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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
Study duration is approximately 12 months.

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Sentinel Cohort: Open label Main Cohort: Open label (Sponsor, except laboratory testing personnel) Blinded (Sites, except for those preparing/administering study intervention)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Quadrivalent Influenza mRNA Vaccine MRT5407 dose level 1<br>participants will receive a single dose of QIV mRNA vaccine (dose level 1) | Biological: Quadrivalent Influenza mRNA Vaccine MRT5407<br>* Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular Injection<br>|
| Experimental: Group 2: Quadrivalent Influenza mRNA Vaccine MRT5407 dose level 2<br>participants will receive a single dose of QIV mRNA vaccine (dose level 2) | Biological: Quadrivalent Influenza mRNA Vaccine MRT5407<br>* Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular Injection<br>|
| Active Comparator: Group 3: RIV4<br>participants will receive a single dose of RIV4 vaccine | Biological: Quadrivalent Recombinant Influenza Vaccine<br>* Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular Injection<br>* Other names: Flublok Quadrivalent®;|
| Active Comparator: Group 4: QIV-SD<br>participants will receive a single dose of QIV-SD vaccine | Biological: Quadrivalent Influenza Standard Dose Vaccine<br>* Pharmaceutical Form: Liquid suspension for injection in pre-filled syringe Route of Administration: Intramuscular Injection<br>* Other names: Fluzone Qudrivalent®;|
| Active Comparator: Group 5: QIV-HD<br>participants will receive a single dose of QIV -HD vaccine (for elderly only) | Biological: Quadrivalent Influenza High-Dose Vaccine<br>* Pharmaceutical Form: Liquid suspension for injection in pre-filled syringe Route of Administration: Intramuscular Injection<br>* 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 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 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 (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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Individual HAI Ab titer ratio |  | Day 1, Day 91, Day 181 and Day 366 | 
| 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 |