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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03999554

Enrollment

206

Registered

2019-06-26

Start date

2019-09-03

Completion date

2020-07-01

Last updated

2022-03-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Influenza A

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.

Interventions

BIOLOGICALLD Sing2016 M2SR H3N2 influenza vaccine

This group will receive a low dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.

BIOLOGICALMD Sing2016 M2SR H3N2 influenza vaccine

This group will receive a medium dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.

BIOLOGICALHD Sing2016 M2SR H3N2 influenza vaccine

This group will receive a high dose of the Sing2016 M2SR H3N2 monovalent influenza vaccine administered intranasally.

BIOLOGICALLD Bris10 M2SR H3N2 influenza vaccine

This group will receive a low dose of the Bris10 M2SR H3N2 monovalent influenza vaccine administered intranasally.

OTHERPlacebo

This group will receive saline placebo administered intranasally.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

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.

Eligibility

Sex/Gender

ALL

Age

18 Years to 49 Years

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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
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.
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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Low Dose Sing2016 M2SR 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.	42
Medium Dose Sing2016 M2SR 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.	41
High Dose Sing2016 M2SR 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.	40
Low Dose Bris10 M2SR 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.	42
Placebo Saline will be administered intranasally on days 1 and 29 Placebo: This group will receive saline placebo administered intranasally.	41
Total	206

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	failure to comply with protocol requirements	0	0	0	1	0
Overall Study	Lost to Follow-up	4	5	4	5	8
Overall Study	Pregnancy	0	0	1	0	0
Overall Study	Protocol Violation	0	0	5	0	0
Overall Study	Withdrawal by Subject	2	2	2	1	1

Baseline characteristics

Characteristic	Low Dose Sing2016 M2SR	Medium Dose Sing2016 M2SR	High Dose Sing2016 M2SR	Low Dose Bris10 M2SR	Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	42 Participants	41 Participants	40 Participants	42 Participants	41 Participants	206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants	16 Participants	18 Participants	20 Participants	18 Participants	96 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants	25 Participants	22 Participants	22 Participants	23 Participants	110 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	4 Participants	7 Participants	6 Participants	7 Participants	11 Participants	35 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Race (NIH/OMB) White	36 Participants	34 Participants	34 Participants	33 Participants	29 Participants	166 Participants
Sex: Female, Male Female	25 Participants	26 Participants	29 Participants	35 Participants	31 Participants	146 Participants
Sex: Female, Male Male	17 Participants	15 Participants	11 Participants	7 Participants	10 Participants	60 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 42	0 / 41	0 / 40	0 / 42	0 / 41
other Total, other adverse events	26 / 42	29 / 41	30 / 40	28 / 42	24 / 41
serious Total, serious adverse events	0 / 42	0 / 41	0 / 40	0 / 42	1 / 41

Outcome results

Primary

Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Bris10 M2SR and Cumulatively Through 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.

Time frame: From baseline through study completion (Day 209)

Population: Study participants who received at least one inoculation were included.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Low Dose Bris10 M2SR	Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Bris10 M2SR and Cumulatively Through Day 209	28 Participants
Placebo	Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Bris10 M2SR and Cumulatively Through Day 209	24 Participants

Primary

Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Sing2016 M2SR and Cumulatively Through 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.

Time frame: From baseline through study completion (Day 209)

Population: Study participants who received at least one inoculation were included.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Low Dose Bris10 M2SR	Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Sing2016 M2SR and Cumulatively Through Day 209	26 Participants
Placebo	Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Sing2016 M2SR and Cumulatively Through Day 209	29 Participants
High Dose Sing2016 M2SR	Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Sing2016 M2SR and Cumulatively Through Day 209	30 Participants
Placebo	Number of Participants With Local and Systemic Adverse Events (AEs) Through 29 Days Post-vaccination With Sing2016 M2SR and Cumulatively Through Day 209	24 Participants

Secondary

Percentage of Bris10 M2SR Subjects Demonstrating Mucosal Responses to Vaccine HA

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)