A Study of mRNA-1010 Seasonal Influenza Vaccine in Adults

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the humoral immunogenicity of mRNA-1010 relative to that of an active comparator against vaccine-matched influenza A and B strains at Day 29, and to evaluate the safety and reactogenicity of mRNA-1010.

Official Title
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A Phase 3, Randomized, Stratified, Observer-blind, Active-Controlled Study to Evaluate the Immunogenicity and Safety of mRNA-1010 Seasonal Influenza Vaccine in Adults 18 Years and Older

Conditions
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Seasonal Influenza

Intervention / Treatment
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* Biological: mRNA-1010
* Biological: Licensed quadrivalent inactivated seasonal influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Investigator has assessed that the participant understands and is willing and physically able to comply with protocol mandated follow-up, including all procedures. For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, and agreement to continue adequate contraception through 90 days following vaccine administration. Exclusion Criteria: Participant has had close contact to someone with SARS-CoV-2 infection or COVID-19 as defined by the United States (US) CDC or has had a positive SARS-CoV-2 test in the past 10 days prior to the Screening Visit. Participant is acutely ill or febrile (temperature ≥38.0℃ [100.4°F]) 72 hours prior to or at the Screening Visit or Day 1. Participants meeting this criterion may be rescheduled within the 28-day screening window and will retain their initially assigned participant number. Participant has a history of a diagnosis or condition that, in the judgment of the investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any mRNA or influenza vaccines or any components of the mRNA or influenza vaccines, including egg protein. Participant has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 180 days prior to the Screening Visit (for corticosteroids, ≥10 mg/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study. Inhaled, nasal, and topical steroids are allowed. Participant has received any vaccine authorized or approved by local health agency ≤28 days prior to study injection (Day 1) or plans to receive a vaccine authorized or approved by local health agency within 28 days before or after the study injection. Participant is not aware whether they have received an influenza vaccine in the past 12 months or has received a seasonal influenza vaccine or any other investigational influenza vaccine within 180 days prior to Day 1. Participant has tested positive for influenza by local health authority-approved testing methods within 180 days prior to the Screening Visit. Participant has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit or plans to donate blood products during the study. Note: Other inclusion and exclusion criteria may apply.

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: mRNA-1010<br>Participants will receive a single dose of mRNA-1010 by intramuscular (IM) injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Active Comparator: Licensed Quadrivalent Inactivated Seasonal Influenza Vaccine<br>Participants will receive a single dose of licensed quadrivalent inactivated seasonal influenza vaccine by IM injection on Day 1. | Biological: Licensed quadrivalent inactivated seasonal influenza vaccine<br>* Sterile suspension for injection<br>* Other names: Fluarix Tetra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of Anti-Hemagglutinin (HA) Antibodies at Day 29, as Measured by Hemagglutination Inhibition (HAI) Assay |  | Day 29 | 
| Percentage of Participants Reaching Seroconversion, as Measured by HAI Assay | Seroconversion is defined as either a pre-vaccination HAI titer <1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination HAI titer ≥1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer. | Day 29 | 
| Number of Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) |  | Up to Day 7 (7 days after vaccination) | 
| Number of Unsolicited Adverse Events (AEs) |  | Up to Day 28 (28 days after vaccination) | 
| Number of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), Medically Attended Adverse Events (MAAEs), and AEs Leading to Discontinuation |  | Day 1 through Day 361 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With First Episode of Reverse Transcription Polymerase Chain Reaction (RT-PCR)-Confirmed Protocol-Defined Influenza-Like Illness (ILI) | A protocol-defined ILI is determined by the occurrence of at least 1 respiratory illness symptom concurrently with at least 1 systemic symptom (Body temperature >37.2 degrees celsius (°C) [> 99 degrees fahrenheit {°F}]; Chills; Tiredness; Headache; Myalgia; Nausea/vomiting; Diarrhea), or the occurrence of any 2 or more respiratory symptoms (Sore throat; Cough/rhinorrhea/nasal congestion [≥ 1 of the 3 symptoms count as 1 respiratory symptom]; Sputum production; Wheezing; Difficulty breathing). Protocol-defined ILI caused by any strain of influenza virus regardless of antigenic match to the strains selected for seasonal vaccine will be reported. | 14 days post-vaccination through Day 181 | 
| Number of Participants With First Episode of RT-PCR Confirmed Centers for Disease Control and Prevention (CDC)-Defined ILI | A CDC-defined ILI is defined as body ≥37.8°C (100°F) accompanied by cough and/or sore throat. CDC-defined ILI caused by any strain of influenza virus regardless of antigenic match to the strains selected for seasonal vaccine will be reported. | 14 days post-vaccination through Day 181 | 
| Number of Participants With First Episode of RT-PCR-Confirmed Protocol-Defined ILI in Participants Aged 50 Years and Older or 65 Years and Older | A protocol-defined ILI is determined by the occurrence of at least 1 respiratory illness symptom concurrently with at least 1 systemic symptom (Body temperature >37.2°C [> 99°F]; Chills; Tiredness; Headache; Myalgia; Nausea/vomiting; Diarrhea), or the occurrence of any 2 or more respiratory symptoms (Sore throat; Cough/rhinorrhea/nasal congestion [≥ 1 of the 3 symptoms count as 1 respiratory symptom]; Sputum production; Wheezing; Difficulty breathing). Protocol-defined ILI caused by any strain of influenza virus regardless of antigenic match to the strains selected for seasonal vaccine will be reported. | 14 days post-vaccination through Day 181 | 
| Percentage of Participants With HAI Titer ≥ 1:40 at Day 29 |  | Day 29 | 
| Change From Baseline in Geometric Mean Fold Rise (GMFR) as Measured by HAI Assays |  | Baseline, Up to Day 29 |