A Phase 1, Randomized, Observer-blind, Placebo-controlled, Age De-escalation Study of the Safety, Tolerability, and Immunogenicity of mRNA-1345 and mRNA-1365 in Participants Aged 5 Months to <24 Months
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 186
- 试验地点
- 62
- 主要终点
- Number of Participants with Medically-Attended Adverse Events (MAAEs)
研究概览
简要总结
The purpose of this study is to assess the safety and immunogenicity of mRNA-1365, an mRNA vaccine targeting respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) and mRNA-1345, an mRNA vaccine targeting RSV, in participants aged 5 months to <24 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Parts A and B are blinded, and Part C is open-label. Part B Extension is unblinded.
入排标准
- 年龄范围
- 5 Months 至 24 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant is 8 months to <24 months (Part A), 5 months to <8 months (Part B), or 8 months to <12 months (Part C) of age at the time of randomization (Day 1/Baseline visit), who is in good general health, in the opinion of the Investigator, based on review of medical history and screening physical examination.
- •In the Investigator's opinion, the parent(s)/ legally authorized representative (LAR)(s) understand and are willing and physically able to comply with protocol-mandated follow up, including all procedures, and provide written informed consent.
- •The participant is growing normally for age in the opinion of the site clinician in the months prior to enrollment.
- •The participant was born at full-term (≥37 weeks gestation) with a minimum birth weight of 2.5 kilograms (kg).
- •For Part C Cohort 7: participant must have received nirsevimab ≥6 months prior to Day 1 Visit.
- •For Part C Cohort 8: participant was eligible at any time since birth, according to national guidelines, to receive nirsevimab prior to Day 1 Visit but did not do so.
排除标准
- •Has a known history of symptomatic RSV (Part A: within 3 months; Part B and Part C: since birth) or hMPV infection (Part A: within 3 months; Part B: since birth) prior to administration of the first dose of investigational product (IP) or has a known close contact with anyone with laboratory-confirmed RSV (Parts A, B, and C) or hMPV infection (Parts A or B) within 14 days prior to administration of the first dose of IP.
- •Is acutely ill or febrile 24 hours prior to or at the screening visit. Fever is defined as a body temperature ≥38.0°Celsius/≥100.4°Fahrenheit. Participants who meet this criterion may have visits rescheduled within the relevant study visit windows.
- •Has previously been administered an investigational or approved vaccine for prevention of RSV (Parts A, B, and C) or hMPV (Parts A and B) infection or if the participant's mother received an investigational or approved vaccine for the prevention of RSV (Parts A, B, and C) or hMPV (Parts A and B) infection during pregnancy.
- •Has received investigational or approved agents for prophylaxis against RSV or hMPV (for example, monoclonal antibodies) or is intending to receive these during the course of the study. For Part C (Cohort 7 only), use of nirsevimab ≥6 months before Day 1 Visit is allowed.
- •Has a known hypersensitivity to a component of the vaccine or its excipients. Hypersensitivity includes, but is not limited to, anaphylaxis or immediate allergic reaction of any severity to a previous dose of an mRNA vaccine or any of its components (including polyethylene glycol or immediate allergic reaction of any severity to polysorbate).
- •Has a medical condition that, according to the Investigator's judgment, may pose additional risk as a result of participation, interfere with safety assessments, or interfere with interpretation of results.
- •Note: Other protocol-defined inclusion/exclusion criteria apply.
- •Inclusion Criteria:
- •For Part B Extension: participants enrolled and dosed in Part B (Cohorts 3 to 6); either reached the end of study of the Main Study or were dosed and subsequently discontinued from the Main Study. This includes participants who were lost to follow-up, if they can be re-engaged.
- •For Part B Extension: participant's parent(s)/LAR(s) has provided written informed consent for participation in Part B of the Main Study and the Part B Extension.
- •Exclusion Criteria:
- •For Part B Extension, there are no specific exclusion criteria.
研究组 & 干预措施
Part A: Placebo (Age Group: 8 to <24 months)
Participants will receive mRNA-1345/ mRNA-1365 vaccine matching placebo by IM injection on Days 1, 57 and 113. In countries where applicable, participants may receive Nimenrix instead of placebo on Day 113.
干预措施: Placebo (Biological)
Part A: mRNA-1365, Dose 1 (Age Group: 8 to <24 months)
Participants will receive mRNA-1365 vaccine by IM injection on Days 1, 57 and 113.
干预措施: mRNA-1365 (Biological)
Part A: Placebo (Age Group: 8 to <24 months)
Participants will receive mRNA-1345/ mRNA-1365 vaccine matching placebo by IM injection on Days 1, 57 and 113. In countries where applicable, participants may receive Nimenrix instead of placebo on Day 113.
干预措施: Nimenrix (Drug)
Part B: Placebo (Age Group: 5 to <8 months)
Participants will receive mRNA-1345/ mRNA-1365 vaccine matching placebo by IM injection on Days 1, 57 and 113. In countries where applicable, participants may receive Nimenrix instead of placebo on Day 113.
干预措施: Nimenrix (Drug)
Part B: mRNA-1365, Dose 2 (Age Group: 5 to <8 months)
Participants will receive mRNA-1365 by IM injection on Days 1, 57 and 113.
干预措施: mRNA-1365 (Biological)
Part B: mRNA-1345 Dose 1 (Age Group: 5 to <8 months)
Participants will receive mRNA-1345 by IM injection on Days 1, 57 and 113.
干预措施: mRNA-1345 (Biological)
Part B: Placebo (Age Group: 5 to <8 months)
Participants will receive mRNA-1345/ mRNA-1365 vaccine matching placebo by IM injection on Days 1, 57 and 113. In countries where applicable, participants may receive Nimenrix instead of placebo on Day 113.
干预措施: Placebo (Biological)
Part B: mRNA-1345, Dose 2 (Age Group: 5 to <8 months)
Participants will receive mRNA-1345 by IM injection on Days 1, 57 and 113.
干预措施: mRNA-1345 (Biological)
Part A: mRNA-1345, Dose 1 (Age Group: 8 to <24 months)
Participants will receive mRNA-1345 vaccine by intramuscular (IM) injection on Days 1, 57 and 113.
干预措施: mRNA-1345 (Biological)
Part B: mRNA-1365 Dose 1 (Age Group: 5 to <8 months)
Participants will receive mRNA-1365 by IM injection on Days 1, 57 and 113.
干预措施: mRNA-1365 (Biological)
Part C: mRNA-1345 Dose 1 (Age Group 8 to <12 months exposed to nirsevimab)
Participants who have been previously exposed to nirsevimab will receive mRNA 1345 by IM injection on Days 1, 57, and 113.
干预措施: mRNA-1345 (Biological)
Part C: mRNA-1345 Dose 1 (Age Group 8 to <12 months not exposed to nirsevimab)
Participants who have not been previously exposed to nirsevimab will receive mRNA 1345 by IM injection on Days 1, 57, and 113.
干预措施: mRNA-1345 (Biological)
结局指标
主要结局
Number of Participants with Medically-Attended Adverse Events (MAAEs)
时间窗: Day 1 through Day 730
Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)
时间窗: Up to Day 120 (7 days after each injection)
Number of Participants with Unsolicited Adverse Events (AEs)
时间窗: Up to Day 141 (28 days after each injection)
Number of Participants with Adverse Event of Special Interests (AESIs), Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation
时间窗: Day 1 through Day 730
Main Study: Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)
时间窗: Up to Day 120 (7 days after each injection)
Main Study: Number of Participants with Unsolicited Adverse Events (AEs)
时间窗: Up to Day 141 (28 days after each injection)
Main Study: Number of Participants with Medically-Attended Adverse Events (MAAEs)
时间窗: Day 1 through Day 730
Main Study: Number of Participants with Adverse Event of Special Interests (AESIs), Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation
时间窗: Day 1 through Day 730
Part B Extension: Number of Participants with MAAEs, AESIs and SAEs
时间窗: Day 1 of the Extension to end of study (EoS) (up to 3 years)
Part B Extension: Number of Participants with Lower Respiratory Tract Illness (LRTI), Severe LRTI, Very Severe LRTI, and Hospitalizations Associated with RSV or hMPV
时间窗: Day 1 of the Extension to EoS (up to 3 years)
次要结局
- Number of Participants with Respiratory Tract Illness (RTI), Lower Respiratory Tract Illness (LRTI), Severe LRTI, Very Severe LRTI, and Hospitalizations Associated with RSV or hMPV(Day 1 through Day 730)
- Parts A and B: Geometric Mean Titer (GMT) of Serum RSV and hMPV Neutralizing Antibodies(Baseline up to Month 12)
- Part C: GMT of Serum RSV Neutralizing Antibodies(Baseline up to Month 12)
- Parts A and B: Geometric Mean Concentration (GMC) of Serum RSV F- and hMPV F-Binding Antibodies(Baseline up to Month 12)
- Part C: GMC of Serum RSV F-Binding Antibodies(Baseline up to Month 12)
- Geometric Mean Fold-Rise (GMFR) Postbaseline/baseline Neutralizing Antibody Titers(Baseline up to Month 12)
- Number of Participants with Vaccine-specific T-cell Responses Measured by Flow Cytometry(Baseline up to month 12)
- Main Study: Number of Participants with Respiratory tract Illness (RTI), LRTI, Severe LRTI, Very Severe LRTI, and Hospitalizations Associated with RSV or hMPV(Day 1 through Day 730)
- Main Study (Parts A and B): Geometric Mean Titer (GMT) of Serum RSV and hMPV Neutralizing Antibodies(Baseline up to Month 12)
- Main Study (Part C): GMT of Serum RSV Neutralizing Antibodies(Baseline up to Month 12)
- Main Study (Parts A and B): Geometric Mean Concentration (GMC) of Serum RSV F- and hMPV F-Binding Antibodies(Baseline up to Month 12)
- Main Study (Part C): GMC of Serum RSV F-Binding Antibodies(Baseline up to Month 12)
- Main Study: Geometric Mean Fold-Rise (GMFR) of Postbaseline/baseline Neutralizing Antibody Titers and Binding Antibody(Month 12)
- Main Study: Number of Participants with Vaccine-specific T-cell Responses Measured by Flow Cytometry(Baseline up to Month 12)
- Part B Extension: Geometric Mean Titer (GMT) of Serum RSV and hMPV Neutralizing Antibodies(Day 1 of the Extension up to EoS (up to 3 years))
- Part B Extension: Geometric Mean Concentration (GMC) of Serum RSV F- and hMPV F-Binding Antibodies(Day 1 of the Extension up to EoS (up to 3 years))
- Part B Extension: Geometric Mean Fold-Rise (GMFR) of Postbaseline/baseline Neutralizing Antibody Titers and Binding Antibody(Day 1 of the Extension up to EoS (up to 3 years))
- Part B Extension: Number of Participants with Vaccine-specific T-cell Responses Measured by Flow Cytometry(Day 1 of the Extension up to EoS (up to 3 years))