A Dose Escalation Study to Evaluate Safety, Reactogenicity, and Immunogenicity of mRNA-1345 in Healthy Adults and in Children Who Are Respiratory Syncytial Virus (RSV)-Seropositive

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the tolerability and reactogenicity of a single injection of up to 5 dose levels of mRNA-1345 in younger adults, women of child-bearing potential, and older adults including Japanese older adults; of 3 injections of the middle dose level of mRNA-1345 given 56 days apart in younger adults; of a booster injection of mRNA-1345 given approximately 12 months after the primary injection in older adults; and of 3 injections of 1 of 2 dose levels of mRNA-1345 given 56 days apart in children who are RSV-seropositive.

Official Title
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A Phase 1, Randomized, Observer-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus (RSV), in Healthy Younger Adults Aged 18 to 49 Years, Women of Child-Bearing Potential Aged 18 to 40 Years, Healthy Older Adults Aged 65 to 79 Years, Japanese Older Adults Aged ≥ 60 Years, and RSV-Seropositive Children Aged 12 to 59 Months

Conditions
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Respiratory Syncytial Virus

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy young adults ≥18 to ≤49 years of age, women of child-bearing potential ≥18 to ≤40 years of age, healthy older adults ≥65 to <80 years of age, Japanese older adults ≥ 60 years of age, and children ≥12 to < 60 months of age. Willing and physically able to comply with protocol-mandated follow-up, including all procedures. Adult participant or parent(s)/legal guardian(s) of pediatric participants has provided written informed consent for participation in this study, including all evaluations and procedures as specified by the protocol. Specific inclusion criteria for adults (younger adults, women of child-bearing potential, and older adults [including Japanese older adults]): Has a body mass index (BMI) from ≥18 kilogram (kg)/meter (m)^2 to ≤35 kg/m^2. Female participants of non-child-bearing potential. This criterion does not apply for women of child-bearing potential Cohorts 12, 13, and 14. Female participants of child-bearing potential may be enrolled in the study, if the participant: 1) has a negative urine pregnancy test at Screening and on the day of vaccination; 2) has practiced adequate contraception or has abstained from all activities that could lead to pregnancy for 28 days prior to vaccination; 3) has agreed to continue adequate contraception through 3 months following the last injection; and 4) is not currently breastfeeding. Specific inclusion criteria for children 12 to 59 months of age: Seropositive for RSV-neutralizing Abs at Screening. Has received routine immunizations appropriate for age per local guidance. Current height and weight above the third percentile for age. Specific inclusion criteria for Japanese older adults: Japanese participants are defined as individuals born in Japan, with both parents and 4 grandparents who were born in Japan. Key Exclusion Criteria: Has Screening laboratory values Grade ≥1 (younger adult, women of child-bearing potential, and pediatric participants) or >Grade 1 (older adult participants, including Japanese older adult participants). Is acutely ill or febrile on the day of the first injection. Has a significant medical history, including but not limited to: Congenital or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection. Chronic hepatitis or suspected active hepatitis. Bleeding disorder that is considered a contraindication to intramuscular (IM) injection or phlebotomy. Dermatologic conditions that could affect local solicited AR assessments. Any history of allergic or anaphylactic reactions following a vaccination that required medical intervention. Autoimmune disease except for Hashimoto's disease. Systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to the day of enrollment. Topical tacrolimus is allowed if not used within 14 days prior to the day of enrollment. Inhaled, nasal, and topical steroids are allowed. Intravenous blood products (red cells, platelets, and immunoglobulins [Ig]) within 3 months prior to enrollment. Has received or plans to receive any licensed or authorized vaccine, to include COVID-19 vaccines, ≤ 28 days prior to the first injection (Day 1) or plans to receive a licensed vaccine within 28 days before or after any study vaccine injection, with the exception of licensed influenza vaccines, which may be received more than 14 days before or after any study vaccine injection. Nonstudy vaccinations should not be delayed. Has a history of myocarditis, pericarditis, or myopericarditis. Specific exclusion criteria for older adults (Cohorts 7-11 and 15): Known history of poorly controlled hypertension (per determination of the Investigator) or systolic blood pressure >160 millimeters of mercury (mmHg) at the Screening visit. Known history of hypotension or systolic blood pressure <85 mmHg at the Screening visit. Poorly controlled diabetes mellitus (per determination of the Investigator). Diagnosis of significant chronic pulmonary disease (per determination of the Investigator) (such as, chronic obstructive pulmonary disease, asthma). Significant chronic cardiovascular disease (per determination of the Investigator). Resides in a nursing home. Anticipates the need for immunosuppressive treatment at any time during participation in the study. Diagnosis of malignancy within previous 10 years (excluding non-melanoma skin cancer and cervical carcinoma in-situ). Specific exclusion criteria for children 12 to 59 months of age (Cohorts 5 and 6): Has received any monoclonal antibody at any time prior to Screening. Prior hospitalization for RSV disease in the last 2 years. Receipt of any prior systemic immunosuppressants or immune-modifying drugs. Any history of febrile seizures (inclusive of single simple febrile seizure). History of epilepsy. History of meningitis.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 79 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: Cohort 1: Dose A in Younger Adults<br>Single injection of Dose A of mRNA-1345 or matching-placebo on Day 1. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 2: Dose B in Younger Adults<br>Single injection of Dose B of mRNA-1345 or matching-placebo on Day 1. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 3: Dose B in Younger Adults<br>Three total injections, 1 injection of either Dose B of mRNA-1345 or matching-placebo per day on Day 1, Day 57, and Day 113. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 4: Dose C in Younger Adults<br>Single injection of Dose C of mRNA-1345 or matching-placebo on Day 1. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 5: Dose D in Children<br>Three total injections, 1 injection of either Dose D of mRNA-1345 or matching-placebo per day on Day 1, Day 57, and Day 113. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 6: Dose G in Children<br>Three total injections, 1 injection of either Dose G of mRNA-1345 or matching-placebo per day on Day 1, Day 57, and Day 113. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 7: Dose A in Older Adults<br>Two total injections, 1 injection of either Dose A of mRNA-1345 or matching-placebo per day on Day 1 and approximately 12 months later. Participants will receive second booster injection of Dose A of mRNA-1345 at Month 24. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 8: Dose B in Older Adults<br>Two total injections, 1 injection of either Dose B of mRNA-1345 or matching-placebo per day on Day 1 and approximately 12 months later. Participants will receive second booster injection of Dose A of mRNA-1345 at Month 24. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 9: Dose C in Older Adults<br>Two total injections, 1 injection of either Dose C of mRNA-1345 or matching-placebo per day on Day 1 and approximately 12 months later. Participants will receive second booster injection of Dose A of mRNA-1345 at Month 24. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 10: Dose E in Older Adults<br>Two total injections, 1 injection of either Dose E of mRNA-1345 or matching-placebo per day on Day 1 and approximately 12 months later. Participants will receive second booster injection of Dose A of mRNA-1345 at Month 24. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 11: Dose F in Older Adults<br>Two total injections, 1 injection of either Dose F of mRNA-1345 or matching-placebo per day on Day 1 and approximately 12 months later. Participants will receive second booster injection of Dose A of mRNA-1345 at Month 24. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 12: Dose E in Women of Child-Bearing Potential<br>Single injection of Dose E of mRNA-1345 or matching-placebo on Day 1. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 13: Dose F in Women of Child-Bearing Potential<br>Single injection of Dose F of mRNA-1345 or matching-placebo on Day 1. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 14: Dose A in Women of Child-Bearing Potential<br>Single injection of Dose A of mRNA-1345 or matching-placebo on Day 1. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Cohort 15: Dose B in Japanese Older Adults<br>Single injection of Dose B of mRNA-1345 or matching-placebo on Day 1. | Biological: mRNA-1345<br>* Formulation for injection<br>Drug: 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 Participants with Solicited Local and Systemic Adverse Reactions (ARs) |  | Up to Day 737 (7 days after each injection) | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 758 (28 days after the last injection) | 
| Number of Participants with Serious AEs or Medically Attended AEs (MAAEs) |  | Up to Day 1095 (End of Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of Serum RSV Neutralizing and Binding Antibodies (Abs) |  | Up to Day 141 (Cohorts 5 and 6), up to Day 169 (Cohorts 1, 2, 4, 12, 13, 14, and 15), up to Day 281 (Cohort 3), and up to Day 1095 (Cohorts 7, 8, 9, 10, and 11) | 
| Geometric Mean Fold-Rise of Postbaseline/Baseline Ab Titers |  | Up to Day 141 (Cohorts 5 and 6), up to Day 169 (Cohorts 1, 2, 4, 12, 13, 14, and 15), up to Day 281 (Cohort 3), and up to Day 1095 (Cohorts 7, 8, 9, 10, and 11) | 
| Proportion of Participants with ≥2-fold and ≥4-fold Increases in Ab Titers from Baseline |  | Up to Day 141 (Cohorts 5 and 6), up to Day 169 (Cohorts 1, 2, 4, 12, 13, 14, and 15), up to Day 281 (Cohort 3), and up to Day 1095 (Cohorts 7, 8, 9, 10, and 11) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Viral Diseases, Messenger RNA, Moderna, mRNA-1345, Respiratory syncytial virus, RSV Seropositive, Safety, Pediatric, Vaccines