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

Study Overview
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Brief Summary
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This is a Phase I/II, randomised, multicentre, partially double-blind (group 1, 2, 4 and 5), parallel-group study designed to primarily evaluate the safety, tolerability and immune response in older adults (age 50 to 75 years) following Immunose™ FLU vaccination at 5 sites in Sweden. A total of 300 subjects will be randomised to 1 of 7 treatment groups. The hypothesis is that Immunose™ FLU is safe and tolerable and will increase the influenza-specific mucosal immune response in older adults.

Official Title
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A Phase I/II, Randomised, Multicentre, Placebo-controlled, Partially-blinded, Parallel-group Study to Assess the Safety, Tolerability and Immune Response Following Vaccination With Immunose™ FLU in Older Adults (Age 50 to 75 Years)

Conditions
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Influenza

Intervention / Treatment
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* Biological: Immunose™ FLU 1%
* Biological: Immunose™ FLU 2%, 200 μl
* Biological: Immunose™ FLU 2%, 300 μl
* Biological: Influenza antigen
* Drug: Placebo
* Biological: i.m comparator


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 50 to75 years of age (both inclusive) at screening. Subjects who the Investigator believes will comply with the requirements of the protocol. 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. All females should have been post-menopausal for at least 12 months or use a highly effective contraceptive method to prevent pregnancy. Non-menopausal females 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 2017/2018 season. Use of any investigational drug product within 3 months before screening or planned use during the study period, including the safety follow-up period. Administration of an influenza vaccine during the 9 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 period. Any contra-indication to intramuscular administration of the comparator influenza vaccine according to its SPC. 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, neomycin sulphate, formaldehyde and sodium deoxycholate). 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. Any history of Guillain-Barré syndrome. Received blood, blood products and/or plasma derivatives or any administration of immunoglobulin preparation within the 3 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 or HIV. Pregnant or lactating female or intent to become pregnant during the clinic phase 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: 50 Years
Maximum Age: 75 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunose™ FLU 1%<br>Immunose™ FLU 1%. QIV, 30 μg HA/strain and 1% Endocine™ 200 μl for intranasal administration, 2 dosing occasions. | Biological: Immunose™ FLU 1%<br>* Quadrivalent influenza vaccine with 30 μg HA/strain and 1% Endocine™, dosing volume 200 μl, intranasal administration x 2<br>|
| Experimental: Immunose™ FLU 2%, 200 μl<br>Immunose™ FLU 2%. QIV, 30 μg HA/strain and 2% Endocine™, 200 μl for intranasal administration, 2 dosing occasions. | Biological: Immunose™ FLU 2%, 200 μl<br>* Quadrivalent influenza vaccine with 30 μg HA/strain and 2% Endocine™, dosing volume 200 μl, intranasal administration x 2<br>|
| Experimental: Immunose™ FLU 2%, 300 μl<br>Immunose™ FLU 2%, 300 μl. QIV, 30 μg HA/strain and 2% Endocine™, 300 μl for intranasal administration, 2 dosing occasions. | Biological: Immunose™ FLU 2%, 300 μl<br>* Quadrivalent influenza vaccine with 30 μg HA/strain and 2% Endocine™, dosing volume 300 μl, intranasal administration x 2<br>|
| Experimental: Influenza antigen<br>Influenza antigen. QIV, 30 μg HA/strain, 200 μl for intranasal administrations, 2 dosing occasions. | Biological: Influenza antigen<br>* Quadrivalent influenza vaccine with 30 μg HA/strain, dosing volume 200 μl, intranasal administration x 2<br>|
| Placebo Comparator: Placebo<br>Placebo. Saline (NaCl), 200 μl for intranasal administration, 2 dosing occasions. | Drug: Placebo<br>* NaCl dosing volume 200 μl, intranasal administration x 2<br>* Other names: Saline (NaCl);|
| Experimental: i.m comparator and Immunose™ FLU 2%<br>i.m comparator: QIV 15 μg HA/strain, 500 µl for a single intramuscular administration, and Immunose FLU 2%: QIV 30 μg HA/strain and 2% Endocine™, 200 μl for intranasal administration. A second dose of Immunose FLU 2% will be administered 3 weeks later. | Biological: Immunose™ FLU 2%, 200 μl<br>* Quadrivalent influenza vaccine with 30 μg HA/strain and 2% Endocine™, dosing volume 200 μl, intranasal administration x 2<br>Biological: i.m comparator<br>* Quadrivalent influenza vaccine containing 15 μg HA/strain, 500 µl for intramuscular administration x 1<br>|
| Active Comparator: i.m comparator<br>i.m comparator. QIV 15 μg HA/strain, 500 µl for a single intramuscular administration. | Biological: i.m comparator<br>* Quadrivalent influenza vaccine containing 15 μg HA/strain, 500 µl for intramuscular administration x 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the clinical phase. | Type and incidence of AEs and SAEs. Treatment group 1-7. | Visit 2 (Day 0) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the clinical phase. | Type and incidence of AEs and SAEs. Treatment group 1-7. | Visit 3 (Day 21) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the clinical phase. | Type and incidence of AEs and SAEs. Treatment group 1-6. | Visit 4 (Day 42) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the safety follow-up phase. | Type and incidence of AEs and SAEs of special intrerest. Treatment group 7. | Day 90 | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the safety follow-up phase. | Type and incidence of AEs and SAEs of special intrerest. Treatment group 1-6. | Day 111 | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the safety follow-up phase. | Type and incidence of AEs and SAEs of special intrerest. Treatment group 7. | Day 180 | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the safety follow-up phase. | Type and incidence of AEs and SAEs of special intrerest. Treatment group 1-6. | Day 201 | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the treatment visits. | Frequency and severity of discomfort in the nose and/or throat before study drug administration and at 15, 30, 60 and 120 minutes after study drug administration. Treatment group 1-5. | Visit 2 (Day 0) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the treatment visits. | Frequency and severity of discomfort in the nose and/or throat and/or arm before study drug administration and at 15, 30, 60 and 120 minutes after study drug administration. Treatment group 6. | Visit 2 (Day 0) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the treatment visits. | Frequency and severity of discomfort in the arm before study drug administration and at 15, 30, 60 and 120 minutes after study drug administration. Treatment group 7. | Visit 2 (Day 0) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, during the treatment visits. | Frequency and severity of discomfort in the nose and/or throat before study drug administration and at 15, 30, 60 and 120 minutes after study drug administration. Treatment group 1-6. | Visit 3 (Day 21) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, from baseline to last clinic visit. | Frequency of clinically significant changes in ECG. Treatment group 1-6. | Visit 1 (Day -42 to -1) to Visit 4 (Day 42) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, from baseline to last clinic visit. | Frequency of clinically significant changes in ECG. Treatment group 7. | Visit 1 (Day -42 to -1) to Visit 3 (Day 21) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, from baseline to last clinic visit. | Frequency of clinically significant changes in vital signs. Treatment group 1-6. | Visit 1 (Day -42 to -1) to Visit 4 (Day 42) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, from baseline to last clinic visit. | Frequency of clinically significant changes in vital signs. Treatment group 7. | Visit 1 (Day -42 to -1) to Visit 3 (Day 21) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, from baseline to last clinic visit. | Frequency of clinically significant changes in physical examination findings. Treatment group 1-6. | Visit 1 (Day -42 to -1) to Visit 4 (Day 42) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, from baseline to last clinic visit. | Frequency of clinically significant changes in physical examination findings. Treatment group 7. | Visit 1 (Day -42 to -1) to Visit 3 (Day 21) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, from baseline to last clinic visit. | Frequency of clinically significant changes in laboratory variables. Treatment group 1-6. | Visit 1 (Day -42 to -1) to Visit 4 (Day 42) | 
| Safety of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens, from baseline to last clinic visit. | Frequency of clinically significant changes in laboratory variables. Treatment group 7. | Visit 1 (Day -42 to -1) to Visit 3 (Day 21) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of HaemaggIutination-inhibition titers in serum. Treatment group 1-7. | Visit 2 (Day 0) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of HaemaggIutination-inhibition titers in serum. Treatment group 1-7. | Visit 3 (Day 21) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of HaemaggIutination-inhibition titers in serum. Treatment group 1-6. | Visit 4 (Day 42) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of Virus Neutralization titers in serum. Treatment group 1-7. | Visit 2 (Day 0) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of Virus Neutralization titers in serum. Treatment group 1-7. | Visit 3 (Day 21) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of Virus Neutralization titers in serum. Treatment group 1-6. | Visit 4 (Day 42) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of Single Radial Haemolysis titres in serum. Treatment group 1-7. | Visit 2 (Day 0) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of Single Radial Haemolysis titres in serum. Treatment group 1-7. | Visit 3 (Day 21) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of Single Radial Haemolysis titres in serum. Treatment group 1-6. | Visit 4 (Day 42) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of Immunoglobulin A (IgA) titers in nasal secretion. Treatment group 1-7. | Visit 2 (Day 0) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of Immunoglobulin A (IgA) titers in nasal secretion. Treatment group 1-7. | Visit 3 (Day 21) | 
| Evaluation of the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens. | Measurement of Immunoglobulin A (IgA) titers in nasal secretion. Treatment group 1-6. | Visit 4 (Day 42) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine