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

Phase 1

Recruiting

• Conditions: Influenza; Healthy Volunteers
• Interventions: Biological: Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1; Biological: TIV mRNA-HA Vaccine 2; Biological: Quadrivalent Influenza Standard Dose Vaccine; Biological: Quadrivalent Influenza Vaccine High Dose; Biological: TIV mRNA-neuraminidase (NA)

• Registration Number: NCT06744205
• Lead Sponsor: Sanofi Pasteur, a Sanofi Company

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.

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 Timeline

• Study First Submitted: 2024-12-16
• Study First Submitted QC: 2024-12-19
• Study First Posted: 2024-12-20
• Study Start: 2025-01-06
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-04
• Primary Completion: 2026-05-01
• Study Completion: 2026-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1158

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 - Hexavalent (Combination 1)	Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 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)
Group 1 - Hexavalent (Combination 1)	TIV mRNA-neuraminidase (NA)	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)
Group 2 - Hexavalent (Combination 2)	Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 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 2)
Group 2 - Hexavalent (Combination 2)	TIV mRNA-neuraminidase (NA)	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)
Group 3 - Hexavalent (Combination 3)	Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 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 3)
Group 3 - Hexavalent (Combination 3)	TIV mRNA-neuraminidase (NA)	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)
Group 4 - Hexavalent (Combination 4)	Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 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 4)
Group 4 - Hexavalent (Combination 4)	TIV mRNA-neuraminidase (NA)	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)
Group 5 - Hexavalent (Combination 5)	Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 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 5)
Group 5 - Hexavalent (Combination 5)	TIV mRNA-neuraminidase (NA)	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)
Group 6 - Hexavalent (Combination 6)	Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 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 6)
Group 6 - Hexavalent (Combination 6)	TIV mRNA-neuraminidase (NA)	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)
Group 7 - TIV mRNA-HA Vaccine 1	Trivalent (TIV) messenger ribonucleic acid (mRNA) hemagglutinin (HA) Vaccine 1	Participants will receive a single dose of TIV mRNA-HA Vaccine 1
Group 8 - TIV mRNA-NA	TIV mRNA-neuraminidase (NA)	Participants will receive a single dose of TIV mRNA-NA
Group 9 - TIV mRNA-HA Vaccine 2	TIV mRNA-HA Vaccine 2	Participants will receive single dose of TIV mRNA-HA Vaccine 2
Group 10 - QIV-SD	Quadrivalent Influenza Standard Dose Vaccine	Participants will receive single dose of QIV-SD vaccine (for participants 50 to 64 years of age only)
Group 11 - QIV-HD	Quadrivalent Influenza Vaccine High Dose	Participants will receive single dose of QIV-HD vaccine

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (24)

Accel Research Sites Network - Birmingham- Site Number : 8400008; 🇺🇸 Birmingham, Alabama, United States

AMR Mobile- Site Number : 8400022; 🇺🇸 Mobile, Alabama, United States

Alliance for Multispeciality Research - Clinical Research Consortium- Site Number : 8400015; 🇺🇸 Tempe, Arizona, United States

AMR Miami- Site Number : 8400021; 🇺🇸 Coral Gables, Florida, United States

Accel Research Sites Network - DeLand Clinical Research Unit- Site Number : 8400003; 🇺🇸 DeLand, Florida, United States

Alliance for Multispeciality Research - Fort Myers- Site Number : 8400013; 🇺🇸 Fort Myers, Florida, United States

Accel Research Sites - Maitland- Site Number : 8400007; 🇺🇸 Maitland, Florida, United States

Innovation Medical Research Center - Palmetto Bay- Site Number : 8400011; 🇺🇸 Palmetto Bay, Florida, United States

Accel Research Site - NeuroStudies.net, LLC - ERN - PPDS- Site Number : 8400001; 🇺🇸 Decatur, Georgia, United States

AMR - Chicago- Site Number : 8400012; 🇺🇸 Oak Brook, Illinois, United States

Alliance for Multispeciality Research - Newton- Site Number : 8400020; 🇺🇸 Newton, Kansas, United States

Alliance for Multispeciality Research - Wichita East- Site Number : 8400014; 🇺🇸 Wichita, Kansas, United States

Alliance for Multispeciality Research - Lexington- Site Number : 8400018; 🇺🇸 Lexington, Kentucky, United States

Boston Clinical Trials- Site Number : 8400009; 🇺🇸 Boston, Massachusetts, United States

ActivMed Practices & Research - Methuen- Site Number : 8400005; 🇺🇸 Methuen, Massachusetts, United States

Quest Research Institute- Site Number : 8400010; 🇺🇸 Farmington Hills, Michigan, United States

Alliance for Multispeciality Research - Kansas City- Site Number : 8400019; 🇺🇸 Kansas City, Missouri, United States

AMR Las Vegas - Site Number : 8400016; 🇺🇸 Las Vegas, Nevada, United States

Coastal Carolina Research Center - North Charleston- Site Number : 8400002; 🇺🇸 North Charleston, South Carolina, United States

Alliance for Multispeciality Research - Knoxville- Site Number : 8400017; 🇺🇸 Knoxville, Tennessee, United States

Charlottesville Medical Research- Site Number : 8400004; 🇺🇸 Charlottesville, Virginia, United States

Investigational Site Number : 0360001; 🇦🇺 Botany, New South Wales, Australia

Investigational Site Number : 0360003; 🇦🇺 Bayswater, Victoria, Australia

Investigational Site Number : 0360002; 🇦🇺 Melbourne, Victoria, Australia