A Phase 2, Observer-Blind, Placebo-Controlled Proof-of-Concept Trial to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus Vaccine in Patients Who Have Undergone Allogeneic Hematopoietic Cell Transplantation (HCT)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 84
- 试验地点
- 3
- 主要终点
- Number of Unsolicited Adverse Events (AEs)
研究概览
简要总结
The main purpose of the study is to evaluate the efficacy and safety of mRNA-1647 compared to placebo to prevent first clinically significant cytomegalovirus infection (CS-CMVi) in the period following cessation of CMV prophylactic treatment (for example, letermovir) on Day 100 post-HCT through Month 9 post-HCT.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Receipt of an allogeneic HCT.
- •CMV-seropositive, defined as a documented positive test for anti-CMV IgG.
- •High-risk for CMV: HCT from related, unrelated, or haploidentical donor with post-transplant cyclophosphamide for graft-versus-host-disease (GVHD) prophylaxis; or HCT from related or unrelated donor with at least one mismatch at any of the following human leukocyte antigen (HLA) gene loci (HLA-A, B, C, and DRB1); or HCT from related or unrelated donor with myeloablative conditioning.
- •Persons of nonchildbearing potential or of childbearing potential with negative urine or serum pregnancy test on the day of first study injection.
- •Persons of childbearing potential who have practiced adequate contraception or have abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose.
- •Persons of childbearing potential who have agreed to continue adequate contraception or abstain from all activities that could result in pregnancy through 3 months after last study injection.
- •Persons who are not currently breast/chestfeeding.
- •Willingness to comply with study procedures and provide written informed consent.
排除标准
- •History of a diagnosis or condition that, in the judgment of the Investigator, may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures.
- •A documented positive human immunodeficiency virus (HIV) test.
- •Treatment with alemtuzumab (Campath®), antithymocyte globulin (ATG), or any equivalent in-vivo T cell depleting agent within 12 months.
- •HCT with ex-vivo T cell depletion.
- •Low risk for CMV: HCT from related or unrelated donor with reduced intensity conditioning (RIC) and no other high-risk features.
- •History of prior hematopoietic cell transplantation within 12 months.
- •Receipt of prior investigational CMV vaccines or participation in another CMV therapeutic study that may interfere with study outcome measures as determined by the Investigator.
- •Suspected or known allergic reaction to any component of any mRNA vaccine or its excipients.
研究组 & 干预措施
Placebo
Participants will receive mRNA-1647 matching placebo by IM injection on Day 42, Day 67, and Day 92, and a booster dose on Day 180.
干预措施: Placebo (Biological)
mRNA-1647
Participants will receive mRNA-1647 by intramuscular (IM) injection on Day 42, Day 67, and Day 92, and a booster dose on Day 180.
干预措施: mRNA-1647 (Biological)
结局指标
主要结局
Number of Unsolicited Adverse Events (AEs)
时间窗: Up to Day 205 (25 days after last study injection)
Number of Participants with Severe AEs
时间窗: Up to Day 365
Number of Participants with Serious Adverse Events (SAEs)
时间窗: Up to Day 365
Time to the First Occurrence of an CS-CMVi Event as Measured by initiation of anti-CMV Antiviral Therapy
时间窗: Day 100 to Month 9
Number of Participants with Grade ≥3 Acute Graft-Versus-Host Disease (GVHD)
时间窗: Up to Day 365
Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)
时间窗: Up to Day 187 (7 days after last study injection)
次要结局
- Number of Participants with First Occurrence of All CS-CMVi Events as Measured by Initiation of Anti-CMV Antiviral and/or End-Organ Disease(Day 100 to Month 9)
- Number of Participants with an Occurrence of CMV Viremia(Day 100 to Month 9)
- Number of Participants with CMV End-Organ Disease(Day 100 to Month 9)
- Duration of CMV Viremia(Day 100 to Month 9)
- Duration of CMV Treatment(Day 100 to Month 9)
- Number of Participants with Non-Relapse Mortality at 9 Months Post-HCT.(Month 9)
- Titer of CMV-Specific Neutralizing Antibody (nAb)(Days 42, 67, 92, 117, 180, 205 and 270)
- Geometric Mean Titer (GMT) of Anti-gB-Specific Immunoglobulin G (IgG) and Anti-Pentamer-Specific IgG as Measured by Enzyme-Linked Immunosorbent Assay (ELISA)(Days 42, 67, 92, 117, 180, 205 and 270)
- Geometric Mean Concentration (GMC) of Anti-gB-Specific Immunoglobulin G (IgG) and Anti-Pentamer-Specific IgG as Measured by Enzyme-Linked Immunosorbent Assay (ELISA)(Days 42, 67, 92, 117, 180, 205 and 270)
- Geometric Mean Fold Rise (GMFR) of Postbaseline/Baseline GMTs or GMCs(Days 42, 67, 92, 117, 180, 205 and 270)