A Study of mRNA-1011.1, mRNA-1011.2, and mRNA-1012.1 Candidate Seasonal Influenza Vaccines in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this study is to measure the safety and the immune response to 3 next-generation influenza vaccine candidates (mRNA-1011.1, mRNA-1011.2, and mRNA-1012.1) compared with influenza vaccine candidate mRNA-1010 controls in healthy adult participants.

Official Title
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A Phase 1/2, Randomized, Open-Label Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1011.1, mRNA-1011.2, and mRNA-1012.1 Candidate Seasonal Influenza Vaccines in Healthy Adults 50 to 75 Years of Age

Conditions
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Seasonal Influenza

Intervention / Treatment
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* Biological: mRNA-1011.1
* Biological: mRNA-1011.2
* Biological: mRNA-1012.1
* Biological: mRNA-1010
* Biological: mRNA-1010.2
* Biological: mRNA-1010.3


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body mass index of 18 kilograms (kg)/square meter (m^2) to 35 kg/m^2 (inclusive) at the Screening Visit. 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, agreement to continue adequate contraception through 3 months following vaccine administration, and not currently breastfeeding. Key Exclusion Criteria: Participant is acutely ill or febrile (temperature ≥38.0 degrees Celsius [°C]/100.4 degrees Fahrenheit [°F]) 72 hours prior to or at the Screening Visit or Day 1. Any medical, psychiatric, or occupational condition, including reported history of substance abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results. Participant has received systemic immunosuppressants for >14 days in total within 180 days prior to the Randomization Visit (for glucocorticosteroids ≥10 milligrams [mg]/day of prednisone equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study (including intra-articular steroid injections). Inhaled, nasal, and topical steroids are allowed. Participant has received or plans to receive any licensed or authorized vaccine, including COVID-19 vaccines, ≤28 days prior to the study injection (Day 1) or plans to receive a licensed or authorized vaccine within 28 days after the study injection. Participant has received a seasonal influenza vaccine or any other influenza vaccine within 180 days prior to the Randomization Visit. Participant tested positive for influenza by local health authority-approved testing methods within 180 days prior to the Randomization Visit. Participant has had close contact to someone with or been diagnosed themselves with respiratory syncytial virus or SARS-CoV-2 infection as defined by the Centers for Disease Control and Prevention (CDC) in the past 10 days prior to the Randomization Visit. Participant has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Randomization Visit or plans to donate blood products during the study. Note: Other inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1011.1<br>Participants will receive mRNA-1011.1 by intramuscular (IM) injection on Day 1. | Biological: mRNA-1011.1<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Experimental: mRNA-1011.2<br>Participants will receive mRNA-1011.2 by IM injection on Day 1. | Biological: mRNA-1011.2<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Experimental: mRNA-1012.1 Dose Level A<br>Participants will receive mRNA-1012.1 at dose level A by IM injection on Day 1. | Biological: mRNA-1012.1<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Experimental: mRNA-1012.1 Dose Level B<br>Participants will receive mRNA-1012.1 at dose level B by IM injection on Day 1. | Biological: mRNA-1012.1<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Active Comparator: mRNA-1010<br>Participants will receive mRNA-1010 by IM injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Active Comparator: mRNA-1010.2<br>Participants will receive mRNA-1010.2 by IM injection on Day 1. | Biological: mRNA-1010.2<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Active Comparator: mRNA-1010.3<br>Participants will receive mRNA-1010.3 by IM injection on Day 1. | Biological: mRNA-1010.3<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|

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 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 Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation of Study |  | Day 1 through Day 181 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Geometric Mean Titer (GMT) of Anti-Hemagglutinin (HA) Antibodies at Day 29, as Measured by Hemagglutination Inhibition (HAI) Assay |  | Baseline (Day 1), Day 29 | 
| Change From Baseline in Geometric Mean Fold-Rise (GMFR) of Anti-HA Antibodies at Day 29, as Measured by HAI Assay |  | Baseline (Day 1), Day 29 | 
| Percentage of Participants With Seroconversion, as Measured by HAI Assay | Seroconversion is defined as a Day 29 titer ≥1:40 if baseline is <1:10 or a 4-fold or greater rise if baseline is ≥1:10 in anti-HA antibodies measured by HAI assay. | Baseline (Day 1) to Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza vaccine, mRNA-1010, mRNA-1011.1, mRNA-1011.2, mRNA-1012.1, Moderna