Further Investigation of an Intramuscular Influenza Vaccine (Multimeric-001)

Influenza Clinical Trial

Official title:

A Phase II, Randomized, Two Stage, Double-Blind, Placebo-Controlled, Safety and Immunogenicity Study of an Intramuscular Influenza Vaccine (Multimeric-001) Injected to Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01146119
• Other study ID #: BVX-004
• Status: Completed
• Phase: Phase 2
• First received: June 13, 2010
• Last updated: July 30, 2012
• Start date: July 2010
• Est. completion date: June 2011

Study information

• Verified date: July 2012
• Source: BiondVax Pharmaceuticals ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, randomized, two stage, double-blind, placebo-controlled administration study comprising 200 healthy participants.

Description:

This is a Phase II multi-center, randomized, two stage, double-blind, placebo-controlled study comprising 200 participants. Eligible subjects will be randomized to receive one of the following administrations (as two single IM injections with an interval of 21 days between each injection Administration A: Prime twice with Adjuvanted Multimeric-001 500 mcg

• 64 subjects.

Administration B: PBS (Placebo) twice - 32 subjects. Administration C: Adjuvanted PBS (Placebo)twice - 32 subjects. Participants from administrations A and B will be further immunized with a 15% dose of commercial seasonal trivalent vaccine for 2011 on day 81.

Administration D: Adjuvanted Multimeric-001 500 mcg coadministered once with 15% of TIV dose

• 24 subjects. Administration E: Adjuvanted Multimeric-001 500 mcg coadministered once with 50% of TIV dose - 24 subjects Administration group F: PBS (Placebo) co-administered once with 50% of TIV dose - 24 subjects

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: June 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• Healthy males and females between the age of 18 and 49 years (inclusive).

• 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 (until termination visit) if female partner is not using an effective contraceptive method.

• Subjects who are seronegative to at least one of the strains included in the seasonal vaccine against influenza for 2011.

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.

• Two or more hospitalizations within the last year prior to screening visit.

• Known 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.

• 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 any clinical study within 30 days prior to study entry

• Subjects who are non-cooperative or unwilling to sign consent form.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• Multimeric-001, 500 mcg
Adjuvanted Multimeric-001 was administered twice with an interval of 19-23 days.
• Adjuvanted PBS
Adjuvanted PBS was administered twice with an interval of 19-23 days.
• PBS and TIV 15%
PBS (Phosphate Buffered Saline) was administered twice with an interval of 19-23 days and then 60 days later a 15% dose of commercial seasonal trivalent vaccine (season 2011) was administered.
• PBS and TIV 50%
PBS (Phosphate Buffered Saline) was administered twice with an interval of 19-23 days and then 60 days later a 50% dose of commercial seasonal trivalent vaccine (season 2011) was administered.

Locations

Country	Name	City	State
Israel	Clinical Research Center, Hadassah Medical Center	Jerusalem
Israel	Clinical Research Center, Tel-Aviv Sourasky Medical Center	Tel-Aviv

Sponsors (1)

Lead Sponsor	Collaborator
BiondVax Pharmaceuticals ltd.

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cellular Immunogenicity	Elevated proliferation of lymphocytes following in vitro incubation with M-001. The proliferation was associated with IFN gamma secretion	21 days after co administration of M-001 and TIV 50%	No
Primary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Number of Participants with Adverse Events possible/probably related to the study drug in each group were similar in the experimental and control groups.	From day 0 until day 221	Yes
Primary	Anti Multimeric-001 antibodies	Direct Elisa assay to test the titer of human antibodies that recognize the Multimeric-001 protein. Humoral immunity was manifested 21 and 60 days post immunization by significantly elevated anti-M-001 IgG levels among subjects administered twice with adjuvanted M-001	21 days after second immunization with M-001	No
Secondary	Hemagglutination Inhibition (HAI) test for anti influenza antibodies	The serum is tested for its ability to adhere to influenza virus and thus inhibit the Hemagglutination reaction. Adjuvanted M-001 co-administered with partial dose of TIV (Vaxigrip, 50%) was effective in enhancing immunity to influenza-related antigens, as manifested by increased HAI antibody responses toward viruses contained in the TIV as well as toward non-TIV virus strains.	21 days post co administration of M-001 and TIV 50%	No