A Phase 1/2, Randomized, Observer-blind, Placebo-controlled Multi-arm Study to Evaluate the Safety and Immunogenicity of an hMPV/RSV mRNA Vaccine Candidate in Adult Participants Aged 60 Years and Older
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,530
- 试验地点
- 24
- 主要终点
- Presence of unsolicited immediate systemic adverse events (AEs) (Stage 1 and Stage 2 Expansion and Booster Cohorts)
研究概览
简要总结
The aim of this study is to evaluate the safety and immunogenicity of a human metapneumovirus (hMPV) / respiratory syncytial virus (RSV) mRNA vaccine candidate encapsulated in a lipid nanoparticle (LNP) based formulation (hereafter referred to as hMPV/RSV vaccine) for the prevention of lower respiratory tract disease (LRTD) caused by hMPV and/or RSV among adults aged 60 years and older.
The study will also evaluate the safety and immunogenicity of a booster vaccination using a bivalent hMPV/RSV mRNA vaccine candidate (hereafter referred to as RSV+hMPV mRNA vaccine candidate).
Overall, the study is designed to address the following goals:
- Assess the safety profile of the candidate formulations.
- Describe the immunogenicity profile of the candidate formulations.
- Select the vaccine formulations (dose) for future development.
- Assess the safety and immunogenicity of a booster vaccination with the RSV + hMPV mRNA vaccine candidate administered 12 months after primary vaccination with a licensed RSV vaccine.
The study duration is as follows:
-Six months each for the Sentinel and Main Cohorts; up to 12 months for the Expansion Cohort, and 6 additional months for the Booster Cohort
Treatment duration:
- Stage 1 Sentinel Cohort: 1 intra-muscular (IM) injection. Participants will be followed for 6 months post vaccination
- Stage 1 Main Cohort: 1 IM injection. Participants will be followed for 6 months post vaccination
- Stage 2 Expansion Cohort: 1 IM injection. Participants in the licensed RSV vaccine arm will be followed for 12 months post-vaccination; the remainder of the participants will be followed up to 8 months post-vaccination
- Stage 2 Booster Cohort: 1 IM injection 12 months post-primary vaccination. Participants will be followed for 6 months post-booster vaccination
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
Stage 1 Sentinel and Main Cohorts: observer-blind; for safety evaluation purposes, the Sponsor Safety Management Team (SMT) will be unblinded for the Sentinel Cohort (including early safety data review [ESDR]) and will be blinded for the Main Cohort.
Stage 2 Expansion Cohort: observer-blind until all participants complete the Month 6 visit, then open-label Stage 2 Booster Cohort: open-label
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 60 years or older on the day of inclusion
- •A female participant is eligible to participate if she is not pregnant or breastfeeding and 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
排除标准
- •Any screening laboratory parameter with laboratory abnormality > Grade 1 deemed clinically significant by the investigator
- •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). Of note, persons living with stable human immunodeficiency virus (HIV) are not excluded
- •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
- •History of RSV and/or hMPV-associated illness, diagnosed serologically or microbiologically in the last 12 months
- •Previous history of myocarditis, pericarditis, and/or myopericarditis
- •Screening electrocardiogram that is consistent with possible myocarditis, pericarditis, and/or myopericarditis or, in the opinion of the investigator, demonstrates clinically relevant abnormalities that may affect participant safety or study results
- •Laboratory-confirmed 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
- •Receipt of any vaccine other than mRNA vaccine in the 28 days preceding any study intervention administration or planned receipt of any vaccine other than mRNA vaccine in the 28 days following any study intervention administration
- •Receipt of any mRNA vaccine in the 60 days preceding any study intervention administration or planned receipt of any mRNA vaccine in the 60 days following any study intervention administration
- •Previous vaccination against RSV and/or hMPV (with a licensed or investigational vaccine either as a monovalent vaccine or any combination of the antigens)
- •Receipt of immune globulins, blood, or blood-derived products in the past 3 months
- •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 C Stage 1 Sentinel Cohort
1 IM injection of placebo
干预措施: Placebo (Biological)
Group A Stage 1 Sentinel Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation A
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group B Stage 1 Sentinel Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation B
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 1 Stage 1 Main Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation C
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 2 Stage 1 Main Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation D
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 3 Stage 1 Main Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation E
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 4 Stage 1 Main Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation F
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 5 Stage 1 Main Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation G
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 6 Stage 1 Main Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation A
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 7 Stage 1 Main Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation B
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 8 Stage 1 Main Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation H
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 9 Stage 1 Main Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation I
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 10 Stage 1 Main Cohort
1 IM injection of investigational hMPV/RSV vaccine formulation J
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 11 Stage 1 Main Cohort
1 IM injection of placebo
干预措施: Placebo (Biological)
Group X Stage 2 Expansion Cohort
1 IM injection of selected investigational hMPV/RSV vaccine formulation from Group 1-9 of Stage 1 Main Cohort
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 12 Stage 2 Expansion Cohort
1 IM injection of investigational RSV monovalent vaccine
干预措施: Investigational RSV vaccine (monovalent) (Biological)
Group 13 Stage 2 Expansion Cohort
1 IM injection of investigational hMPV monovalent vaccine
干预措施: Investigational hMPV vaccine (monovalent) (Biological)
Group 14 Stage 2 Expansion Cohort
1 IM injection of licensed RSV vaccine
干预措施: Licensed RSV Vaccine (Biological)
Group 15 Stage 2 Booster Cohort
1 IM injection of investigational RSV + hMPV vaccine formulation administered to participants from Group 14 of Expansion Cohort
干预措施: Investigational hMPV/RSV vaccine (Biological)
Group 15 Stage 2 Booster Cohort
1 IM injection of investigational RSV + hMPV vaccine formulation administered to participants from Group 14 of Expansion Cohort
干预措施: Investigational RSV+hMPV vaccine (Biological)
结局指标
主要结局
Presence of unsolicited immediate systemic adverse events (AEs) (Stage 1 and Stage 2 Expansion and Booster Cohorts)
时间窗: Within 30 minutes after primary and booster vaccinations
Number of participants reporting immediate unsolicited systemic AEs
Presence of solicited injection site and systemic reactions (Stage 1 and Stage 2 Expansion and Booster Cohorts)
时间窗: Up to 7 days after primary and booster vaccinations
Number of participants reporting solicited injection site and systemic reactions
Presence of unsolicited AEs (Stage 1 and Stage 2 Expansion and Booster Cohorts)
时间窗: Up to 28 days after primary and booster vaccinations
Number of participants reporting unsolicited AEs
Presence of medically attended AEs (MAAEs) (Stage 1 and Stage 2 Expansion and Booster Cohorts)
时间窗: Up to 6 months after primary and booster vaccinations
Number of participants reporting MAAEs
Presence of serious AEs (SAEs) and AEs of special interest (AESIs) (Stage 1 and Stage 2 Expansion and Booster Cohorts)
时间窗: Up to 6 months after primary and booster vaccinations
Number of participants reporting SAEs and AESIs
Presence of related SAEs, related AESIs, and fatal SAEs (regardless of causality) (Stage 1 and Stage 2 Expansion and Booster Cohorts)
时间窗: Throughout the duration of the study (up to approximately 24 months)
Number of participants reporting related SAEs, related AESIs, and fatal SAEs
Presence of out-of-range biological test results (Stage 1)
时间窗: Up to 7 days after primary vaccination
Number of participants with out-of-range biological tests
Presence of out-of-range biological test results (Stage 2 Booster Cohort)
时间窗: Up to 7 days after booster vaccination
Number of participants with out-of-range biological tests
hMPV A serum neutralizing antibodies (nAb) titers in Stage 1 Sentinel and Main Cohorts
时间窗: At pre-vaccination (Day 01) and 28 days post-primary vaccination (Day 29)
nAb titers expressed as geometric mean titers (GMTs)
hMPV B serum neutralizing antibodies (nAb) titers in Stage 1 Sentinel and Main Cohorts
时间窗: At pre-vaccination (Day 01) and 28 days post-primary vaccination (Day 29)
nAb titers expressed as geometric mean titers (GMTs)
RSV A serum nAb titers in Stage 1 Sentinel and Main Cohorts
时间窗: At pre vaccination (D01) and 28 days post-primary vaccination (D29)
nAb titers expressed as geometric mean titers (GMTs)
RSV B serum nAb titers in Stage 1 Sentinel and Main Cohorts
时间窗: At pre vaccination (D01) and 28 days post-primary vaccination (D29)
nAb titers expressed as geometric mean titers (GMTs)
hMPV A serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
时间窗: At (Day 01) pre-vaccination and 28 days after the injection of the hMPV standalone vaccine (Day 29)
nAb titers expressed as geometric mean titers (GMTs)
hMPV B serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
时间窗: At (Day 01) pre-vaccination and 28 days after the injection of the hMPV standalone vaccine (Day 29)
nAb titers expressed as geometric mean titers (GMTs)
RSV A serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
时间窗: At (Day 01) pre-vaccination and 28 days after the injection of the RSV standalone vaccine (Day 29)
nAb titers expressed as geometric mean titers (GMTs)
RSV B serum neutralizing antibodies (nAb) titers in Stage 2 Expansion Chort
时间窗: At (Day 01) pre-vaccination and 28 days after the injection of the RSV standalone vaccine (Day 29)
nAb titers expressed as geometric mean titers (GMTs)
次要结局
- hMPV serum anti-F immunoglobulin G (IgG) antibody (Ab) titers (Stage 1)(At pre-vaccination (Day 01) and 28 days (D29) post-primary vaccination)
- RSV serum anti-F IgG Ab titers (Stage 1)(At pre-vaccination (Day 01) and 28 days (D29) post-primary vaccination)
- hMPV A serum nAb titers (Stage 2 Expansion Cohort)(At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination)
- hMPV B serum nAb titers (Stage 2 Expansion Cohort)(At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination)
- hMPV A serum anti-F IgG Ab titers (Stage 2 Expansion Cohort)(At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination)
- RSV A serum nAb titers (Stage 2 Expansion Cohort)(At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination)
- RSV B serum nAb titers (Stage 2 Expansion Cohort)(At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination)
- RSV serum anti-F IgG Ab titers (Stage 2 Expansion Cohort)(At pre-vaccination (Day 01), 28 days (D29), and 3 and 6 months post-primary vaccination)