Safety and Immunogenicity of a Monovalent mRNA Vaccine Encoding Influenza Hemagglutinin in Adult Participants 18 Years of Age 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 immunogenicity of a single intramuscular (IM) injection of different dose levels of messenger ribonucleic acid (mRNA) vaccine encoding influenza hemagglutinin compared to an active control quadrivalent recombinant influenza vaccine (RIV4) in adults 18 years of age and older. Study details include: Study Duration: approximately 6 months Treatment Duration: 1 injection of mRNA vaccine encoding influenza hemagglutinin encoding influenza hemagglutinin or control. Visit Frequency: Screening visit, Day 01, Day 02, Day 03, Day 09, Day 29, Day 91, Day 181

Detailed Description
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Approximately 6 months

Official Title
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A Phase I, Parallel, Randomized, Active-controlled, Multi-center, Dose-escalation Study With Early Safety Data Reviews to Assess Safety and Immunogenicity of a Monovalent mRNA Vaccine Encoding Influenza Hemagglutinin in Adults 18 Years of Age and Older

Conditions
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Influenza, Influenza Immunization

Intervention / Treatment
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* Biological: Influenza Hemagglutinin mRNA vaccine
* Biological: Quadrivalent Recombinant Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having given written informed consent prior to undertaking any study-related procedure. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Any subject who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sentinel cohort 1<br>20 Participants in each age group will receive either Influenza hemagglutinin mRNA vaccine candidate dose 1 or dose 2 and half number of the participants in each age group also receiving the RIV4 control | Biological: Influenza Hemagglutinin mRNA vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>Biological: Quadrivalent Recombinant Influenza Vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>* Other names: Flublok Quadrivalent®;|
| Experimental: sentinel cohort 2<br>20 Participants in each age group will receive either Influenza hemagglutinin mRNA vaccine candidate dose 3 or dose 4 and half number of the participants in each age group also receiving the RIV4 control | Biological: Influenza Hemagglutinin mRNA vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>Biological: Quadrivalent Recombinant Influenza Vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>* Other names: Flublok Quadrivalent®;|
| Experimental: sentinel cohort 3<br>10 Participants in each age group will receive Influenza hemagglutinin mRNA vaccine candidate dose 5 with half of the participants in each age group also receiving the RIV4 control | Biological: Influenza Hemagglutinin mRNA vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>Biological: Quadrivalent Recombinant Influenza Vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>* Other names: Flublok Quadrivalent®;|
| Experimental: main cohort 1<br>40 Participants in each age group will receive either Influenza hemagglutinin mRNA vaccine candidate dose 1 or dose 2 and half number of the participants in each age group also receiving the RIV4 control | Biological: Influenza Hemagglutinin mRNA vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>Biological: Quadrivalent Recombinant Influenza Vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>* Other names: Flublok Quadrivalent®;|
| Experimental: main cohort 2<br>40 Participants in each age group will receive either Influenza hemagglutinin mRNA vaccine candidate dose 3 or dose 4 and half number of the participants in each age group also receiving the RIV4 control | Biological: Influenza Hemagglutinin mRNA vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>Biological: Quadrivalent Recombinant Influenza Vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>* Other names: Flublok Quadrivalent®;|
| Experimental: main cohort 3<br>20 Participants in each age group will receive Influenza hemagglutinin mRNA vaccine candidate dose 5, and half number of the participants in each age group also receiving the RIV4 control | Biological: Influenza Hemagglutinin mRNA vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>Biological: Quadrivalent Recombinant Influenza Vaccine<br>* Pharmaceutical form:Solution for injection-Route of administration:IM injection<br>* Other names: Flublok Quadrivalent®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of any unsolicited systemic adverse events (AEs) reported in the 30 minutes after injection | Number of participants with unsolicited systemic immediate adverse events (AEs) | Within 30 minutes after injection | 
| Presence of solicited injection site reactions (ie, pre listed in the participant's diary card [DC] and in the electronic case report form [eCRF]) occurring up to 7 days after injection | Number of participants with solicited injection site reactions | Up to 7 days after injection | 
| Presence of solicited systemic reactions (ie, pre-listed in the participant's DC and in the eCRF) occurring up to 7 days after injection | Number of participants with solicited systemic reactions | Up to 7 days after injection | 
| Presence of unsolicited AEs reported up to 28 days after injection | Number of participants with unsolicited AEs | Up to 28 days after injection | 
| Presence of medically attended AEs (MAAEs) reported up to 28 days after injection | Number of participants with medically attended adverse events (MAAE)s | Up to 28 days after injection | 
| Presence of serious adverse events (SAEs) and adverse events of special interest (AESIs) throughout the study | Number of participants with serious adverse events (SAEs) | From baseline up to 6 months | 
| Presence of out-of-range biological test results (including shift from baseline values) up to 28 days after injection | Number of participants with out-of-range biological test results | Up to 28 days after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemagglutination inhibition (HAI) antibody (Ab) titers to homologous H3 strain at D29, D91, and D181 | Antibody titers are expressed as Geometric Mean Titers (GMTs) | At Day 29, Day 91, and Day 181 | 
| Individual HAI Ab titer ratio D29/D01, D91/D01, D91/D29, D181/D01, and D181/D29 | Ratios of antibody titers measured by HAI in each group before and after vaccination | From baseline up to 6 months | 
| HAI Ab titer ≥ 40 [1/dil] at D29, D91, and D181 |  | At Day 29, Day 91 and Day 181 | 
| 2-fold and 4-fold rise in HAI titers from D01 to D91 and D01 to D181 |  | From Day 01 through Day 91 and Day 01 through Day 181 | 
| Neutralizing Ab titers to homologous H3 strain at D29, D91, and D181 |  | At Day 29, Day 91, and Day 181 | 
| Individual neutralizing Ab titer ratio D29/D01, D91/D01, D91/D29, D181/D01, and D181/D29 |  | From baseline up to 6 months | 
| 2-fold and 4-fold rise in neutralizing titers from D01 to D91 and D01 to D181 |  | From Day 01 through Day 29 and Day 01 through Day 181 | 
| HAI Ab titers to selected heterologous H3 strains at D01, D29, D91, and D181 |  | At Day 01, Day 29, D91 and D181 | 
| Neutralizing Ab titers to selected heterologous H3 strains at D01, D29, D91, and D181 |  | At Day 01, Day 29, Day 91, and Day 181 |