MAMS4CL

The challenge

Cutaneous leishmaniasis is not the deadliest form of infection with the Leishmania parasite (visceral leishmaniasis is more severe), but it nevertheless has a major impact, particularly in East Africa, where it is most common. It leads to chronic scarring skin lesions that can interfere with daily life, affect employability and generate social stigma. The condition can therefore have a major impact on people’s quality of life and mental well-being.

The limited number of treatments available for cutaneous leishmaniasis adds to its impact. The most effective therapy involves repeated intramuscular injections with a powerful drug, sodium stibogluconate, which is painful and can trigger a variety of side effects. It is likely that fewer than 1 in 10 patients with cutaneous leishmaniasis actually receive treatment.

The good news is that several new treatments are in development. However, even if sufficient trial capacity existed, it would be very costly to test all in separate trials.

The project

To overcome this bottleneck and advance potentially more effective therapies for cutaneous leishmaniasis, the MAMS4CL project is establishing the infrastructure for a ‘multi-arm, multi-stage’ (MAMS) trial. It focuses on Ethiopia, a country with a particularly high disease burden.

A MAMS study enables multiple drugs to be compared in a single study. A consultation is being organised to determine the final set of compounds to be evaluated, but several options have some positive data available. These include:

• Miltefosine: a more convenient oral medication, but one with significant gastrointestinal side effects.
• Liposomal formulations of amphotericin B: already used to treat visceral leishmaniasis.
• Paramomycin: used alongside sodium stibogluconate to treat visceral leishmaniasis.
• Combinations of the above drugs.

In the first stage of the MAMS trial, initial safety and efficacy data will be collected on the five selected options. A maximum of two options meeting pre-set safety and efficacy criteria will then progress to stage 2, where a full comparison will be made against the current treatment, sodium stibogluconate.

The project will also include pharmacokinetic studies to identify drug levels associated with successful responses, providing additional information on optimal dosing. Other work will include discussions with local communities on their understanding of the condition and perceptions of current treatments.

Impact

The MAMS4CL project will create a platform for evaluating existing and emerging treatments for cutaneous leishmaniasis. It will:

• Enable multiple possible treatment options to be tested in a single trial.
• Generate directly comparable data on the safety and efficacy of the different options.
• Establish a platform for the rapid evaluation of newly developed agents.

The MAMS4CL project will accelerate the development of new treatments for this common, neglected tropical disease and, potentially, identify a safer and more effective alternative to an existing treatment with significant drawbacks.