This is a phase I/II, randomized, single-blind, placebo-controlled escalating double-dose study of the safety and priming potential of an intramuscular Influenza vaccine (Multimeric-001) injected to elderly volunteers.
This is a Phase I/II single-center, randomized, placebo-controlled, single-blind, dose-escalation, double-dose administration study comprising two dosing cohorts (Cohort 1: 250 mcg M-001 per injection and Cohort 2: 500 mcg M-001 per injection) with 20 subjects in each cohort receiving either adjuvanted or non-adjuvanted formulations. The adjuvant used was Montanide ISA VG51. Cohort 3 with 20 subjects was administered placebo. After priming with M-001 or placebo, all participants were administered a boost of a conventional trivalent vaccine on day 42. There was a minimum of 10 days interval between last dosing of the first injection to the last subject of the 250 μg cohort (Cohort 1) and first dosing of the first subject injection with 500 µg cohort (Cohort 2). For each subject, the second injection was performed 21+2 days after his/her first injection, provided they were deemed fit to be dosed by a study physician. The DSMB reviewed the safety data obtained from cohorts 1 and 2 before approving their second injection and before dose escalation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
60
Multimeric-001 (M-001) was administered twice at a dose of 250mcg via the IM route to 10 participants as a primer, followed by TIV boost immunization. in 19-23 days interval between them.
Injection of Multimeric-001 250 mcg with Adjuvant Montonide isa 51 VG, 2 doses with interval of 19-23 days between them
Placebo injected with PBS (Phosphate Buffered Saline), 2 injections with the interval of 19-23 days between them.
Tasmc Crc
Tel Aviv, Israel
To assess the safety, local and systemic tolerability and reactogenicity of Multimeric-001 vaccine when administered intramuscularly twice to elderly male and female subjects, using chemistry, CBC, fibrinogen, and urinalysis measurements.
The Multimeric-001 vaccine exhibits a positive safety profile. The number of subjects reporting adverse events (AEs) after treatment with active vaccines was similar to respective placebo cohorts. Overall AE frequencies for each active group were similar to those of placebo counterparts.
Time frame: From day 0 until termination visit
To characterize the immune response
The Multimeric-001 vaccine induces both humoral and cellular immune responses, confirming previous findings in younger adults.
Time frame: 21 days after second immunization with M-001 and 21 days after TIV boost
To monitor cellular immune responses
PBMC proliferation associated with IFN gamma secretion was detected after prime immunizations following in vitro exposure of the cells to M-001 or influenza viruses.
Time frame: 21 days after second M-001 immunization
To obtain preliminary data on the contribution of the adjuvant
Adjuvant had an impact on anti-M-001 IgG levels but not on HAI antibody levels.
Time frame: 21 days after second M-001 immunization and 21 days after TIV boost
To obtain preliminary evidence about the efficacy of M-001 as a primer
The prime-boost regimen elicits HAI immune responses, which enables assessment of an accepted surrogate marker considered to correlate with influenza vaccine activity.Priming with M-001 before a TIV boost resulted in a greater proportion of subjects seroconverted to TIV and non-TIV strains as compared to subjects given TIV alone.
Time frame: 21 days after TIV boost
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Injection of Placebo with Adjuvant Montonide isa 51 VG, 2 injections with the interval of 19-23 days between them.
Injection of Multimeric-001 with PBS, 2 injections with the interval of 19-23 days between them.
Injection of Multimeric-001 500 mcg with Adjuvant Montonide isa 51 VG, 2 doses with the interval of 19-23 days between them
Injection of the conventional flu vaccine: Vaxigrip to all study participants.