A Study on the Safety and Immunogenicity of Hexavalent Influenza mRNA Vaccine in Adult Participants 50 Years of Age and Older

A Phase I/II, Randomized, Modified Double-blind Study to Investigate the Safety and Immunogenicity of Different Doses of Hexavalent Influenza mRNA HA + mRNA NA Vaccine in Adult Participants 50 Years of Age and Older

The purpose of this study is to evaluate the safety and immunogenicity of a single intramuscular injection of different formulations of a hexavalent influenza messenger ribonucleic acid (mRNA) vaccine composed of differing dose levels of trivalent (TIV) mRNA hemagglutinin (HA) in combination with TIV mRNA-neuraminidase (NA) compared to an active control ((Fluzone standard-dose quadrivalent influenza vaccine (QIV-SD) or Fluzone high-dose quadrivalent influenza vaccine (QIV-HD) in adults 50 years of age and older.

Study Overview

• Status: Active, not recruiting
• Conditions: Influenza; Healthy Volunteers
• Intervention / Treatment: Biological: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1; Biological: TIV mRNA-neuraminidase (NA); Biological: TIV mRNA-HA Vaccine 2; Biological: Quadrivalent Influenza Standard Dose Vaccine; Biological: Quadrivalent Influenza Vaccine High Dose

Detailed Description

Study details include the following:

• Study Duration: approximately 12 months for each participant
• Treatment: 1 injection of hexavalent vaccine, trivalent vaccine, or active control
• Visit frequency: Day (D) 01, D03, D09, D29, and D181; D366 (telephone call)
• Dose escalation with sequential enrollment of sentinel cohorts followed by parallel enrollment of the main cohort

• Study Type: Interventional
• Enrollment (Actual): 1162
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Botany, New South Wales, Australia, 2019
      • Investigational Site Number : 0360001
  • Victoria
    • Bayswater, Victoria, Australia, 3153
      • Investigational Site Number : 0360003
    • Melbourne, Victoria, Australia, 3124
      • Investigational Site Number : 0360002
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Accel Research Sites Network - Birmingham- Site Number : 8400008
    • Mobile, Alabama, United States, 36608
      • AMR Mobile- Site Number : 8400022
  • Arizona
    • Tempe, Arizona, United States, 85281
      • Alliance for Multispeciality Research - Clinical Research Consortium- Site Number : 8400015
  • Florida
    • Coral Gables, Florida, United States, 33134
      • AMR Miami- Site Number : 8400021
    • DeLand, Florida, United States, 32720
      • Accel Research Sites Network - DeLand Clinical Research Unit- Site Number : 8400003
    • Fort Myers, Florida, United States, 33912
      • Alliance for Multispeciality Research - Fort Myers- Site Number : 8400013
    • Maitland, Florida, United States, 32751
      • Accel Research Sites - Maitland- Site Number : 8400007
    • Palmetto Bay, Florida, United States, 33157
      • Innovation Medical Research Center - Palmetto Bay- Site Number : 8400011
  • Georgia
    • Decatur, Georgia, United States, 30030-2627
      • Accel Research Site - NeuroStudies.net, LLC - ERN - PPDS- Site Number : 8400001
  • Illinois
    • Oak Brook, Illinois, United States, 60532
      • AMR - Chicago- Site Number : 8400012
  • Kansas
    • Newton, Kansas, United States, 67114
      • Alliance for Multispeciality Research - Newton- Site Number : 8400020
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispeciality Research - Wichita East- Site Number : 8400014
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Alliance for Multispeciality Research - Lexington- Site Number : 8400018
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials- Site Number : 8400009
    • Methuen, Massachusetts, United States, 03110
      • ActivMed Practices & Research- Site Number : 8400005
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute- Site Number : 8400010
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispeciality Research - Kansas City- Site Number : 8400019
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • AMR Las Vegas - Site Number : 8400016
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center - North Charleston- Site Number : 8400002
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispeciality Research - Knoxville- Site Number : 8400017
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research- Site Number : 8400004

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participant aged 50 years on the day of inclusion

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

  • Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, or surgically sterile.

OR

• Is of childbearing potential and agrees 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 have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 8 hours prior to administration of study intervention.

Exclusion Criteria:

Participants are not eligible for the study if any of the following criteria are met:

• 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 Guillain-Barré syndrome, neuritis (including Bell's palsy), convulsions, encephalitis, transverse myelitis, and vasculitis
• Participants with an electrocardiogram 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 (IM) vaccination based on Investigator's judgment
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination based on Investigator's judgment
• Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion
• Moderate or severe acute illness / infection (according to investigator's judgement) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on the day of vaccination. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
• Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion
• Participant who had acute infectious symptoms or a positive SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to the first 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 or planned receipt of any mRNA vaccine in the 2 months after study vaccination
• Participation at the time of study enrollment (or in the 4 weeks preceding study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
• Self-reported or documented seropositivity for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus

Study Plan

How is the study designed?

Design Details

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

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 - Hexavalent (Combination 1); Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 1)	Biological: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1; Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection; Biological: TIV mRNA-neuraminidase (NA); Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection
Experimental: Group 2 - Hexavalent (Combination 2); Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 2)	Biological: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1; Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection; Biological: TIV mRNA-neuraminidase (NA); Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection
Experimental: Group 3 - Hexavalent (Combination 3); Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 3)	Biological: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1; Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection; Biological: TIV mRNA-neuraminidase (NA); Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection
Experimental: Group 4 - Hexavalent (Combination 4); Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 4)	Biological: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1; Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection; Biological: TIV mRNA-neuraminidase (NA); Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection
Experimental: Group 5 - Hexavalent (Combination 5); Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 5)	Biological: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1; Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection; Biological: TIV mRNA-neuraminidase (NA); Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection
Experimental: Group 6 - Hexavalent (Combination 6); Participants will receive single dose of hexavalent influenza mRNA vaccine composed of differing dose levels of TIV mRNA-HA Vaccine 1 in combination with TIV mRNA-NA (Combination 6)	Biological: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1; Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection; Biological: TIV mRNA-neuraminidase (NA); Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection
Experimental: Group 7 - TIV mRNA-HA Vaccine 1; Participants will receive a single dose of TIV mRNA-HA Vaccine 1	Biological: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1; Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection
Experimental: Group 8 - TIV mRNA-NA; Participants will receive a single dose of TIV mRNA-NA	Biological: TIV mRNA-neuraminidase (NA); Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection
Experimental: Group 9 - TIV mRNA-HA Vaccine 2; Participants will receive single dose of TIV mRNA-HA Vaccine 2	Biological: TIV mRNA-HA Vaccine 2; Pharmaceutical form: solution for injection in a vial; Route of administration: Intramuscular injection
Active Comparator: Group 10 - QIV-SD; Participants will receive single dose of QIV-SD vaccine (for participants 50 to 64 years of age only)	Biological: Quadrivalent Influenza Standard Dose Vaccine; Pharmaceutical form: Liquid suspension for injection in pre-filled syringe; Route of administration: Intramuscular injection; Other Names: Fluzone Qudrivalent®
Active Comparator: Group 11 - QIV-HD; Participants will receive single dose of QIV-HD vaccine	Biological: Quadrivalent Influenza Vaccine High Dose; Pharmaceutical form: Liquid suspension for injection in pre-filled syringe; Route of administration: Intramuscular injection; Other Names: Fluzone High-Dose Quadrivalent®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with unsolicited AEs	AEs that do not fulfill the conditions of solicited reactions	Up to 28 days after injection
Number of participants with out-of-range biological test results	Out-of-range biological test results (including shift from baseline values)	Up to 8 days after injection
Number of participants with immediate unsolicited systemic adverse events (AEs)	Unsolicited systemic AEs that occur within 30 minutes after vaccination	Within 30 minutes after injection
Number of participants with medically attended adverse events (MAAEs)	MAAEs reported up to 180 days after injection	Up to 180 days after injection
Number of participants with solicited injection site reactions	Solicited injection site reactions pre-listed in the participant diary and in the case report form CRF	Up to 7 days after injection
Number of participants with solicited systemic reactions	Solicited systemic reactions pre-listed in the participant diary and in the CRF	Up to 7 days after injection
Number of participants with serious adverse events (SAEs)	Throughout the study	SAEs throughout the study (Up to approximately 12 months)
Number of participants with adverse events of special interest (AESIs)	Throughout the study	AESIs throughout the study (Up to approximately 12 months)
Hemagglutinin inhibition (HAI) titers	HAI titers at D01 and D29	At Day 1 and Day 29
Individual HAI antibody (Ab) titer ratio D29/D01	Individual HAI Ab titer ratio D29/D01	At Day 1 and Day 29
Seroconversion (HAI Ab titer)	Number of participants with HAI Ab titer < 10 [1/dil] at Day 1 and post-injection titer ≥ 40 [1/dil] at Day 29, or titer ≥ 10 [1/dil] at Day 1 and a ≥ 4-fold increase in titer [1/dil] at Day 29	At Day 1 and Day 29
HAI Ab titer ≥ 40 (1/dil)	HAI Ab titer ≥ 40 (1/dil) at D29	At Day 29
Neuraminidase inhibition (NAI) titers	NAI titers at D01 and D29	At Day 1 and Day 29
Individual NAI Ab titer ratio D29/D01	Individual NAI Ab titer ratio D29/D01	At Day 1 and Day 29
Seroconversion (NAI Ab titer)	Number of participants with NAI Ab titer < 10 [1/dil] at D01 and post-injection titer ≥ 40 [1/dil] at D29, or titer ≥ 10 [1/dil] at D01 and a ≥ 4-fold increase in titer [1/dil] at D29)	At Day 1 and Day 29
NAI Ab titer ≥ 40 (1/dil)	NAI Ab titer ≥ 40 (1/dil) at D29	At Day 29
2-fold and 4-fold rise in NAI titers	2-fold and 4-fold rise in NAI titers from D01 to D29	Day 1 to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual neutralizing antibodies titer ratio	Individual neutralizing antibodies titer ratio D29/D01	At Day 1 and Day 29
Neutralizing antibodies titers	Neutralizing antibodies titers at D01 and D29	At Day 1 and Day 29
2-fold and 4-fold increase in neutralizing titers	2-fold and 4-fold increase in neutralizing titers D01 through D29	Day 1 to Day 29

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2025
• Primary Completion (Estimated): April 16, 2026
• Study Completion (Estimated): April 16, 2026

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 19, 2024
• First Posted (Actual): December 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: influenza, flu, vaccine, hexavalent
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Immunologic Factors; Physiological Effects of Drugs; Coagulants; Agglutinins; Vaccines; Hemagglutinins
• Other Study ID Numbers: FBP00021; U1111-1303-3537 (Registry Identifier: WHO 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