Clinical trial NCT03927131: Safety and Immunogenicity of the Butantan Quadrivalent Influenza Vaccine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza, Human
Keywords: Vaccines
Lead sponsor: Butantan Institute
Sponsor class: OTHER_GOV
Collaborators: name: Butantan Foundation
First posted: 2019-04-25
Enrollment: 5822
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety through number of Adverse Events of QIV-IB, TIVV-IB, TIVY-IB per age group
timeFrame: 07 days post-vaccination
measure: Safety through number of Adverse Events of QIV-IB, TIVV-IB, TIVY-IB per age group
timeFrame: 42 days post-vaccination
measure: Superiority for influenza B/Victoria strain
timeFrame: 21 days post-vaccination
measure: Superiority for influenza B/Yamagata strain
timeFrame: 21 days post-vaccination
measure: Non-inferiority for common influenza strains between QIV-IB, TIVV-IB and TIVY-IB
timeFrame: 21 days post-vaccination
measure: Lot-to-lot consistency for immune response to different lots of QIV-IB
timeFrame: 21 days post-vaccination
Secondary outcomes:
Other outcomes:
Locations:
city: Fortaleza
country: Brazil
facility: Centro de Pesquisa Clínica Universidade Federal do Ceará - UFC (Site FOR01)
state: Ceará
city: Fortaleza
country: Brazil
facility: Núcleo de Pesquisa e Desenvolvimento de Medicamentos - NPDM - Universidade Federal do Ceará - UFC (Site FOR 01)
state: Ceará
city: Belo Horizonte
country: Brazil
facility: Centro de Pesquisa e desenvolvimento de fármacos (Site BHZ01)
state: Minas Gerais
city: Recife
country: Brazil
facility: Centro de Pesquisa Clínica Real Hospital Português de Beneficência em Pernambuco (Site REC01)
state: Pernambuco
city: Pelotas
country: Brazil
facility: Centro de Pesquisa Clínica Hospital Escola da Universidade Federal de Pelotas (Site PET01)
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Centro de Pesquisa Clínica do Hospital São Lucas da PUCRS (Site POA01)
state: Rio Grande Do Sul
city: Laranjeiras
country: Brazil
facility: Centro de Pesquisas Clínicas da Universidade Federal de Sergipe (Site AJU01)
state: Sergipe
city: Ribeirão Preto
country: Brazil
facility: Centro de Pesquisa Clínica Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRPUSP) (Site RAO01)
state: São Paulo
city: Serrana
country: Brazil
facility: Centro de Pesquisa Clínica Serrana (Site RAO03)
state: São Paulo
city: São Caetano do Sul
country: Brazil
facility: Centro de Pesquisa Clínica da Universidade Municipal de São Caetano do Sul (Site SCS01)
state: São Paulo
city: São José do Rio Preto
country: Brazil
facility: Centro de Pesquisa Clínica Fundação Faculdade Regional de Medicina de São José do Rio Preto (Site SJP01)
state: São Paulo
city: São Paulo
country: Brazil
facility: Centro de Pesquisas Clínicas do Instituto Central da FMUSP Unidade II (Site SAO01)
Study officials:
affiliation: Instituto Butantan
name: Fernanda Castro Boulos, MD
role: STUDY_DIRECTOR
References: