A Phase III, Randomized, Controlled, Observer-Blind, Multicenter Study to Evaluate the Safety and Immunogenicity and the Consistency of Three Consecutive Lots of a MF59C.1 Adjuvanted Trivalent Subunit Influenza Vaccine in Elderly Subjects Aged 65 Years and Older
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 7,109
- 试验地点
- 70
- 主要终点
- Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV
研究概览
简要总结
The present phase III study aims to evaluate the safety and immunogenicity of MF59-adjuvanted subunit seasonal influenza vaccine and to evaluate the consistency in the manufacturing process of three consecutive lots of MF59-adjuvanted subunit seasonal influenza vaccine with respect to immunogenicity in subjects aged 65 years and older. The active comparator non-adjuvanted seasonal influenza vaccine is approved for use in this age group in the United States and will be used to provide a comparative assessment for immunogenicity and safety.
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
- Single (Outcomes Assessor)
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
- •Males and females subjects aged ≥65 years at day of vaccination who are willing and able to comply to study procedures.
排除标准
- •Individuals with behavioral or cognitive impairment or a psychiatric condition or with a history of any illness that,in the opinion of the investigator, would have interfered with the subject's ability to participate in the study.
- •Individuals who were not able to comprehend and/or follow all required study procedures for the whole period of the study.
- •Known or suspected impairment/alteration of immune function.
- •Individuals with a known bleeding diathesis.
- •History of Guillain-Barré syndrome.
- •Individuals with history of allergy to vaccine components and/or a history of any anaphylaxis, serious vaccine reactions or hypersensitivity to influenza viral proteins, egg proteins (including ovalbumin), polymyxin, neomycin, betapropiolactone, thimerosal/ sodium ethylmercurothiosalicylate/ mercury and nonylphenolethoxylate/ nonoxynol-9 (spermicide).
- •Receipt of another investigational agent within 30 days prior to enrollment in the study or before completion of the safety follow-up period in another study.
- •Individuals who had received any other vaccines within 2 weeks for inactivated vaccines or 4 weeks for live vaccines prior to enrollment in this study or who had planned to receive any vaccine within 3 weeks from the study vaccine.
- •Individuals who had received vaccination against seasonal influenza in the previous 6 months.
- •Individuals with oral temperature ≥38.0°C (≥100.4°F) on day of study vaccination.
- •Individuals with history of substance or alcohol abuse within the past 2 years.
- •Individuals providing consent who did not consent to the retention of their serum samples after study completion.
- •Elective surgery or hospitalization planned to occur during the treatment phase or during the follow-up phase that, according to the opinion of the investigator, might have poses additional risk to the subject.
- •Subjects from whom blood could not be drawn at visit 1.
结局指标
主要结局
Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV
时间窗: Day 22 post vaccination
Immunologic equivalence of 3 consecutive production lots of aTIV (Lot 1, Lot 2 and Lot 3), was assessed in terms of Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) in subjects, at three weeks after vaccination, against each vaccine strain.
Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS
时间窗: Day 22 post vaccination
The non-inferiority of HI antibody responses of aTIV compared to TIV assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.
Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS
时间窗: Day 22 post vaccination
The non-inferiority of HI antibody responses of aTIV compared to TIV assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the three homologous vaccine strains. Seroconversion defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS)
时间窗: Day 22 post vaccination
The superiority of HI antibody responses of aTIV compared to TIV assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.
Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS
时间窗: Day 22 post vaccination
The superiority of HI antibody responses of aTIV compared to TIV assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the three homologous vaccine strains. Seroconversion defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Percentage of Subjects With HI Titers ≥40 Against Homologous Strains
时间窗: Day 22 post vaccination
The percentage of subjects demonstrating HI titers ≥40, in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV.
Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains
时间窗: Day 22 post vaccination
The percentage of subjects achieving seroconversion in HI titers from baseline, in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains
时间窗: Day 22 post vaccination
The GMR of post-vaccination versus pre-vaccination HI titers (day 22/day 1) in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV.
Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains
时间窗: Day 22 post vaccination
The percentage of subjects demonstrating HI titers ≥40, in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV.
Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains
时间窗: Day 22 post vaccination
The GMR of post-vaccination versus pre-vaccination HI titers (day 22/day 1) in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV.
Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains
时间窗: Day 22 post vaccination
The percentage of subjects achieving seroconversion in HI titers from baseline, in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
次要结局
- Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS(Day 22 post vaccination)
- Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS(Day 22 post vaccination)
- Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS(Day 22 post vaccination)
- Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS(Day 22 postvaccination)
- Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS(Day 22 post vaccination)
- Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS(Day 22 post vaccination)
- Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS(Day 22 postvaccination)
- Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS(Day 22 post vaccination)
- Persistence of GMTs Against Homologous and Heterologous Strains(Day 181, Day 366 post vaccination)
- Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains(Day 181, Day 366 post vaccination)
- Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups(Day 22 through Day 366 post vaccination)
- Number of High Risk Subjects With Exacerbation of Preexisting Chronic Disease, Across Vaccine Groups(Day 1 through Day 366 post vaccination)
- Number of Subjects Reporting Healthcare Utilization Across Vaccine Groups(Day 1 through Day 366 post vaccination)
- All Cause Mortality Rate, Across Vaccine Groups(Day 1 through Day 366 post vaccination)
- Number of Subjects Reporting Solicited Adverse Events Following Vaccination(Day 1 through Day 7 post vaccination)