Clinical trial NCT01010737: A Double-Dose Safety Study of An Influenza Vaccine (Multimeric-001) Injected to Elderly Volunteers
Official title: A Phase I/II, Randomized, Single-Blind, Placebo-Controlled Escalating Double-Dose, Safety and Priming Potential Study of an Intramuscular Influenza Vaccine (Multimeric-001) Injected to Elderly Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Influenza
Keywords: Multimeric
Vaccine
Influenza
elderly
phase 1/2
safety
efficacy
tolerability
reactogenicity
Montanide
hemagglutinin inhibition
HAI
TIV
Lead sponsor: BiondVax Pharmaceuticals ltd.
Sponsor class: INDUSTRY
First posted: 2009-11-10
Enrollment: 60
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Males and females between the age of 55 and 75 years (inclusive):

  * Healthy or treated for any or all of the following conditions:

    * Hypertension, under control with standard medications
    * Hyperlipidemia, medically treated
* Subjects who provide written informed consent to participate in the study.
* Subjects able to adhere to the visit schedule and protocol requirements and be 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.
* Female of childbearing age must agree to use an acceptable method of contraception and male subjects should use a condom throughout the study period (including the follow up- where applicable) if female partner is not using an effective contraceptive method.

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.
* Renal dysfunction.
* COPD.
* Chronic cardiovascular system disorders (except hypertension adequately controlled by standard medications).
* Asthma
* Diabetes mellitus.
* Subjects with known Guillain Barré Syndrome in the past.
* Two or more hospitalizations within the last year prior to screening visit.
* Bleeding disorders including hemophilia or thrombocytopenia, or treatment with anticoagulant therapy (risk of bleeding with intramuscular injection).
* Immunocompromised patients and those receiving concomitant immunosuppressive therapy; or other immune modulating drugs including chronic steroid treatment.
* Subjects who have been immunized with anti-influenza vaccine or infected by influenza virus within eight months prior to the screening visit.
* Administration of any vaccine 30 days before the screening visit.
* Known hypersensitivity to 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 vaccine components, in particular, neomycin, formaldehyde, and octoxinol 9,
* Known history of drug or alcohol abuse.
* 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.
* Increased liver enzymes more than 2.5 times above the upper reference level.
* 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 of significance by the Principal Investigator.
* Pregnant or lactating women at entry to study and those who are unwilling to agree to continue to use acceptable methods of contraception for two months after completion of the study (if applicable).
* Positive blood pregnancy test on screening.
* Subjects who participated in another clinical study within 30 days prior to study entry.
* Subjects who are non-cooperative or unwilling to sign consent form.

Primary outcomes:
measure: 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.
timeFrame: From day 0 until termination visit
Secondary outcomes:
measure: To characterize the immune response
timeFrame: 21 days after second immunization with M-001 and 21 days after TIV boost
measure: To monitor cellular immune responses
timeFrame: 21 days after second M-001 immunization
measure: To obtain preliminary data on the contribution of the adjuvant
timeFrame: 21 days after second M-001 immunization and 21 days after TIV boost
measure: To obtain preliminary evidence about the efficacy of M-001 as a primer
timeFrame: 21 days after TIV boost
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Tasmc Crc
Study officials:
affiliation: CRC, Sourascky MC, Israel
name: Jacob Atsmon, MD
role: PRINCIPAL_INVESTIGATOR
References: