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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Influenza, Human

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infant and child of either sex aged between 6 and 35 months on the day of the first study vaccination. Born at term (≥ 37 weeks of gestational age) and birth weight ≥ 2.5 kg. 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. Parents/legal guardians of the infant or child have provided informed consent. Exclusion Criteria: Having received any influenza vaccine from the current season and/or 6 months before the first study vaccination. History of allergy to egg, chicken proteins, or other components of the influenza vaccine. History of serious adverse reaction to any influenza vaccine. Have any clinically significant condition or situation that, in the Investigator's opinion, would interfere with study evaluations or participation. History of Guillain-Barré or other demyelinating diseases. 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). 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. Any confirmed or suspected immunosuppressive condition, congenital or acquired immunodeficiency (including human immunodeficiency virus - HIV) based on medical history and physical examination. Immediate personal or family history of congenital immunodeficiency. 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. Be a solid organ or bone marrow/stem cell transplant recipient. Thrombocytopenia, bleeding disorder, use of anticoagulants, or any condition that contraindicates intramuscular injection. 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. History of seropositivity for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. 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. 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). 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. Infant and institutionalized child. Be related to the Investigator, research site staff member, or employee directly involved in the study. Postponement Criteria: 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). 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. Acute respiratory illness within 14 days preceding the planned date of the first study vaccination.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza Vaccines