FluMist: Study to Evaluate the Safety of 3 New 6:2 Influenza Virus Reassortants in Adults for the 2015-2016 Season

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02473510
• Collaborator: AstraZeneca (Industry)
• Enrollment: 301
• Locations: 3
• Arms: 2
• Duration (Months): 7
• Patients Per Site: 100.3
• Patients Per Site Per Month: 14.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Influenza; Healthy	Biological: Trivalent Influenza Vaccine; Other: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 301 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 4 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of 3 New 6:2 Influenza Virus Reassortants in Adults
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trivalent Influenza Vaccine A single dose of 10^(7.0 +/- 0.5) fluorescent focus units (FFU) per strain of trivalent influenza vaccine will be administered as intranasal spray on Day 1.	Biological: Trivalent 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.
Placebo Comparator: Placebo A single dose of placebo matched to trivalent influenza vaccine will be administered as intranasal spray on Day 1.	Other: Placebo; A single dose of placebo matched to trivalent influenza vaccine will be administered as intranasal spray on Day 1.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	South Miami	Florida	United States
2	Research Site	Stockbridge	Georgia	United States
3	Research Site	Portland	Oregon	United States

Sponsors and Collaborators

• MedImmune LLC
• AstraZeneca

Investigators

• Study Director: Ashwin Swami, MD, MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT02473510
• Other Study ID Numbers: D2560C00009
• First Posted: Jun 16, 2015
• Last Update Posted: Nov 28, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by MedImmune LLC: Trivalent; Influenza; FluMist Quadrivalent; Vaccine; Prevention; Healthy
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Pre-assignment Detail	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).

Arm/Group Title	Placebo	Trivalent Influenza Vaccine
Arm/Group Description	Participants received a single dose of placebo matching with trivalent influenza vaccine by intranasal spray on Day 1.	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.
Period Title: Overall Study
STARTED	60	240
COMPLETED	59	238
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Placebo	Trivalent Influenza Vaccine	Total
Arm/Group Description	Participants received a single dose of placebo matching with trivalent influenza vaccine by intranasal spray on Day 1.	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.	Total of all reporting groups
Overall Participants	60	240	300
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	30.2 (9.2)	32.3 (9.5)	31.9 (9.4)
Sex: Female, Male (Count of Participants)
Female	28 46.7%	136 56.7%	164 54.7%
Male	32 53.3%	104 43.3%	136 45.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Fever Greater Than or Equal to (>=) 101 Degrees Fahrenheit (F)
Description	Percentage of participants with fever defined as oral temperature >=101 degrees F were reported.
Time Frame	Baseline (Day 1) up to Day 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Trivalent Influenza Vaccine
Arm/Group Description	Participants received a single dose of placebo matching with trivalent influenza vaccine by intranasal spray on Day 1.	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.
Measure Participants	60	240
Number [Percentage of Participant]	0	0.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Trivalent Influenza Vaccine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -5.2 to 2.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Solicited Symptoms
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) 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

Outcome Measure Data

Analysis Population Description

The ITT population included all participants that were randomized and treated with investigational product.

Arm/Group Title	Placebo	Trivalent Influenza Vaccine
Arm/Group Description	Participants received a single dose of placebo matching with trivalent influenza vaccine by intranasal spray on Day 1.	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.
Measure Participants	60	240
Up to Day 8	20.0 33.3%	36.7 15.3%
Up to Day 15	21.7 36.2%	39.6 16.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Trivalent Influenza Vaccine
	Comments	Up to Day 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	16.7
	Confidence Interval	(2-Sided) 95%; 3.6 to 27.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Trivalent Influenza Vaccine
	Comments	Up to Day 15
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	17.9
	Confidence Interval	(2-Sided) 95%; 4.4 to 29.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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 within 8 days and 15 days after vaccination.
Time Frame	Baseline (Day 1) up to Day 8 and Day 15

Outcome Measure Data

Analysis Population Description

The ITT population included all participants that were randomized and treated with investigational product.

Arm/Group Title	Placebo	Trivalent Influenza Vaccine
Arm/Group Description	Participants received a single dose of placebo matching with trivalent influenza vaccine by intranasal spray on Day 1.	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.
Measure Participants	60	240
Up to Day 8	3 5%	13 5.4%
Up to Day 15	3 5%	14 5.8%

4. Secondary Outcome

Title	Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) and New Onset Chronic Disease (NOCDs)
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 within 29 days and 181 days after vaccination.
Time Frame	Baseline (Day 1) up to Day 29 and 181

Outcome Measure Data

Analysis Population Description

The ITT population included all participants that were randomized and treated with investigational product.

Arm/Group Title	Placebo	Trivalent Influenza Vaccine
Arm/Group Description	Participants received a single dose of placebo matching with trivalent influenza vaccine by intranasal spray on Day 1.	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.
Measure Participants	60	240
Up to Day 29: TESAEs	0 0%	0 0%
Up to Day 29: NOCDs	0 0%	0 0%
Up to Day 181: TESAEs	0 0%	1 0.4%
Up to Day 181: NOCDs	0 0%	0 0%

5. Secondary Outcome

Title	Percentage of Participants Who Require Antipyretic and/or Analgesic Medication
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

Outcome Measure Data

Analysis Population Description

The ITT population included all participants that were randomized and treated with investigational product.

Arm/Group Title	Placebo	Trivalent Influenza Vaccine
Arm/Group Description	Participants received a single dose of placebo matching with trivalent influenza vaccine by intranasal spray on Day 1.	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.
Measure Participants	60	240
Up to Day 8	0 0%	0.4 0.2%
Up to Day 15	0 0%	0.8 0.3%

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
Arm/Group Title	Placebo		Trivalent Influenza Vaccine
Arm/Group Description	Participants received a single dose of placebo matching with trivalent influenza vaccine by intranasal spray on Day 1.		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.
All Cause Mortality
	Placebo		Trivalent Influenza Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Trivalent Influenza Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		1/240 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/60 (0%)	0	1/240 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Trivalent Influenza Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/60 (5%)		14/240 (5.8%)
Eye disorders
Lacrimation increased	0/60 (0%)	0	1/240 (0.4%)	1
Gastrointestinal disorders
Diarrhoea	0/60 (0%)	0	1/240 (0.4%)	1
Nausea	0/60 (0%)	0	1/240 (0.4%)	1
Infections and infestations
Hordeolum	0/60 (0%)	0	1/240 (0.4%)	1
Pharyngitis streptococcal	0/60 (0%)	0	1/240 (0.4%)	1
Injury, poisoning and procedural complications
Sunburn	0/60 (0%)	0	1/240 (0.4%)	1
Musculoskeletal and connective tissue disorders
Pain in jaw	0/60 (0%)	0	1/240 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	2/60 (3.3%)	2	5/240 (2.1%)	5
Productive cough	0/60 (0%)	0	1/240 (0.4%)	1
Sneezing	0/60 (0%)	0	2/240 (0.8%)	2
Skin and subcutaneous tissue disorders
Rash	1/60 (1.7%)	1	1/240 (0.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.