A Double-Dose Safety Study of An Influenza Vaccine (Multimeric-001) Injected to Elderly Volunteers

NCT ID: NCT01010737

Last Updated: 2012-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2010-03-31

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.

Conditions

Influenza

Keywords

Multimeric; Vaccine; Influenza; elderly; phase 1/2; safety; efficacy; tolerability; reactogenicity; Montanide; hemagglutinin inhibition; HAI; TIV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Multimeric-001 250 mcg

250mcg of Multimeric-001 was administered twice at an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered.

Group Type: EXPERIMENTAL

Multimeric-001 250 mcg

Intervention Type: BIOLOGICAL

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.

TIV

Intervention Type: BIOLOGICAL

Injection of the conventional flu vaccine: Vaxigrip to all study participants.

Adjuvant: Montonide isa 51 VG

Adjuvanted PBS was administered twice with a 19-23 day interval via the IM route to 10 participants and then a TIV boost was administered.

Group Type: ACTIVE_COMPARATOR

Adjuvant: Montonide isa 51 VG

Intervention Type: BIOLOGICAL

Injection of Placebo with Adjuvant Montonide isa 51 VG, 2 injections with the interval of 19-23 days between them.

TIV

Intervention Type: BIOLOGICAL

Injection of the conventional flu vaccine: Vaxigrip to all study participants.

Placebo

PBS was administered twice with a 19-23 day interval via the IM route to 10 participants and then a TIV boost was administered.

Group Type: ACTIVE_COMPARATOR

Adjuvant: Montonide isa 51 VG

Intervention Type: BIOLOGICAL

Injection of Placebo with Adjuvant Montonide isa 51 VG, 2 injections with the interval of 19-23 days between them.

TIV

Intervention Type: BIOLOGICAL

Injection of the conventional flu vaccine: Vaxigrip to all study participants.

Multimeric-001 500 mcg

500mcg of M-001 was administered twice with an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered.

Group Type: EXPERIMENTAL

Adjuvanted Multimeric-001 500mcg

Intervention Type: BIOLOGICAL

Injection of Multimeric-001 500 mcg with Adjuvant Montonide isa 51 VG, 2 doses with the interval of 19-23 days between them

TIV

Intervention Type: BIOLOGICAL

Injection of the conventional flu vaccine: Vaxigrip to all study participants.

Adjuvanted Multimeric-001 500mcg

5000mcg of Adjuvanted M-001 was administered twice with an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered.

Group Type: EXPERIMENTAL

Adjuvanted Multimeric-001 250mcg

Intervention Type: BIOLOGICAL

Injection of Multimeric-001 250 mcg with Adjuvant Montonide isa 51 VG, 2 doses with interval of 19-23 days between them

TIV

Intervention Type: BIOLOGICAL

Injection of the conventional flu vaccine: Vaxigrip to all study participants.

Adjuvanted Multimeric-001 250mcg

250mcg of Adjuvanted M-001 was administered twice with an interval of 19-23 days via the IM route to 10 participants as a primer and then a TIV boost was administered.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: BIOLOGICAL

Placebo injected with PBS (Phosphate Buffered Saline), 2 injections with the interval of 19-23 days between them.

Multimeric-001 500 mcg

Intervention Type: BIOLOGICAL

Injection of Multimeric-001 with PBS, 2 injections with the interval of 19-23 days between them.

TIV

Intervention Type: BIOLOGICAL

Injection of the conventional flu vaccine: Vaxigrip to all study participants.

Interventions

Multimeric-001 250 mcg

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.

Intervention Type: BIOLOGICAL

Adjuvanted Multimeric-001 250mcg

Injection of Multimeric-001 250 mcg with Adjuvant Montonide isa 51 VG, 2 doses with interval of 19-23 days between them

Intervention Type: BIOLOGICAL

Placebo

Placebo injected with PBS (Phosphate Buffered Saline), 2 injections with the interval of 19-23 days between them.

Intervention Type: BIOLOGICAL

Adjuvant: Montonide isa 51 VG

Injection of Placebo with Adjuvant Montonide isa 51 VG, 2 injections with the interval of 19-23 days between them.

Intervention Type: BIOLOGICAL

Multimeric-001 500 mcg

Injection of Multimeric-001 with PBS, 2 injections with the interval of 19-23 days between them.

Intervention Type: BIOLOGICAL

Adjuvanted Multimeric-001 500mcg

Injection of Multimeric-001 500 mcg with Adjuvant Montonide isa 51 VG, 2 doses with the interval of 19-23 days between them

Intervention Type: BIOLOGICAL

TIV

Injection of the conventional flu vaccine: Vaxigrip to all study participants.

Intervention Type: BIOLOGICAL

Other Intervention Names

Vaxigrip

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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

BiondVax Pharmaceuticals ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacob Atsmon, MD

Role: PRINCIPAL_INVESTIGATOR

CRC, Sourascky MC, Israel

Locations

Tasmc Crc

Tel Aviv, , Israel

Countries

Israel

Other Identifiers

BVX-003

Identifier Type: -

Identifier Source: org_study_id