Comparison of the Cellular and the Humoral Immunogenicity, Safety of Different Trivalent Influenza Vaccines (FLUSECUOEKH1)

Comparison of the Cellular and the Humoral Immunogenicity as Well as the Safety of Different Trivalent Influenza Vaccines in Healthy Adults Between 18 and 60 Years of Age

This is a randomized, single-blinded, Phase IV, monocentric study in healthy adults aged > 18 and < 60 years to evaluate the cellular and humoral immunogenicity as well as the reactogenicity of intramuscular, inactivated, trivalent influenza vaccines, including aluminium adjuvanted whole virus vaccine, split vaccine and subunit vaccine.

Study Overview

• Status: Unknown
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: influenza vaccine

Detailed Description

This is a randomized, single-blinded study on vaccines for prevention of influenza.

Three study visits will be scheduled for each study subject, at Day 0, Day 9-11 and Day 30-35. Prior to the performance of any protocol procedures, the investigator is will obtain an informed consent from each participant.

At the first study visit (Day 0), demographic data, medical history, pre-existing conditions and concomitant medication will be recorded. Physical examination with recording of vital signs will be performed and in case of females of childbearing age, a pregnancy test will be performed. After the subject has qualified eligible, before vaccination, 60 ml venous blood will be taken for base-line immunity tests. Each subject will be randomly allocated to receive one of the three study vaccines, administered as a deep intramuscular (i.m.) injection into the deltoid muscle. The subjects will be blinded for the vaccine regimen. The principal investigator will administer the vaccines filled in ampoule or packed in pre-filled ready-to-use syringes and can thus not be blinded, but the staff and sub-investigators responsible for the routine follow-up and assessments and laboratory personnel will be blinded. A diary card will be given to each subject for recording pre-defined solicited adverse events for the vaccination day and 6 subsequent days and all other adverse events and concomitant medications.

At the second study visit (Day 9-11) the diary card will be collected. All adverse events and concomitant medication will be assessed and recorded. A physical examination will be performed and 60 ml venous blood shall be taken for immunity tests. A new diary card will be given to each subject for recording adverse events and concomitant medications.

At the third study visit (Day 30-35), the diary card will be collected. All adverse events and concomitant medication will be assessed and recorded. A physical examination will be performed and 60 ml venous blood shall be taken for immunity tests.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, H-1134
    • National Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult volunteers > 18 and < 60 years of age, both sexes;
• Full contractual capacity of the participants
• Are in good health (as determined by vital signs and medical history);
• Negative urine or serum pregnancy test for females of childbearing potential.
• If the subject is female and of childbearing potential, she must use an acceptable contraception method and not become pregnant for the duration of the study. (Acceptable contraception includes implants, injectables, combined oral contraceptives, effective intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner);
• Are able to understand and comply with planned study procedures;
• Signed informed consent prior to initiation of study procedures;
• Absence of existence of any exclusion criteria

Exclusion Criteria:

• Known allergy to eggs OR other components of any of the vaccines (in particular mercury);
• History of Guillain-Barré syndrome;
• Pregnancy OR breast feeding OR positive pregnancy test prior to vaccination;
• Immunosuppressive therapy in the preceding 36 months;
• Active neoplasm (i.e. requiring any form of anti-neoplastic therapy);
• Concomitant corticosteroid therapy, including inhaled corticosteroids. Local corticosteroid or corticosteroid nasal spray are permitted.
• Psychiatric illness and/or concomitant psychiatric drug therapy that may have effect on full contractual capacity of the participant;
• Immunoglobulin (or similar blood product) therapy within 3 months prior to vaccination;
• Vaccine therapy within 4 weeks prior to the study;
• Influenza vaccination within 2 years prior to the study;
• Chronic illness that, in the opinion of the investigator, may interfere with the evaluation of the immune response;
• Documented HIV, HBV or HCV infection;
• Acute febrile respiratory illness within one week prior to vaccination;
• Experimental drug therapy within 1 month prior to vaccination;
• Alcohol or drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: humoral and cellular immune response	Biological: influenza vaccine; whole virus influenza vaccine adjuvanted with aluminium phosphate, 3 x 15 μg HA / 0.5 ml, for i.m. administration subunit influenza vaccine 3 x 15 μg HA / 0.5 ml, for i.m. administration split influenza vaccine 3 x 15 μg HA / 0.5 ml, for i.m. administration; Other Names: Vaxigrip; Influvac; FluvalAB adjuvanted trivalent seasonal influenza vaccine
Experimental: reactogenicity	Biological: influenza vaccine; whole virus influenza vaccine adjuvanted with aluminium phosphate, 3 x 15 μg HA / 0.5 ml, for i.m. administration subunit influenza vaccine 3 x 15 μg HA / 0.5 ml, for i.m. administration split influenza vaccine 3 x 15 μg HA / 0.5 ml, for i.m. administration; Other Names: Vaxigrip; Influvac; FluvalAB adjuvanted trivalent seasonal influenza vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of seroconversions, > 4-fold increase in Haemagglutination inhibition (HI), mean geometric increase and antibody titre the proportion of subjects achieving an HI titre > 40, virus neutralization assay, Granzyme B, INF-gamma, IL-10, side effects.	There remains substantial uncertainty about the clinical effectiveness of influenza vaccines based on current health care literature. The standard methodology to determine vaccine efficacy is based on hemagglutinin inhibition assay. Assays based on the immune response against the N antigen and based on the cellular immune response are now being designed and validated in the EU-funded Flusecure project. Importantly, recent EMEA regulations for registration of vaccines against avian influenza require an assessment of the cellular and the N-specific immune responses (EMEA/CHMP/VWP/263499/2006).	Day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects	In the course of tolerability assessment the frequency, mean time of appearance, duration and severity of the AEs (local and general) will be assessed according to CPMP/BWP/214/968: "Note for Guidance on Harmonization of Requirements for Influenza Vaccines", 12 March 1997, Para. 2.4., 2.6., and 3.2.	65 days after vaccination

Collaborators and Investigators

• Sponsor: National Centre for Epidemiology, Hungary
• Collaborators: Netherlands Vaccine Institute; National Public Health Institute, Finland
• Investigators: Study Director: Ildikó Visontai, MD, National Centre for Epidemiology

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): March 1, 2009
• Study Completion (Anticipated): August 1, 2010

Study Registration Dates

• First Submitted: May 4, 2010
• First Submitted That Met QC Criteria: May 6, 2010
• First Posted (Estimate): May 7, 2010

Study Record Updates

• Last Update Posted (Estimate): May 7, 2010
• Last Update Submitted That Met QC Criteria: May 6, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: influenza vaccine; cellular immune response; humoral immune response
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: FLUSECURE-OEK-H01; 2008-002307-22 (EudraCT Number)