A phase II study to evaluate the safety and efficacy of topical 3% amphotericin B cream (Anfoleish) for the treatment of uncomplicated cutaneous leishmaniasis in Colombia

Background: Pentavalent antimonials (Sb5) are the first-line drugs for treating cutaneous leishmaniasis in Colombia; however, given problems with toxicity, compliance, availability, and cost, it is imperative to look for better therapeutic options. Intravenous amphotericin B (AmB) has been used extensively to treat visceral leishmaniasis; however, evidence on its topical use for cutaneous leishmaniasis is limited. Anfoleish is a topical formulation based on 3% AmB, which was developed following GMP standards by HUMAX and PECET. Anfoleish was shown to be safe and efficacious in animal model and in an open label study in CL patients. Hereafter we show the results of the first controlled and randomized study assessing the safety and efficacy of Anfoleish administered topically, two or three times per day for 28 days, for the treatment of non-complicated cutaneous leishmaniasis in Colombia. Methods: An open-label, randomized, non-comparative phase Ib/II clinical trial was performed. Adult volunteers with a parasitologically confirmed diagnosis of cutaneous leishmaniasis were randomly allocated to receive Anfoleish cream either 3 (TID group) or 2 (BID group) times per day for 4 weeks. Results: 80 out of 105 subjects screened were included in the study. In intention to treat analysis, final cure was observed in 13 (32.5%) out of 40 subjects (IC 95% = 20.1–48) and in 12 (30%) out of 40 subjects (IC 95% = 18.1–45.5) in the BID and TID group respectively. In the per protocol analysis, cure rates were 39.4% (n = 13) (IC 95% = 24.7–56.3) and 35.3% (n = 12) (IC 95% = 21.5–52.1) in the BID and TID groups respectively. Anfoleish proved to be safe, and the few adverse events reported were local, around the area of application of the cream, and of mild intensity. Conclusion: Anfoleish showed to be a safe and well-tolerated intervention. Its efficacy results however do not support at this time continuing with its clinical development or recommending it for the treatment of CL. Additional, studies to improve its current formulation are needed before thinking in conducting additional studies in patients. Trial registration: Registered in clinicaltrials.gov NCT01845727. Author summary: Cutaneous leishmaniasis is a disease caused by Leishmania parasites and transmitted by sand flies. It is a complex disease and is underresearched disease, that depending on the parasite species, can take multiple forms, which can be less or more aggressive. It manifests as ulcers, nodules or other lesions mostly on the face and extremities. Cutaneous leishmaniasis is found across South and Central America, Africa, Europe, the Middle-East and Asia, and generally it is classified into forms of the Old World and New World. Colombia now ranks second after Brazil, with around 15,000 reported cases per year. Most cases are caused by L. panamensis, L. braziliensis, and L. guyanensis. Since the 1940’s, Pentavalent antimonials (Sb5) parenteral treatment have been the first-line of drugs for treating cutaneous leishmaniasis, however, the cost, the variable efficacy and the toxicity associated with its use, make it necessary to search for new treatments. Although there are other approved treatments for the disease, They also show issues of adverse reactions, and are used is mainly as a second option of treatment depending on the availability of these in health programs. Topical therapy of cutaneous leishmaniasis is a promising approach. Anfoleish is a cream than developed in Colombia. In this paper, we report the results of phase Ib/II, randomized trial in Colombia to assess the safety and therapeutic response of topical Anfoleish for the treatment of Cutaneous leishmaniasis.