Phase I, Randomized, Modified Double-blind, Parallel-group, Active-controlled, Multi-arm, Dose-escalation Study to Assess the Safety and Immunogenicity of Monovalent mRNA NA Vaccine in Adult Participants 18 Years of Age and Older

Study Overview
=================
Brief Summary
-----------------
This is a Phase I, first-in-human, randomized, modified double-blind, active-controlled, dose-escalation study to assess the safety and immunogenicity of up to 3 dose levels of mRNA NA vaccines, administered as a single IM injection in healthy adults aged 18 years and older. Two age groups, 18 to 64 years and ≥65 years, will be included in this study.

Detailed Description
-----------------
This study will include a screening visit, 6 study visits occurring on Days 1, 3, 9, 29, 91, and 181, and a safety follow-up telephone call on Day 366.

Official Title
-----------------
Study to Assess the Safety and Immunogenicity of Monovalent mRNA NA Vaccine in Adult Participants 18 Years of Age and Older

Conditions
-----------------
Healthy Volunteers, Influenza Immunization

Intervention / Treatment
-----------------
* Biological: mRNA NA vaccine
* Biological: High Dose Quadrivalent Influenza Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18 years or older on the day of inclusion. A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, or surgically sterile OR Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 12 weeks after study intervention administration A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 8 hours before administration of study intervention. Informed consent form has been signed and dated. Exclusion Criteria: Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). Known systemic hypersensitivity to any of the study intervention components; history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances Moderate or severe acute illness/infection (according to investigator judgement) or febrile illness (temperature ≥100.4°F) on the day of study intervention administration. Have known or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. Have any diagnosis, current or past, of autoimmune disease. Body mass index of 40 kg/m2 or higher. Receipt of immune globulins, blood, or blood-derived products in the past 3 months. Have taken high-dose inhaled corticosteroid (≥500 μg of fluticasone) within 6 months prior to study vaccination. Self-reported or documented seropositivity for HIV, hepatitis B virus, or hepatitis C virus.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 mRNA NA: Low dose Level<br>Participants will receive a low dose of mRNA vaccine | Biological: mRNA NA vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Experimental: Group 2 mRNA NA: Medium dose level<br>Participants will receive a medium dose of mRNA vaccine | Biological: mRNA NA vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Experimental: Group 3 mRNA NA: High dose level<br>Participants will receive a high dose of mRNA vaccine | Biological: mRNA NA vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Active Comparator: Group 4: QIV-HD<br>Participants will receive QIV-HD (high dose quadrivalent influenza) vaccine | Biological: High Dose Quadrivalent Influenza Vaccine<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>* Other names: Fluzone HD;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with immediate adverse events | Immediate adverse events are unsolicited systemic adverse events reported in the 30 minutes after vaccination | Within 30 minutes after vaccination | 
| Number of participants with solicited injection site or systemic reaction |  | From Day 1 to Day 8 | 
| Number of participants with unsolicited adverse events | Unsolicited (spontaneously reported) adverse events not fulfilling criteria for solicited reactions | From Day 1 to Day 29 | 
| Number of participants with serious adverse events | Serious adverse events are collected throughout the study | From Day 1 to Day 366 | 
| Number of participants with adverse events of special interest | Adverse events of special interest are collected throughout the study | From Day 1 to Day 366 | 
| Number of patients with clinically significant changes in clinical laboratory tests | Laboratory tests include hematology: complete blood count (CBC) with differential, platelet count, coagulation panel (prothrombin time and PTT) and serum chemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and fractionated bilirubin, C-reactive protein, serum creatinine, and blood urea nitrogen | From Day 1 to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuraminidase inhibition (NAI) Antibodies at Day 1 and 29 | Antibody are expressed as GMTs at baseline and post-baseline | Day 1 and 29 | 
| Individual Neuraminidase inhibition (NAI) titer | Antibody titers are expressed as GMTs at baseline and post-baseline | Day 1 and Day 29 | 
| 2-fold and 4-fold rise in NAI antibody titers | Expressed as percentage post-baseline | From Day 1 to Day 29 | 
| Percentage of participants with detectable antibody titers greater than or equal to (≥) 10 [1/dil] | Expressed as percentage at baseline and post-baseline | Day 1 and Day 29 |