A Study of mRNA-1010 Seasonal Influenza Vaccine in Adults 50 Years Old and Older

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of mRNA-1010 in preventing seasonal influenza in adults 50 years and older.

Official Title
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A Phase 3, Randomized, Observer-blind, Active-controlled Study to Evaluate the Safety and Efficacy of mRNA-1010 Candidate Seasonal Influenza Vaccine in Adults 50 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 the first dose on Day 1, and agreement to continue adequate contraception through 90 days following vaccine administration. Exclusion Criteria: Participant has had close contact with someone with laboratory-confirmed influenza infection or with someone who has been treated with antiviral therapies for influenza (for example, Tamiflu®) within the past 5 days prior to the Screening visit. Participant has had close contact to someone with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or COVID-19 as defined by the 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℃elcius [100.4°Fahrenheit]) 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. 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 congenital or acquired immunodeficiency, immunocompromising/ immunosuppressive condition, asplenia, or recurrent severe infections. 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 immunosuppressant drugs for >14 days in total within 180 days prior to the Screening visit (for glucocorticosteroids, ≥10 milligrams (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 intervention (Day 1) or plans to receive a vaccine authorized or approved by local health agency within 28 days before or after the study intervention. Participant is unaware whether they have received an influenza vaccine in the previous influenza season. Participant 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 Day 1. 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: 50 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: Triple


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 |
| --- | --- | --- |
| Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) |  | Up to Day 7 (7 days after vaccination) | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 28 (28 days after vaccination) | 
| Number of Participants with 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 | 
| Time to First Episode of Reverse Transcription Polymerase Chain Reaction (RT-PCR) Confirmed Protocol-Defined Influenza-Like Illness (ILI) Caused by Any Influenza A or B Virus Strains |  | 14 days post-vaccination through Day 181 or end of influenza season, whichever ends later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Episode of RT-PCR Confirmed Protocol-Defined ILI Caused by Any Influenza A or B Virus Strains with Similarity to the Vaccine Strains | Similarity to strains selected for the seasonal vaccine will be determined by antigenicity testing and/or genomic sequencing. | 14 days post-vaccination through Day 181 or end of influenza season, whichever ends later | 
| Time to First Episode of RT-PCR Confirmed Protocol-Defined ILI Caused by Any Influenza A or B Virus Strains Antigenically Matched to the Vaccine Strains | Antigenically matched to strains selected for the seasonal vaccine will be determined by antigenicity testing. | 14 days post-vaccination through Day 181 or end of influenza season, whichever ends later | 
| Time to First Episode of RT-PCR Confirmed United States (US) Centers for Disease Control and Prevention (CDC)-Defined ILI Caused by Any Influenza A or B Virus Strains | Any strains include any influenza A or B strains, influenza A or B strains with similarity to vaccine strains and influenza A or B strains that are antigenically matched to vaccine strains. Antigenically matched to strains selected for the seasonal vaccine will be determined by antigenicity testing. | 14 days post-vaccination through Day 181 or end of influenza season, whichever ends later | 
| Time to First Episode of Culture-Confirmed Protocol-Defined ILI Caused by Any Influenza A or B | Any influenza A or B strains regardless of antigenic match to strains selected for the seasonal vaccine. A positive result for influenza infection by viral culture is needed, following a positive result for influenza infection by RT-PCR. | 14 days post-vaccination through Day 181 or end of influenza season, whichever ends later | 
| Time to First Episode of Culture-Confirmed CDC-Defined ILI Caused by Any Influenza A or B | Any influenza A or B strains regardless of antigenic match to strains selected for the seasonal vaccine. A positive result for influenza infection by viral culture is needed, following a positive result for influenza infection by RT-PCR | 14 days post-vaccination through Day 181 or end of influenza season, whichever ends later | 
| Number of Participants With Hospitalizations Associated With RT-PCR Confirmed Protocol-Defined ILI |  | 14 days post-vaccination through Day 181 or end of influenza season, whichever ends later | 
| Geometric Mean Titer (GMT) as Measured by Hemagglutination Inhibition (HAI) Assay |  | Day 29 | 
| Number of Participants Reaching Seroconversion as measured by HAI Assay | Seroconversion is defined as either a prevaccination HAI titer <1:10 and a postvaccination titer ≥1:40 or a prevaccination HAI titer ≥1:10 and a minimum 4-fold rise in postvaccination HAI antibody titer. | Day 29 | 
| Number of Participants with a Titer ≥1:40 as Measured by HAI Assay |  | Day 29 | 
| Change from Baseline in Geometric Mean Fold Rise (GMFR) at Day 29 as Measured by HAI Assay |  | Baseline, Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Flu, Influenza, Vaccine, mRNA vaccine, mRNA-1010, Moderna