Tolerability, Safety and Immunogenicity Trial of the Flu-M Tetra Vaccine in Children

Influenza Clinical Trial

Official title:

Randomized, Double-blind, Comparative, Controlled Trial of Tolerability, Safety and Immunogenicity of the Flu-M Tetra Vaccine in Children Between 6 Months and 17 Years Old

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05739474
• Other study ID #: FL?-??-05-2021
• Status: Recruiting
• Phase: Phase 3
• Start date: January 19, 2022
• Est. completion date: December 30, 2023

Study information

• Verified date: August 2023
• Source: St. Petersburg Research Institute of Vaccines and Sera
• Contact: Ellina Ruzanova, PhD
• Phone: (812) 660-06-39
• Email: e.a.ruzanova[@]niivs.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to assess tolerability, reactogenicity, safety and immunogenicity of the Flu-M Tetra vaccine as compared to the VaxigripTetra vaccine in terms of prevention of influenza in children aged 6 months to 17 years old inclusive.

Description:

The trial will be conducted in three stages.

• Stage I Participants - children aged 10 to 17 years (10 years 0 months 0 days - 17 years 11 months 30 days), will be vaccinated a single 0.5 mL dose of the Flu-M Tetra vaccine or the VaxigripTetra vaccine intramuscularly.

Once reviewed by the Sponsor, the report will be submitted to the supervisory executive authorities alongside the notice of commencement of Stage II trial.

• Stage II Participants - children aged 3 to 9 years (3 years 0 months 0 days - 9 years 11 months 30 days), will be vaccinated a single 0.5 mL dose of the Flu-M Tetra vaccine or the VaxigripTetra vaccine intramuscularly (double dose for volunteers who have not been vaccinated before).

Once reviewed by the Sponsor, the report will be submitted to the supervisory executive authorities alongside the notice of commencement of Stage III trial.

• Stage III Participants - children aged 6 to 35 months (6 months 0 days - 35 months 30 days), will be vaccinated twice 0.25 mL dose of the Flu-M Tetra vaccine or the VaxigripTetra vaccine intramuscularly.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 948
• Est. completion date: December 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 17 Years

Eligibility

Inclusion Criteria:

For volunteers aged 10 to 17 years:

• Healthy children of both sexes aged 10 to 17 years (10 years 0 months 0 days - 17 years 11 months 30 days);

• The availability of written and dated informed consent of the volunteer (children aged 14 to 17 years) and their parent / legally acceptable representative for participation in the trial;

• If the volunteer has sexual relations, effective contraception methods must be used during the 30 days preceding vaccination and consent must be obtained to continue using these contraceptive methods during the trial and for two months after vaccination;

• The girls with menses in the medical history shall have a negative pregnancy test result.

For volunteers aged 3 to 9 years:

• Healthy children of both sexes aged 3 to 9 years (3 years 0 months 0 days - 9 years 11 months 30 days);

• The availability of written and dated informed consent of a parent / legally acceptable representative for participation in the trial;

For volunteers aged 6 to 35 months:

• Healthy children of both genders aged 6 to 35 months, inclusive (6 months 0 days - 35 months 30 days);

• The availability of written and dated informed consent of a parent / legally acceptable representative for participation in the trial.

• The trial subject of the was born full-term, with the Apgar score of 7-10 points.

For all volunteers:

The ability of a volunteer's parents / legally acceptable representatives to perform the requirements of the Protocol (i.e., fill out the Patient Diary, attend visits together with the volunteer).

Exclusion Criteria:

1. History of influenza (including in mothers for children aged 6 to 35 months) or previous influenza vaccination during 6 months before the trial;

2. Vaccination of the pregnant woman in the 2nd-3rd trimester (for the age group of 6 - 35 months) with an influenza vaccine

3. Positive result of the SARS-CoV-2 test;

4. Vaccination with any vaccine less than 30 days before participating in the trial or scheduled vaccination with any vaccine within 30 days after vaccination with the trial vaccines;

5. A serious post-vaccination reaction (temperature above 40 °C, hyperemia or edema more than 8 cm in diameter at the injection site) 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), encephalopathy;

6. Allergic reactions to vaccine components or any previous vaccination;

7. History of allergic reaction to chicken protein;

8. History of cancer, leukemia, tuberculosis, autoimmune diseases;

9. Carriage of HIV, syphilis, hepatitis B and C in the medical history, including by parents / legally acceptable representatives;

10. Children who received immunoglobulin products or transfusions of whole blood or its components less than 3 months before the start of the trial;

11. Long-term use (more than 14 days) of any immunomodulating medicines less than 3 months before the start of the trial;

12. Any confirmed or suspected immunosuppressive or immunodeficiency condition;

13. History of chronic diseases of the cardiovascular, bronchopulmonary, endocrine systems, blood in the acute stage (recovery less than 4 weeks before vaccination) or in the decompensation stage;

14. Children with hemophilia who may develop bleeding after intramuscular injection;

15. History of progressive neurological pathology, convulsive syndrome, afebrile convulsions;

16. History of acute infectious diseases (fever = 37.5°?): recovery less than 2 weeks before vaccination;

17. Participation in another clinical trial less than 3 months before the start of the trial;

18. History of mental illness of the child and the volunteer's parents;

19. The history of the volunteer's parent / legally acceptable representative being registered with a tuberculosis dispensary and/or a narcological dispensary;

20. Maternal history of drug use or alcohol abuse during pregnancy and/or breastfeeding;

21. Pronounced congenital malformations in a child;

22. Suspected developmental delay in a child.

Related Conditions & MeSH terms

• Influenza
• Influenza Viral Infections
• Influenza, Human
• Vaccine Reaction
• Virus Diseases

Intervention

Biological:
• Influenza vaccine [inactivated]
solution for intramuscular injection, 1 dose (0.5 mL)
• Influenza vaccine [inactivated]
suspension for intramuscular and subcutaneous injection, 1 dose (0.5 mL)

Locations

Country	Name	City	State
Russian Federation	State Autonomous Health Care Institution of the Sverdlovsk Region "Children's City Clinical Hospital No. 11"	Ekaterinburg
Russian Federation	State Autonomous Health Care Institution "Engels City Clinical Hospital No1"	Engel's
Russian Federation	Llc "Olla-Med"	Moscow
Russian Federation	LLC "Professorskaya Clinica"	Perm
Russian Federation	State Budgetary Healthcare Institution of the Perm Territory "City Children's Clinical Clinic No. 5"	Perm
Russian Federation	LLC PiterClinica	Saint Petersburg
Russian Federation	LLC "DNA Research Center"	Saratov

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	Change from Baseline Geometric mean titer (GMT) ratio of antibodies for each virus strain (A (H1N1), A (H3N2) and B)	Geometric mean titer (GMT) of antibodies in the blood serums of vaccinated participants in haemagglutination inhibition assay	Baseline (day 1) and 28 days after vaccination (Stage I, II, III) and revaccination (Stage II, III)
Secondary	Change from Baseline Seroconversion factor for each virus strain (A (H1N1), A (H3N2) and B)	Seroconversion factor is an increase in the geometric mean titers of antibodies at Day 28 vs. the baseline level, expressed in the fold rise	Baseline (day 1) and 28 days after vaccination (Stage I, II, III) and revaccination (Stage II, III)
Secondary	Change from Baseline Seroprotection rate for each virus strain (A (H1N1), A (H3N2) and B)	Seroprotection rate refers to the percentage of subjects with a generated protective HA titer (at least 1:40) vs. the baseline level	Baseline (day 1) and 28 days after vaccination (Stage I, II, III) and revaccination (Stage II, III)
Secondary	Change from Baseline Seroconversion rate for each virus strain (A (H1N1), A (H3N2) and B)	Seroconversion rate refers to the percentage of subjects who have a prevaccination titer of influenza haemagglutinin antibody titer (HA titer) = 1:10 and a post-vaccination HA titer = 1:40 or a prevaccination HA titer > 1:10 and at least a 4-fold increase in post-vaccination HA titer vs. the baseline	Baseline (day 1) and 28 days after vaccination (Stage I, II, III) and revaccination (Stage II, III)
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+3 (for participants with 1 vaccination), Day 1 to 56±3 (for participants with vaccination and revaccination)
Secondary	Withdrawal of a volunteer from the trial due to development of an AE/SAE associated with the use of the trial products		Days 1 to 28+3 (for participants with 1 vaccination), Day 1 to 56±3 (for participants with vaccination and revaccination)
Secondary	Number of participants with abnormal physical examination findings	Physical examination of volunteers includes an interview, discovery of complaints and symptoms, when required, palpation, auscultation, percussion.; It is necessary to conduct an examination of 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	Days 1, 3, 7, 28+3 (for participants with 1 vaccination), Days 1,3,7,28+3,56±3 (for participants with vaccination and revaccination)
Secondary	Number of participants with abnormal changes in vital signs - Blood pressure (BP)	BP is assessed in children aged 36 months and older. BP measurements include the systolic and diastolic blood pressure.	Days 1, 3, 7, 28+3 (for participants with 1 vaccination), Days 1,3,7,28+3,56±3 (for participants with vaccination and revaccination)
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.	Days 1, 3, 7, 28+3 (for participants with 1 vaccination), Days 1,3,7,28+3,56±3 (for participants with vaccination and revaccination)
Secondary	Number of participants with abnormal changes in vital signs - Respiratory rate (RR)	RR is counted with a hand placed on the child's chest or abdomen or by holding a stethoscope at the child's nose. The measurement is conducted during one minute.	Days 1, 3, 7, 28+3 (for participants with 1 vaccination), Days 1,3,7,28+3,56±3 (for participants with vaccination and revaccination)
Secondary	Number of participants with abnormal changes in vital signs - Body temperature	The body temperature is measured with a digital thermometer.	Days 1, 3, 7, 28+3 (for participants with 1 vaccination), Days 1,3,7,28+3,56±3 (for participants with vaccination and revaccination)
Secondary	Number of participants with clinically significant abnormalities - Complete blood count (CBC)	Hemoglobin, Hematocrit, Erythrocytes, Leukocytes, Leukocytic Formula, Platelets, Erythrocyte Sedimentation Rate (ESR)	Days 1, 3
Secondary	Number of participants with clinically significant abnormalities - Biochemical blood test (BBT)	ALT, AST, Alkaline Phosphatase, Total Bilirubin, Total Protein, Urea, Glucose	Days 1, 3
Secondary	Number of participants with clinically significant abnormalities - Urinalysis	pH, Color, Relative Density/Specific Gravity, Protein, Glucose, Red Blood Cells, White Blood Cells	Days 1, 3
Secondary	Number of participants with abnormal changes of total IgE		Days 1, 3
Secondary	Number of participants with abnormal neurological examinations		Days 1, 3, 7, 28+3 (for participants with 1 vaccination), Days 1,3,7,28+3,56±3 (for participants with vaccination and revaccination)