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

NCT06361875 | Completed Phase 1 FDA Drug

• 2 other identifiers: VAV00045U1111-1295-2852
• Study Type: interventional
• Target: 910
• Locations: 3 countries
• Sites: 20

Brief Summary

The purpose of this study is 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.

Conditions

Influenza Immunization

Outcome Measures

Primary Outcomes (13)

• 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

  Adverse reactions pre-listed in the protocol and case report form (CRF) Injection site reactions: Injection site pain, Injection site erythema, and Injection site swelling

  Up to 7 days after injection

• Number of participants with solicited systemic reactions

  Adverse reactions pre-listed in the protocol and case report form (CRF) Systemic reactions: fever, headache, fatigue, myalgia, arthralgia, chills

  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)

  SAEs reported throughout the study

  Throughout the study (approximately 12 months)

• AESIs reported throughout the study

  AESIs reported throughout the study (approximately 12 months)

  AESIs reported throughout the study (approximatley 12 months)

• Number of participants with adverse events of special interests (AESIs)

  AESIs reported throughout the study

  Throughout the study (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

• Geometric Mean Titer (GMT)

  Hemagglutinin inhibition (HAI) antibody (Ab) titers at D01 and D29

  At Day 1 and Day 29

• Geometric Mean of individual Titer Ratio (GMTR)

  Individual HAI Ab titer ratio D29/D01

  At Day 1 and Day 29

• Seroconversion

  Number of participants with HAI Ab titer \< 10 \[1/dil\] at Day 1 and post-vaccination titer ≥ 40 \[1/dil\] at Day 29, or titer ≥ 10 \[1/dil\] at Day 1 and a ≥ 4-fold-rise 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

  Day 29

Secondary Outcomes (3)

• Neutralizing Ab titers at D01 and D29

  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 through Day 29

Study Arms (10)

Quadrivalent Influenza mRNA Vaccine MRT5421 Dose 1

EXPERIMENTAL

participants will receive a single dose of QIV mRNA vaccine MRT5421

Biological: Quadrivalent Influenza mRNA Vaccine MRT5421

Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 1

EXPERIMENTAL

participants will receive a single dose of QIV mRNA vaccine MRT5429

Biological: Quadrivalent Influenza mRNA Vaccine MRT5429

Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 2

EXPERIMENTAL

participants will receive a single dose of QIV mRNA vaccine MRT5429

Biological: Quadrivalent Influenza mRNA Vaccine MRT5429

Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 3

EXPERIMENTAL

participants will receive a single dose of QIV mRNA vaccine MRT5429

Biological: Quadrivalent Influenza mRNA Vaccine MRT5429

Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 4

EXPERIMENTAL

participants will receive a single dose of QIV mRNA vaccine MRT5429

Biological: Quadrivalent Influenza mRNA Vaccine MRT5429

Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 1

EXPERIMENTAL

participants will receive a single dose of QIV mRNA vaccine MRT5424

Biological: Quadrivalent Influenza mRNA Vaccine MRT5424

Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 2

EXPERIMENTAL

participants will receive a single dose of QIV mRNA vaccine MRT5424

Biological: Quadrivalent Influenza mRNA Vaccine MRT5424

Quadrivalent Influenza SD Vaccine

ACTIVE COMPARATOR

participants will receive a single dose of QIV-SD vaccine

Biological: Quadrivalent Influenza Standard Dose Vaccine

Quadrivalent Influenza HD Vaccine

ACTIVE COMPARATOR

participants will receive a single dose of QIV -HD vaccine (for adults ≥ 65 years of age only)

Biological: Quadrivalent Influenza High-Dose Vaccine

Quadrivalent Influenza RIV4 Vaccine

ACTIVE COMPARATOR

participants will receive a single dose of RIV4 vaccine

Biological: Quadrivalent Recombinant Influenza Vaccine

Interventions

Quadrivalent Influenza mRNA Vaccine MRT5421 BIOLOGICAL

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

Quadrivalent Influenza mRNA Vaccine MRT5421 Dose 1

Quadrivalent Influenza mRNA Vaccine MRT5424 BIOLOGICAL

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

Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 1; Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 2

Quadrivalent Influenza mRNA Vaccine MRT5429 BIOLOGICAL

Pharmaceutical form:solution in a vial-Route of administration:Intramuscular Injection

Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 1; Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 2; Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 3; Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 4

Quadrivalent Influenza Standard Dose Vaccine BIOLOGICAL

Pharmaceutical form: suspension for injection in prefilled syringe -Route of administration:Intramuscular injection

Also known as: Fluzone Qudrivalent®

Quadrivalent Influenza SD Vaccine

Quadrivalent Influenza High-Dose Vaccine BIOLOGICAL

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

Also known as: Fluzone High-Dose Quadrivalent®

Quadrivalent Influenza HD Vaccine

Quadrivalent Recombinant Influenza Vaccine BIOLOGICAL

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

Also known as: Flublok Quadrivalent®

Quadrivalent Influenza RIV4 Vaccine

Eligibility Criteria

• Age: 18 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 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.

You may not qualify if:

• 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
• 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 judgment) 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
• 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (20)

Long Beach Clinical Trials Site Number : 8400013

Long Beach, California, 90806, United States

Location

California Research Foundation Site Number : 8400038

San Diego, California, 92123-1881, United States

Location

Accel Clinical Research-Deland Clinical Research Unit- Site Number : 8400001

DeLand, Florida, 32720-0834, United States

Location

SIMEDHealth, LLC- Site Number : 8400011

Gainesville, Florida, 32607, United States

Location

Indago Research and Health Center- Site Number : 8400032

Hialeah, Florida, 33012, United States

Location

Cenexel Research Centers of America- Site Number : 8400037

Hollywood, Florida, 33024, United States

Location

Suncoast Research Group, LLC- Site Number : 8400015

Miami, Florida, 33135, United States

Location

Brengle Family Medicine Site Number : 8400045

Indianapolis, Indiana, 46260, United States

Location

AMR Lexington- Site Number : 8400042

Lexington, Kentucky, 40509, United States

Location

Velocity Clinical Research- New Orleans Site Number : 8400053

New Orleans, Louisiana, 70119, United States

Location

The Alliance for Multispecialty Research - KCM, LLC- Site Number : 8400034

Kansas City, Missouri, 64114, United States

Location

Velocity Clinical Research Norfolk- Site Number : 8400046

Norfolk, Nebraska, 68701, United States

Location

Velocity Clinical Research, Omaha- Site Number : 8400008

Omaha, Nebraska, 68134, United States

Location

Rochester Clinical Research. Inc.- Site Number : 8400005

Rochester, New York, 14609, United States

Location

Coastal Carolina Research Center- Site Number : 8400014

North Charleston, South Carolina, 29405, United States

Location

AMR Knoxville- Site Number : 8400043

Knoxville, Tennessee, 37909, United States

Location

Clinical Trials of Texas, Inc. - PPDS- Site Number : 8400029

San Antonio, Texas, 78229, United States

Location

Cenexel JBR- Site Number : 8400051

Salt Lake City, Utah, 84107, United States

Location

Investigational Site Number : 3400001

San Pedro Sula, 21104, Honduras

Location

Investigational Site Number : 6300002

Barrio Sabana, 00694, Puerto Rico

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

Vaccines; Influenza Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures; Viral Vaccines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Modified double-blind (Participants; Sites except for those preparing/administering study intervention; Sponsor's except Sponsor unblinded internal safety review committee)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel with dose escalation for sentinel cohort

Study Record Dates

• First Submitted: April 4, 2024
• First Posted: April 12, 2024
• Study Start: April 1, 2024
• Primary Completion: June 9, 2025
• Study Completion: June 9, 2025
• Last Updated: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

US (18); PR (1); HO (1)