A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Modified RNA Vaccine Against Influenza

A PHASE 1/2 RANDOMIZED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MODIFIED RNA VACCINE AGAINST INFLUENZA IN HEALTHY INDIVIDUALS

This study will be divided into two substudies - Substudy A (SSA) and Substudy B (SSB)

Substudy A This is a Phase 1 randomized substudy to evaluate the safety and immunogenicity of monovalent influenza modRNA vaccine (mIRV) and bivalent influenza modRNA vaccine (bIRV) at various dose levels, and quadrivalent influenza modRNA vaccine (qIRV), in participants 65 to 85 years of age. Participants will receive at Vaccination 1 either:

• 1 of 4 dose levels of mIRV (either A or B Strain),
• 1 of 4 dose levels of bIRV (containing both A and B strains),
• qIRV (at 1 dose level), or
• A licensed quadrivalent influenza vaccine (QIV).

At approximately 8 weeks following Vaccination 1, participants will be unblinded and QIV (Vaccination 2) administered to participants not having previously received this at Vaccination 1. Additionally, participants who previously received QIV at Vaccination 1 will receive one of the following for Vaccination 2:

• mIRV encoding A strain at dose level 4, or
• mIRV encoding B strain at dose level 4.

Substudy B

This is a randomized substudy to evaluate the safety and immunogenicity of the following vaccination schedules in participants 65 to 85 years of age:

2-Visit Schedules

• 2 doses of qIRV (at a dose level 1), administered 21 days apart.
• 2 doses of licensed QIV, administered 21 days apart (as a control group)

• A dose of licensed QIV following by a dose of bIRV encoding 2 A strains at dose level combination 1 or 2, administered 21 days apart.

  1-Visit Schedules

• A dose of licensed QIV administered concurrently in the opposite arm with bIRV encoding 2 A strains at dose level combination 1 or 2.
• A dose of bIRV encoding 2 A strains administered concurrently in the opposite arm with a dose of bIRV encoding 2 B strains.at dose level 1.
• A dose of qIRV encoding 2 A strains and 2 B strains at dose level 2 (at one of two possible dose level combinations).
• A dose of qIRV encoding 2 A strains and 2 B strains at dose level 3.
• 1 dose of licensed QIV (as a control group).

Substudy B

In participants 18 to 64 years of age:

-A dose of qIRV encoding 2 A strains and 2 B strains at a dose level combination 1 or 2.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: mIRV; Biological: QIV; Biological: bIRV AB; Biological: qIRV; Biological: bIRV AA; Biological: bIRV BB

• Study Type: Interventional
• Enrollment (Actual): 1158
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Athens, Alabama, United States, 35611
      • North Alabama Research Center
    • Athens, Alabama, United States, 35611
      • The Heart Center
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Heart Rhythm Center
    • Phoenix, Arizona, United States, 85018
      • Hope Research Institute
    • Phoenix, Arizona, United States, 85018
      • The Pain Center of Arizona
    • Tucson, Arizona, United States, 85704
      • Noble Clinical Research
    • Tucson, Arizona, United States, 85704
      • Pima Heart and Vascular
  • California
    • Murrieta, California, United States, 92563
      • Inland Valley Cardiovascular Center
    • Orange, California, United States, 92868
      • Orange County Heart Institute
    • Riverside, California, United States, 92503
      • Artemis Institute for Clinical Research
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Pediatrics-Infectious Diseases - Clinical Trials Center at University of Colorado Anschutz Medical C
    • Aurora, Colorado, United States, 80045
      • UCHealth Heart and Vascular Center - Anschutz Medical Campus
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School Of Medicine
    • New Haven, Connecticut, United States, 06519
      • Yale University School Of Medicine
    • New Haven, Connecticut, United States, 06519
      • Yale Cardiology
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Alliance for Multispecialty Research, LLC
    • Daytona Beach, Florida, United States, 32114
      • Halifax Health Medical Center
    • Delray Beach, Florida, United States, 33484
      • NYU Langone Cardiology Associates
    • Fleming Island, Florida, United States, 32003
      • Fleming Island Center for Clinical Research
    • Fleming Island, Florida, United States, 32003
      • First Coast Heart & Vascular Center
    • Fort Lauderdale, Florida, United States, 33308
      • Proactive Clinical Research,LLC
    • Fort Myers, Florida, United States, 33912
      • Alliance for Multispecialty Research, LLC
    • Fort Myers, Florida, United States, 33912
      • Robert B. Pritt, DO
    • Fort Myers, Florida, United States, 33912
      • Millennium Physician Group
    • Hialeah, Florida, United States, 33016
      • Best Quality Research,Inc.
    • Hialeah, Florida, United States, 33012
      • Direct Helpers Research Center.
    • Hollywood, Florida, United States, 33024
      • Elixia Infectious Disease, LLC
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
    • Jacksonville, Florida, United States, 32256
      • First Coast Cardiovascular Institute
    • Jacksonville, Florida, United States, 32216
      • First Coast Heart & Vascular Center
    • Maitland, Florida, United States, 32751
      • Premier Cardiology and Vascular Associates
    • Miami, Florida, United States, 33136
      • University of Miami Hospital
    • Miami, Florida, United States, 33125
      • Optimus U Corporation
    • Miami, Florida, United States, 33176
      • Miami Dade Medical Research Institute, LLC
    • Miami, Florida, United States, 33135
      • Suncoast Research Group
    • Miami, Florida, United States, 33176
      • Entrust Clinical Research
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases/University of Miami
    • Miami, Florida, United States, 33125
      • LMG Research
    • Miami, Florida, United States, 33173
      • Research Institute of South Florida
    • Miami, Florida, United States, 33125
      • Millennium Clinical Research
    • Miami, Florida, United States, 33156
      • Dr Gerardo A. Polanco, MD
    • Miami, Florida, United States, 33176
      • Jackson Medical Group Cardiac Care
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
    • Orlando, Florida, United States, 32803
      • Central Florida Cardiology Group
    • Palmetto Bay, Florida, United States, 33157
      • Innovation Medical Research Center
    • Pembroke Pines, Florida, United States, 33029
      • DBC Research USA
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • South Miami, Florida, United States, 33143
      • My Cardiologist
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Research, LLC
    • Winter Park, Florida, United States, 32789
      • Conquest Research
  • Georgia
    • Columbus, Georgia, United States, 31904
      • IACT Health
    • Columbus, Georgia, United States, 31904
      • Centricity Research Columbus Georgia Multispecialty
    • Rincon, Georgia, United States, 31326
      • IACT Health
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty Research, LLC
    • Wichita, Kansas, United States, 67205
      • Alliance for Multispecialty Research, LLC
    • Wichita, Kansas, United States, 67226
      • Heartland Cardiology, LLC
  • Maryland
    • Elkridge, Maryland, United States, 21075
      • Centennial Medical Group
    • Silver Spring, Maryland, United States, 20910
      • Associates of Cardiology
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Pioneer Heart Institute
    • Norfolk, Nebraska, United States, 68701
      • Velocity Clinical Research, Norfolk
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research - 3345 North 107th Street
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research, Omaha
  • Nevada
    • Henderson, Nevada, United States, 89074
      • Sanjay Vohra, MD, F.A.C.C.
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research, LLC
    • Las Vegas, Nevada, United States, 89106
      • Wr-Crcn, Llc.
    • North Las Vegas, Nevada, United States, 89030
      • Las Vegas Clinical Trials
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
    • Somers Point, New Jersey, United States, 08244
      • Penn Medicine
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10016
      • NYU Langone - Center for the Prevention of Cardiovascular Disease
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Rochester, New York, United States, 14621
      • Rochester General Hospital
    • Rochester, New York, United States, 14621
      • Rochester General Hospital Infectious Disease
    • Syracuse, New York, United States, 13215
      • SUNY Upstate Medical University Global Health Research Unit
    • Syracuse, New York, United States, 13202
      • Upstate Health Care Center-University Cardiovascular Group of Syracuse
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • M3-Emerging Medical Research, LLC
    • Fayetteville, North Carolina, United States, 28303
      • Carolina Institute for Clinical Research
    • Monroe, North Carolina, United States, 28112
      • Monroe Biomedical Research
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc.
    • Columbus, Ohio, United States, 43213
      • Columbus Cardiovascular Associates, Inc
    • Columbus, Ohio, United States, 43213
      • Centricity Research Columbus Ohio Multispecialty
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • Pennsylvania Heart and Vascular Group
  • South Carolina
    • Little River, South Carolina, United States, 29566
      • Main Street Physician's Care
  • Texas
    • Houston, Texas, United States, 77065
      • DM Clinical Research
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center
    • Humble, Texas, United States, 77338
      • DM Clinical Research
    • Irving, Texas, United States, 75062
      • Cedar Health Research
    • Plano, Texas, United States, 75093
      • Harmony Heart Group
    • Sugar Land, Texas, United States, 77479
      • Mt Olympus Medical Research
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
    • Tomball, Texas, United States, 77375
      • Northwest Heart Center
  • Virginia
    • Suffolk, Virginia, United States, 23435
      • Centricity Research Suffolk Primary Care
    • Suffolk, Virginia, United States, 23435
      • Sentara BelleHarbour

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Substudy A

Inclusion Criteria:

• Male or female participants 65 to 85 years of age.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
• Male participant who is able to father children and willing to use an acceptable method of contraception; or female participant not of childbearing potential; or male participant not able to father children.
• Capable of giving 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.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• 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.
• Allergy to egg proteins (egg or egg products) or chicken proteins.
• Participant who has had significant exposure to laboratory-confirmed SARS-CoV-2 infection, COVID-19, or influenza in the past 14 days known prior to Visit 1
• Any participant who has a SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to Visit 1 that has not been confirmed as negative.
• Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study.
• Vaccination with any influenza vaccine within 6 months (175 days) before study intervention administration.
• Any participant who has received or plans to receive a modRNA-platform SARS-CoV-2 vaccine within 60 days of Visit 1
• Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
• Screening hematology/blood chemistry lab >=Grade 1 abnormality. Except Bilirubin, other stable Grade1 abnormalities may be considered eligible by Investigator.
• Screening ECG that is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or study results.
• 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.
• Participation in strenuous or endurance exercise through Visit 3.
• Prior history of heart disease.

Substudy B

Inclusion Criteria:

• Male or female participants 65 to 85 years of age or .Male or female participants 18 to 64 years of age
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
• For participants 65 to 85 years of age at the time of enrollment, receipt of licensed influenza vaccination for the 2021-2022 northern hemisphere season >4 months (120 days) before study intervention administration.
• Capable of giving 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.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• 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.
• Allergy to egg proteins (egg or egg products) or chicken proteins.
• Participant who has had significant exposure to laboratory-confirmed SARS-CoV-2 infection, COVID-19, or influenza in the past 14 days known prior to Visit 201
• Any participant who has a SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to Visit 201 that has not been confirmed as negative.
• Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study.
• Any participant who has received or plans to receive a modRNA-platform SARS-CoV-2 vaccine within 28 days of Visit 201
• Any participant who has received licensed influenza vaccination for the 2022-2023 northern hemisphere influenza season.
• Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
• 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.
• Participation in strenuous or endurance exercise through Visit 205.
• Prior history of heart disease.
• Any abnormal screening troponin I laboratory value
• Screening 12-lead ECG that, as judged by the investigator, is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

28

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SSA: mIRV A (dose level 1) + QIV	Biological: mIRV; Intramuscular injection; Biological: QIV; Intramuscular injection
Experimental: SSA: mIRV A (dose level 2) + QIV	Biological: mIRV; Intramuscular injection; Biological: QIV; Intramuscular injection
Experimental: SSA: mIRV A (dose level 3) + QIV	Biological: mIRV; Intramuscular injection; Biological: QIV; Intramuscular injection
Experimental: SSA: mIRV A (dose level 4) + QIV	Biological: mIRV; Intramuscular injection; Biological: QIV; Intramuscular injection
Experimental: SSA: mIRV B (dose level 1) + QIV	Biological: mIRV; Intramuscular injection; Biological: QIV; Intramuscular injection
Experimental: SSA: mIRV B (dose level 2) + QIV	Biological: mIRV; Intramuscular injection; Biological: QIV; Intramuscular injection
Experimental: SSA: mIRV B (dose level 3) + QIV	Biological: mIRV; Intramuscular injection; Biological: QIV; Intramuscular injection
Experimental: SSA: mIRV B (dose level 4) + QIV	Biological: mIRV; Intramuscular injection; Biological: QIV; Intramuscular injection
Experimental: SSA: bIRV AB (dose level combination 1) + QIV	Biological: QIV; Intramuscular injection; Biological: bIRV AB; Intramuscular injection
Experimental: SSA: bIRV AB (dose level combination 2) + QIV	Biological: QIV; Intramuscular injection; Biological: bIRV AB; Intramuscular injection
Experimental: SSA: bIRV AB (dose level combination 3) + QIV	Biological: QIV; Intramuscular injection; Biological: bIRV AB; Intramuscular injection
Experimental: SSA: bIRV AB (dose level combination 4) + QIV	Biological: QIV; Intramuscular injection; Biological: bIRV AB; Intramuscular injection
Experimental: SSA: QIV + mIRV A strain (dose level 4)	Biological: mIRV; Intramuscular injection; Biological: QIV; Intramuscular injection
Experimental: SSA: qIRV (dose level 1) + QIV	Biological: QIV; Intramuscular injection; Biological: qIRV; Intramuscular injection
Experimental: SSA: QIV + mIRV B strain (dose level 4)	Biological: mIRV; Intramuscular injection; Biological: QIV; Intramuscular injection
Experimental: SSB: 2 doses of qIRV (dose level 1), 2-visit schedule	Biological: qIRV; Intramuscular injection
Experimental: SSB: 2 doses of QIV, 2-visit schedule	Biological: QIV; Intramuscular injection
Experimental: SSB: QIV + bIRV AA (dose level combination 1), 2-visit schedule	Biological: QIV; Intramuscular injection; Biological: bIRV AA; Intramuscular injection
Experimental: SSB: QIV + bIRV AA (dose level combination 2), 2-visit schedule	Biological: QIV; Intramuscular injection; Biological: bIRV AA; Intramuscular injection
Experimental: SSB: QIV + bIRV AA (dose level combination 1), 1-visit schedule	Biological: QIV; Intramuscular injection; Biological: bIRV AA; Intramuscular injection
Experimental: SSB: QIV + bIRV AA (dose level combination 2), 1-visit schedule	Biological: QIV; Intramuscular injection; Biological: bIRV AA; Intramuscular injection
Experimental: SSB: qIRV (dose level 2, dose combination 1), 1-visit schedule; NOTE: Arm Description has not been entered.	Biological: qIRV; Intramuscular injection
Experimental: SSB: qIRV (dose level 2, dose combination 2), 1-visit schedule; NOTE: Arm Description has not been entered	Biological: qIRV; Intramuscular injection
Experimental: SSB: qIRV (dose level 3), 1-visit schedule; NOTE: Arm Description has not been entered	Biological: qIRV; Intramuscular injection
Experimental: SSB: bIRV AA + bIRV BB (both dose level combination 1), 1-visit schedule; NOTE: Arm Description has not been entered	Biological: bIRV AA; Intramuscular injection; Biological: bIRV BB; Intramuscular injection
Experimental: SSB: 1 dose of QIV, 1-visit schedule; NOTE: Arm Description has not been entered	Biological: QIV; Intramuscular injection
Experimental: SSB: qIRV (dose level 1), 1-visit schedule; NOTE: Arm Description has not been entered.	Biological: qIRV; Intramuscular injection
Experimental: SSB: qIRV (dose level 2), 1-visit schedule; NOTE: Arm Description has not been entered.	Biological: qIRV; Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Reporting Local Reactions After Vaccination 1: Substudy A	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 centimeter (cm). Redness and swelling were graded as mild (Grade 1): greater than (>) 2.0 cm to 5.0 cm; moderate (Grade 2): >5.0 cm to 10.0 cm; severe (Grade 3): >10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis (redness) and necrosis (swelling). Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Exact 2-sided confidence interval was based on the Clopper and Pearson method.	From Day 1 to Day 7 after Vaccination 1
Percentage of Participants Reporting Local Reactions After Vaccination 2: Substudy A	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): >2.0 cm to 5.0 cm; moderate (Grade 2): >5.0 cm to 10.0 cm; severe (Grade 3): >10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Exact 2-sided confidence interval was based on the Clopper and Pearson method.	From Day 1 to Day 7 after Vaccination 2
Percentage of Participants Reporting Systemic Events After Vaccination 1: Substudy A	Systemic events included fever, vomiting, diarrhea, headache,fatigue,chills,new/worsened muscle pain & new/worsened joint pain & recorded by participants in an electronic diary.Fever defined as oral temperature greater than equal to(>=)38.0 degrees Celsius(deg C) & categorized as>=38.0 to 38.4 deg C, >38.4 to 38.9 deg C,>38.9 to 40.0 deg C & >40.0 deg C. Vomiting graded as:Grade(G)1:1-2 times in 24 hours(h);G2:>2 times in 24h;G3:required Intravenous (IV) hydration.Diarrhea graded as: G1:2-3 loose stools in 24h;G2: 4-5 loose stools in 24h;G3: 6 or more loose stools in 24h.Headache,fatigue,chills, new/worsened muscle pain & new/worsened joint pain:G1:didn't interfere with activity;G2: some interference with activity;G3:prevented daily routine activity.For all systemic events except fever, Grade 4=emergency room visit or hospitalization. Grade 4 events were classified by the investigator or medically qualified person.Exact 2-sided confidence interval based on Clopper and Pearson method.	From Day 1 to Day 7 After Vaccination 1
Percentage of Participants Reporting Systemic Events After Vaccination 2: Substudy A	Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new/worsened muscle pain & new /worsened joint pain & recorded by participants in electronic diary. Fever defined as oral temperature >=38.0 deg C & categorized as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C & >40.0 deg C. Vomiting graded as: Grade(G) 1: 1-2 times in 24 h; G2: >2 times in 24 h; G3: required IV hydration. Diarrhea graded as: G1: 2-3 loose stools in 24 h; G2: 4-5 loose stools in 24 h; G3: 6 or more loose stools in 24 h. Headache, fatigue, chills, new/worsened muscle pain & new/worsened joint pain: G1: didn't interfere with activity; G2: some interference with activity; G3: prevented daily routine activity. For all systemic events except fever, Grade 4= emergency room visit or hospitalization. Grade 4 events were classified by the investigator or medically qualified person. Exact 2-sided confidence interval based on Clopper and Pearson method.	From Day 1 to Day 7 after Vaccination 2
Percentage of Participants Reporting Adverse Events After Vaccination 1: Substudy A	An adverse event (AE) was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e, excluding local reactions and systematic events) were reported in this outcome measure.	From Day 1 up to 4 weeks After Vaccination 1
Percentage of Participants Reporting Adverse Events After Vaccination 2: Substudy A	An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.	From Day 1 up to 4 weeks After vaccination 2
Percentage of Participants Reporting Serious Adverse Events (SAE) From First Vaccination to 6 Months After Last Vaccination: Substudy A	An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.	From vaccination 1 on day 1 up to 6 months after vaccination 2
Percentage of Participants With Abnormal Hematology Values at 2 Days After Vaccination 1: Substudy A	Hematology parameters included erythrocytes, lymphocytes, neutrophils, eosinophils/leukocytes, erythrocyte (ery) mean corpuscular volume, ery. mean corpuscular hemoglobin and ery. mean corpuscular hemoglobin concentration. The primary criteria were as follows erythrocytes, lymphocytes, neutrophils: <0.8*lower limit of normal (LLN); Lymphocytes/Leukocytes, Eosinophils/Leukocytes, Monocytes/Leukocytes: >1.2*upper limit of normal (ULN); Ery. Mean Corpuscular Volume:>1.1*ULN; Ery. Mean Corpuscular Hemoglobin and Ery.Mean Corpuscular hemoglobin Concentration: < 0.9*LLN. Also add 95% CI was based on Clopper and Pearson method.	2 days after vaccination 1
Percentage of Participants With Abnormal Hematology Values at 1 Week After Vaccination 1: Substudy A	Hematology parameters included erythrocytes, neutrophils, eosinophils/leukocytes, monocytes/leukocytes, ery mean corpuscular hemoglobin. The primary criteria were as follows erythrocytes and neutrophils: <0.8* LLN; Eosinophils/Leukocytes and Monocytes/Leukocytes: >1.2* ULN; Ery. Mean Corpuscular Hemoglobin:>1.1*ULN. 95% CI was based on Clopper and Pearson method.	1 week after vaccination 1
Percentage of Participants With Abnormal Chemistry Values at 2 Days After Vaccination 1: Substudy A	Chemistry parameters included blood urea nitrogen and C-reactive protein. The primary criteria were as follows Blood Urea Nitrogen: > 1.3*ULN; C Reactive Protein: > 1.1*ULN. 95% CI was based on Clopper and Pearson method.	2 days after vaccination 1
Percentage of Participants With Abnormal Chemistry Values at 1 Week After Vaccination 1: Substudy A	Chemistry parameters included blood urea nitrogen and C-reactive protein. The primary criteria were as follows Blood Urea Nitrogen: > 1.3*ULN; C Reactive Protein: > 1.1*ULN. Also add 95% CI was based on Clopper and Pearson method.	1 week after vaccination 1
Percentage of Participants With Grade Shifts in Hematology Values at 2 Days After Vaccination 1: Substudy A	Hematology parameters included hemoglobin, lymphocytes, neutrophils decrease, platelets decrease, white blood cells (WBC) decrease and WBC increase. Laboratory abnormalities were graded by Food and Drug Administration (FDA) toxicity grading scale for healthy adult volunteers enrolled in preventive vaccine clinical trials as grade 1=mild; grade 2=moderate; grade 3=severe and grade 4=potentially life-threatening. Percentage of participants with shift in hematology values were reported in this outcome measure. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 2 days after vaccination 1 were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.	From Baseline (prior to vaccination 1) to 2 days after vaccination 1
Percentage of Participants With Grade Shifts in Hematology Values at 1 Week After Vaccination 1: Substudy A	Hematology parameters included hemoglobin, lymphocytes, neutrophils decrease, WBC decrease and WBC increase. Laboratory abnormalities were graded by FDA toxicity grading scale for healthy adult volunteers enrolled in preventive vaccine clinical trials as grade 1=mild; grade 2=moderate; grade 3=severe and grade 4=potentially life-threatening. Percentage of participants with shift in hematology values were reported in this outcome measure. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 1 week after vaccination 1 were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.	From Baseline (prior to vaccination 1) to 1 week after vaccination 1
Percentage of Participants With Grade Shifts in Chemistry Laboratory Values at 2 Days After Vaccination 1: Substudy A	Chemistry abnormalities were graded by toxicity grading scale for healthy adult volunteers enrolled in preventive vaccine clinical trials as grade 1=mild; grade 2=moderate; grade 3=severe and grade 4=potentially life-threatening. Percentage of participants with shift in chemistry values were reported in this outcome measure. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 2 days after vaccination 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported. The parameters reported were - Alanine Aminotransferase Increased (ALP), Alkaline Phosphatase Increased (ALP), Aspartate Aminotransferase Increased (AST), Creatinine Increased and Urea Nitrogen.	From Baseline (prior to vaccination 1) to 2 days after vaccination 1
Percentage of Participants With Grade Shifts in Chemistry Laboratory Values at 1 Week After Vaccination 1: Substudy A	Chemistry abnormalities were graded by toxicity grading scale for healthy adult volunteers enrolled in preventive vaccine clinical trials as grade 1=mild; grade 2=moderate; grade 3=severe and grade 4=potentially life-threatening. Percentage of participants with shift in chemistry values were reported in this outcome measure. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 1 week after vaccination 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported. The parameters reported were - Alanine Aminotransferase Increased, Alkaline Phosphatase Increased, Aspartate Aminotransferase Increased, Creatinine Increased and Urea Nitrogen.	From Baseline (prior to vaccination 1) to 1 week after vaccination 1
Percentage of Participants With New Electrocardiogram (ECG) Abnormalities at 2 Days After Vaccination 1: Substudy A	An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: Sustained atrial or ventricular arrhythmias, Second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and Diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.	2 days after vaccination 1
Percentage of Participants With New Electrocardiogram (ECG) Abnormalities at 1 Week After Vaccination 1: Substudy A	An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: Sustained atrial or ventricular arrhythmias, Second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and Diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.	1 week after vaccination 1
Percentage of Participants Reporting Local Reactions After Vaccination for 1-Visit Schedule (Initial Enrollment): Substudy B	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): >2.0 cm to 5.0 cm; moderate (Grade 2): >5.0 cm to 10.0 cm; severe (Grade 3): >10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Exact 2-sided confidence interval was based on the Clopper and Pearson method.	From Day 1 to Day 7 after vaccination
Percentage of Participants Reporting Local Reactions After Vaccination 1 for 2- Visit Schedule (Initial Enrollment): Substudy B	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): >2.0 cm to 5.0 cm; moderate (Grade 2): >5.0 cm to 10.0 cm; severe (Grade 3): >10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Exact 2-sided confidence interval was based on the Clopper and Pearson method.	From Day 1 to Day 7 after vaccination 1
Percentage of Participants Reporting Local Reactions After Vaccination 2 for 2- Visit Schedule (Initial Enrollment): Substudy B	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): >2.0 cm to 5.0 cm; moderate (Grade 2): >5.0 cm to 10.0 cm; severe (Grade 3): >10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Exact 2-sided confidence interval was based on the Clopper and Pearson method.	From Day 1 to Day 7 after vaccination 2
Percentage of Participants Reporting Local Reactions After Vaccination for Expanded Enrollment: Substudy B	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): >2.0 cm to 5.0 cm; moderate (Grade 2): >5.0 cm to 10.0 cm; severe (Grade 3): >10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Exact 2-sided confidence interval was based on the Clopper and Pearson method.	From Day 1 to Day 7 after vaccination 1 for all arms; From Day 1 to Day 7 after vaccination 2 for 2 doses of qIRV (dose level 1), 2-visit schedule arm
Percentage of Participants Reporting Systemic Events After Vaccination for 1-Visit Schedule (Initial Enrollment): Substudy B	Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new/worsened muscle pain & new /worsened joint pain & recorded by participants in electronic diary. Fever defined as oral temperature >=38.0 deg C & categorized as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C & >40.0 deg C. Vomiting graded as: G 1: 1-2 times in 24 hrs; G 2: >2 times in 24 hrs; G 3: required IV hydration; G 4: emergency room visit/ hospitalization for hypotensive shock. Diarrhea graded as: G 1: 2-3 loose stools in 24 hrs; G 2: 4-5 loose stools in 24 hrs; G 3: 6 or more loose stools in 24 hrs & G 4: emergency room visit/ hospitalization. Headache, fatigue, chills, new/worsened muscle pain & new/worsened joint pain: G 1: didn't interfere with activity; G 2: some interference with activity; G 3: prevented daily routine activity & G 4: emergency room visit/ hospitalization. Exact 2-sided confidence interval based on Clopper and Pearson method.	From Day 1 to Day 7 after vaccination
Percentage of Participants Reporting Systemic Events After Vaccination 1 for 2- Visit Schedule (Initial Enrollment): Substudy B	Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new/worsened muscle pain & new /worsened joint pain & recorded by participants in electronic diary. Fever defined as oral temperature >=38.0 deg C & categorized as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C & >40.0 deg C. Vomiting graded as: G 1: 1-2 times in 24 hrs; G 2: >2 times in 24 hrs; G 3: required IV hydration; G 4: emergency room visit/ hospitalization for hypotensive shock. Diarrhea graded as: G 1: 2-3 loose stools in 24 hrs; G 2: 4-5 loose stools in 24 hrs; G 3: 6 or more loose stools in 24 hrs & G 4: emergency room visit/ hospitalization. Headache, fatigue, chills, new/worsened muscle pain & new/worsened joint pain: G 1: didn't interfere with activity; G 2: some interference with activity; G 3: prevented daily routine activity & G 4: emergency room visit/ hospitalization. Exact 2-sided confidence interval based on Clopper and Pearson method.	From Day 1 to Day 7 after vaccination 1
Percentage of Participants Reporting Systemic Events After Vaccination 2 for 2-Visit Schedule (Initial Enrollment) : Substudy B	Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new/worsened muscle pain & new /worsened joint pain & recorded by participants in electronic diary. Fever defined as oral temperature >=38.0 deg C & categorized as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C & >40.0 deg C. Vomiting graded as: G 1: 1-2 times in 24 hrs; G 2: >2 times in 24 hrs; G 3: required IV hydration; G 4: emergency room visit/ hospitalization for hypotensive shock. Diarrhea graded as: G: 1: 2-3 loose stools in 24 hrs; G 2: 4-5 loose stools in 24 hrs; G 3: 6 or more loose stools in 24 hrs & G 4: emergency room visit/ hospitalization. Headache, fatigue, chills, new/worsened muscle pain & new/worsened joint pain: G 1: didn't interfere with activity; G 2: some interference with activity; G 3: prevented daily routine activity & G 4: emergency room visit/ hospitalization. Exact 2-sided confidence interval based on Clopper and Pearson method.	From day 1 to day 7 of vaccination 2
Percentage of Participants Reporting Systemic Events After Vaccination for Expanded Enrollment: Substudy B	Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new/worsened muscle pain & new /worsened joint pain & recorded by participants in electronic diary. Fever defined as oral temperature >=38.0 deg C & categorized as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C & >40.0 deg C. Vomiting graded as: G 1: 1-2 times in 24 hrs; G 2: >2 times in 24 hrs; G 3: required IV hydration; G 4: emergency room visit/ hospitalization for hypotensive shock. Diarrhea graded as: G 1: 2-3 loose stools in 24 hrs; G 2: 4-5 loose stools in 24 hrs; G 3: 6 or more loose stools in 24 hrs & G 4: emergency room visit/ hospitalization. Headache, fatigue, chills, new/worsened muscle pain & new/worsened joint pain: G 1: didn't interfere with activity; G 2: some interference with activity; G 3: prevented daily routine activity & G 4: emergency room visit/ hospitalization. Exact 2-sided confidence interval based on Clopper and Pearson method.	From Day 1 to Day 7 after vaccination 1 for all arms; From Day 1 to Day 7 after vaccination 2 for 2 doses of qIRV (dose level 1), 2-visit schedule arm
Percentage of Participants Reporting Adverse Events From First Vaccination Until 4 Weeks After Last Vaccination: Substudy B	An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Only AEs collected by non-systematic assessment (i.e, excluding local reactions and systematic events) were reported in this outcome measure.	From first vaccination to 4 weeks after last vaccination (i.e., Vaccination 1 for 1-visit schedule arms and Vaccination 2 for 2-visit schedule arms)
Percentage of Participants Reporting Serious Adverse Events From First Vaccination Until 6 Months After Last Vaccination: Substudy B	An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.	From first vaccination to 6 month after last vaccination (i.e., Vaccination 1 for 1-visit schedule arms and Vaccination 2 for 2-visit schedule arms)
Percentage of Participants Reporting Abnormal Troponin I Laboratory Values 2 Days After Vaccination 1 for 2-Visit Schedule (Initial Enrollment): Substudy B	Percentage of participants reporting abnormal troponin I laboratory values 2 days after vaccination 1 were reported in this outcome measure.	2 days after vaccination 1
Percentage of Participants Reporting Abnormal Troponin I Laboratory Values 2 Days After Vaccination 2 for 2-Visit Schedule (Initial Enrollment): Substudy B	Percentage of participants reporting abnormal troponin I laboratory values 2 days after vaccination 2 were reported in this outcome measure.	2 days after vaccination 2
Percentage of Participants Reporting Abnormal Troponin I Laboratory Values 2 Days After Vaccination for 1-Visit Schedule (Initial Enrollment): Substudy B	Percentage of participants reporting abnormal troponin I laboratory values 2 days after vaccination were reported in this outcome measure.	2 days after vaccination
Percentage of Participants Reporting Abnormal Troponin I Laboratory Values 2 Days After Vaccination for Expanded Enrollment: Substudy B	Percentage of participants reporting abnormal troponin I laboratory values 2 days after vaccination were reported in this outcome measure.	2 days after last vaccination (i.e., Vaccination 1 for 1-visit schedule arms and Vaccination 2 for 2-visit schedule arms)
Percentage of Participants Reporting New ECG Abnormalities 2 Days After Vaccination 1 for 2-Visit Schedule (Initial Enrollment): Substudy B	Twelve lead ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: Sustained atrial or ventricular arrhythmias, Second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and Diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.	2 days after vaccination 1
Percentage of Participants Reporting New ECG Abnormalities 2 Days After Vaccination 2 for 2-Visit Schedule (Initial Enrollment): Substudy B	Twelve lead ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: Sustained atrial or ventricular arrhythmias, Second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and Diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.	2 days after vaccination 2
Percentage of Participants Reporting New ECG Abnormalities 2 Days After Vaccination 1 for 1-Visit Schedule (Initial Enrollment): Substudy B	Twelve lead ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: Sustained atrial or ventricular arrhythmias, Second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and Diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.	2 days after vaccination 1
Percentage of Participants Reporting New ECG Abnormalities 2 Days After Vaccination for Expanded Enrollment: Substudy B	Twelve lead ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: Sustained atrial or ventricular arrhythmias, Second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and Diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.	2 days after last vaccination (i.e., Vaccination 1 for 1-visit schedule arms and Vaccination 2 for 2-visit schedule arms)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HAI) Titers at Weeks 1, 4 and 8 After Vaccination 1: Substudy A	GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLQ.	Weeks 1, 4 and 8 after vaccination 1
Geometric Mean Fold Rise (GMFR) in HAI Titers From Before Vaccination to 1, 4, and 8 Weeks After Vaccination 1: Substudy A	Geometric mean fold rise (GMFR) was defined as ratios of the results after vaccination to the results before vaccination. GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. When prevaccination assay results were lower than the LLOQ and the postvaccination results were greater than or equal to the LLOQ, the prevaccination assay results were set to LLOQ for the GMFR calculation.	Before vaccination to 1, 4 and 8 weeks after vaccination 1
Percentage of Participants Achieving HAI Seroconversion for Each Strain At 1, 4, and 8 Weeks After Vaccination 1: Substudy A	Seroconversion was defined as an HAI titer <1:10 prior to vaccination and >=1:40 at the time point of interest, or an HAI titer of >=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method.	At 1, 4 and 8 Weeks after vaccination 1
Percentage of Participants With HAI Titer >=1:40 for Each Strain Before Vaccination 1 and at 1, 4, and 8 Weeks After Vaccination 1: Substudy A	Percentage of participants with HAI titer >=1:40 for each strain before vaccination 1 and at 1, 4 and 8 weeks after vaccination 1 is presented in this outcome measure. Exact 2-sided 95% CI was based on the Clopper and Pearson method.	Before vaccination 1 on day 1 and 1, 4 and 8 weeks after vaccination 1
Percentage of Participants Who Achieved HAI Seroconversion for All Strains at 1, 4, and 8 Weeks After Vaccination 1: qIRV Versus Licensed QIV, Substudy A	Seroconversion was defined as an HAI titer <1:10 prior to vaccination and >=1:40 at the time point of interest, or an HAI titer of >=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method.	At 1, 4, and 8 weeks After vaccination 1
Percentage of Participants With HAI Titers>=1:40 for All Strains Before Vaccination and at 1, 4, and 8 Weeks After Vaccination 1: qIRV Versus Licensed QIV, Substudy A	Percentage of participants with HAI titer >=1:40 for all strains before vaccination 1 and 1, 4 and 8 weeks after vaccination 1 is presented in this outcome measure. Exact 2-sided 95% CI was based on the Clopper and Pearson method.	Before vaccination 1 on day 1 and 1, 4, and 8 weeks after vaccination 1
Geometric Mean Ratio (GMR) of HAI Titers for Each Strain at 4 Weeks After Vaccination 1: qIRV Versus Licensed QIV, Substudy A	GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution) and were reported in the descriptive section. GMRs were estimated by the ratio of the GMTs between vaccine groups, using licensed QIV group as reference and were reported in the statistical analysis section.	4 weeks After vaccination 1
Difference in Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination 1: qIRV Versus Licensed QIV, Substudy A	Seroconversion was defined as an HAI titer <1:10 prior to vaccination and >=1:40 at the time point of interest, or an HAI titer of >=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Percentage of participants achieving seroconversion for each strain at 4 weeks after vaccination 1 and exact 2-sided 95% CI based on the Clopper and Pearson method is presented in the descriptive section. Difference in percentage of participants achieving HAI seroconversion for each strain at 4 weeks after vaccination 1 is presented in the statistical analysis section.	4 weeks after vaccination 1
HAI GMTs Before Vaccination 1 and 2 and at 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85): Expanded Enrollment: Substudy B	GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	Before vaccination 1, 2 and, 1, 4, and 8 weeks after the last vaccination (i.e. after vaccination 1 for 1-vist schedule arms and after vaccination 2 for 2-visit schedule arms)
HAI GMTs Before Vaccination 1 and 2, and at 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85 Years of Age): Initial Enrollment: Substudy B	GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ.	Prior to vaccination 1 and 2, and at 1, 4, and 8 weeks after the last vaccination (i.e. after vaccination 1 for 1-vist schedule arms and after vaccination 2 for 2-visit schedule arms)
HAI GMFR From Before Vaccination 2 to 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85 Years): Expanded Enrollment: Substudy B	GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5* LLOQ. When prevaccination assay results were lower than the LLOQ and the postvaccination results were greater than or equal to the LLOQ, the prevaccination assay results were set to LLOQ for the GMFR calculation.	From before vaccination 2 to 1, 4, and 8 weeks after the last vaccination
HAI GMFR From Before Vaccination 1 to Prior to Vaccination 2 and to 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85 Years): Initial Enrollment: Substudy B	GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. When prevaccination assay results were lower than the LLOQ and the postvaccination results were greater than or equal to the LLOQ, the prevaccination assay results were set to LLOQ for the GMFR calculation.	From before vaccination 1 to prior to vaccination 2, 1, 4, and 8 weeks after the last vaccination (i.e., vaccination 1 and 2 for 1-visit schedule and 2 visit schedule, respectively)
Percentage of Participants Achieving HAI Seroconversion for Each Strain Prior to Vaccination 2 and at 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85 Years): Expanded Enrollment: Substudy B	Seroconversion was defined as an HAI titer <1:10 prior to vaccination and >=1:40 at the time point of interest, or an HAI titer >=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided CI was based on the Clopper and Pearson method.	Prior to vaccination 2 and at 1, 4, and 8 Weeks After last Vaccination
Percentage of Participants Achieving HAI Seroconversion for Each Strain Prior to Vaccination 2 and at 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85 Years): Initial Enrollment: Substudy B	Seroconversion was defined as an HAI titer<1:10 prior to vaccination and>=1:40 at the time point of interest,or an HAI titer>=1:10 prior to vaccination with a 4-fold rise at the time point of interest.Exact 2-sided CI was based on the Clopper and Pearson method.	Prior to vaccination 2 (2-visit arms only), 1, 4 and 8 weeks after last vaccination (i.e., vaccination 1 for 1 visit and vaccination 2 for 2 visit)
Percentage of Participants With HAI Titers >=1:40 for Each Strain Before Vaccinations 1 and 2, and at 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85 Years): Expanded Enrollment: Substudy B	Proportion of participants achieving HAI titers >= 1:40 for each strain before vaccination and at 1, 4 and 8 weeks after vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method.	Before vaccination 1 and 2 and at 1, 4 and 8 weeks after last vaccination (i.e. after vaccination 1 for 1-vist schedule arms and after vaccination 2 for 2-visit schedule arms)
Percentage of Participants With HAI Titers >=1:40 for Each Strain Before Vaccinations 1 and 2 and at 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85 Years): Initial Enrollment: Substudy B	Percentage of participants achieving HAI titers >= 1:40 for each strain before vaccinations 1 and 2 and at 1, 4 and 8 weeks after last vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method.	Before vaccination 1 and 2 (for 2-visit only), and 1, 4 and 8 weeks after last vaccination (i.e., vaccination 1 for 1-visit arms and vaccination 2 for 2-visit arms)
Percentage of Participants Achieving HAI Seroconversion for All Strains Prior to Vaccination 2, and at 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85 Years): Expanded Enrollment: Substudy B	Seroconversion was defined as an HAI titer<1:10 prior to vaccination and>=1:40 at the time point of interest,or an HAI titer>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided CI was based on the Clopper and Pearson method.	Prior to vaccination 2 (for 2-visit schedule only) and at 1, 4, and 8 weeks after last vaccination (after vaccination 1 for 1-visit schedule and after vaccination 2 for 2-visit schedule)
Percentage of Participants Achieving HAI Seroconversion for All Strains Prior to Vaccination 2 and at 1, 4, and 8 Weeks the Last Vaccination (Participants Aged 65-85 Years): Initial Enrollment: Substudy B	Seroconversion was defined as an HAI titer<1:10 prior to vaccination and>=1:40 at the time point of interest,or an HAI titer>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided CI was based on the Clopper and Pearson method.	Prior to vaccination 2 (for 2-visit schedule only) and at 1, 4, and 8 weeks after last vaccination (after vaccination 1 for 1-visit schedule and after vaccination 2 for 2-visit schedule)
Percentage of Participants With HAI Titers >=1:40 for All Strains Before Vaccinations 1 and 2 and 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85 Years): Expanded Enrollment: Substudy B	Percentage of participants with HAI titers >=1:40 for all strains before vaccinations 1 and 2 and 1, 4, and 8 weeks after the last vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method.	Prior to vaccination 1 and 2, and at 1, 4, and 8 weeks after last vaccination (after vaccination 1 for 1-visit schedule and after vaccination 2 for 2-visit schedule)
Percentage of Participants With HAI Titers >=1:40 for All Strains Before Vaccinations 1 and 2 and 1, 4, and 8 Weeks After the Last Vaccination (Participants Aged 65-85 Years): Initial Enrollment: Substudy B	Percentage of participants with HAI titers >=1:40 for all strains before vaccinations 1 and 2 and 1, 4, and 8 weeks after the last vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method.	Prior to vaccination 1 and 2 and at 1, 4, and 8 Weeks After the Last Vaccination (after vaccination 1 for 1-visit schedule and after vaccination 2 for 2-visit schedule)
HAI GMTs Before Vaccination and at 1, 4, and 8 Weeks After Vaccination (Participants Aged 18-64 Years): Substudy B	HAI GMT before vaccination and at 1, 4, and 8 weeks after vaccination was described in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).	Before vaccination and 1, 4, and 8 Weeks After the Vaccination
HAI GMFR From Before Vaccination to 1, 4, and 8 Weeks After Vaccination (Participants Aged 18-64 Years): Substudy B	GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. When prevaccination assay results were lower than the LLOQ and the postvaccination results were greater than or equal to the LLOQ, the pre vaccination assay results were set to LLOQ for the GMFR calculation.	Before vaccination to 1, 4, and 8 Weeks After Vaccination
Percentage of Participants Achieving HAI Seroconversion for Each Strain at 1, 4, and 8 Weeks After Vaccination (Participants Aged 18-64 Years): Substudy B	Seroconversion was defined as an HAI titer<1:10 prior to vaccination and>=1:40 at the time point of interest,or an HAI titer>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided CI was based on the Clopper and Pearson method.	1, 4, and 8 Weeks After Vaccination
Percentage of Participants With HAI Titers >=1:40 for Each Strain Before Vaccination and at 1, 4, and 8 Weeks After Vaccination (Participants Aged 18-64 Years): Substudy B	Percentage of participants with HAI titers >=1:40 for each strain before vaccination and 1, 4, and 8 weeks after vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method.	Before vaccination and 1, 4, and 8 Weeks After Vaccination
Percentage of Participants Achieving HAI Seroconversion for All Strains at 1, 4, and 8 Weeks After Vaccination (Participants Aged 18-64 Years): Substudy B	Seroconversion was defined as an HAI titer<1:10 prior to vaccination and>=1:40 at the time point of interest,or an HAI titer>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided CI was based on the Clopper and Pearson method.	1, 4, and 8 Weeks After Vaccination
Percentage of Participants With HAI Titers >=1:40 for All Strains Before Vaccination and 1, 4, and 8 Weeks After Vaccination (Participants Aged 18-64 Years): Substudy B	Percentage of participants with HAI titers >=1:40 for all strains before vaccination and 1, 4, and 8 weeks after vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method.	Before vaccination and 1, 4, and 8 Weeks After Vaccination

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Actual): January 27, 2023
• Study Completion (Actual): January 27, 2023

Study Registration Dates

• First Submitted: June 28, 2021
• First Submitted That Met QC Criteria: September 13, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Influenza; Vaccine; Flu; Grippe; RNA vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: C4781001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No