Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02991495 |
| Other study ID # |
YEFE_2017 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
November 6, 2017 |
| Est. completion date |
December 31, 2021 |
Study information
| Verified date |
January 2022 |
| Source |
Epicentre |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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 will be selected for
the studies in children and HIV positive adults.
Description:
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 broaden and also possibly simplify WHO recommendations of
fractional dose use in case of need for emergency campaigns, additional data is needed to
respond to the important data gaps. These include 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.
Following these data gaps, WHO called for research to be conducted.
This study aims to respond to some of the research questions that would allow to broaden 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 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 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 aims to recruit 960 adults (480 in
Mbarara, Uganda, and 480 in Kilifi, Kenya). Results for the main outcome will be reviewed by
the study Data and Safety Monitoring Board (DSMB) and if results are considered satisfactory,
the study will continue with the recruitment of 420 children in Uganda and 250 HIV infected
adults in Kenya, to assess non-inferiority of one of the WHO prequalified vaccines.
