Influenza
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALGrippol® Quadri
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).
BIOLOGICALGrippol® Plus, trivalent (Yamagata lineage)
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).
BIOLOGICALGrippol® Plus, trivalent (Victoria lineage)
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).
Sponsors
NPO Petrovax
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Signed and dated volunteer's informed consent for participation in the study. 2. Men and women from 18 to 60 years old. 3. Healthy volunteers without signs of acute or chronic disorders, without history of chronic respiratory, cardiovascular, nervous system disorders, hepatic or renal disorders. 4. Previously not immunized, or previous influenza immunization occurring ≥ 12 months before this study. 5. Subjects without history of influenza within ≥ 12 months before this study. 6. Consent of volunteers (men and women) to use adequate methods of contraception (cervical caps with spermicide, diaphragms with spermicide, condoms with spermicide, intrauterine devices, oral contraceptives) or full abstinence for the whole period of the study. Specific: 1. Contraindications listed in the protocol and prescribing information for inactivated influenza vaccines: * acute infections and non-communicable disorders, including the period of reconvalescence of at least one month from the time of clinical and laboratory evidence of recovery; * hepatitis or meningococcal infection occurred less than 6 months after recovery; * exacerbations of chronic disorder or decompensated disorders that may impact the study (organic central nervous system disorders, decompensated cardiovascular disorder, acute renal or hepatic failure); * malignant neoplasms (including hematological disorders); * primary immunodeficiency (laboratory-confirmed); * HIV infection or HIV-associated disorders; * systemic disorders of connective tissue; * haemophilia (and other blood coagulation disorders); * severe neurological disorders; * Guillain-Barré syndrome (post infection demyelinating polyradiculoneuropathy of autoimmune nature with peripheral limb muscle palsy related to inflammation and destruction of myelin sheath of peripheral nerves; may acquire an ascending nature, involving muscles of face, pharynx, larynx); * history of severe vaccine-associated reactions (body temperature exceeding 38.5 °С) or local reactions (hyperemia and/or oedema at the site of injection of over 5 cm in diameter); * history of severe allergic disorders (angioedema, polymorphic exudative erythema, serum disease, etc.); * hypersensitivity to chicken protein or vaccine components; * blood and components transfusion within the last 6 months. 2. Indications for immunomodulating therapy. 3. Body temperature over 37.0 °С at screening or before injection. 4. Potential evidence of a chronic infection (periodic episodes of fever within the last 6 months), or antiviral (and/or antibacterial) treatment indicated. 5. History of disorders or conditions, which, according to investigator's judgment may impact the thermal regulation (chronic infections, neuroendocrine disorders \[thyrotoxicosis, pheochromocytoma, etc.\], climacteric syndrome, malignant hyperthermia, diseases of the central nervous system, malignant neoplasm, connective tissue disorders, systemic vasculitis, and information on excessive physical stress or work-rest regimen deviations \[within the last 2 months: night shifts, significant change of time zones, overheating\]). 6. Use of antipyretics (including non-steroidal anti-inflammatory drugs and anilides) within 24 hours before randomization. 7. Surgical interventions within less than 90 days before the screening visit. 8. Systolic blood pressure of over 130 mm Hg or less than 100 mm Hg and/or diastolic blood pressure of over 90 mm Hg or less than 60 mm Hg. 9. Any other disorder, which, in the opinion of the investigator, may prevent inclusion of the volunteer due to safety reasons or may impact the study results. General: 10. Pregnant and nursing women. 11. Lack of ability to visit daytime inpatient facility according to the study schedule, unavailability for adequate follow-up of the volunteer. 12. Body mass index of less than 18.5 or over 30.0 kg/m2 based on the weight-height Quetelet's index. 13. Participation in another clinical study of medicinal drugs within 3 months before the start of this study. 14. Mental, physical, or other reasons which prevent adequate assessment of own behavior and prevent from meeting the study protocol conditions. 15. History of narcotic and/or drug abuse, and/or inhalant addiction, current signs of alcoholic intoxication. 16. Intake of at least 5 alcohol units per week or history of alcohol, drug, or medicinal product abuse. One alcohol unit corresponds to 360 ml of beer, 120 ml of wine, or 30 ml of a strong alcoholic beverage. 17. Suspected lack of compliance with treatment or inability to undergo treatment and observe the limitations according to the study protocol. 18. Volunteers acknowledged by the court to be disabled or under guardianship. 19. Any other conditions that make the volunteer ineligible for the study according to a justified opinion of the study doctor or Sponsor.
Exclusion criteria
* Informed consent recall. * Occurrence of a severe adverse events (AE) or serious adverse events. * The volunteer is found to meet any of the non-inclusion criteria related to the safety of the volunteer participation in the study. * If a female-volunteer becomes pregnant. * The volunteer takes medicines not allowed in this study. * The volunteer is lost to follow-up. * In a situation, which, to the investigator's judgment, may adversely impact the volunteer if he/she continues participating in the study. * For administrative reasons (study termination by the Sponsor or regulatory authorities) or in case of major protocol violations which may significantly impact the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 21 after immunization (Visit 7) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 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. |
| Incidence of Influenza and Acute Respiratory Infection (ARI) | Day 180±5 after immunization (Visit 11) | Incidence of influenza and acute respiratory infection (ARI) based on assessment at Visit 11. |
| The Average Value of the Total Duration of the Disease in Patients With Acute Respiratory Viral Infections or Influenza in Days . | Day 180±5 after immunization (Visit 11) | 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. |
| Fold Change in Geometric Mean Titer of Serum Antibodies | 21 days following vaccination (visit 7). | Fold Change in Geometric Mean Titer of Serum Antibodies (antigens H1N1,H3N2, Yamagata and Victoria lineages) based on assessment data at visit 7. |
| Geometric Mean of Serum Antibodies | Day 21 after immunization (Visit 7) | 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. |
| Average Time (Months) to the First Reported Episode of Influenza and ARI | Day 180±5 after immunization (Visit 11) | Average time (months) to the first reported episode of influenza and ARI based on assessment at 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) | Day 21 after immunization (Visit 7) | 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. |
| Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Day 180±5 (Visit 11) | 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. |
| Severity of Reported Cases of Influenza and ARI. | Day 180±5 after immunization (Visit 11) | 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. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Grippol® Quadri Grippol® Quadri, a quadrivalent inactivated subunit influenza vaccine. Dosage form: suspension for intramuscular and subcutaneous injection. Dosage: 0.5 ml (1 dose)
Active ingredients:
* type A (H1N1) influenza virus antigen 5 µg;
* type A (H3N2) influenza virus antigen 5 µg;
* type B (Yamagata lineage) influenza virus antigen 5 µg;
* type B (Victoria lineage) influenza virus antigen 5 µg;
* immunoadjuvant Polyoxidonium® (azoximer bromide) 500 µg.
Grippol® Quadri: 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). | 205 |
| Grippol® Plus, Trivalent (Yamagata Lineage) Grippol® Plus, trivalent inactivated polymer-subunit influenza vaccine containing Yamagata lineage type B influenza virus antigen.
Dosage form: suspension for intramuscular and subcutaneous injection. Dosage: 0.5 ml (1 dose)
Active ingredients:
* type A (H1N1) influenza virus antigen 5 µg;
* type A (H3N2) influenza virus antigen 5 µg;
* type B (Yamagata lineage) influenza virus antigen 5 µg;
* immunoadjuvant Polyoxidonium® (azoximer bromide) 500 µg.
Grippol® Plus, trivalent (Yamagata lineage): 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). | 205 |
| Grippol® Plus, Trivalent (Victoria Lineage) Grippol® Plus, trivalent inactivated polymer-subunit influenza vaccine containing Victoria lineage type B influenza virus antigen.
Dosage form: suspension for intramuscular and subcutaneous injection. Dosage: 0.5 ml (1 dose)
Active ingredients:
* type A (H1N1) influenza virus antigen 5 µg;
* type A (H3N2) influenza virus antigen 5 µg;
* type B (Victoria lineage) influenza virus antigen 5 µg;
* immunoadjuvant Polyoxidonium® (azoximer bromide) 500 µg.
Grippol® Plus, trivalent (Victoria lineage): 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). | 202 |
| Total | 612 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Grippol® Quadri | Grippol® Plus, Trivalent (Yamagata Lineage) | Grippol® Plus, Trivalent (Victoria Lineage) | Total |
|---|---|---|---|---|
| Age, Continuous | 28.37 years STANDARD_DEVIATION 10.15 | 28.97 years STANDARD_DEVIATION 10.48 | 29.29 years STANDARD_DEVIATION 10.55 | 28.87 years STANDARD_DEVIATION 10.39 |
| Body mass index | 22.97 kg/m2 STANDARD_DEVIATION 2.86 | 23.09 kg/m2 STANDARD_DEVIATION 2.9 | 23.04 kg/m2 STANDARD_DEVIATION 3.08 | 23.03 kg/m2 STANDARD_DEVIATION 2.94 |
| Height | 171.9 centimeters STANDARD_DEVIATION 9.18 | 172.0 centimeters STANDARD_DEVIATION 9.28 | 172.3 centimeters STANDARD_DEVIATION 9.45 | 172.1 centimeters STANDARD_DEVIATION 9.29 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment Russia | 205 participants | 205 participants | 202 participants | 612 participants |
| Sex: Female, Male Female | 114 Participants | 110 Participants | 111 Participants | 335 Participants |
| Sex: Female, Male Male | 91 Participants | 95 Participants | 91 Participants | 277 Participants |
| Weight | 68.3 kilograms STANDARD_DEVIATION 12.23 | 68.7 kilograms STANDARD_DEVIATION 12.41 | 68.7 kilograms STANDARD_DEVIATION 11.97 | 68.5 kilograms STANDARD_DEVIATION 12.19 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 205 | 0 / 205 | 0 / 202 |
| other Total, other adverse events | 90 / 205 | 92 / 205 | 93 / 202 |
| serious Total, serious adverse events | 0 / 205 | 0 / 205 | 0 / 202 |
Outcome results
Primary
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)
Population: 612 patients were randomized, 1 people dropped out during the trial (due to withdrawal of informed consent). 611 patients completed the study, data from 607 participants were accepted for the final analysis of efficacy (4 patients were excluded from the analysis due to the lack of baseline values for analysis of immunological efficacy).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Grippol® Quadri | 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 | H1N1 | 133 Participants |
| Grippol® Quadri | 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 | H3N2 | 140 Participants |
| Grippol® Quadri | 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 | Victoria (VICT) | 137 Participants |
| Grippol® Quadri | 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 | Yamagata (YAMA) | 132 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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 | Yamagata (YAMA) | 121 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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 | H1N1 | 127 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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 | Victoria (VICT) | 38 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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 | H3N2 | 123 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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 | Yamagata (YAMA) | 59 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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 | H3N2 | 127 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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 | Victoria (VICT) | 127 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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 | H1N1 | 126 Participants |
95% CI: [0.82, 1.82]
95% CI: [1.08, 2.3]
95% CI: [0.9, 2.15]
95% CI: [0.68, 1.63]
Secondary
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)
Population: 612 patients were randomized, 1 patient dropped out during the trial (due to withdrawal of informed consent).There were data for this parameter only from 610 patients (1 patient dropped out during the trial, data for another patient is absent for unknown reason).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Grippol® Quadri | Average Time (Months) to the First Reported Episode of Influenza and ARI | 4.626 months |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Average Time (Months) to the First Reported Episode of Influenza and ARI | 5.111 months |
| Grippol® Plus, Trivalent (Victoria Lineage) | Average Time (Months) to the First Reported Episode of Influenza and ARI | 4.819 months |
Secondary
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).
Population: 612 patients were randomized, 1 patient dropped out during the trial, data of these patients were used for safety analysis. 611 patients completed the study, data from 607 participants were accepted for the final analysis of immunological efficacy - primary outcome measure (4 patients were excluded from the analysis due to lack of baseline values for analysis of immunological efficacy), data from 609 participants were used for analysis of secondary outcome measures.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Grippol® Quadri | Fold Change in Geometric Mean Titer of Serum Antibodies | H1N1 | 4.86 Ratio of geometric means |
| Grippol® Quadri | Fold Change in Geometric Mean Titer of Serum Antibodies | H3N2 | 5.32 Ratio of geometric means |
| Grippol® Quadri | Fold Change in Geometric Mean Titer of Serum Antibodies | VICT | 4.77 Ratio of geometric means |
| Grippol® Quadri | Fold Change in Geometric Mean Titer of Serum Antibodies | YAMA | 5.47 Ratio of geometric means |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Fold Change in Geometric Mean Titer of Serum Antibodies | YAMA | 4.04 Ratio of geometric means |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Fold Change in Geometric Mean Titer of Serum Antibodies | H1N1 | 4.21 Ratio of geometric means |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Fold Change in Geometric Mean Titer of Serum Antibodies | VICT | NA Ratio of geometric means |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Fold Change in Geometric Mean Titer of Serum Antibodies | H3N2 | 5.22 Ratio of geometric means |
| Grippol® Plus, Trivalent (Victoria Lineage) | Fold Change in Geometric Mean Titer of Serum Antibodies | YAMA | NA Ratio of geometric means |
| Grippol® Plus, Trivalent (Victoria Lineage) | Fold Change in Geometric Mean Titer of Serum Antibodies | H3N2 | 5.17 Ratio of geometric means |
| Grippol® Plus, Trivalent (Victoria Lineage) | Fold Change in Geometric Mean Titer of Serum Antibodies | VICT | 4.72 Ratio of geometric means |
| Grippol® Plus, Trivalent (Victoria Lineage) | Fold Change in Geometric Mean Titer of Serum Antibodies | H1N1 | 4.60 Ratio of geometric means |
Comparison: Coefficient of increase of mean geometric antibody titer for H1N1 in Grippol® Quadri group95% CI: [4.22, 5.6]
Comparison: Coefficient of increase of mean geometric antibody titer for H3N2 in Grippol® Quadri group95% CI: [4.53, 6.24]
Comparison: Coefficient of increase of mean geometric antibody titer for Yamagata in Grippol® Quadri group95% CI: [4.78, 6.25]
Comparison: Coefficient of increase of mean geometric antibody titer for Victoria in Grippol® Quadri group95% CI: [4.14, 5.49]
Comparison: Coefficient of increase of mean geometric antibody titer for H1N1 in Grippol® Plus, trivalent (Yamagata lineage) group95% CI: [3.59, 4.94]
Comparison: Coefficient of increase of mean geometric antibody titer for H3N2 in Grippol® Plus, trivalent (Yamagata lineage) group95% CI: [4.45, 6.12]
Comparison: Coefficient of increase of mean geometric antibody titer for Yamagata in Grippol® Plus, trivalent (Yamagata lineage) group95% CI: [3.48, 4.69]
Comparison: Coefficient of increase of mean geometric antibody titer for H1N1 in Grippol® Plus, trivalent (Victoria lineage) group95% CI: [3.97, 5.34]
Comparison: Coefficient of increase of mean geometric antibody titer for H3N2 in Grippol® Plus, trivalent (Victoria lineage) group95% CI: [4.38, 6.12]
Comparison: Coefficient of increase of mean geometric antibody titer for Victoria in Grippol® Plus, trivalent (Victoria lineage) group95% CI: [4, 5.56]
Secondary
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)
Population: 612 patients were randomized, 1 patient dropped out during the trial, data of these patients were used for safety analysis. 611 patients completed the study (FAS), data from 607 participants were accepted for the final analysis of immunological efficacy - primary outcome measure (4 patients were excluded from the analysis due to lack of baseline values for analysis of immunological efficacy), data from 609 participants were used for analysis of secondary outcome measures.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Grippol® Quadri | Geometric Mean of Serum Antibodies | H1N1 | 102.30 Titers |
| Grippol® Quadri | Geometric Mean of Serum Antibodies | H3N2 | 70.99 Titers |
| Grippol® Quadri | Geometric Mean of Serum Antibodies | VICT | 41.39 Titers |
| Grippol® Quadri | Geometric Mean of Serum Antibodies | YAMA | 65.63 Titers |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Geometric Mean of Serum Antibodies | YAMA | 52.85 Titers |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Geometric Mean of Serum Antibodies | H1N1 | 87.39 Titers |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Geometric Mean of Serum Antibodies | VICT | 17.05 Titers |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Geometric Mean of Serum Antibodies | H3N2 | 56.95 Titers |
| Grippol® Plus, Trivalent (Victoria Lineage) | Geometric Mean of Serum Antibodies | YAMA | 34.87 Titers |
| Grippol® Plus, Trivalent (Victoria Lineage) | Geometric Mean of Serum Antibodies | H3N2 | 62.06 Titers |
| Grippol® Plus, Trivalent (Victoria Lineage) | Geometric Mean of Serum Antibodies | VICT | 47.65 Titers |
| Grippol® Plus, Trivalent (Victoria Lineage) | Geometric Mean of Serum Antibodies | H1N1 | 94.32 Titers |
Comparison: Non-inferiority of Grippol® Quadri over Grippol® Plus, trivalent (Yamagata lineage) and Grippol® Plus, trivalent (Victoria lineage) for the strain A/H1N195% CI: [0.7762, 1.03]
Comparison: Non-inferiority of Grippol® Quadri over Grippol® Plus, trivalent (Yamagata lineage) and Grippol® Plus, trivalent (Victoria lineage) for the strain A/H3N295% CI: [0.7516, 1.0593]
Comparison: Non-inferiority of Grippol® Quadri over Grippol® Plus, trivalent (Yamagata lineage) for the strain B/Yamagata95% CI: [0.6918, 0.9683]
Comparison: Non-inferiority of Grippol® Quadri over Grippol® Plus, trivalent (Victoria lineage) for the strain B/Victoriap-value: 0.0595% CI: [0.857, 1.2445]ANCOVA
Secondary
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)
Population: 612 patients were randomized, 1 patient dropped out during the trial (due to withdrawal of informed consent).There were data for this parametr only from 610 patients (1 patient dropped out during the trial, data for another patient is absent for unknown reason).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Grippol® Quadri | Incidence of Influenza and Acute Respiratory Infection (ARI) | 66 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Incidence of Influenza and Acute Respiratory Infection (ARI) | 59 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | Incidence of Influenza and Acute Respiratory Infection (ARI) | 61 Participants |
p-value: 0.452Log Rank
p-value: 0.639Log Rank
Secondary
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)
Population: Overall Number of Participants Analyzed here represents the number of participants with incidence of Influenza and ARI;
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Grippol® Quadri | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Myalgia | 5 Participants |
| Grippol® Quadri | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Feeling of being unwell | 61 Participants |
| Grippol® Quadri | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Cough | 30 Participants |
| Grippol® Quadri | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Respiratory difficulty | 38 Participants |
| Grippol® Quadri | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Headache | 27 Participants |
| Grippol® Quadri | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Chills or fever | 19 Participants |
| Grippol® Quadri | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Sore throat | 41 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Feeling of being unwell | 56 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Sore throat | 41 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Chills or fever | 22 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Headache | 24 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Respiratory difficulty | 40 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Cough | 18 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Myalgia | 1 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Sore throat | 39 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Cough | 28 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Chills or fever | 21 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Feeling of being unwell | 56 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Myalgia | 5 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Respiratory difficulty | 38 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups | Headache | 28 Participants |
Secondary
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)
Population: Additional method of analysis only for 149 volunteers
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Grippol® Quadri | 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) | H3N2 | 31 Participants |
| Grippol® Quadri | 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) | H1N1 | 31 Participants |
| Grippol® Quadri | 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) | Yamagata | 29 Participants |
| Grippol® Quadri | 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) | Victoria | 26 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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) | Victoria | 10 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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) | Yamagata | 20 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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) | H1N1 | 23 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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) | H3N2 | 26 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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) | H1N1 | 27 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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) | H3N2 | 34 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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) | Yamagata | 13 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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) | Victoria | 26 Participants |
Secondary
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)
Population: 612 patients were randomized, 1 patient dropped out during the trial, data of these patients were used for safety analysis. 611 patients completed the study (FAS), data from 607 participants were accepted for the final analysis of immunological efficacy - primary outcome measure (4 patients were excluded from the analysis due to lack of baseline values for analysis of immunological efficacy), data from 609 participants were used for analysis of secondary outcome measures.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Grippol® Quadri | 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). | H1N1 before vaccination (Baseline) | 84 Participants |
| Grippol® Quadri | 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). | H1N1 day 21 after vaccination | 185 Participants |
| Grippol® Quadri | 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). | H3N2 before vaccination (Baseline) | 48 Participants |
| Grippol® Quadri | 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). | H3N2 day 21 after vaccination | 168 Participants |
| Grippol® Quadri | 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). | Yamagata before vaccination (Baseline) | 55 Participants |
| Grippol® Quadri | 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). | Yamagata day 21 after vaccination | 173 Participants |
| Grippol® Quadri | 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). | Victoria before vaccination (Baseline) | 11 Participants |
| Grippol® Quadri | 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). | Victoria day 21 after vaccination | 154 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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). | H3N2 before vaccination (Baseline) | 35 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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). | Victoria before vaccination (Baseline) | 27 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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). | H3N2 day 21 after vaccination | 152 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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). | Yamagata before vaccination (Baseline) | 52 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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). | Yamagata day 21 after vaccination | 166 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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). | H1N1 before vaccination (Baseline) | 86 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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). | H1N1 day 21 after vaccination | 184 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | 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). | Victoria day 21 after vaccination | 61 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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). | H3N2 before vaccination (Baseline) | 48 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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). | H1N1 day 21 after vaccination | 189 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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). | H1N1 before vaccination (Baseline) | 81 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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). | H3N2 day 21 after vaccination | 168 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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). | Victoria before vaccination (Baseline) | 27 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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). | Yamagata day 21 after vaccination | 115 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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). | Yamagata before vaccination (Baseline) | 62 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | 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). | Victoria day 21 after vaccination | 156 Participants |
p-value: 0.758Fisher Exact
p-value: 0.282Fisher Exact
p-value: 0.352Fisher Exact
p-value: 0.815Fisher Exact
Secondary
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)
Population: Overall Number of Participants Analyzed here represents the number of participants with incidence of Influenza and ARI
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Grippol® Quadri | Severity of Reported Cases of Influenza and ARI. | mild | 60 Participants |
| Grippol® Quadri | Severity of Reported Cases of Influenza and ARI. | moderate | 6 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Severity of Reported Cases of Influenza and ARI. | mild | 54 Participants |
| Grippol® Plus, Trivalent (Yamagata Lineage) | Severity of Reported Cases of Influenza and ARI. | moderate | 5 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | Severity of Reported Cases of Influenza and ARI. | mild | 51 Participants |
| Grippol® Plus, Trivalent (Victoria Lineage) | Severity of Reported Cases of Influenza and ARI. | moderate | 10 Participants |
Secondary
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)
Population: Overall Number of Participants Analyzed here represents the number of participants with incidence of Influenza and ARI
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Grippol® Quadri | The Average Value of the Total Duration of the Disease in Patients With Acute Respiratory Viral Infections or Influenza in Days . | 7.00 days | Standard Deviation 4.743 |
| Grippol® Plus, Trivalent (Yamagata Lineage) | The Average Value of the Total Duration of the Disease in Patients With Acute Respiratory Viral Infections or Influenza in Days . | 8.05 days | Standard Deviation 5.35 |
| Grippol® Plus, Trivalent (Victoria Lineage) | The Average Value of the Total Duration of the Disease in Patients With Acute Respiratory Viral Infections or Influenza in Days . | 9.61 days | Standard Deviation 7.086 |