  As measured at the central laboratory
• Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values [ Time Frame: 7 days after dose 1 ]
  As measured at the central laboratory
• Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values [ Time Frame: 7 days after dose 2 ]
  As measured at the central laboratory
• Percentage of sentinel cohort participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between baseline and 1 day after dose 1 ]
  As measured at the central laboratory
• Percentage of sentinel cohort participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between baseline and 7 days after dose 1 ]
  As measured at the central laboratory
• Percentage of sentinel cohort participants with grading shifts in hematology and chemistry laboratory assessments [ Time Frame: Between before dose 2 and 7 days after dose 2 ]
  As measured at the central laboratory

• In Phase 1 participants, SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• In Phase 1 participants, GMFR in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 serum neutralizing antibody levels [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• In Phase 1 participants, SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels, expressed as GMCs [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• In Phase 1 participants, GMFR in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels from before vaccination to each subsequent time point [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• In Phase 1 participants, GMR of the geometric mean of SARS-CoV-2 serum neutralizing titers to the geometric mean of SARS CoV 2 (anti-S1 and anti-RBD) binding antibody levels [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination [ Time Frame: From 14 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination [ Time Frame: From 14 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination [ Time Frame: From 7 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination [ Time Frame: From 14 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination [ Time Frame: From 7 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination [ Time Frame: From 14 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination [ Time Frame: From 7 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination [ Time Frame: From 14 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination [ Time Frame: From 7 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination [ Time Frame: From 14 days after the second dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up
• GMR of SARS CoV 2 neutralizing titers in the 2 age groups (12-15 years of age to 16-25 years of age) [ Time Frame: 1 month after the second dose ]
  As measured at the central laboratory

• SARS-CoV-2-specific WT serum neutralizing antibody levels, expressed as GMTs [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• GMFR in SARS-CoV-2-specific WT serum neutralizing titers from before vaccination to each subsequent time point [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• Proportion of participants achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2-specific WT serum neutralizing antibody levels [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• SARS-CoV-2--spike protein-specific binding antibody levels and RBD-specific binding antibody levels, expressed as GMCs [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• Proportion of participants achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2--spike protein-specific binding antibody levels and RBD-specific binding antibody levels [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• GMFR in SARS-CoV-2-spike protein-specific binding antibody levels and RBD-specific binding antibody levels from before vaccination to each subsequent time point [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• GMR of the geometric mean of SARS-CoV-2-specific WT serum neutralizing titers to the geometric mean of SARS CoV 2 (spike protein and RBD) specific binding antibody levels [ Time Frame: Through 2 years after the final dose ]
  As measured at the central laboratory
• Confirmed COVID-19 incidence [ Time Frame: From the last dose of study intervention to the end of the study, up to 2 years ]
  Per 1000 person-years of follow-up

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

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: ≥12 years of age [stratified as 12-15, 16-55 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, ≥12 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, ≥12 years of age
  Intervention: Other: Placebo
• Experimental: High dose, 18-55 years of age (2 doses)
  Intervention: Biological: BNT162b1

• Walsh EE, Frenck RW Jr, Falsey AR, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Mulligan MJ, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi PY, Türeci Ö, Tompkins KR, Lyke KE, Raabe V, Dormitzer PR, Jansen KU, Şahin U, Gruber WC. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med. 2020 Oct 14. doi: 10.1056/NEJMoa2027906. [Epub ahead of print]
• Mulligan MJ, Lyke KE, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Raabe V, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi PY, Türeci Ö, Tompkins KR, Walsh EE, Frenck R, Falsey AR, Dormitzer PR, Gruber WC, Şahin U, Jansen KU. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature. 2020 Oct;586(7830):589-593. doi: 10.1038/s41586-020-2639-4. Epub 2020 Aug 12.

Inclusion Criteria:

• Male or female participants between the ages of 18 and 55 years, inclusive, 65 and 85 years, inclusive, or ≥12 years, inclusive, at randomization (dependent upon study phase). Note that participants <18 years of age cannot be enrolled in the EU.
• 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.
• Phases 1 and 2 only: 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 (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) 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.