Safety and Immunogenicity of a Subunit Trivalent Influenza Vaccine, Northern Hemisphere Formulation 2013/2014, in Healthy Adults Aged 18 Years and Above

Study Overview
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Brief Summary
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The present study is designed to confirm the safety and immunogenicity of trivalent, surface antigen, inactivated influenza vaccine in 2 age cohorts: 18 to ≤60 years and ≥61 years. For the immunogenicity endpoint the antibody response to each influenza vaccine antigen will be evaluated by means of Single Radial Hemolysis (SRH) or Hemagglutination Inhibition (HI) at approximately 21 days post vaccination. The vaccine composition will be based on the WHO-recommended influenza strains for the 2013/2014 Northern Hemisphere vaccine, and the results of this study are intended to support the use of this vaccine in future influenza seasons if the recommended vaccine composition remains the same, in compliance with the requirements of the current European Union (EU) recommendations for clinical trials related to yearly licensing of influenza vaccines.

Official Title
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A Phase II, Open-Label, Single-Arm, Multicenter Study to Evaluate the Safety and Immunogenicity of a Trivalent, Surface Antigen Inactivated Subunit Influenza Virus Vaccine (Agrippal®) in Healthy Adults

Conditions
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Human Influenza

Intervention / Treatment
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* Biological: TIV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female volunteers aged 18 years or older, mentally competent, who were willing and able to give written informed consent prior to study entry; Were able to comply with all the study requirements; and Were in good health as determined by the outcome of medical history, physical examination, and clinical judgment of the investigator Exclusion Criteria: Had behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may have interfered with the subject's ability to participate in the study; Had a serious chronic or acute disease (in the judgment of the investigator) including, but not limited to: medically significant cancer (except for benign or localized skin cancer, cancer in remission for ≥10 years, or localized prostate cancer that had been clinically stable for >2 years without treatment) medically significant advanced congestive heart failure (ie, New York Heart Association [NYHA] class III and IV) chronic obstructive pulmonary disease (ie, Global initiative for chronic Obstructive Lung Disease [GOLD] stage III and IV) autoimmune disease (including rheumatoid arthritis and excepting Hashimoto's thyroiditis that has been clinically stable for ≥5 years) diabetes mellitus type I poorly controlled diabetes mellitus type II advanced arteriosclerotic disease history of underlying medical condition such as major congenital abnormalities requiring surgery, chronic treatment, or associated with developmental delay (eg, Down's syndrome) acute or progressive hepatic disease acute or progressive renal disease severe neurological (especially Guillain-Barré syndrome) or psychiatric disorder severe asthma Had a history of any anaphylactic reaction and/or serious allergic reaction to any component of the study vaccine; Had a known or suspected (or have a high risk of developing) impairment/alteration of immune function (excluding that normally associated with advanced age) resulting, for example, from: receipt of immunosuppressive therapy (any parenteral or oral corticosteroid or cancer chemotherapy/radiotherapy) within the past 60 days and for the full length of the study, receipt of immunostimulants within the past 6 months, receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivates within the past 3 months and for the full length of the study, or suspected or known human immunodeficiency virus (HIV) infection or HIV related disease Had known or suspected drug or alcohol abuse within the past 2 years; Had bleeding diathesis or conditions associated with prolonged bleeding time that, in the investigator's opinion, would interfere with the safety of the subject; Was not able to comprehend and to follow all required study procedures for the whole period of the study; Had a history or any illness that, in the opinion of the investigator, would pose additional risk to the subjects because of participation in the study; Had the following within the past 6 months: any laboratory confirmed seasonal or pandemic influenza disease received any seasonal or pandemic influenza vaccine Had received any other vaccine within 4 weeks prior to enrollment in this study or were planning to receive any vaccine during the study; Had acute or chronic infections requiring antiviral therapy within the last 7 days; Had experienced fever (ie, body temperature [preferably oral] ≥38.0°C) within the last 3 days of intended study vaccination; Had been participating in any clinical trial with another investigational product 4 weeks prior to first study visit or intends to participate in another clinical study at any time during the conduct of this study; Was part of study personnel or has close family members conducting this study; Had a body mass index (BMI) >35 kg/m2 (BMI is calculated by dividing the subject's weight in kilograms by the subject's height in meters multiplied by the subject's height in meters). Was pregnant (confirmed by positive urine pregnancy test) or nursing (breastfeeding) or was a female of childbearing potential who refused to use an acceptable method of birth control for the whole duration of the study.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TIV (18 to ≤ 60 years)<br>Adult subjects 18 to ≤60 years received one dose of a trivalent, surface antigen inactivated subunit influenza virus vaccine (TIV) formulation 2013/2014 Northern Hemisphere | Biological: TIV<br>* Trivalent Influenza Virus Vaccine (surface antigen, inactivated, egg-derived)<br>|
| Experimental: TIV (≥ 61 years)<br>Adult subjects ≥61 years received one dose of a trivalent, surface antigen inactivated subunit influenza virus vaccine (TIV) formulation 2013/2014 Northern Hemisphere | Biological: TIV<br>* Trivalent Influenza Virus Vaccine (surface antigen, inactivated, egg-derived)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIV | Immunogenicity was assessed in terms of percentages of subjects in both age groups with SRH areas ≥25mm2 against each of the three vaccine strains, three weeks after receiving one dose of TIV . The related European Committee for Human Medicinal Products (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is >70% for adults aged 18 to ≤60 years and >60% for subjects aged ≥61 years. | Day 1 (baseline) and Day 22 (postvaccination) | 
| Percentages of Subjects With Seroconversion or Significant Increase in SRH Area, Against Each of Three Vaccine Strains After Receiving One Dose of TIV | Immunogenicity was assessed in terms of percentages of subjects in both age groups achieving seroconversion or significant increase by SRH area against each of the three vaccine strains, three weeks after receiving one dose of TIV. Seroconversion is defined as percentage of subjects with a pre vaccination SRH area ≤4mm2 achieving a post vaccination SRH area ≥25 mm2. Significant increase is defined as percentage of subjects with a pre-vaccination SRH area >4mm2 achieving at least 50% increase in post vaccination SRH area. The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is >40% for adults aged 18 to ≤60 years and >30% for subjects aged ≥61 years. | Day 22 (postvaccination) /Day 1 (baseline) | 
| Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination Geometric Mean Areas (GMAs), After One Dose of TIV | The antibody responses were evaluated in terms of GMRs of post vaccination GMAs to pre vaccination GMAs against each of the three vaccine strains, three weeks after receiving one dose of TIV. The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is >2.5 for adults aged 18 to ≤60 years and > 2.0 in for subjects aged ≥61 years. | Day 22 (postvaccination) / Day 1 (baseline) | 
| Percentages of Subjects With Haemagglutination Inhibition (HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of TIV | Immunogenicity was assessed in terms of percentages of subjects in both age groups with HI titers ≥40, against each of the three vaccine strains, three weeks after receiving one dose of TIV. The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving HI titers ≥ 40 is >70% for adults aged 18 to ≤60 years and >60% for subjects aged ≥61 years. | Day 1 (baseline) and Day 22 (postvaccination) | 
| Percentages of Subjects With Seroconversion or Significant Increase in HI Antibody Titers After Receiving One Dose of TIV | Immunogenicity was assessed in terms of percentages of subjects in both age groups achieving seroconversion or significant increase in HI antibody titers after receiving one dose of TIV. Seroconversion is defined as percentage of subjects with a pre vaccination HI titer <10 to a post vaccination titer ≥40. Significant increase is defined as percentage of subjects with a pre vaccination HI titer ≥10 to at least a 4-fold increase in post vaccination HI antibody titers. The related European (CHMP) criterion for the assessment of immunogenicity is met if >40% for adults aged 18 to ≤60 years and >30% for subjects aged ≥61 years achieve seroconversion or significant increase in post-vaccination HI titers. | Day 22 (postvaccination) / Day 1 (baseline) | 
| Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination HI Antibody Titers, After Receiving One Dose of TIV | The antibody responses following one dose of TIV were evaluated in terms of GMRs of post vaccination against pre vaccination geometric mean HI titers against each of the three vaccine strains, three weeks after receiving one dose of TIV. The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is >2.5 for adults aged 18 to ≤60 years and > 2.0 for subjects aged ≥61 years. | Day 22 (postvaccination)/ Day 1 (baseline) | 
| Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIV | The number of adult and elderly subjects reporting solicited local and systemic adverse events and other solicited adverse events after receiving one dose of TIV are reported. | Day 1 to Day 4 post vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIV | The number of subjects in both age groups reporting any unsolicited AEs (between Day 1 to 4), serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal (Day 1 to Day 22), after receiving one dose of TIV is reported. | Day 1 through Day 22 post vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza,, Adults,, Elderly,, Immunology,, Safety