A Study of mRNA-1345 Vaccine Targeting Respiratory Syncytial Virus in Pregnant Women and in Infants Born to Vaccinated Mothers

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the reactogenicity, safety, and immunogenicity of an investigational respiratory syncytial virus (RSV) vaccine, mRNA-1345, in pregnant women, and safety and immunogenicity in infants born to vaccinated mothers.

Official Title
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A Phase 2, Randomized, Observer-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Reactogenicity, Safety, and Immunogenicity of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, in Pregnant Women, and Safety and Immunogenicity in Infants Born to Vaccinated Mothers

Conditions
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Respiratory Syncytial Virus

Intervention / Treatment
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* Biological: mRNA-1345
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Maternal Participants Are adults ≥18 years to <40 years of age inclusive, at the time of signing the informed consent. Will be 28 to 36 weeks pregnant at the time of vaccination (confirmed by an obstetric ultrasound report). Intend to deliver at a maternity unit where study procedures can be performed. Are willing and able to attend all study visits, to undergo all study procedures/or have their infant undergo all study procedures, and to comply with study requirements, including a means of communication (for example, phone, text message or email) with study site staff. Have received local standard of antenatal care prior to enrollment and expect to continue to do so through the remainder of their pregnancy. Have had an antenatal obstetric ultrasound at ≥18 weeks of pregnancy or be willing to have an antenatal obstetric ultrasound at Screening if not already conducted. Infant Participants Have consent from infant participant's parent(s)/legally authorized representative (LAR) if required by local regulations. Key Exclusion Criteria: Maternal Participants Acutely ill or febrile (temperature ≥38.0 degrees Celsius [℃]/100.4 degrees Fahrenheit [°F]) within 72 hours prior to or at the Screening Visit or Day 1. Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any mRNA vaccine or therapeutic or any components of an mRNA-1345 vaccine. Any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results. Have conditions in the current pregnancy or in previous pregnancies that may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. Received or plans to receive any mRNA vaccine or COVID-19 vaccine within 4 weeks before or after Day 1 and/or any other nonstudy vaccine within 2 weeks before or after Day 1. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation. Infant Participants Is a child who has been placed under the control or protection of an agency, organization, institution, or entity by the courts, the government, or a government body acting in accordance with powers conferred on them by laws and regulation (for example, foster care). This does not include a child who is adopted or has an appointed LAR. Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1345 Dose A<br>Participants will be vaccinated in the period from 28 weeks to 36 weeks of gestation with a single intramuscular (IM) injection of mRNA-1345 Dose A. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1345 Dose B<br>Participants will be vaccinated in the period from 28 weeks to 36 weeks of gestation with a single IM injection of mRNA-1345 Dose B. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>|
| Experimental: mRNA-1345 Dose C<br>Participants will be vaccinated in the period from 28 weeks to 36 weeks of gestation with a single IM injection of mRNA-1345 Dose C. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>|
| Placebo Comparator: Placebo<br>Participants will receive single IM injection of mRNA-1345 vaccine matching placebo in the period from 28 weeks to 36 weeks of gestation. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Maternal Participants with Solicited Local and Systemic Adverse Reactions (ARs) |  | Up to Day 7 (7 days post vaccination) | 
| Number of Maternal Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 28 (28 days post vaccination) | 
| Number of Maternal Participants with Medically-Attended AEs (MAAEs) |  | Day 1 to Month 6 (6 months postdelivery) | 
| Number of Maternal Participants with Adverse Events of Special Interest (AESIs) |  | Day 1 to Month 12 (12 months postdelivery) | 
| Number of Maternal Participants with Serious Adverse Events (SAEs) |  | Day 1 to Month 12 (12 months postdelivery) | 
| Number of Maternal Participants with AEs Leading to Discontinuation |  | Day 1 to Month 12 (12 months postdelivery) | 
| Number of Maternal Participants With Pregnancy Outcomes | Pregnancy outcomes will include stillbirth, live birth, vaginal delivery, and cesarean section delivery. | Day 1 to Month 12 (12 months postdelivery) | 
| Number of Infant Participants with MAAEs |  | Day 1 (birth) to Month 12 | 
| Number of Infant Participants with AESIs |  | Day 1 (birth) to Month 12 | 
| Number of Infant Participants with SAEs |  | Day 1 (birth) to Month 12 | 
| Number of Infant Participants With Birth Outcomes | Birth outcomes will include gestational age and anthropometric measurements. | Day 1 (birth) to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of Serum RSV-A and RSV-B Neutralizing Antibodies in Maternal Participants |  | Day 1, Day 29, delivery, and Month 6 (6 months postdelivery) | 
| Geometric Mean Concentration (GMC) of Serum RSV-F Binding Antibodies in Maternal Participants |  | Day 1, Day 29, delivery, and Month 6 (6 months postdelivery) | 
| Geometric Mean Fold-Rise (GMFR) of Postbaseline/Baseline Neutralizing Antibody Titers and Binding Antibody Concentrations in Maternal Participants |  | Day 29, delivery, and Month 6 (6 months postdelivery) | 
| Percentage of Maternal Participants With ≥4-fold Increase From Baseline in Neutralizing Antibody Titers and Binding Antibody Concentrations |  | Baseline up to Month 6 (6 months postdelivery) | 
| GMT of Serum RSV-A and RSV-B Neutralizing Antibodies in Infant Participants |  | Day 1 (birth), and Months 2, 6, and 12 | 
| GMC of Serum RSV-F Binding Antibodies in Infant Participants |  | Day 1 (birth), and Months 2, 6, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-1345, RSV vaccine, Viral Diseases, Messenger RNA, Moderna