A Phase 3 Randomized, Observer-Blind, Multi-center, Controlled Study to Evaluate Safety, Immunogenicity, and Lot-to-Lot Consistency of an Adjuvanted Cell Culture-Derived, H5N1 Subunit Influenza Virus Vaccine in Healthy Adult Subjects ≥18 Years of Age
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 3,196
- 试验地点
- 24
- 主要终点
- Primary Immunogenicity Endpoint: Geometric Mean Titer (GMT) at Day 43 by Lot
研究概览
简要总结
This Phase 3 study evaluates the safety, immunogenicity and lot-to lot consistency of 3 lots of aH5N1c vaccine for pandemic avian influenza, in approximately 2394 healthy adults ≥18 years of age receiving the vaccine and 797 healthy adults receiving placebo. Subjects were randomized in a 3:1 ratio to receive either aH5N1c vaccine or saline placebo. Enrollment was stratified by age: 18 to <65 years of age and ≥65 years of age, to allow adequate safety assessment of the entire age spectrum.
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)
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
- •Subjects ≥ 18 years of age, mentally competent, in good health as determined by medical history, physical examination and clinical judgment by the Investigator; able to comply with all study procedures, to be contacted, and to be available for study visits according to the protocol.
排除标准
- •Individuals who are pregnant or breastfeeding. Female subjects of childbearing potential must have a negative pregnancy test prior to study vaccines being administered.
- •Females of childbearing potential who refuse to use an acceptable method of birth control from Day 1 (1st vaccination) to 3 weeks after the second study vaccination, and, if sexually active, who have not used a reliable birth control method for at least two months prior to study entry.
- •Individuals with a body temperature ≥38.0 °C (≥100.4 °F) or any acute illness within 3 days of intended study vaccination.
- •Individuals who received any type of influenza vaccine (e.g., "seasonal") within 7 days prior to enrolment in this study or who are planning to receive any type of influenza vaccine within 7 days (before or after) from the study vaccines.
- •Individuals who received any other licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this study or who are planning to receive any (non-influenza) vaccine within 28 days (before or after) from the study vaccines.
- •Individuals with known or suspected impairment of the immune system.
研究组 & 干预措施
Group A
aH5N1c lot #1; receive 2 doses (on Day 1 and Day 22)
干预措施: aH5N1c (Biological)
Group B
aH5N1c lot #2; receive 2 doses (on Day 1 and Day 22)
干预措施: aH5N1c (Biological)
Group C
aH5N1c lot #3; receive 2 doses (on Day 1 and Day 22)
干预措施: aH5N1c (Biological)
Group D
Placebo; receive 2 doses (on Day 1 and Day 22)
干预措施: Placebo (Biological)
结局指标
主要结局
Primary Immunogenicity Endpoint: Geometric Mean Titer (GMT) at Day 43 by Lot
时间窗: Day 1, Day 43
Hemagglutination Inhibition (HI) GMT was assessed at Day 1 and Day 43 for 3 consecutively produced lots.
Percentage of Subjects With Solicited Local, Solicited Systemic, and Other Adverse Events (AEs) as Measured for 7 Days (Inclusive) Following Each Vaccination
时间窗: Day 1 to Day 7
Percentages of subjects with solicited local, solicited systemic, and other AEs as measured for 7 days (inclusive) following each vaccination (first and second) and any (first or second) vaccination, by treatment group and calculated for several time intervals after vaccination : 30 minutes, 1 to 3 days (without 30 minutes), 4 to 7 days, and 1 to 7 days (without 30 minutes), and 1 to 3 days (including 30 minutes) and 1 to 7 days (including 30 minutes). Analysis for intervals of the first 30 minutes, days 1 to 3, and days 4 to 7 was not performed.
Percentages of Subjects With Any Unsolicited AEs Reported Through 21 Day After Vaccination
时间窗: Day 1 to Day 43
Percentages of subjects with any unsolicited AEs reported through 21 days after each (first and second) and any (first or second) vaccination by treatment group.
Primary Immunogenicity Endpoint: Percentage of Subjects With Haemagglutination Inhibition (HI) Titer ≥ 1:40 at Day 43 by Age Cohort
时间窗: Day 1, Day 43
Percentage of subjects with HI titer ≥ 1:40 at Day 43 was assessed by age cohort (18 to \<65 years of age and ≥65 years of age) for the pooled lots. Center for Biologics Evaluation and Research (CBER) criterion for subjects aged 18 to \<65 years: The lower bound of the 2-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 70%. CBER criterion for subjects aged ≥65 years: The lower bound of the 2-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 60%.
Percentages of Subjects Reporting SAEs, AESIs, NOCD, AEs Leading to Vaccine/Study Withdrawal, and Medically Attended AEs, and Concomitant Medications Associated With These Events as Collected From Day 1 to Day 387, by Vaccine Group.
时间窗: Day 1 to Day 387
Percentages of subjects with any adverse events (AE), adverse events of special interest (AESI), new onset of chronic disease (NOCD), and serious adverse event (SAE) through study termination by treatment group.
次要结局
- Secondary Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion on Day 22, and Day 43 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <60 Years of Age and ≥60 Years of Age)(Day 22, and Day 43)
- Secondary Immunogenicity Endpoint: Geometric Mean Titer (GMT) at Day 1, Day 22, Day 43, and Day 183 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <65 Years of Age and ≥65 Years of Age).(Day 1, Day 22, Day 43, and Day 183)
- Secondary Immunogenicity Endpoint: Percentage of Subjects With Haemagglutination Inhibition (HI) Titer ≥ 1:40 on Day 1, Day 22, Day 43 and Day 183 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <65 Years of Age and ≥65 Years of Age).(Day 1, Day 22, Day 43 and Day 183)
- Secondary Immunogenicity Endpoint: Geometric Mean Titer (GMT) at Day 1, Day 22, Day 43 and Day 183 by Vaccine Group (aH5N1c or Placebo) and By Age Cohort (18 to <60 Years of Age and ≥60 Years of Age)(Day 1, Day 22, Day 43 and Day 183)
- Secondary Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion on Day 22, and Day 43 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <65 Years of Age and ≥65 Years of Age).(Day 22, and Day 43)
- Secondary Immunogenicity Endpoint: Percentage of Subjects With Haemagglutination Inhibition (HI) Titer ≥ 1:40 on Day 1, Day 22, Day 43, and Day 183 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <60 Years of Age and ≥60 Years of Age)(Day 1, Day 22, Day 43, and Day 183)
- Secondary Immunogenicity Endpoint: Geometric Mean Ratio (GMR) of Haemagglutination Inhibition (HI) Titer: Day 22/Day 1, Day 43/Day 1 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <60 Years of Age and ≥60 Years of Age)(Day 1, Day 22, Day 43)