A Phase 1/2a Open-Label Dose-Ranging and Observer-Blind Placebo-Controlled, Safety and Immunogenicity Study of mRNA-1647 Cytomegalovirus Vaccine in Female and Male Participants 9 to 15 Years of Age and Participants 16 to 25 Years of Age
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 873
- 试验地点
- 113
- 主要终点
- Number of Participants with ≥2-Fold, 3-Fold, and 4-Fold increases Over Baseline of Anti-CMV Antibodies
研究概览
简要总结
The main purpose of study is to evaluate the safety and immunogenicity of different dose levels of mRNA-1647 versus control in healthy cytomegalovirus (CMV)-seronegative and CMV-seropositive female and male participants 9 to 15 years of age. In addition, mRNA-1647 will be evaluated in female participants 16 to 25 years as a comparator cohort.
详细描述
The study will be conducted in 2 parts: Part 1 Dose-Ranging and Part 2 Safety Expansion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part 1 of this study will be open-label and blinding is not applicable. Part 2 of the study will be observer-blinded.
入排标准
- 年龄范围
- 9 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Is a female or male 9 to 15 years of age or is a female 16 to 25 years of age at the time of consent.
- •Is in good general health, in the opinion of the Investigator, and is capable of complying with study procedures.
- •For the CMV-seronegative cohorts: At the Screening visit, is CMV IgG-negative and CMV immunoglobulin M (IgM)-negative.
- •For the CMV-seropositive cohorts: At the Screening visit, is CMV IgG-positive and CMV IgM-negative, CMV IgG-positive and CMV IgM-positive, or CMV IgG-positive and CMV IgM-indeterminate. Participants with an isolated positive or indeterminate result for CMV IgM (that is, CMV IgG-negative and either CMV IgM-positive or CMV IgM-indeterminate) will not be eligible for enrollment but may be rescreened after at least 6 weeks from the initial CMV Screening. Participants with an indeterminate result for CMV IgG, regardless of IgM result, will not be eligible for enrollment but may be rescreened after at least 6 weeks from the initial CMV screening.
- •If 9 to 15 years of age, has a body mass index (BMI) at or above the third percentile according to World Health Organization (WHO) Child Growth Standards. If 16 to 25 years of age: has a BMI of 15 to 35 kilograms (kg)/square meter (m^2).
- •For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, agreement to continue adequate contraception through 3 months following vaccine administration.
排除标准
- •Has a history of a diagnosis or condition that, in the judgment of Investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. Clinically unstable is defined as diagnosis or condition requiring significant changes in management or medication within the 2 months prior to Screening and includes ongoing workup of an undiagnosed illness that could lead to a new diagnosis or condition.
- •Has received, or plans to receive, any nonstudy vaccine < 28 days prior to or after any study injection.
- •Has a screening liver function test (aspartate aminotransferase, alanine aminotransferase, total bilirubin) or a screening creatinine result of Toxicity Grade ≥
- •Has a Screening hematology or coagulation result of Toxicity Grade ≥
- •Is acutely ill or febrile (body temperature ≥38.0 degrees Celsius [°C]/100.4 degrees Fahrenheit [°F]) at the Screening Visit.
- •Has received systemic immunosuppressants or immune-modifying drugs for > 14 days in total within 6 months prior to the day of enrollment (for corticosteroids, ≥1 milligrams (mg)/kg/day or ≥10 mg/day prednisone equivalent).
- •Has received an antiviral with activity against CMV (ganciclovir, valganciclovir, foscarnet, cidofovir, letermovir, acyclovir, valacyclovir) <2 weeks prior to the day of the first study injection (Day 1) or plans to do so during the course of the study.
- •Reports a history of myocarditis, pericarditis, or myopericarditis.
- •Has reported medical history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV); or a positive screening test for hepatitis B surface antigen (HBsAg), hepatitis C antibodies, or HIV 1 or 2 antibodies.
- •Has previously received an investigational CMV vaccine.
- •Has received systemic immunoglobulins or blood products <3 months prior to the day of the first study injection (Day 1).
- •Has donated ≥ 450 milliliter (mL) of blood products <28 days prior to the day of the first study injection (Day 1).
- •Has participated in an interventional clinical study <28 days prior to the day of the first study injection (Day 1) or plans to do so while enrolled in the study.
- •Note: Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
mRNA-1647 Dose A
CMV-seronegative or CMV-seropositive participants 9 to 15 years of age will receive mRNA-1647 at Dose Level A by intramuscular (IM) injection given as a 3-injection series on Day 1, Month 2, and Month 6.
干预措施: mRNA-1647 (Biological)
Dose Expansion: Placebo (3-dose Schedule)
CMV-seronegative or CMV-seropositive participants 9 to 15 years of age will receive placebo by IM injection given as a 3-injection series on Day 1, Month 2, and Month 6.
干预措施: Placebo (Other)
Dose Expansion: Placebo (2-dose Schedule)
CMV-seronegative participants 9 to 15 years of age will receive placebo by IM injection given as a 2-injection series on Day 1 and Month 6.
干预措施: Placebo (Other)
mRNA-1647 Dose B
CMV-seronegative or CMV-seropositive participants 9 to 15 years of age will receive mRNA-1647 at Dose Level B by IM injection given as a 3-injection series on Day 1, Month 2, and Month 6.
干预措施: mRNA-1647 (Biological)
mRNA-1647 Dose C
CMV-seronegative or CMV-seropositive participants 9 to 15 years of age and 16 to 25 years of age will receive mRNA-1647 at Dose Level C by IM injection given as a 3-injection series on Day 1, Month 2, and Month 6.
干预措施: mRNA-1647 (Biological)
Dose Expansion: mRNA-1647 (3-dose Schedule)
CMV-seronegative or CMV-seropositive participants 9 to 15 years of age will receive mRNA-1647 at selected dose level by IM injection given as a 3-injection series on Day 1, Month 2, and Month 6.
干预措施: mRNA-1647 (Biological)
Dose Expansion: mRNA-1647 (2-dose Schedule)
CMV-seronegative participants 9 to 15 years of age will receive mRNA-1647 at selected dose level by IM injection given as a 2-injection series on Day 1 and Month 6.
干预措施: mRNA-1647 (Biological)
结局指标
主要结局
Number of Participants with ≥2-Fold, 3-Fold, and 4-Fold increases Over Baseline of Anti-CMV Antibodies
时间窗: Up to Day 527 (end of study)
Serum functional antibody levels against vaccine antigens will be measured by nAb titer against epithelial cell infection and nAb titer against fibroblast infection.
Number of Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)
时间窗: Up to Day 176 (7 days after each study injection)
Number of Medically Attended Adverse Events (MAAEs)
时间窗: Up to Day 347 (6 months after the last study injection)
Geometric Mean Titer (GMT) of Anti-CMV Neutralizing Antibodies (nAbs)
时间窗: Up to Day 527 (end of study)
Serum functional antibody levels against vaccine antigens will be measured by nAb titer against epithelial cell infection and nAb titer against fibroblast infection.
Geometric Mean Fold-Rise (GMFR) of Anti-CMV nAbs
时间窗: Up to Day 527 (end of study)
Serum functional antibody levels against vaccine antigens will be measured by nAb titer against epithelial cell infection and nAb titer against fibroblast infection.
Number of Unsolicited Adverse Events (AEs)
时间窗: Up to Day 197 (28 days after each study injection)
Number of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and AEs Leading to Discontinuation
时间窗: Up to Day 527 (end of study)
次要结局
- Number of Participants with ≥2-Fold, 3-Fold, and 4-Fold Increases Over Baseline of Binding Anti-gB and Anti-pentamer Specific IgG(Up to Day 527 (end of study))
- Geometric Mean Concentration (GMC) of Binding Anti-Glycoprotein B (gB) Specific Immunoglobulin G (IgG) and Anti-Pentamer Specific IgG(Up to Day 527 (end of study))
- GMFR of Binding Anti-gB and Anti-pentamer Specific IgG(Up to Day 527 (end of study))