Influenza
Conditions
Keywords
influenza
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.
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.
Interventions
DRUGFluMist
FluMist Intranasal Vaccine
Sponsors
Henry M. Jackson Foundation for the Advancement of Military Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects | 28+/- 7 days post-vaccination |
Secondary
| Measure | Time frame |
|---|---|
| Difference and Proportion in Seroresponse of Subjects | 28+/- 7 days post-vaccination |
| Difference and Proportion in Seroconversion of Subjects | 28+/- 7 days post-vaccination |
Other
| Measure | Time frame |
|---|---|
| Feasibility of Self-administration Prior to Vaccine Administration | 28+/- 7 days post-vaccination |
| Feasibility of Self-administration Following Vaccine Administration | 28+/- 7 days post-vaccination |
Countries
United States
Participant flow
Recruitment details
Recruitment and enrollment was conducted in San Antonio, Texas and San Diego, California.
Participants by arm
| Arm | Count |
|---|---|
| Healthcare Worker Administration FluMist administered by a Healthcare Worker | 523 |
| Self-Administration FluMist self-administered by subject | 501 |
| Total | 1,024 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 15 | 18 |
| Overall Study | personal reasons | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 7 | 8 |
| Overall Study | unknown reasons | 1 | 1 |
Baseline characteristics
| Characteristic | Healthcare Worker Administration | Total | Self-Administration |
|---|---|---|---|
| Age, Continuous | 30 years | 29 years | 28 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 103 Participants | 204 Participants | 101 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 420 Participants | 820 Participants | 400 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 88 Participants | 143 Participants | 55 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 103 Participants | 202 Participants | 99 Participants |
| Race (NIH/OMB) White | 332 Participants | 679 Participants | 347 Participants |
| Region of Enrollment United States | 523 participants | 1024 participants | 501 participants |
| Sex: Female, Male Female | 157 Participants | 298 Participants | 141 Participants |
| Sex: Female, Male Male | 366 Participants | 726 Participants | 360 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 548 | 24 / 529 |
| serious Total, serious adverse events | 2 / 548 | 3 / 529 |
Outcome results
Primary
Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects
Time frame: 28+/- 7 days post-vaccination
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Healthcare Worker Administration | Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects | A/H1N1 | 45.8 titer ratio |
| Healthcare Worker Administration | Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects | A/H3N2 | 45.5 titer ratio |
| Healthcare Worker Administration | Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects | B/Yamagata | 17.2 titer ratio |
| Healthcare Worker Administration | Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects | B/Brisbane (2013-2014 only; HCWA n=346; SA n=359) | 16.2 titer ratio |
| Self-Administration | Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects | B/Brisbane (2013-2014 only; HCWA n=346; SA n=359) | 14.7 titer ratio |
| Self-Administration | Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects | A/H1N1 | 48.7 titer ratio |
| Self-Administration | Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects | B/Yamagata | 17.8 titer ratio |
| Self-Administration | Post-vaccination Geometric Mean Titer (GMT) Ratios Between HCWA and SA Subjects | A/H3N2 | 46.4 titer ratio |
Comparison: A/H1N1p-value: 0.43Farrington-Manning Method
Comparison: A/H3N2p-value: 0.8Farrington-Manning Method
Comparison: B/Yamagatap-value: 0.55Farrington-Manning Method
Comparison: B/Brisbanep-value: 0.16Farrington-Manning Method
Secondary
Difference and Proportion in Seroconversion of Subjects
Time frame: 28+/- 7 days post-vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthcare Worker Administration | Difference and Proportion in Seroconversion of Subjects | A/H1N1 | 15 participants |
| Healthcare Worker Administration | Difference and Proportion in Seroconversion of Subjects | A/H3N2 | 8 participants |
| Healthcare Worker Administration | Difference and Proportion in Seroconversion of Subjects | B/Yamagata | 2 participants |
| Healthcare Worker Administration | Difference and Proportion in Seroconversion of Subjects | B/Brisbane (2013-2014 only; HCWA n=346; SA n=359) | 23 participants |
| Self-Administration | Difference and Proportion in Seroconversion of Subjects | B/Brisbane (2013-2014 only; HCWA n=346; SA n=359) | 14 participants |
| Self-Administration | Difference and Proportion in Seroconversion of Subjects | A/H1N1 | 5 participants |
| Self-Administration | Difference and Proportion in Seroconversion of Subjects | B/Yamagata | 3 participants |
| Self-Administration | Difference and Proportion in Seroconversion of Subjects | A/H3N2 | 7 participants |
Secondary
Difference and Proportion in Seroresponse of Subjects
Time frame: 28+/- 7 days post-vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthcare Worker Administration | Difference and Proportion in Seroresponse of Subjects | A/H1N1 | 340 participants |
| Healthcare Worker Administration | Difference and Proportion in Seroresponse of Subjects | A/H3N2 | 335 participants |
| Healthcare Worker Administration | Difference and Proportion in Seroresponse of Subjects | B/Yamagata | 141 participants |
| Healthcare Worker Administration | Difference and Proportion in Seroresponse of Subjects | B/Brisbane (2013-2014 only; HCWA n=346; SA n=359) | 84 participants |
| Self-Administration | Difference and Proportion in Seroresponse of Subjects | B/Brisbane (2013-2014 only; HCWA n=346; SA n=359) | 79 participants |
| Self-Administration | Difference and Proportion in Seroresponse of Subjects | A/H1N1 | 344 participants |
| Self-Administration | Difference and Proportion in Seroresponse of Subjects | B/Yamagata | 137 participants |
| Self-Administration | Difference and Proportion in Seroresponse of Subjects | A/H3N2 | 336 participants |
Other Pre-specified
Feasibility of Self-administration Following Vaccine Administration
Time frame: 28+/- 7 days post-vaccination
Population: Numbers include participants randomized to the SA group only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthcare Worker Administration | Feasibility of Self-administration Following Vaccine Administration | HCWA preferred method | 29 participants |
| Healthcare Worker Administration | Feasibility of Self-administration Following Vaccine Administration | SA preferred method | 319 participants |
| Healthcare Worker Administration | Feasibility of Self-administration Following Vaccine Administration | No preference | 153 participants |
Other Pre-specified
Feasibility of Self-administration Prior to Vaccine Administration
Time frame: 28+/- 7 days post-vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthcare Worker Administration | Feasibility of Self-administration Prior to Vaccine Administration | HCWA preferred method | 71 participants |
| Healthcare Worker Administration | Feasibility of Self-administration Prior to Vaccine Administration | SA preferred method | 132 participants |
| Healthcare Worker Administration | Feasibility of Self-administration Prior to Vaccine Administration | No preference | 320 participants |
| Self-Administration | Feasibility of Self-administration Prior to Vaccine Administration | HCWA preferred method | 65 participants |
| Self-Administration | Feasibility of Self-administration Prior to Vaccine Administration | SA preferred method | 129 participants |
| Self-Administration | Feasibility of Self-administration Prior to Vaccine Administration | No preference | 307 participants |