A Phase 1/2, Parallel, Observer-blind Study to Assess the Safety and Immunogenicity of an Egg-based H5N8 Influenza Vaccine at Multiple Dose Levels Adjuvanted With Matrix-M in Healthy Participants 18 Years of Age and Above.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Sanofi
- 入组人数
- 640
- 试验地点
- 16
- 主要终点
- Number of participants with immediate Adverse Events (AEs)
研究概览
简要总结
The study aims to evaluate an egg-based H5N8 influenza vaccine up to 3 dose levels (low, medium, and high dose) given with or without adjuvant to see if the adjuvant improves vaccine effectiveness.
The study will enroll healthy adults aged 18 years and over. Participants will receive 2 injections in their arm of either one of the 3 dose levels of the study vaccine (low, medium, or high dose) with the adjuvant or the unadjuvanted vaccine (high dose).
Study duration per participant: approximately 14 months (including screening visit).
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)
盲法说明
Observer-blind study. Participants, Sponsor study staff, investigators and study staff, will remain blinded during the study conduct, except dedicated study staff preparing/administering the study interventions and who are not involved in the safety evaluation; dedicated Sponsor staff involved in Safety Governance for the early safety data review (ESDRs) and, if necessary, in case of a safety signal; dedicated Sponsor staff who will be unblinded for ESDRs and interim analyses; dedicated monitoring staff performing unblinded IMP monitoring tasks.
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 above on the day of inclusion
- •Participants who are healthy as determined by medical evaluation including medical history
- •Not pregnant/breastfeeding; non-childbearing potential or uses effective contraception/abstinence from ≥4 weeks before the first study intervention dose to ≥8 weeks after the last dose
- •Informed consent form has been signed and dated
- •Able to attend all scheduled visits and to comply with all study procedures
- •Covered by health insurance, if required by local regulations
排除标准
- •Known or suspected immunodeficiency; immunosuppressive therapy in past 6 months; or long-term systemic corticosteroid (eg, prednisone for more than 2 weeks in the past 3 months)
- •Known hepatitis B or hepatitis C infection (based on medical history)
- •Known personal or family history of previous episodes of Guillan-Barré syndrome (GBS), neuritis (including Bell's palsy), convulsions, encephalitis, transverse myelitis, and vasculitis
- •Known systemic hypersensitivity to any of the study intervention components or history of life-threatening reaction to the study interventions or products with same substances
- •Self-reported thrombocytopenia contraindicating intramuscular (IM) injection based on investigator's judgment
- •Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM injection based on investigator's judgment
- •Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion
- •History of A/H5 infection prior to the study participation
- •Moderate or severe acute illness/infection (per investigator judgment)/fever (≥ 38.0°C [≥ 100.4°F]) on study intervention day. Include participant only after the condition or fever has resolved
- •Alcohol, prescription drug, or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion
- •Any vaccine given 4 weeks before first study intervention or any planned vaccination to be given prior to Day 43 (ie, approximately 21 days after the second study intervention)
- •Previous vaccination against A(H5) with an investigational or marketed vaccine. This includes, but is not limited to, influenza subtypes A(H5N1), A(H5N8), and A(H5N6)
- •Has received a blood transfusion or blood-derived products, including immunoglobulins in the past 3 months
- •Participation in another clinical study for a vaccine, drug, medical device, or medical procedure within 4 weeks before enrollment or planned participation during the present study period
- •Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
- •Is an investigator, investigator/study center employee, or immediate family member (parent, spouse, natural/adopted child) of the investigator/employee with direct involvement in the study
- •Any screening safety laboratory parameters out of normal ranges and assessed as > Grade 2
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Group 4: Flu H5 Egg Pandemic high dose vaccine, without adjuvant
Participants receive 2 intramuscular injections of flu H5 egg pandemic high dose vaccine, without adjuvant
干预措施: Flu H5 Egg Pandemic high dose vaccine, without adjuvant (Biological)
Group 1: Flu H5 egg pandemic low dose vaccine, with adjuvant
Participants receive 2 intramuscular injections of flu H5 egg pandemic low dose vaccine, with adjuvant
干预措施: Flu H5 egg pandemic low dose vaccine, with adjuvant (Biological)
Group 2: Flu H5 Egg Pandemic medium dose vaccine, with adjuvant
Participants receive 2 intramuscular injections of flu H5 egg pandemic medium dose vaccine, with adjuvant
干预措施: Flu H5 Egg Pandemic medium dose vaccine, with adjuvant (Biological)
Group 3: Flu H5 Egg Pandemic high dose vaccine, with adjuvant
Participants receive 2 intramuscular injections of flu H5 egg pandemic high dose vaccine, with adjuvant
干预措施: Flu H5 Egg Pandemic high dose vaccine, with adjuvant (Biological)
结局指标
主要结局
Number of participants with immediate Adverse Events (AEs)
时间窗: Within 30 minutes after each vaccination
Immediate adverse events are medically relevant unsolicited systemic adverse events reported in the 30 minutes after vaccination
Number of participants experiencing solicited administration site reactions (pre-listed in the participant diary and case report form [CRF])
时间窗: Within 8 days of each vaccination, including the day of vaccination
A solicited reaction is an adverse reaction (sign or symptom) observed and reported under the conditions pre-listed (for example: injection site pain or headache). Solicited administration site reactions are reactions at and around the injection/administration site
Number of participants experiencing solicited systemic reactions (pre-listed in the participant diary and CRF)
时间窗: Within 8 days of each vaccination, including the day of vaccination
All solicited reactions that are not solicited injection or administration site reactions
Number of participants experiencing unsolicited AEs
时间窗: Within 21 days after the first vaccination, including the day of the first vaccination, and within 28 days after the second vaccination, including the day of the second vaccination
Unsolicited AE: an observed AE that does not fulfill the conditions of solicited reactions
Number of participants experiencing Medically Attended Adverse Events (MAAEs)
时间窗: From Day 01 until the end of the study, approximately 14 months
MAAEs are collected throughout the study
Number of participants experiencing Adverse Events of Special Interest (AESIs)
时间窗: From Day 01 until the end of the study, approximately 14 months
AESIs are collected throughout the study
Number of participants experiencing Serious Adverse Events (SAEs)
时间窗: From Day 01 until the end of the study, approximately 14 months
SAEs are collected throughout the study
Number of participants experiencing out-of-range biological test results (including shift from baseline values)
时间窗: Up to 8 days after each vaccination
Safety laboratory assessments will include clinical chemistry and hematology
Number of participants experiencing AEs leading to discontinuation
时间窗: From Day 01 until the end of the study, approximately 14 months
AEs leading to discontinuation are collected throughout the study
Geometric mean titer of hemagglutination inhibition (HAI) assay antibody (Ab) titer
时间窗: Day 01 and Day 43
Influenza vaccine antibody titers are measured by HAI assay
Number of participants with HAI Ab titer ≥ 40 (1 dilution [dil]; ie, seroprotection)
时间窗: Day 43
Influenza vaccine antibody titers are measured by HAI assay
Number of participants with seroconversion
时间窗: Day 01 and Day 43
Seroconversion is defined as HAI Ab titer \< 10 (1/dil) on Day 01 and post-injection titer ≥ 40 (1/dil) on Day 43; or defined as HAI Ab titer ≥ 10 (1/dil) on Day 01 and a ≥ 4-fold increase in titer (1/dil) on Day 43
Geometric mean titer ratio of individual HAI Ab titer ratio Day 43/Day 01
时间窗: Day 01 and Day 43
Influenza vaccine antibody titers are measured by HAI assay
次要结局
- Geometric mean titer of hemagglutination inhibition (HAI) assay antibody (Ab) titer obtained on Day 01, Day 22, Day 43, Day 202(Day 01, Day 22, Day 43, Day 202)
- Geometric mean titer ratio of individual HAI Ab titer ratios Day 22/Day 01, Day 43/Day 01, Day 202/Day 43(Day 01, Day 22, Day 43, Day 202)
- Number of participants with individual HAI Ab titer ≥ 40 (1/dil) on Day 01, Day 22, Day 43, Day 202(Day 01, Day 22, Day 43, Day 202)
- Number of participants with seroconversion on Day 22 compared to Day 01 (baseline)(Day 01, Day 22)
- Number of participants with detectable HAI Ab titer(Day 01, Day 22, Day 43, Day 202)
- Geometric mean titer of neutralization (NT) Ab titer(Day 01, Day 22, Day 43, Day 202)
- Geometric mean titer ratio of individual NT Ab titer ratio(Day 01, Day 22, Day 43, Day 202)
- Number of participants with NT Ab titer ≥ 20 (1/dil)(Day 01, Day 43, Day 202)
- Number of participants with NT Ab titer ≥ 40 (1/dil)(Day 01, Day 43, Day 202)
- Number of participants with NT Ab titer ≥ 80 (1/dil)(Day 01, Day 43, Day 202)
- Geometric mean fold-rise of fold increase in NT Ab titer [post/pre] ≥ 2 and ≥ 4(Day 43)
- Number of participants with detectable NT Ab titer(Day 01, Day 22, Day 43, Day 202)