Safety and Immunogenicity of mRNA-1653, a Combined Human Metapneumovirus (hMPV) and Parainfluenza Virus Type 3 (PIV3) Vaccine, in Healthy Adults, and Children 12 to 59 Months of Age With Serologic Evidence of Prior Exposure

Study Overview
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Brief Summary
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This clinical study will assess the safety and immunogenicity of 2 dose levels of mRNA-1653, a combined human metapneumovirus and human parainfluenza virus type 3 vaccine, in healthy adults (18 to 49 years of age) and 2 dose levels in children (12 to 59 months of age) with serologic evidence of prior exposure. The safety profile of the adult cohort will permit enrollment of the pediatric cohort.

Official Title
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A Phase 1b, Randomized, Observer-Blind, Placebo-Controlled, Dose Ranging Trial to Evaluate the Safety and Immunogenicity of mRNA-1653, a Combined Human Metapneumovirus (hMPV) and Parainfluenza Virus Type 3 (PIV3) Vaccine When Administered to Adults, and to Children 12 to 59 Months of Age With Serologic Evidence of Prior Exposure

Conditions
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Human Metapneumovirus and Human Parainfluenza Infection

Intervention / Treatment
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* Biological: mRNA-1653
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Adults 18 to 49 years of age and children 12 to 59 months of age at the time of consent who, in the opinion of the Investigator, are in good health based on review of medical history and screening physical examination Adult participant or parent(s)/legal guardian(s) has provided written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol Screening laboratory values Grade ≤1 Specific inclusion criteria for adults 18 to 49 years of age: Body mass index (BMI) from ≥18 kg/m^2 and ≤35 kg/m^2 Female participants must be either of non-childbearing potential or if of childbearing potential may be enrolled if the participant: 1) has a negative pregnancy test at Screening and on the day of vaccination, and 2) has practiced adequate contraception or has abstained from all activities that could lead to pregnancy for 28 days prior to vaccination, and 3) has agreed to continue adequate contraception through 3 months following the last vaccination, and 4) is not currently breastfeeding Specific inclusion criteria for children 12 to 59 months of age: Seropositive for both hMPV and PIV3 neutralizing antibody at Screening Has received routine immunizations appropriate for age per the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) Current height and weight above the third percentile for age Key Exclusion Criteria: Adult and pediatric participants eligible for this study must not meet any of the following criteria: Acutely ill or febrile (temperature ≥38.0℃/100.4°F, regardless of route) on the day of the first vaccination Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care Receipt of, or plans for receipt of an inactivated vaccine(s) 14 days prior to though 14 days following each study injection or a live virus vaccine(s) within 28 days prior to, or plans to through 28 days following each study injection. The exception is any COVID-19 vaccine (regardless of type of vaccine) that becomes available to the participant during the study; efforts should be made to space study vaccinations and COVID-19 vaccinations by at least 7 and preferably 14 days, but COVID-19 vaccinations should not be delayed. Any chronic administration of an immunosuppressant or other immune modifying drug Prior administration of investigational agent using lipid nanoparticle formulations Donation of blood or blood products ≥450 mL within 28 days of the Screening visit (for the Adult Cohort) Intravenous blood products (red cells, platelets, immunoglobulins) within 3 months prior to enrollment Participated in an interventional clinical trial within 28 days prior to the day of enrollment, or plans to do so while enrolled in this trial Has a family member or household contact who is an employee of the research center or otherwise involved with the conduct of the study

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 49 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: Parallel for the Adult Cohort, followed by Sequential Assignment for the Pediatric Cohort
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1653, Adult participants<br>Participants will receive 1 of 2 doses of mRNA-1653, administered via intramuscular injection, on Day 1 and Day 57. | Biological: mRNA-1653<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1653 Pediatric participants<br>Participants will receive 1 of 2 possible doses of mRNA-1653, administered via intramuscular injection, on Day 1 and Day 57. | Biological: mRNA-1653<br>* Sterile liquid for injection<br>|
| Placebo Comparator: Placebo, Adult participants<br>Participants will receive mRNA-1653-matching placebo, administered via intramuscular injection, on Day 1 and Day 57. | Biological: Placebo<br>* Sterile liquid for injection<br>* Other names: saline;|
| Placebo Comparator: Placebo, Pediatric participants<br>Participants will receive mRNA-1653-matching placebo, administered via intramuscular injection, on Day 1 and Day 57. | Biological: Placebo<br>* Sterile liquid for injection<br>* Other names: saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with Solicited Local and Systemic Adverse Reactions (ARs) |  | Up to 7 days after each dose administration | 
| Proportion of Participants with Unsolicited Adverse Events (AEs) |  | Up to 28 days after each dose administration | 
| Proportion of Participants with Serious Adverse Events (SAEs) and Medically-Attended AEs |  | Up to 1 year after the last dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean titer (GMT) of Serum Anti-hMPV and Anti-PIV3 Neutralizing Antibodies |  | Day 29, 57, 85, and 224 for adults; Day 29 and 85 for pediatric participants | 
| Geometric Mean Ratio (GMR) of Post-Baseline/Baseline Titers of Serum Anti-hMPV and Anti-PIV3 Neutralizing Antibodies |  | Day 29, 57, 85, and 224 for adults; Day 29 and 85 for pediatric participants | 
| Proportion of Participants with ≥2-Fold and ≥4-Fold Increases in Serum Anti-hMPV or Anti-PIV3 Neutralizing Antibody Titer from Baseline |  | Day 29, 57, 85, and 224 for adults; Day 29 and 85 for pediatric participants | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ModernaTX, mRNA-1653, human metapneumovirus, human parainfluenza, human parainfluenza vaccine, virus diseases, RNA virus infections, paramyxoviridae infections, mononegavirales infections