Protocol No: ECCT/20/10/04 Date of Protocol: 16-09-2020

Study Title:

A Phase III double-blind, randomized, active comparator controlled study in healthy Kenyan adolescents, young children and infants to assess the safety and immunogenicity of Beijing Institute of Biologic Products (BIBP) yellow fever vaccine in comparison to a WHO 17D-204 prequalified comparator yellow fever vaccine, as well as lot-to-lot consistency of immune response to the BIBP yellow fever vaccine”, CVIA 079.

Study Objectives:

1.1Study Objectives

1.1.1Primary Objectives:   

Safety

  • To evaluate the safety and tolerability of the BIBP YFV in healthy adolescents, young children and infants in Kenya and compare with that of a WHO PQ YFV

 

Immunogenicity

  • To assess the immunogenicity of BIBP YFV, administered at ≥4.2 log10 PFU/dose and ≥3.0 log10 IU/dose, and compare with that of a WHO PQ YFV in healthy 9-month old flavivirus-naïve Kenyan infants
  • To assess the lot-to-lot consistency of immune response across three lots of BIBP YFV, administered at ≥4.2 log10 PFU/dose, in healthy 9-month old flavivirus-naïve Kenyan infants

1.1.2Secondary Objectives:

Immunogenicity

To further assess the immunogenicity (in terms of seroprotection, post-vaccination median neutralizing antibody titer, and post-vaccination geometric mean neutralizing antibody titer [GMT]) of BIBP YFV, administered at ≥4.2 log10 PFU/dose and ≥3.0 log10

  • IU/dose, and compare with that of a WHO PQ YFV in healthy adolescents, young children and infants in Kenya. Seroprotection will be defined as PRNT50 titer ≥10.
  • To assess and compare the immune responses to the co-administered measles-rubella vaccine of infants receiving either ≥4.2 log10 PFU/dose or ≥3.0 log10 IU/dose BIBP YFV with those receiving the WHO PQ YFV
  • To further assess the immune responses to co-administered measles-rubella vaccine, in terms of geometric mean concentrations (GMC)
Laymans Summary:

A study among healthy Kenyan adolescents, young children and infants to determine if a yellow fever vaccine manufactured by BIBP, and used in China for many years, is safe, and induces immunity against yellow fever consistently across different manufacturing runs and to a level similar to that of a vaccine prequalified by WHO

as well as lot-to-lot consistency of immune response to the BIBP yellow fever vaccine

Lay Title: A study among healthy Kenyan adolescents, young children and infants to determine if a yellow fever vaccine manufactured by BIBP, and used in China for many years, is safe, and induces immunity against yellow fever consistently across different manufacturing runs and to a level similar to that of a vaccine prequalified by WHO.

Around 200,000 yellow fever cases occur globally every year, 90% of which are in Africa. YF is a significant public health threat to hundreds of millions of those who live in the affected areas. In Africa and South America, yellow fever circulates in a cycle of transmission of the virus between non-human primates (e.g., monkeys) and mosquitoes, with incidental transmission by mosquitoes from monkeys to humans. This makes eradication of yellow fever virus difficult. Once infecting humans, yellow fever virus can range from mild to life-threatening disease such as multiple organ failure, jaundice (yellowness of skin) and bleeding. The death rate of patients who get the severe form of disease reaches as high as 50%. Some anti-viral drugs have been used to treat the disease but are only effective if started within two days of getting infected with the virus, before the disease gets worse.  Therefore, prevention of disease by vaccination plays a critical role in reducing the burden of yellow fever.

Abstract of Study:

Around 200,000 yellow fever (YF) cases occur globally every year, 90% of which are in Africa. YF is a significant public health threat to hundreds of millions of those who live in the affected areas. In Africa and South America, because yellow fever circulates in a sylvatic cycle where non-human primates serve as a reservoir, eradication of yellow fever virus is highly unlikely. Once infecting humans, yellow fever virus can range from subclinical to life-threatening disease such as multiple organ failure, jaundice and bleeding. The death rate of patients who enter the toxic period reaches as high as 50%. Although anti-viral drugs like ribavirin and immune modulator like α interferon are effective if treatment is initiated within two days of onset, once the infection progresses these drugs become ineffective. Therefore, vaccination plays a critical role in reducing the burden of yellow fever.  This is a Phase 3 study of safety and immunogenicity of Beijing Institute of Biologic Products (BIBP) Yellow Fever Vaccine (YFV). The purpose of the study is to evaluate the safety and tolerability of the BIBP YFV in healthy adolescents, young children and infants in Kenya and compare with that of a World Health Organization (WHO) prequalified (PQ) YFV and to assess the immunogenicity of the BIBP YFV and compare with that of a WHO PQ YFV in healthy 9-month old flavivirus-naïve Kenyan infants. Participants will be randomized to receive either the BIBP YFV or the WHO PQ YFV comparator.