Clinical trial NCT03849560: Safety, Reactogenicity, Immunogenicity, Efficacy of Influenza Vaccines Grippol® Quadri and Grippol® Plus in Volunteers
Official title: A Multicenter, Double-Blind, Randomized, Parallel Group Study of Safety, Reactogenicity, Immunogenicity, and Efficacy of Quadrivalent Influenza Vaccine Grippol Quadri and Trivalent Influenza Vaccine Grippol Plus in Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Influenza
Lead sponsor: NPO Petrovax
Sponsor class: INDUSTRY
First posted: 2019-02-21
Enrollment: 612
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Day 21 after immunization (Visit 7)
Secondary outcomes:
measure: Geometric Mean of Serum Antibodies
timeFrame: Day 21 after immunization (Visit 7)
measure: 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).
timeFrame: Day 21 after immunization (Visit 7)
measure: Incidence of Influenza and Acute Respiratory Infection (ARI)
timeFrame: Day 180±5 after immunization (Visit 11)
measure: The Average Value of the Total Duration of the Disease in Patients With Acute Respiratory Viral Infections or Influenza in Days .
timeFrame: Day 180±5 after immunization (Visit 11)
measure: Fold Change in Geometric Mean Titer of Serum Antibodies
timeFrame: 21 days following vaccination (visit 7).
measure: Severity of Reported Cases of Influenza and ARI.
timeFrame: Day 180±5 after immunization (Visit 11)
measure: Average Time (Months) to the First Reported Episode of Influenza and ARI
timeFrame: Day 180±5 after immunization (Visit 11)
measure: 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)
timeFrame: Day 21 after immunization (Visit 7)
measure: Number of Participants With Symptoms of Influenza and ARI in Vaccination Groups
timeFrame: Day 180±5 (Visit 11)
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Smorodintsev Research Institute of Influenza
state: Leningrad Oblast
city: Saint Petersburg
country: Russian Federation
facility: 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.
state: Leningrad Region
city: Saint Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution "Children's Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency"
state: Leningrad Region
Study officials:
affiliation: NPO Petrovax
name: Natalia Chirun, PhD
role: STUDY_DIRECTOR
affiliation: 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.
name: Dmitri Lioznov, PhD
role: PRINCIPAL_INVESTIGATOR
References: