Safety and Immunogenicity of Cam2020 M2SR H3N2 Monovalent Influenza Vaccine Alone or With Licensed IIV in Older Adults

Study Overview
=================
Brief Summary
-----------------
This is a randomized, double-blind, double-dummy, placebo-controlled Phase 1b study evaluating the safety and immunogenicity of the investigational Cam2020 M2SR H3N2 influenza vaccine delivered IN alone or concomitantly with inactivated influenza vaccine (IIV) delivered IM to a healthy adult population age 65 to 85 years at time of enrollment.

Detailed Description
-----------------
This is a randomized, double-blind, double-dummy, placebo-controlled Phase 1b study evaluating the safety and immunogenicity of the investigational Cam2020 M2SR H3N2 influenza vaccine delivered IN alone or concomitantly with IIV delivered IM to a healthy adult population age 65 to 85 years at time of enrollment. Eligible subjects will be randomized concurrently in a 3:3:3:1 ratio to receive one administration of Cam2020 M2SR alone (Cohort 1, n=90), Cam2020 M2SR along with IIV (Cohort 2, n=90), IIV alone (Cohort 3, n=90), or placebo (Cohort 4, n=30).

Official Title
-----------------
Phase 1b Study to Investigate the Safety and Immunogenicity of Cam2020 (A/Cambodia/e0826360/2020) M2SR H3N2 Monovalent Influenza Vaccine Administered Alone or With Licensed, Inactivated Influenza Vaccine in Adults 65 to 85 Years Old

Conditions
-----------------
Influenza Vaccine

Intervention / Treatment
-----------------
* Biological: Cam2020 M2SR H3N2 influenza vaccine
* Biological: Fluzone HD IIV
* Other: IN Placebo
* Other: IM Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must be willing and able to provide written informed consent to participate; a legally authorized representative (LAR) may not be used. Males and nonchildbearing potential females 65-85 years of age at the time of consent. Subjects must be willing to adhere to the requirements of the study and willing and able to communicate with the Investigator and understand the requirements of the study. Healthy adults and those with stable chronic conditions as determined by medical history, physical examination, vital signs, clinical safety laboratory examinations and clinical judgment of the Investigator to be eligible for study inclusion. Exclusion Criteria: Any acute or chronic physical or mental health condition that would limit the subject's ability to complete the study, increase risk of study participation or participant, or may interfere with interpretation of study results as based on the assessment by the Investigator. Abnormal screening hematology or chemistry value per the US FDA Guidance: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials Currently receiving, or planned to receive during the study, any immunosuppressive therapy. Had a flu-like illness, influenza treatment, or prophylactic influenza viral drug administered in the previous 6 months before investigational product administration. History of receipt of any live virus vaccine within 56 days of study entry, licensed or investigational vaccine within 28 days of Visit 01 or investigational drug within the past 6 months. An exception is made for receipt of a Covid-19 vaccine whether licensed or under EUA as long as the final dose was given at least 28 days prior to Visit 01. Planned receipt of licensed vaccine, other than the study-provided licensed influenza vaccine, during the 28 days following Visit 01 or another investigational vaccine or investigational drug during the study period. Receipt of blood/plasma products or immunoglobulin within 6 months before administration of the investigational product or planned for during the period of study participation.

Ages Eligible for Study
-----------------
Minimum Age: 65 Years
Maximum Age: 85 Years

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

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

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

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects assigned randomly to one of four cohorts concurrently
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M2SR only dose<br>Intranasal M2SR vaccine and intramuscular placebo dose | Biological: Cam2020 M2SR H3N2 influenza vaccine<br>* Administered intranasally on Day 1<br>Other: IM Placebo<br>* Administered intramuscularly on Day 1<br>|
| Experimental: M2SR with IIV dose<br>Intranasal M2SR vaccine and intramuscular IIV dose | Biological: Cam2020 M2SR H3N2 influenza vaccine<br>* Administered intranasally on Day 1<br>Biological: Fluzone HD IIV<br>* Administered intramuscularly on Day 1<br>|
| Active Comparator: IIV only dose<br>Intranasal placebo dose and intramuscular IIV dose | Biological: Fluzone HD IIV<br>* Administered intramuscularly on Day 1<br>Other: IN Placebo<br>* Administered intranasally on Day 1<br>|
| Placebo Comparator: Placebo only dose<br>Intranasal placebo dose and intramuscular placebo dose | Other: IN Placebo<br>* Administered intranasally on Day 1<br>Other: IM Placebo<br>* Administered intramuscularly on Day 1<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited AEs during 7 days after experimental treatment | The number and percentage of subjects who experience solicited local and systemic reactions during the 7 days after vaccine administration of M2SR administration alone or with IIV | Day 1 to Day 8 | 
| Unsolicited AEs during 28 days after experimental treatment | The number and percentage of subjects who experience unsolicited AEs during the 28 days after vaccine administration of M2SR alone or with IIV. | Day 1 to Day 29 | 
| SAEs through 28 days after experimental treatment | The number and percentage of subjects who experience SAEs from the time of informed consent through 28 days after vaccine administration of M2SR alone or with IIV. | Day 1 to Day 29 |