Anti-viral drugs for dengue prophylaxis and therapy.

Dengue is the world's most important arboviral disease with more than 1 million cases of severe dengue reported to the WHO annually and 2.5 billion people in over 100 countries at risk of infection. In the last 40 years, disease incidence has grown exponentially with major implications for health care resources and lost economic activity. There has never been a published therapeutic trial of an anti-viral compound for acute dengue. We propose to establish a world-first Proof-of-Concept clinical trial program - to assess in the clinic the efficacy of a pipeline of promising anti-dengue virus compounds being developed by the Novartis Institute for Tropical Diseases (NITD), Singapore. The program will be executed by the collaborative efforts of The Hospital for Tropical Diseases, Vietnam (HTD), the Wellcome Trust Major Overseas Programme in Vietnam, and the NITD. Through this collaborative effort we aim to advance the development of at least one anti-dengue virus compound to phase III efficacy trials. The project milestones are the filing of a Clinical Trial Authorization (CTA) application or equivalent in Singapore, completion of a Phase I clinical trial study (in Singapore) with the objective of establishing drug tolerability in healthy adult,s and completion of Phase IIa study (in Ho Chi Minh City, Vietnam) with the objective of demonstrating a reduction in plasma viral concentration in dengue patients. We will also register the trial with a European drug regulatory authority.