Study to Evaluate the Safety of 1 New 6:2 Influenza Virus Reassortant in Adults for the 2016-2017 season - FluMist

Study identifier:D2560C00012

ClinicalTrials.gov identifier:NCT02743117

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 4 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of 1 New 6:2 Influenza Virus Reassortant in Adults

Medical condition

Influenza, Healthy

Phase

Phase 4

Healthy volunteers

Yes

Study drug

Sex

All

Actual Enrollment

301

Study type

Interventional

Age

18 Years - 49 Years

Date

Study Start Date: 02 May 2016

Primary Completion Date: 30 Nov 2016

Study Completion Date: 30 Nov 2016

Study design

Allocation: Randomized
Endpoint Classification: Safety
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Prevention

Verification:

Verified 01 Oct 2017 by MedImmune, LLC

Collaborators

AstraZeneca

Inclusion and exclusion criteria

Location

Research Site

Portland, OR, United States, 97239

Location

Research Site

Stockbridge, GA, United States, 30281

Location

Research Site

South Miami, FL, United States, 33143

Arms	Assigned Interventions
Experimental: Monovalent Influenza Vaccine A single dose of 10^(7.0 +/- 0.5) fluorescent focus units (FFU) strain of monovalent influenza vaccine will be administered as intranasal spray on Day 1.	Biological/Vaccine: Monovalent 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.
Placebo Comparator: Placebo A single dose of placebo matched to monovalent influenza vaccine will be administered as intranasal spray on Day 1.	Other: Placebo A single dose of placebo matched to monovalent influenza vaccine will be administered as intranasal spray on Day 1.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One participant was considered as screen failure and 300 randomized participants were treated in the study.

Reporting Groups

	Description
Placebo	Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1.
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.

Participant Flow: Overall Study

	Placebo	Monovalent Influenza Vaccine
STARTED	60	241
Treated	59	241
COMPLETED	59	240
NOT COMPLETED	1	1
Lost to Follow-up	0	1
Unspecified	1	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The intent-to-treat (ITT) population included all participants that were randomized and treated with investigational product.

Reporting Groups

	Description
Placebo	Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1.
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.

Baseline Measures

	Placebo	Monovalent Influenza Vaccine	Total
Number of Participants [units: Participants]	59	241	300
Age Continuous [units: Years] Mean ± Standard Deviation	33.2 ± 9.4	33.3 ± 9.5	33.3 ± 9.4
Gender, Male/Female [units: Participants]
Female	33	139	128
Male	26	102	172

Outcome Measures

1. Primary Outcome Measure: Percentage of Participants With Fever Greater than or Equal to (>=) 101 Degrees Fahrenheit (F) [ Time Frame: Baseline (Day 1) up to Day 8 ]

Measure Type	Primary
Measure Name	Percentage of Participants With Fever Greater than or Equal to (>=) 101 Degrees Fahrenheit (F)
Measure Description	Percentage of participants with fever defined as oral temperature >=101 degrees F were reported.
Time Frame	Baseline (Day 1) up to Day 8
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The intent-to-treat (ITT) population included all participants that were randomized and treated with investigational product.

Reporting Groups

	Description
Placebo	Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1.
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.

Measured Values

	Placebo	Monovalent Influenza Vaccine
Number of Participants Analyzed [units:participants]	59	241
Percentage of Participants With Fever Greater than or Equal to (>=) 101 Degrees Fahrenheit (F) [units: Percentage of participants]	1.7	0.4

Statistical Analysis 1 for Percentage of Participants With Fever Greater than or Equal to (>=) 101 Degrees Fahrenheit (F)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Other^[5]	-1.3
95% Confidence Interval	( -8.1 to 1.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Percentage of Participants With Solicited Symptoms [ Time Frame: Baseline (Day 1) up to Day 8 and Day 15 ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Solicited Symptoms
Measure Description	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
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT population included all participants that were randomized and treated with investigational product.

Reporting Groups

	Description
Placebo	Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1.
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.

Measured Values

	Placebo	Monovalent Influenza Vaccine
Number of Participants Analyzed [units:participants]	59	241
Percentage of Participants With Solicited Symptoms [units: Percentage of participants]
Up to Day 8	33.9	25.7
Up to Day 15	37.3	29.9

Statistical Analysis 1 for Percentage of Participants With Solicited Symptoms

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Other^[5]	-8.2
95% Confidence Interval	( -22.2 to 4.6 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Up to Day 8
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Percentage of Participants With Solicited Symptoms

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Other^[5]	-7.4
95% Confidence Interval	( -21.6 to 5.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Up to Day 15
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline (Day 1) up to Day 8 and Day 15 ]

Measure Type	Secondary
Measure Name	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Measure Description	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
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT population included all participants that were randomized and treated with investigational product.

Reporting Groups

	Description
Placebo	Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1.
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.

Measured Values

	Placebo	Monovalent Influenza Vaccine
Number of Participants Analyzed [units:participants]	59	241
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [units: Participants]
Up to Day 8	1	9
Up to Day 15	1	14

No statistical analysis provided for Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

4. Secondary Outcome Measure: Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) [ Time Frame: Baseline (Day 1) up to Day 29 and Day 181 ]

Measure Type	Secondary
Measure Name	Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs)
Measure Description	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
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT population included all participants that were randomized and treated with investigational product.

Reporting Groups

	Description
Placebo	Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1.
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.

Measured Values

	Placebo	Monovalent Influenza Vaccine
Number of Participants Analyzed [units:participants]	59	241
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs) [units: Participants]
Up to Day 29: TESAEs	0	0
Up to Day 29: NOCDs	0	0
Up to Day 181: TESAEs	0	0
Up to Day 181: NOCDs	0	0

No statistical analysis provided for Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Diseases (NOCDs)

5. Secondary Outcome Measure: Percentage of Participants Who Require Antipyretic and/or Analgesic Medication [ Time Frame: Baseline (Day 1) up to Day 8 and Day 15 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Who Require Antipyretic and/or Analgesic Medication
Measure Description	Percentage of participants who require antipyretic and/or analgesic medication were reported.
Time Frame	Baseline (Day 1) up to Day 8 and Day 15
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITT population included all participants that were randomized and treated with investigational product.

Reporting Groups

	Description
Placebo	Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1.
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.

Measured Values

	Placebo	Monovalent Influenza Vaccine
Number of Participants Analyzed [units:participants]	59	241
Percentage of Participants Who Require Antipyretic and/or Analgesic Medication [units: Percentage of participants]
Up to Day 8	3.4	1.2
Up to Day 15	5.1	1.7

No statistical analysis provided for Percentage of Participants Who Require Antipyretic and/or Analgesic Medication

Serious Adverse Events

Time Frame	Adverse Events: From Screening (Day -14) up to Day 15, and Serious Adverse Events: From Screening (Day -14) up to Day 181
Additional Description	No text entered.

Reporting Groups

	Description
Placebo	Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1.
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.

Serious Adverse Events

	Placebo	Monovalent Influenza Vaccine
Total, serious adverse events
# participants affected / at risk	0/59 (0.00%)	0/241 (0.00%)

Other Adverse Events

Time Frame	Adverse Events: From Screening (Day -14) up to Day 15, and Serious Adverse Events: From Screening (Day -14) up to Day 181
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Placebo	Participants received a single dose of placebo matching with monovalent influenza vaccine by intranasal spray on Day 1.
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.