Trial of Tolerability, Reactogenicity, Safety and Immunogenicity of Flu-M [Inactivated Split Influenza Vaccine] in Pregnant Women

Randomized, Double-blind, Comparative, Controlled Trial of Tolerability, Reactogenicity, Safety and Immunogenicity of Flu-M [Inactivated Split Influenza Vaccine] in Pregnant Women During the 2nd - 3rd Trimester

Comparative study of tolerability, reactogenicity, safety and immunogenicity Flu-M [Inactivated Split Influenza Vaccine] vs. the Ultrix® vaccine for the prevention of influenza in pregnant women in the 2nd-3rd trimesters of pregnancy

Study Overview

• Status: Completed
• Conditions: Influenza, Human; Vaccination; Infection; Vaccines
• Intervention / Treatment: Biological: Flu-M, Inactivated split influenza vaccine; Biological: Ultrix®, Inactivated Split Influenza Vaccine

Detailed Description

This is a randomized, double-blind, comparative, controlled trial. A design with a control group treated with Ultrix®, inactivated influenza vaccine, was chosen to obtain objective findings.Trial population: healthy women aged 18 to 35 years during the 2nd and 3rd trimesters of pregnancy. Subjects were randomized into 4 groups in a ratio of 1:1:1:1, 50 subjects per group.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Ekaterinburg, Russian Federation
    • Municipal Budgetary Institution "Central City Hospital No.7"
  • Saint Petersburg, Russian Federation
    • "Curator" Limited Liability Company
  • Saint Petersburg, Russian Federation
    • KOROLEV MEDICINE Limited Liability Company
  • Altai Territory
    • Barnaul, Altai Territory, Russian Federation
      • Federal State Budgetary Educational Institution of Higher Education "Altai State Medical University" of the Ministry of Health of the Russian Federation
  • Tomsk Region
    • Seversk, Tomsk Region, Russian Federation
      • Federal State Budgetary Institution "Siberian Federal Scientific and Clinical Center of Federal Medical and Biologic Agency"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Presence of signed Informed Consent of the female patient to participate in the trial
2. Healthy women aged 18 to 35 years in their 2nd and 3rd trimesters of pregnancy with gestational age of no more than 32 weeks
3. Singleton pregnancy progressing normally
4. No contraindications for vaccination
5. Pregnant women that are able to fulfill the requirements of the protocol (i.e., fill out the Self-Observation Diary, come to follow-up visits)
6. The investigator is given the opportunity to collect data about somatic, infectious, and allergic diseases within at least 3 months from vaccination (one or more calls from the clinical investigator or visits per month (as needed))

Exclusion Criteria:

1. Body temperature above 37°С
2. History of influenza or previous influenza vaccination during 6 months before the screening
3. History of allergic reactions to chicken protein
4. Allergic reactions to vaccine components or any previous vaccination
5. Gestational toxicosis
6. Any disorders of pregnancy
7. Thyroid disorders
8. Bronchial asthma
9. Clotting disorders
10. 1, 2 type diabetes mellitus
11. High risk of fetal chromosomal abnormalities (individual risk of at least 1/100) in the 1st trimester of pregnancy and/or the detection of fetal congenital anomalies / developmental defects in the 1st, 2nd, and 3rd trimesters of pregnancy
12. Strong 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 from prior vaccination; convulsions accompanied or not accompanied by a fever due to any prior vaccination
13. Acute infectious or non-infectious diseases less than 4 weeks before the screening, exacerbation of chronic diseases (the vaccination can be carried out after recovery or in the period of remission)
14. Immunomodulatory therapy, including immune-enhancing, immunosuppressive therapy (corticosteroids, cytotoxic and radioactive drugs) in the 6 months preceding the trial
15. Any other contraindications against vaccination according to the investigator.
16. Leukemia, cancer or a positive reaction to HIV infection, hepatitis B and C, syphilis in the medical history
17. Volunteers who received immunoglobulin or blood products within the last three months before the trial
18. History of Guillain-Barré syndrome (acute polyneuropathy)
19. Autoimmune diseases
20. Any confirmed or suspected immunosuppressive or immunodeficiency condition
21. Respiratory, cardiovascular failure, impaired liver or kidney function.
22. Severe birth defects or serious chronic diseases, including any clinically significant chronic diseases of lungs, kidneys, cardiovascular, nervous system, psychiatric diseases or metabolic disorders, confirmed by medical history or objective examination
23. Vaccination with any vaccine less than 30 days before the screening or scheduled vaccination with any vaccine within 30 days from vaccination with the trial vaccines
24. The woman is/was a patient of a tuberculosis dispensary and/or narcological dispensary and/or neuropsychiatric dispensary
25. Chronic alcohol abuse and/or use of drugs in the past history
26. Smoking
27. Participation in another clinical trial during the last 3 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Flu-M, II trimester of pregnancy; Subjects during their II trimester of pregnancy (gestational age: 14-26 weeks), immunized once with the Flu-M vaccine.	Biological: Flu-M, Inactivated split influenza vaccine; solution for intramuscular injection, 0.5 ml
Active Comparator: Ultrix®, II trimester of pregnancy; Subjects during their II trimester of pregnancy (gestational age: 14-26 weeks), immunized once with Ultrix®.	Biological: Ultrix®, Inactivated Split Influenza Vaccine; solution for intramuscular injection, 0.5 ml
Experimental: Flu-M, III trimester of pregnancy; Subjects during their III trimester of pregnancy (gestational age: 27-32 weeks), will be immunized once with the Flu-M vaccine.	Biological: Flu-M, Inactivated split influenza vaccine; solution for intramuscular injection, 0.5 ml
Active Comparator: Ultrix®, III trimester of pregnancy; Subjects during their III trimester of pregnancy (gestational age: 27-32 weeks), immunized once with Ultrix®.	Biological: Ultrix®, Inactivated Split Influenza Vaccine; solution for intramuscular injection, 0.5 ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Seroprotection rate at day 21 after vaccination	The percentage of vaccinees who have an antibody titer of more than 1:40 by Day 21 after vaccination. Antibodies to influenza B, А (H1N1), А (H3N2) viruses Seroprotection rate ≥ 70%.	Days 0 (screening), 21
Change from Baseline Seroconversion rate at day 21 after vaccination	The relative number of vaccinees, whose titer of hemagglutinin inhibiting antibodies has increased by more than 4 times vs. baseline among all immunoprotective persons. Antibodies to influenza B, А (H1N1), А (H3N2) viruses Seroconversion rate ≥ 40%	Days 0 (screening), 21
Change from Baseline Seroconversion factor at day 21 after vaccination	An increase in the geometric mean titers of hemagglutinin inhibiting antibodies on Day 21 vs. baseline, expressed in multiplicity of increase. Antibodies to influenza B, А (H1N1), А (H3N2) viruses Seroconversion factor ≥ 2.5	Days 0 (screening), 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AEs and SAEs associated with vaccination	The degree of intensity or severity of AE was evaluated on a 4-point scale: 0 - none (no symptoms); - mild (mild symptoms); - moderate (symptoms that disrupt normal daily activities to a certain extent); - severe (symptoms that disrupt normal daily activities)	Day 1 (30 minutes, 3 and 5 hours after vaccination), days 2-21
Number of participants with abnormal changes in physical examination data	Physical examination includes examination of the general appearance, condition of the skin and mucous membranes, neck (including the thyroid gland), eyes, ears, nasopharynx, lungs, heart, abdomen, liver, back, lymph nodes Table 6	Days 0-7, day 21
Number of participants with abnormal changes in vital signs - Blood pressure (BP)	BP is measured in a sitting position after 10 minutes of rest	Days 0-7, day 21
Number of participants with abnormal changes in vital signs - Heart rate (HR)	HR is measured in a sitting position after 10 minutes of rest	Days 0-7, day 21
Number of participants with abnormal changes in vital signs - Respiratory rate (RR)	RR is measured in a sitting position after 10 minutes of rest	Days 0-7, day 21
Number of participants with abnormal changes in vital signs - Body temperature	Body temperature is measured in the armpit	Days 0, 1 (10 minutes before vaccination, 30 minutes and 2 and 5 hours after vaccination), days 2-7, day 21
Incidence and severity of systemic post-injection reactions		Day 1 (30 minutes, 3 and 5 hours after vaccination), days 2-21
Incidence and severity of local post-injection reactions		Day 1 (30 minutes, 3 and 5 hours after vaccination), days 2-21
Number of participants with abnormal changes data obtained from examinations by immunologist-allergist	Number of participants with clinically significant abnormalities	Days 1-7, day 21
Number of participants with abnormal changes of neurological examination data	Number of participants with clinically significant abnormalities	Days 0-7, day 21
Number of participants with abnormal changes data obtained from examinations by obstetrician-gynecologist	Examination: Respiratory organs, Blood circulation organs, Digestive organs, Organs of the urinary system, Mammary glands, Tone of the uterus, Fetal palpation results, Fetal auscultation results	Days 0-7, day 21
Number of participants with abnormal changes in the ultrasound data assessment of fetus and uterus		Days 0 (screening), 21
Number of participants with clinically significant abnormalities - Complete blood count (CBC)	Red cells, Hemoglobin, ESR, White cells, Platelets, Relating to stab neutrophile, Segmented neutrophils, Lymphocytes, Eosinophils, Basophils, Monocytes	Days 0 (screening), 3, 21
Number of participants with clinically significant abnormalities - Biochemical blood test (BBT)	Creatinine, Urea, Aspartate aminotransferase (AST), Alanine transaminase (ALT), Lactate dehydrogenase (LDH), Total protein, C-reactive protein, Alkaline phosphatase, Bilirubin, Glucose, Cholesterol, Prothrombin complex, Thymol test, β-lipoproteins	Days 0 (screening), 3, 21
Number of participants with clinically significant abnormalities - Urinalysis	Density, Leukocytes, pH, color, urine glucose, urine erythrocytes, bacteria	Days 0 (screening), 3, 21
Number of participants with abnormal changes of total IgE		Days 0 (screening), 3, 21

Collaborators and Investigators

• Sponsor: St. Petersburg Research Institute of Vaccines and Sera
• Investigators: Study Director: Ellina Ruzanova, PhD, St. Petersburg Research Institute of Vaccines and Sera

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2020
• Primary Completion (Actual): March 11, 2021
• Study Completion (Actual): July 26, 2021

Study Registration Dates

• First Submitted: July 11, 2022
• First Submitted That Met QC Criteria: July 11, 2022
• First Posted (Actual): July 14, 2022

Study Record Updates

• Last Update Posted (Actual): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Influenza; Vaccine; Flu; SPbSRIVS; FLU-M; Ultrix
• 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: FM-2019-01

Drug and device information, study documents

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