PREV_PKDL

Clinical development of a therapeutic vaccine for prevention of post kala azar dermal leishmaniasis

Background

The leishmaniases are poverty-related neglected diseases with a major impact on health worldwide. They affects the poorest of the poor and present a severe barrier to socio-economic development. There are 3 main forms of leishmaniases – visceral (VL, also known as kala-azar and the most serious form of the disease), cutaneous (CL, the most common), and mucocutaneous (tegumentary leishmaniasis). There is no vaccines currently licensed for any form of human leishmaniasis and the drug arsenal is limited, shows significant adverse effects and is increasingly compromised by drug resistance. 

The post kala azar dermal leishmaniasis (PKDL) usually develops after treatment for the visceral leishmaniasis. PKDL significantly affects quality of life, is often mistaken for leprosy, and can result in stigmatisation that has lifetime impact. In addition to its impact on patients, PKDL patients are also believed to be source of Leishmania infections that lead to outbreaks and epidemics of VL. Current treatments may cause serious side effects and/or only work well in some settings. Thus, prevention of PKDL represents the most clinically beneficial solution.
PKDL is an immunological disease involving a dysregulation of innate and /or acquired immunity that allows parasite persistence in the skin and sustained inflammation. A novel adenoviral-based vaccine (ChAd63-KH) that can stimulate immune responses that are known to be defective in PKDL patients has been developed and evaluated in first in human trial (1). During the course of this project, the ChAd63-KH vaccine will further be evaluated in two clinical trials in Sudan.
Additionally, to better understand the disease as well as drug and vaccine responses, multidimensional, multiparameter phenotyping will be conducted on patient cohorts recruited across the Leishmaniasis East Africa Platform (LEAP; Ethiopia, Kenya, Sudan and Uganda). A major aim of this project is to support LEAP in its ambitions, by extending its research capacity in immunology and vaccine development.  This will be achieved through a program to strengthen immunology research capacity through the development of a flow cytometry network across LEAP. This capacity strengthening will help LEAP to develop as a major force for research and training on poverty-related neglected diseases in the East African Region.  
The PREV_PDKL is part of the European & Developing Countries Clinical Trials Partnership (EDCTP2) Programme supported by the European Union
 

Objectives:

The main objective of the PREV_PKDL project is to evaluate ChAd63-KH as a vaccine for prevention of PKDL.

  1.  Conduct an open label phase IIa trial to assess safety, reactogenicity and immunogenicity of ChAd63-KH in cured VL patients in Sudan
  2. Conduct a phase IIb randomised controlled trial to evaluate safety and efficacy of ChAd63-KH for prevention of PKDL in cured VL patients in Sudan
  3. Conduct an in depth analysis of the immune set point at cure from VL in patient cohorts from Ethiopia, Kenya, Sudan and Uganda
  4. Provide novel mechanistic insights into natural history of VL / PKDL and biomarkers of PKDL development through multi-dimensional, multiparameter phenotyping;
  5. Enhance immunology research capacity in East African Region, encouraging new North-South and South-South collaboration.

References

  1. Osman M, Mistry A, Keding A, Gabe R, Cook E, Forrester S, Wiggins R, Di Marco S, Colloca S, Siani L, Cortese R, Smith DF, Aebischer T, Kaye PM, Lacey CJ.. A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH.. PLoS neglected tropical diseases. 2017;11(5): e0005527.

 

PREV_PKDL-work-package_1.jpg

Work Package (WP) organisation within the PREV_PKDL project.