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

NCT06744205 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: FBP00021U1111-1303-3537
• Study Type: interventional
• Target: 1,162
• Locations: 2 countries
• Sites: 24

Brief Summary

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.

Conditions

Influenza; Healthy Volunteers

Keywords

influenza, flu, vaccine, hexavalent

Outcome Measures

Primary Outcomes (17)

• 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 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 unsolicited AEs

  AEs that do not fulfill the conditions of solicited reactions

  Up to 28 days 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 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)

• 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

• 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 Outcomes (3)

• Neutralizing antibodies titers

  At Day 1 and Day 29

• Individual neutralizing antibodies titer ratio

  At Day 1 and Day 29

• 2-fold and 4-fold increase in neutralizing titers

  Day 1 to Day 29

Study Arms (11)

Group 1 - Hexavalent (Combination 1)

EXPERIMENTAL

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; Biological: TIV mRNA-neuraminidase (NA)

Group 2 - Hexavalent (Combination 2)

EXPERIMENTAL

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; Biological: TIV mRNA-neuraminidase (NA)

Group 3 - Hexavalent (Combination 3)

EXPERIMENTAL

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; Biological: TIV mRNA-neuraminidase (NA)

Group 4 - Hexavalent (Combination 4)

EXPERIMENTAL

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; Biological: TIV mRNA-neuraminidase (NA)

Group 5 - Hexavalent (Combination 5)

EXPERIMENTAL

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; Biological: TIV mRNA-neuraminidase (NA)

Group 6 - Hexavalent (Combination 6)

EXPERIMENTAL

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; Biological: TIV mRNA-neuraminidase (NA)

Group 7 - TIV mRNA-HA Vaccine 1

EXPERIMENTAL

Participants will receive a single dose of TIV mRNA-HA Vaccine 1

Biological: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1

Group 8 - TIV mRNA-NA

EXPERIMENTAL

Participants will receive a single dose of TIV mRNA-NA

Biological: TIV mRNA-neuraminidase (NA)

Group 9 - TIV mRNA-HA Vaccine 2

EXPERIMENTAL

Participants will receive single dose of TIV mRNA-HA Vaccine 2

Biological: TIV mRNA-HA Vaccine 2

Group 10 - QIV-SD

ACTIVE COMPARATOR

Participants will receive single dose of QIV-SD vaccine (for participants 50 to 64 years of age only)

Biological: Quadrivalent Influenza Standard Dose Vaccine

Group 11 - QIV-HD

ACTIVE COMPARATOR

Participants will receive single dose of QIV-HD vaccine

Biological: Quadrivalent Influenza Vaccine High Dose

Interventions

Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1 BIOLOGICAL

* Pharmaceutical form: solution for injection in a vial * Route of administration: Intramuscular injection

Group 1 - Hexavalent (Combination 1); Group 2 - Hexavalent (Combination 2); Group 3 - Hexavalent (Combination 3); Group 4 - Hexavalent (Combination 4); Group 5 - Hexavalent (Combination 5); Group 6 - Hexavalent (Combination 6); Group 7 - TIV mRNA-HA Vaccine 1

TIV mRNA-neuraminidase (NA) BIOLOGICAL

* Pharmaceutical form: solution for injection in a vial * Route of administration: Intramuscular injection

Group 1 - Hexavalent (Combination 1); Group 2 - Hexavalent (Combination 2); Group 3 - Hexavalent (Combination 3); Group 4 - Hexavalent (Combination 4); Group 5 - Hexavalent (Combination 5); Group 6 - Hexavalent (Combination 6); Group 8 - TIV mRNA-NA

TIV mRNA-HA Vaccine 2 BIOLOGICAL

* Pharmaceutical form: solution for injection in a vial * Route of administration: Intramuscular injection

Group 9 - TIV mRNA-HA Vaccine 2

Quadrivalent Influenza Standard Dose Vaccine BIOLOGICAL

* Pharmaceutical form: Liquid suspension for injection in pre-filled syringe * Route of administration: Intramuscular injection

Also known as: Fluzone Qudrivalent®

Group 10 - QIV-SD

Quadrivalent Influenza Vaccine High Dose BIOLOGICAL

* Pharmaceutical form: Liquid suspension for injection in pre-filled syringe * Route of administration: Intramuscular injection

Also known as: Fluzone High-Dose Quadrivalent®

Group 11 - QIV-HD

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (24)

Accel Research Sites Network - Birmingham- Site Number : 8400008

Birmingham, Alabama, 35216, United States

Location

AMR Mobile- Site Number : 8400022

Mobile, Alabama, 36608, United States

Location

Alliance for Multispeciality Research - Clinical Research Consortium- Site Number : 8400015

Tempe, Arizona, 85281, United States

Location

AMR Miami- Site Number : 8400021

Coral Gables, Florida, 33134, United States

Location

Accel Research Sites Network - DeLand Clinical Research Unit- Site Number : 8400003

DeLand, Florida, 32720, United States

Location

Alliance for Multispeciality Research - Fort Myers- Site Number : 8400013

Fort Myers, Florida, 33912, United States

Location

Accel Research Sites - Maitland- Site Number : 8400007

Maitland, Florida, 32751, United States

Location

Innovation Medical Research Center - Palmetto Bay- Site Number : 8400011

Palmetto Bay, Florida, 33157, United States

Location

Accel Research Site - NeuroStudies.net, LLC - ERN - PPDS- Site Number : 8400001

Decatur, Georgia, 30030-2627, United States

Location

AMR - Chicago- Site Number : 8400012

Oak Brook, Illinois, 60532, United States

Location

Alliance for Multispeciality Research - Newton- Site Number : 8400020

Newton, Kansas, 67114, United States

Location

Alliance for Multispeciality Research - Wichita East- Site Number : 8400014

Wichita, Kansas, 67207, United States

Location

Alliance for Multispeciality Research - Lexington- Site Number : 8400018

Lexington, Kentucky, 40509, United States

Location

Boston Clinical Trials- Site Number : 8400009

Boston, Massachusetts, 02131, United States

Location

ActivMed Practices & Research- Site Number : 8400005

Methuen, Massachusetts, 03110, United States

Location

Quest Research Institute- Site Number : 8400010

Farmington Hills, Michigan, 48334, United States

Location

Alliance for Multispeciality Research - Kansas City- Site Number : 8400019

Kansas City, Missouri, 64114, United States

Location

AMR Las Vegas - Site Number : 8400016

Las Vegas, Nevada, 89119, United States

Location

Coastal Carolina Research Center - North Charleston- Site Number : 8400002

North Charleston, South Carolina, 29405, United States

Location

Alliance for Multispeciality Research - Knoxville- Site Number : 8400017

Knoxville, Tennessee, 37920, United States

Location

Charlottesville Medical Research- Site Number : 8400004

Charlottesville, Virginia, 22911, United States

Location

Investigational Site Number : 0360001

Botany, New South Wales, 2019, Australia

Location

Investigational Site Number : 0360003

Bayswater, Victoria, 3153, Australia

Location

Investigational Site Number : 0360002

Melbourne, Victoria, 3124, Australia

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

RNA, Messenger; Hemagglutinins; Vaccines; Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

RNA; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides; Agglutinins; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Coagulants; Hematologic Agents; Therapeutic Uses; Biological Products; Complex Mixtures; Viral Vaccines

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Modified double-blind (participants; sites, except for those preparing/administering study intervention; and Sponsor will be blinded. Sponsor's internal safety monitoring team could be unblinded if necessary)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation with sequential enrollment of sentinel cohorts followed by parallel enrollment of the main cohort.

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: December 20, 2024
• Study Start: January 6, 2025
• Primary Completion: April 16, 2026
• Study Completion: April 16, 2026
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (21); AU (3)