A Study to Investigate the Safety and Immunogenicity of the Quadrivalent Influenza mRNA Vaccines in Adults Aged 18 Years and Above

A Phase I/II Study to Investigate the Safety and Immunogenicity of Quadrivalent Influenza mRNA Vaccines MRT5421, MRT5424, and MRT5429 in Healthy Participants Aged 18 Years and Above

The purpose of this study was to evaluate the safety and immunogenicity of a single intramuscular (IM) injection of different formulations of Quadrivalent Influenza Vaccine (QIV) messenger ribonucleic acid (mRNA) (MRT5421, MRT5424, and MRT5429) compared to an active control (QIV- standard dose (SD), QIV- high dose (HD) [adults ≥ 65 years of age only], or quadrivalent recombinant influenza vaccine (RIV4)) in adults 18 years of age and older.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Influenza Immunization
• Intervention / Treatment: Biological: Quadrivalent Influenza mRNA Vaccine MRT5421; Biological: Quadrivalent Influenza mRNA Vaccine MRT5429; Biological: Quadrivalent Influenza mRNA Vaccine MRT5424; Biological: Quadrivalent Influenza Standard Dose Vaccine; Biological: Quadrivalent Influenza High-Dose Vaccine; Biological: Quadrivalent Recombinant Influenza Vaccine

Detailed Description

Study duration per participant was approximately 12 months.

• Treatment duration: 1 injection of one of the 7 QIV mRNA or one of the controls
• Dose escalation with sequential enrollment

• Study Type: Interventional
• Enrollment (Actual): 908
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Honduras
  • San Pedro Sula, Honduras, 21104
    • Investigational Site Number : 3400001
• Puerto Rico
  • Barrio Sabana, Puerto Rico, 00694
    • Investigational Site Number : 6300002
• United States
  • California
    • San Diego, California, United States, 92123-1881
      • California Research Foundation Site Number : 8400038
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center- Site Number : 8400032
    • Hollywood, Florida, United States, 33024
      • Cenexel Research Centers of America- Site Number : 8400037
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Brengle Family Medicine Site Number : 8400045
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • AMR Lexington- Site Number : 8400042
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Velocity Clinical Research- New Orleans Site Number : 8400053
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Alliance for Multispecialty Research - KCM, LLC- Site Number : 8400034
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Velocity Clinical Research Norfolk- Site Number : 8400046
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • AMR Knoxville- Site Number : 8400043
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc. - PPDS- Site Number : 8400029
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Cenexel JBR- Site Number : 8400051

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged from 18 years on the day of inclusion or aged from 21 years on the days of inclusion, depending on the countries.

• A female participant was eligible to participate if she was not pregnant or breastfeeding and one of the following conditions applied:

  • Was of non-childbearing potential. To be considered of non-childbearing potential, a female must of been postmenopausal for at least 1 year, or surgically sterile OR
  • Was of childbearing potential and agreed to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 12 weeks after study intervention administration.
• A female participant of childbearing potential must of had a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 8 hours before the 1st dose of study intervention

Exclusion Criteria: Participants were excluded from the study if any of the following criteria applied:

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Known systemic hypersensitivity to any of the study intervention components (eg, polyethylene glycol, polysorbate); history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances; any allergic reaction (eg, anaphylaxis) after administration of mRNA vaccine
• Previous history of myocarditis, pericarditis, and / or myopericarditis
• Known history of previous episodes of Gillian-Barre Syndrome (GBS), neuritis (including Bell's palsy), convulsions, encephalitis, transverse myelitis, and vasculitis
• Participants with an ECG that is consistent with possible myocarditis or pericarditis or, in the opinion of the investigator, demonstrates clinically relevant abnormalities that may affect participant safety or study results
• Self-reported thrombocytopenia, contraindicating Intramuscular vaccination based on Investigator's judgment
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating Intramuscular vaccination based on Investigator's judgment
• Chronic illness that, in the opinion of the Investigator, was at a stage where it might have interfered with study conduct or completion
• Moderate or severe acute illness / infection (according to Investigator's judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on the day of vaccination. A prospective participant was not included in the study until the condition was resolved or the febrile event subsided
• Participant who had acute infection symptoms or a positive SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to the 1st visit (V01)
• Receipt of any vaccine in the 4 weeks preceding study intervention administration or planned receipt of any vaccine in the 4 weeks following study intervention administration
• Receipt of immune globulins, blood or blood-derived products in the past 3 months
• Previous vaccination against influenza in the previous 6 months with an investigational or marketed vaccine
• Receipt of any mRNA vaccine/product in the 2 months preceding study intervention administration

NOTE: The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Quadrivalent Influenza mRNA Vaccine MRT5421 Dose 1; participants received a single dose of QIV mRNA vaccine MRT5421	Biological: Quadrivalent Influenza mRNA Vaccine MRT5421; Pharmaceutical form:solution in a vial-Route of administration:Intramuscular injection
Experimental: Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 1; participants received a single dose of QIV mRNA vaccine MRT5429	Biological: Quadrivalent Influenza mRNA Vaccine MRT5429; Pharmaceutical form:solution in a vial-Route of administration:Intramuscular Injection
Experimental: Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 2; participants received a single dose of QIV mRNA vaccine MRT5429	Biological: Quadrivalent Influenza mRNA Vaccine MRT5429; Pharmaceutical form:solution in a vial-Route of administration:Intramuscular Injection
Experimental: Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 3; participants received a single dose of QIV mRNA vaccine MRT5429	Biological: Quadrivalent Influenza mRNA Vaccine MRT5429; Pharmaceutical form:solution in a vial-Route of administration:Intramuscular Injection
Experimental: Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 4; participants received a single dose of QIV mRNA vaccine MRT5429	Biological: Quadrivalent Influenza mRNA Vaccine MRT5429; Pharmaceutical form:solution in a vial-Route of administration:Intramuscular Injection
Experimental: Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 1; participants received a single dose of QIV mRNA vaccine MRT5424	Biological: Quadrivalent Influenza mRNA Vaccine MRT5424; Pharmaceutical form:solution in a vial-Route of administration:Intramuscular injection
Experimental: Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 2; participants received a single dose of QIV mRNA vaccine MRT5424	Biological: Quadrivalent Influenza mRNA Vaccine MRT5424; Pharmaceutical form:solution in a vial-Route of administration:Intramuscular injection
Active Comparator: Quadrivalent Influenza SD Vaccine; participants received a single dose of QIV-SD vaccine	Biological: Quadrivalent Influenza Standard Dose Vaccine; Pharmaceutical form: suspension for injection in prefilled syringe -Route of administration:Intramuscular injection; Other Names: Fluzone Qudrivalent®
Active Comparator: Quadrivalent Influenza HD Vaccine; participants received a single dose of QIV -HD vaccine (for adults ≥ 65 years of age only)	Biological: Quadrivalent Influenza High-Dose Vaccine; Pharmaceutical form:suspension for injection in pre filled syringe -Route of administration:Intramuscular injection; Other Names: Fluzone High-Dose Quadrivalent®
Active Comparator: Quadrivalent Influenza RIV4 Vaccine; participants received a single dose of RIV4 vaccine	Biological: Quadrivalent Recombinant Influenza Vaccine; Pharmaceutical form:suspension for injection in pre filled syringe-Route of administration:Intramuscular injection; Other Names: Flublok Quadrivalent®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs) After Vaccine Administration	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions, that is, pre-listed in the case report form in terms of diagnosis and onset window post-vaccination. Systemic AEs are all AEs that were not injection or administration site reactions. Immediate events are recorded to capture medically relevant unsolicited systemic AEs which occur within the first 30 minutes after vaccination.	Within 30 minutes after vaccine administration on Day 1
Number of Participants With Solicited Injection Site Reactions After Vaccine Administration	An adverse reaction (AR) is any noxious and unintended response to a study vaccine related to any dose. Solicited injection site reactions are reactions at and around the injection site of the vaccine observed and reported under the conditions (nature and onset) pre-listed in the protocol and case report form.	Within 7 days after vaccine administration on Day 1
Number of Participants With Solicited Systemic Reactions After Vaccine Administration	An AR is any noxious and unintended response to a study vaccine related to any dose. Solicited systemic reactions are systemic AEs observed and reported under the conditions (nature and onset) pre-listed in the protocol and case report form.	Within 7 days after vaccine administration on Day 1
Number of Participants With Unsolicited Adverse Events After Vaccine Administration	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions, that is, pre-listed in the case report form in terms of diagnosis and onset window post-vaccination.	Within 28 days after vaccine administration on Day 1
Number of Participants With Medically Attended Adverse Events (MAAEs)	An MAAE is a new onset or a worsening of a condition that prompts the participant or participant's parent/legally acceptable representative to seek unplanned medical advice at a physician's office or emergency department.	Within 180 days after vaccine administration on Day 1
Number of Participants With Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESIs)	An SAE is any untoward medical occurrence that at any dose results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect or is an important medical event. An AESI (serious or non-serious) is 1 of scientific and medical concern specific to the Sponsor's study vaccine or program, for which ongoing monitoring and rapid communication by the investigator to the Sponsor can be appropriate. The AESIs was defined as anaphylactic reactions (including bronchospasms, and laryngeal spasms), Guillain-Barré syndrome, neuritis (including Bell's palsy), myocarditis, pericarditis, myopericarditis and vasculitis.	From the vaccine administration (Day 1) until 12 months after vaccine administration, approximately 366 days
Number of Participants With Abnormal Biological Test Results	Blood samples were collected for the assessment of abnormal hematology and clinical chemistry parameters. Only participants with outside the normal range hematology and clinical chemistry parameters are reported.	Within 8 days after vaccine administration on Day 1
Geometric Mean of Hemagglutination Inhibition (HAI) Antibody (Ab) Titer at Day 1	The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% confidence interval (CI) was based on the Clopper-Pearson method.	Day 1
Geometric Mean of Hemagglutination Inhibition Antibody Titer at Day 29	The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI was based on the Clopper-Pearson method.	Day 29
Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 1	The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.	Day 1
Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 29	The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.	Day 29
Geometric Mean Ratio of Hemagglutination Inhibition Antibody Titer at Day 29	The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Clopper-Pearson method.	Days 1 and 29
Percentage of Participants With Seroconversion of Hemagglutination Inhibition Antibody Titer at Day 29	The seroconversion was defined as titer <10 on Day 1 and post-injection titer >=40 on Day 29; or defined as titer >=10 on Day 1 and a >=4-fold increase in titer on Day 29. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.	Day 29
Percentage of Participants With Hemagglutination Inhibition Antibody Titer >=1:40 at Day 29	The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.	Day 29
Percentage of Participants With >=2 and >=4 Fold Increase in Hemagglutination Inhibition Antibody Titer at Day 29	The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.	Days 1 and 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean of Neutralization Test (NT) Antibody Titer at Days 1 and 29	The NT Ab was planned to be measured using seroneutralization (SN) measurement method. The 95% CI was planned to be calculated using the Clopper-Pearson method.	Days 1 and 29
Geometric Mean Ratio of Neutralization Test Antibody Titer at Day 29	The NT Ab was planned to be measured using SN measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination was planned to be reported. The 95% CI was planned to be calculated using the Clopper-Pearson method.	Days 1 and 29
Percentage of Participants With >=2 and >=4 Fold Increase in Neutralization Test Antibody Titer at Day 29	The NT Ab was planned to be measured using SN measurement method. The 95% CI for the single percentage was planned to be calculated using the Clopper-Pearson method.	Days 1 and 29

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

Helpful Links

• VAV00045 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Actual): June 9, 2025
• Study Completion (Actual): June 9, 2025

Study Registration Dates

• First Submitted: April 4, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Biological Products; Complex Mixtures; Viral Vaccines; Vaccines; Influenza Vaccines
• Other Study ID Numbers: VAV00045; U1111-1295-2852 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

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