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

Pfizer1,158 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Interventions

mIRVBIOLOGICAL

Intramuscular injection

bIRV ABBIOLOGICAL

Intramuscular injection

qIRVBIOLOGICAL

Intramuscular injection

QIVBIOLOGICAL

Intramuscular injection

bIRV AABIOLOGICAL

Intramuscular injection

bIRV BBBIOLOGICAL

Intramuscular injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (100)

North Alabama Research Center

Athens, Alabama, United States

The Heart Center

Athens, Alabama, United States

Arizona Heart Rhythm Center

Phoenix, Arizona, United States

HOPE Research Institute

Phoenix, Arizona, United States

The Pain Center of Arizona

Phoenix, Arizona, United States

Noble Clinical Research

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 2 days after vaccination 1

Percentage of Participants With Abnormal Chemistry Values at 1 Week After Vaccination 1: Substudy A

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 2 days after vaccination 1

Percentage of Participants With New Electrocardiogram (ECG) Abnormalities at 1 Week After Vaccination 1: Substudy A

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 2 days after vaccination 1

Percentage of Participants Reporting New ECG Abnormalities 2 Days After Vaccination for Expanded Enrollment: Substudy B

Time frame: 2 days after last vaccination (i.e., Vaccination 1 for 1-visit schedule arms and Vaccination 2 for 2-visit schedule arms)

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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

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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Prior to vaccination 2 and at 1, 4, and 8 Weeks After last Vaccination

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Before vaccination and 1, 4, and 8 Weeks After Vaccination

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

Overview

Conditions

Interventions

Eligibility

Locations (100)

Outcomes

Primary Outcomes

Secondary Outcomes