Phase II Study to Assess Safety & Immunogenicity of Multimeric-001 Influenza Vaccine, Followed by TIV

Study Overview
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Brief Summary
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This is a single-site, randomized, double-blind, placebo-controlled study of Multimeric-001 in thirty six (36) volunteers 50-65 years of age. All subjects will receive an intramuscular (IM) injection, in each one of three visits, with a 21±2 days interval between treatments.

Detailed Description
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Subjects will undergo screening procedures within 30 days prior to first vaccination which will include medical history, vital signs, ECG, physical examination and safety blood and urine lab tests. On the first treatment visit, eligible subjects will undergo pre-dose physical examination and vital signs, and a blood sample will be drawn for baseline cellular immunogenicity and circulating Interferon gamma (IFN-g). They will then receive an IM injection of either vaccine or placebo, according to the above treatment assignment, into the deltoid muscle preferably of the same arm. The subjects will remain under medical supervision for 2 hrs (± 15 min) at which time they will be released from the Clinical research center. The second treatment will take place 21 (±2) days after the first vaccination. Procedures will be the same as that of Visit 2 Additional two follow-up visits will take place at approximately 24 hrs and 48h The third treatment will take place 21 (±2) days after the second vaccination. Procedures will be the same as that of Visit 2 21 days later, each subject will be immunized with the seasonal influenza vaccine approved for 2014/15 year. A Study Termination visit will take place at 21 (±2) days after last vaccination. Adverse events (AEs) and changes in concomitant medications will be recorded, vital signs will be measured and the subjects will undergo physical examination and ECG. Blood and urine samples will be collected for safety.

Official Title
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A Phase II, Randomized, Placebo-Controlled, Double-Blind Study to Assess the Safety and Immunogenicity of Multimeric-001 Influenza Vaccine, Followed by a Seasonal Trivalent Influenza Vaccine (TIV)

Conditions
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Influenza

Intervention / Treatment
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* Biological: M-001
* Drug: TIV
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between ≥50 - ≤65 years old at the time expected for the first injection. Eligible to receive the standard seasonal influenza vaccine according to the ministry of health guidelines. Subjects who provide written informed consent to participate in the study. Subjects able to adhere to the visit schedule and protocol requirements and are available to complete the study. Pre-menopausal female subjects must have a negative serum pregnancy test at screening and be willing and able to use a medically acceptable method of birth control or declare that they are abstaining from sexual intercourse, from the screening visit through the study termination visit or be surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy). Postmenopausal women, defined as women with menstruation cessation for 12 consecutive months prior to signing of the informed consent form. Subjects must agree to use an acceptable contraceptive method the full term of the study period (including follow up). Exclusion Criteria: Subjects who are likely, in the opinion of the investigator, to confound the results of the study or may be exposed to additional risks by participation in the study, based on medical history, vital signs, ECG, physical examination and safety lab tests. Subjects with known Guillain Barré Syndrome in the past. Subjects who have been immunized with anti-influenza vaccine or infected by influenza virus (based on the assessment of the investigator) within eight months prior to first vaccination. Known hypersensitivity associated with previous influenza vaccination. Use of an influenza antiviral medication within 4 weeks of first vaccination. Known allergy to egg protein Known hypersensitivity and/or allergy to any drug or vaccine. Persons deficient in producing antibodies, whether due to genetic defect, immunodeficiency disease, or immunosuppressive therapy. History of any bleeding disorder or subjects with thrombocytopenia (since bleeding may occur following an intramuscular administration to these subjects). Positive serology for Human immunodeficiency virus (HIV) , Hepatitis C Virus (HCV) antibody or HBsAg. Any acute medical situation (e.g. acute infection, ongoing flu symptoms) with or without fever within 48 hours of vaccination, which is considered significant by the Investigator. Pregnant or currently lactating women. Subjects who participated in another interventional clinical study within 30 days prior to first dose. Subjects who are non-cooperative or unwilling to sign consent form.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 65 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: M-001 0.5mg & TIV<br>M-001 (0.5mg) administered intramuscular 3 times at 21 days intervals followed by vaccination with Trivalent Influenza Vaccine (TIV) | Biological: M-001<br>* A recombinant epitope based universal vaccine against seasonal and pandemic influenza<br>* Other names: Multimeric-001;Drug: TIV<br>* HA based seasonal influenza vaccine, for 2014/15 seson<br>|
| Experimental: M-001 1.0mg & TIV<br>M-001 (1.0mg) administered intramuscular 3 times at 21 days intervals followed by vaccination with Trivalent Influenza Vaccine (TIV) | Biological: M-001<br>* A recombinant epitope based universal vaccine against seasonal and pandemic influenza<br>* Other names: Multimeric-001;Drug: TIV<br>* HA based seasonal influenza vaccine, for 2014/15 seson<br>|
| Placebo Comparator: Placebo & TIV<br>0.3ml Saline administered Intramuscular 3 times at 21 days intervals followed by vaccination with Trivalent Influenza Vaccine (TIV) | Drug: TIV<br>* HA based seasonal influenza vaccine, for 2014/15 seson<br>Other: Saline<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events in treatment vs control group | Number of Participants with Adverse Events as a Measure of Safety and Tolerability will be measured in the experimental and control group, both local and systemic adverse events will be followed. | 3 months (from first visit to termination visit for each subject) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunity induced by priming and boosting, measured by HAI (Hemagglutination Inhibition) | To characterize humoral immunity, Hemagglutination Inhibition (HAI) test for anti influenza antibodies to TIV strains will be measured after boosting with TIV, proportion of participants achieving seroconversion in the groups primed with M-001 and boosted with TIV, will be compared to participants given TIV alone. | Day 84 (21 days after TIV injection) | 
| Number of participants with cell mediated immune response in treatment vs control group | To characterize the cell mediated immune response, Fluorescence activated cell sorter (FACS) analysis for CD4/CD8 lymphocytes will be performed after 3 immunizations with M-001 as compared to the control group (injected 3 times with saline) | Day 63 (21 days after immunization with M-001) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza Prime universal vaccine M-001 Multimeric