A Parallel-group, Phase I/II, Randomized, Modified Double-blind, 3-arm, Active Comparator, Multi-center, Prevention Study to Evaluate the Immunogenicity and Safety of Two Adjuvanted Dose Levels of Panblok H7+MF59 Influenza Vaccine Compared With an Unadjuvanted Dose of Panblok H7 in Participants 18 Years of Age and Older
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 581
- 试验地点
- 16
- 主要终点
- Geometric Mean of Hemagglutination Inhibition (HAI) Antibody (Ab) Titer at Day 22
研究概览
简要总结
VAM00001 is a Phase I/II, randomized, modified double-blind, multi-center study.
The purpose of this study is to compare 2 dose levels of Panblok H7 (dose 1 and dose 2 of rHA) with a standard squalene dose of adjuvant MF59 to Panblok H7 (dose 3) unadjuvanted in approximately 700 adult participants in order to select one dose formulation to be used for further clinical development. The randomization ratio will be 3:3:1 for Panblok H7 (dose 1) + MF59, Panblok H7 (dose 2) + MF59, and Panblok H7 (dose 3) unadjuvanted, respectively. Each study group will be stratified into the age groups 18-64 years and ≥ 65 years of age.
The study duration for each participant will be approximately 13 months.
详细描述
The study duration for each participant will be approximately 13 months.
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
Modified double-blind:
- Investigators and study staff who conduct the safety assessment, laboratory personnel who analyze the blood samples, Sponsor's personnel and study Team members, and the participant will not know which study dose is administered
- Only the study staff who prepare and administer the study intervention and are not involved with the safety evaluation will know which study dose is administered
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
- •Aged 18 years or older on the day of inclusion
- •Participants who are healthy as determined by medical evaluation including medical history and physical examination
- •A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:
- •Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, or surgically sterile.
- •OR Is of childbearing potential and agrees to use a highly effective contraceptive method or abstinence from at least 4 weeks prior to each study intervention administration until at least 12 weeks after the last study intervention administration.
- •A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 24 hours before the first dose of study intervention
- •Informed consent form has been signed and dated
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
- •Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances
- •Thrombocytopenia or bleeding disorder contraindicating intramuscular injection based on investigator's judgement
- •Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion (1)
- •(1) Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, auto-immune disorders, diabetes, psychiatric disorders, or chronic infection
- •Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that is stable at the time of study intervention administration in the absence of therapy, and participants who have a history of neoplastic disease and who have been disease-free for ≥ 5 years)
- •Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 100.4°F) on the day of study intervention administration. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
- •Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion
- •Receipt of any vaccine in the 14 days preceding Visit 1 or planned receipt of any vaccine prior to Visit 3, except for seasonal flu vaccine, which may be received at least 2 weeks after Visit 2
- •Previous vaccination against H7N9 with an investigational vaccine
- •Receipt of immune globulins, blood or blood-derived products in the past 3 months
- •Participation at the time of study enrollment (or in the 4 weeks preceding the first study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
- •Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
- •Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
- •Personal or family history of Guillain-Barré syndrome
- •Self-reported seropositivity for Hepatitis B antigen or Hepatitis C
- •"The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial."
研究组 & 干预措施
Group 1
2 doses, 21 days apart, of Panblok H7 dose 1 + MF59
干预措施: Panblok + MF59 Dose 1 (Biological)
Group 2
2 doses, 21 days apart, of Panblok H7 dose 2 + MF59
干预措施: Panblok + MF59 Dose 2 (Biological)
Group 3
2 doses, 21 days apart, of Panblok H7 dose 3 unadjuvanted
干预措施: Unadjuvanted Panblok Dose 3 (Biological)
结局指标
主要结局
Geometric Mean of Hemagglutination Inhibition (HAI) Antibody (Ab) Titer at Day 22
时间窗: Day 22
The HAI antibody was measured by hemagglutination inhibition using horse red blood cells (HIH) measurement method. The 95% confidence interval (CI) was based on the Student t-distribution of log10-transformed values.
Geometric Mean of Hemagglutination Inhibition Antibody Titer at Day 43
时间窗: Day 43
The HAI antibody was measured by HIH measurement method. The 95% CI was based on the Student t-distribution of log10-transformed values.
Geometric Mean Ratio of Hemagglutination Inhibition Antibody Titer at Day 22
时间窗: Days 1 and 22
The HAI antibody was measured by HIH measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Student t-distribution of log10-transformed values.
Geometric Mean Ratio of Hemagglutination Inhibition Antibody Titer at Day 43
时间窗: Days 1 and 43
The HAI antibody was measured by HIH measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Student t-distribution of log10-transformed values.
Geometric Mean Ratio of Hemagglutination Inhibition Antibody Titer at Day 202
时间窗: Days 1 and 202
The HAI antibody was measured by HIH measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Student t-distribution of log10-transformed values.
Geometric Mean Ratio of Hemagglutination Inhibition Antibody Titer at Day 387
时间窗: Days 1 and 387
The HAI antibody was measured by HIH measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Student t-distribution of log10-transformed values.
Percentage of Participants With Seroconversion of Hemagglutination Inhibition Antibody Titer at Day 22
时间窗: Day 22
The seroconversion was defined as titer \<10 on Day 1 and post-injection titer \>=40 on Day 22 or Day 43; or defined as titer \>=10 on Day 1 and a \>=4-fold increase in titer on Day 22 or Day 43. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Seroconversion of Hemagglutination Inhibition Antibody Titer at Day 43
时间窗: Day 43
The seroconversion was defined as titer \<10 on Day 1 and post-injection titer \>=40 on Day 22 or Day 43; or defined as titer \>=10 on Day 1 and a \>=4-fold increase in titer on Day 22 or Day 43. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Hemagglutination Inhibition Antibody Titer >=1:40 at Day 1
时间窗: Day 1
The HAI antibody was measured by HIH measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Hemagglutination Inhibition Antibody Titer >=1:40 at Day 22
时间窗: Day 22
The HAI antibody was measured by HIH measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Hemagglutination Inhibition Antibody Titer >=1:40 at Day 43
时间窗: Day 43
The HAI antibody was measured by HIH measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Hemagglutination Inhibition Antibody Titer >=1:40 at Day 202
时间窗: Day 202
The HAI antibody was measured by HIH measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Hemagglutination Inhibition Antibody Titer >=1:40 at Day 387
时间窗: Day 387
The HAI antibody was measured by HIH measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 1
时间窗: Day 1
The HAI antibody was measured by HIH measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 22
时间窗: Day 22
The HAI antibody was measured by HIH measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 43
时间窗: Day 43
The HAI antibody was measured by HIH measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 202
时间窗: Day 202
The HAI antibody was measured by HIH measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 387
时间窗: Day 387
The HAI antibody was measured by HIH measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Geometric Mean of Neutralization Test (NT) Antibody Titer at Day 22
时间窗: Day 22
The NT antibody was measured by seroneutralization (SN) measurement method. The 95% CI was based on the Student t-distribution of log10-transformed values.
Geometric Mean of Neutralization Test Antibody Titer at Day 43
时间窗: Day 43
The NT antibody was measured by SN measurement method. The 95% CI was based on the Student t-distribution of log10-transformed values.
Geometric Mean Ratio of Neutralization Test Antibody Titer at Day 22
时间窗: Days 1 and 22
The NT antibody was measured by SN measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Student t-distribution of log10-transformed values.
Geometric Mean Ratio of Neutralization Test Antibody Titer at Day 43
时间窗: Days 1 and 43
The NT antibody was measured by SN measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Student t-distribution of log10-transformed values.
Geometric Mean Ratio of Neutralization Test Antibody Titer at Day 202
时间窗: Days 1 and 202
The NT antibody was measured by SN measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Student t-distribution of log10-transformed values.
Geometric Mean Ratio of Neutralization Test Antibody Titer at Day 387
时间窗: Days 1 and 387
The NT antibody was measured by SN measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Student t-distribution of log10-transformed values.
Percentage of Participants With Neutralization Test Antibody Titer >=1:20, >=1:40, and >=1:80 at Day 22
时间窗: Day 22
The NT antibody was measured by SN measurement method. The 95% CI was the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Neutralization Test Antibody Titer >=1:20, >=1:40, and >=1:80 at Day 43
时间窗: Day 43
The NT antibody was measured by SN measurement method. The 95% CI was the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With >=2 and >=4 Fold Increase in Neutralization Test Antibody Titer at Day 22
时间窗: Day 22
The NT antibody was measured by SN measurement method. The 95% CI was the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With >=2 and >=4 Fold Increase in Neutralization Test Antibody Titer at Day 43
时间窗: Day 43
The NT antibody was measured by SN measurement method. The 95% CI was the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Neutralization Test Antibody Titer >=1:10 at Day 1
时间窗: Day 1
The NT antibody was measured by SN measurement method. The 95% CI was the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Neutralization Test Antibody Titer >=1:10 at Day 22
时间窗: Day 22
The NT antibody was measured by SN measurement method. The 95% CI was the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Neutralization Test Antibody Titer >=1:10 at Day 43
时间窗: Day 43
The NT antibody was measured by SN measurement method. The 95% CI was the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Neutralization Test Antibody Titer >=1:10 at Day 202
时间窗: Day 202
The NT antibody was measured by SN measurement method. The 95% CI was the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Neutralization Test Antibody Titer >=1:10 at Day 387
时间窗: Day 387
The NT antibody was measured by SN measurement method. The 95% CI was the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
次要结局
- Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)(Up to 30 minutes after each vaccination)
- Number of Participants With Solicited Injection Site Reactions and Systemic Reactions(Up to 7 days after each vaccination)
- Number of Participants With Unsolicited AEs(Up to 21 days after each vaccination)
- Number of Participants With Serious Adverse Events (SAEs), Adverse Event of Special Interest (AESIs) and Medically Attended Adverse Events (MAAEs)(From first dose vaccine administration (Day 1) until 12 months after the last dose administration, 387 days)