A Phase 1, Randomized, Observer-Blind, Multi-Center, Dose Ranging Study to Evaluate the Immunogenicity, Safety and Tolerability of Different Formulations of an Adjuvanted or Non-Adjuvanted Cell Culture-derived A/H2N3 Subunit Influenza Virus Vaccine in Healthy Subjects 18 Years and Above
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 600
- 试验地点
- 5
- 主要终点
- GMFI of HI antibodies against homologous H2N3 strain - Day 29
研究概览
简要总结
This Phase 1, randomized, observer-blind, dose-ranging clinical study is evaluating 6 different formulations of MF59-adjuvanted and non-adjuvanted H2N3 influenza vaccine. Approximately 600 healthy adult subjects are to be randomized into 1 of 6 possible treatment groups with 100 subjects per group, stratified by age group (born after or before 1968). Each subject will receive an influenza vaccine injection on Day 1 and Day 22. Subjects will be followed up for approximately 12 months after the second vaccine injection.
The primary immunogenicity analysis is based on the Day 1, Day 8, Day 22, Day 29, and Day 43 serology data. The primary safety analysis is based on solicited local and systemic adverse events (AEs) reported within 10 days after each vaccination, unsolicited AEs reported within 3 weeks after each vaccination, and serious AEs (SAEs), medically attended AEs (MAAEs), AEs leading to withdrawal from the study, and AEs of special interest (AESIs) reported throughout the study.
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
- Triple (Participant, 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
- •Individuals of 18 years of age and older on the day of informed consent who were not born in
- •Individuals who have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
- •Individuals who can comply with study procedures including follow-up.
- •Males, females of non-childbearing potential or females of childbearing potential who are using an effective birth control method, at least 30 days prior to informed consent, which they intend to use for at least 2 months after the last study vaccination.
排除标准
- •Females of childbearing potential who are pregnant, lactating, or who have not adhered to a specified set of contraceptive methods from at least 30 days prior to study entry and who do not plan to do so until 2 months after the last study vaccination.
- •A body mass index (BMI) ≥35 kg/m
- •Progressive, unstable, or uncontrolled clinical conditions as per investigator's assessment. Subjects must be stable and unchanged for a minimum of 3 months.
- •Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
- •Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
- •Abnormal function of the immune system resulting from:
- •Clinical conditions.
- •Systemic administration of corticosteroids at a dose of ≥20 mg/day of prednisone or equivalent for more than 14 consecutive days within 90 days prior to informed consent. Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted.
- •Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent.
- •History of any medical condition considered an adverse event of special interest (AESI).
- •Received immunoglobulins with immunomodulating effects or any blood products within 180 days prior to informed consent.
- •Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
- •Study personnel or immediate family or household member of study personnel.
- •Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.
- •Individuals who received any other vaccines (with the exception of COVID-19 vaccines) within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine within 28 days from the study vaccines.
- •Receipt of any (investigational or licensed) COVID-19 vaccine within 14 days (non-replicating vaccines) or 28 days (replicating vaccines) prior to enrollment or plan to receive any COVID-19 vaccine within 14 days from study vaccination.
- •A known history of Guillain-Barre Syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis.
研究组 & 干预措施
Group A
Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of low dose A/H2N3c + standard dose MF59 adjuvant
干预措施: Low dose A/H2N3c + standard dose MF59 (Biological)
Group B
Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of intermediate dose A/H2N3c + standard dose MF59 adjuvant
干预措施: Intermediate dose A/H2N3c + standard dose MF59 (Biological)
Group C
Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of high dose A/H2N3c + standard dose MF59 adjuvant
干预措施: High dose A/H2N3c + standard dose MF59 (Biological)
Group D
Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of high dose A/H2N3c non-adjuvanted
干预措施: High dose A/H2N3c non-adjuvanted (Biological)
Group E
Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of lowest dose A/H2N3c + high dose MF59 adjuvant
干预措施: Lowest dose A/H2N3c + high dose MF59 (Biological)
Group F
Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of low dose A/H2N3c + high dose MF59 adjuvant
干预措施: Low dose A/H2N3c + high dose MF59 (Biological)
结局指标
主要结局
GMFI of HI antibodies against homologous H2N3 strain - Day 29
时间窗: Day 29
GMFI (HI) 1 week postvaccination 2 compared to prevaccination
Geometric mean titer (GMT) of hemagglutination inhibition (HI) antibodies against homologous H2N3 strain - Day 1
时间窗: Day 1
GMT (HI) prevaccination
GMT of HI antibodies against homologous H2N3 strain - Day 29
时间窗: Day 29
GMT (HI) 1 week postvaccination 2
GMT of MN antibodies against homologous H2N3 strain - Day 22
时间窗: Day 22
GMT (MN) 3 weeks postvaccination 1
GMT of MN antibodies against homologous H2N3 strain - Day 29
时间窗: Day 29
GMT (MN) 1 week postvaccination 2
GMT of MN antibodies against homologous H2N3 strain - Day 43
时间窗: Day 43
GMT (MN) 3 weeks postvaccination 2
Geometric mean fold increase (GMFI) of HI antibodies against homologous H2N3 strain - Day 8
时间窗: Day 8
GMFI (HI) 1 week postvaccination 1 compared to prevaccination
GMFI of HI antibodies against homologous H2N3 strain - Day 22
时间窗: Day 22
GMFI (HI) 3 weeks postvaccination 1 compared to prevaccination
GMT of HI antibodies against homologous H2N3 strain - Day 8
时间窗: Day 8
GMT (HI) 1 week postvaccination 1
GMFI of MN antibodies against homologous H2N3 strain - Day 8
时间窗: Day 8
GMFI (MN) 1 week postvaccination 1 compared to prevaccination
Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 1
时间窗: Day 1
% ≥1:40 (HI) prevaccination
Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 1
时间窗: Day 1
% ≥1:40 (MN) prevaccination
Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 22
时间窗: Day 22
% seroconversion (MN) 3 weeks postvaccination 1, defined as a ≥4-fold increase in MN titer postvaccination in those with prevaccination titer ≥lower limit of quantification (LLOQ), or a postvaccination MN titer ≥4×LLOQ for subjects with baseline titer \<LLOQ
GMT of HI antibodies against homologous H2N3 strain Day 22
时间窗: Day 22
GMT (HI) 3 weeks postvaccination 1
GMT of microneutralization (MN) antibodies against homologous H2N3 strain - Day 1
时间窗: Day 1
GMT (MN) prevaccination
Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 22
时间窗: Day 22
% ≥1:40 (HI) 3 weeks postvaccination 1
Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 43
时间窗: Day 43
% seroconversion (HI) 3 weeks postvaccination 2, defined as a ≥4-fold increase in HI titer postvaccination in those with prevaccination titer ≥1:10, or a postvaccination HI titer ≥1:40 for subjects with baseline titer \<1:10
Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 43
时间窗: Day 43
% seroconversion (MN) 3 weeks postvaccination 2, defined as a ≥4-fold increase in MN titer postvaccination in those with prevaccination titer ≥lower limit of quantification (LLOQ), or a postvaccination MN titer ≥4×LLOQ for subjects with baseline titer \<LLOQ
GMT of HI antibodies against homologous H2N3 strain - Day 43
时间窗: Day 43
GMT (HI) 3 weeks postvaccination 2
GMT of MN antibodies against homologous H2N3 strain - Day 8
时间窗: Day 8
GMT (MN) 1 week postvaccination 1
GMFI of HI antibodies against homologous H2N3 strain - Day 43
时间窗: Day 43
GMFI (HI) 3 weeks postvaccination 2 compared to prevaccination
Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 29
时间窗: Day 29
% ≥1:40 (HI) 1 week postvaccination 2
Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 22
时间窗: Day 22
% ≥1:40 (MN) 3 weeks postvaccination 1
Number and percentages of subjects reporting solicited local and systemic adverse events (AEs) - Day 1 through Day 10
时间窗: Day 1 through Day 10
10 consecutive days postvaccination 1
GMFI of MN antibodies against homologous H2N3 strain - Day 43
时间窗: Day 43
GMFI (MN) 3 weeks postvaccination 2 compared to prevaccination
Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 43
时间窗: Day 43
% ≥1:40 (HI) 3 weeks postvaccination 2
Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 22
时间窗: Day 22
% seroconversion (HI) 3 weeks postvaccination 1, defined as a ≥4-fold increase in HI titer postvaccination in those with prevaccination titer ≥1:10, or a postvaccination HI titer ≥1:40 for subjects with baseline titer \<1:10
Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 29
时间窗: Day 29
% seroconversion (HI) 1 week postvaccination 2, defined as a ≥4-fold increase in HI titer postvaccination in those with prevaccination titer ≥1:10, or a postvaccination HI titer ≥1:40 for subjects with baseline titer \<1:10
Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 29
时间窗: Day 29
% seroconversion (MN) 1 week postvaccination 2, defined as a ≥4-fold increase in MN titer postvaccination in those with prevaccination titer ≥lower limit of quantification (LLOQ), or a postvaccination MN titer ≥4×LLOQ for subjects with baseline titer \<LLOQ
Number and percentages of subjects reporting solicited local and systemic AEs - Day 22 through Day 31
时间窗: Day 22 through Day 31
10 consecutive days postvaccination 2
Number and percentage of subjects reporting serious AEs (SAEs), AEs leading to withdrawal, AEs of special interest (AESI) and medically attended AEs (MAAEs)
时间窗: Day 1 through Day 387
From vaccination until study completion
GMFI of MN antibodies against homologous H2N3 strain - Day 22
时间窗: Day 22
GMFI (MN) 3 weeks postvaccination 1 compared to prevaccination
GMFI of MN antibodies against homologous H2N3 strain - Day 29
时间窗: Day 29
GMFI (MN) 1 week postvaccination 2 compared to prevaccination
Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 8
时间窗: Day 8
% ≥1:40 (HI) 1 week postvaccination 1
Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 8
时间窗: Day 8
% ≥1:40 (MN) 1 week postvaccination 1
Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 29
时间窗: Day 29
% ≥1:40 (MN) 1 week postvaccination 2
Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 43
时间窗: Day 43
% ≥1:40 (MN) 3 weeks postvaccination 2
Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 8
时间窗: Day 8
% seroconversion (HI) 1 week postvaccination 1, defined as a ≥4-fold increase in HI titer postvaccination in those with prevaccination titer ≥1:10, or a postvaccination HI titer ≥1:40 for subjects with baseline titer \<1:10
Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 8
时间窗: Day 8
% seroconversion (MN) 1 week postvaccination 1, defined as a ≥4-fold increase in MN titer postvaccination in those with prevaccination titer ≥lower limit of quantification (LLOQ), or a postvaccination MN titer ≥4×LLOQ for subjects with baseline titer \<LLOQ
Number and percentage of subjects reporting any unsolicited AEs
时间窗: Day 1 through Day 43
For 3 weeks following each vaccination
次要结局
- GMFI of ELLA titers as a measure of anti-NA immunogenicity(Day 8, Day 22, Day 29, Day 43)
- GMFI of HI antibodies against homologous H2N3 strain - Persistence(Day 202, Day 387)
- GMFI of MN antibodies against homologous H2N3 strain - Persistence(Day 202, Day 387)
- GMT of ELLA titer as a measure of anti-NA immunogenicity- Persistence(Day 202, Day 387)
- GMFI of ELLA titer as a measure of anti-NA immunogenicity- Persistence(Day 202, Day 387)
- Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Persistence(Day 202, Day 387)
- GMT of ELLA titers as a measure of anti-neuraminidase (NA) immunogenicity(Day 1, Day 8, Day 22, Day 29, Day 43)
- GMT of HI antibodies against homologous H2N3 strain - Persistence(Day 202, Day 387)
- GMT of MN antibodies against homologous H2N3 strain - Persistence(Day 202, Day 387)
- Percentages of subjects with MN titers ≥1:40, ≥1:80 and ≥1:160 against homologous H2N3 strain - Persistence(Day 202, Day 387)
- Percentage of subjects with ≥4-fold increase in ELLA titer as a measure of anti-NA immunogenicity - Persistence(Day 202, Day 387)
- Percentage of subjects with ≥4-fold increase in ELLA titer as a measure of anti-NA immunogenicity(Day 8, Day 22, Day 29, Day 43)
- Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Persistence(Day 202, Day 387)
- Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Persistence(Day 202, Day 387)