Healthy, Influenza
Conditions
Keywords
Trivalent, Influenza, FluMist Quadrivalent, Vaccine, Prevention, Healthy, Monovalent
Brief summary
This prospective annual release study is designed to evaluate the safety of 1 new influenza virus vaccine strain to be included in FluMist Quadrivalent for the 2016-2017 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 subjects will be randomly assigned in a 4:1 fashion to receive a single dose of monovalent 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 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
BIOLOGICALMonovalent Influenza Vaccine
A single dose of 10\^(7.0 ± 0.5) FFU strain of monovalent influenza vaccine will be administered as intranasal spray on Day 1.
OTHERPlacebo
A single dose of placebo matched to monovalent 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 * 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), 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) up to 8 days after vaccination and all solicited symptoms up to 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 up to 8 days and 15 days after vaccination. |
| Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | Baseline (Day 1) up to Day 29 and Day 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 up to 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
Recruitment details
A total of 301 participants were randomized and participated in the study from 02-May-2016 through 30-Nov-2016 at 3 sites in the United States of America (USA).
Pre-assignment details
One participant was considered as screen failure and 300 randomized participants were treated in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1. | 59 |
| Monovalent Influenza Vaccine Participants received a single dose of monovalent influenza vaccine \[10\^7.0 +/- 0.5 fluorescent focus unit (FFU) of each of 1 cold adapted (ca), attenuated (att), temperature sensitive (ts) 6:2 reassortant influenza strains\] by intranasal spray on Day 1. | 241 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | Monovalent Influenza Vaccine |
|---|---|---|---|
| Age, Continuous | 33.3 Years STANDARD_DEVIATION 9.4 | 33.2 Years STANDARD_DEVIATION 9.4 | 33.3 Years STANDARD_DEVIATION 9.5 |
| Sex: Female, Male Female | 172 Participants | 33 Participants | 139 Participants |
| Sex: Female, Male Male | 128 Participants | 26 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 59 | 14 / 241 |
| serious Total, serious adverse events | 0 / 59 | 0 / 241 |
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) | 1.7 Percentage of participants |
| Monovalent Influenza Vaccine | Percentage of Participants With Fever Greater Than or Equal to (>=) 101 Degrees Fahrenheit (F) | 0.4 Percentage of participants |
95% CI: [-8.1, 1.3]
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 up to 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 | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to Day 15 | 1 Participants |
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to Day 8 | 9 Participants |
| Monovalent 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 Diseases (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 up to 29 days and 181 days after vaccination.
Time frame: Baseline (Day 1) up to Day 29 and Day 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 Diseases (NOCDs) | Up to Day 29: TESAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | Up to Day 29: NOCDs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | Up to Day 181: TESAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | Up to Day 181: NOCDs | 0 Participants |
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | Up to Day 181: NOCDs | 0 Participants |
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | Up to Day 29: TESAEs | 0 Participants |
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | Up to Day 181: TESAEs | 0 Participants |
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (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 | 3.4 Percentage of participants |
| Placebo | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 15 | 5.1 Percentage of participants |
| Monovalent Influenza Vaccine | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 8 | 1.2 Percentage of participants |
| Monovalent Influenza Vaccine | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 15 | 1.7 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) up to 8 days after vaccination and all solicited symptoms up to 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 | 33.9 Percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Up to Day 15 | 37.3 Percentage of participants |
| Monovalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Up to Day 8 | 25.7 Percentage of participants |
| Monovalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Up to Day 15 | 29.9 Percentage of participants |
Comparison: Up to Day 895% CI: [-22.2, 4.6]
Comparison: Up to Day 1595% CI: [-21.6, 5.9]