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

Primary Purpose

Influenza

Status
Completed
Phase
Phase 1
Locations
Israel
Study Type
Interventional
Intervention
Multimeric-001 250 mcg
Adjuvanted Multimeric-001 250mcg
Placebo
Adjuvant: Montonide isa 51 VG
Multimeric-001 500 mcg
Adjuvanted Multimeric-001 500mcg
TIV
Sponsored by
BiondVax Pharmaceuticals ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza focused on measuring Multimeric, Vaccine, Influenza, elderly, phase 1/2, safety, efficacy, tolerability, reactogenicity, Montanide, hemagglutinin inhibition, HAI, TIV

Eligibility Criteria

55 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Tasmc Crc

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Active Comparator

Active Comparator

Experimental

Experimental

Experimental

Arm Label

Multimeric-001 250 mcg

Adjuvant: Montonide isa 51 VG

Placebo

Multimeric-001 500 mcg

Adjuvanted Multimeric-001 500mcg

Adjuvanted Multimeric-001 250mcg

Arm Description

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.

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.

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

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

To characterize the immune response
The Multimeric-001 vaccine induces both humoral and cellular immune responses, confirming previous findings in younger adults.
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.
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.
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.

Full Information

First Posted
October 18, 2009
Last Updated
July 30, 2012
Sponsor
BiondVax Pharmaceuticals ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT01010737
Brief Title
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

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BiondVax Pharmaceuticals ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
Multimeric, Vaccine, Influenza, elderly, phase 1/2, safety, efficacy, tolerability, reactogenicity, Montanide, hemagglutinin inhibition, HAI, TIV

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Multimeric-001 250 mcg
Arm Type
Experimental
Arm Description
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.
Arm Title
Adjuvant: Montonide isa 51 VG
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
PBS was administered twice with a 19-23 day interval via the IM route to 10 participants and then a TIV boost was administered.
Arm Title
Multimeric-001 500 mcg
Arm Type
Experimental
Arm Description
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.
Arm Title
Adjuvanted Multimeric-001 500mcg
Arm Type
Experimental
Arm Description
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.
Arm Title
Adjuvanted Multimeric-001 250mcg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Multimeric-001 250 mcg
Intervention Description
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
Intervention Name(s)
Adjuvanted Multimeric-001 250mcg
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
Placebo injected with PBS (Phosphate Buffered Saline), 2 injections with the interval of 19-23 days between them.
Intervention Type
Biological
Intervention Name(s)
Adjuvant: Montonide isa 51 VG
Intervention Description
Injection of Placebo with Adjuvant Montonide isa 51 VG, 2 injections with the interval of 19-23 days between them.
Intervention Type
Biological
Intervention Name(s)
Multimeric-001 500 mcg
Intervention Description
Injection of Multimeric-001 with PBS, 2 injections with the interval of 19-23 days between them.
Intervention Type
Biological
Intervention Name(s)
Adjuvanted Multimeric-001 500mcg
Intervention Description
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
Intervention Name(s)
TIV
Other Intervention Name(s)
Vaxigrip
Intervention Description
Injection of the conventional flu vaccine: Vaxigrip to all study participants.
Primary Outcome Measure Information:
Title
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.
Description
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
Secondary Outcome Measure Information:
Title
To characterize the immune response
Description
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
Title
To monitor cellular immune responses
Description
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
Title
To obtain preliminary data on the contribution of the adjuvant
Description
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
Title
To obtain preliminary evidence about the efficacy of M-001 as a primer
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacob Atsmon, MD
Organizational Affiliation
CRC, Sourascky MC, Israel
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tasmc Crc
City
Tel Aviv
Country
Israel

12. IPD Sharing Statement

Learn more about this trial

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

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