A PHASE 3, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A COMBINED MODIFIED RNA VACCINE CANDIDATE AGAINST COVID-19 AND INFLUENZA IN HEALTHY INDIVIDUALS
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- BioNTech SE
- 入组人数
- 8,795
- 试验地点
- 95
- 主要终点
- Cohort 1: Percentage of Participants With Any Local Reactions for up to 7 Days Following Vaccination in Investigational Vaccine Extremity
研究概览
简要总结
The purpose of this study is to understand the safety and effects of a combined influenza and COVID-19 vaccine. This combined vaccine is compared to separate vaccines for the protection against influenza and SARS-CoV-2. Influenza and COVID-19 are diseases that can spread easily from one person to another and cause body aches, fever, cough, and other symptoms. Giving both influenza and COVID-19 vaccines together against influenza and SARS-CoV-2 could provide great benefits to both patients and caregivers in terms of simple and easy care. Around 8550 participants will be assigned into 1 of 8 vaccination groups (Group A, B, C, D, E, F, G or H) by chance.
Cohort 1: Approximately 450 participants will be assigned by chance to one of the following:
- Group A:Influenza and COVID-19 combination A vaccine, given at the same time in one arm and placebo (an injection consisting of just salt water and no medicines in it) in the opposite arm.
- Group B: COVID-19 vaccine, given at the same time to one arm and licensed influenza vaccine in the opposite arm.
Cohort 2: Approximately 4500 participants will be assigned by chance to one of the following:
- Group C: Influenza and COVID-19 combination B vaccine, given at the same time in one arm and placebo in the opposite arm.
- Group D: COVID-19 vaccine, given at the same time in one arm and licenced influenza vaccine in the opposite arm.
Cohort 3: Approximately 3600 participants will be assigned by chance to one of the following:
- Group E: Influenza and COVID-19 combination B vaccine.
- Group F: COVID-19 vaccine.
- Group G: Licenced influenza vaccine.
- Group H: Investigational influenza vaccine.
All participants in cohort 1 and cohort 2 will receive 2 injections and participants in cohort 3 will receive 1 injection as per their assigned study group at Visit 1. The participants will be followed for about 6 months. During this time, researchers will assess safety and the body's reaction to the vaccination over approximately 6 months. This will help understand if the study medicine is safe.
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
- Double (Participant, Investigator)
盲法说明
This is an observer-blinded study. Study staff dispensing and administering the vaccine will be unblinded, but all other study personnel, including the principal investigator, and the participant, will be blinded.
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants 18 through 64 years of age (or the minimum age of consent in accordance with local regulations) at Visit
- •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.
排除标准
- •Vaccination with any investigational or licensed influenza vaccine within 6 months (175 days) before study intervention administration, or ongoing receipt of chronic antiviral therapy with activity against influenza.
- •Vaccination with any investigational or licensed COVID-19 vaccine within 6 months (175 days) before study intervention administration.
- •Please refer to the study contact for further eligibility details
研究组 & 干预措施
Cohort 2 Arm D: COVID-19 vaccine and licensed influenza vaccine concomitant administration group
Cohort 2 Arm D: COVID-19 vaccine and licensed influenza vaccine concomitant administration group
干预措施: Licensed influenza vaccine (Biological)
Cohort 1 Arm A: Influenza and COVID-19 Combination A and Placebo
Cohort 1 Arm A: Influenza and COVID-19 combination A vaccine and Placebo
干预措施: Influenza and COVID-19 Combination A (Biological)
Cohort 1 Arm A: Influenza and COVID-19 Combination A and Placebo
Cohort 1 Arm A: Influenza and COVID-19 combination A vaccine and Placebo
干预措施: Placebo (Biological)
Cohort 1 Arm B: COVID-19 vaccine and licensed influenza vaccine concomitant administration group
Cohort 1 Arm B: COVID-19 vaccine and licensed influenza vaccine concomitant administration group
干预措施: Licensed influenza vaccine (Biological)
Cohort 1 Arm B: COVID-19 vaccine and licensed influenza vaccine concomitant administration group
Cohort 1 Arm B: COVID-19 vaccine and licensed influenza vaccine concomitant administration group
干预措施: COVID-19 Vaccine (Biological)
Cohort 2 Arm C:Influenza and COVID-19 Combination B and Placebo
Cohort 2 Arm C: Influenza and COVID-19 Combination B vaccine and Placebo
干预措施: Influenza and COVID-19 Combination B (Biological)
Cohort 2 Arm C:Influenza and COVID-19 Combination B and Placebo
Cohort 2 Arm C: Influenza and COVID-19 Combination B vaccine and Placebo
干预措施: Placebo (Biological)
Cohort 2 Arm D: COVID-19 vaccine and licensed influenza vaccine concomitant administration group
Cohort 2 Arm D: COVID-19 vaccine and licensed influenza vaccine concomitant administration group
干预措施: COVID-19 Vaccine (Biological)
Cohort 3 Arm E:Influenza and COVID-19 Combination B
Cohort 3 Arm E:Influenza and COVID-19 Combination B
干预措施: Influenza and COVID-19 Combination B (Biological)
Cohort 3 Arm F: COVID-19 vaccine
Cohort 3 Arm F: COVID-19 vaccine
干预措施: COVID-19 Vaccine (Biological)
Cohort 3 Arm G: Licensed influenza vaccine
Cohort 3 Arm G: Licensed influenza vaccine
干预措施: Licensed influenza vaccine (Biological)
Cohort 3 Arm H: Investigational influenza vaccine
Cohort 3 Arm H: Investigational influenza vaccine
干预措施: Investigational influenza vaccine (Biological)
结局指标
主要结局
Cohort 1: Percentage of Participants With Any Local Reactions for up to 7 Days Following Vaccination in Investigational Vaccine Extremity
时间窗: From Day 1 through Day 7 after Vaccination [Vaccination on Day 1]
Local reactions included redness, swelling, and pain at the injection site, were recorded in the electronic dairy (e-diary) or case report form (CRF) after vaccination. Local reactions were graded per the 'Local Reaction Grading Scale' per protocol. Percentage of participants with at least 1 local reaction of grade 1 and above were reported in this outcome measure.
Cohort 2: Percentage of Participants With Any Local Reactions for up to 7 Days Following Vaccination in Investigational Vaccine Extremity
时间窗: From Day 1 through Day 7 after Vaccination [Vaccination on Day1]
Local reactions included redness, swelling, and pain at the injection site, were recorded in the e-diary or CRF after vaccination. Local reactions were graded per the 'Local Reaction Grading Scale' per protocol. Percentage of participants with at least 1 local reaction of grade 1 and above were reported in this outcome measure.
Cohort 3: Percentage of Participants With Any Local Reactions for up to 7 Days Following Vaccination in Investigational Vaccine Extremity
时间窗: From Day 1 through Day 7 after Vaccination [Vaccination on Day 1]
Local reactions included redness, swelling, and pain at the injection site, were recorded in the e-diary or CRF after vaccination. Local reactions were graded per the 'Local Reaction Grading Scale' per protocol. Percentage of participants with at least 1 local reaction of grade 1 and above were reported in this outcome measure.
Cohort 1: Percentage of Participants With Any Systemic Events for up to 7 Days Following Vaccination
时间窗: From Day 1 through Day 7 after Vaccination [Vaccination on Day 1]
Systemic events including fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain were recorded in an e-diary or CRF after vaccination. Systemic events were graded per the 'Systemic Events Grading Scale' per protocol. Percentage of participants with at least 1 systemic event of grade 1 and above were reported in this outcome measure.
Cohort 2: Percentage of Participants With Any Systemic Events for up to 7 Days Following Vaccination
时间窗: From Day 1 through Day 7 after Vaccination [Vaccination on Day 1]
Systemic events including fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain were recorded in an e-diary or CRF after vaccination. Systemic events were graded per the 'Systemic Events Grading Scale' per protocol. Percentage of participants with at least 1 systemic event of grade 1 and above were reported in this outcome measure.
Cohort 3: Percentage of Participants With Any Systemic Events for up to 7 Days Following Vaccination
时间窗: From Day 1 through Day 7 after Vaccination [Vaccination on Day 1]
Systemic events including fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain were recorded in an e-diary or CRF after vaccination. Systemic events were graded per the 'Systemic Events Grading Scale' per protocol. Percentage of participants with at least 1 systemic event of grade 1 and above were reported in this outcome measure.
Cohort 1: Percentage of Participants Reporting Adverse Events (AEs) From Vaccination Through 4 Weeks After Vaccination
时间窗: From Vaccination on Day 1 through 4 Weeks after Vaccination
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. AEs included both serious and all non-serious AEs. Serious AE (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, any other pre-specified criteria in protocol of the study or other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.
Cohort 2: Percentage of Participants Reporting AEs From Vaccination Through 4 Weeks After Vaccination
时间窗: From Vaccination on Day 1 through 4 Weeks after Vaccination
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. AEs included both serious and all non-serious AEs. 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, any other pre-specified criteria in protocol of the study or other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.
Cohort 3: Percentage of Participants Reporting AEs From Vaccination Through 4 Weeks After Vaccination
时间窗: From Vaccination on Day 1 through 4 Weeks after Vaccination
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. AEs included both serious and all non-serious AEs. 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, any other pre-specified criteria in protocol of the study or other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.
Cohort 1: Percentage of Participants Reporting SAEs From Vaccination Through 6 Months After Vaccination
时间窗: From Vaccination on Day 1 through 6 Months after Vaccination
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 any other pre-specified criteria in protocol of the study or other important medical event.
Cohort 2: Percentage of Participants Reporting SAEs From Vaccination Through 6 Months After Vaccination
时间窗: From Vaccination on Day 1 through 6 Months after Vaccination
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 any other pre-specified criteria in protocol of the study or other important medical event.
Cohort 3: Percentage of Participants Reporting SAEs From Vaccination Through 6 Months After Vaccination
时间窗: From Vaccination on Day 1 through 6 Months after Vaccination
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 any other pre-specified criteria in protocol of the study or other important medical event.
Cohort 2: Geometric Mean Titer (GMT) and Geometric Mean Ratio (GMR) of Strain-Specific Hemagglutination Inhibition Assay (HAI) Titers at 4 Weeks After Vaccination: Non-inferiority
时间窗: At 4 Weeks after Vaccination
GMTs and the corresponding 2-sided confidence interval (CIs) were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the lower limit of quantitation (LLOQ) were set to 0.5 \*LLOQ. GMTs were reported in the descriptive data section of this outcome measure. GMRs were reported in the statistical analysis section. Data was reported for the following strains: H1N1, H3N2 and Victoria.
Cohort 2: Percentage of Participants and Difference in Percentage of Participants With Strain-Specific HAI Seroconversion at 4 Weeks After Vaccination: Non-inferiority
时间窗: At 4 Weeks after Vaccination
Seroconversion was defined as having an HAI titer \<1:10 prior to vaccination and greater than or equal to (\>=) 1:40 at the postvaccination time point of interest, or an HAI titer of \>=1:10 prior to vaccination with a minimum 4-fold rise at the postvaccination time point of interest. Percentage of participants with seroconversion were reported in the descriptive data section of this outcome measure. Difference in percentage of participants with seroconversion were reported in the statistical analysis section. Data was reported for the following strains: H1N1, H3N2 and Victoria.
Cohort 2: GMT and GMR of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Neutralizing Titers at 4 Weeks After Vaccination: Non-inferiority
时间窗: At 4 Weeks after Vaccination
GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 \*LLOQ. GMTs were reported in the descriptive data section of this outcome measure. GMRs were reported in the statistical analysis section.
Cohort 2: Percentage of Participants and Difference in Percentage of Participants With SARS-CoV-2 Seroresponse at 4 Weeks After Vaccination: Non-inferiority
时间窗: At 4 Weeks after Vaccination
Seroresponse was defined as achieving a postvaccination \>=4-fold rise from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of \>=4\*LLOQ was considered seroresponse. Percentage of participants with seroresponse were reported in the descriptive data section of this outcome measure. Difference in percentage of participants with seroresponse were reported in the statistical analysis section.
次要结局
- Cohort 3: GMT and GMR of Strain-Specific HAI Titers at 4 Weeks After Vaccination: Non-inferiority(At 4 Weeks after Vaccination)
- Cohort 3: GMT and GMR of SARS-CoV-2 Neutralizing Titers at 4 Weeks After Vaccination: Non-inferiority(At 4 Weeks after Vaccination)