Tolerability, Safety and Immunogenicity Trial of the Flu-M Quadro, Tetravalent Inactivated Split Influenza Vaccine

Influenza Clinical Trial

Official title:

Double-blind Comparative Randomized Tolerability, Safety and Immunogenicity Trial of the Flu-M Quadro Tetravalent Inactivated Split Influenza Vaccine, Solution for Intramuscular Injection, FSUE SPbSRIVS FMBA of Russia, in Volunteers Aged 18-60 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05869201
• Other study ID #: FMK-II/III-02/20
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 6, 2020
• Est. completion date: December 8, 2020

Study information

• Verified date: May 2023
• Source: St. Petersburg Research Institute of Vaccines and Sera
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to assess tolerability, safety and immunogenicity of the Flu-M Quadro vaccine as compared to the Ultrix® Quadri vaccine in volunteers aged between 18 and 60. Participants were given Flu-M Quadro [inactivated split influenza vaccine] with preservative or Flu-M Quadro [inactivated split influenza vaccine] without preservative or Ultrix® Quadri vaccine.The volunteers of each group were vaccinated with a single dose vaccine. Researchers assessed the tolerability, safety and immunogenicity of the Flu-M Quadro quadrivalent inactivated split influenza vaccine. Researchers performed a comparative assessment of the tolerability, safety, and immunogenicity of the Flu-M Quadro quadrivalent inactivated split influenza vaccine and the Ultrix® Quadri vaccine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 450
• Est. completion date: December 8, 2020
• Est. primary completion date: December 8, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers (men and women) aged 18-60;
• Written informed consent of the volunteers to participate in the clinical trial;
• Volunteers able to fulfill requirements of the protocol (i.e., fill out the patient's diary, come to follow-up visits);
• For fertile women - a negative result of the pregnancy test and consent to observe adequate methods of contraception (usage of contraceptives one month before vaccination and at least two months after vaccination). All females with childbearing potential must have a negative pregnancy test result during the screening period. In the course of the trial women should use barrier contraceptives with a reliability exceeding 90 %, or be sterile, or be in a postmenopausal state. Barrier contraceptives with a reliability exceeding 90 % of common use include cervical caps with spermicide, diaphragms with spermicide, condoms, intra-uterine spirals;
• For the men, are able to conceive - consent to use adequate contraception methods. In the course of the trial and during at least two months after vaccination, men and their sexual partners should use barrier contraceptives with a reliability exceeding 90 %, or be sterile. Barrier contraceptives with a reliability exceeding 90 % of common use include cervical caps with spermicide, diaphragms with spermicide, condoms, intra-uterine spirals;

Exclusion Criteria:

• History of influenza or ARVI or previous influenza vaccination during 9 moths before the trial;
• 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);
• Allergic reactions to vaccine components or any previous vaccination;
• History of allergic reaction to chicken protein;
• History of Guillain-Barré syndrome (acute polyneuropathy);
• 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;
• Use of any vaccines within 1 month before the vaccination, excluding vaccines according to the National Calendar of Preventive Vaccination, including for epidemic reasons;
• History of leukemia, tuberculosis, cancer, autoimmune diseases;
• Positive blood test results for HIV, syphilis, hepatitis B/C.
• Volunteers who received immunoglobulin or blood products or had a blood transfusion during the last three months before the trial;
• History of long-term use (more than 14 days) of immunosuppressants or other immunomodulatory drugs for six months before the trial;
• History of any confirmed or suspected immunosuppressive or immunodeficiency condition;
• 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);
• History of progressive neurological pathology, convulsive syndrome; Diabetes mellitus, thyrotoxicosis or other diseases of the endocrine system;
• History of eczema;
• 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 during the last three months);
• According to the medical history, the volunteer was/is a patient of a tuberculosis dispensary and/or narcological dispensary and/or neuropsychiatric dispensary and/or other;
• History of acute infectious diseases (recovery less than 4 weeks before vaccination);
• Consumption of more than 10 units of alcoholic drinks per week or history of alcohol addiction, drug addiction or abuse of pharmaceutical products;
• Smoking of more than 10 cigarettes per day;
• Participation in another clinical trial during the last 3 months;
• Pregnancy or lactation;
• Serious concurrent illnesses or pathological conditions not listed above which, in the opinion of the investigator, could complicate the assessment of the results of the trial including pathological deviations from age norms and laboratory norms of blood and urine parameters, which are clinically significant in the opinion of the investigator

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Influenza
• Influenza Viral Infections
• Influenza, Human
• Vaccination; Infection
• Vaccine Reaction
• Virus Diseases

Intervention

Biological:
• Influenza vaccine [inactivated]
Solution for intramuscular injection, 0.5 ml (1 dose) Vaccination with a single dose vaccine
• Influenza vaccine [inactivated]
Solution for intramuscular injection, 0.5 ml (1 dose) Vaccination with a single dose vaccine
• Influenza vaccine [inactivated]
Solution for intramuscular injection, 0.5 ml (1 dose) Vaccination with a single dose vaccine

Locations

Country	Name	City	State
Russian Federation	Federally Funded Healthcare Institution Primary Healthcare Unit No. 163,of Federal Medical and Biologic Agency (FFHI PHU No. 163, FMBA of Russia)	Kol'tsovo	Novosibirsk Region
Russian Federation	Bessalar Clinic. Clinical Trial Center Limited Liability Company (Bessalar Clinic. Clinical Trial Center LLC)	Moscow
Russian Federation	Federation (FSBEI of Higher Education "E. A. Wagner PSMU" of the of the Ministry of Health of the Russian Federation)	Perm
Russian Federation	Baltic Medicine Limited Liability Company (Baltic Medicine LLC)	Saint-Petersburg
Russian Federation	Eco-Safety Scientific Research and Development Center Limited Liability Company (Eco-Safety Scientific Research and Development Center LLC)	Saint-Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
St. Petersburg Research Institute of Vaccines and Sera

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seroconversion rate for each virus strain (A (H1N1), A (H3N2) and B (Yamagata line and Victoria line)) The percentage of subjects who have a prevaccination titer of influenza haemagglutinin antibody titer (HA titer) = 1:10 and a postvaccination HA titer		Screening (Days 0+5), Day 28
Secondary	Change from Baseline Geometric mean titer (GMT) ratio of antibodies for each virus strain (A (H1N1), A (H3N2) and B (Yamagata line and Victoria line))	Geometric mean titer (GMT) of antibodies in the blood serums of vaccinated participants in haemagglutination inhibition assay	Screening (Days 0+5), Day 28
Secondary	Seroconversion factor for each virus strain (A (H1N1), A (H3N2) and B (Yamagata line and Victoria line)) Seroconversion factor is an increase in the geometric mean titers of antibodies at Day 28 vs. the baseline level, expressed in the fold rise		Screening (Days 0+5), Day 28
Secondary	Seroprotection rate for each virus strain (A (H1N1), A (H3N2) and B (Yamagata line and Victoria line)) Seroprotection rate is the percentage of subjects with a generated protective HA titer (at least 1:40) vs. the baseline level		Screening (Days 0+5), Day 28
Secondary	Incidence of influenza and ARVI	Incidence, severity, and duration of influenza and ARVI during 6 months after vaccination detected outside of the Protocol.	During 6 months after vaccination
Secondary	Incidence of immediate adverse events (allergic reactions)		2 hours after vaccination
Secondary	Incidence of local adverse events		7 days after vaccination
Secondary	Incidence of systemic adverse events		7 days after vaccination
Secondary	Incidence of other adverse reactions		Days 8 to 28 after vaccination
Secondary	Incidence of severe adverse events		Days 1 to 28 after vaccination
Secondary	Incidence of withdrawal of a volunteer from the trial due to development of an AE/SAE associated with the use of the trial products		Days 1-7, 14
Secondary	Number of participants with abnormal physical examination findings	Physical examination of volunteers included an interview, discovery of complaints and symptoms, when required, palpation, auscultation, percussion. During the interview, all complaints and symptoms that had developed since the last visit were identified and assessed. An examination and (when applicable) palpation, auscultation, percussion were performed for the following organs and systems: skin, mucosa, eyes, oral cavity and pharynx, lungs/chest, heart/cardiovascular system, abdominal organs, nervous system, lymph nodes, musculoskeletal system, thyroid gland. The palpation analysis of lymph nodes (submandibular, cervical, ulnar) included an assessment of their size, consistency, pain, mobility, adhesion between themselves and with surrounding tissues and skin	Screening (Days 0+5), Days 1-7, 14, 28
Secondary	Number of participants with abnormal changes in vital signs - Blood pressure (BP)	BP measurements include the systolic and diastolic blood pressure	Screening (Days 0+5), Days 1-7, 14, 28
Secondary	Number of participants with abnormal changes in vital signs - Heart rate (HR)	HR is measured using a phonendoscope at the apex of the heart during 1 minute	Screening (Days 0+5), Days 1-7, 14, 28
Secondary	Number of participants with abnormal changes in vital signs - Respiratory rate (RR)		Screening (Days 0+5), Days 1-7, 14, 28
Secondary	Number of participants with abnormal changes in vital signs - Body temperature	Body temperature was measured using mercury or digital thermometer, in the armpit for at least 5 minutes	Screening (Days 0+5), Day 1 - before vaccination, 20 minutes and 2, 5-8 hours after vaccination; Days 2-7, 14, 28
Secondary	Number of participants with clinically significant abnormalities - Complete blood count (CBC)	Red blood cells, Hemoglobin, ESR, Differential Leukocyte Count (segmented and rod neutrophils, lymphocytes, monocytes, eosinophils, basophils), Platelets	Screening (Days 0+5), Days 3, 14, 28
Secondary	Number of participants with clinically significant abnormalities - Biochemical blood test (BBT)	ALT, AST, Alkaline phosphatase, Total Bilirubin, Total Protein, Urea, Glucose, C-reactive protein, Creatinine, Cholesterol	Screening (Days 0+5), Days 3, 14, 28
Secondary	Number of participants with clinically significant abnormalities - Urinalysis	pH, Relative Density/Specific Gravity, Protein, Glucose, Red Blood Cells, White Blood Cells	Screening (Days 0+5), Days 3, 14, 28
Secondary	Number of participants with abnormal changes of total IgE		Screening (Days 0+5), Days 3, 14, 28
Secondary	Number of participants with abnormal neurological examinations		Screening (Days 0+5), Days 1, 3 (When the interval between the screening visit and visit 1 is more than 3 days), 14, 28
Secondary	Number of participants with abnormal electrocardiography results	Standard 12-lead ECG	Screening (Days 0+5), Day 3