A Study of mRNA-based Influenza and SARS-CoV-2 (COVID-19) Multi-component Vaccines in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this study is to generate sufficient safety, reactogenicity, and immunogenicity data to enable selection of an mRNA-1083 vaccine composition and dose level to evaluate in a subsequent Phase 3 clinical trial in adults.

Detailed Description
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Participants will be enrolled into 1 of 2 age cohorts: Cohort A for adults ≥65 to <80 years of age or Cohort B for adults ≥18 to <65 year of age. In Cohort A, approximately 600 participants will be randomized (in equal allocation ratio) into the investigational treatment arms, stratified by influenza vaccine status in the most recent influenza season (received or not received since September 2022). In Cohort B, approximately 624 participants will be randomized (in equal allocation ratio) into the investigational treatment arms, stratified by 2 age groups: ≥18 to <50 years and ≥50 to <65 years of age and by influenza vaccine status in the most recent influenza season (received or not received since September 2022).

Official Title
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A Phase 1/2, Randomized, Observer-blind, Active-Control Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-based Influenza and SARS-CoV-2 Multi-component Vaccines in Healthy Adults

Conditions
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SARS-CoV-2, Influenza

Intervention / Treatment
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* Biological: Fluarix
* Biological: mRNA-1083.1
* Biological: mRNA-1083.2
* Biological: mRNA-1083.3
* Biological: mRNA-1010.4
* Biological: mRNA-1283.222
* Biological: mRNA-1273.222
* Biological: mRNA-1010
* Biological: Fluzone HD


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body mass index (BMI) of 18 kilograms (kg)/m2 to 35 kg/square meter (m^2) (inclusive) at the Screening Visit. Healthy as determined by medical evaluation, including medical history, physical examination, and laboratory tests. 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 90 days following vaccine administration, and not currently breastfeeding. Fully vaccinated for COVID-19 primary series according to the locally authorized or approved regimen, and their last COVID-19 vaccine (primary series or booster) was ≥120 days prior to Day 1. 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 drug or alcohol abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the clinical trial or could interfere with the interpretation of study results. Participant has received systemic immunosuppressants for >14 days in total within 180 days prior to Screening Visit (for glucocorticoids ≥10 milligrams [mg]/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the clinical trial (including intra-articular steroid injections). Inhaled, nasal, and topical steroids are allowed. Participant has received or plans to receive any vaccine authorized or approved by a local health agency ≤28 days prior to study intervention administration or plans to receive a vaccine authorized or approved by a local health agency within 28 days after study intervention administration. Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine within 150 days prior to Day 1. Participant tested positive for influenza by local health authority-approved testing methods ≤150 days prior to Day 1. Participant has had close contact to someone with COVID-19 as defined by the Centers for Disease Control and Prevention (CDC) in the past 10 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 clinical trial. Note: Other inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: Cohort A2: mRNA-1083.1 Dose B<br>Participants will receive single intramuscular (IM) injection of mRNA-1083.1 at Dose Level B on Day 1. | Biological: mRNA-1083.1<br>* Sterile liquid for injection<br>|
| Experimental: Cohort A3: mRNA-1083.1 Dose C<br>Participants will receive single IM injection of mRNA-1083.1 at Dose Level C on Day 1. | Biological: mRNA-1083.1<br>* Sterile liquid for injection<br>|
| Experimental: Cohort A4: mRNA-1083.2 Dose A<br>Participants will receive single IM injection of mRNA-1083.2 at Dose Level A on Day 1. | Biological: mRNA-1083.2<br>* Sterile liquid for injection<br>|
| Experimental: Cohort A5: mRNA-1083.2 Dose B<br>Participants will receive single IM injection of mRNA-1083.2 at Dose Level B on Day 1. | Biological: mRNA-1083.2<br>* Sterile liquid for injection<br>|
| Experimental: Cohort A6: mRNA-1083.2 Dose C<br>Participants will receive single IM injection of mRNA-1083.2 at Dose Level C on Day 1. | Biological: mRNA-1083.2<br>* Sterile liquid for injection<br>|
| Experimental: Cohort A7: mRNA-1083.3<br>Participants will receive single IM injection of mRNA-1083.3 on Day 1. | Biological: mRNA-1083.3<br>* Sterile liquid for injection<br>|
| Active Comparator: Cohort A8: mRNA-1010.4<br>Participants will receive single IM injection of mRNA-1010.4 on Day 1. | Biological: mRNA-1010.4<br>* Sterile liquid for injection<br>|
| Active Comparator: Cohort A9: mRNA-1283.222<br>Participants will receive single IM injection of mRNA-1283.222 on Day 1. | Biological: mRNA-1283.222<br>* Sterile liquid for injection<br>|
| Active Comparator: Cohort A10: mRNA-1273.222<br>Participants will receive single IM injection of mRNA-1273.222 on Day 1. | Biological: mRNA-1273.222<br>* Sterile liquid for injection<br>|
| Active Comparator: Cohort A11: mRNA-1010<br>Participants will receive single IM injection of mRNA-1010 on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>|
| Active Comparator: Cohort A12: Fluarix<br>Participants will receive single IM injection of Fluarix on Day 1. | Biological: Fluarix<br>* quadrivalent seasonal influenza vaccine<br>|
| Active Comparator: Cohort A13: Fluzone HD<br>Participants will receive single IM injection of Fluzone HD on Day 1. | Biological: Fluzone HD<br>* quadrivalent seasonal influenza vaccine<br>|
| Experimental: Cohort B1: mRNA-1083.1 Dose A<br>Participants will receive single IM injection of mRNA-1083.1 at Dose Level A on Day 1. | Biological: mRNA-1083.1<br>* Sterile liquid for injection<br>|
| Experimental: Cohort B2: mRNA-1083.1 Dose B<br>Participants will receive single IM injection of mRNA-1083.1 at Dose Level B on Day 1. | Biological: mRNA-1083.1<br>* Sterile liquid for injection<br>|
| Experimental: Cohort B3: mRNA-1083.1 Dose C<br>Participants will receive single IM injection of mRNA-1083.1 at Dose Level C on Day 1. | Biological: mRNA-1083.1<br>* Sterile liquid for injection<br>|
| Experimental: Cohort B4: mRNA-1083.2 Dose A<br>Participants will receive single IM injection of mRNA-1083.2 at Dose Level A on Day 1. | Biological: mRNA-1083.2<br>* Sterile liquid for injection<br>|
| Experimental: Cohort B5: mRNA-1083.2 Dose B<br>Participants will receive single IM injection of mRNA-1083.2 at Dose Level B on Day 1. | Biological: mRNA-1083.2<br>* Sterile liquid for injection<br>|
| Experimental: Cohort B6: mRNA-1083.2 Dose C<br>Participants will receive single IM injection of mRNA-1083.2 at Dose Level C on Day 1. | Biological: mRNA-1083.2<br>* Sterile liquid for injection<br>|
| Experimental: Cohort B7: mRNA-1083.3<br>Participants will receive single IM injection of mRNA-1083.3 on Day 1. | Biological: mRNA-1083.3<br>* Sterile liquid for injection<br>|
| Active Comparator: Cohort B8: mRNA-1010.4<br>Participants will receive single IM injection of mRNA-1010.4 on Day 1. | Biological: mRNA-1010.4<br>* Sterile liquid for injection<br>|
| Active Comparator: Cohort B9: mRNA-1283.222<br>Participants will receive single IM injection of mRNA-1283.222 on Day 1. | Biological: mRNA-1283.222<br>* Sterile liquid for injection<br>|
| Active Comparator: Cohort B10: mRNA-1273.222<br>Participants will receive single IM injection of mRNA-1273.222 on Day 1. | Biological: mRNA-1273.222<br>* Sterile liquid for injection<br>|
| Active Comparator: Cohort B11: mRNA-1010<br>Participants will receive single IM injection of mRNA-1010 on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>|
| Active Comparator: Cohort B12: Fluarix<br>Participants will receive single IM injection of Fluarix on Day 1. | Biological: Fluarix<br>* quadrivalent seasonal influenza vaccine<br>|

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) and Severe AEs |  | Up to Day 28 (28 days after vaccination) | 
| Number of Participants With Unsocilited 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 Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay |  | Baseline (Day 1), Day 29, and Day 181 | 
| Change From Baseline in GMT of Antibodies for SARS-CoV-2, as Measured by Pseudovirus Neutralization Assay (PsVNA) |  | Baseline (Day 1), Day 29, and Day 181 | 
| Change From Baseline in Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay |  | Baseline (Day 1), Day 29, and Day 181 | 
| Change From Baseline in GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA |  | Baseline (Day 1), Day 29, and Day 181 | 
| Influenza: Percentage of Participants with Seroconversion, as Measured by HAI Assay | Seroconversion is defined as a Day 29 and Day 181 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, and Day 181 | 
| SARS-CoV-2: Percentage of Participants with Seroresponse, as Measured by PsVNA | Seroresponse is defined as a Day 29 and Day 181 titer ≥4-fold if baseline is ≥lower limit of quantification (LLOQ) or ≥4*LLOQ if baseline titer is <LLOQ in neutralizing antibody (nAb) titers measured by PsVNA. | Baseline (Day 1) to Day 29, and Day 181 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-1083, mRNA-1083 Vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, Moderna, Influenza Vaccine