Healthy, Influenza
Conditions
Keywords
Trivalent, Influenza, FluMist Quadrivalent, Vaccine, Prevention, Healthy
Brief summary
This prospective annual release study is designed to evaluate the safety on new influenza virus vaccine strains to be included in FluMist Quadrivalent for the 2013-2014 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 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 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
BIOLOGICALTrivalent Influenza Vaccine
A single dose of 10\^(7.0 ± 0.5) FFU 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 * 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) | Within 7 days after vaccination | 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 | Within 7 and 14 days after vaccination | Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily after vaccine administration up to 14 days after vaccination. The solicited symptoms included 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 are reported for all solicited symptoms except fever \>=101 degrees F (reported as primary outcome) within 7 days after vaccination and all solicited symptoms within 14 days after vaccination. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Within 7 and 14 days after vaccination | An adverse event (AE) was 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 14 days after vaccination that were absent before treatment or that worsened relative to pre-treatment state. Results are given for AEs reported within 7 days and 14 days after vaccination. |
| Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | Within 28 and 180 days after vaccination | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was 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 180 days after the dose that were absent before treatment or that worsen relative to pretreatment state. An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Results are given for TESAEs and NOCDs reported within 28 days and 180 days after vaccination. |
| Percentage of Participants Who Required Antipyretic and/or Analgesic Medication | Within 7 and 14 days after vaccination | — |
Countries
United States
Participant flow
Pre-assignment details
One participant randomized to receive placebo received trivalent influenza vaccine on Day 1 instead of placebo and was included in trivalent influenza vaccine group in the safety population.
Participants by arm
| Arm | Count |
|---|---|
| Trivalent Influenza Vaccine A single dose of 10\^(7.0 +/- 0.5) fluorescent focus units (FFU) of trivalent influenza vaccine administered as intranasal spray on Day 1. | 240 |
| Placebo A single dose of placebo matched to trivalent influenza vaccine administered as intranasal spray on Day 1. | 60 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | Trivalent Influenza Vaccine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 33.1 years STANDARD_DEVIATION 9.4 | 33.6 years STANDARD_DEVIATION 9 | 33.2 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 137 Participants | 34 Participants | 171 Participants |
| Sex: Female, Male Male | 103 Participants | 26 Participants | 129 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 28 / 241 | 5 / 59 |
| serious Total, serious adverse events | 1 / 241 | 2 / 59 |
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: Within 7 days after vaccination
Population: Safety population included all participants who received any amount of investigational drug and had safety data available. Participants were included in the safety population according to the investigational drug received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trivalent Influenza Vaccine | Percentage of Participants With Fever Greater Than or Equal to (>=) 101 Degrees Fahrenheit (F) | 0.4 percentage of participants |
| Placebo | Percentage of Participants With Fever Greater Than or Equal to (>=) 101 Degrees Fahrenheit (F) | 0.0 percentage of participants |
95% CI: [-5.3, 2.6]
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was 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 14 days after vaccination that were absent before treatment or that worsened relative to pre-treatment state. Results are given for AEs reported within 7 days and 14 days after vaccination.
Time frame: Within 7 and 14 days after vaccination
Population: Safety population included all participants who received any amount of investigational drug and had safety data available. Participants were included in the safety population according to the investigational drug received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trivalent Influenza Vaccine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Within 7 days | 26 participants |
| Trivalent Influenza Vaccine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Within 14 days | 28 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Within 7 days | 4 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Within 14 days | 5 participants |
Secondary
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was 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 180 days after the dose that were absent before treatment or that worsen relative to pretreatment state. An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Results are given for TESAEs and NOCDs reported within 28 days and 180 days after vaccination.
Time frame: Within 28 and 180 days after vaccination
Population: Safety population included all participants who received any amount of investigational drug and had safety data available. Participants were included in the safety population according to the investigational drug received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trivalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | TESAEs within 28 days | 1 participants |
| Trivalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | TESAEs within 180 days | 1 participants |
| Trivalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | NOCDs within 28 days | 0 participants |
| Trivalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | NOCDs within 180 days | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | NOCDs within 180 days | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | TESAEs within 28 days | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | NOCDs within 28 days | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | TESAEs within 180 days | 2 participants |
Secondary
Percentage of Participants Who Required Antipyretic and/or Analgesic Medication
Time frame: Within 7 and 14 days after vaccination
Population: Safety population included all participants who received any amount of investigational drug and had safety data available. Participants were included in the safety population according to the investigational drug received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trivalent Influenza Vaccine | Percentage of Participants Who Required Antipyretic and/or Analgesic Medication | Anti-pyretic or analgesic within 7 days | 9.1 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants Who Required Antipyretic and/or Analgesic Medication | Anti-pyretic and analgesic within 7 days | 8.7 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants Who Required Antipyretic and/or Analgesic Medication | Anti-pyretic or analgesic within 14 days | 9.1 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants Who Required Antipyretic and/or Analgesic Medication | Anti-pyretic and analgesic within 14 days | 8.7 percentage of participants |
| Placebo | Percentage of Participants Who Required Antipyretic and/or Analgesic Medication | Anti-pyretic and analgesic within 14 days | 6.8 percentage of participants |
| Placebo | Percentage of Participants Who Required Antipyretic and/or Analgesic Medication | Anti-pyretic or analgesic within 7 days | 5.1 percentage of participants |
| Placebo | Percentage of Participants Who Required Antipyretic and/or Analgesic Medication | Anti-pyretic or analgesic within 14 days | 6.8 percentage of participants |
| Placebo | Percentage of Participants Who Required Antipyretic and/or Analgesic Medication | Anti-pyretic and analgesic within 7 days | 5.1 percentage of participants |
Secondary
Percentage of Participants With Solicited Symptoms
Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily after vaccine administration up to 14 days after vaccination. The solicited symptoms included 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 are reported for all solicited symptoms except fever \>=101 degrees F (reported as primary outcome) within 7 days after vaccination and all solicited symptoms within 14 days after vaccination.
Time frame: Within 7 and 14 days after vaccination
Population: Safety population included all participants who received any amount of investigational drug and had safety data available. Participants were included in the safety population according to the investigational drug received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Fever: greater than 102 degrees F within 7 days | 0.0 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Fever: greater than 100 degrees F within 14 days | 1.2 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Vomiting within 7 days | 0.0 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Fever: >= 101 degrees F within 14 days | 0.8 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Runny nose within 7 days | 20.7 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Fever: greater than 102 degrees F within 14 days | 0.0 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Muscle aches within 7 days | 3.3 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Fever: greater than 103 degrees F within 14 days | 0.0 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Fever: greater than 100 degrees F within 7 days | 0.8 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Runny nose within 14 days | 21.6 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Chills within 7 days | 1.7 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Sore throat within 14 days | 11.2 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Sore throat within 7 days | 9.5 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Cough within 14 days | 5.4 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Decreased activity (tiredness) within 7 days | 10.0 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Vomiting within 14 days | 0.4 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Fever: greater than 103 degrees F within 7 days | 0.0 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Muscle aches within 14 days | 3.7 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Headache within 7 days | 15.4 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Chills within 14 days | 2.5 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Cough within 7 days | 4.6 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Decreased activity (tiredness) within 14 days | 11.2 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Any symptom within 14 days | 39.4 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Headache within 14 days | 16.6 percentage of participants |
| Trivalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Any symptom within 7 days | 37.3 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Headache within 14 days | 13.6 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Any symptom within 7 days | 25.4 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Fever: greater than 100 degrees F within 7 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Fever: greater than 102 degrees F within 7 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Fever: greater than 103 degrees F within 7 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Runny nose within 7 days | 11.9 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Sore throat within 7 days | 3.4 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Cough within 7 days | 5.1 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Vomiting within 7 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Muscle aches within 7 days | 3.4 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Chills within 7 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Decreased activity (tiredness) within 7 days | 6.8 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Headache within 7 days | 11.9 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Any symptom within 14 days | 27.1 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Fever: greater than 100 degrees F within 14 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Fever: >= 101 degrees F within 14 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Fever: greater than 102 degrees F within 14 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Fever: greater than 103 degrees F within 14 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Runny nose within 14 days | 11.9 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Sore throat within 14 days | 6.8 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Cough within 14 days | 5.1 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Vomiting within 14 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Muscle aches within 14 days | 3.4 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Chills within 14 days | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Decreased activity (tiredness) within 14 days | 6.8 percentage of participants |
95% CI: [-1.9, 23.9]
95% CI: [-4.9, 3.3]
95% CI: [-6.1, 1.8]
95% CI: [-6.1, 1.8]
95% CI: [-2.6, 17.7]
95% CI: [-2.2, 11.6]
95% CI: [-9.3, 4.7]
95% CI: [-6.1, 1.8]
95% CI: [-8, 4.3]
95% CI: [-4.1, 4.4]
95% CI: [-6.5, 9.8]
95% CI: [-7.8, 11.9]
95% CI: [-1.6, 24.4]
95% CI: [-4.5, 3.9]
95% CI: [-4.9, 3.3]
95% CI: [-6.1, 1.8]
95% CI: [-6.1, 1.8]
95% CI: [-1.8, 18.6]
95% CI: [-5.3, 11.2]
95% CI: [-8.6, 5.7]
95% CI: [-5.3, 2.6]
95% CI: [-7.8, 4.8]
95% CI: [-3.3, 5.5]
95% CI: [-5.3, 11.2]
95% CI: [-8.7, 12]