Safety and Immunogenicity of the Bris10 M2SR and Sing2016 M2SR H3N2 Monovalent Influenza Vaccines

• Sponsor: FluGen Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03999554
• Collaborator: (none)
• Enrollment: 206
• Locations: 4
• Arms: 5
• Actual Duration (Months): 9.9
• Patients Per Site: 51.5
• Patients Per Site Per Month: 5.2

Study Details

Study Description

Brief Summary

This is a Phase I double-blind, randomized, placebo-controlled study in 250 healthy adults, 18-49 years of age, inclusive, who are in good health and meet all eligibility criteria. The purpose of this dose escalation clinical study is to assess the safety, tolerability/reactogenicity, and immunogenicity of H3N2 M2SR investigational vaccines for prevention of influenza, when delivered at higher dosages or in two doses . Eligible subjects will be screened and randomized to receive two administrations 28 days apart of Sing2016 M2SR at three dose levels (low, medium, high), Bris10 M2SR at one dose level (low), or placebo in a 1:1:1:1:1 ratio. Study duration will be approximately 8 months with subject participation duration approximately 7 months. The primary study objective is to assess the safety and reactogenicity of a monovalent live single replication influenza H3N2 M2SR vaccine.

Condition or Disease	Intervention/Treatment	Phase
Influenza A	Biological: LD Sing2016 M2SR H3N2 influenza vaccine; Biological: MD Sing2016 M2SR H3N2 influenza vaccine; Biological: HD Sing2016 M2SR H3N2 influenza vaccine; Biological: LD Bris10 M2SR H3N2 influenza vaccine; Other: Placebo	Phase 1

Detailed Description

This is a Phase I double-blind, randomized, placebo-controlled study in 250 healthy adults, 18-49 years of age, inclusive, who are in good health and meet all eligibility criteria. This dose escalation clinical study is designed to assess the safety, tolerability/reactogenicity, and immunogenicity of H3N2 M2SR investigational vaccines for prevention of influenza, when delivered at increasing dosages or in two doses. Subjects will be enrolled in five groups in a 1:1:1:1:1 ratio. Arm 1 will receive a low dose of Sing2016 M2SR intranasally on days 1 and 29. Arm 2 will receive a medium dose of Sing2016 M2SR intranasally on days 1 and 29. Arm 3 will receive a high dose of Sing2016 M2SR intranasally on days 1 and 29. Arm 4 will receive a low dose of Bris16 M2SR intranasally on days 1 and 29. Arm 5 will receive a placebo intranasally on days 1 and 29. Study duration will be approximately 8 months with subject participation duration approximately 7 months. The primary study objective is to assess the safety and reactogenicity of a monovalent live single replication influenza H3N2 M2SR vaccine. The secondary study objectives are to evaluate systemic and mucosal immune responses induced by H3N2 M2SR vaccination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 206 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a randomized, double-blind, placebo-controlled Phase 1 study evaluating the safety and immunogenicity of the Bris10 M2SR and Sing2016 M2SR H3N2 influenza vaccines delivered intranasally to healthy adults. Eligible subjects will be screened and randomized to receive two administrations 28 days apart of Sing2016 M2SR at three dose levels, Bris10 M2SR at one dose level, or placebo in a 1:1:1:1:1 ratio.This is a randomized, double-blind, placebo-controlled Phase 1 study evaluating the safety and immunogenicity of the Bris10 M2SR and Sing2016 M2SR H3N2 influenza vaccines delivered intranasally to healthy adults. Eligible subjects will be screened and randomized to receive two administrations 28 days apart of Sing2016 M2SR at three dose levels, Bris10 M2SR at one dose level, or placebo in a 1:1:1:1:1 ratio.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Phase 1b Clinical Study to Investigate the Safety and Immunogenicity of the Bris10 (A/Brisbane/10/2007) M2SR and Sing2016 (A/Singapore/INFIMH-16-0019/2016) M2SR H3N2 Monovalent Influenza Vaccines
• Actual Study Start Date: Sep 3, 2019
• Actual Primary Completion Date: Jul 1, 2020
• Actual Study Completion Date: Jul 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low dose Sing2016 M2SR Low dose Sing2016 M2SR will be administered intranasally on days 1 and 29	Biological: LD Sing2016 M2SR H3N2 influenza vaccine; This group will receive a low dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.
Experimental: Medium dose Sing2016 M2SR Medium dose Sing2016 M2SR will be administered intranasally on days 1 and 29	Biological: MD Sing2016 M2SR H3N2 influenza vaccine; This group will receive a medium dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.
Experimental: High dose Sing2016 M2SR High dose Sing2016 M2SR will be administered intranasally on days 1 and 29	Biological: HD Sing2016 M2SR H3N2 influenza vaccine; This group will receive a high dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.
Active Comparator: Low dose Bris10 M2SR Low dose Bris10 M2SR will be administered intranasally on days 1 and 29	Biological: LD Bris10 M2SR H3N2 influenza vaccine; This group will receive a low dose of the Bris10 M2SR H3N2 monovalent influenza vaccine administered intranasally.
Placebo Comparator: Placebo Saline will be administered intranasally on days 1 and 29	Other: Placebo; This group will receive saline placebo administered intranasally.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Bris10 M2SR and Cumulatively Through Day 209 [From baseline through study completion (Day 209)]

   Record adverse events following one and two administrations of the Bris10 M2SR influenza vaccine to determine the number and percentage of study participants who experience any vaccine associated adverse events (AEs) or serious adverse events (SAEs) after Bris10 M2SR or placebo administration.

2. Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Sing2016 M2SR and Cumulatively Through Day 209 [From baseline through study completion (Day 209)]

   Record adverse events following one and two administrations of the Sing2016 M2SR influenza vaccine to determine the number and percentage of study participants who experience any vaccine associated adverse events (AEs) or serious adverse events (SAEs) after Sing2016 M2SR or placebo administration.

Secondary Outcome Measures

1. Percentage of Bris10 M2SR Subjects Demonstrating Seroconversion to Vaccine HA [From baseline through 28 days post-dose 1 (Day 29)]

   Assess the humoral immunogenicity of one administration of Bris10 M2SR vaccine to Bris 10 by HAI at day 29.

2. Percentage of Sing2016 M2SR Subjects Demonstrating Seroconversion to Vaccine HA [From baseline through 28 days post-dose 1 (Day 29)]

   Assess the humoral immunogenicity of one administration of Sing2016 M2SR vaccine to Sing2016 by HAI at day 29

3. Percentage of Bris10 M2SR Subjects Demonstrating Seroconversion to Vaccine HA [From baseline through 28 days post-dose 2 (Day 57)]

   Assess the humoral immunogenicity of two administrations of Bris10 M2SR vaccine to Bris 10 by HAI at d57.

4. Percentage of Sing2016 M2SR Subjects Demonstrating Seroconversion to Vaccine HA [From baseline through 28 days post-dose 2 (Day 57)]

   Assess the humoral immunogenicity of two administrations of Sing2016 M2SR vaccine to Sing2016 by HAI at day 57

5. Percentage of Bris10 M2SR Subjects Demonstrating Mucosal Responses to Vaccine HA [From baseline through 28 days post-dose 1 (Day 29)]

   Assess the mucosal immunogenicity of one administration of Bris10 M2SR vaccine to Bris 10 by ELISA at day 29.

6. Percentage of Bris10 M2SR Subjects Demonstrating Mucosal Responses to Vaccine HA [From baseline through 28 days post-dose 2 (Day 57)]

   Assess the mucosal immunogenicity of two administrations of Bris10 M2SR vaccine to Bris 10 by ELISA at day 57.

7. Percentage of Sing2016 M2SR Subjects Demonstrating Mucosal Responses to Vaccine HA [From baseline through 28 days post-dose 2 (Day 57)]

   Assess the mucosal immunogenicity of two administrations of Sing2016 M2SR vaccine to Sing2016 by ELISA at day 57

8. Percentage of Sing2016 M2SR Subjects Demonstrating Mucosal Responses to Vaccine HA [From baseline through 28 days post-dose 1 (Day 29)]

   Assess the mucosal immunogenicity of one administration of Sing2016 M2SR vaccine to Sing2016 by ELISA at day 29

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Give written informed consent to participate.

2. Age 18 - 49 years old.

3. Judged suitable by the PI, as determined by medical history, physical examination, vital signs, and clinical safety laboratory examinations.

4. Willing to use oral, implantable, transdermal or injectable contraceptives, or sexual abstinence, from screening and until 28 days after second vaccine dose.

5. 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.

Exclusion Criteria:

1. Abnormal screening hematology or chemistry value per the FDA Toxicity Guidance.

2. Pulse rate or blood pressure outside the reference range for this study population and considered as clinically significant by the Investigator.

3. Has an 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.

4. Presence or clinically significant history of lung disease, asthma, chronic obstructive pulmonary disease (COPD), or otherwise poor lung function.

5. Any confirmed or suspected immunosuppressive or immunodeficient state.

6. Presence of household member or close personal or professional (i.e., healthcare worker) who is a child under one year of age; is pregnant; has known immunodeficiency or is receiving immunosuppressant medication; is undergoing or soon to undergo cancer chemotherapy; has been diagnosed with emphysema, COPD, or other severe lung disease and resides in a nursing home; and/or has received a bone marrow or solid organ transplant.

7. Females who are pregnant or lactating.

8. Acute febrile illness within 72 hours prior to vaccination.

9. Any condition, in the opinion of the Investigator, (such as subjects who have medically high-risk conditions) that might interfere with the primary study objectives for safety of the study subject.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	RCA	Hollywood	Florida	United States	33024
2	JCCT	Lenexa	Kansas	United States	66219
3	AMR Lexington	Lexington	Kentucky	United States	40509
4	AMR Norfolk	Norfolk	Virginia	United States	23507

Sponsors and Collaborators

• FluGen Inc

Investigators

• Study Director: Pamuk Bilsel, FluGen Inc
• Principal Investigator: Carlos Fierro, MD, JCCT

Study Documents (Full-Text)

• Study Protocol - May 18, 2020
• Statistical Analysis Plan - Jul 28, 2020

More Information

Publications

None provided.

• Responsible Party: FluGen Inc
• ClinicalTrials.gov Identifier: NCT03999554
• Other Study ID Numbers: FLUGEN-H3N2-V003
• First Posted: Jun 26, 2019
• Last Update Posted: Mar 4, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Arm/Group Title	Low Dose Sing2016 M2SR	Medium Dose Sing2016 M2SR	High Dose Sing2016 M2SR	Low Dose Bris10 M2SR	Placebo
Arm/Group Description	Low dose Sing2016 M2SR will be administered intranasally on days 1 and 29 LD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Medium dose Sing2016 M2SR will be administered intranasally on days 1 and 29 MD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a medium dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	High dose Sing2016 M2SR will be administered intranasally on days 1 and 29 HD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a high dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Low dose Bris10 M2SR will be administered intranasally on days 1 and 29 LD Bris10 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Bris10 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Period Title: Overall Study
STARTED	42	41	40	42	41
COMPLETED	36	34	28	35	32
NOT COMPLETED	6	7	12	7	9

Baseline Characteristics

Arm/Group Title	Low Dose Sing2016 M2SR	Medium Dose Sing2016 M2SR	High Dose Sing2016 M2SR	Low Dose Bris10 M2SR	Placebo	Total
Arm/Group Description	Low dose Sing2016 M2SR will be administered intranasally on days 1 and 29 LD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Medium dose Sing2016 M2SR will be administered intranasally on days 1 and 29 MD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a medium dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	High dose Sing2016 M2SR will be administered intranasally on days 1 and 29 HD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a high dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Low dose Bris10 M2SR will be administered intranasally on days 1 and 29 LD Bris10 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Bris10 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.	Total of all reporting groups
Overall Participants	42	41	40	42	41	206
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	42 100%	41 100%	40 100%	42 100%	41 100%	206 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	25 59.5%	26 63.4%	29 72.5%	35 83.3%	31 75.6%	146 70.9%
Male	17 40.5%	15 36.6%	11 27.5%	7 16.7%	10 24.4%	60 29.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 57.1%	16 39%	18 45%	20 47.6%	18 43.9%	96 46.6%
Not Hispanic or Latino	18 42.9%	25 61%	22 55%	22 52.4%	23 56.1%	110 53.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	1 2.4%	1 0.5%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	1 2.4%	0 0%	0 0%	0 0%	0 0%	1 0.5%
Black or African American	4 9.5%	7 17.1%	6 15%	7 16.7%	11 26.8%	35 17%
White	36 85.7%	34 82.9%	34 85%	33 78.6%	29 70.7%	166 80.6%
More than one race	0 0%	0 0%	0 0%	1 2.4%	0 0%	1 0.5%
Unknown or Not Reported	1 2.4%	0 0%	0 0%	1 2.4%	0 0%	2 1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Bris10 M2SR and Cumulatively Through Day 209
Description	Record adverse events following one and two administrations of the Bris10 M2SR influenza vaccine to determine the number and percentage of study participants who experience any vaccine associated adverse events (AEs) or serious adverse events (SAEs) after Bris10 M2SR or placebo administration.
Time Frame	From baseline through study completion (Day 209)

Outcome Measure Data

Analysis Population Description

Study participants who received at least one inoculation were included.

Arm/Group Title	Low Dose Bris10 M2SR	Placebo
Arm/Group Description	Low dose Bris10 M2SR will be administered intranasally on days 1 and 29 LD Bris10 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Bris10 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Measure Participants	42	41
Count of Participants [Participants]	28 66.7%	24 58.5%

2. Primary Outcome

Title	Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Sing2016 M2SR and Cumulatively Through Day 209
Description	Record adverse events following one and two administrations of the Sing2016 M2SR influenza vaccine to determine the number and percentage of study participants who experience any vaccine associated adverse events (AEs) or serious adverse events (SAEs) after Sing2016 M2SR or placebo administration.
Time Frame	From baseline through study completion (Day 209)

Outcome Measure Data

Analysis Population Description

Study participants who received at least one inoculation were included.

Arm/Group Title	Low Dose Sing2016 M2SR	Medium Dose Sing2016 M2SR	High Dose Sing2016 M2SR	Placebo
Arm/Group Description	Low dose Sing2016 M2SR will be administered intranasally on days 1 and 29 LD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Medium dose Sing2016 M2SR will be administered intranasally on days 1 and 29 MD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a medium dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	High dose Sing2016 M2SR will be administered intranasally on days 1 and 29 HD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a high dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Measure Participants	42	41	40	41
Count of Participants [Participants]	26 61.9%	29 70.7%	30 75%	24 57.1%

3. Secondary Outcome

Title	Percentage of Bris10 M2SR Subjects Demonstrating Seroconversion to Vaccine HA
Description	Assess the humoral immunogenicity of one administration of Bris10 M2SR vaccine to Bris 10 by HAI at day 29.
Time Frame	From baseline through 28 days post-dose 1 (Day 29)

Outcome Measure Data

Analysis Population Description

Study subjects who received at least one inoculation were included.

Arm/Group Title	Low Dose Bris10 M2SR	Placebo
Arm/Group Description	Low dose Bris10 M2SR will be administered intranasally on days 1 and 29 LD Bris10 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Bris10 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Measure Participants	38	38
Number (95% Confidence Interval) [Percentage of subjects]	28.9	10.5

4. Secondary Outcome

Title	Percentage of Sing2016 M2SR Subjects Demonstrating Seroconversion to Vaccine HA
Description	Assess the humoral immunogenicity of one administration of Sing2016 M2SR vaccine to Sing2016 by HAI at day 29
Time Frame	From baseline through 28 days post-dose 1 (Day 29)

Outcome Measure Data

Analysis Population Description

Study subjects who received at least one inoculation were included.

Arm/Group Title	Low Dose Sing2016 M2SR	Medium Dose Sing2016 M2SR	High Dose Sing2016 M2SR	Placebo
Arm/Group Description	Low dose Sing2016 M2SR will be administered intranasally on days 1 and 29 LD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Medium dose Sing2016 M2SR will be administered intranasally on days 1 and 29 MD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a medium dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	High dose Sing2016 M2SR will be administered intranasally on days 1 and 29 HD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a high dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Measure Participants	40	38	31	38
Number (95% Confidence Interval) [Percentage of participants]	27.5 65.5%	36.8 89.8%	71.0 177.5%	0 0%

5. Secondary Outcome

Title	Percentage of Bris10 M2SR Subjects Demonstrating Seroconversion to Vaccine HA
Description	Assess the humoral immunogenicity of two administrations of Bris10 M2SR vaccine to Bris 10 by HAI at d57.
Time Frame	From baseline through 28 days post-dose 2 (Day 57)

Outcome Measure Data

Analysis Population Description

Study subjects who received at least one inoculation were included.

Arm/Group Title	Low Dose Bris10 M2SR	Placebo
Arm/Group Description	Low dose Bris10 M2SR will be administered intranasally on days 1 and 29 LD Bris10 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Bris10 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Measure Participants	37	35
Number (95% Confidence Interval) [Percentage of subjects]	40.5	14.3

6. Secondary Outcome

Title	Percentage of Sing2016 M2SR Subjects Demonstrating Seroconversion to Vaccine HA
Description	Assess the humoral immunogenicity of two administrations of Sing2016 M2SR vaccine to Sing2016 by HAI at day 57
Time Frame	From baseline through 28 days post-dose 2 (Day 57)

Outcome Measure Data

Analysis Population Description

Study subjects who received at least one inoculation were included.

Arm/Group Title	Low Dose Sing2016 M2SR	Medium Dose Sing2016 M2SR	High Dose Sing2016 M2SR	Placebo
Arm/Group Description	Low dose Sing2016 M2SR will be administered intranasally on days 1 and 29 LD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Medium dose Sing2016 M2SR will be administered intranasally on days 1 and 29 MD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a medium dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	High dose Sing2016 M2SR will be administered intranasally on days 1 and 29 HD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a high dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Measure Participants	38	36	31	35
Number (95% Confidence Interval) [Percentage of subjects]	47.4	55.6	80.6	0

7. Secondary Outcome

Title	Percentage of Bris10 M2SR Subjects Demonstrating Mucosal Responses to Vaccine HA
Description	Assess the mucosal immunogenicity of one administration of Bris10 M2SR vaccine to Bris 10 by ELISA at day 29.
Time Frame	From baseline through 28 days post-dose 1 (Day 29)

Outcome Measure Data

Analysis Population Description

Study subjects who received at least one inoculation were included.

Arm/Group Title	Low Dose Bris10 M2SR	Placebo
Arm/Group Description	Low dose Bris10 M2SR will be administered intranasally on days 1 and 29 LD Bris10 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Bris10 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Measure Participants	36	36
Number (95% Confidence Interval) [Percentage of subjects]	22.2	25.0

8. Secondary Outcome

Title	Percentage of Bris10 M2SR Subjects Demonstrating Mucosal Responses to Vaccine HA
Description	Assess the mucosal immunogenicity of two administrations of Bris10 M2SR vaccine to Bris 10 by ELISA at day 57.
Time Frame	From baseline through 28 days post-dose 2 (Day 57)

Outcome Measure Data

Analysis Population Description

Study subjects who received at least one inoculation were included.

Arm/Group Title	Low Dose Bris10 M2SR	Placebo
Arm/Group Description	Low dose Bris10 M2SR will be administered intranasally on days 1 and 29 LD Bris10 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Bris10 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Measure Participants	33	31
Number (95% Confidence Interval) [Percentage of subjects]	39.4	25.8

9. Secondary Outcome

Title	Percentage of Sing2016 M2SR Subjects Demonstrating Mucosal Responses to Vaccine HA
Description	Assess the mucosal immunogenicity of two administrations of Sing2016 M2SR vaccine to Sing2016 by ELISA at day 57
Time Frame	From baseline through 28 days post-dose 2 (Day 57)

Outcome Measure Data

Analysis Population Description

Study subjects who received at least one inoculation were included.

Arm/Group Title	Low Dose Sing2016 M2SR	Medium Dose Sing2016 M2SR	High Dose Sing2016 M2SR	Placebo
Arm/Group Description	Low dose Sing2016 M2SR will be administered intranasally on days 1 and 29 LD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Medium dose Sing2016 M2SR will be administered intranasally on days 1 and 29 MD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a medium dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	High dose Sing2016 M2SR will be administered intranasally on days 1 and 29 HD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a high dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Measure Participants	35	33	28	31
Number (95% Confidence Interval) [Percentage of subjects]	20	45.5	60.7	19.4

10. Secondary Outcome

Title	Percentage of Sing2016 M2SR Subjects Demonstrating Mucosal Responses to Vaccine HA
Description	Assess the mucosal immunogenicity of one administration of Sing2016 M2SR vaccine to Sing2016 by ELISA at day 29
Time Frame	From baseline through 28 days post-dose 1 (Day 29)

Outcome Measure Data

Analysis Population Description

Study subjects who received at least one inoculation were included.

Arm/Group Title	Low Dose Sing2016 M2SR	Medium Dose Sing2016 M2SR	High Dose Sing2016 M2SR	Placebo
Arm/Group Description	Low dose Sing2016 M2SR will be administered intranasally on days 1 and 29 LD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Medium dose Sing2016 M2SR will be administered intranasally on days 1 and 29 MD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a medium dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	High dose Sing2016 M2SR will be administered intranasally on days 1 and 29 HD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a high dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.	Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
Measure Participants	38	36	29	36
Number (95% Confidence Interval) [Percentage of subjects]	15.8	22.2	37.9	19.4

Adverse Events

Time Frame	Adverse events were monitored continuously from first administration of IP until study day 57. SAEs were collected until study day 209.
Adverse Event Reporting Description	Administration site and solicited AEs were recorded through 7 days after each vaccination (Days 8 and 29), unsolicited AEs were recorded through 28 days after the last vaccination (Day 57) and SAEs were recorded until Day 209.
Arm/Group Title	Low Dose Sing2016 M2SR		Medium Dose Sing2016 M2SR		High Dose Sing2016 M2SR		Low Dose Bris10 M2SR		Placebo
Arm/Group Description	Low dose Sing2016 M2SR will be administered intranasally on days 1 and 29 LD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.		Medium dose Sing2016 M2SR will be administered intranasally on days 1 and 29 MD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a medium dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.		High dose Sing2016 M2SR will be administered intranasally on days 1 and 29 HD Sing2016 M2SR H3N2 influenza vaccine: This group will receive a high dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.		Low dose Bris10 M2SR will be administered intranasally on days 1 and 29 LD Bris10 M2SR H3N2 influenza vaccine: This group will receive a low dose of the Bris10 M2SR H3N2 monovalent influenza vaccine administered intranasally.		Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.
All Cause Mortality
	Low Dose Sing2016 M2SR		Medium Dose Sing2016 M2SR		High Dose Sing2016 M2SR		Low Dose Bris10 M2SR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/41 (0%)		0/40 (0%)		0/42 (0%)		0/41 (0%)
Serious Adverse Events
	Low Dose Sing2016 M2SR		Medium Dose Sing2016 M2SR		High Dose Sing2016 M2SR		Low Dose Bris10 M2SR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/41 (0%)		0/40 (0%)		0/42 (0%)		1/41 (2.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
papillary thyroid cancer	0/42 (0%)	0	0/41 (0%)	0	0/40 (0%)	0	0/42 (0%)	0	1/41 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Low Dose Sing2016 M2SR		Medium Dose Sing2016 M2SR		High Dose Sing2016 M2SR		Low Dose Bris10 M2SR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/42 (61.9%)		29/41 (70.7%)		30/40 (75%)		28/42 (66.7%)		24/41 (58.5%)
Cardiac disorders
bradycardia	0/42 (0%)		2/41 (4.9%)		0/40 (0%)		1/42 (2.4%)		0/41 (0%)
Gastrointestinal disorders
nausea	4/42 (9.5%)		1/41 (2.4%)		2/40 (5%)		2/42 (4.8%)		5/41 (12.2%)
General disorders
fatigue	13/42 (31%)		8/41 (19.5%)		10/40 (25%)		14/42 (33.3%)		8/41 (19.5%)
pyrexia	5/42 (11.9%)		3/41 (7.3%)		3/40 (7.5%)		1/42 (2.4%)		1/41 (2.4%)
Investigations
AAT increase	2/42 (4.8%)		0/41 (0%)		0/40 (0%)		0/42 (0%)		0/41 (0%)
blood creatinine phosphate increase	1/42 (2.4%)		2/41 (4.9%)		0/40 (0%)		1/42 (2.4%)		1/41 (2.4%)
blood urine	0/42 (0%)		0/41 (0%)		2/40 (5%)		0/42 (0%)		0/41 (0%)
white blood cell increase	0/42 (0%)		2/41 (4.9%)		0/40 (0%)		0/42 (0%)		0/41 (0%)
Metabolism and nutrition disorders
hyperkalemia	0/42 (0%)		0/41 (0%)		2/40 (5%)		0/42 (0%)		0/41 (0%)
Musculoskeletal and connective tissue disorders
myalgia	9/42 (21.4%)		6/41 (14.6%)		9/40 (22.5%)		7/42 (16.7%)		4/41 (9.8%)
arthralgia	6/42 (14.3%)		4/41 (9.8%)		3/40 (7.5%)		2/42 (4.8%)		3/41 (7.3%)
Nervous system disorders
headache	12/42 (28.6%)		9/41 (22%)		11/40 (27.5%)		14/42 (33.3%)		10/41 (24.4%)
Respiratory, thoracic and mediastinal disorders
nasal congestion	11/42 (26.2%)		9/41 (22%)		15/40 (37.5%)		13/42 (31%)		14/41 (34.1%)
cough	9/42 (21.4%)		9/41 (22%)		10/40 (25%)		5/42 (11.9%)		6/41 (14.6%)
rhinorrhea	8/42 (19%)		12/41 (29.3%)		12/40 (30%)		8/42 (19%)		10/41 (24.4%)
throat irritation	8/42 (19%)		4/41 (9.8%)		5/40 (12.5%)		4/42 (9.5%)		6/41 (14.6%)
oropharyngeal pain	4/42 (9.5%)		5/41 (12.2%)		8/40 (20%)		7/42 (16.7%)		3/41 (7.3%)
nasal discomfort	3/42 (7.1%)		3/41 (7.3%)		1/40 (2.5%)		3/42 (7.1%)		2/41 (4.9%)
upper airway cough syndrome	2/42 (4.8%)		0/41 (0%)		0/40 (0%)		0/42 (0%)		1/41 (2.4%)
epistaxis	0/42 (0%)		2/41 (4.9%)		1/40 (2.5%)		1/42 (2.4%)		1/41 (2.4%)
nasal dryness	0/42 (0%)		3/41 (7.3%)		2/40 (5%)		1/42 (2.4%)		1/41 (2.4%)
nasal pruritis	0/42 (0%)		3/41 (7.3%)		0/40 (0%)		1/42 (2.4%)		0/41 (0%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

SPONSOR has exclusive right to publish and authorize study publications or communications. INVESTIGATOR makes no presentations/publications of the Study or its results without prior SPONSOR review and approval. SPONSOR will have 90 days to request amendments including but not limited to details that may be detrimental to its intellectual property interests or to the conduct, completion, or analysis of the results of the Study by SPONSOR or its affiliates.