SNIF: Self-Administered Nasal Influenza Feasibility Study

• Sponsor: Uniformed Services University of the Health Sciences (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01933048
• Collaborator: (none)
• Enrollment: 1,077
• Locations: 2
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 538.5
• Patients Per Site Per Month: 41.5

Study Details

Study Description

Brief Summary

The purpose of this prospective, open-label clinical trial is to evaluate the immunogenicity of self-administered (SA) live, attenuated influenza vaccine (LAIV) in comparison with healthcare worker administered (HCWA) LAIV and to evaluate the feasibility of group self-administration of LAIV.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: FluMist	Phase 4

Detailed Description

This Phase IV, open-label, prospective clinical trial assesses SA-LAIV, testing whether the immunogenicity of SA-LAIV is non-inferior to that of HCWA-LAIV, as well as evaluating the feasibility of utilizing group administration for SA-LAIV. Subjects will be enrolled into one of two major treatment arms: HCWA-LAIV (Estimated N = 550) and SA-LAIV (Estimated N = 550). Enrollment into each major treatment arm will be stratified by study site. Enrollment in the HCWA-LAIV and SA-LAIV treatment arms may occur concurrently at each site. Subjects enrolling in the study will be randomized to HCWA or SA, and within the SA arm to either individual self-administration, or group administration. Specifically, following self-administration of LAIV to 190 individual subjects, 180 subjects will be vaccinated in 36 groups of 5 and 180 subjects will be vaccinated in 18 groups of 10. All vaccinations in the SA-LAIV arm will be given under the direction and supervision of a research staff member who is trained to administer LAIV vaccines. Following immunization all subjects will return for one visit at approximately 28 (± 7) days for follow-up.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1077 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Self-Administered Nasal Influenza Vaccine: Immunogenicity and Feasibility of Group Administration
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Other: Healthcare Worker Administration FluMist administered by a Healthcare Worker	Drug: FluMist; FluMist Intranasal Vaccine; Other Names: influenza virus vaccine LAIV4
Experimental: Self-Administration FluMist self-administered by subject	Drug: FluMist; FluMist Intranasal Vaccine; Other Names: influenza virus vaccine LAIV4

Outcome Measures

Primary Outcome Measures

1. Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects [28+/- 7 days post-vaccination]

Secondary Outcome Measures

1. Difference and Proportion in Seroresponse of Subjects [28+/- 7 days post-vaccination]

2. Difference and Proportion in Seroconversion of Subjects [28+/- 7 days post-vaccination]

Other Outcome Measures

1. Feasibility of Self-administration Prior to Vaccine Administration [28+/- 7 days post-vaccination]

2. Feasibility of Self-administration Following Vaccine Administration [28+/- 7 days post-vaccination]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Healthy males or healthy, non-pregnant females

• 18-49 years of age

• Department of Defense beneficiary including active duty members

• Able to speak and understand English, and provide written informed consent

Exclusion Criteria:

• Known hypersensitivity to eggs, egg-proteins, gentamicin, gelatin, or arginine or life-threatening reactions to previous influenza vaccination

• Prior receipt of the 2012-2013 seasonal influenza vaccine for 2012-2013 season or prior receipt of the 2013-2014 seasonal influenza vaccine for 2013-2014 season

• Known clinical diagnosis of reactive airway disease, wheezing, or asthma (excluding exercise-induced asthma)

• Reported febrile upper respiratory illness (oral or tympanic temperature greater than 100°F or a subjective fever) at the time of or within the 24 hours prior to immunization

• Known to be pregnant, possibly pregnant or breast-feeding

• Known diagnosis of human immunodeficiency virus (HIV) infection, chronic active hepatitis B infection, or chronic hepatitis C infection

• History of Guillain-Barre Syndrome

• Household member known to be immunocompromised (either a known disease or disorder such as HIV, or other acquired or congenital immunodeficiency disorder, or taking systemic steroids (any dose) or high daily dose inhaled steroids, tumor necrosis factor-alpha inhibitors, or monoclonal antibodies used to treat autoimmune disease)

• Receipt of medications with activity against influenza A and/or B (ex: Tamiflu®, Relenza®, amantadine, or rimantadine) within 48 hours prior to vaccine administration

• Use of any oral or intravenous systemic steroids (any dose) or any daily dose inhaled steroids

• At the time of enrollment, any person who is trained to administer intranasal vaccines or who has been involved in any recurring role associated with the administration of intranasal vaccines to others in the clinic or military treatment facility (MTF)

• Prior participation in this research study

• Any acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe, interfere with the evaluation of responses, or render the subject unable to meet the requirements of the protocol. These conditions may include, but are not limited to: history of significant renal impairment (dialysis and treatment for kidney disease, including diabetic and hypertensive kidney disease); poorly controlled diabetes mellitus or patients with diabetes mellitus on insulin (subjects with well-controlled diabetes mellitus on oral agents may enroll as long there has been no dosage increase within the past 6 months); cardiac insufficiency, if heart failure is present; an arteriosclerotic event during the 6 months prior to enrollment (e.g., history of myocardial infarction, stroke, recanalization of femoral arteries, or transient ischemic attack).

• If the individual received a live virus vaccine (e.g., Varicella, Measles-Mumps-Rubella, Yellow Fever, Smallpox) in the past 4 weeks, they should wait 28 days before receiving LAIV. There is no reason to defer vaccination if the individual was vaccinated with an inactivated vaccine or if they have recently received blood or other antibody-containing blood products.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Naval Medical Center San Diego	San Diego	California	United States	92134
2	San Antonio Military Health System	Fort Sam Houston	Texas	United States	78234

Sponsors and Collaborators

• Uniformed Services University of the Health Sciences

Investigators

• Study Director: Timothy Burgess, MD, MPH, Uniformed Services University of the Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Timothy Burgess, MD, MPH, Captain, Medical Corps, US Navy, Uniformed Services University of the Health Sciences
• ClinicalTrials.gov Identifier: NCT01933048
• Other Study ID Numbers: IDCRP-070
• First Posted: Aug 30, 2013
• Last Update Posted: Sep 12, 2017
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Timothy Burgess, MD, MPH, Captain, Medical Corps, US Navy, Uniformed Services University of the Health Sciences: influenza
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Recruitment Details	Recruitment and enrollment was conducted in San Antonio, Texas and San Diego, California.

Arm/Group Title	Healthcare Worker Administration (HCWA)	Self-Administration (SA)
Arm/Group Description	FluMist administered by a Healthcare Worker	FluMist self-administered by subject
Period Title: Overall Study
STARTED	548	529
COMPLETED	523	501
NOT COMPLETED	25	28

Baseline Characteristics

Arm/Group Title	Healthcare Worker Administration	Self-Administration	Total
Arm/Group Description	FluMist administered by a Healthcare Worker	FluMist self-administered by subject	Total of all reporting groups
Overall Participants	523	501	1024
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	30	28	29
Sex: Female, Male (Count of Participants)
Female	157 30%	141 28.1%	298 29.1%
Male	366 70%	360 71.9%	726 70.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	103 19.7%	101 20.2%	204 19.9%
Not Hispanic or Latino	420 80.3%	400 79.8%	820 80.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	88 16.8%	55 11%	143 14%
White	332 63.5%	347 69.3%	679 66.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	103 19.7%	99 19.8%	202 19.7%
Region of Enrollment (participants) [Number]
United States	523 100%	501 100%	1024 100%

Outcome Measures

1. Primary Outcome

Title	Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects
Time Frame	28+/- 7 days post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthcare Worker Administration	Self-Administration
Arm/Group Description	FluMist administered by a Healthcare Worker	FluMist self-administered by subject
Measure Participants	523	501
A/H1N1	45.8	48.7
A/H3N2	45.5	46.4
B/Yamagata	17.2	17.8
B/Brisbane (2013-2014 only; HCWA n=346; SA n=359)	16.2	14.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthcare Worker Administration, Self-Administration
	Comments	A/H1N1
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	non-inferiority
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	Farrington-Manning Method
	Comments	based on margin of 0.05

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Healthcare Worker Administration, Self-Administration
	Comments	A/H3N2
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	non-inferiority
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	Farrington-Manning Method
	Comments	based on margin of 0.05

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Healthcare Worker Administration, Self-Administration
	Comments	B/Yamagata
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	non-inferiority
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Farrington-Manning Method
	Comments	based on margin of 0.05

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Healthcare Worker Administration, Self-Administration
	Comments	B/Brisbane
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	non-inferiority
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Farrington-Manning Method
	Comments	based on margin of 0.05

2. Secondary Outcome

Title	Difference and Proportion in Seroresponse of Subjects
Time Frame	28+/- 7 days post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthcare Worker Administration	Self-Administration
Arm/Group Description	FluMist administered by a Healthcare Worker	FluMist self-administered by subject
Measure Participants	523	501
A/H1N1	340 65%	344 68.7%
A/H3N2	335 64.1%	336 67.1%
B/Yamagata	141 27%	137 27.3%
B/Brisbane (2013-2014 only; HCWA n=346; SA n=359)	84 16.1%	79 15.8%

3. Secondary Outcome

Title	Difference and Proportion in Seroconversion of Subjects
Time Frame	28+/- 7 days post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthcare Worker Administration	Self-Administration
Arm/Group Description	FluMist administered by a Healthcare Worker	FluMist self-administered by subject
Measure Participants	523	501
A/H1N1	15 2.9%	5 1%
A/H3N2	8 1.5%	7 1.4%
B/Yamagata	2 0.4%	3 0.6%
B/Brisbane (2013-2014 only; HCWA n=346; SA n=359)	23 4.4%	14 2.8%

4. Other Pre-specified Outcome

Title	Feasibility of Self-administration Prior to Vaccine Administration
Time Frame	28+/- 7 days post-vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthcare Worker Administration (HCWA)	Self-Administration (SA)
Arm/Group Description	FluMist administered by a Healthcare Worker FluMist: FluMist Intranasal Vaccine Health care worker-administered (HCWA; n=523)	FluMist self-administered by subject FluMist: FluMist Intranasal Vaccine Self-administered (SA)/singleton (n=178), SA/groups of 5 (n=163), and SA/groups of 10 (n=160).
Measure Participants	523	501
HCWA preferred method	71 13.6%	65 13%
SA preferred method	132 25.2%	129 25.7%
No preference	320 61.2%	307 61.3%

5. Other Pre-specified Outcome

Title	Feasibility of Self-administration Following Vaccine Administration
Time Frame	28+/- 7 days post-vaccination

Outcome Measure Data

Analysis Population Description

Numbers include participants randomized to the SA group only.

Arm/Group Title	Self-Administration (SA)
Arm/Group Description	FluMist self-administered by subject FluMist: FluMist Intranasal Vaccine Self-administered (SA)/singleton (n=178), SA/groups of 5 (n=163), and SA/groups of 10 (n=160).
Measure Participants	501
HCWA preferred method	29 5.5%
SA preferred method	319 61%
No preference	153 29.3%

Adverse Events

Time Frame	2 years
Arm/Group Title	Healthcare Worker Administration		Self-Administration
Arm/Group Description	This group includes healthcare worker administration of FluMist to subjects.		This group includes subjects who self-administered FluMist.
All Cause Mortality
	Healthcare Worker Administration		Self-Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Healthcare Worker Administration		Self-Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/548 (0.4%)		3/529 (0.6%)
Hepatobiliary disorders
Cholecystectomy	0/548 (0%)	0	1/529 (0.2%)	1
Injury, poisoning and procedural complications
Hematoma	1/548 (0.2%)	1	0/529 (0%)	0
Hernia	1/548 (0.2%)	1	0/529 (0%)	0
Vascular disorders
Pulmonary Embolism	0/548 (0%)	0	1/529 (0.2%)	1
Deep Vein Thrombosis	0/548 (0%)	0	1/529 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Healthcare Worker Administration		Self-Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/548 (2.4%)		24/529 (4.5%)
Gastrointestinal disorders
Nausea and diarrhea	2/548 (0.4%)	2	1/529 (0.2%)	1
General disorders
Headache	0/548 (0%)	0	3/529 (0.6%)	3
Tiredness and weakness	2/548 (0.4%)	2	3/529 (0.6%)	3
Pain	0/548 (0%)	0	2/529 (0.4%)	2
Respiratory, thoracic and mediastinal disorders
Nasal and chest congestion	2/548 (0.4%)	2	5/529 (0.9%)	5
Sinusitus	1/548 (0.2%)	1	0/529 (0%)	0
Rhinorrhea	1/548 (0.2%)	1	3/529 (0.6%)	3
Cough and sore throat	4/548 (0.7%)	4	5/529 (0.9%)	5
Sneezing	1/548 (0.2%)	1	0/529 (0%)	0
Surgical and medical procedures
Syncope	0/548 (0%)	0	2/529 (0.4%)	2

Limitations/Caveats

Subjects were not followed for clinical outcomes during the influenza season.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.