Trial of the Reactogenicity, Safety and Immunogenicity of the Flu-M Vaccine Manufactured by FSUE SPbSRIVS FMBA

Study Overview
=================
Brief Summary
-----------------
To trial the reactogenicity, safety and immunogenicity of the Flu-M inactivated split influenza vaccine in volunteers aged 18-60 years

Detailed Description
-----------------
All subjects will be followed up for 21 days post-randomization. The subjects will further be assessed at 2 days, 7 days, 21 days following the booster vaccination. Blood samples will be collected for reactogenicity and safety and immunogenicity assessments before injection and 21 days after vaccination.

Official Title
-----------------
Trial of the Reactogenicity, Safety and Immunogenicity of the Flu-M Vaccine Manufactured by FSUE SPbSRIVS FMBA vs. the Vaxigrip® Inactivated Influenza Split Vaccine Manufactured by Sanofi Pasteur, France, in Volunteers Aged 18-60 Years

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Biological: Flu-M [Inactivated split influenza vaccine]
* Biological: Inactivated influenza split vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent of the volunteers to participate in the clinical trial; Healthy volunteers (men and women) aged 18-60 years; Volunteers able to fulfill requirements of the protocol (fill out the patient's diary, come to follow-up visits); If the participant is female, she was required to have negative pregnancy test results and use contraceptives throughout the follow-up period (complete contraception of women of reproductive period) Exclusion Criteria: Allergic reactions to chicken protein or any previous influenza vaccination; Leukemia, cancer or a positive reaction to human immunodeficiency virus infection, hepatitis B and C, syphilis in the past medical history; Volunteers who received immunoglobulin or blood products within the last 3 months before the trial; Guillain-Barré syndrome (acute polyneuropathy) in the medical history; Long-term use (more than 14 days) of immunosuppressants or other immunomodulatory drugs for 6 months prior to the trial. Any confirmed or suspected immunosuppressive or immunodeficiency condition; Respiratory, cardiovascular failure, impaired liver or kidney function found during a physical examination or laboratory tests during Visit 1; Severe birth defects or serious chronic diseases, including any clinically significant chronic diseases of lungs, kidneys, cardiovascular, nervous system, psychiatric diseases or metabolic disorders, confirmed by medical history or objective examination; Being (or having been) a patient of a tuberculosis dispensary and/or narcological dispensary and/or neuropsychiatric dispensary; acute infectious and/or non-infectious diseases at the time of inclusion in the trial; Exacerbation of chronic diseases; chronic alcohol abuse and/or use of drugs in the past history; Pregnancy and lactation; Participation in another clinical trial within the last 3 months; Immunization with influenza vaccines in the last 6 months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Flu-M<br>200 volunteers were vaccinated with the Flu-M inactivated split influenza vaccine with a preservative | Biological: Flu-M [Inactivated split influenza vaccine]<br>* solution for intramuscular injection, 0.5 ml<br>|
| Active Comparator: Vaxigrip<br>200 volunteers were vaccinated with the Vaxigrip® inactivated split influenza vaccine | Biological: Inactivated influenza split vaccine<br>* solution for intramuscular injection, 0.5 ml<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of observed local reactions and their relationship with the vaccination | % of patients with: • Pain at the injection site at pressing Measurement tool: 4-point scale: 0 - none, 1 - mild, 2 - moderate, 3 - severe. Unit of measure: % of symptomatic patients at each severity | days 1-21 post-vaccination | 
| Severity of observed local reactions and their relationship with the vaccination | % of patients with: • Hyperemia; Measurement tool: 4-point scale: 0 - none, 1 - mild, 2 - moderate, 3 - severe. Unit of measure: % of symptomatic patients at each severity | days 1-21 post-vaccination | 
| Severity of observed local reactions and their relationship with the vaccination | % of patients with: • Infiltrate Measurement tool: 4-point scale: 0 - none, 1 - mild, 2 - moderate, 3 - severe. Unit of measure: % of symptomatic patients at each severity | days 1-21 post-vaccination | 
| Severity of observed local reactions and their relationship with the vaccination | % of patients with: • Swelling Measurement tool: 4-point scale: 0 - none, 1 - mild, 2 - moderate, 3 - severe. Unit of measure: % of symptomatic patients at each severity | days 1-21 post-vaccination | 
| Severity of observed system reactions and their relationship with the vaccination | % of patients with: • Fever Measurement tool: 4-point scale: 0 - none (≤ 37°С), 1 - mild (> 37°С - ≤ 37.5°С), 2 - moderate (> 37.6°С - ≤ 38.5°С), 3 - severe (> 38.6°С). Unit of measure: % of symptomatic patients at each severity | days 1-21 post-vaccination | 
| Severity of observed system reactions and their relationship with the vaccination | % of patients with: • Chills Measurement tool: 4-point scale: 0 - none, 1 - mild, 2 - moderate, 3 - severe. Unit of measure: % of symptomatic patients at each severity | days 1-21 post-vaccination | 
| Severity of observed system reactions and their relationship with the vaccination | % of patients with: • Increased sweating Measurement tool: 4-point scale: 0 - none, 1 - mild, 2 - moderate, 3 - severe. Unit of measure: % of symptomatic patients at each severity | days 1-21 post-vaccination | 
| Results of assessment of heart rate (HR) | The measurement of HR at each visit of the trial site by the volunteer | days 1-21 post-vaccination | 
| Results of assessment of systolic and diastolic blood pressure (BP) | The measurement of systolic and diastolic BP at each visit of the trial site by the volunteer | days 1-21 post-vaccination | 
| Results of biochemical blood tests | ALT (U/L) AST (U/L) Alkaline phosphatase (U/L) | days 3, 7 and 21 | 
| Results of biochemical blood tests | Bilirubin total (µmol/l) | days 3, 7 and 21 | 
| Results of biochemical blood tests | Total protein (g/l) | days 3, 7 and 21 | 
| Results of biochemical blood tests | C-reactive protein (mg/l) | days 3, 7 and 21 | 
| Results of biochemical blood tests | Urea (mmol/l) Glucose (mmol/l) Creatinine (mmol/l) | days 3, 7 and 21 | 
| Results of complete blood counts | Erythrocytes (10^12/L) | days 3, 7 and 21 | 
| Results of complete blood counts | Hemoglobin (g/L) | days 3, 7 and 21 | 
| Results of complete blood counts | Erythrocyte sedimentation reaction (ESR) (mm/h) | days 3, 7 and 21 | 
| Results of complete blood counts | Leukocytes, (х 10^9/L) Leukocytic formula: Stab neutrophils, % Segmented neutrophils (%) Eosinophils, (%) Basophils, (%) Lymphocytes, (%) Monocytes, (%) | days 3, 7 and 21 | 
| Results of complete blood counts | Platelets, (х 10^9/L) | days 3, 7 and 21 | 
| Incidence of AEs associated with the vaccination |  | days 1-21 post-vaccination | 
| Incidence of SAEs associated with the vaccination |  | days 1-21 post-vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
influenza, flu, vaccine, Flu-M