Study to Assess the Safety, Tolerability and Immune Response Following Vaccination With Immunose™ FLU

Study Overview
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Brief Summary
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The main purpose of the this study is to evaluate the safety and tolerability of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigen.

Official Title
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A Phase I/II, Randomised, Placebo-controlled, Partially-blinded, Parallel-group Study to Assess the Safety, Tolerability and Immune Response Following Vaccination With Immunose™ FLU

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: 15 µg HA/strain and 1% Endocine™
* Biological: 15 µg HA/strain and 2% Endocine™
* Biological: 15 µg HA/strain
* Biological: intramuscular comparator
* Biological: intranasal comparator
* Biological: Placebo, Saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunose™ FLU 1%,<br>15 µg haemagglutinin(HA)/strain and 1% Endocine™ | Biological: 15 µg HA/strain and 1% Endocine™<br>* intranasal administration<br>|
| Experimental: Immunose™ FLU 2%,<br>15 µg HA/strain and 2% Endocine™ | Biological: 15 µg HA/strain and 2% Endocine™<br>* intranasal administration<br>|
| Experimental: Influenza antigen,<br>15 µg HA/strain | Biological: 15 µg HA/strain<br>* intranasal administration<br>|
| Placebo Comparator: Saline (NaCl),<br>Placebo | Biological: Placebo, Saline<br>* intranasal administration<br>|
| Active Comparator: i.m. comparator,<br>15 µg HA/strain | Biological: intramuscular comparator<br>* intramuscular administration<br>|
| Active Comparator: i.n. comparator<br> | Biological: intranasal comparator<br>* intranasal administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Pre-dose, and 15 and 120 min after study drug administration (Visit 2). | 
| 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. | Pre-dose, and 15 and 120 min after second study drug administration (Visit 3). |