Assessing safety, efficacy and transmission blocking properties of the new anti-malarial KAF156 combined with a new formulation of lumefantrine in children and adults with uncomplicated Plasmodium sp. malaria in West and Central Africa (WANECAM II)
WANECAM II is focusing on a new antimalarial drug, KAF156 (ganaplacide), from an entirely novel chemical class. Its mode of action appears to be different to that of artemisinin-based drugs, and it is highly active against several stages of the malaria parasite and against Plasmodium vivax as well as P. falciparum. It is being teamed up with a new formulation of an existing antimalarial, lumefantrine, that is less affected by food intake and would allow the new combination to be given as a single dose.
The WANECAM II team is carrying out a phase IIb trial with groups of children from 12 years down to six months of age. A phase III trial will then be conducted in adults and infants of six months of age and older.
This objective will be achieved through:
- to accelerate the clinical development and registration of this new innovative anti-malarial drug candidate KAF156 combined with a new formulation of lumefantrine (solid dispersion formulation, LUM-SDF) and evaluate its safety, tolerability and efficacy in the treatment of uncomplicated P. falciparum malaria in children 6 months and above and adults in West and Central Africa;
- to develop capacities in clinical research, laboratory skills and infrastructure in sub-Saharan Africa by building a new clinical research team in Niger, improving targeted capacities and other infrastructure in all teams involved as well as training young African and European scientists;
- to strengthen and expand the existing previously EDCTP funded West African network for clinical trials of antimalarial drugs (WANECAM) through intra-European, European-African and intra-African collaborative activities.
Despite major progress in the past decade malaria remains a major public health problem in sub-Saharan Africa, where 90% of the 216 million new cases and 91% of the 445 000 deaths from malaria in 2016 occurred. West and Central Africa account for nearly 2/3 of the morbidity and mortality currently attributable to Plasmodium falciparum malaria. Artemisinin-based combination therapies (ACT) are a cornerstone of our strategy for controlling and eventually eliminating malaria. However, reduced responsiveness/resistance to artemisinin derivatives and to ACTs is now an increasing problem in South-East Asia. In Africa, although artemisinins remain efficacious, failure of ACTs due to resistance to partner drugs is also of concern. Therefore, it is of utmost importance to develop new antimalarial drugs that are from novel chemical classes and thus can break resistance.
KAF156, an imidazolepiperazine, is one of the leading candidates in the antimalarial drug development pipeline. It is a novel antimalarial drug being developed by Novartis with scientific and financial support from MMV (in collaboration with the Bill & Melinda Gates Foundation). Its structure and mode of action are different from currently marketed antimalarial drugs and other antimalarial drug candidates. The Solid Dispersion Formulation of lumefantrine (LUM-SDF) is an improved form of lumefantrine that is less susceptible to food effects and can be used once daily instead of twice daily. The new combination of KAF156 with LUM-SDF is expected to be fast acting, fully curative, improve patient adherence and can potentially reduce malaria transmission.
Building on the successful experience of effectively contributing to line extension and label variation of Pyramax during EDCTP1 through our WANECAM I consortium (www.wanecam.org), here we propose to substantially advance the clinical development of KAF156. We will also build a new clinical research team in Niger, a grossly underrepresented country in the African research landscape, and improve targeted capacities and infrastructure in all teams involved. We will train young African and European scientists through short courses, MSc and PhD training. All of these activities will be undertaken in the context of networking, team-building, leadership development and community engagement schemes that will involve intra-European, European-African and intra-African collaborative activities. By the end of the five years of this project, we intend to contribute to the registration of KAF156/LUM-SDF through stringent regulatory health authorities, increase biomedical research capacity in the Consortium and effectively promote networking among our respective teams.