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 2017-2018 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 participants 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 2 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 180 days after study vaccination.
Interventions
BIOLOGICALMonovalent Influenza Vaccine
A single dose of monovalent influenza vaccine \[10\^7.0 +/- 0.5 FFU of each of 1 ca, att, ts 6:2 reassortant influenza strain\] will be administered as intranasal spray on Day 1.
OTHERPlacebo
A single dose of placebo matching with 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)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
Key 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 Key
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 to randomization * Any known immunosuppressive condition or immune deficiency diseases, including human immunodeficiency virus infection, or ongoing immunosuppressive therapy * History of Guillain-Barre syndrome * Receipt of any investigational agent within 30 days prior to randomization, or expected receipt through 30 days after the dose of investigational product (use of licensed agents for indications not listed in the Package Insert is permitted) * Receipt of any non-study vaccine within 30 days prior to randomization, or expected receipt through 30 days after receipt of investigational product * Expected receipt of antipyretic or analgesic medication on a daily or every other day basis from randomization through 14 days after receipt of investigational product * Administration of intranasal medications within 14 days prior to randomization, or expected receipt through 14 days after administration of investigational product * Receipt of influenza antiviral therapy or influenza antiviral agents within 48 hours prior to investigational product administration or expected receipt of influenza antiviral therapy or influenza antiviral agents through 14 days after receipt of investigational product
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 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. 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
The study was conducted from 30 May 2017 to 14 Dec 2017 at 2 sites in the United States of America (USA).
Pre-assignment details
A total of 300 participants were randomized and participated in the study.
Participants by arm
| Arm | Count |
|---|---|
| Monovalent Influenza Vaccine Participants received a single dose of monovalent influenza vaccine \[10\^7.0 +/- 0.5 fluorescent focus unit (FFU) of each of 1 cold adapted (ca), attenuated (att), temperature sensitive (ts) 6:2 reassortant influenza strain\] by intranasal spray on Day 1. | 240 |
| Placebo Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1. | 60 |
| Total | 300 |
Baseline characteristics
| Characteristic | Placebo | Total | Monovalent Influenza Vaccine |
|---|---|---|---|
| Age, Continuous | 32.5 Years STANDARD_DEVIATION 10.5 | 30.4 Years STANDARD_DEVIATION 9.8 | 29.9 Years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 16 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 284 Participants | 227 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 42 Participants | 36 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 9 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 52 Participants | 243 Participants | 191 Participants |
| Sex: Female, Male Female | 33 Participants | 171 Participants | 138 Participants |
| Sex: Female, Male Male | 27 Participants | 129 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 240 | 0 / 60 |
| other Total, other adverse events | 19 / 240 | 1 / 60 |
| serious Total, serious adverse events | 1 / 240 | 0 / 60 |
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 who were randomized and treated with investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monovalent Influenza Vaccine | Percentage of Participants With Fever Greater Than or Equal to (>=) 101 Degrees Fahrenheit (F) | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Fever Greater Than or Equal to (>=) 101 Degrees Fahrenheit (F) | 0 Percentage of Participants |
95% CI: [-6.7, 1.9]
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 who were randomized and treated with investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to Day 8 | 13 Participants |
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to Day 15 | 19 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to Day 8 | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to Day 15 | 1 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 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. 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 who were randomized and treated with investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | TESAEs: Up to Day 29 | 1 Participants |
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | NOCDs: Up to Day 29 | 0 Participants |
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | TESAEs: Up to Day 181 | 1 Participants |
| Monovalent Influenza Vaccine | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | NOCDs: Up to Day 181 | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | NOCDs: Up to Day 181 | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | TESAEs: Up to Day 29 | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | TESAEs: Up to Day 181 | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) | NOCDs: Up to Day 29 | 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 who were randomized and treated with investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monovalent Influenza Vaccine | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 8 | 2.1 Percentage of participants |
| Monovalent Influenza Vaccine | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 15 | 3.3 Percentage of participants |
| Placebo | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 8 | 1.7 Percentage of participants |
| Placebo | Percentage of Participants Who Require Antipyretic and/or Analgesic Medication | Up to Day 15 | 6.7 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 who were randomized and treated with investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Monovalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Up to Day 8 | 27.9 Percentage of Participants |
| Monovalent Influenza Vaccine | Percentage of Participants With Solicited Symptoms | Up to Day 15 | 32.1 Percentage of Participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Up to Day 8 | 26.7 Percentage of Participants |
| Placebo | Percentage of Participants With Solicited Symptoms | Up to Day 15 | 31.7 Percentage of Participants |
Comparison: Statistical analysis up to Day 895% CI: [-12.8, 13.2]
Comparison: Statistical analysis up to Day 1595% CI: [-14.1, 13.2]