Influenza, Human
Conditions
Keywords
Injections, Jet, Influenza Vaccines
Brief summary
The purpose of this study is to determine if the administration of a seasonal flu vaccine using a PharmaJet's needle-free injection device (STRATIS) is equivalent to needle and syringe administration, as measured by laboratory tests of immune response.
Interventions
BIOLOGICALAFLURIA vaccine (2012-2013 formulation)
Patients will receive a single 0.5 mL injection of AFLURIA vaccine in the deltoid region.
DEVICENeedle-Syringe
DEVICEStratis needle-free injection device
Sponsors
PharmaJet, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults aged ≥18 and ≤64 years of age at the time of enrollment * Willing and able to give informed consent after reading the consent form and adequate opportunity to discuss the study with the investigator or qualified designee * Willing and able to adhere to all protocol required study procedures and to attend scheduled visits. * Able to receive the TIV influenza vaccine, based on University of Colorado Health (UCH) employee health flu screening guidelines. * Stable health status with no exclusionary medical or neuropsychiatric conditions as determined during the screening evaluation and based on the clinical judgment of the investigator or qualified designee. * Access to a consistent means of telephone contact
Exclusion criteria
* Presence of any febrile illness (oral temperature \>38°C) on the day of immunization. Such subjects will be reevaluated for enrollment after resolution of illness. * Presence of significant acute or chronic uncontrolled medical or neuropsychiatric illness and /or presence of any significant condition that may prohibit inclusion as determined by the investigator or his qualified designee. Uncontrolled is defined as: requiring institution of a new treatment within 1 month prior to study enrollment or change in medication dosage in the month prior to study enrollment. * Any immunosuppressive condition including: history of HIV infection, cancer or cancer treatment within 3 years of study enrollment, systemic glucocorticoids (in a dose ≥10 mg prednisone daily or equivalent for more than 7 consecutive days or for 10 or more days in total) within 1 month of study enrollment, or any other cytotoxic or immunosuppressive drug within 3 months of study enrollment. Any significant disorder of coagulation that would increase the risk of intramuscular injections or treatment with Coumadin derivatives or heparin. * Known or suspected to be allergic to eggs, chicken protein, gentamicin or influenza vaccine. * History of severe or previous serious adverse reaction after an influenza vaccination. * Receipt of any immunoglobulin and/or blood products within 3 months of immunization or planned administration of any of these products during the study period. * Prior history of any demyelinating disease including Guillain-Barre syndrome. * Presence of an active neurological disorder. * History of significant alcohol or drug abuse within one year prior to study enrollment. * Influenza vaccination or laboratory confirmed influenza infection within the previous six months before study vaccination or planned influenza vaccination during the study period. * Planned administration of any non-influenza vaccines 30 days prior to the study or during the study period. * Pregnant or plans to become pregnant during the study period. * Currently enrolled in another vaccine or drug study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti Influenza Type B Seroconversion | 28 days | Seroconversion is defined as a 4-fold rise in HAI titer in post-immunization serum relative to pre-immunization serum, or if pre-immunization serum had an undetectable titer (\<1:10), attainment of a post-immunization titer of ≥1:40. |
| Anti Influenza Type A/H2N3 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | 28 days | The GMT criterion for non-inferiority for the upper limit of the 95% CIs of the GMT ratio(GMT with NS / GMT with PJ Stratis) for each antigen to not exceed 1.5 fold. |
| Anti Influenza Type B Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | 28 days | The GMT criterion for non-inferiority for the upper limit of the 95% CIs of the GMT ratio(GMT with NS / GMT with PJ Stratis) for each antigen to not exceed 1.5 fold. |
| Anti Influenza Type A/H1N1 Seroconversion | 28 days | Seroconversion is defined as a 4-fold rise in HAI titer in post-immunization serum relative to pre-immunization serum, or if pre-immunization serum had an undetectable titer (\<1:10), attainment of a post-immunization titer of ≥1:40. |
| Anti Influenza Type A/H3N2 Seroconversion | 28 days | Seroconversion is defined as a 4-fold rise in HAI titer in post-immunization serum relative to pre-immunization serum, or if pre-immunization serum had an undetectable titer (\<1:10), attainment of a post-immunization titer of ≥1:40. |
| Anti Influenza Type A/H1N1 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | 28 days | The GMT criterion for non-inferiority for the upper limit of the 95% CIs of the GMT ratio(GMT with NS / GMT with PJ Stratis) for A/H1N1 antigen will not exceed 1.5 fold. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Vaccine Reactogenicity Events | Day 0, 1, 2, 3, 4, 5, and 6 | Vaccine reactogenicity will be collected on a patient-completed diary card during checkout from Day 0 and on the next six evenings post-vaccination. The following adverse events will be solicited on the diary card: pain at injection site, tenderness at injection site, redness where the injection is given; induration/swelling (lump) where the injection is given; bruising where the injection is given; itching where the injection is given; headache; tiredness/fatigue (asthenia, lethargy, malaise); general muscle ache (myalgia); chills; nausea; vomiting. Subjects will also record their oral temperature on the diary card each evening. |
| Number of Subjects With Spontaneously Reported Adverse Events | 28 days | Subjects will be asked to report any other symptoms experienced in addition to the solicited immediate and vaccine reactogenicity events. Any other events reported will be tabulated as spontaneously reported adverse events. |
| Percentage of Subjects Who Received a PJ Stratis Injection Would Choose to Receive This Type of Injection Again | 28 Days | — |
| Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Within 30 minutes post-vaccination | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| STRATIS Patients assigned to this arm will receive AFLURIA vaccine administered using the STRATIS needle-free injection device.
AFLURIA vaccine (2012-2013 formulation): Patients will receive a single 0.5 mL injection of AFLURIA vaccine in the deltoid region.
STRATIS needle-free injection device | 624 |
| Needle-Syringe Patients assigned to this arm will receive AFLURIA vaccine administered using a needle and syringe.
AFLURIA vaccine (2012-2013 formulation): Patients will receive a single 0.5 mL injection of AFLURIA vaccine in the deltoid region.
Needle-Syringe | 623 |
| Total | 1,247 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | informed consent | 3 | 0 |
| Overall Study | Lost to Follow-up | 7 | 13 |
| Overall Study | Physician Decision | 6 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | STRATIS | Needle-Syringe | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 624 Participants | 623 Participants | 1247 Participants |
| Age, Continuous | 41.3 Years STANDARD_DEVIATION 12.92 | 41.5 Years STANDARD_DEVIATION 12.49 | 41.4 Years STANDARD_DEVIATION 12.7 |
| Region of Enrollment United States | 624 participants | 623 participants | 1247 participants |
| Sex: Female, Male Female | 449 Participants | 432 Participants | 881 Participants |
| Sex: Female, Male Male | 175 Participants | 191 Participants | 366 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 586 / 624 | 516 / 623 |
| serious Total, serious adverse events | 1 / 624 | 2 / 623 |
Outcome results
Primary
Anti Influenza Type A/H1N1 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT)
The GMT criterion for non-inferiority for the upper limit of the 95% CIs of the GMT ratio(GMT with NS / GMT with PJ Stratis) for A/H1N1 antigen will not exceed 1.5 fold.
Time frame: 28 days
Population: The immunogenicity analyses were conducted using data from subjects in the Immunogenicity Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PJ STRATIS | Anti Influenza Type A/H1N1 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 0 | 4.43 Titers | Standard Deviation 1.348 |
| PJ STRATIS | Anti Influenza Type A/H1N1 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 28 | 5.64 Titers | Standard Deviation 1.006 |
| Needle-Syringe | Anti Influenza Type A/H1N1 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 0 | 4.38 Titers | Standard Deviation 1.352 |
| Needle-Syringe | Anti Influenza Type A/H1N1 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 28 | 5.64 Titers | Standard Deviation 0.997 |
Comparison: For a sample size of 550 per group each test has an individual power of \> 99% to rule out the 1.5-fold difference using a two-sided α = 0.05, assuming equal GMTs between the two treatment groups. The overall power for the study to demonstrate the non-inferiority for the 6 co-primary endpoints is \> 80%, computed as product of 6 individual powers.95% CI: [0.88, 1.12]
Primary
Anti Influenza Type A/H1N1 Seroconversion
Seroconversion is defined as a 4-fold rise in HAI titer in post-immunization serum relative to pre-immunization serum, or if pre-immunization serum had an undetectable titer (\<1:10), attainment of a post-immunization titer of ≥1:40.
Time frame: 28 days
Population: The immunogenicity analyses were conducted using data from subjects in the Immunogenicity Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PJ STRATIS | Anti Influenza Type A/H1N1 Seroconversion | 37.5 Percent of Participants |
| Needle-Syringe | Anti Influenza Type A/H1N1 Seroconversion | 38.4 Percent of Participants |
Comparison: For a sample size of 550 per group each test has an individual power of \> 95% to rule out the 10 percentage points difference using a one-sided α = 0.025, assuming equal seroconversion rates between the two treatment groups. The overall power for the study to demonstrate the non-inferiority for the 6 co-primary endpoints is \> 80%, computed as product of 6 individual powers.95% CI: [-4.8, 6.5]
Primary
Anti Influenza Type A/H2N3 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT)
The GMT criterion for non-inferiority for the upper limit of the 95% CIs of the GMT ratio(GMT with NS / GMT with PJ Stratis) for each antigen to not exceed 1.5 fold.
Time frame: 28 days
Population: The immunogenicity analyses were conducted using data from subjects in the Immunogenicity Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PJ STRATIS | Anti Influenza Type A/H2N3 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 28 | 5.51 Titers | Standard Deviation 1.022 |
| PJ STRATIS | Anti Influenza Type A/H2N3 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 0 | 4.22 Titers | Standard Deviation 1.283 |
| Needle-Syringe | Anti Influenza Type A/H2N3 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 28 | 5.58 Titers | Standard Deviation 0.987 |
| Needle-Syringe | Anti Influenza Type A/H2N3 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 0 | 4.32 Titers | Standard Deviation 1.29 |
Comparison: For a sample size of 550 per group each test has an individual power of \> 99% to rule out the 1.5-fold difference using a two-sided α = 0.05, assuming equal GMTs between the two treatment groups. The overall power for the study to demonstrate the non-inferiority for the 6 co-primary endpoints is \> 80%, computed as product of 6 individual powers.95% CI: [0.96, 1.21]
Primary
Anti Influenza Type A/H3N2 Seroconversion
Seroconversion is defined as a 4-fold rise in HAI titer in post-immunization serum relative to pre-immunization serum, or if pre-immunization serum had an undetectable titer (\<1:10), attainment of a post-immunization titer of ≥1:40.
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PJ STRATIS | Anti Influenza Type A/H3N2 Seroconversion | 43.8 Percent of Participants |
| Needle-Syringe | Anti Influenza Type A/H3N2 Seroconversion | 45.1 Percent of Participants |
Comparison: For a sample size of 550 per group each test has an individual power of \> 95% to rule out the 10 percentage points difference using a one-sided α = 0.025, assuming equal seroconversion rates between the two treatment groups. The overall power for the study to demonstrate the non-inferiority for the 6 co-primary endpoints is \> 80%, computed as product of 6 individual powers.95% CI: [-4.5, 7.1]
Primary
Anti Influenza Type B Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT)
The GMT criterion for non-inferiority for the upper limit of the 95% CIs of the GMT ratio(GMT with NS / GMT with PJ Stratis) for each antigen to not exceed 1.5 fold.
Time frame: 28 days
Population: The immunogenicity analyses were conducted using data from subjects in the Immunogenicity Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PJ STRATIS | Anti Influenza Type B Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 0 | 2.60 Titers | Standard Deviation 1.028 |
| PJ STRATIS | Anti Influenza Type B Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 28 | 3.75 Titers | Standard Deviation 1.037 |
| Needle-Syringe | Anti Influenza Type B Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 0 | 2.54 Titers | Standard Deviation 1.003 |
| Needle-Syringe | Anti Influenza Type B Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titer (GMT) | Day 28 | 3.68 Titers | Standard Deviation 1.061 |
Comparison: For a sample size of 550 per group each test has an individual power of \> 99% to rule out the 1.5-fold difference using a two-sided α = 0.05, assuming equal GMTs between the two treatment groups. The overall power for the study to demonstrate the non-inferiority for the 6 co-primary endpoints is \> 80%, computed as product of 6 individual powers.95% CI: [0.83, 1.06]
Primary
Anti Influenza Type B Seroconversion
Seroconversion is defined as a 4-fold rise in HAI titer in post-immunization serum relative to pre-immunization serum, or if pre-immunization serum had an undetectable titer (\<1:10), attainment of a post-immunization titer of ≥1:40.
Time frame: 28 days
Population: The immunogenicity analyses were conducted using data from subjects in the Immunogenicity Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PJ STRATIS | Anti Influenza Type B Seroconversion | 34.9 Percent of Participants |
| Needle-Syringe | Anti Influenza Type B Seroconversion | 35.2 Percent of Participants |
Comparison: For a sample size of 550 per group each test has an individual power of \> 91% to rule out the 10 percentage points difference using a one-sided α = 0.025, assuming equal seroconversion rates between the two treatment groups. The overall power for the study to demonstrate the non-inferiority for the 6 co-primary endpoints is \> 80%, computed as product of 6 individual powers.95% CI: [-5.2, 5.9]
Secondary
Number of Subjects With Complaints Within 30 Minutes Following Vaccination
Time frame: Within 30 minutes post-vaccination
Population: The safety population included 1247 subjects (N=624 PJ Stratis, N=623 NS).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PJ STRATIS | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Tenderness | 104 participants |
| PJ STRATIS | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Redness | 113 participants |
| PJ STRATIS | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Pain | 163 participants |
| PJ STRATIS | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Swelling | 5 participants |
| PJ STRATIS | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Itching | 63 participants |
| PJ STRATIS | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Bruising | 0 participants |
| Needle-Syringe | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Itching | 17 participants |
| Needle-Syringe | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Pain | 69 participants |
| Needle-Syringe | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Tenderness | 36 participants |
| Needle-Syringe | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Bruising | 0 participants |
| Needle-Syringe | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Redness | 11 participants |
| Needle-Syringe | Number of Subjects With Complaints Within 30 Minutes Following Vaccination | Swelling | 0 participants |
p-value: <0.001Fisher Exact
Secondary
Number of Subjects With Spontaneously Reported Adverse Events
Subjects will be asked to report any other symptoms experienced in addition to the solicited immediate and vaccine reactogenicity events. Any other events reported will be tabulated as spontaneously reported adverse events.
Time frame: 28 days
Population: The safety population included 1247 subjects (N=624 PJ Stratis, N=623 NS).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PJ STRATIS | Number of Subjects With Spontaneously Reported Adverse Events | 92 participants with spontaneous AEs |
| Needle-Syringe | Number of Subjects With Spontaneously Reported Adverse Events | 73 participants with spontaneous AEs |
Secondary
Number of Subjects With Vaccine Reactogenicity Events
Vaccine reactogenicity will be collected on a patient-completed diary card during checkout from Day 0 and on the next six evenings post-vaccination. The following adverse events will be solicited on the diary card: pain at injection site, tenderness at injection site, redness where the injection is given; induration/swelling (lump) where the injection is given; bruising where the injection is given; itching where the injection is given; headache; tiredness/fatigue (asthenia, lethargy, malaise); general muscle ache (myalgia); chills; nausea; vomiting. Subjects will also record their oral temperature on the diary card each evening.
Time frame: Day 0, 1, 2, 3, 4, 5, and 6
Population: The safety population included 1247 subjects (N=624 PJ Stratis, N=623 NS). Eight subjects (624-616) in the PJ Stratis group and 16 (623-607) in the NS group did not return the 7-Day Diary Card.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Headache | 151 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Redness | 366 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Tenderness | 551 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Malaise | 191 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Swelling | 392 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Myalgia | 222 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Chills | 43 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Itching | 151 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Nausea | 40 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Bruising | 107 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Vomiting | 8 participants |
| PJ STRATIS | Number of Subjects With Vaccine Reactogenicity Events | Pain | 397 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Vomiting | 11 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Pain | 299 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Itching | 50 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Redness | 115 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Swelling | 115 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Bruising | 32 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Tenderness | 472 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Headache | 133 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Malaise | 171 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Chills | 43 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Nausea | 39 participants |
| Needle-Syringe | Number of Subjects With Vaccine Reactogenicity Events | Myalgia | 214 participants |
p-value: <0.001Fisher Exact
Secondary
Percentage of Subjects Who Received a PJ Stratis Injection Would Choose to Receive This Type of Injection Again
Time frame: 28 Days
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PJ STRATIS | Percentage of Subjects Who Received a PJ Stratis Injection Would Choose to Receive This Type of Injection Again | 89 Percent of Participants |