Healthy, Influenza
Conditions
Keywords
Bivalent., Influenza., FluMist Quadrivalent., Vaccine Prevention in Healthy Adults.
Brief summary
This prospective annual release study is designed to evaluate the safety of 2 new influenza virus vaccine strains to be included in FluMist Quadrivalent for the 2018-2019 influenza season.
Detailed description
This prospective. randomized, double-blind. placebo-controlled release study will enroll approximately 300 healthy adults 18 to 49 years of age (not yet reached their 50th birthday). Eligible subjects will be randomly assigned in a 4:1 fashion to receive a single dose of bivalent vaccine or placebo by intranasal spray. Randomization will be stratified by site. This study will be conducted at 2 sites in the United States of America. Each subject will receive 1 dose of investigational product on Day 1. The duration of study participation for each subject is the time from study vaccination through 180 days after study vaccination.
Interventions
BIOLOGICALBivalent influenza vaccine
A single dose of bivalent vaccine (10\^7±5 fluorescent focus unit of 2 cold-adapted, attenuated, temperature-sensitive, 6:2 reassortant influenza strain) will be administered as intranasal spray on Day 1.
OTHERPlacebo
A single dose of placebo matched to bivalent influenza vaccine will be administered as intranasal spray on Day 1.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 through 49 years * Written informed consent * Subject available by telephone * Ability to understand and comply with the requirements of the protocol, as judged by the Investigator
Exclusion criteria
* Concurrent enrollment in another clinical study up to 180 days after receipt of investigational product (Day 181) * History of hypersensitivity to any component of the vaccine, including egg or egg protein or serious, life threatening, or severe reactions to previous influenza vaccinations * Any condition for which the inactivated influenza vaccine is indicated, including chronic disorders of the pulmonary or cardiovascular systems (example (eg\], asthma), chronic metabolic diseases (eg, diabetes mellitus), renaldysfunction, or hemoglobinopathies that required regular medical follow-up or hospitalization during the preceding year * Acute febrile (greater than \[\>\]100.0 degrees Fahrenheit \[F\] oral or equivalent) and/or clinically significant respiratory illness (example, cough or sore throat) within 14 days to randomization * Any known immunosuppressive condition or immune deficiency diseases, including human immunodeficiency virus infection, or ongoing immunosuppressive therapy * History of Guillain-Barre syndrome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Reporting Fever (Oral Temperature >= 101 Degrees Fahrenheit) Through Day 8 | Day 1 through Day 8 | Percentage of participants with fever (oral temperature \>= 101 degrees Fahrenheit) through Day 8 is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Solicited Symptoms Through Day 8 | Day 1 through Day 8 | For this study, solicited symptoms included oral fever (\> 100 degrees Fahrenheit), runny nose, sore throat, cough, vomiting, muscle aches, chills, decreased activity (tiredness), and headache. |
| Number of Participants With Solicited Symptoms Through Day 15 | Day 1 through Day 15 | For this study, solicited symptoms included oral fever (\> 100 degrees Fahrenheit), runny nose, sore throat, cough, vomiting, muscle aches, chills, decreased activity (tiredness), and headache. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Through Day 8 and Day 15 | Day 1 through Day 8; Day 1 through Day 15 | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
| Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Through Day 29 and Day 181 | Day 1 through Day 29; Day 1 through Day 181 | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
| Number of Participants With New Onset Chronic Diseases (NOCDs) Through Day 29 and Day 181 | Day 1 through Day 29; Day 1 through Day 181 | An NOCD is a newly diagnosed medical condition that is of a chronic, ongoing nature and is assessed by the investigator as medically significant. |
Countries
United States
Participant flow
Recruitment details
The study was conducted between 06Jun2018 and 27Dec2018 in the USA.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single dose of placebo matched to bivalent vaccine by intranasal spray. | 60 |
| Bivalent Vaccine Participants received a single dose of bivalent vaccine by intranasal spray. | 240 |
| Total | 300 |
Baseline characteristics
| Characteristic | Bivalent Vaccine | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 30.5 Years STANDARD_DEVIATION 8.9 | 30.3 Years STANDARD_DEVIATION 8.9 | 29.5 Years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 16 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 228 Participants | 284 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 52 Participants | 64 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 11 Participants | 11 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 167 Participants | 214 Participants | 47 Participants |
| Sex: Female, Male Female | 139 Participants | 173 Participants | 34 Participants |
| Sex: Female, Male Male | 101 Participants | 127 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 240 |
| other Total, other adverse events | 2 / 60 | 19 / 240 |
| serious Total, serious adverse events | 0 / 60 | 1 / 240 |
Outcome results
Primary
Percentage of Participants Reporting Fever (Oral Temperature >= 101 Degrees Fahrenheit) Through Day 8
Percentage of participants with fever (oral temperature \>= 101 degrees Fahrenheit) through Day 8 is reported.
Time frame: Day 1 through Day 8
Population: The ITT population included all randomized and treated participants, grouped according to actual treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Reporting Fever (Oral Temperature >= 101 Degrees Fahrenheit) Through Day 8 | 0 Percentage of participants |
| Bivalent Vaccine | Percentage of Participants Reporting Fever (Oral Temperature >= 101 Degrees Fahrenheit) Through Day 8 | 0 Percentage of participants |
95% CI: [-6.7, 1.9]
Secondary
Number of Participants With New Onset Chronic Diseases (NOCDs) Through Day 29 and Day 181
An NOCD is a newly diagnosed medical condition that is of a chronic, ongoing nature and is assessed by the investigator as medically significant.
Time frame: Day 1 through Day 29; Day 1 through Day 181
Population: The ITT population included all randomized and treated participants, grouped according to actual treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With New Onset Chronic Diseases (NOCDs) Through Day 29 and Day 181 | NOCDs through Day 29 | 0 Participants |
| Placebo | Number of Participants With New Onset Chronic Diseases (NOCDs) Through Day 29 and Day 181 | NOCDs through Day 181 | 0 Participants |
| Bivalent Vaccine | Number of Participants With New Onset Chronic Diseases (NOCDs) Through Day 29 and Day 181 | NOCDs through Day 29 | 0 Participants |
| Bivalent Vaccine | Number of Participants With New Onset Chronic Diseases (NOCDs) Through Day 29 and Day 181 | NOCDs through Day 181 | 0 Participants |
Secondary
Number of Participants With Solicited Symptoms Through Day 15
For this study, solicited symptoms included oral fever (\> 100 degrees Fahrenheit), runny nose, sore throat, cough, vomiting, muscle aches, chills, decreased activity (tiredness), and headache.
Time frame: Day 1 through Day 15
Population: The ITT population included all randomized and treated participants, grouped according to actual treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | >=101 degrees Fahrenheit | 0 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | Cough | 3 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | >103 degrees Fahrenheit | 0 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | Vomiting | 1 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | >100 degrees Fahrenheit | 0 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | Muscle aches | 0 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | Runny nose | 4 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | Chills | 0 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | >102 degrees Fahrenheit | 0 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | Decreased activity (tiredness) | 3 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | Headache | 8 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 15 | Sore throat | 4 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | Headache | 33 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | >100 degrees Fahrenheit | 1 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | >=101 degrees Fahrenheit | 1 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | >102 degrees Fahrenheit | 1 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | >103 degrees Fahrenheit | 0 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | Runny nose | 37 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | Sore throat | 17 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | Cough | 9 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | Vomiting | 0 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | Muscle aches | 8 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | Chills | 4 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 15 | Decreased activity (tiredness) | 13 Participants |
Secondary
Number of Participants With Solicited Symptoms Through Day 8
For this study, solicited symptoms included oral fever (\> 100 degrees Fahrenheit), runny nose, sore throat, cough, vomiting, muscle aches, chills, decreased activity (tiredness), and headache.
Time frame: Day 1 through Day 8
Population: The ITT population included all randomized and treated participants, grouped according to actual treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | Runny nose | 4 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | Vomiting | 1 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | >103 degrees Fahrenheit | 0 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | Muscle aches | 0 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | Sore throat | 2 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | Chills | 0 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | >102 degrees Fahrenheit | 0 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | Decreased activity (tiredness) | 2 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | Cough | 3 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | Headache | 6 Participants |
| Placebo | Number of Participants With Solicited Symptoms Through Day 8 | >100 degrees Fahrenheit | 0 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | Headache | 27 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | >100 degrees Fahrenheit | 0 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | >102 degrees Fahrenheit | 0 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | >103 degrees Fahrenheit | 0 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | Runny nose | 33 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | Sore throat | 14 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | Cough | 7 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | Vomiting | 0 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | Muscle aches | 7 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | Chills | 3 Participants |
| Bivalent Vaccine | Number of Participants With Solicited Symptoms Through Day 8 | Decreased activity (tiredness) | 9 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Through Day 8 and Day 15
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time frame: Day 1 through Day 8; Day 1 through Day 15
Population: The ITT population included all randomized and treated participants, grouped according to actual treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Through Day 8 and Day 15 | TEAEs through Day 8 | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Through Day 8 and Day 15 | TEAEs through Day 15 | 2 Participants |
| Bivalent Vaccine | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Through Day 8 and Day 15 | TEAEs through Day 8 | 15 Participants |
| Bivalent Vaccine | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Through Day 8 and Day 15 | TEAEs through Day 15 | 19 Participants |
Secondary
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Through Day 29 and Day 181
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time frame: Day 1 through Day 29; Day 1 through Day 181
Population: The ITT population included all randomized and treated participants, grouped according to actual treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Through Day 29 and Day 181 | TESAEs through Day 29 | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Through Day 29 and Day 181 | TESAEs through Day 181 | 0 Participants |
| Bivalent Vaccine | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Through Day 29 and Day 181 | TESAEs through Day 29 | 1 Participants |
| Bivalent Vaccine | Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) Through Day 29 and Day 181 | TESAEs through Day 181 | 1 Participants |