A Safety, Reactogenicity, and Immunogenicity Study of mRNA-1073 (COVID-19/Influenza) Vaccine in Adults 18 to 75 Years Old

Study Overview
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Brief Summary
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The primary goal of this study is to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1073 compared to co-administered mRNA-1010 and mRNA-1273 vaccines and to the individual vaccines alone in healthy participants.

Official Title
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Phase 1/2, Randomized, Stratified, Observer-blind Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1073 (SARS-CoV-2 and Influenza Vaccine) Compared to Co-administered mRNA-1010 (Influenza) and mRNA-1273 (SARS-CoV-2) Vaccines and to mRNA- 1010 Vaccine and mRNA-1273 Vaccine Alone in Healthy Adults 18-75 Years of Age

Conditions
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SARS-CoV-2, Influenza

Intervention / Treatment
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* Biological: mRNA-1073
* Biological: mRNA-1010
* Biological: mRNA-1273
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) of 18 kilograms per meter squared (kg/m^2) to 35 kg/m^2 (inclusive) at the Screening Visit. Participants must have been 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 the randomization visit (or less per local guidance). Exclusion Criteria: 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. Clinically unstable is defined as a diagnosis or condition requiring significant changes in management or medication ≤ 60 days prior to Screening and includes ongoing workup of an undiagnosed illness that could lead to a new diagnosis or condition. Asymptomatic conditions and conditions with no evidence of end organ involvement (for example, mild hypertension, dyslipidemia) are not exclusionary, provided that they are being appropriately managed and are clinically stable (for example, unlikely to result in symptomatic illness within the time course of this study). Illnesses or conditions may be exclusionary, even if otherwise stable, due to therapies used to treat them (for example, immune-modifying treatments), at the discretion of the investigator. Participant has a reported history of congenital or acquired immunodeficiency, immunosuppressive condition, or immune-mediated disease. Participant has dermatologic conditions that could affect local solicited adverse reaction (AR) assessments (for example, tattoos, psoriasis patches affecting skin over the deltoid areas). Participant has a reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any mRNA vaccine(s) or any components of the mRNA vaccines. Participant has a reported history of bleeding disorder that is considered a contraindication to IM injection or phlebotomy. Participant has a diagnosis of malignancy within previous 10 years (excluding nonmelanoma skin cancer). Participant has 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 study or could interfere with the interpretation of study results. Participant has received systemic immunosuppressants or immune-modifying drugs for > 14 days in total within 6 months prior to Screening (for corticosteroids ≥ 10 mg/day of prednisone or equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. Inhaled, nasal, topical steroids are not exclusionary. Participant has received or plans to receive any vaccine authorized or approved by a local health agency ≤ 28 days prior to study injections (Day 1) or plans to receive a vaccine authorized or approved by a local health agency within 28 days before or after the study injections. Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine ≤ 180 days prior to the randomization visit. Participant has tested positive for influenza by local health authority approved testing methods ≤ 180 days prior to the Screening Visit. Participant has had close contact to someone with SARS-CoV-2 infection or COVID-19 as defined by the US CDC in the past 10 days prior to the Screening Visit. Participant has known history of SARS-CoV-2 infection within ≤ 90 days. Participant has received systemic immunoglobulins or blood products ≤ 90 days prior to the Screening Visit or plans to receive systemic immunoglobulins or blood products during the study. Participant has a history of myocarditis, pericarditis, or myopericarditis. 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. Participated in an interventional clinical study within 28 days prior to the Screening Visit based on the medical history interview or plans to do so while participating in this study. Participant is an immediate family member or household member of study personnel, study site staff, or Sponsor personnel. Phase 1 Specific Exclusion Criteria: Participant has clinical screening laboratory values (total white blood cell count, hemoglobin, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, alkaline phosphatase, and total bilirubin) > Grade 1.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1273 Plus Placebo<br>Participants will receive 2 intramuscular (IM) injections, one in each arm, of mRNA-1273 plus placebo at the specified dose level on Day 1. | Biological: mRNA-1273<br>* Sterile liquid for injection<br>Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: mRNA-1010 Plus Placebo<br>Participants will receive 2 IM injections, one in each arm, of mRNA-1010 plus placebo at the specified dose level on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: mRNA-1010 Plus mRNA-1273<br>Participants will receive 2 IM injections, one in each arm, of mRNA-1010 plus mRNA-1273 at the specified dose level on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>|
| Experimental: Dose A: mRNA-1073 Plus Placebo<br>Participants will receive 2 IM injections, one in each arm, of mRNA-1073 plus placebo at the specified dose level on Day 1. | Biological: mRNA-1073<br>* Sterile liquid for injection<br>Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Dose B: mRNA-1073 Plus Placebo<br>Participants will receive 2 IM injections, one in each arm, of mRNA-1073 plus placebo at the specified dose level on Day 1. | Biological: mRNA-1073<br>* Sterile liquid for injection<br>Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>|
| Experimental: Dose C: mRNA-1073 Plus Placebo<br>Participants will receive 2 IM injections, one in each arm, of mRNA-1073 plus placebo at the specified dose level on Day 1. | Biological: mRNA-1073<br>* Sterile liquid for injection<br>Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<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 8 (7 days post vaccination) | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 29 (28 days post vaccination) | 
| Number of Participants with Serious Adverse Events (SAEs) |  | Up to Day 181 | 
| Number of Participants with Adverse Events of Special Interest (AESIs) |  | Up to Day 181 | 
| Number of Participants with Medically-Attended AEs (MAAEs) |  | Up to Day 181 | 
| Number of Participants with AEs Leading to Discontinuation |  | Up to Day 181 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Geometric Mean Titer (GMT) as Measured by Hemagglutination Inhibition (HAI) Assay |  | Baseline (Day 1), Days 8, 29, and 181 | 
| Change From Baseline in GMT as Measured by Pseudovirus Neutralization Assay (PsVNA) (or Binding Antibody Assay) |  | Baseline (Day 1), Days 8, 29, and 181 | 
| Change From Baseline in Geometric Mean Fold-Rise (GMFR) as Measured by HAI Assay |  | Baseline (Day 1), Days 8, 29, and 181 | 
| Change From Baseline in GMFR as Measured by PsVNA (or Binding Antibody Assay) |  | Baseline (Day 1), Days 8, 29, and 181 | 
| Influenza: 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), Days 8, 29, and 181 | 
| SARS-CoV-2: Percentage of Participants with Seroresponse as Measured by PsVNA (or Binding Antibody Assay) | Seroresponse is defined as a Day 29 titer ≥4-fold if baseline is ≥lower limit of quantification (LLOQ) or ≥4 × LLOQ if baseline titer is <LLOQ in nAb titers measured by PsVNA (or binding antibody assay). | Baseline (Day 1), Days 8, 29, and 181 |