Safety and Immunogenicity of GPO Seasonal Trivalent Inactivated Influenza Vaccine in Healthy Thai Adults

Phase 1

Completed

Brief Summary: The study is aim to evaluate the safety and immunogenicity of one dose (15 μg HA per strain per dose) of the GPO seasonal trivalent inactivated split virion influenza vaccine (Tri Fluvac) in healthy adults aged 18 to 49 years over 90 days post-injection.

Detailed Description: This is a double blind randomized study consisting of two phases - Phase I and Phase II. The same vaccine, a seasonal trivalent inactivated split virion influenza vaccine \[A/California/7/2009, reassortant virus NYMC X-181 (H1N1), A/Victoria/210/2009, reassortant virus NYMC X-187 (H3N2), and B/Brisbane/60/2008, reassortant virus NYMC BX-35 virus strains\] will be given in both Phase I and Phase II of the study.

The vaccine will be administered via the intramuscular route; the preferred injection site will be the deltoid of the non-dominant arm. After vaccination volunteers will remain at the clinic for at least 30 minutes to observe for any reactogenicity after immunization. Total follow-up is 90 days.

Blood specimens will be collected on Day 0 prior to vaccination, Day 21, Day 60, and day 90.

Recruitment & Eligibility

Inclusion Criteria

Healthy
Age 18-49 years old
Having Thai ID card or equivalent
All hematology, biochemistry and urine analysis are within normal range or of no clinical significance (not higher than 1.5 time of normal value without any clinical finding from history and physical examination)
Able to read and write and sign written informed consent form or assent form.

Exclusion Criteria

Known history of egg allergy
Having had recently influenza infection confirmed as H1N1, H3N2, or Flu B within 3 months preceding enrolment to the trial
Vaccination against influenza in the past 6 months preceding enrolment to the trial
History of bronchial asthma, chronic lung diseases, chronic rhinitis
History of immunodeficiency state
History of immunosuppression < 6 months prior to immunization
History of anaphylactic or other allergic reactions to influenza vaccine or any vaccine component or excipient (e.g. gentamicin or thimerosal)
Acute infectious with fever > 38 degree Celsius and noninfectious diseases (within 72 hours) preceding enrollment in the trial
The volunteers who have been taking immunoglobulin products or have had a blood transfusion during past 3 months before the beginning of the experiment
Participation in other research study
Pregnancy or plan to become pregnant for 60 days after enrollment or breast feeding
Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures
Any condition that in the opinion of the investigator would pose a health risk to the subject if enrolled, or could interfere with the evaluation of the vaccine

Arm && Interventions

Group	Intervention	Description
an inactivated influenza vaccine	an inactivated influenza vaccine	20 volunteers in phase I study and 200 volunteers in phase II study will receive a single dose of a seasonal trivalent inactivated split virion influenza vaccine \[A/California/7/2009, reassortant virus NYMC X-181 (H1N1), A/Victoria/210/2009, reassortant virus NYMC X-187 (H3N2), and B/Brisbane/60/2008, reassortant virus NYMC BX-35 virus strains\] will be administered via the intramuscular route; the preferred injection site will be the deltoid of the non-dominant arm.
Placebo	Placebo	20 volunteers in phase I study and 100 volunteers in phase II study will receive a single dose of placebo will be administered via the intramuscular route; the preferred injection site will be the deltoid of the non-dominant arm.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	90 days	All Adverse Events during 90 days will be analysed in terms of percentage and relationship to study vaccine

Secondary Outcome Measures

Name	Time	Method
Geometric Mean of Immune Response Increase > 2.5 From Baseline of H1N1,H3N2 and B/Brisbane/60/2008 Antibody Titer	90 days	The analysis was performed only as intention-to-treat (ITT). The antibody titer values were transformed into log10 titers for calculation of the GMT at every time of assessment (Days 0, 21, 60 and 90). Proportion of increased in GMT Titer \> 2.5 at each time of assessment compared with baseline (Day 0) was reported both phase I and phase II
Geometric Mean of Immune Response at Every Time of Assessment	90 days	The analysis was performed only as intention-to-treat (ITT). The antibody titer values were transformed into log10 titers for calculation of the GMT at every time of assessment (Days 0,21, 60 and 90)
Number (Percentage) of Participants With Achieving Seroconversions or Significant Increase in Antihemagglutinin Antibody Titer.	90 days	Seroconversion is defined as a 4-fold rise in HAI titer in post-immunization serum relative to pre-immunization serum, or if pre-immunization serum had an undetectable titer (\<1:10), attainment of a post-immunization titer of ≥1:40.