Safety, Reactogenicity, and Immunogenicity Study of a Self-Amplifying mRNA Influenza Vaccine in Healthy Adults

Study Overview
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Brief Summary
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This is a Phase 1, first-in-human, randomized, placebo-controlled, observer blind study. The effect of one or two doses of an investigational vaccine on safety, reactogenicity, kinetics and magnitude of the post-vaccination antibody response will be evaluated at different timepoints as compared to placebo in healthy adults. Approximately 128 evaluable subjects will be enrolled in this study; n=96 receiving investigational vaccine and n=32 receiving placebo. The study has a screening period (Day -28 to Day -1), a treatment period (Day 1 to Day 43) and a follow-up period (Day 44 to Day 202).

Official Title
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Phase 1, Randomized, Placebo-Controlled, Observer Blind Study to Evaluate the Safety, Reactogenicity and Immunogenicity of an Investigational Self-Amplifying mRNA Influenza Vaccine in Healthy Adults

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: sa-mRNA vaccine Dose 1
* Biological: sa-mRNA vaccine Dose 2
* Biological: sa-mRNA vaccine Dose 3
* Biological: sa-mRNA vaccine Dose 4
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals 18 to 49 years of age OR 65 to 85 years of age, inclusive on the day of informed consent. Individuals with body mass index (BMI) between 18 and 32 kg/m2, inclusive, at screening . Individuals who can comply with study procedures including follow-up . Exclusion Criteria: Female participants of childbearing potential who are pregnant, lactating, or who have not adhered to a specified set of highly effective contraceptive methods from at least 30 days prior to informed consent and who do not plan to do so for the duration of the study. Male participants who have not adhered to using barrier contraception such as a condom during at least 60 days after each vaccination, to prevent semen transfer to their sexual partners and prevent pregnancy of a female partner. Progressive, unstable, or uncontrolled clinical conditions Known hypersensitivity or allergy to any study vaccine component Known history of Guillain-Barré syndrome or other demyelinating disease Condition representing a contraindication to vaccination or blood draw Abnormal function of immune system due to clinical condition, medications, or radiotherapy. Receipt or planning to receive blood products, non-study vaccine, influenza vaccine, mRNA-platform vaccine within different timeframes; previous or from study vaccination. Baseline abnormal clinically significant ECG, laboratory safety parameters or vital signs. Plan to donate blood products (other than for this study), sperm, ova, tissues, or organs up to 60 days following the last vaccination.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: sa-mRNA vaccine dose 1<br> | Biological: sa-mRNA vaccine Dose 1<br>* self-amplifying mRNA vaccine<br>|
| Experimental: sa-mRNA vaccine dose 2<br> | Biological: sa-mRNA vaccine Dose 2<br>* self-amplifying mRNA vaccine<br>|
| Experimental: sa-mRNA vaccine dose 3<br> | Biological: sa-mRNA vaccine Dose 3<br>* self-amplifying mRNA vaccine<br>|
| Experimental: sa-mRNA vaccine dose 4<br> | Biological: sa-mRNA vaccine Dose 4<br>* self-amplifying mRNA vaccine<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Saline for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of subjects with clinically significant abnormal vital signs and/or acute reactions |  | up to 60 minutes or within 6 hours post vaccination | 
| Number and percentage of subjects reporting reactogenicity: Solicited local and systemic AEs |  | Day 1 to Day 14 of each post vaccination period | 
| Number and percentage of subjects reporting unsolicited AEs |  | Day 1 to Day 43 | 
| Number and percentage of subjects reporting AEs leading to study withdrawal, Adverse Events of Special Interest (AESIs), medically attended AEs (MAAEs), and serious adverse events (SAEs). |  | Day 1 to Day 202 | 
| Number and percentage of subjects with Grade 3 or greater abnormal clinically significant hematology and chemistry laboratory values |  | Day 3 to Day 43 | 
| Number and percentage of subjects with grading shifts in hematology and chemistry laboratory assessments |  | Day 3 to Day 43 | 
| Serum antibody titer against the HA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via HI assay |  | Day 1, Day 22, Day 43 | 
| Number and percentage of subjects with HAI titer ≥1:10 and <1:10 (lower limit of quantification [LLOQ]) |  | Day 1, Day 22, Day 43 | 
| Number and percentage of subjects with HAI titer ≥1:40, ≥1:80, ≥1:160 and ≥1:320 |  | Day 1, Day 22, Day 43 | 
| Seroconversion rate (SCR) by HAI assay | SCR defined as the percentage of subjects with either a prevaccination HAI titer <1:10 and a post-vaccination HAI titer ≥1:40, or a prevaccination HAI titer ≥1:10 and a ≥4-fold increase in post-vaccination | Day 1, Day 22, Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum antibody titer against the HA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via HI assay |  | Day 1, Day 202 | 
| Number and percentage of subjects with ≥4-fold increase in post-vaccination HAI titer |  | Day 1, Day 202 | 
| Number and percentage of subjects with HAI titer ≥1:10 and <1:10 (LLOQ) |  | Day 202 | 
| Number and percentage of subjects with HAI titer ≥1:40, ≥1:80, ≥1:160 and ≥1:320 |  | Day 202 | 
| Seroconversion rate (SCR) by HAI assay |  | Day 1, Day 202 | 
| Serum antibody titer against the NA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via ELLA assay |  | Day 1, Day 22, Day 43, Day 202 | 
| Number and percentage of subjects with ≥4-fold increase in post-vaccination ELLA titer |  | Day 1, Day 22, Day 43, Day 202 | 

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