A Study to Evaluate a Modified RNA Vaccine Against Influenza in Adults 18 Years of Age or Older

Study Overview
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Brief Summary
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This is a Phase 3, randomized, observer-blinded study to evaluate the efficacy, safety, tolerability, and immunogenicity of a single dose of a quadrivalent influenza modRNA vaccine compared to licensed inactivated influenza vaccine in healthy adults 18 years of age and older.

Detailed Description
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This is a Phase 3, randomized, observer-blinded study to evaluate the efficacy, safety, tolerability, and immunogenicity of a quadrivalent influenza modRNA vaccine (qIRV) encoding HA of 4 seasonally recommended strains (2 A strains and 2 B strains) compared to licensed quadrivalent influenza vaccine (QIV) in healthy adults 18 years of age and older. Participants may be enrolled in either the reactogenicity subset, immunogenicity subset, or both/neither subset(s). Efficacy will be assessed in this study through surveillance for influenza-like illness.

Official Title
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A PHASE 3, RANDOMIZED, OBSERVER-BLINDED STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MODIFIED RNA VACCINE AGAINST INFLUENZA COMPARED TO LICENSED INACTIVATED INFLUENZA VACCINE IN HEALTHY ADULTS 18 YEARS OF AGE OR OLDER

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: Quadrivalent influenza modRNA vaccine
* Biological: Quadrivalent influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants ≥18 years of age at Visit 1 (Day 1). Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures. Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study. Capable of giving signed informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Exclusion Criteria: Medical or psychiatric condition, including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality, that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s). Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection. Allergy to egg proteins (egg or egg products) or chicken proteins. Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), eg, for cancer or an autoimmune disease, or planned receipt throughout the study. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted. Receipt of blood/plasma products or immunoglobulin from 60 days before study intervention administration, or planned receipt throughout the study. Vaccination with any investigational or licensed influenza vaccine within 6 months (175 days) before study intervention administration, or ongoing receipt of chronic antiviral therapy with activity against influenza. Any participant who has received or plans to receive a modRNA-platform SARS CoV-2 vaccine within 14 days before or after study vaccination at Visit 1. Participation in other studies involving administration of a study intervention within 28 days prior to, and/or during, participation in this study. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quadrivalent influenza modRNA vaccine, 18 through 64 years of age<br>Quadrivalent influenza modRNA vaccine (single dose), participants 18 through 64 years of age | Biological: Quadrivalent influenza modRNA vaccine<br>* Quadrivalent influenza modRNA vaccine (single dose)<br>|
| Active Comparator: Quadrivalent influenza vaccine, 18 through 64 years of age<br>Licensed quadrivalent influenza vaccine (single dose), participants 18 through 64 years of age | Biological: Quadrivalent influenza vaccine<br>* Licensed quadrivalent influenza vaccine (single dose)<br>|
| Experimental: Quadrivalent influenza modRNA vaccine, ≥65 years of age<br>Quadrivalent influenza modRNA vaccine (single dose), participants ≥65 years of age | Biological: Quadrivalent influenza modRNA vaccine<br>* Quadrivalent influenza modRNA vaccine (single dose)<br>|
| Active Comparator: Quadrivalent influenza vaccine, ≥65 years of age<br>Licensed quadrivalent influenza vaccine (single dose), participants ≥65 years of age | Biological: Quadrivalent influenza vaccine<br>* Licensed quadrivalent influenza vaccine (single dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants reporting laboratory-confirmed influenza (LCI) cases with associated per-protocol influenza-like illness (ILI) in each vaccine group, 18 through 64 years of age | As measured at the central laboratory | At least 14 days after vaccination | 
| The proportion of participants reporting laboratory-confirmed influenza (LCI) cases with associated per-protocol influenza-like illness (ILI) in each vaccine group, ≥65 years of age | As measured at the central laboratory | At least 14 days after vaccination | 
| Percentage of participants reporting local reactions, 18 through 64 years of age and ≥65 years of age separately | Pain at the injection site, redness, and swelling | For up to 7 days following vaccination | 
| Percentage of participants reporting systemic events, 18 through 64 years of age and ≥65 years of age separately | Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain | For up to 7 days following vaccination | 
| Percentage of participants reporting adverse events, 18 through 64 years of age and ≥65 years of age separately and combined | As elicited by investigational site staff | From the time the participant provides informed consent through 4 weeks after vaccination | 
| Percentage of participants reporting serious adverse events, 18 through 64 years of age and ≥65 years of age separately and combined | As elicited by investigational site staff | From the time the participant provides informed consent through 6 months after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants reporting LCI cases with associated per-protocol ILI caused by all matched strains, each matched strain, or unmatched strains in each vaccine group, 18 through 64 years of age and ≥65 years of age separately | As measured at the central laboratory | At least 14 days after vaccination | 
| The proportion of participants reporting culture-confirmed influenza (CCI) cases with associated per-protocol ILI in each vaccine group, 18 through 64 years of age and ≥65 years of age separately | As measured at the central laboratory | At least 14 days after vaccination | 
| The proportion of participants reporting LCI associated with ILI, as defined by applying a modified CDC definition, in each vaccine group, 18 through 64 years of age and ≥65 years of age separately | As measured at the central laboratory | At least 14 days after vaccination | 
| The proportion of participants reporting LCI cases associated with ILI, as defined by applying the WHO definition, in each vaccine group, 18 through 64 years of age and ≥65 years of age separately | As measured at the central laboratory | At least 14 days after vaccination | 
| The proportion of participants reporting cases of influenza, as confirmed by central RT-PCR, local RT-PCR or culture, with associated per-protocol ILI in each vaccine group, 18 through 64 years of age and ≥65 years of age separately | As measured at the central laboratory | At least 14 days after vaccination | 
| Geometric mean ratio (GMR) of hemagglutination inhibition (HAI) titers for each strain in qIRV recipients compared to QIV recipients, 18 through 64 and ≥65 years of age separately | As measured at the central laboratory | 4 weeks after vaccination | 
| Difference in percentage of participants achieving seroconversion for each strain between qIRV recipients and QIV recipients, 18 through 64 and ≥65 years of age separately | As measured at the central laboratory | 4 weeks after vaccination | 
| HAI geometric mean titers (GMTs) for each strain, 18 through 64 years of age and ≥65 years of age separately | As measured at the central laboratory | 4 weeks after vaccination | 
| HAI geometric mean fold rise (GMFR) for each strain, 18 through 64 years of age and ≥65 years of age separately | As measured at the central laboratory | 4 weeks after vaccination | 
| The proportion of participants achieving HAI seroconversion for each strain, 18 through 64 years of age and ≥65 years of age separately | As measured at the central laboratory | 4 weeks after vaccination | 
| The proportion of participants with HAI titers ≥1:40 for each strain, 18 through 64 years of age and ≥65 years of age separately | As measured at the central laboratory | Baseline and 4 weeks after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Grippe, Flu, Influenza, Vaccine, RNA vaccine