A Study to Assess the Safety and Immunogenicity of M-001 Influenza Vaccine as a Primer to TIV in Elderly Volunteers
Primary Purpose
Influenza, Healthy
Status
Completed
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
Two Multimeric-001 administrations followed by TIV
One administration of Multimeric-001 followed by TIV
One administration of adjuvanted M-001 followed by TIV
One administration of placebo followed by TIV
Sponsored by
About this trial
This is an interventional prevention trial for Influenza focused on measuring influenza vaccine, peptide, universal, prime, boost, TIV, HAI, Hemagglutination Inhibition, elderly
Eligibility Criteria
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.
Sites / Locations
- Hadassah medical center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
Group A
Group B
Group C
Group D
Arm Description
Two Multimeric-001 administrations followed by TIV
One administration of Multimeric-001 followed by TIV
One administration of adjuvanted M-001 followed by TIV
One administration of placebo followed by TIV
Outcomes
Primary Outcome Measures
Number of participants with adverse events
Number of Participants with Adverse Events as a Measure of Safety and Tolerability were similar (not statistically significant) in the experimental and control group
Number of Participants with Adverse Events possible/probably related to the study drug in each treatment group:
Group A: Twice M-001 - 9 AEs Group B: Once M-001 - 5 AEs Group C: Once Alum-M-001 - 13 AEs Group D: Placebo - 7 AEs
Secondary Outcome Measures
Immunity induced by priming and boosting, measured by HAI
Hemagglutination Inhibition (HAI) test for anti influenza antibodies to TIV strains revealed an elevated proportion of participants achieving seroconversion in the groups primed with M-001 and boosted with TIV, as compared to participants given TIV alone. The viruses contained in the TIV were A/California/7/09, A/Perth/16/09 or B/Brisbane/60/08 . Enhanced Seroconversion and GMT post immunization were found in the experimental group primed with either adjuvanted or non adjuvanted M-001. Note that the superior HAI responses were demonstrated for both seasonal (H3N2 and B strain) and pandemic strains (swine H1N1 strain that is contained in the TIV).
Cellular immunity
Intracellular staining followed by FACS analysis of CD4/CD8 lymphocytes secreting IFN gamma showed elevated proportions of CD4+ cells secreting IFN gamma following exposure of PBMC from subjects immunized with M-001 to influenza antigens and to M-001. Note that the test was performed before boosting with TIV and hence demonstrates the cross immunity offered by immunization with M-001 alone and suggests a CD4+ mediated mechanism of action for M-001 as a universal primer.
Full Information
NCT ID
NCT01419925
First Posted
August 17, 2011
Last Updated
May 12, 2014
Sponsor
BiondVax Pharmaceuticals ltd.
1. Study Identification
Unique Protocol Identification Number
NCT01419925
Brief Title
A Study to Assess the Safety and Immunogenicity of M-001 Influenza Vaccine as a Primer to TIV in Elderly Volunteers
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BiondVax Pharmaceuticals ltd.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
"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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Healthy
Keywords
influenza vaccine, peptide, universal, prime, boost, TIV, HAI, Hemagglutination Inhibition, elderly
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Description
Two Multimeric-001 administrations followed by TIV
Arm Title
Group B
Arm Type
Experimental
Arm Description
One administration of Multimeric-001 followed by TIV
Arm Title
Group C
Arm Type
Experimental
Arm Description
One administration of adjuvanted M-001 followed by TIV
Arm Title
Group D
Arm Type
Active Comparator
Arm Description
One administration of placebo followed by TIV
Intervention Type
Biological
Intervention Name(s)
Two Multimeric-001 administrations followed by TIV
Intervention Description
Two administrations of non adjuvanted M-001, 500 mcg followed by TIV at intervals of 19-23 days
Intervention Type
Biological
Intervention Name(s)
One administration of Multimeric-001 followed by TIV
Intervention Description
One administration of non adjuvanted Multimeric-001, 500 mcg, followed by TIV at intervals of 19-23 days
Intervention Type
Biological
Intervention Name(s)
One administration of adjuvanted M-001 followed by TIV
Intervention Description
One administration of adjuvanted (Aluminum phosphate) Multimeric-001, 500 mcg, followed by TIV at intervals of 19-23 days
Intervention Type
Biological
Intervention Name(s)
One administration of placebo followed by TIV
Intervention Description
One administration of saline (Placebo)followed by TIV at intervals of 19-23 days (serving as an active comparator)
Primary Outcome Measure Information:
Title
Number of participants with adverse events
Description
Number of Participants with Adverse Events as a Measure of Safety and Tolerability were similar (not statistically significant) in the experimental and control group
Number of Participants with Adverse Events possible/probably related to the study drug in each treatment group:
Group A: Twice M-001 - 9 AEs Group B: Once M-001 - 5 AEs Group C: Once Alum-M-001 - 13 AEs Group D: Placebo - 7 AEs
Time Frame
63 days
Secondary Outcome Measure Information:
Title
Immunity induced by priming and boosting, measured by HAI
Description
Hemagglutination Inhibition (HAI) test for anti influenza antibodies to TIV strains revealed an elevated proportion of participants achieving seroconversion in the groups primed with M-001 and boosted with TIV, as compared to participants given TIV alone. The viruses contained in the TIV were A/California/7/09, A/Perth/16/09 or B/Brisbane/60/08 . Enhanced Seroconversion and GMT post immunization were found in the experimental group primed with either adjuvanted or non adjuvanted M-001. Note that the superior HAI responses were demonstrated for both seasonal (H3N2 and B strain) and pandemic strains (swine H1N1 strain that is contained in the TIV).
Time Frame
21 days after boost immunization with TIV
Title
Cellular immunity
Description
Intracellular staining followed by FACS analysis of CD4/CD8 lymphocytes secreting IFN gamma showed elevated proportions of CD4+ cells secreting IFN gamma following exposure of PBMC from subjects immunized with M-001 to influenza antigens and to M-001. Note that the test was performed before boosting with TIV and hence demonstrates the cross immunity offered by immunization with M-001 alone and suggests a CD4+ mediated mechanism of action for M-001 as a universal primer.
Time Frame
21 days after M-001 immunization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Jacob Atzmon, MD
Organizational Affiliation
Tel Aviv Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hadassah medical center
City
Jerusalem
Country
Israel
12. IPD Sharing Statement
Citations:
PubMed Identifier
25173483
Citation
Atsmon J, Caraco Y, Ziv-Sefer S, Shaikevich D, Abramov E, Volokhov I, Bruzil S, Haima KY, Gottlieb T, Ben-Yedidia T. Priming by a novel universal influenza vaccine (Multimeric-001)-a gateway for improving immune response in the elderly population. Vaccine. 2014 Oct 7;32(44):5816-23. doi: 10.1016/j.vaccine.2014.08.031. Epub 2014 Aug 28.
Results Reference
derived
Learn more about this trial
A Study to Assess the Safety and Immunogenicity of M-001 Influenza Vaccine as a Primer to TIV in Elderly Volunteers
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