Clinical Trial: Immunogenicity and Safety of Fractional Doses of Yellow Fever Vaccines (YEFE)

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Randomized, Blinded Non-inferiority Trial on the Immunogenicity and Safety of Fractional Doses of Yellow Fever Vaccines in Kenya and Uganda

Brief Summary:

In July 2016, the demand for yellow fever vaccines in response to the large urban outbreaks occurring concurrently and the risk of further spread through the African continent and even to Asia, was larger than the available supply. In this situation, the World Health Organization (WHO) developed recommendations for the use of fractional-dose of yellow fever vaccine as a dose-sparing strategy. These recommendations were based on limited number of clinical trials and additional studies should assess the applicability of the fractional dose to all WHO-prequalified vaccines, the persistence of neutralizing antibodies and the performance of the fractional dose in young children and populations in Africa including those with HIV.

This study aims to respond to some of the research questions that would allow broadening the recommendations on the use of fractional doses of yellow fever vaccine in emergency situations. The study will be conducted in Uganda and Kenya and the main objective is to assess the non-inferiority is seroconversion 28 days after vaccination of a fractional dose compared to full dose for each WHO-prequalified manufacturer. As secondary objectives the study will assess seroprotection 10 days and 1 year after vaccination, to assess rapidity and persistence of protective antibody levels; describe the geometric mean titre and the change in neutralizing antibody on Day 28 days after vaccination with fractional and full doses; and assess the occurrence of adverse events and serious adverse events (SAE) during 28 days after administration of fractional and full doses.

The study consists of a randomized non-inferiority trial. The study aims to start in April 2017 in the two sites and aims to recruit 960 adults. Results for the main outcome will be reviewed by the study Data and Safety Monitoring Board and one vaccine

Detailed Summary:

Yellow fever (YF) is a mosquito-borne viral disease that is endemic in 34 countries in the African region and 14 in South America. YF virus infection can be asymptomatic or cause a wide spectrum of disease, from mild symptoms to severe, potentially lethal illness with jaundice, renal failure and haemorrhage. The vast majority of reported cases and deaths occur in sub-Saharan Africa where yellow fever is a major health problem occurring in epidemic patterns. There is no specific treatment for yellow fever infection. However, YF vaccine is shown to be very effective for outbreak control as well as for the prevention of outbreaks. YF vaccination confers protection in most vaccinated individuals and this is considered to be life-long.

In 2016, YF outbreaks occurred in Africa (Angola, Democratic Republic of Congo (DRC) and Uganda) as well as in South America (Brazil, Colombia and Peru). Factors such increased urbanization in poor areas without proper water and sanitation systems and population movements, have the potential to contribute to increasing incidence of yellow fever and large epidemics. In July 2016, the demand for yellow fever vaccines in response to the large urban outbreaks occurring concurrently and the risk of further spread through the African continent and even to Asia, was larger than the available supply. In this situation, the World Health Organization (WHO) developed recommendations for the use of fractional-dose of yellow fever vaccine as a dose-sparing strategy. This strategy consisted on delivering 1/5th of the conventional dose and was used to vaccinate over 7 million people in Kinshasa, the capital city of DRC.

The evidence to recommend the use of fractional dosing was based on a limited number of clinical studies. However this was considered sufficient to provide emergency recommendations. In order to
Sponsor: Epicentre

Current Primary Outcome: Seroconversion by PRNT50 (Plaque Reduction Neutralization Test 50 value) [ Time Frame: 28 days post-vaccination ]

Original Primary Outcome: Seroconversion by PRNT50 [ Time Frame: 28 days post-vaccination ]

Current Secondary Outcome:

• Assessment of protection by PRNT50 (Plaque Reduction Neutralization Test 50 value) [ Time Frame: 10 days post-vaccination ]
  Plaque reduction neutralization test will be used to quantify the titer of neutralising antibody for the virus
• Duration of immunity [ Time Frame: 1 year post-vaccination ]
  Assessment of duration of immunity at 1 year after vaccination
• Assessment of adverse events and serious adverse events [ Time Frame: 28 days post-vaccination ]
  Brighton collaboration definitions will be used to assess adverse events following immunization. The investigation of SAE will follow WHO guidelines for "Detection and investigation of serious adverse events following yellow fever vaccination" WHO 2010

Original Secondary Outcome:

• Assessment of protection by PRNT50 [ Time Frame: 10 days post-vaccination ]
• Duration of immunity [ Time Frame: 1 year post-vaccination ]
• Assessment of adverse events and serious adverse events [ Time Frame: 28 days post-vaccination ]
  Brighton collaboration definitions will be used to assess adverse events following immunization. The investigation of SAE will follow WHO guidelines for "Detection and investigation of serious adverse events following yellow fever vaccination" WHO 2010

Information By: Epicentre

Dates:
Date Received: December 7, 2016
Date Started: June 2017
Date Completion: May 2019
Last Updated: April 27, 2017
Last Verified: April 2017