Safety and Immunogenicity of Quadrivalent Influenza mRNA Vaccine MRT5407 in Adult Participants18 Years of Age and Older

Safety and Immunogenicity of Quadrivalent Influenza mRNA Vaccine MRT5407 in Adults Aged 18 Years and Older

The purpose of this study is to evaluate the safety and immunogenicity of a single intramuscular (IM) injection of up to 2 dose levels of Quadrivalent Influenza messenger ribonucleic acid (mRNA) Vaccine MRT5407 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: Completed
• Conditions: Influenza Immunization
• Intervention / Treatment: Biological: Quadrivalent Influenza mRNA Vaccine MRT5407; Biological: Quadrivalent Recombinant Influenza Vaccine; Biological: Quadrivalent Influenza Standard Dose Vaccine; Biological: Quadrivalent Influenza High-Dose Vaccine

Detailed Description

Study duration is approximately 12 months.

• Study Type: Interventional
• Enrollment (Actual): 560
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Barrio Sabana, Puerto Rico, 00694
    • Investigational Site Number : 6300003
  • San Juan, Puerto Rico, 00909
    • Investigational Site Number : 6300002
• United States
  • California
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates Site Number : 8400025
    • San Diego, California, United States, 92108
      • Optimal Research Site Number : 8400059
    • San Diego, California, United States, 92123-1881
      • California Research Foundation Site Number : 8400008
  • Florida
    • DeLand, Florida, United States, 32720-0834
      • Accel Clinical Research-Deland Clinical Research Unit Site Number : 8400052
    • Gainesville, Florida, United States, 32607
      • SIMEDHealth, LLC Site Number : 8400024
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center Site Number : 8400014
    • Hollywood, Florida, United States, 33024
      • Research Centers of America Site Number : 8400048
    • Miami, Florida, United States, 33135
      • Dade Research Center Site Number : 8400011
    • Miami, Florida, United States, 33135
      • Suncoast Research Group, LLC Site Number : 8400038
    • Miami, Florida, United States, 33173
      • Florida International Research Center Site Number : 8400051
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center Site Number : 8400020
  • Illinois
    • River Forest, Illinois, United States, 60305
      • DM Clinical Research - Chicago Site Number : 8400028
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Brengle Family Medicine Site Number : 8400005
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • AMR Lexington Site Number : 8400054
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • AMR Kansas City Site Number : 8400006
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research Site Number : 8400003
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center - N Charleston Site Number : 8400010
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • AMR Knoxville Site Number : 8400046
  • Texas
    • Austin, Texas, United States, 78704
      • Elligo Health Research Site Number : 8400056
    • Humble, Texas, United States, 77338
      • DM Clinical Research Site Number : 8400032
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute Site Number : 8400030
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc. Site Number : 8400026
    • Sugar Land, Texas, United States, 77478
      • DM Clinical Research - Sugar Land Site Number : 8400031

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 18 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.

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)
• Previous history of myocarditis, pericarditis, and / or myopericarditis
• 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
• 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
• Self-reported or documented seropositivity for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
• 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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Quadrivalent Influenza mRNA Vaccine MRT5407 dose level 1; participants will receive a single dose of QIV mRNA vaccine (dose level 1)	Biological: Quadrivalent Influenza mRNA Vaccine MRT5407; Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular Injection
Experimental: Group 2: Quadrivalent Influenza mRNA Vaccine MRT5407 dose level 2; participants will receive a single dose of QIV mRNA vaccine (dose level 2)	Biological: Quadrivalent Influenza mRNA Vaccine MRT5407; Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular Injection
Active Comparator: Group 3: RIV4; participants will receive a single dose of RIV4 vaccine	Biological: Quadrivalent Recombinant Influenza Vaccine; Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular Injection; Other Names: Flublok Quadrivalent®
Active Comparator: Group 4: QIV-SD; participants will receive a single dose of QIV-SD vaccine	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 5: QIV-HD; participants will receive a single dose of QIV -HD vaccine (for elderly only)	Biological: Quadrivalent Influenza High-Dose Vaccine; 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 immediate adverse events (AEs)	Unsolicited systemic AEs that occur within 30 minutes after vaccination	Within 30 minutes 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 serious adverse events (SAEs)	SAEs reported throughout the study	From Day one to Day 366
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
Individual Hemagglutination inhibition (HAI) titer	Antibody titers are expressed as GMTs at baseline and post-baseline	At Day 1 and Day 29
Percentage of participants with detectable antibody HAI titers greater than or equal to (≥) 10 [1/dil]		At Day 1 and Day 29
Individual HAI titer ratio	Ratios of antibody titers measured by HAI in each group before and after vaccination	At Day 1 and Day 29
Number of participants archiving HAI seroconversion against Antigens	Number of participants with 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
Percentage of participants with antibody HAI titers greater than or equal to (≥) 40 [1/dil]		At Day 29
Percentage of participants with 2-fold and 4-fold rise in HAI titers		At Day 1 and Day 29
Number of participants with solicited injection site and systemic reactions	Adverse reactions pre-listed in the protocol and case report form (CRF) Injection site reactions: pain, redness, swelling, hardening, bruising Systemic reactions: fever, headache, malaise, myalgia, arthralgia, chills	Up to 7 days after injection
Number of participants with medically attended adverse events (MAAE)s	AEs with a new onset or a worsening of a condition that prompts the participant or participant to seek unplanned medical advice at a physician's office or Emergency Department	Up to 28 days after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual HAI Ab titer ratio		Day 1, Day 91, Day 181 and Day 366
Neutralizing Ab titers	Neutralizing Ab titers expressed as GMTs	At Day 1 and Day 29
Individual neutralizing antibodies titer ratio		At Day 1 and Day 29
Percentage of participants with 2-fold and 4-fold increase in neutralizing titers		At Day 1 and Day 29
Percentage of participants with antibody HAI titers greater than or equal to (≥) 40 [1/dil]		At Day 91, Day 181 and Day 366
Individual neutralizing Ab titer ratio		Day 1, Day 91, Day 181 and Day 366

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): October 3, 2022
• Primary Completion (Actual): January 19, 2024
• Study Completion (Actual): January 19, 2024

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 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: VAV00002; U1111-1271-1302 (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
• product manufactured in and exported from the U.S.: Yes