A Phase IIa/IIb clinical trial to evaluate the therapeutic efficacy of ChAd63-KH vaccine in patients with persistent post kala-azar dermal leishmaniasis (PKDL)” (360G-Wellcome-108518_Z_15_Z)

Translation Fund Award to Professor Paul Kaye, University of York Visceral leishmaniasis (or kala azar) is a chronic and life threatening parasitic disease caused by infection with Leishmania donovani and L. infantum. There are approximately 400,000 new cases each year, mainly in Sudan, South Sudan, India, Bangladesh, Ethiopia and Brazil, with a case fatality rate of ~10%. Although a handful of drugs are available, efficacy varies geographically and emerging drug resistance is a major threat. In East Africa and South East Asia, the lack of complete efficacy of these drugs can also lead to patients developing a chronic and stigmatizing skin disease, called post kala azar dermal leishmaniasis (PKDL). The development of new preventative and/or therapeutic measures to combat this infection is therefore a major international research priority. An international research team, funded by the Wellcome Trust and led by Professor Paul Kaye at the University of York, has developed a new adenovirus-based vaccine for visceral leishmaniasis, which has shown efficacy in animal models and safety and immunogenicity in a human Phase I clinical trial. This new study will allow the team to evaluate the vaccine for safety and therapeutic efficacy in Sudanese patients with persistent PKDL. The study will first identify a safe dose of the vaccine to use in adults and children with PKDL and then proceed to test whether a single dose therapeutic immunization can stimulate immune responses leading to clinical cure or reduction in symptoms. If successful, these clinical trials will determine whether therapeutic vaccination has the potential to be developed further, as an alternative treatment option for patients with PKDL and perhaps other forms of leishmaniasis.