A PHASE 1/2 RANDOMIZED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MODIFIED RNA VACCINE AGAINST INFLUENZA IN HEALTHY INDIVIDUALS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 1,158
- 试验地点
- 190
- 主要终点
- Percentage of Participants Reporting Local Reactions After Vaccination 1: Substudy A
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
SSA: observer-blinded, sponsor unblind SSB: single-blind, sponsor unblind
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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
- •Prior history of heart disease.
- •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
- •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.
结局指标
主要结局
Percentage of Participants Reporting Local Reactions After Vaccination 1: Substudy A
时间窗: From Day 1 to Day 7 after Vaccination 1
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.
Percentage of Participants Reporting Systemic Events After Vaccination 1: Substudy A
时间窗: From Day 1 to Day 7 After Vaccination 1
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.
Percentage of Participants Reporting Systemic Events After Vaccination 2: Substudy A
时间窗: From Day 1 to Day 7 after Vaccination 2
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.
Percentage of Participants With Grade Shifts in Hematology Values at 1 Week After Vaccination 1: Substudy A
时间窗: From Baseline (prior to vaccination 1) to 1 week after vaccination 1
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.
Percentage of Participants Reporting Local Reactions After Vaccination 2: Substudy A
时间窗: From Day 1 to Day 7 after Vaccination 2
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.
Percentage of Participants Reporting Adverse Events After Vaccination 1: Substudy A
时间窗: From Day 1 up to 4 weeks After Vaccination 1
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.
Percentage of Participants Reporting Serious Adverse Events (SAE) From First Vaccination to 6 Months After Last Vaccination: Substudy A
时间窗: From vaccination 1 on day 1 up to 6 months after vaccination 2
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.
Percentage of Participants With New Electrocardiogram (ECG) Abnormalities at 1 Week After Vaccination 1: Substudy A
时间窗: 1 week after vaccination 1
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.
Percentage of Participants Reporting Local Reactions After Vaccination for 1-Visit Schedule (Initial Enrollment): Substudy B
时间窗: From Day 1 to Day 7 after vaccination
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.
Percentage of Participants Reporting Adverse Events After Vaccination 2: Substudy A
时间窗: From Day 1 up to 4 weeks After vaccination 2
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.
Percentage of Participants With Abnormal Hematology Values at 1 Week After Vaccination 1: Substudy A
时间窗: 1 week after vaccination 1
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.
Percentage of Participants With Abnormal Chemistry Values at 2 Days After Vaccination 1: Substudy A
时间窗: 2 days after vaccination 1
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.
Percentage of Participants With Grade Shifts in Hematology Values at 2 Days After Vaccination 1: Substudy A
时间窗: From Baseline (prior to vaccination 1) to 2 days after vaccination 1
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.
Percentage of Participants With Abnormal Hematology Values at 2 Days After Vaccination 1: Substudy A
时间窗: 2 days after vaccination 1
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.
Percentage of Participants With Grade Shifts in Chemistry Laboratory Values at 2 Days After Vaccination 1: Substudy A
时间窗: From Baseline (prior to vaccination 1) to 2 days after vaccination 1
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.
Percentage of Participants With Grade Shifts in Chemistry Laboratory Values at 1 Week After Vaccination 1: Substudy A
时间窗: From Baseline (prior to vaccination 1) to 1 week after vaccination 1
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.
Percentage of Participants With Abnormal Chemistry Values at 1 Week After Vaccination 1: Substudy A
时间窗: 1 week after vaccination 1
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.
Percentage of Participants With New Electrocardiogram (ECG) Abnormalities at 2 Days After Vaccination 1: Substudy A
时间窗: 2 days after vaccination 1
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.
Percentage of Participants Reporting Local Reactions After Vaccination 1 for 2- Visit Schedule (Initial Enrollment): Substudy B
时间窗: From Day 1 to Day 7 after vaccination 1
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.
Percentage of Participants Reporting Local Reactions After Vaccination 2 for 2- Visit Schedule (Initial Enrollment): Substudy B
时间窗: From Day 1 to Day 7 after vaccination 2
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.
Percentage of Participants Reporting Systemic Events After Vaccination for 1-Visit Schedule (Initial Enrollment): Substudy B
时间窗: From Day 1 to Day 7 after vaccination
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.
Percentage of Participants Reporting Systemic Events After Vaccination 1 for 2- Visit Schedule (Initial Enrollment): Substudy B
时间窗: From Day 1 to Day 7 after vaccination 1
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.
Percentage of Participants Reporting Local Reactions After Vaccination for Expanded Enrollment: Substudy B
时间窗: 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
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.
Percentage of Participants Reporting Systemic Events After Vaccination 2 for 2-Visit Schedule (Initial Enrollment) : Substudy B
时间窗: From day 1 to day 7 of vaccination 2
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.
Percentage of Participants Reporting Systemic Events After Vaccination for Expanded Enrollment: Substudy B
时间窗: 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
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.
Percentage of Participants Reporting Adverse Events From First Vaccination Until 4 Weeks After Last Vaccination: Substudy B
时间窗: 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)
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.
Percentage of Participants Reporting Serious Adverse Events From First Vaccination Until 6 Months After Last Vaccination: Substudy B
时间窗: 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)
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.
Percentage of Participants Reporting Abnormal Troponin I Laboratory Values 2 Days After Vaccination 1 for 2-Visit Schedule (Initial Enrollment): Substudy B
时间窗: 2 days after vaccination 1
Percentage of participants reporting abnormal troponin I laboratory values 2 days after vaccination 1 were reported in this outcome measure.
Percentage of Participants Reporting Abnormal Troponin I Laboratory Values 2 Days After Vaccination 2 for 2-Visit Schedule (Initial Enrollment): Substudy B
时间窗: 2 days after vaccination 2
Percentage of participants reporting abnormal troponin I laboratory values 2 days after vaccination 2 were reported in this outcome measure.
Percentage of Participants Reporting Abnormal Troponin I Laboratory Values 2 Days After Vaccination for 1-Visit Schedule (Initial Enrollment): Substudy B
时间窗: 2 days after vaccination
Percentage of participants reporting abnormal troponin I laboratory values 2 days after vaccination were reported in this outcome measure.
Percentage of Participants Reporting Abnormal Troponin I Laboratory Values 2 Days After Vaccination for Expanded Enrollment: Substudy B
时间窗: 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 abnormal troponin I laboratory values 2 days after vaccination were reported in this outcome measure.
Percentage of Participants Reporting New ECG Abnormalities 2 Days After Vaccination 2 for 2-Visit Schedule (Initial Enrollment): Substudy B
时间窗: 2 days after vaccination 2
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.
Percentage of Participants Reporting New ECG Abnormalities 2 Days After Vaccination 1 for 2-Visit Schedule (Initial Enrollment): Substudy B
时间窗: 2 days after vaccination 1
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.
Percentage of Participants Reporting New ECG Abnormalities 2 Days After Vaccination 1 for 1-Visit Schedule (Initial Enrollment): Substudy B
时间窗: 2 days after vaccination 1
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.
Percentage of Participants Reporting New ECG Abnormalities 2 Days After Vaccination for Expanded Enrollment: Substudy B
时间窗: 2 days after last vaccination (i.e., Vaccination 1 for 1-visit schedule arms and Vaccination 2 for 2-visit schedule arms)
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.
次要结局
- 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(Before vaccination 1 on day 1 and 1, 4, and 8 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(4 weeks after vaccination 1)
- 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(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): Initial Enrollment: Substudy B(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 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(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(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 Vaccination and 1, 4, and 8 Weeks After Vaccination (Participants Aged 18-64 Years): Substudy B(Before vaccination and 1, 4, and 8 Weeks After Vaccination)
- Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HAI) Titers at Weeks 1, 4 and 8 After Vaccination 1: Substudy A(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(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(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(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(At 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(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(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(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(From before vaccination 2 to 1, 4, and 8 weeks after the 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): Expanded Enrollment: Substudy B(Prior to vaccination 2 and at 1, 4, and 8 Weeks After last Vaccination)
- 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(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(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(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): Initial Enrollment: Substudy B(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(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(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(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(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(1, 4, and 8 Weeks After Vaccination)