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

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.

Conditions

• Yellow Fever

Interventions

BIOLOGICAL

Stamaril, Sanofi Pasteur

1. Full dose 2. Fractional dose: one fifth (1/5)

BIOLOGICAL

Yellow fever vaccine, Bio-Manguinhos

1. Full dose 2. Fractional dose: one fifth (1/5)

BIOLOGICAL

Yellow fever vaccine, Institut Pasteur

1. Full dose 2. Fractional dose: one fifth (1/5)

BIOLOGICAL

Yellow fever vaccine, Chumakov Institute

1. Full dose 2. Fractional dose: one fifth (1/5)

BIOLOGICAL

Yellow fever vaccine, Chumakov Institute

1. Full dose 2. Fractional dose: one fifth (1/5)

BIOLOGICAL

Yellow fever vaccine, Chumakov Institute

1. Full dose 2. Fractional dose: one fifth (1/5)

Sponsors & Collaborators

• Kenya Medical Research Institute

  collaborator OTHER

• Epicentre

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

9 Months

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-11-06

Primary Completion

2018-02-21

Completion

2021-12-31

Countries

• Kenya
• Uganda

Study Locations