Reactogenicity, Safety and Immunogenicity Study of a Allantoic Split Inactivated Seasonal Influenza Vaccine

Study Overview
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Brief Summary
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The study is a single centre, phase I, double-blind, randomized, placebo-controlled trial that explored the safety and immunogenicity of single dose a allantoic split inactivated seasonal influenza vaccine in healthy adults.

Official Title
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A Randomized, Blinded, Placebo-controlled Study of Phase I Allantoic Split Inactivated Seasonal Influenza Vaccine in Healthy Adults

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: influenza vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers of both sexes aged 18-60 years. Persons seronegative against A/H1N1 influenza virus, A/H3N2 and type B (with antibody titers ≤1: 10, according to hemagglutination-inhibition (HI) assay to determine). Literate and willing to provide written informed consent. A signed informed consent. Exclusion Criteria: Available in anamnaze volunteer at any allergic reactions. Allergic reactions to chicken proteins, or any preceding vaccination. Acute illness with a fever (37.0 C). Vaccination against influenza in the 2012/2013 season. Seropositive volunteers against A/H1N1 influenza virus, A/H3N2 and type B (with antibody titers greater than 1:10 according HI). Current or recent (within two weeks of enrollment) acute respiratory illness with or without fever. Hypersensitivity after previous administration of any vaccine. History of chronic alcohol abuse and/or illegal drug use. Any clinically significant abnormal laboratory finding. A positive pregnancy test for all women of childbearing potential. Administration of immunosuppressive drugs or other immune modifying drugs within 4 weeks prior to study enrollment. Acute or chronic clinically significant pulmonary disease, cardiovascular disease, gastrointestinal disease, liver disease, neurological illness, liver disease, blood disease, skin disorder, endocrine disorder, neurological illness and psychiatric disorder as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives. History of leukemia or any other blood or solid organ cancer. Seropositive for HIV, hepatitis B surface antigen and/or hepatitis C antibodies. Receipt of antivirals, antibiotics, immunoglobulins or other blood products within 4 weeks prior to study enrollment or planned receipt of such products during the period of subject participation in the study. Participation in another clinical trial within the previous three months or planned enrollment in such a trial during the period of this study. Subjects who are, in the opinion of the investigator, at significantly increased risk of non-cooperation with requirements of the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum 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 |
| --- | --- |
| Active Comparator: Allantoic split inactivated seasonal influenza vaccine<br>Allantoic split inactivated seasonal influenza vaccine | Biological: influenza vaccine<br>* A allantoic split inactivated seasonal influenza vaccine has been prepared on eggs and is made from inactivated parts of the following influenza virus strains: NIBRG-121xp (A/California/7/2009 (H1N1)v and А/PR/8/34 (H1N1)), NYMC X-217 (A/Victoria/361/2011(H3N2) and А/PR/8/34 (H1N1)), NYMC BX-49 (B/Texas/06/2011 (Yamagata lineage) - like High Yield Reassortant (1:1:6) With B/Lee/40 NP, B/Panama/45/90 NS genes).<br>|
| Placebo Comparator: Placebo<br>Water for Injection | Biological: Placebo<br>* water for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Solicited Local and Systemic Adverse Events (AEs) | Participants recorded solicited injection site and systemic adverse events in a Subject Diary. Solicited Locals AEs were: Injection Site Pain, Injection Site Redness, Injection Site Swelling, Injection Site Induration and Injection Site Ecchymosis. Solicited Systemic AEs were: Pyrexia, Malaise, Chills, Fatigue, Headache, Sweaty, Myalgia, Arthralgia, Nausea and Vomiting. | Two hours | 
| Percentage of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | Adverse events are defined as unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product, regardless of relationship to the medicinal product. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. | Greater than 2 hours after administration of any dose of vaccine or placebo through 7 days following any dose | 
| Percentage of Participants With Abnormal Safety Laboratory Tests at Least Once Post Dose Reported as AEs | The percentage of participants with any abnormal standard safety laboratory values (Chemistry, Hematology and Urinalysis) collected throughout the study reported as AEs. | Greater than 2 hours after administration of any dose of vaccine or placebo through 7 days | 
| Serious adverse events (SAEs), including abnormal laboratory findings | Serious adverse events (SAEs) are medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | Three weeks of receipt | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Fold Increase in HI Antibody Titer | Geometric mean fold increase in HI antibody titer for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after vaccination, as compared with Baseline. | Change from Baseline HI Antibody Titer at 21 days | 
| Seroconversion Rate of Hemagglutination Inhibition (HI) Antibody Titer | Seroconversion rate was measured by hemagglutination inhibition (HI) antibody titer for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after vaccination. Seroconversion rate was defined as the percentage of participants achieving a minimal 4-fold increase from the Baseline HI antibody titer in participants with a Baseline titer ≥10, or achieving an HI antibody titer of ≥40 in participants with a Baseline titer <10. | Change from Baseline HI Antibody Titer at 21 days | 
| Seroprotection Rate of HI Antibody Titer | Seroprotection rate, defined as the percentage of participants with HI antibody titer of ≥40, was measured by HI antibody titer for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after vaccination. Day 1 data is reported for reference. | Change from Baseline HI Antibody Titer at 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, 1 phase, safety