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 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.

Study Overview

• Status: Recruiting
• Conditions: 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 is 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 (Estimated): 1002
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Puerto Rico
  • Barrio Sabana, Puerto Rico, 00694
    • Recruiting
    • Investigational Site Number : 6300002
• United States
  • California
    • La Mesa, California, United States, 91942
      • Recruiting
      • Velocity Clinical Research Site Number : 8400048
    • San Diego, California, United States, 92123-1881
      • Recruiting
      • California Research Foundation Site Number : 8400038
  • Florida
    • DeLand, Florida, United States, 32720-0834
      • Recruiting
      • Accel Clinical Research-Deland Clinical Research Unit Site Number : 8400001
    • Hialeah, Florida, United States, 33012
      • Recruiting
      • Indago Research and Health Center Site Number : 8400032
    • Hollywood, Florida, United States, 33024
      • Recruiting
      • Research Centers of America Site Number : 8400037
    • Miami, Florida, United States, 33135
      • Recruiting
      • Suncoast Research Group, LLC Site Number : 8400015
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • Brengle Family Medicine Site Number : 8400045
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Recruiting
      • AMR Lexington Site Number : 8400042
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Recruiting
      • Velocity Clinical Research Site Number : 8400053
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Recruiting
      • Optimal Research, LLC Rockville Site Number : 8400025
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Recruiting
      • The Alliance for Multispecialty Research - KCM, LLC Site Number : 8400034
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Recruiting
      • Velocity Clinical Research Norfolk Site Number : 8400046
    • Omaha, Nebraska, United States, 68134
      • Recruiting
      • Velocity Clinical Research, Omaha Site Number : 8400008
  • New York
    • Rochester, New York, United States, 14609
      • Recruiting
      • Rochester Clinical Research. Inc. Site Number : 8400005
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Recruiting
      • Aventiv Research Columbus Site Number : 8400020
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Recruiting
      • Coastal Carolina Research Center Site Number : 8400014
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Recruiting
      • AMR Knoxville Site Number : 8400043
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Clinical Trials of Texas, Inc. - PPDS Site Number : 8400029
    • Tomball, Texas, United States, 77375
      • Recruiting
      • DM Clinical Research/Pediatric Healthcare of Northwest Houston Site Number : 8400056
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Recruiting
      • JBR Clinical Research 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 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 before the 1st dose of study intervention Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply:
• 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, 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.

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 will receive 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 will receive 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 will receive 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 will receive 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 will receive 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 will receive 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 will receive 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 will receive 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 will receive 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 will receive 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 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 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 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)
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): May 22, 2025
• Study Completion (Estimated): May 22, 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): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; 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