A Phase 3 Randomized, Observer-Blind, Controlled Study to Evaluate the Clinical Efficacy of an mRNA Based Seasonal Influenza Vaccine in Older Adults ≥65 Years of Age
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 54,000
- 试验地点
- 161
- 主要终点
- Laboratory-confirmed protocol-defined influenza-like illness (ILI) assessed by incidence rate ratio
研究概览
简要总结
This study will compare an investigational mRNA flu vaccine with a licensed flu vaccine in adults 65 years of age and older. Participants will receive one injection and will be followed during the flu season. The study will measure prevention of laboratory-confirmed flu illness, side effects, and immune responses.
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
This is an Observer-Blind study.
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol independently or with the assistance of a caregiver.
- •Written or witnessed (physically or digitally) informed consent obtained from the participant/Legally acceptable representative [LAR(s)] of the participant prior to performance of any study-specific procedure.
- •Healthy participants or medically stable patients as established by medical history and clinical examination. Participants with chronic medical conditions with or without specific treatment are allowed to participate in this study if considered by the investigator as medically stable. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during 3 months before enrollment.
- •A male or female participant at least 65 YOA at the time of the study intervention administration.
排除标准
- •History of test-confirmed influenza infection within 180 days prior to study intervention administration.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition. HIV-infected individuals may be enrolled if they have been stable on antiretroviral therapy for the past 6 consecutive months, their CD4 cell count is ≥ 200/mm³ and their viral load has been undetectable.
- •Hypersensitivity to latex.
- •History of myocarditis or pericarditis considered causally associated with mRNA vaccine.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
- •History of hypersensitivity or allergic reaction to any previous influenza vaccine.
- •History of hypersensitivity or allergic reaction to any previous mRNA vaccine.
- •History of Guillain-Barré syndrome (GBS) within 6 weeks of receiving any vaccine.
- •Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study
- •Acute or unstable chronic conditions [clinically significant pulmonary, cardiovascular, hepatic, metabolic/endocrine disorders, renal functional abnormality, or psychiatric conditions], as determined by medical history and clinical examination.
- •Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant, due to participation in the clinical study.
- •Condition that in the judgment of the investigator would make intramuscular injection unsafe.
- •Administration of an influenza vaccine in the period starting 180 days before the study intervention administration or planned administration at any time during the study.
- •Planned administration/administration of any mRNA-based vaccine, live vaccine or adjuvanted protein-based vaccine in the period starting 30 days before the study intervention administration (Day -29 to Day 1) and ending 28 days after the study intervention administration (Day 1 to Day 28) or a non-replicating vaccine in the period starting 15 days before the study intervention administration (Day -14 to Day 1) and ending 14 days after the study intervention administration (Day 1 to Day 14).
- •Use of any investigational or non-registered product (drug, vaccine or invasive medical device in the country of enrollment) other than the study intervention during the period beginning 30 days before the dose of study intervention (Day -29 to Day 1), or their planned use during the study period.
- •Administration of immunoglobulins or other blood products or plasma derivatives during the period starting 90 days before the study intervention (Day -89 to Day 1) or planned administration during the study period.
- •Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study.
- •Up to 90 days prior to the study intervention administration:
- •For systemic corticosteroids: prednisone equivalent ≥20 mg/day for >14 days. Inhaled, intra articular/intra-bursal, and topical steroids are allowed.
- •Long-acting immune-modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies, antitumoral medication.
- •Administration of antitumoral medication during the period starting 90 days before the study intervention (Day -89 to Day 1) or planned administration during the study period.
- •Administration of any vaccine in a clinical trial investigating an influenza mRNA vaccine in the period starting 1 year before the study intervention administration.
- •Concurrently participating in another clinical study at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug/invasive medical device).
- •For enrollment in Season 2: Previous participation (i.e., during previous season) in this clinical study.
- •Planned move during the study period that will prohibit participating in the study until study end.
- •Planned leave or holiday of 4 consecutive weeks or more during the influenza season covered by the study, that would prohibit the reporting of ILI cases and attendance to ILI visit.
- •Any study personnel or their immediate dependents, family, or household members.
研究组 & 干预措施
mRNA Seasonal Flu Vaccine
Participants will receive a single dose of investigational mRNA Seasonal Flu vaccine on Day 1.
干预措施: mRNA Seasonal Flu vaccine (Combination Product)
Active Comparator
Participants will receive a single dose of an age-appropriate and season-adapted licensed influenza vaccine Day 1.
干预措施: Licensed Influenza Vaccine (Combination Product)
结局指标
主要结局
Laboratory-confirmed protocol-defined influenza-like illness (ILI) assessed by incidence rate ratio
时间窗: From Day 15 through the end of the influenza Season
First occurrence of laboratory-confirmed protocol-defined ILI caused by influenza A subtypes and B lineage. Protocol-defined ILI is defined as the simultaneous occurrence of at least 1 respiratory symptom and at least 1 systemic symptom. Respiratory symptoms include nasal congestion, sore throat, new or increased sputum, new or increased cough, new or increased dyspnea, or wheezing. Systemic symptoms include temperature \>37.2°C/99°F or feverishness, fatigue, myalgia, or headache. The endpoint will be assessed using an incidence rate approach. Relative vaccine efficacy will be calculated as 100 × (1 - incidence rate ratio).
Number of Participants with Solicited Administration Site Adverse Events (AEs)
时间窗: From Day 1 to Day 7
The solicited administration site AEs considered are pain, redness, swelling and lymphadenopathy. Lymphadenopathy is defined as localized axillary, cervical or supraclavicular swelling or tenderness ipsilateral to the injection arm.
Number of Participants with Solicited Systemic AEs
时间窗: From Day 1 to Day 7
The solicited systemic AEs considered are fever, headache, fatigue, myalgia, arthralgia and chills. Fever is defined as temperature greater than or equal to (\>=) 38 °C/100.4 °F regardless the location of measurement.
Number of Participants with Unsolicited AEs
时间窗: From Day 1 to Day 28
An unsolicited AE is an AE that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events.
Number of Participants with Serious Adverse Events (SAEs)
时间窗: From Day 1 up to the end of the influenza season (with at least 180 days of follow-up)
SAE is an AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or other situations that are considered serious per medical or scientific judgment.
Number of Participants with Adverse Events of Special Interest (AESIs)
时间窗: From Day 1 up to the end of the influenza season (with at least 180 days of follow-up)
An adverse event of special interest is an adverse event of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate. AESIs include protocol-defined events such as potential immune-mediated disorders, myocarditis, pericarditis, severe hypersensitivity reactions, and other AESIs defined in the protocol.
Number of Participants with any Laboratory abnormalities
时间窗: At Day 1 (pre-dose) and at Day 29 (post -dose)
次要结局
- Laboratory-confirmed protocol-defined ILI assessed for relative vaccine efficacy by incidence rate ratio(From Day 15 through the end of the influenza Season)
- Severe Influenza Disease (SID) assessed by incidence rate ratio(From Day 15 through the end of the influenza Season)
- Laboratory-confirmed Centers for Disease Control and Prevention-defined ILI assessed by incidence rate ratio(From Day 15 through the end of the influenza Season)
- Laboratory-confirmed modified Centers for Disease Control and Prevention-defined ILI assessed by incidence rate ratio(From Day 15 through the end of the influenza Season)
- Laboratory-confirmed protocol-defined ILI by antigenic matching status(From Day 15 through the end of the influenza Season ,)
- All-cause protocol-defined ILI assessed by incidence rate ratio(From Day 15 through the end of the influenza Season)
- Influenza-related medically attended event assessed by incidence rate ratio(From Day 15 through the end of the influenza Season)
- Influenza-related oxygen support for more than 24 hours assessed by incidence rate ratio(From Day 15 through the end of the influenza Season)
- Influenza-related intensive care unit admission assessed by incidence rate ratio(From Day 15 through the end of the influenza Season)
- Influenza-related major adverse cardiovascular event assessed by incidence rate ratio(From Day 15 through the end of the influenza Season)
- To evaluate the impact of the study interventions on healthcare resource utilization during laboratory-confirmed influenza episodes(From Day 15 through the end of the influenza Season)
- Geometric mean titers (GMT) Ratio of Antigen 1, Antigen 2 and Virus Neutralization Antibody Titers(At Day 29)
- Geometric mean increase (GMI) of Antigen 1, Antigen 2 and Virus Neutralization Antibody Titers(From Day 1 to Day 29)
- Percentage of Participants with Antigen 1, Antigen 2 and Virus Neutralization Seroconversion Rate (SCR)(From Day 1 to Day 29)
- Percentage of Participants with Antigen 1 Seroprotection Rate (SPR)(At Day 1 and Day 29)