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

Phase 1

Completed

• Conditions: Influenza A
• Interventions: Other: Placebo; 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

• Registration Number: NCT03999554
• Lead Sponsor: FluGen Inc

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.

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 Timeline

• Study First Submitted: 2019-06-18
• Study First Submitted QC: 2019-06-25
• Study First Posted: 2019-06-26
• Study Start: 2019-09-03
• Primary Completion: 2020-07-01
• Study Completion: 2020-07-01
• Results First Submitted: 2021-08-11
• Status Verified: 2021-12
• Results First Submitted QC: 2021-12-10
• Last Update Submitted: 2021-12-10
• Results First Posted: 2022-03-04
• Last Update Posted: 2022-03-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 206

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Saline will be administered intranasally on days 1 and 29
Low dose Sing2016 M2SR	LD Sing2016 M2SR H3N2 influenza vaccine	Low dose Sing2016 M2SR will be administered intranasally on days 1 and 29
Medium dose Sing2016 M2SR	MD Sing2016 M2SR H3N2 influenza vaccine	Medium dose Sing2016 M2SR will be administered intranasally on days 1 and 29
High dose Sing2016 M2SR	HD Sing2016 M2SR H3N2 influenza vaccine	High dose Sing2016 M2SR will be administered intranasally on days 1 and 29
Low dose Bris10 M2SR	LD Bris10 M2SR H3N2 influenza vaccine	Low dose Bris10 M2SR will be administered intranasally on days 1 and 29

Primary Outcome Measures

Name	Time	Method
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.
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

Name	Time	Method
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.
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
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.
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

Trial Locations

Locations (4)

AMR Lexington; 🇺🇸 Lexington, Kentucky, United States

AMR Norfolk; 🇺🇸 Norfolk, Virginia, United States

JCCT; 🇺🇸 Lenexa, Kansas, United States

RCA; 🇺🇸 Hollywood, Florida, United States