Safety and Immunogenicity of the Butantan Quadrivalent Influenza Vaccine

Double-blind, Randomized Clinical Trial With Active Controls to Assess Safety, Immunogenicity and Lot-to-lot Consistency of Inactivated Split-virion Quadrivalent Influenza Vaccine of Butantan Institute

Studies have shown that a broader spectrum influenza vaccine may help in reducing the influenza burden of disease. Butantan Institute is currently developing a quadrivalent influenza vaccine candidate. This study is will provide safety and immunogenicity data on this quadrivalent influenza vaccine candidate.

The study will be conducted in an open population of healthy participants (3 years old and above) recruited in different clinical sites in Brazil and will be adequately powered to assess safety, immune response (measured by GMT HI antibodies) to each viral strain in the vaccines and lot-to-lot consistency.

This is a double blinded, randomized active-control comparator study to assess the safety and immunogenicity of QIV-IB, the Butantan Institute quadrivalent influenza vaccine candidate. As active controls, two trivalent influenza vaccines with different Influenza B strains, one with influenza B/Victoria strain (TIVV-IB) and other with influenza B/Yamagata strain (TIVY-IB).

The study is designed to build a safety database of the quadrivalent influenza vaccine in adults to detect adverse events with a frequency of 1:1000 or higher and safety databases for elderly and pediatric age groups to detect adverse events with frequency of 1:100 or higher.

In terms of immune response, the study aims to demonstrate superiority of HI (Hemagglutinin inhibition) GMT (Geometric Mean Titer) of the QIV-IB for the Influenza B strain that is not present in each trivalent vaccine control. Regarding the Influenza A and B strains common to QIV-IB and both trivalent vaccine controls, the study aims to demonstrate non-inferiority on those strains.

Finally, a lot-to-lot consistency test will be performed in a sub-group of adult participants.

Inclusion Criteria:

• Male or female, age 3 years or older at the time of enrollment.
• Provide written informed consent
• Agrees to complete all study visits, procedures and contacts
• Women and adolescents of childbearing age: Negative pregnancy test with understanding (through informed consent process).

Exclusion Criteria:

• Chronic medical conditions such as psychiatric conditions, diabetes, hypertension or any other conditions that might place the subjects at high risk of adverse events. Study clinicians will use clinical judgment on a case-by-case basis to assess safety risks under this criterion.
• Clinically significant abnormalities on physical examination.
• Use of immunosuppressive medications such as systemic corticosteroids or chemotherapeutics, or immunosuppressive illness.
• Women who are pregnant or planning to become pregnant during the study period plus 3 months beyond the last vaccine dose and currently nursing women.
• Participation in research involving another investigational product within 30 days before planned date of first vaccination or anytime through the last study safety visit.
• Clinically significant abnormalities on basic laboratory screening tests.
• Acute febrile illness (axillar temperature ≥ 37.8°C)
• Hypersensitivity to egg or chicken proteins or any of the vaccine constituents
• Thrombocytopenia or a bleeding disorder contraindicating intramuscular vaccination
• Unstable chronic illness (defined as illness requiring hospitalization or a clinically significant change in medication in the previous 12 weeks).
• Alcohol abuse of alcohol or drug addiction
• Any vaccination within the previous 4 weeks
• Seasonal influenza vaccination in the current year