A Study to Assess the Safety and Immunogenicity of M-001 Influenza Vaccine as a Primer to TIV in Elderly Volunteers

A Phase II Multicenter, Randomized, Placebo Controlled Study to Assess the Safety and Immunogenicity of an IM Influenza Vaccine (Multimeric-001) Followed by Administration of TIV to Elderly Volunteers.

"Multimeric-001" (M-001) has been recently developed, containing conserved, common linear influenza epitopes that activate both cellular and humoral arms of the immune system against a wide variety of influenza A and B strains. Apart from its direct action, M-001 is an attractive candidate for priming immune responses to seasonal influenza vaccine in the elderly population. The current clinical study was designed to assess M-001's standalone and priming action in subjects over 65 years old.

This is a second Phase II study comprising 120 participants. Eligible subjects were randomized to receive to receive either two sequential non-adjuvanted or a single non-adjuvanted or a single adjuvanted intramuscular injection of 500 mcg M-001 (treatment), or one placebo (saline) injection, before receiving the TIV.

This was a two-center, randomized, placebo-controlled study. 120 subjects were randomized 1:1:1:1 into four groups to receive either two sequential non-adjuvanted or a single non-adjuvanted or a single adjuvanted intramuscular injection of 500 mcg M-001 (treatment), or one placebo (saline) injection, before receiving the TIV. Due to visual differences between placebo and treatment the study was partially blinded. Hemagglutinin inhibition (HAI) was evaluated at baseline and 3 weeks after standard trivalent inactivated influenza vaccine (TIV) vaccination as a measure of M-001's efficacy. Cell mediated immune (CMI) responses were also evaluated in some of the subjects who received non-adjuvanted and adjuvanted M-001 vaccinations. The subjects were monitored for safety throughout the study.

Inclusion Criteria:

• Males and females at the age of at least 65 years old
• Eligible to receive the standard seasonal influenza vaccine according to the MOH 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.
• Haematology, chemistry and urinalysis values with no clinical significance or do not reflect a medical condition which, according to the physician's judgment, might confound the results of the study or pose additional risk to the subject by participation in the study.
• Male subjects must agree to use a condom during the full term of the study period (including follow up) if female partner is not using an acceptable contraceptive method.
• Subjects who are seronegative to at least one of the strains included in the seasonal vaccine against influenza for 2011- 2012

Exclusion Criteria:

• Known history of significant medical disorder which, in the investigator's judgment, might confound the results of the study or pose additional risk to the subject by participation in the study.
• Subjects with known Guillain Barré Syndrome in the past.
• Subjects who have been immunized with anti-influenza vaccine or infected by influenza virus within eight months prior to the screening visit.
• Known hypersensitivity associated with previous influenza vaccination.
• Use of an influenza antiviral medication within 4 weeks of vaccination.
• Known hypersensitivity and/or allergy to any drug or vaccine.
• Known hypersensitivity to egg proteins (eggs or egg products), chicken proteins, or any of the components of the commercial vaccine (e.g., formaldehyde, and octoxinol 9 (Triton X-100) and neomycin).
• 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).
• Any clinically significant abnormality upon physical examination or in the clinical laboratory tests at screening visit which, according to the physician's judgment, might confound the results of the study or pose additional risk to the subject by participation in the study.
• Positive serology for HIV, 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.
• 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.