Cutaneous leishmaniasis (CL) is a neglected tropical disease affecting more than one million people globally each year. In Ethiopia alone more than 40,000 people are thought to be affected annually. Infection results in stigmatising, visible, chronic, scarring skin lesions which cause permanent morbidity and significantly affect mental health, household financial stability and life chances. There is a major need for new therapeutics for CL. The current first line therapy is intramuscular sodium stibogluconate. Treatment is often ineffective, painful, and associated with adverse effects. The complexities of administration mean treatment is restricted to a small number of centralised facilities. As a result the majority of patients receive no treatment. There are a number of promising alternative and novel therapeutics for cutaneous leishmaniasis which may be more effective, more tolerable and more suitable for widespread scale up. However the evidence for these therapies is lacking and this vacuum means that policy cannot be easily changed. Our consortium of leading European and African research institutions proposes a step-change in the evidence base for CL. We will use a multi-arm, multi-stage randomised trial – MAMS4CL - to simultaneously evaluate multiple novel therapeutic interventions. This approach will reduce the time required to identify optimal treatment strategies for CL and transform the therapeutic landscape. We will identify and test five candidate interventions and assess their safety, efficacy, cost-effectiveness, and acceptability. The interventions have been selected as they offer: more tolerable administration, shorter treatment duration or home-based therapy. We will embed within MAMS4CL detailed pharmacokinetic, health economic and social science studies to provide a comprehensive analysis to inform regulators, policy makers and programmes.