A Study of mRNA-1345 Vaccine Targeting Respiratory Syncytial Virus (RSV) in Adults ≥50 Years of Age (RSVictory)

A Phase 3 Randomized, Observer-Blind, Study to Evaluate Safety, Tolerability, and Immunogenicity of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus (RSV), When Given Alone or Coadministered With a Seasonal Influenza Vaccine or SARS-CoV-2 Vaccine and When Given as an Open-label Boost at 1 Year Following a Primary Dose in Adults ≥ 50 Years of Age

The main purposes of Part A of this study are to evaluate the safety, tolerability, and immunogenicity of mRNA-1345 coadministered with a seasonal influenza vaccine (Afluria® Quadrivalent); to evaluate the impact of coadministered influenza vaccine on the immune response to RSV-A; and to evaluate the impact of coadministered RSV vaccine on the immune response to influenza.

The main purposes of Part B of this study are to evaluate the safety, tolerability, and immunogenicity of mRNA-1345 coadministered with mRNA-1273.214; to evaluate the effect of coadministered mRNA-1273.214 on the immune response to RSV-A; and to evaluate the effect of coadministered RSV vaccine on the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The main purposes of Part C (single arm, open-label) of this study are to evaluate the safety and tolerability of a booster dose (BD) of mRNA-1345 administered at 1 Year following a primary dose; to evaluate the immune response to RSV-A of a BD of mRNA 1345 administered at 1 Year following a primary dose; and to evaluate the immune response to RSV-B of a BD of mRNA-1345 administered at 1 Year following a primary dose.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus
• Intervention / Treatment: Biological: Placebo; Biological: mRNA-1345; Biological: Afluria® Quadrivalent; Biological: mRNA-1273.214

• Study Type: Interventional
• Enrollment (Actual): 3317
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates Inc
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Del Sol Research Management - Clinedge - PPDS
  • California
    • Garden Grove, California, United States, 92703-1811
      • Paragon Rx Clinical, Inc
    • Long Beach, California, United States, 90806
      • ARK Clinical Research
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials, LLC (Site 1)
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials, LLC (Site 2)
    • Modesto, California, United States, 95350
      • Central Valley Research, LLC
    • Panorama City, California, United States, 91402-3022
      • Velocity Clinical Research - Panorama City
    • Pomona, California, United States, 91786
      • Empire Clinical Research
    • San Diego, California, United States, 92120
      • Acclaim Clinical Research
    • San Diego, California, United States, 92120
      • Medical Center For Clinical Research - M3 WR - ERN - PPDS
    • Tustin, California, United States, 92780
      • ARK Clinical Research
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research LLC
  • Florida
    • Brandon, Florida, United States, 33511-4925
      • Teradan Clinical Trials
    • Doral, Florida, United States, 33122
      • Revival Research Corporation - Clinedge - PPDS
    • Doral, Florida, United States, 33172
      • Dolphin Medical Research
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center
    • Jacksonville, Florida, United States, 32205
      • Westside Center for Clinical Research - ERN - PPDS
    • Miami, Florida, United States, 33135
      • Suncoast Research Group LLC - ERN-PPDS
    • Miami, Florida, United States, 33173
      • Suncoast Research Associates LLC - ERN - PPDS
    • Miami Lakes, Florida, United States, 33016
      • Floridian Clinical Research - ClinEdge - PPDS
  • Georgia
    • Chamblee, Georgia, United States, 30341
      • Tekton Research - Georgia - Platinum - PPDS
    • Lilburn, Georgia, United States, 30047-2832
      • Lifeline Primary Care / CCT Research
    • Norcross, Georgia, United States, 30092-4544
      • Georgia Clinic / CCT Research
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research (Savannah Georgia) - Platinum - PPDS
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Iowa
    • Sioux City, Iowa, United States, 51106
      • Meridian Clinical Research (Sioux City - Iowa)
  • Kansas
    • Overland Park, Kansas, United States, 66210-1863
      • Meridian Clinical Research, LLC (Overland Park, Kansas) - Platinum - PPDS
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Meridian Clinical Research (Baton Rouge-Louisiana) - Platinum - PPDS
    • Lake Charles, Louisiana, United States, 70601
      • Clinical Trials of SWLA, LLC
  • Maryland
    • Rockville, Maryland, United States, 20854-2957
      • Meridian Clinical Research (Rockville Maryland) - Platinum - PPDS
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute, Inc - CRN - PPDS
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Meridian Clinical Research (Grand Island) - Platinum - PPDS
    • Lincoln, Nebraska, United States, 68510
      • Meridian Clinical Research, LLC (Lincoln Nebraska) - Platinum - PPDS
    • Lincoln, Nebraska, United States, 68516
      • Be Well Clinical Studies, LLC
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research (Omaha-Nebraska) - Platinum - PPDS
    • Omaha, Nebraska, United States, 68144
      • Midwest Regional Health Services - CCT Research
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Clinical Research Center of Nevada - ERN - PPDS
    • Las Vegas, Nevada, United States, 89119-5483
      • Santa Rosa Medical Centers of Nevada - CCT Research
  • New York
    • Endwell, New York, United States, 13760
      • Meridian Clinical Research (Endwell-New York) - Platinum - PPDS
    • New York, New York, United States, 10036-4103
      • IMA Medical Research, PC.
    • The Bronx, New York, United States, 10455-3908
      • CHEAR Center LLC - ClinEdge - PPDS
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Javara Research Inc. - Charlotte - Javara - PPDS
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc - M3 WR - ERN - PPDS
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Velocity Clinical Research - Cleveland - ERN - PPDS
    • Springdale, Ohio, United States, 45246
      • Meridian Clinical Research - Cincinnati - Platinum - PPDS
  • Oklahoma
    • Moore, Oklahoma, United States, 73160-1386
      • Tekton Research
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Velocity Clinical Research - Anderson - ERN - PPDS
    • Greenville, South Carolina, United States, 29615
      • Velocity Clinical Research - Greenville - ERN - PPDS
    • Myrtle Beach, South Carolina, United States, 29572-4612
      • Trial Management Associates LLC - ERN - PPDS
    • Spartanburg, South Carolina, United States, 29303-4225
      • Velocity Clinical Research - Spartanburg - ERN - PPDS
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • New Phase Research & Development
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Research - Austin - HyperCore - PPDS
    • Beaumont, Texas, United States, 77706
      • Tekton Research - Beaumont - Platinum - PPDS
    • Dallas, Texas, United States, 75230
      • Zenos Clinical Research
    • Laredo, Texas, United States, 78041
      • Milton Haber, M.D.
    • San Antonio, Texas, United States, 78215-1922
      • Sun Research Institute
  • Utah
    • Bountiful, Utah, United States, 84010-4862
      • Cope Family Medicine - Ogden Clinic
    • Springville, Utah, United States, 84663
      • CCT Research at Springville Dermatology
  • Virginia
    • Forest, Virginia, United States, 24551
      • Javara Inc./Privia Medical Group INC
    • Portsmouth, Virginia, United States, 23703
      • Meridian Clinical Research - Family Practice Ports - Portsmouth - Platinum - PPDS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

Parts A and B both:

• Adults ≥50 years of age on the day of the Randomization Visit (Day 1) who are primarily responsible for self-care and activities of daily living. Participants may have one or more chronic medical diagnoses, but should be medically stable as assessed by: Absence of changes in medical therapy within 1 month due to treatment failure or toxicity; Absence of medical events qualifying as SAEs within 1 month of the planned vaccination on 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.
• Able to comply with study requirements, including access to transportation for study visits.

Part B only:

• Fully vaccinated for COVID-19 with an approved primary series according to the locally authorized or approved regimen. If the most recent COVID-19 vaccine was part of a primary series, it must be ≥ 150 days before (or less per local guidance) Day 1. If the most recent COVID-19 vaccine was a booster dose, it must be ≥ 120 days before (or less per local guidance) Day 1.

Part C:

• Participants at Part C study sites who have been enrolled in Part B (Groups 4 and 5) of this study; have immunogenicity blood sampling at Part B baseline and Day 29; completed the Day 211/end-of-study visits for Part B; were included in the per-protocol (PP) set; and received 1 dose of mRNA-1345 at least 12 months (but no later than 15 months) prior to the time of enrollment.
• Able to comply with study requirements, including access to transportation for study visits.

Key Exclusion Criteria:

Part A:

• 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) or plans to receive a vaccine authorized or approved by a local health agency within 28 days after the study injections.
• Prior participation in research involving receipt of any investigational product (drug/biologic/device including any investigational RSV product) within 45 days before the planned date of the Day 1 study injection.
• Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine ≤180 days prior to the Randomization Visit (Day 1).
• History of a serious reaction to any prior vaccination, or Guillain-Barré syndrome within 6 weeks of any prior influenza immunization.
• Participated in an interventional clinical study within 28 days prior to the Screening Visit based on the medical history interview or plans to do so while participating in this study.

Part B:

• 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) or plans to receive a vaccine authorized or approved by a local health agency within 28 days after the study injections (with the exception of SARS-Cov-2 vaccination).
• Prior participation in research involving receipt of any investigational product (drug/biologic/device with the exception of RSV investigation products) within 45 days before the planned date of the Day 1 study injection.
• Prior receipt of any investigational/approved RSV product within 1 year of the Day 1 study injection.
• Has known history of SARS-CoV-2 infection within 90 days prior to enrollment.

Parts A and B both:

• Participant had significant exposure to someone with SARS-CoV-2 infection or COVID-19 in the past 10 days, as defined by the United States (US) Centers for Disease Control and Prevention (CDC) as a close contact of someone who has had COVID-19.

Part C:

• Participation in another interventional clinical research study where participant has received an investigational product (drug/biologic/device) within 6 months before the planned date of the BD Day 1 study injection. Any prior receipt of an investigational or approved vaccine against RSV, except as part of mRNA-1345 Study P302 Part B, is exclusionary.
• Participant has received or plans to receive any vaccine authorized or approved by a local health agency ≤28 days prior to the study injection (BD Day 1) or plans to receive a vaccine authorized or approved by a local health agency within 28 days after the study injections.
• History of a serious reaction to any prior vaccination or Guillain-Barré syndrome 6 weeks after any prior influenza immunization.

Other inclusion and/or exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: mRNA-1345 + Placebo; Single injection of mRNA-1345 and placebo, administered intramuscularly (IM), one in each arm on Day 1.	Biological: Placebo; 0.9% sodium chloride (normal saline) injection; Biological: mRNA-1345; Sterile liquid for injection
Experimental: Part A: mRNA-1345 + Afluria® Quadrivalent; Single injection of mRNA-1345 and Afluria® quadrivalent, administered IM, one in each arm on Day 1.	Biological: mRNA-1345; Sterile liquid for injection; Biological: Afluria® Quadrivalent; single-dose, pre-filled syringe for injection
Active Comparator: Part A: Afluria® Quadrivalent + Placebo; Single injection of Afluria® quadrivalent and placebo, administered IM, one in each arm on Day 1.	Biological: Placebo; 0.9% sodium chloride (normal saline) injection; Biological: Afluria® Quadrivalent; single-dose, pre-filled syringe for injection
Experimental: Part B: mRNA-1345 + mRNA-1273.214; Single injection of mRNA-1345 and mRNA-1273.214, administered IM, one in each arm on Day 1. An additional injection of placebo administered on Day 29.	Biological: Placebo; 0.9% sodium chloride (normal saline) injection; Biological: mRNA-1345; Sterile liquid for injection; Biological: mRNA-1273.214; Sterile liquid for injection
Active Comparator: Part B: mRNA-1273.214 + Placebo; Single injection of mRNA-1273.214 and placebo, administered IM, one in each arm on Day 1. An additional injection of placebo administered on Day 29.	Biological: Placebo; 0.9% sodium chloride (normal saline) injection; Biological: mRNA-1273.214; Sterile liquid for injection
Experimental: Part B: mRNA-1345 + Placebo; Single injection of mRNA-1345 and placebo, administered IM, one in each arm on Day 1. An additional injection of mRNA-1273.214, administered on Day 29.	Biological: Placebo; 0.9% sodium chloride (normal saline) injection; Biological: mRNA-1345; Sterile liquid for injection; Biological: mRNA-1273.214; Sterile liquid for injection
Experimental: Part C: mRNA-1345; Single injection of mRNA-1345 administered IM on BD Day 1.	Biological: mRNA-1345; Sterile liquid for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: 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
Part A: Number of Participants With Unsolicited Adverse Events (AEs) 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.	Day 1 through Day 28 (28 days after Day 1 injection)
Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal	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 181 (end of Study Part A)
Part A: Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) Neutralizing Antibodies (NAbs) at Day 29	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. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 29
Part A: Percentage of Participants With Seroresponse in RSV-A NAbs at Day 29	Seroresponse was defined as ≥4 × lower limit of quantification (LLOQ) if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 29
Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29	Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington 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. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure.	Day 29
Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 1 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 1 injection
Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 29 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 29 injection
Part B: Number of Participants With Unsolicited AEs 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 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.	Day 1 through Day 28 (28 days after Day 1 injection)
Part B: Number of Participants With Unsolicited AEs After Day 29 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.	Day 29 through Day 57 (28 days after Day 29 injection)
Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal	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 211
Part B: GMT of Serum RSV-A at Day 29	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 29
Part B: Percentage of Participants With Seroresponse for RSV-A Neutralizing Abs From Baseline to Day 29	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Baseline to Day 29
Part B: Geometric Mean Concentration (GMC) of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 29	The model-based GM titer was estimated on ANCOVA model. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. 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 arbitrary units (AU)/milliliters (mL) and ULOQ was 111433 AU/mL for Wuhan-Hu-1. LLOQ was 8 and ULOQ was B.1.1.529 for B1.1.529. As prespecified, only arms where participants received mRNA-1273.214 are presented for this outcome measure.	Day 29
Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 29	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. mRNA-As prespecified, only arms where participants received mRNA-1273.214 are presented for this outcome measure.	Baseline to Day 29
Part C: Number of Participants With Solicited Local and Systemic Within 7 Days After Revaccination Day 1	Solicited ARs were collected in an electronic 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 1 revaccination
Part C: Number of Participants With Unsolicited AEs Within 28 Days After Revaccination Day 1	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.	Revaccination Day 1 through Day 28 (28 days after revaccination Day 1)
Part C: Number of Participants With MAAEs	A MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner.	Revaccination Day 1 through Day 181
Part C: Number of Participants With SAEs, AESIs, and AEs Leading to Withdrawal	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. 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. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.	Revaccination Day 1 through Day 361
Part C: GMT of Serum RSV-A and RSV-B NAbs mRNA-1345 Revaccination Day 29 Compared to Primary Vaccination Day 29	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 and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 IU/mL for RSV-B. mRNA-1345 Revaccination Day 29 and mRNA-1345 primary vaccination Day 29 (received in Part B) are presented.	Primary Vaccination Day 29 to Revaccination Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: GMT of Serum RSV-B NAbs at Day 29	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 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 29
Part A: Percentage of Participants With Seroresponse in RSV-B NAbs at Day 29	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 29
Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181	Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington and Phuket strains. Seroconversion was defined as a titer ≥1:40 if baseline was <1:10 or a 4-fold or greater rise from baseline in the titers if Baseline was ≥1:10. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure.	Day 181
Part A: GMT of Serum RSV-A and RSV-B NAbs at Day 181	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 and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 181
Part A: Geometric Mean Fold Rise (GMFR) of Serum RSV-A and RSV-B NAbs at Day 181	95% CI for GMFR (postinjection/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. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 181
Part A: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ.As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 181
Part A: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181	≥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. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Baseline to Day 181
Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181	Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington 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. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure.	Day 181
Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181	Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington 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. 95% CI for GMFR (postinjection/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. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure.	Day 181
Part B: GMT of Serum RSV-B NAbs at Day 29	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 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 29
Part B: Percentage of Participants With Seroresponse in RSV-B NAbs From Baseline to Day 29	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Baseline to Day 29
Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 181	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 and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 181
Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 181	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 181
Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181	95% CI for GM value was calculated based on the t-distribution of the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. 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 AU/mL and ULOQ was 111433 AU/mL for Wuhan-Hu-1. LLOQ was 8 AU/mL and ULOQ was 24503 for B1.1.529.	Day 181
Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181	95% CI for GMFR (postinjection/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.	Day 181
Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 181	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. 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 111433 for Wuhan-Hu-1. LLOQ was 8 and ULOQ was B.1.1.529 for B1.1.529.	Baseline to Day 181
Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 181
Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181	≥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. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Baseline to Day 181
Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 211	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 and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 211
Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 211	Antibody values reported as below LLOQ were replaced by 0.5*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 211
Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211	95% CI for GM value was calculated based on the t-distribution of the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. 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 AU/mL and ULOQ was 111433 AU/mL for Wuhan-Hu-1. LLOQ was 8 AU/mL and ULOQ was 24503 for B1.1.529.	Day 211
Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211	95% CI for GMFR (postinjection/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.	Day 211
Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs at Day 211	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. 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 111433 for Wuhan-Hu-1. LLOQ was 8 and ULOQ was B.1.1.529 for B1.1.529.	Day 211
Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 211	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 211
Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 211	≥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. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.	Day 211
Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs From Baseline (Before Primary Vaccination) to Revaccination Day 29	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. Primary vaccination Day 29 (received in Part B) and Revaccination Day 29 are presented.	Baseline (Before Primary Vaccination in Part B) to Revaccination Day 29
Part C: GMT of Serum RSV-A and RSV-B NAbs at Revaccination Day 361	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 and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 IU/mL for RSV-B.	Revaccination Day 361
Part C: GMFR of Serum RSV-A and RSV-B NAbs at Revaccination Day 361	95% CI for GMFR (postinjection/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.	Revaccination Day 361
Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs at Revaccination Day 361	Seroresponse was defined as ≥4 × LLOQ if baseline was <LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ.	Baseline to Revaccination Day 361
Part C: Percentage of Participants With ≥2-fold Increases From Baseline (Before Primary Vaccination) in RSV-A and RSV-B NAb Titers at Revaccination Day 361	≥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 IU/mL for RSV-B.	Baseline to Revaccination Day 361

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Deaths During the Study	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.	Up to Day 181 for Part A, up to Day 211 for Part B, and up to Day 361 for Part C

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Publications and helpful links

General Publications

• Goswami J, Cardona JF, Caso J, Hsu DC, Simorellis AK, Wilson L, Dhar R, Wang X, Kapoor A, Collins A, Righi V, Lan L, Du J, Zhou H, Stoszek SK, Shaw CA, Reuter C, Wilson E, Das R. Safety, Tolerability, and Immunogenicity of Revaccination with mRNA-1345, an mRNA Vaccine Against RSV, Administered 12 Months Following a Primary Dose in Adults Aged >/=50 Years. Clin Infect Dis. 2025 Sep 23:ciaf515. doi: 10.1093/cid/ciaf515. Online ahead of print.
• Goswami J, Cardona JF, Hsu DC, Simorellis AK, Wilson L, Dhar R, Tomassini JE, Wang X, Kapoor A, Collins A, Righi V, Lan L, Du J, Zhou H, Stoszek SK, Shaw CA, Reuter C, Wilson E, Miller JM, Das R; study investigators. Safety and immunogenicity of mRNA-1345 RSV vaccine coadministered with an influenza or COVID-19 vaccine in adults aged 50 years or older: an observer-blinded, placebo-controlled, randomised, phase 3 trial. Lancet Infect Dis. 2025 Apr;25(4):411-423. doi: 10.1016/S1473-3099(24)00589-9. Epub 2024 Nov 25.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Actual): November 8, 2024
• Study Completion (Actual): November 8, 2024

Study Registration Dates

• First Submitted: April 8, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Safety; Vaccines; Respiratory syncytial virus; Moderna; Messenger RNA; Viral Diseases; mRNA-1345
• Additional Relevant MeSH Terms: Infections; Virus Diseases; mRNA-1345 respiratory syncytial virus vaccine; mRNA-1273.214 COVID-19 vaccine
• Other Study ID Numbers: mRNA-1345-P302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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