Immunogenicity, Safety and Tolerability of a Trivalent Subunit Inactivated Vaccine in Healthy Subjects 50 Years and Above

Study Overview
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Brief Summary
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Demonstrate non-inferiority of the post-vaccination (Day 22) Hemagglutination inhibition (HI) Geometric Mean Titers (GMTs) of trivalent, inactivated, subunit influenza vaccine (TIV) over the corresponding GMTs of the comparator vaccine for all three strains, in healthy adults aged 50 years and above. Demonstrate non-inferiority of the percentages of subjects achieving seroconversion in antibody titers at Day 22 in the TIV group over the corresponding percentages of subjects in the comparator group for all three strains, in healthy adults aged 50 years and above.

Official Title
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A Multi-Center, Phase IV, Randomized, Controlled, Observer Blind Study to Evaluate the Immunogenicity, Safety, and Tolerability of a Trivalent Subunit Inactivated Influenza Vaccine in Healthy Subjects Aged 50 Years and Above

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluvirin(TIVf)
* Biological: Agriflu (TIV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 50 years and above, mentally competent, willing and able to give written informed consent prior to study entry and after the nature of the study has been explained according to local regulatory requirements. Individuals able to comply with all the study requirements. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. Exclusion Criteria: Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study. Individuals with any progressive or severe neurologic disorder, seizure disorder or Guillain-Barré syndrome. Individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study. Individuals who have received any seasonal or pandemic influenza vaccine or have had a laboratory confirmed seasonal or pandemic influenza disease within the past 6 months. Individuals with history or any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study. Individuals with positive HIV test result, with history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system, or under immunosuppressive therapy within 6 months or use of any parenteral or oral corticosteroids within the previous 30 days. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. Individuals with any serious chronic or progressive disease according to judgment of the investigator (neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease). Individuals who have any malignancy (excluding nonmelanotic skin cancer) or lymphoproliferative disorder. Individuals with history of any anaphylactic adverse event and/or serious allergic adverse event following a vaccination, a proven hypersensitivity to any component of the study vaccine (eg, to eggs or eggs product as well as ovalbumin, chicken protein, chicken feathers, influenza viral protein, kanamycin and neomycin sulphate) or latex allergy. Individuals participating in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study. Receipt of nonstudy vaccines (with the exception of post-exposure vaccination in a medical emergency, eg, hepatitis, rabies, tetanus) within 3 weeks prior to Visit 1. Individuals who have ever received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 12 weeks. Individuals who have received antibiotics within 6 days before vaccination. Individuals with body temperature (axillary temperature) ≥38 degrees Celsius (≥ 100.4° F) within the last 3 days of intended study vaccination. BMI > 35 kg/m2. Female who are pregnant or nursing (breastfeeding) mothers or females of childbearing potential do not plan to use acceptable birth control measures, for the whole duration of the study. Adequate contraception is defined as hormonal (eg, oral, injection, transdermal patch, implant, cervical ring), barrier (eg, condom with spermicide or diaphragm with spermicide), intrauterine device (IUD), or monogamous relationship with vasectomized partner who has been vasectomized for 6 months or more prior to the subject's study entry; Abstinence. Individuals who are part of study personnel or close family members conducting this study. Individuals with history of substance or alcohol abuse within the past 2 years.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Agriflu<br>A single 0.5 mL dose of Investigational vaccine TIV (Agriflu) at visit 1, administered intramuscularly | Biological: Agriflu (TIV)<br> <br> * Other names: Trivalent Influenza Virus Vaccine (purified surface antigen, inactivated, egg-derived);|
| Active Comparator: Fluvirin<br>A single 0.5 mL dose of control vaccine TIVf (Fluvirin) at visit 1, administered intramuscularly | Biological: Fluvirin(TIVf)<br> <br> * Other names: Trivalent Influenza Virus Vaccine (purified surface antigen, inactivated, egg-derived);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) of TIV Group and TIVf Group for All Three Strains, in Healthy Adults Aged ≥50 Years | Non-inferiority of Postvaccination Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) of TIV (Trivalent Subunit Inactivated Influenza Vaccine) Group Over the Corresponding TIVf Group for All Three Strains, three weeks after vaccination (day 22). The upper limit of the two-sided 95% confidence interval (CI) on the ratio of GMTs (GMT TIVf/GMT TIV) should not exceed the non-inferiority margin of 1.5. | Day 22 | 
| Percentages of Subjects Achieving Seroconversion (SC) in Antibody Titers in the TIV Group Compared With the Corresponding Percentages of Subjects in the TIVf Group for All Three Strains At Day 22, in Healthy Adults Aged ≥50 Years | Non-Inferiority was measured as the percentages of subjects who achieved seroconversion in HI titers three weeks (day 22) after vaccination of TIV compared with TIVf, against each of three vaccine strains. Seroconversion is defined as a prevaccination titer <10 and postvaccination HI ≥40 or as a prevaccination titer ≥10 and at minimum four-fold rise in postvaccination antibody titer. The upper limit of the two-sided 95% CI on the difference between the seroconversion rates (Seroconversion TIVf - SeroconversionTIV) should not exceed 10%. | Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIV and TIVf Vaccine | Percentage of subjects achieving HI seroconversion against each of three vaccine strains was measured three weeks after vaccination of TIV and TIVf vaccine (day 22). Percentage of subjects who achieved HI titer ≥1:40 against each of three vaccine strains was measured three weeks after one vaccination of TIV and TIVf vaccine. According to Center for Biologics Evaluation and Research recommendations (CBER 2007), the criterion for seroconversion is considered met if the lower limit of the two-sided 95% CI for the percentage of subjects with HI seroconversion is ≥40% (<65 years) or ≥30% (≥65 years). As per the CBER criteria, the lower limit of the two-sided 95% CI for the percentage of subjects who achieved HI titer ≥ 1:40 should be ≥70% (<65 years) or ≥60% (≥65 years). | Day 22 | 
| Geometric Mean Ratio of Subjects Against Each of Three Strains After One Vaccination of TIV and TIVf Vaccine | Geometric mean ratio (GMR) of subjects was calculated as the ratio of postvaccination to prevaccination HI GMTs against each of three vaccine strains, three weeks after vaccination of TIV and TIVf vaccine (day 22). | Day 22 | 
| Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV and TIVf | Safety was assessed as the number of subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after vaccination of TIV and control. | Day 1 to 7 postvaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trivalent inactivated subunit influenza vaccines, 50 years and above, healthy subjects