A Study to Assess the Safety and Immunogenicity of M-001 Influenza Vaccine as a Primer to TIV in Elderly Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BiondVax Pharmaceuticals ltd.
ClinicalTrials.gov Identifier:
NCT01419925
First received: August 17, 2011
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

"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.


Condition Intervention Phase
Influenza
Healthy
Biological: Two Multimeric-001 administrations followed by TIV
Biological: One administration of Multimeric-001 followed by TIV
Biological: One administration of adjuvanted M-001 followed by TIV
Biological: One administration of placebo followed by TIV
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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.

Resource links provided by NLM:


Further study details as provided by BiondVax Pharmaceuticals ltd.:

Primary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: 63 days ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: 21 days after boost immunization with TIV ] [ Designated as safety issue: No ]
    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 [ Time Frame: 21 days after M-001 immunization ] [ Designated as safety issue: No ]
    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.


Enrollment: 120
Study Start Date: August 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Two Multimeric-001 administrations followed by TIV
Biological: Two Multimeric-001 administrations followed by TIV
Two administrations of non adjuvanted M-001, 500 mcg followed by TIV at intervals of 19-23 days
Experimental: Group B
One administration of Multimeric-001 followed by TIV
Biological: One administration of Multimeric-001 followed by TIV
One administration of non adjuvanted Multimeric-001, 500 mcg, followed by TIV at intervals of 19-23 days
Experimental: Group C
One administration of adjuvanted M-001 followed by TIV
Biological: One administration of adjuvanted M-001 followed by TIV
One administration of adjuvanted (Aluminum phosphate) Multimeric-001, 500 mcg, followed by TIV at intervals of 19-23 days
Active Comparator: Group D
One administration of placebo followed by TIV
Biological: One administration of placebo followed by TIV
One administration of saline (Placebo)followed by TIV at intervals of 19-23 days (serving as an active comparator)

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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01419925

Locations
Israel
Hadassah medical center
Jerusalem, Israel
Sponsors and Collaborators
BiondVax Pharmaceuticals ltd.
Investigators
Principal Investigator: Dr. Jacob Atzmon, MD Tel Aviv Medical Center
  More Information

No publications provided

Responsible Party: BiondVax Pharmaceuticals ltd.
ClinicalTrials.gov Identifier: NCT01419925     History of Changes
Other Study ID Numbers: BVX-005
Study First Received: August 17, 2011
Last Updated: May 12, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by BiondVax Pharmaceuticals ltd.:
influenza vaccine
peptide
universal
prime
boost
TIV
HAI
Hemagglutination Inhibition
elderly

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 30, 2014