Immunogenicity and Safety of Butantan Quadrivalent Influenza Vaccine (Split Virion, Inactivated) in Infants and Children .

Phase 3

Active, not recruiting

• Conditions: Influenza, Human
• Interventions: Biological: Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Victoria lineage; Biological: Quadrivalent Influenza Vaccine (split virion, inactivated); Biological: Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Yamagata lineage

• Registration Number: NCT05779020
• Lead Sponsor: Butantan Institute

Brief Summary

This is a Phase III Randomized Clinical Trial, blind, multicenter, with active controls, to evaluate the immunogenicity and safety of the Quadrivalent Influenza Vaccine (split virion, inactivated) from Instituto Butantan, in two dose scheme (0.25ml and 0.50ml), in infants and children under 3 years of age.

Detailed Description

The study will be carried out in multiple sites in Brazil, using a community-based recruitment strategy.

The study interventions are the Butantan Quadrivalent Influenza Vaccine (split virion, inactivated) in two dose scheme (QIV-IB/0.25ml and QIV-IB/0.50ml) and the active controls Butantan Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Victoria or Yamagata lineage (TIVV-IB and TIVY-IB), in a ratio 1:1:1:1.

The study population is healthy infants and children aged 6 to 35 months and all participants will be followed up 6 months after the last vaccination.

Study Timeline

• Study First Submitted: 2023-03-09
• Study First Submitted QC: 2023-03-09
• Study First Posted: 2023-03-22
• Study Start: 2023-04-25
• Status Verified: 2024-06
• Primary Completion: 2024-09-12
• Last Update Submitted: 2025-01-30
• Last Update Posted: 2025-01-31
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1373

Inclusion Criteria

1. Healthy infant and child of either sex aged between 6 and 35 months on the day of the first study vaccination.
2. Born at term (≥ 37 weeks of gestational age) and birth weight ≥ 2.5 kg.
3. Parents/legal guardians of the infant or child able and willing to attend all scheduled visits and comply with all study procedures, including blood draws.
4. Parents/legal guardians of the infant or child have provided informed consent.

Exclusion Criteria

1. Having received any influenza vaccine from the current season and/or 6 months before the first study vaccination.
2. History of allergy to egg, chicken proteins, or other components of the influenza vaccine.
3. History of serious adverse reaction to any influenza vaccine.
4. Have any clinically significant condition or situation that, in the Investigator's opinion, would interfere with study evaluations or participation.
5. History of Guillain-Barré or other demyelinating diseases.
6. History of neurological disease and/or clinically significant developmental delay (at the discretion of the Investigator), or seizure (except for an isolated febrile seizure episode).
7. Having received immune globulin, blood, or any blood product 3 months before the planned date of the first study vaccination or planned administration during the study period.
8. Any confirmed or suspected immunosuppressive condition, congenital or acquired immunodeficiency (including human immunodeficiency virus - HIV) based on medical history and physical examination.
9. Immediate personal or family history of congenital immunodeficiency.
10. Having received or are using radiation therapy, chemotherapy, immunosuppressive drugs, or other immunomodulatory drugs within three months before the planned date of the first study vaccination or planned use during the study.
11. Be a solid organ or bone marrow/stem cell transplant recipient.
12. Thrombocytopenia, bleeding disorder, use of anticoagulants, or any condition that contraindicates intramuscular injection.
13. Significant chronic disease (cancer, autoimmune disease, diabetes mellitus, acute or progressive liver disease, acute or progressive kidney disease, severe heart or lung disease) or which in the Investigator's opinion poses a risk to the health of the infant or child participating in the study or which may interfere with the conduct or conclusion of the study.
14. History of seropositivity for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
15. Major surgery or surgery using general anesthesia planned to occur during the period between the first vaccination and 28 days after full vaccination in the study.
16. Any condition that, in the opinion of the Investigator, may interfere with the conduct or completion of the study (such as travelling or planned moving of residence, among others).
17. Participation in another clinical trial involving another experimental or unregistered product 1 year before the planned date of the study's first vaccination, or plans to entering a clinical trial during the study.
18. Infant and institutionalized child.
19. Be related to the Investigator, research site staff member, or employee directly involved in the study.

Postponement Criteria:

1. Have received any vaccine (including routine childhood vaccines) within 28 days of the first study vaccination (delay until the 28-day deadline from the date of the last vaccination).
2. Moderate or severe (as judged by the Investigator) acute illness/infection or febrile illness (temperature ≥ 37.8°C) 48 hours before the planned date of the first study vaccination.
3. Acute respiratory illness within 14 days preceding the planned date of the first study vaccination.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TIVV-IB	Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Victoria lineage	Butantan Trivalent Influenza Vaccine (split virion, inactivated)/dose 0.25ml containing Influenza B virus - Victoria lineage
QIV-IB/dose 0.50ml	Quadrivalent Influenza Vaccine (split virion, inactivated)	Butantan Quadrivalent Influenza Vaccine (split virion, inactivated)/dose 0.50ml
QIV-IB/dose 0.25ml	Quadrivalent Influenza Vaccine (split virion, inactivated)	Butantan Quadrivalent Influenza Vaccine (split virion, inactivated)/dose 0.25ml
TIVY-IB	Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Yamagata lineage	Butantan Trivalent Influenza Vaccine (split virion, inactivated)/dose 0.25ml containing Influenza B virus - Yamagata lineage

Primary Outcome Measures

Name	Time	Method
Ratio of Geometric Mean Titers (rGMT) of antibodies induced by QIV-IB/0.25ml compared to those induced by TIVV-IB and TIVY-IB, for each strain, in infants and children from 6 to 35 months of age.	28 days after last vaccination	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.
Ratio of Geometric Mean Titers (rGMT) of antibodies induced by QIV-IB/0.50ml compared to those induced by TIVV-IB and TIVY-IB, for each strain, in infants and children from 6 to 35 months of age.	28 days after last vaccination	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.
Ratio of Geometric Mean Titers (rGMT) of antibodies induced by QIV-IB/0.25ml compared to those induced by TIV that does not contain the B strain, for B lineage Victoria and Yamagata, in infants and children aged 6 to 35 months age.	28 days after last vaccination	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.
Ratio of Geometric Mean Titers (rGMT) of antibodies induced by QIV-IB/0.50ml compared to those induced by TIV that does not contain the B strain, for B lineage Victoria and Yamagata, in infants and children aged 6 to 35 months age.	28 days after last vaccination	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.

Secondary Outcome Measures

Name	Time	Method
Related Unsolicited Adverse Events	28 days after last vaccination	Percentage of subjects with Related Unsolicited Adverse Events
Ratio of Geometric Mean Titers (rGMT) of antibodies induced by QIV-IB/0.50ml compared to those induced by QIV-IB/0.25ml, for each strain, in infants and children from 6 to 35 months of age.	28 days after last vaccination	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.
Pre- and post-vaccination Geometric Mean Titers (GMT) induced by QIV-IB/0.25ml, QIV-IB/0.50ml, TIVV-IB e TIVY-IB, for each strain, in infants and children from 6 to 35 months of age.	At Days 0 and 28/56	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.
Ratio of Pre- and post-vaccination Geometric Mean Titers (rGMT) induced by QIV-IB/0.25ml, QIV-IB/0.50ml, TIVV-IB e TIVY-IB, for each strain, in infants and children from 6 to 35 months of age.	At Days 0 and 28/56	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.
Solicited local Site or Systemic Reactions After each Injection	Day 0 up to Day 7 post-injection	Percentage of subjects with Solicited local Site or Systemic Reactions After each Injection
Percentage of Participants achieving seroprotection (Seroprotection Rate - SPR) to Influenza Vaccine Antigens.	At Days 0 and 28/56	Seroprotection Rate is defined as the percentage of subjects with HAI titer ≥1:40
Serious Adverse Events (SAE) and adverse events of special interest (AESI)	Entire study participant's follow-up period (6 months after the last vaccination)	Percentage of subjects with Serious Adverse Events (SAE) and adverse events of special interest (AESI)
Percentage of Participants With Seroconversion (Seroconversion Rate - SCR) to Influenza Vaccine Antigens.	At Days 0 and 28/56	SCR is defined as the percentage of subjects with either a prevaccination HAI titer \< 1:10 and a postvaccination HI titer ≥ 1:40, or a prevaccination HI titer ≥ 1:10 and a ≥ 4-fold increase in postvaccination HI titer.

Trial Locations

Locations (10)

Instituto Auto Imune de Pesquisa e Educação Continuada - Real Hospital Português de Beneficência em Pernambuco (Site REC01); 🇧🇷 Recife, Pernambuco, Brazil

Centro Oncológico de Roraima - CECOR (Site BVB-01); 🇧🇷 Boa Vista, Roraima, Brazil

Centro de Pesquisas Clínicas da Universidade Federal de Sergipe (Site AJU01); 🇧🇷 Laranjeiras, Sergipe, Brazil

Hospital das Clínicas da Faculdade de Medicina Ribeirão Preto - USP (Site RAO 04); 🇧🇷 Ribeirão Preto, São Paulo, Brazil

Centro de Pesquisa Clínica S (Site RAO03); 🇧🇷 Serrana, São Paulo, Brazil

CPMC Pesquisa Clínica - Clinica De Alergia Martti Antila Sorocaba; 🇧🇷 Sorocaba, São Paulo, Brazil

A2Z Clinical Centro Avançado de Pesquisa Clínica Ltda.(Site 001); 🇧🇷 Valinhos, São Paulo, Brazil

CPQuali Pesquisa Clínica Ltda (Site 002); 🇧🇷 São Paulo, Brazil

Instituto de Pesquisa PENSI (Site SAO09); 🇧🇷 São Paulo, Brazil

Centro de Pesquisa Clínica do Instituto da Criança - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (Site SAO08); 🇧🇷 São Paulo, Brazil