A Study of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, in Children 2 to <18 Years of Age at High Risk of Respiratory Syncytial Virus

ModernaTX, Inc.349 enrolled

Overview

Part A: The purpose is to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1345 in children aged 2 to \<5 years (Cohort 1) and in children at high risk of respiratory syncytial virus (RSV) disease 5 to \<18 years of age (Cohort 2) to inform the dose level selection for the next phase of development (Phase 3). Part B: The purpose is to provide surveillance for RSV disease for the next RSV season (6 months after re-enrollment) and safety follow-up for Cohort 1 participants that were enrolled and dosed in Part A.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

349

Conditions

Respiratory Syncytial Virus

Interventions

mRNA-1345

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 YearsHealthy volunteers:

Medical Language ↔ Plain English

Key Inclusion Criteria: Part A Cohort 1: * 2 to \<5 years of age at Day 1. * Healthy, or with stable chronic conditions increasing the risk of RSV disease, per the clinical judgment of the Investigator. Cohort 2: * 5 to \<18 years of age at Day 1. * Participants with stable chronic conditions increasing the risk of RSV disease. * 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 injection (Day 1); 2) has practiced adequate contraception or has abstained from all activities that could lead to pregnancy for 28 days prior to Day 1; 3) has agreed to continue adequate contraception through 90 days following injection; and 4) is not currently breastfeeding. Part B: Cohort 1 Re-enrollment Participants are eligible to be included in the study only if all of the following criteria apply: 1. Enrolled and dosed in Part A of Cohort 1; either reached EoS for Part A or were dosed and subsequently discontinued from study for various reasons. This includes participants who were lost to follow-up, if they can be re-engaged. 2. Participant's parent(s)/LAR(s) has provided written informed consent for participation in this study. Key Exclusion Criteria (All Cohorts): * Acutely ill or febrile (temperature ≥38.0°Celsius \[100.4°Fahrenheit\]) within 72 hours prior to or at the Screening Visit or Day 1. * History of a diagnosis or condition that, in the judgment of the Investigator, may affect study assessment or compromise participant safety. * Has received or plans to receive any licensed or authorized vaccine ≤14 days prior to the study vaccine injection (Day 1) or plans to receive a licensed or authorized vaccine within 14 days after the study vaccine injection. * Receipt of any prior systemic immunosuppressants. Short courses (\<7 days) of oral corticosteroids are allowed if completed at least 3 months prior to enrollment. * Receipt of RSV monoclonal antibodies within 6 months prior to enrollment in the study. * Participated in an interventional clinical study within 28 days (6 months for a study assessing a product unlicensed/unauthorized in this age group in country of residence at time of enrollment) prior to the day of enrollment or plans to do so while enrolled in this study. Part B: Cohort 1 Re-enrollment 1\. Participant is currently enrolled in another interventional clinical study. Note: Other protocol-defined inclusion and exclusion criteria may apply.

Locations (50)

Velocity Clinical Research, Phoenix

Phoenix, Arizona, United States

Headlands Research - Scottsdale

Scottsdale, Arizona, United States

Velocity Clinical Research - Banning

Banning, California, United States

ASCADA Research, LLC - Family Medicine

Fullerton, California, United States

Ark Clinical Research

Long Beach, California, United States

Outcomes

Primary Outcomes

Part A (Cohorts 1 and 2): Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)

Solicited ARs were collected in an electronic diary (eDiary). Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered adverse events (AEs). Investigator reviewed whether the solicited AR was also to be recorded as an AE. A summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.

Time frame: Up to 7 days post-injection

Part A (Cohorts 1 and 2): Number of Participants With Unsolicited Adverse Events (AEs)

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Any abnormal laboratory test result (hematology, clinical chemistry, or prothrombin time \[PT\]/partial thromboplastin time \[PTT\]) or other safety assessment (for example, electrocardiogram, radiological scan, vital sign measurement), including one that worsened from baseline and was considered clinically significant in the medical and scientific judgment of the Investigator was recorded as an AE. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.

Time frame: Up to 28 days post-injection

Part A (Cohorts 1 and 2): Number of Participants With Medically Attended AEs (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Study Discontinuation

A MAAE was an AE that led to an unscheduled visit to a healthcare practitioner. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly/birth defect, or was an important medical event. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.

Time frame: Day 1 through end of Part A (Month 6)

Part B (Cohort 1): Number of Participants With RSV-RTD, Respiratory Syncytial Virus- Lower Respiratory Tract Disease (RSV-LRTD), Severe RSV-LRTD, Very Severe RSV-LRTD and RSV Hospitalization Classified by Clinical Assessment Team (CAT)

RSV-RTD: Runny nose or blocked nose or cough and confirmed RSV infection. RSV-LRTD: Cough or difficulty breathing (Based on Investigator's observation; difficulty breathing included signs of wheezing, stridor, tachypnoea, chest in-drawing or subcostal or intercostal retractions) and peripheral oxygen saturation (SpO2) \<95%, or respiratory rate (RR) increased and confirmed RSV infection. RSV Severe-LRTD: Meeting the definition of RSV-LRTD and SpO2 \<93%, or lower chest wall in-drawing. RSV Very Severe LRTD: Meeting the definition of RSV-LRTD and SpO2 \<90%, or failure to respond/unconscious. RSV Hospitalization: Confirmed RSV and hospitalized for acute medical condition.

Time frame: Day 1 through end of Part B (Month 6)

Secondary Outcomes

Part A (Cohort 1): Geometric Mean Titer (GMT) of Serum RSV Neutralizing Antibody

Antibody values reported as below lower limit of quantification (LLOQ) were replaced by 0.5\*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ. LLOQ was 13 international units (IU)/milliliter (mL) for RSV-A and 10 IU/mL for RSV-B. ULOQ was 259061 IU/mL for RSV-A and 112476 IU/mL for RSV-B. 95% confidence interval (CI) for geometric mean (GM) value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation.

Time frame: Day 1, Day 29, and Month 6

Part A (Cohort 1): Geometric Mean Concentration (GMC) of Serum RSV Prefusion F (Pre-F) Binding Antibody

Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than ULOQ were replaced by the ULOQ. LLOQ was 35 arbitrary units (AU)/mL and ULOQ was 580553 AU/mL for RSV Pre-F immunoglobulin G (IgG) antibody. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation.

Time frame: Day 1, Day 29, and Month 6

Part A (Cohort 1): Geometric Mean Fold Rise (GMFR) of Post-baseline/Baseline Neutralizing Antibody Titers

Antibody values reported as below lower LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL for RSV-A and 10 IU/mL for RSV-B. ULOQ was 259061 IU/mL for RSV-A and 112476 IU/mL for RSV-B. 95% CI for GMFR (post-injection/baseline titers) was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation.

Time frame: Day 29 and Month 6

Part A (Cohort 1): GMFR of Post-baseline/Baseline Binding Antibody Concentrations

Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than ULOQ were replaced by the ULOQ. LLOQ was 35 AU/mL and ULOQ was 580553 AU/mL for RSV Pre-F IgG antibody. 95% CI for GMFR (post-injection/baseline titers) was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation.

Part A (Cohort 2): GMT of Serum RSV Neutralizing Antibody

Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL for RSV-A and 15 IU/mL for RSV-B. ULOQ was 259061 IU/mL for RSV-A and 162163 IU/mL for RSV-B. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation.

Time frame: Day 1 and Day 29

Part A (Cohort 2): GMC of Serum RSV Pre-F Binding Antibody

Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than ULOQ were replaced by the ULOQ. LLOQ was 35 AU/mL and ULOQ was 580553 AU/mL for RSV Pre-F IgG antibody. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation.

Time frame: Day 1 and Day 29

Part A (Cohort 2): GMFR of Post-baseline/Baseline Neutralizing Antibody Titers

Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL for RSV-A and 15 IU/mL for RSV-B. ULOQ was 259061 IU/mL for RSV-A and 162163 IU/mL for RSV-B. 95% CI for GMFR (post-injection/baseline titers) was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation.

Time frame: Day 29

Part A (Cohort 2): GMFR of Post-baseline/Baseline Binding Antibody Concentrations

Time frame: Day 29

Part B (Cohort 1): Number of Participants With AESIs and SAEs

An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly/birth defect, or was an important medical event. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.

Time frame: Day 1 through Part B EOS (Month 6)