The aim of the study to assess the safety, reactogenicity, immunogenicity, and efficacy of quadrivalent inactivated subunit influenza vaccine Grippol® Quadri (NPO Petrovax Pharm, LLC, Russia) versus trivalent inactivated polymer-subunit vaccine Grippol® Plus (NPO Petrovax Pharm, LLC, Russia) in subjects from 18 to 60 years old.
The first Russian quadrivalent influenza vaccine was developed to improve the effectiveness of vaccination and the cost-effectiveness of preventive immunization. Task of the study: 1. Study and comparative assessment of the immunogenicity of the influenza quadrivalent inactivated subunit Grippol® Quadri vaccine in comparison with the trivalent inactivated polymer-subunit influenza vaccine Grippol® plus in volunteers aged 18-60 years. 2. Evaluation of the safety and reactogenicity of the influenza quadrivalent inactivated subunit Grippol® Quadri vaccine in comparison with the trivalent inactivated polymer-subunit influenza vaccine Grippol® plus in volunteers aged 18-60 years. 3. Study and comparative evaluation of the efficacy of the influenza quadrivalent inactivated subunit Grippol® Quadri vaccine in comparison with the trivalent inactivated polymer-subunit influenza vaccine Grippol® plus in volunteers aged 18-60 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
612
Single intramuscular injection of 0.5 ml (1 dose) of vaccine Grippol® Quadri into the upper third of the outer surface of the shoulder (the deltoid muscle).
Single intramuscular injection of 0.5 ml (1 dose) of vaccine Grippol® Plus, trivalent (Yamagata lineage) into the upper third of the outer surface of the shoulder (the deltoid muscle).
Single intramuscular injection of 0.5 ml (1 dose) of vaccine Grippol® Plus, trivalent (Victoria lineage) into the upper third of the outer surface of the shoulder (the deltoid muscle).
Federal State Budgetary Educational Institution of Higher Education "First St. Petersburg State Medical University named after academician I.P. Pavlova "of the Ministry of Health of the Russian Federation.
Saint Petersburg, Leningradskaya Oblast', Russia
Federal State Budgetary Institution "Children's Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency"
Saint Petersburg, Leningradskaya Oblast', Russia
Smorodintsev Research Institute of Influenza
Saint Petersburg, Leningradskaya Oblast', Russia
Percent of Subjects Achieving Seroconversion Increased More Than 4-fold Versus Baseline for Antigens: Influenza Virus Type А - H1N1, Influenza Virus Type А - H3N2, Influenza Virus Type В - Yamagata and Victoria Lineage
Percent of subjects achieving seroconversion (the number of volunteers with antibody titer \[of at least 1:40\] increased more than 4-fold versus baseline \[assessed by HAIR\]) for antigens: influenza virus type А - H1N1, influenza virus type А - H3N2, influenza virus type В - Yamagata and Victoria lineage, based on assessment at Visit 7.
Time frame: Day 21 after immunization (Visit 7)
Geometric Mean of Serum Antibodies
To antigens: influenza virus type А - H1N1, influenza virus type А - H3N2, influenza virus type В - Yamagata and Victoria lineage. Based on assessment at Visit 7.
Time frame: Day 21 after immunization (Visit 7)
Seroprotection: Percent of Subjects Achieving Protective Antibody Titer (1:40 and More) to Antigens H1N1, H3N2, Yamagata and Victoria Lineage, Based on Assessment at Day 21 After Immunization (Visit 7).
Antibody titer is determined using the hemagglutination inhibition reaction (HAIR), the method recommended by the World Health Organization (WHO) for influenza vaccine efficacy evaluation. As an additional method for 150 volunteers (50 volunteers in each group), a microneutralization assay is planned (the data will be used to evaluate seroprotection). Seroprotection: share of subjects achieving protective antibody titer (1:40 and more, assessed by HAIR and microneutralization test) to antigens H1N1, H3N2, Yamagata and Victoria lineages.
Time frame: Day 21 after immunization (Visit 7)
Incidence of Influenza and Acute Respiratory Infection (ARI)
Incidence of influenza and acute respiratory infection (ARI) based on assessment at Visit 11.
Time frame: Day 180±5 after immunization (Visit 11)
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The Average Value of the Total Duration of the Disease in Patients With Acute Respiratory Viral Infections or Influenza in Days .
A case of influenza and ARI is considered as a case of flu-like symptoms (according to: European center for Disease Prevention and Control (ECDC) TECHNICAL DOCUMENT Protocol for case-control studies to measure pandemic and seasonal influenza vaccine effectiveness in the European Union and European Economic Area Member States/ ECDC, 2009): if a subject seeks physician's advice regarding unexpected occurrence of at least one of 4 systemic symptoms: 1) chills or fever, 2) distress, 3) headache, 4) myalgia and at least one of 3 respiratory symptoms: 1) cough, 2) sore throat, 3) respiratory distress. Study doctor will perform evaluation of influenza or ARI duration and severity, making phone calls to subject. A case with at least 1 of the complications listed below will be considered severe: the necessity of hospitalization; influenza-associated pneumonia; influenza-associated cardiovascular disorder; death.
Time frame: Day 180±5 after immunization (Visit 11)
Fold Change in Geometric Mean Titer of Serum Antibodies
Fold Change in Geometric Mean Titer of Serum Antibodies (antigens H1N1,H3N2, Yamagata and Victoria lineages) based on assessment data at visit 7.
Time frame: 21 days following vaccination (visit 7).
Severity of Reported Cases of Influenza and ARI.
A case of influenza and ARI is considered as a case of flu-like symptoms (according to: ECDC TECHNICAL DOCUMENT Protocol for case-control studies to measure pandemic and seasonal influenza vaccine effectiveness in the European Union and European Economic Area Member States/ European center for Disease Prevention and Control, 2009): if a subject seeks physician's advice regarding unexpected occurrence of at least one of 4 systemic symptoms: 1) chills or fever, 2) distress, 3) headache, 4) myalgia and at least one of 3 respiratory symptoms: 1) cough, 2) sore throat, 3) respiratory distress. Study doctor will perform evaluation of influenza or ARI duration and severity, making phone calls to subject. A case with at least 1 of the complications listed below will be considered severe: the necessity of hospitalization; influenza-associated pneumonia; influenza-associated cardiovascular disorder; death.
Time frame: Day 180±5 after immunization (Visit 11)
Average Time (Months) to the First Reported Episode of Influenza and ARI
Average time (months) to the first reported episode of influenza and ARI based on assessment at Visit 11.
Time frame: Day 180±5 after immunization (Visit 11)
Seroprotection: Percent of Subjects Achieving Protective Antibody Titer (1:40 and More) to Antigens H1N1, H3N2, Yamagata and Victoria Lineage, Based on Assessment at Day 21 After Immunization (Additional Method of Analysis: a Microneutralization Assay)
As an additional method for 149 volunteers, a microneutralization assay is planned (the data will be used to evaluate seroprotection). Seroprotection: share of subjects achieving protective antibody titer (1:40 and more, assessed by HAIR and microneutralization test) to antigens H1N1, H3N2, Yamagata and Victoria lineages.
Time frame: Day 21 after immunization (Visit 7)
Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups
The presence of ARI symptoms in participants in each group is assessed throughout the study. The presence of a symptom at least once is taken into account in the analysis if the participant has several filling out of the questionnaire.
Time frame: Day 180±5 (Visit 11)