Healthy, Influenza
Conditions
Keywords
Trivalent, Influenza, FluMist Quadrivalent, Vaccine, Prevention, Healthy
Brief summary
This prospective annual release study is designed to evaluate the safety of 3 new influenza virus vaccine strains to be included in FluMist Quadrivalent for the 2015-2016 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. Eligible participants will be randomly assigned in a 4:1 fashion to receive a single dose of trivalent vaccine or placebo by intranasal spray. Randomization will be stratified by site. This study will be conducted at 3 sites in the United States of America. Each participant will receive 1 dose of investigational product on Day 1. The duration of study participation for each participant is the time from study vaccination through 181 days after study vaccination.
Interventions
BIOLOGICALTrivalent Influenza Vaccine
A single dose of 10\^(7.0 ± 0.5) FFU per strain of trivalent influenza vaccine will be administered as intranasal spray on Day 1.
OTHERPlacebo
A single dose of placebo matched to trivalent influenza vaccine will be administered as intranasal spray on Day 1.
Sponsors
AstraZeneca
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 * Participant 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), renal dysfunction, 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 prior to randomization * Any known immunosuppressive condition or immune deficiency disease, including human immunodeficiency virus infection, or ongoing immunosuppressive therapy * History of Guillain-Barré syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Fever Greater Than or Equal to (>=) 101 Degrees Fahrenheit (F) | Baseline (Day 1) up to Day 8 | Percentage of participants with fever defined as oral temperature \>=101 degrees F were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Solicited Symptoms | Baseline (Day 1) up to Day 8 and Day 15 | Solicited symptoms are predefined symptoms or events specifically inquired about and assessed daily after vaccine administration up to 15 days after vaccination. The solicited symptoms include fever greater than (\>) 100.0 degrees F (37.8 degrees Celsius), runny nose, sore throat, cough, vomiting, muscle aches, chills, decreased activity and headache. Results were reported for all solicited symptoms except fever \>=101 degrees F (reported as primary outcome) within 8 days after vaccination and all solicited symptoms within 15 days after vaccination. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Baseline (Day 1) up to 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. Treatment-emergent AEs were events between administration of study drug and up to 15 days after vaccination that are absent before treatment or that worsened relative to pre-treatment state. Results were given for AEs reported within 8 days and 15 days after vaccination. |
| Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs) | Baseline (Day 1) up to Day 29 and 181 | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. Treatment-emergent SAEs were serious events between administration of study drug and up to 181 days after the dose that are absent before treatment or that worsen relative to pretreatment state. An NOCD is a newly diagnosed medical condition that is of a chronic, ongoing nature and is assessed by the investigator as medically significant. Results were given for TESAEs and NOCDs reported within 29 days and 181 days after vaccination. |
| Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Baseline (Day 1) up to Day 8 and Day 15 | Percentage of participants who require antipyretic and/or analgesic medication were reported. |
Countries
United States
Participant flow
Pre-assignment details
A total of 300 participants were randomized and participated in the study from 15-Jun-2015 through 15-Jan-2016 at 3 sites in the United States of America (USA).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single dose of placebo matching with trivalent influenza vaccine by intranasal spray on Day 1. | 60 |
| Trivalent Influenza Vaccine Participants received a single dose of trivalent influenza vaccine \[10\^7.0 +/- 0.5 fluorescent focus unit (FFU) of each of 3 cold adapted (ca), attenuated (att), temperature sensitive (ts) 6:2 reassortant influenza strains\] by intranasal spray on Day 1. | 240 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Trivalent Influenza Vaccine | Total |
|---|---|---|---|
| Age, Continuous | 30.2 Years STANDARD_DEVIATION 9.2 | 32.3 Years STANDARD_DEVIATION 9.5 | 31.9 Years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 28 Participants | 136 Participants | 164 Participants |
| Sex: Female, Male Male | 32 Participants | 104 Participants | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 60 | 14 / 240 |
| serious Total, serious adverse events | 0 / 60 | 1 / 240 |
Outcome results
Primary
Percentage of Participants With Fever Greater Than or Equal to (>=) 101 Degrees Fahrenheit (F)
Percentage of participants with fever defined as oral temperature \>=101 degrees F were reported.
Time frame: Baseline (Day 1) up to Day 8
Population: The intent-to-treat (ITT) population included all participants that were randomized and treated with investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Fever Greater Than or Equal to (>=) 101 Degrees Fahrenheit (F) | 0 Percentage of Participant |
| Trivalent Influenza Vaccine | Percentage of Participants With Fever Greater Than or Equal to (>=) 101 Degrees Fahrenheit (F) | 0.4 Percentage of Participant |
95% CI: [-5.2, 2.6]
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs were events between administration of study drug and up to 15 days after vaccination that are absent before treatment or that worsened relative to pre-treatment state. Results were given for AEs reported within 8 days and 15 days after vaccination.
Time frame: Baseline (Day 1) up to Day 8 and Day 15
Population: The ITT population included all participants that were randomized and treated with investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to Day 8 | 3 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to Day 15 | 3 Participants |
| Trivalent Influenza Vaccine | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to Day 8 | 13 Participants |
| Trivalent Influenza Vaccine | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to Day 15 | 14 Participants |
Secondary
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. Treatment-emergent SAEs were serious events between administration of study drug and up to 181 days after the dose that are absent before treatment or that worsen relative to pretreatment state. An NOCD is a newly diagnosed medical condition that is of a chronic, ongoing nature and is assessed by the investigator as medically significant. Results were given for TESAEs and NOCDs reported within 29 days and 181 days after vaccination.
Time frame: Baseline (Day 1) up to Day 29 and 181
Population: The ITT population included all participants that were randomized and treated with investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs) | Up to Day 29: TESAEs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs) | Up to Day 29: NOCDs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs) | Up to Day 181: TESAEs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs) | Up to Day 181: NOCDs | 0 Participants |
| Trivalent Influenza Vaccine | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs) | Up to Day 181: NOCDs | 0 Participants |
| Trivalent Influenza Vaccine | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs) | Up to Day 29: TESAEs | 0 Participants |
| Trivalent Influenza Vaccine | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs) | Up to Day 181: TESAEs | 1 Participants |
| Trivalent Influenza Vaccine | Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs) | Up to Day 29: NOCDs | 0 Participants |
Secondary
Percentage of Participants Who Require Antipyretic and/or Analgesic Medication
Percentage of participants who require antipyretic and/or analgesic medication were reported.
Time frame: Baseline (Day 1) up to Day 8 and Day 15
Population: The ITT population included all participants that were randomized and treated with investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 8 | 0 Percentage of Participants |
| Placebo | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 15 | 0 Percentage of Participants |
| Trivalent Influenza Vaccine | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 8 | 0.4 Percentage of Participants |
| Trivalent Influenza Vaccine | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 15 | 0.8 Percentage of Participants |
Secondary
Percentage of Participants With Solicited Symptoms
Solicited symptoms are predefined symptoms or events specifically inquired about and assessed daily after vaccine administration up to 15 days after vaccination. The solicited symptoms include fever greater than (\>) 100.0 degrees F (37.8 degrees Celsius), runny nose, sore throat, cough, vomiting, muscle aches, chills, decreased activity and headache. Results were reported for all solicited symptoms except fever \>=101 degrees F (reported as primary outcome) within 8 days after vaccination and all solicited symptoms within 15 days after vaccination.
Time frame: Baseline (Day 1) up to Day 8 and Day 15
Population: The ITT population included all participants that were randomized and treated with investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Solicited Symptoms | Up to Day 8 | 20.0 Percentage of Participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Up to Day 15 | 21.7 Percentage of Participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Up to Day 8 | 36.7 Percentage of Participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Up to Day 15 | 39.6 Percentage of Participants |
Comparison: Up to Day 895% CI: [3.6, 27.6]
Comparison: Up to Day 1595% CI: [4.4, 29.3]