A Study to Evaluate Safety and Immunogenicity of Trivalent Influenza Vaccine, Formulation 2015 Southern Hemisphere, When Administered to Healthy Adult Subjects.

Study Overview
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Brief Summary
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The present study is designed to evaluate 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 2015 Southern Hemisphere vaccine, and the data from this study are intended to support the use of this vaccine in future influenza seasons if the recommended vaccine composition remains the same.

Official Title
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A Phase II, Open-Label, Single-Arm, Multicenter Study to Evaluate the Safety and Immunogenicity of a Surface Antigen, Inactivated, Egg-Derived, Trivalent Influenza (Agrippal®) Virus Vaccine, Southern Hemisphere Formulation 2015, in Healthy Adults.

Conditions
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Human Influenza

Intervention / Treatment
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* Biological: Aggripal®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals of 18 years of age and above on the day of informed consent. Individuals who have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. Individuals who can comply with study procedures including follow-up. Males or females of non-child bearing potential or females of childbearing potential who are using an effective birth control method which they intend to use for at least 30 days after the last study vaccination. Exclusion Criteria: Progressive, unstable or uncontrolled clinical conditions. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study. Clinical conditions representing a contraindication to intramuscular vaccination and blood drawn. Abnormal function of the immune system resulting from: Clinical conditions, Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to informed consent, Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent, Received immunoglobulins or any blood products within 180 days prior to enrollment. Received an investigational or non-registered medicinal product within 30 days prior to enrollment. Study personnel as an immediate family or household member. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine within 28 days from the study vaccines. Has behavioral or cognitive impairment, psychiatric disease, severe neurological (especially Guillain-Barré syndrome) that, in the opinion of the investigator may interfere with the subject's ability to participate in the study. Has a serious chronic or acute disease (in the judgment of the investigator may interfere with the result of the study or pose additional risk to the subject) 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 has been clinically stable for >2 years without treatment), medically significant advanced congestive heart failure (i.e., New York Heart Association [NYHA] class III and IV), chronic obstructive pulmonary disease (ie, Global initiative for chronic Obstructive Lung Disease 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 (e.g., Down's syndrome), acute or progressive hepatic disease, acute or progressive renal disease, severe asthma. Has known or suspected drug or alcohol abuse within the past 2 years; Has the following within the past 6 months: had any laboratory-confirmed seasonal or pandemic influenza disease, received any seasonal or pandemic influenza vaccine, Has acute or chronic infections requiring systemic antibiotic treatment or antiviral therapy within the last 7 days; Has experienced fever (i.e., body temperature [preferably axillary] ≥38.0°C) within the last 3 days of intended study vaccination; Has 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.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trivalent Influenza Vaccine<br>One injection of Agrippal® | Biological: Aggripal®<br>* TIV<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 ≥25mm^2, 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 ≥25mm^2 against each of the three vaccine strains, three weeks after receiving one dose of TIV. The related European Committee for Medicinal Products for Human Use (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm^2 is >70% for adults aged 18 to ≤60 years and >60% for subjects aged ≥61 years. | Day 1 and Day 22 post vaccination | 
| 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 ≤ 4mm^2 achieving a post vaccination SRH area ≥ 25mm^2. Significant increase is defined as percentage of subjects with a pre-vaccination SRH area > 4mm^2 achieving at least 50% increase in post vaccination SRH area. 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 SRH areas. | Day 22 post vaccination | 
| Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination Geometric Mean Area (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/ Day1 post vaccination | 
| 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 and Day 22 post vaccination | 
| 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 and a post vaccination titer ≥40. Significant increase is defined as percentage of subjects with a pre vaccination HI titer ≥10 and 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 post vaccination | 
| GMR of Post Vaccination Versus Pre Vaccination HI Antibody Titers, After Receiving One Dose of TIV. | The antibody responses following one vaccination 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/Day 1 post vaccination | 
| Number of Subjects Reporting Local and Systemic Solicited Adverse Events (AEs) After Receiving One Dose of TIV. | The number of adult and elderly subjects reporting solicited local and systemic AEs and other solicited AEs after receiving one dose of TIV are reported. | Day 1 to Day 4 post vaccination (including 30 mins) | 
| Number of Subjects Reporting Unsolicited AEs After Receiving One Dose of TIV. | The number of subjects in both age groups reporting any unsolicited AEs between Day 1 to Day 4 after receiving one dose of TIV. | Day 1 to Day 4 post vaccination | 
| Number of Subjects Reporting Unsolicited AEs After Receiving One Vaccination 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 vaccination of TIV is reported. | Day 1 to Day 22 post vaccination |