A Study to Evaluate the Safety and Immune Response of mRNA-1345, a Vaccine Targeting Respiratory Syncytial Virus (RSV), When Co-administered With a Fluzone HD, in Adults ≥65 Years of Age

A Phase 3, Randomized, Observer-Blind Study to Evaluate Safety, Tolerability, and Immunogenicity of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, When Coadministered With a High-Dose, Quadrivalent Seasonal Influenza Vaccine in Adults ≥65 Years of Age

The main purpose of this study is to evaluate the safety and immunogenicity of mRNA-1345 RSV vaccine when coadministered with a high dose (HD) quadrivalent seasonal influenza vaccine (Fluzone HD) in adults ≥65 years of age. The study will examine the impact of Fluzone HD on the immune response to mRNA-1345 against RSV-A and RSV-B, as well as the impact of mRNA-1345 on the immune response to Fluzone HD against 4 vaccine-matched Influenza A and B strains.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus
• Intervention / Treatment: Biological: Placebo; Biological: mRNA-1345; Biological: Fluzone HD

• Study Type: Interventional
• Enrollment (Actual): 1900
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Clinical Trials
    • Scottsdale, Arizona, United States, 85260
      • Headlands Research, Inc.
  • California
    • Dublin, California, United States, 94568
      • West Coast Research LLC
    • Riverside, California, United States, 92503
      • Artemis Institute for Clinical Research
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates (PRA)
    • San Diego, California, United States, 92120
      • Acclaim Clinical Research
  • Florida
    • Hialeah, Florida, United States, 33016
      • Neoclinical Research
    • Jupiter, Florida, United States, 33458
      • Health Awareness Inc
    • Miami, Florida, United States, 33173
      • Suncoast Research Associates, LLC
    • Miami, Florida, United States, 33135
      • South Florida Research Center, Inc.
    • Orlando, Florida, United States, 32819
      • Headlands Research - Orlando
    • Tampa, Florida, United States, 33603
      • New Tampa Health, Inc
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta/Headlands
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Bingham Memorial Hospital
  • Illinois
    • River Forest, Illinois, United States, 60305
      • DM Clinical Research- River Forest
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Velocity Clinical Research-Baton Rouge
    • Prairieville, Louisiana, United States, 70769
      • DelRicht Research @ Neighborhood Health
  • Massachusetts
    • Brookline, Massachusetts, United States, 02445
      • DM Clinical Research - Brookline
  • Michigan
    • Southfield, Michigan, United States, 48076
      • DM Clinical Research - Southfield
  • Mississippi
    • Gulfport, Mississippi, United States, 39503
      • DelRicht Research at Gulfport Memorial
  • Missouri
    • Springfield, Missouri, United States, 65807
      • DelRicht Research
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Be Well Clinical Studies, LLC
    • Norfolk, Nebraska, United States, 68701
      • Velocity Clinical Research-Norfolk
  • North Carolina
    • Wilmington, North Carolina, United States, 28403
      • Trial Management Associates, LLC
  • Ohio
    • Akron, Ohio, United States, 44311
      • Synexus AES - Akron
    • Columbus, Ohio, United States, 43213
      • Centricity Research
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • Delricht Tate
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • DM Clinical Research - Philadelphia
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Tennessee
    • Hendersonville, Tennessee, United States, 37075
      • Delricht Moyer
  • Texas
    • Houston, Texas, United States, 77065
      • DM Clinical Research - Houston
    • McKinney, Texas, United States, 75070
      • Delricht Research At Zomnir Family Medicine
    • Sugar Land, Texas, United States, 77054
      • Javara Inc. /Privia Medical Group Gulf Coast, PLLC
    • Tomball, Texas, United States, 77375
      • DM Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

• Participants may have one or more chronic medical diagnoses, but should be medically stable as assessed by:

  • Absence of changes in medical therapy within 60 days of Day 1 due to treatment failure or toxicity,
  • Absence of serious or significant medical events within 30 days of Day 1, and
  • Absence of known, current, and life-limiting diagnoses which, in the opinion of the Investigator, would make completion of the protocol unlikely.
• A participant assigned female at birth is eligible to participate if they are postmenopausal or not a person of childbearing potential.

Key Exclusion Criteria:

• Close contact with someone with laboratory-confirmed influenza and/or RSV infection or with someone who has been treated with antiviral therapies for influenza (for example, Tamiflu®) within the past 5 days prior to Day 1.
• Reported history of congenital or acquired immunodeficiency, immunosuppressive condition or immune-mediated disease, asplenia, or recurrent severe infections.
• Participant has tested positive for influenza or RSV by local health authority-approved testing methods ≤6 months prior to Day 1.
• Participant has received or plans to receive any vaccine authorized or approved by a local health agency ≤28 days prior to study injections (Day 1 and Day 22) or plans to receive a vaccine authorized or approved by a local health agency within 28 days after study injections.
• Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine ≤6 months prior to Day 1.
• Participant has received any RSV vaccine (authorized/approved by local health agency or investigational) prior to Day 1.

Note: Other protocol-defined inclusion and/or exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluzone HD + mRNA-1345; Participants will receive Fluzone HD + mRNA-1345 by intramuscular (IM) injection on Day 1 followed by placebo by IM injection on Day 22.	Biological: Placebo; 0.9% sodium chloride (normal saline) injection; Biological: mRNA-1345; Suspension for injection; Biological: Fluzone HD; Suspension for injection
Experimental: Fluzone HD Followed by mRNA-1345; Participants will receive Fluzone HD + placebo by IM injection on Day 1 followed by mRNA-1345 by IM injection on Day 22.	Biological: Placebo; 0.9% sodium chloride (normal saline) injection; Biological: mRNA-1345; Suspension for injection; Biological: Fluzone HD; Suspension for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) Within 7 Days After Day 1 Injection	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.	Within 7 days after Day 1 injection
Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 22 Injection	Solicited ARs were collected in an 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 AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of SAEs and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Within 7 days after Day 22 injection
Number of Participants With Unsolicited Adverse Events (AEs) Up to 21 Days After Day 1 Injection	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.	Up to 21 days after Day 1 injection
Number of Participants With Unsolicited AEs Up to 21 Days After Day 22 Injection	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 PT/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.	Up to 21 days after Day 22 injection
Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation	A MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner. An AESI is 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.	Day 1 through Day 202
Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) and Respiratory Syncytial Virus Subtype B (RSV-B) Neutralizing Antibodies (nAbs)	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) and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B.	Day 22 (for Arm 1) and Day 43 (for Arm 2)
GMT of Serum Anti-Hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay	Influenza A strains included H1N1 and H3N2 and influenza B strains included Austria and Phuket strains. Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 2560 for Influenza A. LLOQ was 10 and ULOQ was 640 for Influenza B.	Day 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroresponse for RSV-A and RSV-B nAbs, as Measured by HAI Assay	Seroresponse at a participant level was defined as a change from below the LLOQ to equal or above 4 * LLOQ, or at least a 4-fold increase if baseline was equal to or above the LLOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B.	Baseline to Day 22 (for Arm 1) or Day 43 (for Arm 2)
Geometric Mean Fold-Rise (GMFR) of Postinjection RSV-A and RSV-B nAbs Antibodies for Influenza, as Measured by HAI Assay	95% CI for GMFR 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.	Day 22 (for Arm 1) or Day 43 (for Arm 2)
Percentage of Participants With ≥2-fold Increase in RSV-A and RSV-B nAbs	≥2-fold increase from baseline at participant level was defined as a change from below the LLOQ to equal or above 2 * LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B.	Day 22 (Arm 1) or Day 43 (Arm 2)
Percentage of Participants With Seroconversion, as Measured by HAI Assay	Influenza A strains included H1N1 and H3N2 and influenza B strains included Austria and Phuket strains. Seroconversion at a participant level was defined as a titer ≥1:40 if baseline is < 1:10 or at least a 4-fold increase from baseline if baseline was ≥1:10. Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 2560 for Influenza A. LLOQ was 10 and ULOQ was 640 for Influenza B.	Day 22
GMFR of Serum Ab Level, as Measured by HAI Assay	95% CI for GMFR 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.	Day 22

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Deaths Related to Study Drug	A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, whether or not it was considered related to study drug. The investigator assessed causality (that is, whether there is a reasonable possibility that the study drug caused the death). The relationship was characterized using the following classifications: Not related: There was not a reasonable possibility of a relationship to the study drug. The temporal sequence of the death relative to administration of the study drug was not reasonable AND/OR the death was more likely explained by a cause other than the study drug. Related: There was a reasonable possibility of a relationship to the study drug. There was evidence of exposure to the study drug. The temporal sequence of the death relative to the administration of the study drug was reasonable. The death was more likely explained by the study drug than by another cause.	Day 1 through Day 202

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2023
• Primary Completion (Actual): June 7, 2024
• Study Completion (Actual): June 7, 2024

Study Registration Dates

• First Submitted: September 23, 2023
• First Submitted That Met QC Criteria: September 23, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Vaccines; Respiratory syncytial virus; Moderna; Messenger RNA; Viral Diseases; mRNA-1345; RSV Vaccine
• Additional Relevant MeSH Terms: Infections; Virus Diseases
• Other Study ID Numbers: mRNA-1345-P304

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No