A Safety, Tolerability, and Immunogenicity Study of mRNA-1345 and mRNA-1365 in Participants Aged 5 Months to <24 Months

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and immunogenicity of mRNA-1365, an mRNA vaccine targeting respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) and mRNA-1345, an mRNA vaccine targeting RSV, in participants aged 5 months to <24 months.

Official Title
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A Phase 1, Randomized, Observer-blind, Placebo-controlled, Age De-escalation Study of the Safety, Tolerability, and Immunogenicity of mRNA-1345 and mRNA-1365 in Participants Aged 5 Months to <24 Months

Conditions
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Respiratory Syncytial Virus, Human Metapneumovirus

Intervention / Treatment
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* Biological: mRNA-1345
* Biological: mRNA-1365
* Biological: Placebo
* Drug: Nimenrix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant is 8 months to <24 months (Part A) or 5 months to <8 months (Part B) of age at the time of randomization (Day 1/Baseline visit), who is in good general health, in the opinion of the Investigator, based on review of medical history and screening physical examination. In the Investigator's opinion, the parent(s)/ legally authorized representative (LAR)(s) understand and are willing and physically able to comply with protocol-mandated follow up, including all procedures, and provide written informed consent. The participant is growing normally for age in the opinion of the site clinician in the months prior to enrollment. The participant was born at full-term (≥37 weeks gestation) with a minimum birth weight of 2.5 kilograms (kg). Exclusion Criteria: Has a known history of symptomatic RSV or hMPV infection (Part A: within 3 months; Part B: since birth) prior to administration of the first dose of investigational product (IP) or has a known close contact with anyone with laboratory-confirmed RSV or hMPV infection within 14 days prior to administration of the first dose of IP (Part A and Part B). Is acutely ill or febrile 24 hours prior to or at the screening visit. Fever is defined as a body temperature ≥38.0°Celsius/≥100.4°Fahrenheit. Participants who meet this criterion may have visits rescheduled within the relevant study visit windows. Has previously been administered an investigational or approved vaccine for prevention of RSV or hMPV infection or if the participant's mother received an investigational or approved vaccine for the prevention of RSV or hMPV infection during pregnancy. Has received investigational or approved agents for prophylaxis against RSV or hMPV (for example, monoclonal antibodies) or is intending to receive these during the course of the study. Has a known hypersensitivity to a component of the vaccine or its excipients. Hypersensitivity includes, but is not limited to, anaphylaxis or immediate allergic reaction of any severity to a previous dose of an mRNA vaccine or any of its components (including polyethylene glycol or immediate allergic reaction of any severity to polysorbate). Has a medical condition that, according to the Investigator's judgment, may pose additional risk as a result of participation, interfere with safety assessments, or interfere with interpretation of results. Note: Other protocol-defined inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 5 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: mRNA-1345, Dose 1 (Age Group: 8 to <24 months)<br>Participants will receive mRNA-1345 vaccine by intramuscular (IM) injection on Days 1, 57 and 113. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1365, Dose 1 (Age Group: 8 to <24 months)<br>Participants will receive mRNA-1365 vaccine by IM injection on Days 1, 57 and 113. | Biological: mRNA-1365<br>* Sterile liquid for injection<br>|
| Placebo Comparator: Part A: Placebo (Age Group: 8 to <24 months)<br>Participants will receive mRNA-1345/ mRNA-1365 vaccine matching placebo by IM injection on Days 1, 57 and 113. In countries where applicable, participants may receive Nimenrix instead of placebo on Day 113. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) solution for injection<br>Drug: Nimenrix<br>* Solution for injection<br>|
| Experimental: Part B: mRNA-1345, Dose 2 (Age Group: 5 to <8 months)<br>Participants will receive mRNA-1345 by IM injection on Days 1, 57 and 113. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>|
| Experimental: Part B: mRNA-1365, Dose 2 (Age Group: 5 to <8 months)<br>Participants will receive mRNA-1365 by IM injection on Days 1, 57 and 113. | Biological: mRNA-1365<br>* Sterile liquid for injection<br>|
| Experimental: Part B: mRNA-1345 Dose 1 (Age Group: 5 to <8 months)<br>Participants will receive mRNA-1345 by IM injection on Days 1, 57 and 113. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>|
| Experimental: Part B: mRNA-1365 Dose 1 (Age Group: 5 to <8 months)<br>Participants will receive mRNA-1365 by IM injection on Days 1, 57 and 113. | Biological: mRNA-1365<br>* Sterile liquid for injection<br>|
| Placebo Comparator: Part B: Placebo (Age Group: 5 to <8 months)<br>Participants will receive mRNA-1345/ mRNA-1365 vaccine matching placebo by IM injection on Days 1, 57 and 113. In countries where applicable, participants may receive Nimenrix instead of placebo on Day 113. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) solution for injection<br>Drug: Nimenrix<br>* Solution for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) |  | Up to Day 120 (7 days after each injection) | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 141 (28 days after each injection) | 
| Number of Participants with Medically-Attended Adverse Events (MAAEs) |  | Day 1 through Day 730 | 
| Number of Participants with Adverse Event of Special Interests (AESIs), Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation |  | Day 1 through Day 730 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Respiratory Tract Illness (RTI), Lower Respiratory Tract Illness (LRTI), Severe LRTI, Very Severe LRTI, and Hospitalizations Associated with RSV |  | Day 1 through Day 730 | 
| Geometric Mean Titer (GMT) of Serum RSV and hMPV Neutralizing Antibodies |  | Baseline up to Month 12 | 
| GMT of Serum RSV F- and hMPV F-Binding Antibodies |  | Baseline up to Month 12 | 
| Geometric Mean Fold-Rise (GMFR) Postbaseline/baseline Neutralizing Antibody Titers |  | Baseline up to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-1345, mRNA-1365, RSV vaccine, hMPV vaccine