Influenza, Human
Conditions
Brief summary
The main purpose of the this study is to evaluate the safety and tolerability of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigen.
Interventions
BIOLOGICAL15 µg HA/strain and 1% Endocine™
intranasal administration
BIOLOGICAL15 µg HA/strain and 2% Endocine™
intranasal administration
BIOLOGICAL15 µg HA/strain
intranasal administration
BIOLOGICALintramuscular comparator
intramuscular administration
BIOLOGICALintranasal comparator
intranasal administration
BIOLOGICALPlacebo, Saline
intranasal administration
Sponsors
Eurocine Vaccines AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent prior to any study related procedures. * Male or female 18-39 years of age (both inclusive) at screening * Subjects who the Investigator believes will comply with the requirements of the protocol. * BMI: 18.0 and 30.0 kg/m2 (inclusive). * Judged by the Investigator to have no serious illness based on medical history, physical examination, ECG, vital signs and blood and urine assessments at screening. * From the signing of the informed consent until 2 months after the last vaccination (Visit 3 for group 1 to 4 and Visit 2 for group 5 and 6) female subjects have to use contraceptive methods with a failure rate of \< 1% to prevent pregnancy (combined \[oestrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, transdermal\], progestogen- only hormonal contraception associated with inhibition of ovulation \[oral, injectable, implantable\], intrauterine device \[IUD\], intrauterine hormone-releasing system \[IUS\], bilateral tubal occlusion, sexual abstinence). Any male partner should be willing to use condom or should be vasectomized.
Exclusion criteria
* Diagnosis of laboratory-confirmed influenza in the 2015/2016 season. * Use of any investigational drug product within 3 months before screening or planned use during the study period, including the safety follow-up. * Administration of an influenza vaccine during the 6 months before screening. * Previously received another vaccine within 28 days before administration of the study vaccine, or is scheduled to receive another vaccine during the study period, excluding the safety follow-up. * Any contra-indication to intramuscular administration of the influenza vaccine AdimFlu-S according to its prescribing information. * Any contra-indication to administration of the influenza vaccine Fluenz Tetra according to its summary of product characteristics (SmPC). * History of any anaphylactic reaction and/or serious allergic reaction following a vaccination, a proven hypersensitivity to any component of the study vaccine (e.g., to eggs or egg product as well as ovalbumin, chicken protein, chicken feathers, influenza viral protein, kanamycin, gentamycin and neomycin sulphate). * Diagnosis of asthma with poor disease control as assessed by the Investigator. * Potent immunosuppressive therapy including cytostatics, antibodies, drugs acting on immunophilins, interferons and other drugs used to prevent rejection of organ transplants, within 6 months before screening. * Use of any parenteral or oral corticosteroids within 30 days prior to screening. Inhaled steroids are allowed. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * Any progressive or severe neurologic disorder, seizure disorder or Guillain-Barré syndrome. * History of Guillain-Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine. * Received blood, blood products and/or plasma derivatives or any administration of immunoglobulin preparation within the three months prior to Visit 2, or planned during the study. * Participation in blood donation within 3 months or plasma donation within 1 month prior to Visit 2. * History of substance or alcohol abuse within the past 2 years. * History or any illness/condition that, in the opinion of the Investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study. * Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and HIV. * Pregnant or lactating female or intent to become pregnant during the clinic phase (up until and including Visit 4 for group 1 to 4 and Visit 3 for group 5 and 6) and for 2 months after the last vaccination. * History of Bell's palsy. * Ongoing regular use of intranasal sprays including corticosteroids and decongestants. * Ongoing cough, sinusitis, allergic rhinitis, nasal polyps or obstruction, including septum deviation significant enough to prevent bilateral administration of study vaccine. * Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. * Subjects that are prone to nosebleed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Tolerability - First Dose | Pre-dose, and 15 and 120 min after study drug administration (Visit 2). | Local tolerability, as measured by at least one of the administration site reactions swelling, redness, pain and pruritus, regardless of severity. |
| Local Tolerability - Second Dose (Group 1-4 Only) | Pre-dose, and 15 and 120 min after second study drug administration (Visit 3). | Local tolerability, as measured by at least one of the administration site reactions swelling, redness, pain and pruritus, regardless of severity. |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Immunose™ FLU 1%, 15 µg haemagglutinin(HA)/strain and 1% Endocine™
15 µg HA/strain and 1% Endocine™: intranasal administration | 36 |
| Immunose™ FLU 2%, 15 µg HA/strain and 2% Endocine™
15 µg HA/strain and 2% Endocine™: intranasal administration | 35 |
| Influenza Antigen, 15 µg HA/strain
15 µg HA/strain: intranasal administration | 36 |
| Saline (NaCl), Placebo
Placebo, Saline: intranasal administration | 18 |
| i.m. Comparator, 15 µg HA/strain
intramuscular comparator: intramuscular administration | 18 |
| i.n. Comparator intranasal comparator: intranasal administration | 19 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Family reasons | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Immunose™ FLU 2%, | Influenza Antigen, | Saline (NaCl), | Immunose™ FLU 1%, | i.m. Comparator, | i.n. Comparator | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 36 Participants | 18 Participants | 36 Participants | 18 Participants | 19 Participants | 162 Participants |
| Age, Continuous | 26.34 years STANDARD_DEVIATION 5.46 | 25.11 years STANDARD_DEVIATION 4.8 | 27.72 years STANDARD_DEVIATION 5.6 | 26.36 years STANDARD_DEVIATION 5.69 | 27.22 years STANDARD_DEVIATION 4.75 | 24.68 years STANDARD_DEVIATION 4.32 | 26.13 years STANDARD_DEVIATION 5.2 |
| Race/Ethnicity, Customized Ethnicity African descent | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Ethnicity Asian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Caucasian | 32 Participants | 34 Participants | 17 Participants | 35 Participants | 17 Participants | 19 Participants | 154 Participants |
| Race/Ethnicity, Customized Ethnicity Mixed/multi-racial | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Region of Enrollment Sweden | 35 participants | 36 participants | 18 participants | 36 participants | 18 participants | 19 participants | 162 participants |
| Sex: Female, Male Female | 19 Participants | 20 Participants | 15 Participants | 20 Participants | 9 Participants | 8 Participants | 91 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 3 Participants | 16 Participants | 9 Participants | 11 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 35 | 0 / 36 | 0 / 18 | 0 / 18 | 0 / 19 |
| other Total, other adverse events | 32 / 36 | 30 / 35 | 26 / 36 | 10 / 18 | 13 / 18 | 10 / 19 |
| serious Total, serious adverse events | 2 / 36 | 0 / 35 | 0 / 36 | 0 / 18 | 0 / 18 | 0 / 19 |
Outcome results
Primary
Local Tolerability - First Dose
Local tolerability, as measured by at least one of the administration site reactions swelling, redness, pain and pruritus, regardless of severity.
Time frame: Pre-dose, and 15 and 120 min after study drug administration (Visit 2).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Immunose™ FLU 1%, | Local Tolerability - First Dose | 15 min post-dose | 11 Participants |
| Immunose™ FLU 1%, | Local Tolerability - First Dose | Pre-dose | 5 Participants |
| Immunose™ FLU 1%, | Local Tolerability - First Dose | 120 min post-dose | 9 Participants |
| Immunose™ FLU 2%, | Local Tolerability - First Dose | 15 min post-dose | 10 Participants |
| Immunose™ FLU 2%, | Local Tolerability - First Dose | Pre-dose | 4 Participants |
| Immunose™ FLU 2%, | Local Tolerability - First Dose | 120 min post-dose | 5 Participants |
| Influenza Antigen, | Local Tolerability - First Dose | 15 min post-dose | 7 Participants |
| Influenza Antigen, | Local Tolerability - First Dose | 120 min post-dose | 7 Participants |
| Influenza Antigen, | Local Tolerability - First Dose | Pre-dose | 9 Participants |
| Saline (NaCl), | Local Tolerability - First Dose | 15 min post-dose | 0 Participants |
| Saline (NaCl), | Local Tolerability - First Dose | Pre-dose | 0 Participants |
| Saline (NaCl), | Local Tolerability - First Dose | 120 min post-dose | 0 Participants |
| i.m. Comparator, | Local Tolerability - First Dose | 15 min post-dose | 9 Participants |
| i.m. Comparator, | Local Tolerability - First Dose | Pre-dose | 0 Participants |
| i.m. Comparator, | Local Tolerability - First Dose | 120 min post-dose | 6 Participants |
| i.n. Comparator | Local Tolerability - First Dose | Pre-dose | 4 Participants |
| i.n. Comparator | Local Tolerability - First Dose | 120 min post-dose | 1 Participants |
| i.n. Comparator | Local Tolerability - First Dose | 15 min post-dose | 3 Participants |
Primary
Local Tolerability - Second Dose (Group 1-4 Only)
Local tolerability, as measured by at least one of the administration site reactions swelling, redness, pain and pruritus, regardless of severity.
Time frame: Pre-dose, and 15 and 120 min after second study drug administration (Visit 3).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Immunose™ FLU 1%, | Local Tolerability - Second Dose (Group 1-4 Only) | Pre-dose | 8 Participants |
| Immunose™ FLU 1%, | Local Tolerability - Second Dose (Group 1-4 Only) | 120 min post-dose | 10 Participants |
| Immunose™ FLU 1%, | Local Tolerability - Second Dose (Group 1-4 Only) | 15 min post-dose | 16 Participants |
| Immunose™ FLU 2%, | Local Tolerability - Second Dose (Group 1-4 Only) | Pre-dose | 8 Participants |
| Immunose™ FLU 2%, | Local Tolerability - Second Dose (Group 1-4 Only) | 120 min post-dose | 8 Participants |
| Immunose™ FLU 2%, | Local Tolerability - Second Dose (Group 1-4 Only) | 15 min post-dose | 12 Participants |
| Influenza Antigen, | Local Tolerability - Second Dose (Group 1-4 Only) | 15 min post-dose | 10 Participants |
| Influenza Antigen, | Local Tolerability - Second Dose (Group 1-4 Only) | Pre-dose | 7 Participants |
| Influenza Antigen, | Local Tolerability - Second Dose (Group 1-4 Only) | 120 min post-dose | 5 Participants |
| Saline (NaCl), | Local Tolerability - Second Dose (Group 1-4 Only) | Pre-dose | 2 Participants |
| Saline (NaCl), | Local Tolerability - Second Dose (Group 1-4 Only) | 120 min post-dose | 1 Participants |
| Saline (NaCl), | Local Tolerability - Second Dose (Group 1-4 Only) | 15 min post-dose | 2 Participants |