Influenza, Human
Conditions
Keywords
Needle Free, Influenza
Brief summary
The purpose of this study is to determine if the administration of flu vaccine using Needle-Free is equivalent to Needle and Syringe administration as measured by laboratory tests of immune response.
Detailed description
Primary: To evaluate the non-inferiority of flu vaccine administered by needle-free intramuscular (IM) injection versus needle and syringe IM injection as determined with serum hemagglutination inhibition (HAI) reciprocal titers in healthy adults between 18-64 years. Secondary: To compare tolerability and safety of the vaccine in the same population based on specifically solicited local and systemic reactions occurring through 7 days post-immunization and adverse events spontaneously reported through approximately 28 days post immunization.
Interventions
BIOLOGICALInfluenza Vaccine
Influenza Vaccine
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 time of enrollment * Willing and able to give informed consent after reading the consent form and given 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 trivalent influenza vaccine (TIV) or quadrivalent influenza vaccine (QIV) based on PI judgment * 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 known immunosuppressive condition including: history of human immunodeficiency virus (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, neomycin, polymyxin 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 Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | 28 Days | The GMT criterion for non-inferiority for the upper limit of the 95% CIs of the GMT ratio (GMT with Needle-Free / GMT with Needle and Syringe) antigen will not exceed 1.5 fold. |
| The Number of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titer. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Immediate Complaints | Day 0 | The following possible immediate complaints will be solicited following the 30 minute safety observation period post-vaccination: local pain, redness, induration/swelling, itching where the injection was given. The data will be reported as immediate complaints and presumed to be related to the test article. Any other symptom experienced at 30 minutes will be recorded as an adverse event. |
| Percentage of Subjects With Solicited Local or Systemic Adverse Events | 7 Days | vaccine reactogenicity will be collected on a patient-completed diary card daily for seven days post-vaccination. The following adverse events will be solicited on the diary card: injection site pain, injection site tenderness, injection site itching, injection site swelling, injection site redness, injection site bruising, fever, fatigue, headache, nausea, chills, muscle ache. |
| Percentage 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. |
Countries
United States
Participant flow
Recruitment details
Study participants were enrolled from 05 November 2014 to 15 January 2015 at six clinical centers in the United States.
Pre-assignment details
A total of 984 participants who met all inclusion criteria and not of the exclusion criteria were enrolled and vaccinated in the study.
Participants by arm
| Arm | Count |
|---|---|
| Needle- Free Subjects will receive a single 0.5mL injection of inactivated influenza vaccine in the deltoid region on Day 0.
Influenza Vaccine: Influenza Vaccine | 496 |
| Needle and Syringe Subjects will receive a single 0.5mL injection of inactivated Influenza Vaccine in the deltoid region on Day 0.
Influenza Vaccine: Influenza Vaccine | 488 |
| Total | 984 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 7 |
| Overall Study | Noncompliance | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Needle- Free | Needle and 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 | 496 Participants | 488 Participants | 984 Participants |
| Sex: Female, Male Female | 241 Participants | 255 Participants | 496 Participants |
| Sex: Female, Male Male | 255 Participants | 233 Participants | 488 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 496 | 0 / 488 |
| other Total, other adverse events | 486 / 496 | 475 / 488 |
| serious Total, serious adverse events | 1 / 496 | 0 / 488 |
Outcome results
Primary
Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT)
The GMT criterion for non-inferiority for the upper limit of the 95% CIs of the GMT ratio (GMT with Needle-Free / GMT with Needle and Syringe) antigen will not exceed 1.5 fold.
Time frame: 28 Days
Population: Geometric mean titers of antibodies against the hemagglutinin (HA) antigens were assessed in the immunogenicity population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Needle and Syringe | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | A/ H1N1 Day 0 | 3.80 Titers | Standard Deviation 1.406 |
| Needle and Syringe | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | A H1N1 Day 28 | 5.72 Titers | Standard Deviation 1.109 |
| Needle and Syringe | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | A/H3N2 Day 0 | 4.09 Titers | Standard Deviation 1.549 |
| Needle and Syringe | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | A/H3N2 Day 28 | 6.04 Titers | Standard Deviation 1.104 |
| Needle and Syringe | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | B1 Day 0 | 2.83 Titers | Standard Deviation 1.128 |
| Needle and Syringe | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | B1 Day 28 | 4.27 Titers | Standard Deviation 1.102 |
| Needle and Syringe | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | B2 Day 0 | 2.40 Titers | Standard Deviation 0.904 |
| Needle and Syringe | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | B2 Day 28 | 3.83 Titers | Standard Deviation 0.978 |
| Needle- Free | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | B2 Day 28 | 3.78 Titers | Standard Deviation 1.038 |
| Needle- Free | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | A/ H1N1 Day 0 | 3.77 Titers | Standard Deviation 1.441 |
| Needle- Free | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | B1 Day 0 | 2.94 Titers | Standard Deviation 1.198 |
| Needle- Free | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | A H1N1 Day 28 | 5.70 Titers | Standard Deviation 1.103 |
| Needle- Free | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | B2 Day 0 | 2.52 Titers | Standard Deviation 0.909 |
| Needle- Free | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | A/H3N2 Day 0 | 4.09 Titers | Standard Deviation 1.527 |
| Needle- Free | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | B1 Day 28 | 4.25 Titers | Standard Deviation 1.15 |
| Needle- Free | Anti Influenza Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) | A/H3N2 Day 28 | 5.99 Titers | Standard Deviation 1.129 |
Primary
The Number of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titer.
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: Seroconversion against the hemagglutinin antigens contained in the vaccine were assessed in the Immunogenicity Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Needle and Syringe | The Number of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titer. | A/H1N1 | 457 participants |
| Needle and Syringe | The Number of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titer. | A/H3N2 | 456 participants |
| Needle and Syringe | The Number of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titer. | B1 | 326 participants |
| Needle and Syringe | The Number of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titer. | B2 | 177 participants |
| Needle- Free | The Number of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titer. | B2 | 167 participants |
| Needle- Free | The Number of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titer. | A/H1N1 | 461 participants |
| Needle- Free | The Number of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titer. | B1 | 365 participants |
| Needle- Free | The Number of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titer. | A/H3N2 | 468 participants |
Secondary
Percentage of Subjects With Immediate Complaints
The following possible immediate complaints will be solicited following the 30 minute safety observation period post-vaccination: local pain, redness, induration/swelling, itching where the injection was given. The data will be reported as immediate complaints and presumed to be related to the test article. Any other symptom experienced at 30 minutes will be recorded as an adverse event.
Time frame: Day 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Needle and Syringe | Percentage of Subjects With Immediate Complaints | 13.6 percentage of participants |
| Needle- Free | Percentage of Subjects With Immediate Complaints | 30.2 percentage of participants |
Secondary
Percentage of Subjects With Solicited Local or Systemic Adverse Events
vaccine reactogenicity will be collected on a patient-completed diary card daily for seven days post-vaccination. The following adverse events will be solicited on the diary card: injection site pain, injection site tenderness, injection site itching, injection site swelling, injection site redness, injection site bruising, fever, fatigue, headache, nausea, chills, muscle ache.
Time frame: 7 Days
Population: Data included in the analysis were collected on a 7-Day Diary Card from the safety population and grade \>1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Tenderness | 46.9 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Headache | 16.0 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Redness | 8.2 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Fatigue | 15.1 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Pain | 33.7 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Muscle Ache | 21.6 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Swelling | 6.7 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Itching | 6.9 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Nausea | 6.3 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Bruising | 4.0 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Vomiting | 1.9 percentage of subjects |
| Needle and Syringe | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Chills | 6.3 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Vomiting | 1.0 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Pain | 48.6 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Tenderness | 65.6 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Itching | 24.3 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Redness | 35.5 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Swelling | 29.8 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Bruising | 10.3 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Headache | 14.8 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Fatigue | 11.9 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Muscle Ache | 20.3 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Chills | 4.9 percentage of subjects |
| Needle- Free | Percentage of Subjects With Solicited Local or Systemic Adverse Events | Nausea | 4.1 percentage of subjects |
Secondary
Percentage 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Needle and Syringe | Percentage of Subjects With Spontaneously Reported Adverse Events | 26.5 percentage of subjects |
| Needle- Free | Percentage of Subjects With Spontaneously Reported Adverse Events | 24.4 percentage of subjects |