A Phase 2, Randomized, Observer-Blind, Multicenter Study to Evaluate the Immunogenicity and Safety of Several Doses of Antigen and MF59 Adjuvant Content in a Monovalent H5N1 Pandemic Influenza Vaccine in Healthy Pediatric Subjects 6 Months to < 9 Years of Age
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 420
- 试验地点
- 14
- 主要终点
- Safety Endpoint 1: Percentages of Subjects With Solicited Local and Systemic Adverse Events (AEs)
研究概览
简要总结
This study is a pediatric dose-ranging study to evaluate the safety and immunogenicity of vaccination with different MF59-adjuvanted H5N1 vaccine formulations.
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)
入排标准
- 年龄范围
- 6 Months 至 8 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female subjects of 6 months through <9 years of age on the day of informed consent/assent.
- •Documented consent provided by the subject's parent(s)/LAR(s) have voluntarily given written informed consent/assent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
- •Subject's parent(s)/LAR(s) able to comprehend and comply with all study procedures, and available for all clinic visits and telephone contacts scheduled in the study.
- •Subjects must provide a baseline blood sample within 10 days prior to the Day 1 vaccination.
排除标准
- •Each subject must not have:
- •Progressive, unstable or uncontrolled clinical conditions.
- •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, ie,
- •Subjects who have had a fever (body temperature measurement ≥ 38°C) within three days prior to vaccination. The subject may return for vaccination after they have been free of fever for three days.
- •History of epilepsy or convulsions (excluding febrile convulsions).
- •A subject who has any medical condition meeting the definition of AESI defined for the purposes of this trial (see appendix A).
- •Subjects who have received antipyretic medication within the past 24 hours prior to vaccination. The subject may return for vaccination after a period of 24 hours has passed since the administration of an antipyretic.
- •Abnormal function of the immune system resulting from:
- •Clinical conditions.
- •Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to informed consent/assent. 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 from within 90 days prior to informed consent/assent.
- •Suspicion of pandemic influenza illness within past six months or have ever received previous pandemic H5N1 flu vaccination.
- •Received immunoglobulins or any blood products within 180 days prior to informed consent/assent.
- •Received an investigational or non-registered medicinal within 30 days prior to informed consent/assent.
- •Children of study site staff (this includes research or clinic staff) or children who are otherwise related to study site staff or have household members who are study site staff. Study site staff are employees with direct or indirect contact with study subjects and/or have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, medical assistants, document scanners, etc. study personnel as an immediate family or household member.
- •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 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 prior to day
- •Following day 43 other vaccines may be administered, including seasonal flu.
研究组 & 干预措施
Lowest dose, less adjuvant aH5N1 vaccine
Two consecutive intramuscular (IM) administrations (Day 1 and Day 22)
干预措施: H5N1 antigen combined with MF59 adjuvant (Biological)
Low dose, less adjuvant aH5N1 vaccine
Two consecutive IM administrations (Day 1 and Day 22)
干预措施: H5N1 antigen combined with MF59 adjuvant (Biological)
Mid dose, less adjuvant aH5N1 vaccine
Two consecutive IM administrations (Day 1 and Day 22)
干预措施: H5N1 antigen combined with MF59 adjuvant (Biological)
Lowest dose, adjuvanted aH5N1 vaccine
Two consecutive IM administrations (Day 1 and Day 22)
干预措施: H5N1 antigen combined with MF59 adjuvant (Biological)
Low dose, adjuvanted aH5N1 vaccine
Two consecutive IM administrations (Day 1 and Day 22)
干预措施: H5N1 antigen combined with MF59 adjuvant (Biological)
Mid dose, adjuvanted aH5N1 vaccine
Two consecutive IM administrations (Day 1 and Day 22)
干预措施: H5N1 antigen combined with MF59 adjuvant (Biological)
结局指标
主要结局
Safety Endpoint 1: Percentages of Subjects With Solicited Local and Systemic Adverse Events (AEs)
时间窗: Day 1 through Day 7 and Day 22 through Day 28
Percentages of subjects with solicited local and systemic AEs that occurred within 7 days following each vaccination, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.
Safety Endpoint 2: Percentages of Subjects With Any Unsolicited AEs
时间窗: Day 1 through Day 43
Percentages of subjects with any unsolicited AEs reported within 21 days after each vaccination within each vaccine group, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.
Primary Immunogenicity Endpoint 1a: Geometric Mean Titers (GMTs), as Measured by Hemagglutination Inhibition (HI) and Microneutralization (MN) Assays Against the Homologous H5N1 Strain
时间窗: Day 1 (baseline), Day 22, and Day 43
GMTs on Day 1 (prior to the first vaccination), Day 22 (3 weeks after the first vaccination), and Day 43 (3 weeks after the second vaccination) as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.
Primary Immunogenicity Endpoint 1b: Geometric Mean Ratios (GMR), as Measured by HI and MN Assays Against the Homologous H5N1 Strain
时间窗: Day 1 (baseline), Day 22, and Day 43
GMRs calculated as follows: Day 22/Day 1 and Day 43/Day 1 as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.
Safety Endpoint 3: Percentages of Subjects Reporting Serious Adverse Events (SAEs), New-onset Chronic Disease (NOCD), Adverse Events of Special Interest (AESI), and AEs Leading to Vaccine and/or Study Withdrawal
时间窗: Day 1 through Day 387
Percentages of subjects reporting SAEs, NOCDs, AESIs, and AEs leading to vaccine and/or study withdrawal, as collected from Day 1 through Day 387, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.
Primary Immunogenicity Endpoint 1c: Percentage of Subjects Achieving Seroconversion (Non-detectable to ≥1:40, or 4-fold Increase From a Detectable Day 1 Titer)
时间窗: Day 1 (baseline), Day 22, and Day 43
Percentage of subjects achieving seroconversion (non-detectable to ≥1:40, or 4-fold increase from a detectable Day 1 titer) on Day 22 and Day 43 as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.
Primary Immunogenicity Endpoint 1d: Percentage of Subjects Achieving Seroconversion With a Titer ≥1:40
时间窗: Day 1 (baseline), Day 22, and Day 43
Percentage of subjects achieving seroconversion with a titer ≥1:40 on Day 1, Day 22, and Day 43 as determined by HI and MN assays against the homologous H5N1 pandemic influenza strain, by total population and by age cohort. No statistical analyses have been specified for this primary endpoint. The statistical analysis was descriptive in nature without any prespecified inferential analyses.
次要结局
- Secondary Immunogenicity Endpoint 1b: GMRs, as Measured by HI and MN Assays Against the Homologous H5N1 Strain(Day 1 (baseline) and Day 202)
- Secondary Immunogenicity Endpoint 1d: Percentage of Subjects Achieving Seroconversion With a Titer ≥1:40(Day 1 (baseline) and Day 202)
- Secondary Immunogenicity Endpoint 1a: GMTs, as Measured by HI and MN Assays Against the Homologous H5N1 Strain(Day 1 (baseline) and Day 202)
- Secondary Immunogenicity Endpoint 1c: Percentage of Subjects Achieving Seroconversion (Non-detectable to ≥1:40, or 4-fold Increase From a Detectable Day 1 Titer)(Day 1 (baseline) and Day 202)