A Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1010 in Healthy Adults

Study Overview
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Brief Summary
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The main purpose of the study is to evaluate the safety, reactogenicity, and the humoral immunogenicity of mRNA-1010 and comparator influenza vaccines against homologous influenza A and B strains at Day 29.

Detailed Description
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The study consists of two parts. Part A of the study was conducted for the 2022-23 influenza season. Part B of the study will be conducted in 2023-24 influenza season.

Official Title
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Phase 2, Open-Label Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1010 and Comparator Seasonal Influenza Vaccines in Healthy Adults

Conditions
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Influenza

Intervention / Treatment
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* Biological: mRNA-1010
* Biological: Egg-based Quadrivalent Influenza Vaccine
* Biological: Adjuvanted Quadrivalent Influenza Vaccine
* Biological: Inactivated Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A only: Body mass index (BMI) of 18 kilograms (kg)/meter (m)^2 to < 40 kg/m^2 at the screening visit. There will be no BMI requirement for inclusion in Part B. Female participants of childbearing potential: has a negative pregnancy test on the day of vaccination (D1); practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days before D1; has agreed to continue adequate contraception through 3 months after vaccine administration; and is not currently breastfeeding. Exclusion Criteria: Acutely ill or febrile (temperature ≥ 38.0°Celsius (C)/100.4° Fahrenheit (F) hours before or at the D1 vaccination visit. Participants meeting this criterion may be rescheduled within the 28-day screening window. 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. Reported history of congenital or acquired immunodeficiency, immunocompromising or immunosuppressive condition, asplenia, or history of recurrent severe infections. Certain immune-mediated conditions that are stable and well-controlled (for example, Hashimoto's thyroid disease) or that do not require systemic immunosuppressive therapy may be permitted at the discretion of the Investigator. Dermatologic conditions that could affect local solicited AR assessments (tattoos, psoriatic patches or vitiligo affecting skin over the deltoid injection site area). Has received systemic immunosuppressants (for glucocorticoids ≥ 10 mg/day of prednisone or equivalent) for > 14 days in total within 180 days before vaccination visit (D1) 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. Has received systemic immunoglobulins or long-acting biological therapies that may suppress or alter immune responses (for example, Infliximab®) or blood products within 90 days before the vaccination visit or plans to receive them during the study. Has a 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. Other protocol-defined inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: The study design for Part A is randomized and Part B is non-randomized.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1010 (Age Group 18-50 years)<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>|
| Active Comparator: Egg-based Quadrivalent Influenza Vaccine (Age Group 18-50 years)<br>Participants will receive a single dose of egg-based quadrivalent influenza vaccine by IM injection on Day 1. | Biological: Egg-based Quadrivalent Influenza Vaccine<br>* Sterile suspension for injection<br>* Other names: Fluarix®;|
| Active Comparator: Adjuvanted Quadrivalent Influenza Vaccine (Age Group 65-80 years)<br>Participants will receive a single dose of adjuvanted quadrivalent influenza vaccine by IM injection on Day 1. | Biological: Adjuvanted Quadrivalent Influenza Vaccine<br>* Sterile injectable emulsion<br>* Other names: Fluad®;|
| Active Comparator: Inactivated Influenza Vaccine (Age Group 65-80 years)<br>Participants will receive a single dose of inactivated influenza vaccine by IM injection on Day 1. | Biological: Inactivated Influenza Vaccine<br>* Sterile suspension for injection<br>* Other names: Fluzone®;|
| Experimental: mRNA-1010 (Age Group 65-80 years)<br>Participants will receive a single dose of mRNA-1010 by IM injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 181 | 
| Change from Baseline in Geometric Mean Titer (GMT) of Anti-Hemagglutinin (HA) Antibodies at Day 29, as Measured by Hemagglutinin Inhibition (HAI) Assay |  | Baseline, 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 29 | 
| Percentage of Participants with Seroresponse, as Measured by HAI Assay | Seroresponse is defined as a Day 29 titer > 1:40 if baseline is < 1:10 or a minimum 4-fold rise if baseline is >1:10 in anti-HA antibodies measured by HAI assay. | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in GMT of Anti-HA Antibodies at Days 121 and 181, as Measured by HAI Assay or Microneutralization (MN) Assay |  | Baseline, Days 121 and 181 | 
| Change from Baseline in GMFR of Anti-HA Antibodies at Days 121 and 181, as Measured by HAI Assay or MN Assay |  | Baseline, Days 121 and 181 | 

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