Tolerability, Safety and Immunogenicity Trial of the Flu-M® Inactivated Vaccine in Volunteers Aged 18 to 60 Years

Multicenter, Double-blind, Comparative, Randomized Tolerability, Safety and Immunogenicity Trial of the Flu-M® Inactivated Vaccine in Volunteers Aged 18 to 60 Years

Comparative assessment of the tolerability, safety, and immunogenicity of the Flu-M® Inactivated Split Influenza Vaccine (without preservative) and the Flu-M® vaccine (with preservative) in volunteers aged between 18 and 60

Study Overview

• Status: Completed
• Conditions: Influenza; Flu, Human
• Intervention / Treatment: Biological: Flu-M [inactivated split influenza vaccine] without preservative; Biological: Flu-M [inactivated split influenza vaccine] with preservative

Detailed Description

1. Assessment of the tolerability and safety of the Flu-M® inactivated split influenza vaccine (without preservative) and Flu-M® (with preservative).
2. Assessment of the immunogenicity of the Flu-M® inactivated split influenza vaccine (with preservative) and Flu-M® (without preservative).

Single administration of the trial products. Duration of follow-up - 28+3 (outpatient visit) and Long-term follow-up - 180±3 days.

• Study Type: Interventional
• Enrollment (Actual): 654
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Engels, Russian Federation
    • State Autonomous Health Institution "Engels City Clinical Hospital No1"
  • Perm, Russian Federation
    • Limited Liability Company "Professorskaya Clinica"
  • Saint Petersburg, Russian Federation
    • Limited Liability Company "Clinika Zvezdnaya"
  • Saint Petersburg, Russian Federation
    • Limited Liability Company "MEDICINSKAYA CLINIKA"
  • Saint Petersburg, Russian Federation
    • Limited Liability Company "PeterClinic"
  • Saint Petersburg, Russian Federation
    • Limited Liability Company "Scientific Research Center Eco-Safety"
  • Saint Petersburg, Russian Federation
    • Saint Petersburg State Budgetary Healthcare Institution "State Polyclinic No. 117"
  • Yaroslavl, Russian Federation
    • Limited Liability Company "Medical Center Diagnostics and Prevention Plus"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy volunteers (men and women) aged 18-60 years;
2. Written informed consent of volunteers to participate in the clinical trial;
3. Volunteers able to fulfill requirements of the Protocol (i.e. fill out the patient's diary, come to follow-up visits);
4. For fertile women - a negative result of the pregnancy test and consent to observe adequate methods of contraception during the trial and at least two months after vaccination
5. For fertile men - consent to observe adequate methods of contraception during the trial and at least two months after vaccination, except for men after vasectomy with documented azoospermia, and their sexual partners should use methods of contraception that ensure more than 90% reliability or be incapable of conception after a surgical sterilization or have a natural menopause for at least 2 years.

Exclusion Criteria:

1. History of influenza/ARVI or previous influenza vaccination during 6 months before the trial;
2. Positive result of the SARS-CoV-2 test;
3. A serious post-vaccination reaction (temperature above 40 °C, hyperemia or edema more than 8 cm in diameter) or complications (collapse or shock-like condition that developed within 48 hours after vaccination; convulsions accompanied or not accompanied by a fever due to any previous vaccination);
4. Allergic reactions to vaccine components or any previous vaccination;
5. History of allergic reaction to chicken protein;
6. Guillain-Barré syndrome (acute polyneuropathy) in the medical history;
7. Previous vaccination with rabies vaccines less than 2 months before immunization or scheduled vaccination with rabies vaccines within 1 month after immunization with the trial vaccines;
8. Use of any vaccines within 1 month before the vaccination, excluding vaccines according to the National Calendar of Preventive Vaccination, including for epidemic reasons;
9. History of leukemia, cancer, autoimmune diseases;
10. (Positive blood test results for HIV, syphilis, hepatitis B/C;
11. Volunteers who received immunoglobulin or blood products or had a blood transfusion during the last three months before the trial;
12. History of long-term use (more than 14 days) of immunosuppressants or immunomodulatory drugs for six months before the trial;
13. History of any confirmed or suspected immunosuppressive or immunodeficiency condition;
14. History of chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, the gastrointestinal tract, liver, kidneys, hematopoietic or immune systems, mental disease in the acute stage or in the decompensation stage (recovery less than 4 weeks before vaccination);
15. Diabetes mellitus, thyrotoxicosis or other diseases of the endocrine system;
16. History of eczema;
17. Treatment with glucocorticosteroids, including in small doses, as well as local use of drugs containing steroids (> 10 mg of prednisolone or its equivalent for more than 14 days before the screening);
18. Tuberculosis, neurological or mental disorders, a convulsive syndrome, including in the past medical history;
19. History of acute infectious diseases (recovery less than 4 weeks before vaccination);
20. Consumption of more than 10 units of alcohol per week or history of alcohol addiction, drug addiction or abuse of pharmaceutical products;
21. Smoking of more than 10 cigarettes per day;
22. Participation in another clinical trial during the last 3 months;
23. Pregnancy or lactation;
24. Coagulopathy, including hemophilia;
25. Taking aspirin or other antiplatelet agents in high doses.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FLU-M w/o/p; Volunteers were vaccinated with a single dose of the Flu-M vaccine (without preservative) intramuscularly in a dose of 0.5 mL.	Biological: Flu-M [inactivated split influenza vaccine] without preservative; Solution for intramuscular injection, 0.5 ml
Experimental: FLU-M w/p; Volunteers were vaccinated with a single dose of the Flu-M vaccine (with preservative) intramuscularly in a dose of 0.5 mL.	Biological: Flu-M [inactivated split influenza vaccine] with preservative; Solution for intramuscular injection, 0.5 ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline geometric mean titer ratio of antibodies for each virus strain (GMT (Flu-M w/p) / GMT (Flu-M w/o/p) at 6 months	The upper limit of bilateral 95% CI for the GMT ratio (GMT (Flu-M w/p) / GMT (Flu-M w/o/p) should not exceed 1.5	days 0-180
Change from baseline the difference between seroconversion rates (seroconversion rate Flu-M w/p - seroconversion rate Flu-M w/o/p) at 6 months	The upper limit of bilateral 95% CI for the difference between seroconversion rates (seroconversion rate Flu-M w/p - seroconversion rate Flu-M w/o/p) should not exceed 10%	days 0-180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titer of antibodies for each virus strain (A (H1N1), A (H3N2) and B)	Specific anti-influenza antibodies were determined using haemagglutination inhibition assay (HI assay)	days 0,28,180
Seroconversion rate for each virus strain (A (H1N1), A (H3N2) and B)		days 0,28,180
Seroconversion factor for each virus strain (A (H1N1), A (H3N2) and B)		days 0,28,180
Seroprotection rate for each virus strain (A (H1N1), A (H3N2) and B)		days 0,28,180
Incidence, severity, and duration of influenza or ARVI during 6 months after vaccination		days 1-180
Incidence of adverse events (AEs)		days 1-180
Incidence of serious adverse events (SAEs)		days 1-180
Number of patients with abnormal results of blood pressure (BP)	BP measurements include the systolic and diastolic blood pressure.BP is measured on the brachial artery according to the Korotkoff method using a certified sphygmomanometer or tonometer. It is also allowed to use a certified electronic tonometer for measuring.	days 0,1,7,28,180
Number of patients with abnormal results of heart rate (HR)	The HR is measured during auscultation of the heart in parallel with determining the pulse rate on the radial artery (or on the carotid artery in case of weak pulsation in the radial artery) for a minute while sitting.	days 0,1,7,28,180
Number of patients with abnormal results of respiratory rate (RR)	The RR is measured for a minute at rest in the sitting position, by registering the breathing movements of the chest or abdominal wall.	days 0,1,7,28,180
Number of patients with abnormal results of body temperature (>37 °С)	Body temperature (°C) is measured with a mercury or digital thermometer in the armpit for at least 5 minutes or with a non-contact infrared digital thermometer.	days 0,1,7,28,180
Number of patients with abnormal results of physical examination	Physical examination of volunteers includes an interview, discovery of complaints and symptoms, when required, palpation, auscultation, percussion.	days 0,1,7,28,180
Number of patients with abnormal results of neurological status	Assessment of: Cranial nerve function; Motor sphere; Reflex sphere; Sensitive sphere; Coordination sphere; Pelvic functions; Higher mental functions	days 0,7,28
Determination of total IgE		days 0,7,28
Number of patients with abnormal results of electrocardiography (ECG)	2-lead electrocardiography (ECG). Assessment of: PQ, QT,QTc intervals, QRS complex	days 0,7

Collaborators and Investigators

• Sponsor: St. Petersburg Research Institute of Vaccines and Sera

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Actual): September 3, 2021
• Study Completion (Actual): November 15, 2021

Study Registration Dates

• First Submitted: March 17, 2022
• First Submitted That Met QC Criteria: March 28, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Influenza; Vaccine; Flu; SPbSRIVS; FLU-M
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: FLM-03-2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No