Safety and Immunogenicity of the Sing2016 M2SR H3N2 Monovalent Influenza Vaccine in Adults Ages 50 to 85 Years Old

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled Phase 1b study to evaluate safety and immunogenicity of the investigational Sing2016 M2SR H3N2 influenza vaccine delivered intranasally to a healthy adult population age 50 to 85 years.

Detailed Description
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This is a randomized, double-blind, placebo-controlled Phase 1b study to evaluate safety and immunogenicity of the investigational Sing2016 M2SR H3N2 influenza vaccine delivered intranasally to a healthy adult population age 50 to 85 years. Eligible subjects will be randomized 2:1 to receive one administration of Sing2016 M2SR or placebo followed by a dose of age-appropriate licensed inactivated influenza vaccine (IIV) at least 28 days later. Two lead-in groups of adults ages 50-64 years (Cohort 1) and 65 - 85 years (Cohort 2) will be followed by enrollment of an expansion group, ages 65 - 85 (Cohort 3). Safety data will be reviewed between enrollment of successive cohorts.

Official Title
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Phase 1b Clinical Study to Investigate the Safety and Immunogenicity of the Sing2016 (A/Singapore/INFIMH-16-0019/2016) M2SR H3N2 Monovalent Influenza Vaccine in Adults Ages 50 to 85 Years Old.

Conditions
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Influenza Vaccine

Intervention / Treatment
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* Biological: Sing2016 M2SR H3N2 influenza vaccine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be willing and able to provide written informed consent. Cohort 1: age 50-64 years at time of enrollment; Cohorts 2 and 3: age 65 to 85 years at time of enrollment (signing of informed consent form). Subject 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. Women of child-bearing potential must agree to abstain from sexual intercourse or to correctly use an acceptable method of contraception from 30 days prior to vaccination until 30 days after the last study vaccination. Women of childbearing potential must have a negative urine pregnancy test within 24 hours prior to vaccination with investigational product. Exclusion Criteria: Any acute or chronic physical or mental 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. Acute or chronic medical condition or history of a medical condition that, in the opinion of the Investigator, would render the study procedures unsafe or would interfere with the evaluation of the responses. Abnormal screening hematology or chemistry value per the FDA Guidance: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials. Currently receiving, or planned to receive during the study, any immunosuppressive therapy. Had a flu-like illness, influenza treatment, influenza vaccination, or prophylactic influenza viral drug administered in the previous 6 months before investigational product administration. Females who are pregnant or nursing; non-vasectomized males, with female partners of child-bearing potential, who are unwilling to use a highly effective form of contraception from the time of enrollment through at least 28 after administration of the investigational product. History of receipt of any investigational vaccine within 28 days of visit 1 or investigational drug within the past six months. An exception is made for receipt of a Covid-19 vaccine whether licensed or under emergency use authorization (EUA) as long as the second dose was given at least 28 days prior to dosing with investigational vaccine. Acute febrile illness within 72 hours prior to investigational product vaccination 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. Planned donation of blood or blood product of at least approximately 1 pint within 3 months after investigational product administration.

Ages Eligible for Study
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Minimum Age: 50 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: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Three Cohorts will be enrolled sequentially with safety data reviewed between enrollment of successive cohorts.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M2SR dose, 50-64 years of age<br>Intranasal M2SR vaccine followed by standard, licensed IIV | Biological: Sing2016 M2SR H3N2 influenza vaccine<br>* This group will receive a dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally on Day 1 followed by IIV at least 28 days later.<br>|
| Placebo Comparator: Placebo dose, 50-64 years of age<br>Intranasal physiological saline followed by standard, licensed IIV | Other: Placebo<br>* This group will receive saline placebo administered intranasally on Day 1 followed by IIV at least 28 days later.<br>|
| Experimental: M2SR dose, 65-85 years of age<br>Intranasal M2SR vaccine followed by licensed IIV recommended for people 65 years and older | Biological: Sing2016 M2SR H3N2 influenza vaccine<br>* This group will receive a dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally on Day 1 followed by IIV at least 28 days later.<br>|
| Placebo Comparator: Placebo dose, 65-85 years of age<br>Intranasal physiological saline followed by licensed IIV recommended for people 65 years and older | Other: Placebo<br>* This group will receive saline placebo administered intranasally on Day 1 followed by IIV at least 28 days later.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent AEs During 7 Days After Experimental Treatment | The number and percentage of study participants who experience local (at the dose administration site) and systemic (throughout the body) reactions during the 7 days after administration of investigational M2SR vaccine or placebo. Solicited and unsolicited signs and symptoms were reported as AEs after review by the Investigator or designee, either separately using the corresponding Medical Dictionary for Regulatory Activities (MedDRA) terminology of the sign or symptom or combined using the appropriate term. | Day 1 to Day 8 | 
| Treatment Emergent AEs During 28 Days After Experimental Treatment | The number and percentage of study participants who experience a treatment emergent AE during the 28 days after administration of investigational M2SR vaccine or placebo. Unsolicited signs and symptoms were reported as AEs after review by the Investigator or designee, either separately using the corresponding MedDRA terminology of the sign or symptom or combined using the appropriate term. | Day 1 to Day 29 | 
| SAEs Through 28 Days After Licensed IIV Treatment | The number and percentage of study participants who experience SAEs from the time of study entry through 28 days after receipt of IIV. Unsolicited signs and symptoms were reported as AEs after review by the Investigator or designee, either separately using the corresponding MedDRA terminology of the sign or symptom or combined using the appropriate term. | Time of enrollment through 28 days after receipt of IIV where the IIV was administered an average of 49 days post-IP and with an interval up to 91 days later. |