A Phase I/II, Randomized, Modified Double-blind Study to Investigate the Safety and Immunogenicity of Different Doses of Hexavalent Influenza mRNA HA + mRNA NA Vaccine in Adult Participants 50 Years of Age and Older
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 1,162
- 试验地点
- 48
- 主要终点
- Number of participants with immediate unsolicited systemic adverse events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety and immunogenicity of a single intramuscular injection of different formulations of a hexavalent influenza messenger ribonucleic acid (mRNA) vaccine composed of differing dose levels of trivalent (TIV) mRNA hemagglutinin (HA) in combination with TIV mRNA-neuraminidase (NA) compared to an active control ((Fluzone standard-dose quadrivalent influenza vaccine (QIV-SD) or Fluzone high-dose quadrivalent influenza vaccine (QIV-HD) in adults 50 years of age and older.
详细描述
Study details include the following:
- Study Duration: approximately 12 months for each participant
- Treatment: 1 injection of hexavalent vaccine, trivalent vaccine, or active control
- Visit frequency: Day (D) 01, D03, D09, D29, and D181; D366 (telephone call)
- Dose escalation with sequential enrollment of sentinel cohorts followed by parallel enrollment of the main cohort
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 (participants; sites, except for those preparing/administering study intervention; and Sponsor will be blinded. Sponsor's internal safety monitoring team could be unblinded if necessary)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant aged 50 years 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 study intervention administration until at least 12 weeks after 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 prior to administration of study intervention.
排除标准
- •Participants are not eligible for the study if any of the following criteria are met:
- •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 mRNA vaccine
- •Previous history of myocarditis, pericarditis, and/or myopericarditis
- •Known history of previous episodes of Guillain-Barré syndrome, 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 intramuscular (IM) vaccination based on Investigator's judgment
- •Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination 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 judgement) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on the day of vaccination. 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 SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to the first visit (V01)
- •Receipt of any vaccine in the 4 weeks preceding study intervention administration or planned receipt of any vaccine in the 4 weeks following study intervention administration
- •Receipt of immune globulins, blood or blood-derived products in the past 3 months
- •Previous vaccination against influenza in the previous 6 months with an investigational or marketed vaccine
- •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 study vaccination
- •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
- •Self-reported or documented seropositivity for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
研究组 & 干预措施
Group 1 - Hexavalent (Combination 1)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 1)
干预措施: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1 (Biological)
Group 1 - Hexavalent (Combination 1)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 1)
干预措施: TIV mRNA-neuraminidase (NA) (Biological)
Group 7 - TIV mRNA-HA Vaccine 1
Participants will receive a single dose of TIV mRNA-HA Vaccine 1
干预措施: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1 (Biological)
Group 8 - TIV mRNA-NA
Participants will receive a single dose of TIV mRNA-NA
干预措施: TIV mRNA-neuraminidase (NA) (Biological)
Group 9 - TIV mRNA-HA Vaccine 2
Participants will receive single dose of TIV mRNA-HA Vaccine 2
干预措施: TIV mRNA-HA Vaccine 2 (Biological)
Group 2 - Hexavalent (Combination 2)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 2)
干预措施: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1 (Biological)
Group 2 - Hexavalent (Combination 2)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 2)
干预措施: TIV mRNA-neuraminidase (NA) (Biological)
Group 3 - Hexavalent (Combination 3)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 3)
干预措施: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1 (Biological)
Group 3 - Hexavalent (Combination 3)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 3)
干预措施: TIV mRNA-neuraminidase (NA) (Biological)
Group 4 - Hexavalent (Combination 4)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 4)
干预措施: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1 (Biological)
Group 4 - Hexavalent (Combination 4)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 4)
干预措施: TIV mRNA-neuraminidase (NA) (Biological)
Group 5 - Hexavalent (Combination 5)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 5)
干预措施: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1 (Biological)
Group 5 - Hexavalent (Combination 5)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 5)
干预措施: TIV mRNA-neuraminidase (NA) (Biological)
Group 6 - Hexavalent (Combination 6)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 6)
干预措施: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1 (Biological)
Group 6 - Hexavalent (Combination 6)
Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 6)
干预措施: TIV mRNA-neuraminidase (NA) (Biological)
Group 10 - QIV-SD
Participants will receive single dose of QIV-SD vaccine (for participants 50 to 64 years of age only)
干预措施: Quadrivalent Influenza Standard Dose Vaccine (Biological)
Group 11 - QIV-HD
Participants will receive single dose of QIV-HD vaccine
干预措施: Quadrivalent Influenza Vaccine High Dose (Biological)
结局指标
主要结局
Number of participants with immediate unsolicited systemic adverse events (AEs)
时间窗: Within 30 minutes after injection
Unsolicited systemic AEs that occur within 30 minutes after vaccination
Number of participants with solicited injection site reactions
时间窗: Up to 7 days after injection
Solicited injection site reactions pre-listed in the participant diary and in the case report form CRF
Neuraminidase inhibition (NAI) titers
时间窗: At Day 1 and Day 29
NAI titers at D01 and D29
Number of participants with solicited systemic reactions
时间窗: Up to 7 days after injection
Solicited systemic reactions pre-listed in the participant diary and in the CRF
Number of participants with unsolicited AEs
时间窗: Up to 28 days after injection
AEs that do not fulfill the conditions of solicited reactions
Number of participants with medically attended adverse events (MAAEs)
时间窗: Up to 180 days after injection
MAAEs reported up to 180 days after injection
Number of participants with serious adverse events (SAEs)
时间窗: SAEs throughout the study (Up to approximately 12 months)
Throughout the study
Number of participants with adverse events of special interest (AESIs)
时间窗: AESIs throughout the study (Up to approximately 12 months)
Throughout the study
Number of participants with out-of-range biological test results
时间窗: Up to 8 days after injection
Out-of-range biological test results (including shift from baseline values)
Hemagglutinin inhibition (HAI) titers
时间窗: At Day 1 and Day 29
HAI titers at D01 and D29
Individual HAI antibody (Ab) titer ratio D29/D01
时间窗: At Day 1 and Day 29
Individual HAI Ab titer ratio D29/D01
Seroconversion (HAI Ab titer)
时间窗: At Day 1 and Day 29
Number of participants with HAI Ab titer \< 10 \[1/dil\] at Day 1 and post-injection titer ≥ 40 \[1/dil\] at Day 29, or titer ≥ 10 \[1/dil\] at Day 1 and a ≥ 4-fold increase in titer \[1/dil\] at Day 29
HAI Ab titer ≥ 40 (1/dil)
时间窗: At Day 29
HAI Ab titer ≥ 40 (1/dil) at D29
Individual NAI Ab titer ratio D29/D01
时间窗: At Day 1 and Day 29
Individual NAI Ab titer ratio D29/D01
Seroconversion (NAI Ab titer)
时间窗: At Day 1 and Day 29
Number of participants with NAI Ab titer \< 10 \[1/dil\] at D01 and post-injection titer ≥ 40 \[1/dil\] at D29, or titer ≥ 10 \[1/dil\] at D01 and a ≥ 4-fold increase in titer \[1/dil\] at D29)
NAI Ab titer ≥ 40 (1/dil)
时间窗: At Day 29
NAI Ab titer ≥ 40 (1/dil) at D29
2-fold and 4-fold rise in NAI titers
时间窗: Day 1 to Day 29
2-fold and 4-fold rise in NAI titers from D01 to D29
次要结局
- Neutralizing antibodies titers(At Day 1 and Day 29)
- Individual neutralizing antibodies titer ratio(At Day 1 and Day 29)
- 2-fold and 4-fold increase in neutralizing titers(Day 1 to Day 29)