A Phase 1/2, Randomized, Placebo-Controlled, Observer-Blind, Dose-Ranging Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1403 and mRNA-1405, Multivalent Candidate Vaccines to Prevent Norovirus Acute Gastroenteritis in Healthy Adults 18 to 80 Years of Age
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 1,405
- 试验地点
- 16
- 主要终点
- Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)
研究概览
简要总结
The purpose of the Part A Phase 1 of this study is to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1403 and mRNA-1405 in healthy adult participants 18 to 49 years of age and 60 to 80 years of age. The purpose of Part B Phase 2 and Part C Phase 2 is to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1403 in healthy adult participants (18 to 80 years of age).
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part A Phase 1: Adults 18 to 49 years of age at the time of consent or adults 60 to 80 years of age at the time of consent.
- •Part B Phase 2 and Part C Phase 2: Adults 18 to 80 years of age at the time of consent.
- •Body mass index of 18 to 39 kilogram/meter^2 (inclusive) at the Screening Visit.
- •Participants assigned female at birth are eligible to participate if they are not pregnant or breast/chest/body feeding.
- •A person of childbearing potential is using a highly effective contraceptive method.
- •Participant has provided written informed consent for participation in this study.
排除标准
- •Is acutely ill or febrile (temperature ≥38.0°C [100.4°F]) 72 hours prior to or at the Screening Visit or Day
- •Part B Phase 2 booster extension period: acute disease or febrile 72 hours prior to or on Day
- •History of a diagnosis or condition that, in the judgment of the Investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures.
- •Has a medical, psychiatric, or occupational condition, including reported history of substance abuse, which may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment.
- •Has a current or previous diagnosis of immunosuppressive condition, to include human immunodeficiency virus, or immune-mediated (autoimmune) disease that requires immunosuppressive therapies.
- •(drugs or biologics). The use of topical corticosteroids or other immunosuppressive agents (for example, topical calcineurin inhibitor) may be eligible for participation at the discretion of the Investigator.
- •History of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine or intervention that includes one or more of the same components contained in the study vaccine.
- •Part A Phase 1 and Part B Phase 2 base period: Any history of myocarditis or pericarditis.
- •Part B Phase 2 booster extension period and Part C Phase 2: Any history of myocarditis, pericarditis, or Guillain-Barré Syndrome.
- •Coagulopathy or bleeding disorder considered a contraindication to IM injection or phlebotomy.
- •Dermatologic conditions that could affect local solicited AR assessments (for example, tattoos, psoriasis patches affecting skin over the deltoid areas).
- •Has received systemic immunosuppressive therapies (drugs or biologics) for >14 days in total within 6 months prior to Screening or Day 365 (Part B Phase 2 booster extension period only) (for corticosteroids ≥10 mg/day of prednisone equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. Inhaled, nasal, intra-articular, and topical steroids are allowed.
- •Has received or plans to receive any licensed/authorized vaccine (to include severe acute respiratory syndrome-related coronavirus-2 vaccine) ≤28 days prior to or within 28 days after each study intervention, with the exception of influenza vaccines, which may be given 14 days before or after receipt of a study intervention.
- •Has received systemic immunoglobulins or blood products within 3 months prior to Screening or Day 365 (Part B Phase 2 booster extension period only) or plans for receipt during the study.
- •Has donated protocol-specified volume of blood products within protocol-specified timeframe.
- •Participated or plans to participate in an interventional clinical study within protocol-specified timeframe.
- •Part B Phase 2: Individuals who are participating/have participated in the Part A Phase 1 part of the study are excluded.
- •Part A Phase 1: Any individual with laboratory abnormalities achieving thresholds defined in the protocol.
- •Part C Phase 2: Individuals who have received an experimental NoV vaccine are excluded, including but not limited to individuals who are participating/have participated in Part A Phase 1 or Part B Phase 2 of the current study, or who are participating/have participated in mRNA-1403-P.301.
研究组 & 干预措施
Phase 2 Part B: mRNA-1403 Dose Level 3
Participants will receive 1 IM injection of mRNA-1403 at Dose Level 3 and if participating in the booster extension will receive a second dose of mRNA-1403 at Dose Level 3 12-15 months after first dose.
干预措施: mRNA-1403 (Biological)
Phase 1 Part A: mRNA-1403 Dose Level 1
Participants will receive 2 intramuscular (IM) injections of mRNA-1403 at Dose Level 1.
干预措施: mRNA-1403 (Biological)
Phase 1 Part A: mRNA-1403 Dose Level 2
Participants will receive 2 IM injections of mRNA-1403 at Dose Level 2.
干预措施: mRNA-1403 (Biological)
Phase 1 Part A: mRNA-1403 Dose Level 3
Participants will receive 2 IM injections of mRNA-1403 at Dose Level 3.
干预措施: mRNA-1403 (Biological)
Phase 1 Part A: mRNA-1403 Dose Level 4 Regimen 1
Participants will receive 2 IM injections of mRNA-1403 at Dose Level 4.
干预措施: mRNA-1403 (Biological)
Phase 1 Part A: mRNA-1403 Dose Level 4 Regimen 2
Participants will receive 1 IM injection of mRNA-1403 at Dose Level 4 and 1 IM injection of study vaccine-matching placebo.
干预措施: mRNA-1403 (Biological)
Phase 1 Part A: mRNA-1403 Dose Level 4 Regimen 2
Participants will receive 1 IM injection of mRNA-1403 at Dose Level 4 and 1 IM injection of study vaccine-matching placebo.
干预措施: Placebo (Biological)
Phase 1 Part A: mRNA-1405 Dose Level 1
Participants will receive 2 IM injections of mRNA-1405 at Dose Level 1.
干预措施: mRNA-1405 (Biological)
Phase 1 Part A: mRNA-1405 Dose Level 2
Participants will receive 2 IM injections of mRNA-1405 at Dose Level 2.
干预措施: mRNA-1405 (Biological)
Phase 1 Part A: mRNA-1405 Dose Level 3
Participants will receive 2 IM injections of mRNA-1405 at Dose Level 3.
干预措施: mRNA-1405 (Biological)
Phase 1 Part A: mRNA-1405 Dose Level 4 Regimen 1
Participants will receive 2 IM injections of mRNA-1405 at Dose Level 4.
干预措施: mRNA-1405 (Biological)
Phase 1 Part A: mRNA-1405 Dose Level 4 Regimen 2
Participants will receive 1 IM injections of mRNA-1405 at Dose Level 4 and 1 IM injection of study vaccine-matching placebo.
干预措施: mRNA-1405 (Biological)
Phase 1 Part A: mRNA-1405 Dose Level 4 Regimen 2
Participants will receive 1 IM injections of mRNA-1405 at Dose Level 4 and 1 IM injection of study vaccine-matching placebo.
干预措施: Placebo (Biological)
Phase 1 Part A: Placebo
Participants will receive 2 IM injections of study vaccine-matching placebo.
干预措施: Placebo (Biological)
Phase 2 Part B: mRNA-1403 Dose Level 1
Participants will receive 1 IM injection of mRNA-1403 at Dose Level 1.
干预措施: mRNA-1403 (Biological)
Phase 2 Part B: mRNA-1403 Dose Level 2
Participants will receive 1 IM injection of mRNA-1403 at Dose Level 2 and if participating in the booster extension will receive a second dose of study vaccine-matching placebo 12-15 months after first dose.
干预措施: mRNA-1403 (Biological)
Phase 2 Part B: mRNA-1403 Dose Level 2
Participants will receive 1 IM injection of mRNA-1403 at Dose Level 2 and if participating in the booster extension will receive a second dose of study vaccine-matching placebo 12-15 months after first dose.
干预措施: Placebo (Biological)
Phase 2 Part B: mRNA-1403 Dose Level 3
Participants will receive 1 IM injection of mRNA-1403 at Dose Level 3 and if participating in the booster extension will receive a second dose of mRNA-1403 at Dose Level 3 12-15 months after first dose.
干预措施: Placebo (Biological)
Phase 2 Part B: Placebo
Participants will receive 1 IM injection of study vaccine-matching placebo.
干预措施: Placebo (Biological)
Phase 2 Part C: mRNA-1403 Dose Level 3
Participants will receive 1 IM injection of mRNA-1403 at Dose Level 3.
干预措施: mRNA-1403 (Biological)
Phase 2 Part C: Placebo
Participants will receive 1 IM injection of study vaccine-matching placebo.
干预措施: Placebo (Biological)
结局指标
主要结局
Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)
时间窗: Up to a maximum of Day 36 (7 days after each study injection)
Number of Participants with Unsolicited Adverse Events (AEs)
时间窗: Up to a maximum of Day 57 (28 days after each study injection)
Number of Participants with Medically Attended AEs (MAAEs)
时间窗: Day 1 up to a maximum of Day 546
Number of Participants with Any Serious Adverse Events (SAEs), AEs Leading to Withdrawal From Study, and Adverse Events of Special Interest (AESIs)
时间窗: Day 1 up to a maximum of Day 730
次要结局
- Geometric Mean Concentration (GMC) of Binding Antibody (bAb) Against Vaccine-matched NoV Genotypes(Days 1, 29, and 57)
- Percentage of Participants with Seroresponse Based on bAb Levels(Days 29 and 57)
- Geometric Mean Titers (GMT) of Histo-blood Group Antigen (HBGA)-blocking Antibodies Against Vaccine-matched Norovirus (NoV) Genotypes(Phase 1: Days 1, 29, and 57; Phase 2: Days 1, 29, 169, 365, and 393)
- Geometric Mean Fold Rise (GMFR) of HBGA-blocking Antibodies Titers(Phase 1: Days 29, and 57; Phase 2: Days 29, 169, 365, and 393)
- Percentage of Participants with Seroresponse Based on HBGA-blocking Antibody Titers(Phase 1: Days 29, and 57; Phase 2: Days 29, 169, and 393)
- GMFR of bAb Levels(Days 29 and 57)