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

Phase 3
Completed
Conditions
Influenza, Human
Vaccines
Vaccination; Infection
Interventions
Biological: Flu-M, Inactivated split influenza vaccine
Biological: Ultrix®, Inactivated Split Influenza Vaccine
Registration Number
NCT05457894
Lead Sponsor
St. Petersburg Research Institute of Vaccines and Sera
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
207
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Flu-M, III trimester of pregnancyFlu-M, Inactivated split influenza vaccineSubjects during their III trimester of pregnancy (gestational age: 27-32 weeks), will be immunized once with the Flu-M vaccine.
Flu-M, II trimester of pregnancyFlu-M, Inactivated split influenza vaccineSubjects during their II trimester of pregnancy (gestational age: 14-26 weeks), immunized once with the Flu-M vaccine.
Ultrix®, II trimester of pregnancyUltrix®, Inactivated Split Influenza VaccineSubjects during their II trimester of pregnancy (gestational age: 14-26 weeks), immunized once with Ultrix®.
Ultrix®, III trimester of pregnancyUltrix®, Inactivated Split Influenza VaccineSubjects during their III trimester of pregnancy (gestational age: 27-32 weeks), immunized once with Ultrix®.
Primary Outcome Measures
NameTimeMethod
Change from Baseline Seroconversion rate at day 21 after vaccinationDays 0 (screening), 21

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%

Change from Baseline Seroconversion factor at day 21 after vaccinationDays 0 (screening), 21

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

Change from Baseline Seroprotection rate at day 21 after vaccinationDays 0 (screening), 21

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%.

Secondary Outcome Measures
NameTimeMethod
Number of participants with abnormal changes in physical examination dataDays 0-7, day 21

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

Incidence of AEs and SAEs associated with vaccinationDay 1 (30 minutes, 3 and 5 hours after vaccination), days 2-21

The degree of intensity or severity of AE was evaluated on a 4-point scale:

0 - none (no symptoms)

1. - mild (mild symptoms)

2. - moderate (symptoms that disrupt normal daily activities to a certain extent)

3. - severe (symptoms that disrupt normal daily activities)

Number of participants with abnormal changes of neurological examination dataDays 0-7, day 21

Number of participants with clinically significant abnormalities

Number of participants with clinically significant abnormalities - Biochemical blood test (BBT)Days 0 (screening), 3, 21

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

Number of participants with abnormal changes in vital signs - Blood pressure (BP)Days 0-7, day 21

BP is measured in a sitting position after 10 minutes of rest

Number of participants with abnormal changes in vital signs - Heart rate (HR)Days 0-7, day 21

HR is measured in a sitting position after 10 minutes of rest

Number of participants with abnormal changes in vital signs - Respiratory rate (RR)Days 0-7, day 21

RR is measured in a sitting position after 10 minutes of rest

Number of participants with abnormal changes in vital signs - Body temperatureDays 0, 1 (10 minutes before vaccination, 30 minutes and 2 and 5 hours after vaccination), days 2-7, day 21

Body temperature is measured in the armpit

Incidence and severity of local post-injection reactionsDay 1 (30 minutes, 3 and 5 hours after vaccination), days 2-21
Number of participants with abnormal changes data obtained from examinations by immunologist-allergistDays 1-7, day 21

Number of participants with clinically significant abnormalities

Number of participants with abnormal changes in the ultrasound data assessment of fetus and uterusDays 0 (screening), 21
Number of participants with clinically significant abnormalities - Complete blood count (CBC)Days 0 (screening), 3, 21

Red cells, Hemoglobin, ESR, White cells, Platelets, Relating to stab neutrophile, Segmented neutrophils, Lymphocytes, Eosinophils, Basophils, Monocytes

Number of participants with clinically significant abnormalities - UrinalysisDays 0 (screening), 3, 21

Density, Leukocytes, pH, color, urine glucose, urine erythrocytes, bacteria

Number of participants with abnormal changes of total IgEDays 0 (screening), 3, 21
Incidence and severity of systemic post-injection reactionsDay 1 (30 minutes, 3 and 5 hours after vaccination), days 2-21
Number of participants with abnormal changes data obtained from examinations by obstetrician-gynecologistDays 0-7, day 21

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

Trial Locations

Locations (5)

Municipal Budgetary Institution "Central City Hospital No.7"

🇷🇺

Ekaterinburg, Russian Federation

KOROLEV MEDICINE Limited Liability Company

🇷🇺

Saint Petersburg, Russian Federation

Federal State Budgetary Educational Institution of Higher Education "Altai State Medical University" of the Ministry of Health of the Russian Federation

🇷🇺

Barnaul, Altai Territory, Russian Federation

Federal State Budgetary Institution "Siberian Federal Scientific and Clinical Center of Federal Medical and Biologic Agency"

🇷🇺

Seversk, Tomsk Region, Russian Federation

"Curator" Limited Liability Company

🇷🇺

Saint Petersburg, Russian Federation

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