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

A Blind Randomized Clinical Trial, With Active Controls, to Evaluate the Immunogenicity and Safety of the Quadrivalent Influenza Vaccine (Split Virion, Inactivated) From Instituto Butantan, in Infants and Children Aged 6 to 35 Months.

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.

Study Overview

• Status: Recruiting
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: Quadrivalent Influenza Vaccine (split virion, inactivated); Biological: Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Victoria lineage; Biological: Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Yamagata lineage

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 Type: Interventional
• Enrollment (Estimated): 1412
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Fernanda Boulos, M.D./PhD.; Phone Number: +55 11 3723-2150; Email: fernanda.boulos@butantan.gov.br
• Study Contact Backup: Name: Carolina Barbieri, M.D./PhD.; Phone Number: +55 11 3723-2150; Email: carolina.barbieri@butantan.gov.br

Study Locations

• Brazil
  • São Paulo, Brazil, 01228-000
    • Recruiting
    • CPQuali Pesquisa Clínica Ltda (Site 002)
    • Contact: Gustavo Akerman Augusto, MD; Phone Number: +55 (11) 2776-6801; Email: guakau@gmail.com
  • São Paulo, Brazil, 01228-200
    • Recruiting
    • Instituto de Pesquisa PENSI (Site SAO09)
    • Contact: Fátima Rodrigues Fernandes; Phone Number: (11) 2155-2055
  • São Paulo, Brazil, 05403-000
    • Recruiting
    • Centro de Pesquisa Clínica do Instituto da Criança - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (Site SAO08)
    • Contact: Lucia Maria Mattei de Arruda Campos; Phone Number: (11) 2661-8833
  • Pernambuco
    • Recife, Pernambuco, Brazil
      • Recruiting
      • Instituto Auto Imune de Pesquisa e Educação Continuada - Real Hospital Português de Beneficência em Pernambuco (Site REC01)
      • Contact: Carlos Alexandre Antunes de Brito; Phone Number: (81) 3416-1450
  • Roraima
    • Boa Vista, Roraima, Brazil, 69304-015
      • Recruiting
      • Centro Oncológico de Roraima - CECOR (Site BVB-01)
      • Contact: Juliana Gomes da Rocha; Phone Number: (95) 99162-1921
  • Sergipe
    • Laranjeiras, Sergipe, Brazil, 49170-000
      • Recruiting
      • Centro de Pesquisas Clínicas da Universidade Federal de Sergipe (Site AJU01)
      • Contact: Ricardo Queiroz Gurgel; Phone Number: (79) 9997-0480
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 14051-140
      • Recruiting
      • Hospital das Clínicas da Faculdade de Medicina Ribeirão Preto - USP (Site RAO 04)
      • Contact: Marisa Márcia MD Mussi; Phone Number: (16) 3963-6523
    • Serrana, São Paulo, Brazil
      • Recruiting
      • Centro de Pesquisa Clínica S (Site RAO03)
      • Contact: Marcos de Carvalho MD Borges; Phone Number: (16) 99281-5253
    • Sorocaba, São Paulo, Brazil, 18040-425
      • Recruiting
      • CPMC Pesquisa Clínica - Clinica De Alergia Martti Antila Sorocaba
      • Contact: Martti Anton Antila; Phone Number: (15) 99735-5812
    • Valinhos, São Paulo, Brazil, 13271-130
      • Recruiting
      • A2Z Clinical Centro Avançado de Pesquisa Clínica Ltda.(Site 001)
      • Contact: Ricardo Sobhie Diaz, MD; Phone Number: +55 (19) 3829-6160; Email: rsdiaz@catg.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (Child)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QIV-IB/dose 0.25ml; Butantan Quadrivalent Influenza Vaccine (split virion, inactivated)/dose 0.25ml	Biological: Quadrivalent Influenza Vaccine (split virion, inactivated); Quadrivalent Influenza Vaccine (split virion, inactivated) from Instituto Butantan (dose 0.25ml and 0.50ml)
Experimental: QIV-IB/dose 0.50ml; Butantan Quadrivalent Influenza Vaccine (split virion, inactivated)/dose 0.50ml	Biological: Quadrivalent Influenza Vaccine (split virion, inactivated); Quadrivalent Influenza Vaccine (split virion, inactivated) from Instituto Butantan (dose 0.25ml and 0.50ml)
Active Comparator: TIVV-IB; Butantan Trivalent Influenza Vaccine (split virion, inactivated)/dose 0.25ml containing Influenza B virus - Victoria lineage	Biological: Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Victoria lineage; Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Victoria lineage/dose 0.50ml
Active Comparator: TIVY-IB; Butantan Trivalent Influenza Vaccine (split virion, inactivated)/dose 0.25ml containing Influenza B virus - Yamagata lineage	Biological: Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Yamagata lineage; Trivalent Influenza Vaccine (split virion, inactivated) containing Influenza B virus - Yamagata lineage/dose 0.25ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.	28 days after last vaccination
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.	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.	28 days after last vaccination
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.	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.	28 days after last vaccination
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.	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.	28 days after last vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.	28 days after last vaccination
Percentage of Participants With Seroconversion (Seroconversion Rate - SCR) to Influenza Vaccine Antigens.	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.	At Days 0 and 28/56
Percentage of Participants achieving seroprotection (Seroprotection Rate - SPR) to Influenza Vaccine Antigens.	Seroprotection Rate is defined as the percentage of subjects with HAI titer ≥1:40	At Days 0 and 28/56
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.	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.	At Days 0 and 28/56
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.	Immunogenicity outcomes assessed in serum samples by hemagglutination inhibition (HAI) assay.	At Days 0 and 28/56
Solicited local Site or Systemic Reactions After each Injection	Percentage of subjects with Solicited local Site or Systemic Reactions After each Injection	Day 0 up to Day 7 post-injection
Related Unsolicited Adverse Events	Percentage of subjects with Related Unsolicited Adverse Events	28 days after last vaccination
Serious Adverse Events (SAE) and adverse events of special interest (AESI)	Percentage of subjects with Serious Adverse Events (SAE) and adverse events of special interest (AESI)	Entire study participant's follow-up period (6 months after the last vaccination)

Collaborators and Investigators

• Sponsor: Butantan Institute
• Collaborators: Fundação Butantan

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2023
• Primary Completion (Estimated): March 15, 2024
• Study Completion (Estimated): October 15, 2024

Study Registration Dates

• First Submitted: March 9, 2023
• First Submitted That Met QC Criteria: March 9, 2023
• First Posted (Actual): March 22, 2023

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Influenza Vaccines
• 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: FLQ-02-IB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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