A Phase 1/2, Randomized, Modified Double-blind, Placebo-controlled, Multi-center, Dose Escalating Study to Evaluate the Safety and Immunogenicity of a Pandemic Flu H5 mRNA Vaccine in Healthy Adults Aged 18 Years and Older
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 276
- 试验地点
- 14
- 主要终点
- Presence of immediate adverse events (AEs) within 30 minutes after each/any injection
研究概览
简要总结
The purpose of this study is to evaluate a pandemic flu H5 strain messenger ribonucleic acid (mRNA) vaccine at 3 dose levels (low, medium, and high) in comparison with placebo in 276 healthy adult participants to select the adequate dose for further clinical development.
The duration per participant will be approximately 13 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Modified double blind (participants; sites, except for those preparing/administering study intervention; and Sponsor will be blinded). Sponsor's internal safety monitoring team will be unblinded if necessary. "Evaluation of the Safety of the sentinel cohorts will be unmasked for the Sponsor's safety Team".
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.
- •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 postmenopausal for at least 1 year, or surgically sterile.
- •Is of childbearing potential and agrees to use an 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 8 hours before the first dose of study intervention.
排除标准
- •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 (eg, polyethylene glycol, polysorbate); history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances; any allergic reaction (eg, anaphylaxis) after administration of an mRNA vaccine .
- •Previous history of myocarditis, pericarditis, and/or myopericarditis.
- •Known history of previous episodes of Guillain-Barré Syndrome (GBS), neuritis (including Bell's palsy), convulsions , encephalitis, transverse myelitis, and vasculitis.
- •Participants with an electrocardiogram that is consistent with possible myocarditis or pericarditis or, in the opinion of the investigator, demonstrates clinically relevant abnormalities that may affect participant safety or study results.
- •Self-reported thrombocytopenia, contraindicating 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.
- •Moderate or severe acute illness / infection (according to investigator's judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on the day of study intervention. 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.
- •Participant who had acute infectious symptoms or a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase polymerase chain reaction (RT PCR) or antigen test in the past 10 days prior to the first visit (V)
- •Receipt of any vaccine other than an mRNA vaccine in the 4 weeks preceding study intervention administration or planned receipt of any vaccine other than an mRNA vaccine in the 3 weeks following the second dose of the study intervention .
- •Receipt of immune globulins, blood or blood-derived products in the past 3 months.
- •Receipt of any mRNA vaccine/product in the 2 months preceding study intervention administration or planned receipt of any mRNA vaccine in the 2 months after the second dose of the study intervention.
- •Participation at the time of study enrollment (or in the 4 weeks preceding study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.
- •Previous history of participation in an H5 influenza A vaccine study. This includes any influenza subtypes that contain H5 such as H5N1, H5N8, or H5N
- •Note: 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: Low Dose Pandemic flu H5 mRNA vaccine
Participants will receive 2 injections of pandemic flu H5 mRNA vaccine 21 days apart (at Day 01 and Day 22)
干预措施: Pandemic flu H5 mRNA vaccine (Biological)
Group 2: Medium Dose Pandemic flu H5 mRNA vaccine
Participants will receive 2 injections of pandemic flu H5 mRNA vaccine 21 days apart (at Day 01 and Day 22)
干预措施: Pandemic flu H5 mRNA vaccine (Biological)
Group 3: High Dose Pandemic flu H5 mRNA vaccine
Participants will receive 2 injections of pandemic flu H5 mRNA vaccine 21 days apart (at Day 01 and Day 22)
干预措施: Pandemic flu H5 mRNA vaccine (Biological)
Group 4: Placebo
Participants will receive 2 injections of placebo 21 days apart (at Day 01 and Day 22)
干预措施: Placebo (Other)
结局指标
主要结局
Presence of immediate adverse events (AEs) within 30 minutes after each/any injection
时间窗: Within 30 minutes of any/each injections
Number of participants experiencing immediate AEs
Presence of solicited injection site reactions through 7 days after each/any injection
时间窗: Through 7 days after each/any injections
Number of participants experiencing solicited injection site reactions
Presence of solicited systemic site reactions through 7 days after each/any injection
时间窗: Through 7 days after each/any injections
Number of participants experiencing solicited systemic site reactions
Presence of unsolicited AEs through 21 days after the first injection and through 28 days after the second injection
时间窗: Through 21 days after the first injection and through 28 days after the second injection
Number of participants experiencing unsolicited AEs
Presence of medically attended adverse events (MAAEs) through 180 days after the last injection
时间窗: Through 180 days after the last injection
Number of participants experiencing MAAEs
Presence of adverse events of special interest (AESIs) throughout the study
时间窗: Throughout the study, approximately 13 months
Number of participants experiencing AESIs
Presence of serious adverse events (SAEs) throughout the study
时间窗: Throughout the study, approximately 13 months
Number of participants experiencing SAEs
Presence of out-of-range biological test results (including shift from baseline values) through a maximum of 8 days after each injection
时间窗: Through a maximum of 8 days after each injection
Number of participants with out-of-range biological test results
次要结局
- Antibody titers measured by Hemagglutination Inhibition (HAI) Assay(At Day 01, Day 22, Day 43, Day 112, and Day 202)
- Individual HAI titer ratio(At Day 22/Day 01, Day 43/Day 01, Day 112/Day 01, and Day 202/Day 01)
- ≥ 4-fold increase in HAI titer [1/dilution])(At Day 22 or Day 43)
- HAI titer ≥ 10 [1/dilution](At day 01)
- HAI titer ≥ 40 [1/dilution](At Day 01, Day 22, Day 43, Day 112, and Day 202)
- Detectable HAI titer ≥ 10 [1/dilution](At Day 01, Day 22, Day 43, Day 112, and Day 202)
- Antibody titers measured by Seroneutralization (SN) test(At Day 01, Day 22, Day 43, Day 112, and Day 202)
- Individual SN titer ratio(Day 22/Day 01, Day 43/Day 01, Day 112/Day 01, and Day 202/Day 01)
- SN titer ≥ 20 (1/dilution)(At Day 01, Day 22, Day 43, Day 112, and Day 202)
- SN titer ≥ 40 (1/dilution)(At Day 01, Day 22, Day 43, Day 112, and Day 202)
- SN titer ≥ 80 (1/dilution)(At Day 01, Day 22, Day 43, Day 112, and Day 202)
- Detectable SN titer ≥ 10 (1/dilution)(At Day 01, Day 22, Day 43, Day 112, and Day 202)
- 2-fold rise in SN titer(At Day 22 and Day 43)
- 4-fold rise in SN titer(At Day 22 and Day 43)