A PHASE 3, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MODIFIED RNA VACCINE AGAINST INFLUENZA COMPARED TO LICENSED INACTIVATED INFLUENZA VACCINE IN HEALTHY ADULTS 18 YEARS OF AGE OR OLDER
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 45,789
- 试验地点
- 299
- 主要终点
- Percentage of Participants Reporting First Episode of LCI Cases With Associated Per-Protocol ILI Caused by Any Strain at Least 14 Days After Vaccination: 18-64 Years
研究概览
简要总结
This is a Phase 3, randomized, observer-blinded study to evaluate the efficacy, safety, tolerability, and immunogenicity of a single dose of a quadrivalent influenza modRNA vaccine compared to licensed inactivated influenza vaccine in healthy adults 18 years of age and older.
详细描述
This is a Phase 3, randomized, observer-blinded study to evaluate the efficacy, safety, tolerability, and immunogenicity of a quadrivalent influenza modRNA vaccine (qIRV) encoding HA of 4 seasonally recommended strains (2 A strains and 2 B strains) compared to licensed quadrivalent influenza vaccine (QIV) in healthy adults 18 years of age and older.
Participants may be enrolled in either the reactogenicity subset, immunogenicity subset, or both/neither subset(s). Efficacy will be assessed in this study through surveillance for influenza-like illness.
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
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female participants ≥18 years of age at Visit 1 (Day 1).
- •Participants who are willing and able to comply with all scheduled visits, investigational 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.
- •Capable of giving signed informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
排除标准
- •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 any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
- •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.
- •Allergy to egg proteins (egg or egg products) or chicken proteins.
- •Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), eg, for cancer or an autoimmune disease, or planned receipt throughout the study. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
- •Receipt of blood/plasma products or immunoglobulin from 60 days before study intervention administration, or planned receipt throughout the study.
- •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.
- •Any participant who has received or plans to receive a modRNA-platform SARS CoV-2 vaccine within 14 days before or after study vaccination at Visit
- •Participation in other studies involving administration of a study intervention within 28 days prior to, and/or during, participation in this study.
- •Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
研究组 & 干预措施
Quadrivalent influenza vaccine, 18 through 64 years of age
Licensed quadrivalent influenza vaccine (single dose), participants 18 through 64 years of age
干预措施: Quadrivalent influenza vaccine (Biological)
Quadrivalent influenza modRNA vaccine, ≥65 years of age
Quadrivalent influenza modRNA vaccine (single dose), participants ≥65 years of age
干预措施: Quadrivalent influenza modRNA vaccine (Biological)
Quadrivalent influenza modRNA vaccine, 18 through 64 years of age
Quadrivalent influenza modRNA vaccine (single dose), participants 18 through 64 years of age
干预措施: Quadrivalent influenza modRNA vaccine (Biological)
Quadrivalent influenza vaccine, ≥65 years of age
Licensed quadrivalent influenza vaccine (single dose), participants ≥65 years of age
干预措施: Quadrivalent influenza vaccine (Biological)
结局指标
主要结局
Percentage of Participants Reporting First Episode of LCI Cases With Associated Per-Protocol ILI Caused by Any Strain at Least 14 Days After Vaccination: 18-64 Years
时间窗: Day 15 to surveillance cut-off (approximately 6 months)
LCI was defined as influenza infection confirmed through through reverse transcription- polymerase chain reaction (RT-PCR) or culture at the central laboratory, unless otherwise specified. Per-protocol ILI was defined as occurrence (new onset or worsening of preexisting condition) of at least 1 respiratory symptoms concurrently with at least 1 systemic symptoms. Data was obtained during the 2022-2023 northern hemisphere influenza season up to surveillance cut-off decided by Sponsor.
Percentage of Participants Reporting First Episode of Laboratory-Confirmed Influenza (LCI) Cases With Associated Per-Protocol Influenza-Like Illness (ILI) Caused by Any Strain at Least 14 Days After Vaccination: >= 65 Years
时间窗: Day 15 up to primary surveillance cut-off (approximately 1 year)
LCI was defined as influenza infection confirmed through RT-PCR or culture at the central laboratory, unless otherwise specified. Per-protocol ILI was defined as occurrence (new onset or worsening of preexisting condition) of at least 1 respiratory symptoms concurrently with at least 1 systemic symptoms. Data was obtained during the 2022-2023 northern and southern hemisphere influenza season up to surveillance cut-off decided by Sponsor.
Percentage of Participants Reporting Any Local Reactions Within 7 Days After Study Vaccination: 18-64 Years
时间窗: From Day 1 to Day 7 after study vaccination
Local reactions included redness, swelling and pain at the injection site and were recorded by participants in an e-diary. All local reactions were graded based on Center for Biologics Evaluation and Research (CBER) toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure data is reported for any local reaction and any grade.
Percentage of Participants Reporting Any Local Reactions Within 7 Days After Study Vaccination: >=65 Years
时间窗: From Day 1 to Day 7 after study vaccination
Local reactions included redness, swelling and pain at the injection site and were recorded by participants in an e-diary. All local reactions were graded based on Center for Biologics Evaluation and Research (CBER) toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure data is reported for any local reaction and any grade.
Percentage of Participants Reporting Any Systemic Events Within 7 Days After Study Vaccination: 18-64 Years
时间窗: From Day 1 to Day 7 after study vaccination
Systemic events (vomiting, diarrhoea, headache, Fatigue/tiredness, chills, new or worsened muscle pain and joint pain) were recorded by participants in an e-diary. All systemic events were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure data is reported for any systemic reaction and any grade.
Percentage of Participants Reporting Any Systemic Events Within 7 Days After Study Vaccination: >=65 Years
时间窗: From Day 1 to Day 7 after study vaccination
Systemic events (vomiting, diarrhoea, headache, Fatigue/tiredness, chills, new or worsened muscle pain and joint pain) were recorded by participants in an e-diary. All systemic events were graded based on CBER toxicity guidelines as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (potentially life-threatening). In this outcome measure data is reported for any systemic reaction and any grade.
Percentage of Participants Reporting Adverse Events (AEs) From Study Vaccination Through 4 Weeks After Study Vaccination: 18-64 Years
时间窗: From study vaccination on Day 1 through 4 weeks after study 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. Results excluded local reactions and systemic events data.
Percentage of Participants Reporting AEs From Study Vaccination Through 4 Weeks After Study Vaccination: >=65 Years
时间窗: From study vaccination on Day 1 through 4 weeks after study 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. Results excluded local reactions and systemic events data.
Percentage of Participants Reporting AEs From Study Vaccination Through 4 Weeks After Study Vaccination: >=18 Years
时间窗: From study vaccination on Day 1 through 4 weeks after study 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. Results excluded local reactions and systemic events data.
Percentage of Participants Reporting Serious Adverse Events (SAEs) From Study Vaccination Through 6 Months After Study Vaccination: 18-64 Years
时间窗: From Day 1 up to 6 months after vaccination
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.
Percentage of Participants Reporting SAEs From Study Vaccination Through 6 Months After Study Vaccination: >=65 Years
时间窗: From Day 1 up to 6 months after vaccination
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.
Percentage of Participants Reporting SAEs From Study Vaccination Through 6 Months After Study Vaccination: >=18 Years
时间窗: From Day 1 up to 6 months after vaccination
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.
次要结局
- HAI GMTs at Baseline for 2022-2023 Northern Hemisphere - Based on HAI Assay 1: 18-64 Years(Baseline)
- HAI GMTs at Baseline for 2022-2023 Northern Hemisphere- Based on HAI Assay 1: >=65 Years(Baseline)
- Percentage of Participants Reporting First Episode of LCI Cases With Associated Per-Protocol ILI Caused by All Matched Strains at Least 14 Days After Vaccination: 18-64 Years(Day 15 to surveillance cut-off (approximately 6 months))
- Percentage of Participants Reporting First Episode of LCI Cases With Associated Per-Protocol ILI Caused by All Matched Strains at Least 14 Days After Vaccination: >=65 Years(Day 15 up to primary surveillance cut-off (approximately 1 year))
- Percentage of Participants Reporting First Episode of Culture Confirmed Influenza (CCI) With Associated Per-Protocol ILI Caused by Any Strain at Least 14 Days After Vaccination: 18-64 Years(Day 15 to surveillance cut-off (approximately 6 months))
- Percentage of Participants Reporting First Episode of CCI With Associated Per-Protocol ILI Caused by Any Strain at Least 14 Days After Vaccination: >=65 Years(Day 15 up to primary surveillance cut-off (approximately 1 year))
- Percentage of Participants Reporting First Episode of LCI Cases With Associated ILI as Defined by Modified Centers for Disease Control and Prevention (CDC) Caused by Any Strain at Least 14 Days After Vaccination: 18-64 Years(Day 15 to surveillance cut-off (approximately 6 months))
- Percentage of Participants Reporting First Episode of LCI Cases With Associated ILI as Defined by Modified CDC Caused by Any Strain at Least 14 Days After Vaccination: >=65 Years(Day 15 up to primary surveillance cut-off (approximately 1 year))
- Percentage of Participants With HAI Titers >=1:40 at Baseline and 4 Weeks After Vaccination for 2023 Southern Hemisphere - Based on HAI Assay 1: 18-64 Years(Baseline and 4 weeks after vaccination)
- Percentage of Participants Reporting First Episode of LCI Cases With Associated ILI as Defined by World Health Organization (WHO) Caused by Any Strain at Least 14 Days After Vaccination: 18-64 Years(Day 15 to surveillance cut-off (approximately 6 months))
- Percentage of Participants Reporting First Episode of LCI Cases With Associated ILI as Defined by WHO Caused by Any Strain at Least 14 Days After Vaccination: >=65 Years(Day 15 up to primary surveillance cut-off (approximately 1 year))
- Percentage of Participants Reporting First Episode Cases of Influenza as Confirmed by RT-PCR or Local RT-PCR or Culture, With Associated Per-Protocol ILI at Least 14 Days After Vaccination: 18-64 Years(Day 15 to surveillance cut-off (approximately 6 months))
- Percentage of Participants Reporting First Episode Cases of Influenza as Confirmed by Central RT-PCR or Local RT-PCR or Culture, With Associated Per-Protocol ILI at Least 14 Days After Vaccination: >=65 Years(Day 15 up to primary surveillance cut-off (approximately 1 year))
- HAI GMTs Used to Determine GMRs of qIRV to Licensed QIV at 4 Weeks After Vaccination for 2022-2023 Northern Hemisphere- Based on HAI Assay 2: 18-64 Years(4 Weeks after vaccination)
- HAI GMTs Used to Determine GMRs of qIRV to Licensed QIV for 2022-2023 Northern Hemisphere at 4 Weeks After Vaccination- Based on HAI Assay 2: >=65 Years(4 Weeks after vaccination)
- Percentage of Participants and Difference in Percentage of Participants Achieving Seroconversion at 4 Weeks After Vaccination With qIRV and Licensed QIV for 2022-2023 Northern Hemisphere- Based on HAI Assay 2: 18-64 Years(4 Weeks after vaccination)
- Percentage of Participants and Difference in Percentage of Participants Achieving Seroconversion at 4 Weeks After Vaccination With qIRV and Licensed QIV for 2022-2023 Northern Hemisphere- Based on HAI Assay 2: >=65 Years(4 Weeks after vaccination)
- HAI GMTs Used to Determine GMRs of qIRV to Licensed QIV for 2022-2023 Northern Hemisphere at 4 Weeks After Vaccination- Based on HAI Assay 1: 18-64 Years(4 Weeks after vaccination)
- HAI GMTs Used to Determine GMRs of qIRV to Licensed QIV for 2022-2023 Northern Hemisphere at 4 Weeks After Vaccination - Based on HAI Assay 1: >=65 Years(4 Weeks after vaccination)
- Percentage of Participants and Difference in Percentage of Participants Achieving Seroconversion at 4 Weeks After Vaccination With qIRV and Licensed QIV for 2022-2023 Northern Hemisphere-Based on HAI Assay 1: 18-64 Years(4 Weeks after vaccination)
- Percentage of Participants and Difference in Percentage of Participants Achieving Seroconversion at 4 Weeks After Vaccination With qIRV and Licensed QIV for 2022-2023 Northern Hemisphere- Based on HAI Assay 1: >=65 Years(4 Weeks after vaccination)
- HAI GMTs at Baseline for the 2022-2023 Northern Hemisphere - Based on HAI Assay 2: 18-64 Years(Baseline (Before Vaccination))
- HAI GMTs at Baseline for 2022-2023 Northern Hemisphere - Based on HAI Assay 2: >=65 Years(Baseline (Before Vaccination))
- HAI Geometric Mean Fold Rise (GMFR) From Before Vaccination to 4 Weeks After Vaccination for 2022-2023 Northern Hemisphere- Based on HAI Assay 2: 18-64 Years(Before vaccination (Baseline) to 4 weeks after vaccination)
- HAI GMFR Before Vaccination to 4 Weeks After Vaccination for 2022-2023 Northern Hemisphere- Based on HAI Assay 2: >=65 Years(Before vaccination (Baseline) to 4 weeks after vaccination)
- Percentage of Participants With HAI Titers >=1:40 at Baseline and 4 Weeks After Vaccination for 2022-2023 Northern Hemisphere- Based on HAI Assay 2: 18-64 Years(Baseline and 4 weeks after vaccination)
- Percentage of Participants With HAI Titers >=1:40 at Baseline and 4 Weeks After Vaccination for 2022-2023 Northern Hemisphere - Based on HAI Assay 2: >=65 Years(Baseline and 4 weeks after vaccination)
- Percentage of Participants With HAI Titers >=1:40 at Baseline and 4 Weeks After Vaccination for 2023 Southern Hemisphere - Based on HAI Assay 1: >=65 Years(Baseline and 4 weeks after vaccination)
- HAI GMFR Before Vaccination to 4 Weeks After Vaccination for 2022-2023 Northern Hemisphere- Based on HAI Assay 1: 18-64 Years(Before vaccination (Baseline) to 4 weeks after vaccination)
- HAI GMFR Before Vaccination to 4 Weeks After Vaccination for 2022-2023 Northern Hemisphere- Based on HAI Assay 1: >=65 Years(Before vaccination (Baseline) to 4 weeks after vaccination)
- Percentage of Participants With HAI Titers >=1:40 at Baseline and 4 Weeks After Vaccination for 2022-2023 Northern Hemisphere - Based on HAI Assay 1: 18-64 Years(Baseline and 4 weeks after vaccination)
- Percentage of Participants With HAI Titers >=1:40 at Baseline and 4 Weeks After Vaccination for 2022-2023 Northern Hemisphere - Based on HAI Assay 1: >=65 Years(Baseline and 4 weeks after vaccination)
- HAI GMTs at Baseline and 4 Weeks After Vaccination for 2023 Southern Hemisphere - Based on HAI Assay 2: 18-64 Years(Baseline and 4 weeks after vaccination)
- HAI GMTs at Baseline and 4 Weeks After Vaccination for 2023 Southern Hemisphere - Based on HAI Assay 2: >=65 Years(Baseline and 4 weeks after vaccination)
- HAI GMFR Before Vaccination to 4 Weeks After Vaccination for 2023 Southern- Based on HAI Assay 2: 18-64 Years(Before vaccination (Baseline) to 4 weeks after vaccination)
- HAI GMFR Before Vaccination to 4 Weeks After Vaccination for 2023 Southern Hemisphere- Based on HAI Assay 2: >=65 Years(Before vaccination (Baseline) to 4 weeks after vaccination)
- Percentage of Participants Achieving HAI Seroconversion at 4 Weeks After Vaccination for the 2023 Southern Hemisphere - Based on HAI Assay 2: 18-64 Years(4 weeks after vaccination)
- Percentage of Participants Achieving HAI Seroconversion at 4 Weeks After Vaccination for 2023 Southern Hemisphere- Based on HAI Assay 2: >=65 Years(4 weeks after vaccination)
- Percentage of Participants With HAI Titers >=1:40 at Baseline and 4 Weeks After Vaccination for 2023 Southern Hemisphere - Based on HAI Assay 2: 18-64 Years(Baseline and 4 weeks after vaccination)
- Percentage of Participants With HAI Titers >=1:40 at Baseline and 4 Weeks After Vaccination for 2023 Southern Hemisphere - Based on HAI Assay 2: >=65 Years(Baseline and 4 weeks after vaccination)
- HAI GMTs at Baseline and 4 Weeks After Vaccination for 2023 Southern Hemisphere - Based on HAI Assay 1: 18-64 Years(Baseline and 4 weeks after vaccination)
- HAI GMTs at Baseline and 4 Weeks After Vaccination for 2023 Southern Hemisphere - Based on HAI Assay 1: >=65 Years(Baseline and 4 weeks after vaccination)
- HAI GMFR Before Vaccination to 4 Weeks After Vaccination for 2023 Southern Hemisphere- Based on HAI Assay 1: 18-64 Years(Before Vaccination (baseline) to 4 weeks after vaccination)
- HAI GMFR Before Vaccination to 4 Weeks After Vaccination for the 2023 Southern Hemisphere - Based on HAI Assay 1: >=65 Years(Before vaccination (baseline) to 4 weeks after vaccination)
- Percentage of Participants Achieving HAI Seroconversion at 4 Weeks After Vaccination for 2023 Southern Hemisphere - Based on HAI Assay 1: 18-64 Years(4 weeks after vaccination)
- Percentage of Participants Achieving HAI Seroconversion at 4 Weeks After Vaccination for 2023 Southern Hemisphere - Based on HAI Assay 1: >=65 Years(4 weeks after vaccination)