Influenza Vaccine
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALSing2016 M2SR H3N2 influenza vaccine
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.
OTHERPlacebo
This group will receive saline placebo administered intranasally on Day 1 followed by IIV at least 28 days later.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
FluGen Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Three Cohorts will be enrolled sequentially with safety data reviewed between enrollment of successive cohorts.
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subjects must be willing and able to provide written informed consent. 2. 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). 3. 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 4. 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. 5. 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. 6. Women of childbearing potential must have a negative urine pregnancy test within 24 hours prior to vaccination with investigational product.
Exclusion criteria
1. 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. 2. 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. 3. 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. 4. Currently receiving, or planned to receive during the study, any immunosuppressive therapy. 5. Had a flu-like illness, influenza treatment, influenza vaccination, or prophylactic influenza viral drug administered in the previous 6 months before investigational product administration. 6. 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. 7. 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. 8. Acute febrile illness within 72 hours prior to investigational product vaccination 9. 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. 10. Planned donation of blood or blood product of at least approximately 1 pint within 3 months after investigational product administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Emergent AEs During 7 Days After Experimental Treatment | Day 1 to Day 8 | 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. |
| Treatment Emergent AEs During 28 Days After Experimental Treatment | Day 1 to Day 29 | 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. |
| SAEs Through 28 Days After Licensed IIV Treatment | 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. | 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. |
Countries
United States
Participant flow
Pre-assignment details
Cohort 1 included subjects ages 50-64 years as a safety check prior to age-escalating to older adults. Cohort 2 included a lead-in group of subjects 65-85 years as a safety check prior to enrolling the expansion group, Cohort 3, in the same age range. Cohorts 2 and 3 received the same treatments and results are combined for these subjects.
Participants by arm
| Arm | Count |
|---|---|
| M2SR Dose, 50-64 Years of Age Intranasal M2SR vaccine followed by standard, licensed IIV
Sing2016 M2SR H3N2 influenza vaccine: 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. | 10 |
| Placebo Dose, 50-64 Years of Age Intranasal physiological saline followed by standard, licensed IIV
Placebo: This group will receive saline placebo administered intranasally on Day 1 followed by IIV at least 28 days later. | 5 |
| M2SR Dose, 65-85 Years of Age Intranasal M2SR vaccine followed by licensed IIV recommended for people 65 years and older
Sing2016 M2SR H3N2 influenza vaccine: 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. | 70 |
| Placebo Dose, 65-85 Years of Age Intranasal physiological saline followed by licensed IIV recommended for people 65 years and older
Placebo: This group will receive saline placebo administered intranasally on Day 1 followed by IIV at least 28 days later. | 37 |
| Total | 122 |
Baseline characteristics
| Characteristic | Placebo Dose, 50-64 Years of Age | M2SR Dose, 65-85 Years of Age | M2SR Dose, 50-64 Years of Age | Placebo Dose, 65-85 Years of Age | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 70 Participants | 0 Participants | 37 Participants | 107 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 0 Participants | 10 Participants | 0 Participants | 15 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 2.9 | 70 years STANDARD_DEVIATION 4.2 | 57 years STANDARD_DEVIATION 3.1 | 73 years STANDARD_DEVIATION 4.6 | 72 years STANDARD_DEVIATION 6.6 |
| Baseline HAI titer to A/Sing2016 <40 | 3 Participants | 34 Participants | 8 Participants | 18 Participants | 63 Participants |
| Baseline HAI titer to A/Sing2016 40 to <=320 | 2 Participants | 36 Participants | 2 Participants | 19 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 8 Participants | 0 Participants | 2 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 62 Participants | 10 Participants | 35 Participants | 112 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 7 Participants | 0 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 61 Participants | 10 Participants | 34 Participants | 110 Participants |
| Region of Enrollment United States | 5 participants | 70 participants | 10 participants | 37 participants | 122 participants |
| Sex: Female, Male Female | 4 Participants | 46 Participants | 5 Participants | 23 Participants | 78 Participants |
| Sex: Female, Male Male | 1 Participants | 24 Participants | 5 Participants | 14 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 5 | 0 / 70 | 0 / 37 |
| other Total, other adverse events | 1 / 10 | 1 / 5 | 2 / 70 | 3 / 37 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 | 0 / 70 | 0 / 37 |
Outcome results
Primary
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 frame: 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.
Population: Numbers of subjects analyzed for SAEs includes 2 subjects who were administered IIV but who did not have biological samples collected and therefore were not considered to have completed trial. Thus, the participant flow shows 9 subjects completed while safety shows 10 subjects for the M2SR dose 50-64 years of age. Similarly, the participant flow shows 67 subjects completed while safety shows 68 subjects for the M2SR dose 65-85 years of age.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M2SR Dose, 50-64 Years of Age | SAEs Through 28 Days After Licensed IIV Treatment | 0 Participants |
| Placebo Dose, 50-64 Years of Age | SAEs Through 28 Days After Licensed IIV Treatment | 0 Participants |
| M2SR Dose, 65-85 Years of Age | SAEs Through 28 Days After Licensed IIV Treatment | 0 Participants |
| Placebo Dose, 65-85 Years of Age | SAEs Through 28 Days After Licensed IIV Treatment | 0 Participants |
Primary
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.
Time frame: Day 1 to Day 29
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M2SR Dose, 50-64 Years of Age | Treatment Emergent AEs During 28 Days After Experimental Treatment | 1 Participants |
| Placebo Dose, 50-64 Years of Age | Treatment Emergent AEs During 28 Days After Experimental Treatment | 1 Participants |
| M2SR Dose, 65-85 Years of Age | Treatment Emergent AEs During 28 Days After Experimental Treatment | 16 Participants |
| Placebo Dose, 65-85 Years of Age | Treatment Emergent AEs During 28 Days After Experimental Treatment | 8 Participants |
Primary
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.
Time frame: Day 1 to Day 8
Population: All subjects who received an IP dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M2SR Dose, 50-64 Years of Age | Treatment Emergent AEs During 7 Days After Experimental Treatment | 1 Participants |
| Placebo Dose, 50-64 Years of Age | Treatment Emergent AEs During 7 Days After Experimental Treatment | 0 Participants |
| M2SR Dose, 65-85 Years of Age | Treatment Emergent AEs During 7 Days After Experimental Treatment | 12 Participants |
| Placebo Dose, 65-85 Years of Age | Treatment Emergent AEs During 7 Days After Experimental Treatment | 3 Participants |