A Study of mRNA-1647 Cytomegalovirus Vaccine in Healthy Participants 9 to 15 Years of Age and Participants 16 to 25 Years of Age

Study Overview
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Brief Summary
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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.

Detailed Description
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The study will be conducted in 2 parts: Part A Dose-Ranging and Part B Safety Expansion.

Official Title
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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

Conditions
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Cytomegalovirus

Intervention / Treatment
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* Biological: mRNA-1647
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 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. 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. Key Exclusion Criteria: 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 elevated liver function tests, defined as aspartate aminotransferase , alanine aminotransferase, or elevated creatinine or reduced platelets, with a toxicity score of Grade ≥1 at Screening. Has results of Screening laboratory test (hematology, chemistry, [excluding random glucose] and coagulation) with a toxicity score of Grade ≥1. 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.

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part A: Dose-escalating, non-randomized Part B: Randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1647 Dose A<br>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. | Biological: mRNA-1647<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1647 Dose B<br>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. | Biological: mRNA-1647<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1647 Dose C<br>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. | Biological: mRNA-1647<br>* Sterile liquid for injection<br>|
| Experimental: Dose Expansion: mRNA-1647<br>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. | Biological: mRNA-1647<br>* Sterile liquid for injection<br>|
| Placebo Comparator: Dose Expansion: Placebo<br>Participants will receive placebo by IM injection given as a 3-injection series on Day 1, Month 2, and Month 6. | Other: Placebo<br>* 0.9% sodium chloride injection (normal saline)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) |  | Up to Day 176 (7 days after the last study injection) | 
| Number of Unsolicited Adverse Events (AEs) |  | Up to Day 197 (28 days after the last study injection) | 
| Number of Medically Attended Adverse Events (MAAEs) |  | Up to Day 347 (6 months after the last study injection) | 
| Number of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and AEs Leading to Discontinuation |  | Up to Day 527 (end of study) | 
| Geometric Mean Titer (GMT) of Anti-CMV Neutralizing Antibodies (nAbs) | Serum functional antibody levels against vaccine antigens will be measured by nAb titer against epithelial cell infection and nAb titer against fibroblast infection. | Up to Day 527 (end of study) | 
| Geometric Mean Fold-Rise (GMFR) of Anti-CMV nAbs | Serum functional antibody levels against vaccine antigens will be measured by nAb titer against epithelial cell infection and nAb titer against fibroblast infection.. | Up to Day 527 (end of study) | 
| Number of Participants with ≥2-Fold, 3-Fold, and 4-Fold increases Over Baseline of Anti-CMV Antibodies | Serum functional antibody levels against vaccine antigens will be measured by nAb titer against epithelial cell infection and nAb titer against fibroblast infection. | Up to Day 527 (end of study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration (GMC) of Binding Anti-Glycoprotein B (gB) Specific Immunoglobulin G (IgG) and Anti-Pentamer Specific IgG | Serum antigen-specific binding antibody titers against vaccine antigens will be measured by enzyme-linked immunosorbent assay (ELISA) specific to the gB and pentamer proteins. | Up to Day 527 (end of study) | 
| Number of Participants with ≥2-Fold, 3-Fold, and 4-Fold Increases Over Baseline of Binding Anti-gB and Anti-pentamer Specific IgG | Serum antigen-specific binding antibody titers against vaccine antigens will be measured by ELISA specific to the gB and pentamer proteins. | Up to Day 527 (end of study) | 
| GMFR of Binding Anti-gB and Anti-pentamer Specific IgG | Serum antigen-specific binding antibody titers against vaccine antigens will be measured by ELISA specific to the gB and pentamer proteins. | Up to Day 527 (end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CMV, mRNA-1647 Vaccine, Moderna