Enrolment in the Phase III study was completed, with 127 participants included: 64 in the miltefosine monotherapy arm, and 63 in the miltefosine + thermotherapy arm. Patient demographics and baseline characteristics were similar across both treatment arms. Most adverse events reported were mild and aligned with the expected safety profile of the study interventions. The combination arm was shown to be non-inferior to standard miltefosine monotherapy in the per-protocol analysis at day 90 (65.5% vs. 75.0%, respectively). However, the combination treatment appears to be more efficacious than miltefosine alone for lesions due to L. braziliensis.

The last patient in the Phase III study was enrolled in August. A total of 182 patients were enrolled, including 63 in the miltefosine monotherapy arm, 63 in the combination thermotherapy and miltefosine arm, and 56 in the meglumine antimoniate arm prior to its removal from the protocol. A new protocol amendment was made to address WHO recommendations for the prevention, early detection, and management of ocular adverse events in patients exposed to miltefosine and submitted to all ethics committees in early March.

To align with the new treatment guidelines adopted by the World Health Organization and Pan American Health Organization in July 2022, and as requested by local investigators, the study protocol was amended to remove the arm of the study using antimonial therapy. This is in line with DNDi’s position promoting therapies that are less toxic and easier to administer in field settings. The enrolment of patients continued throughout the year and is expected to be completed in the second quarter of 2023.   

The Phase III trial was initiated at four of the five study sites in 2021 with 67 patients enrolled, and no serious adverse events were recorded during the year. Approval to initiate the trial at the study site in Bolivia has been obtained with the study initiation visit planned for the first quarter of 2022. New waves of COVID-19, related travel restrictions, and the decision to prioritize the medical treatment of people with COVID-19 have proven challenging, particularly with regard to the recruitment of study participants.    

Preparations for a Phase III trial at five study sites in Bolivia, Brazil, Panama, and Peru continued, although enrolment of the first patients was delayed slightly due to the COVID-19 pandemic. Patient enrolment at all five study sites is expected to begin during the first half of 2021.

Preliminary results of a Phase II study completed in April 2019 show the combination of thermotherapy with a shorter course of oral miltefosine to be significantly better than thermotherapy alone for the treatment of uncomplicated cutaneous leishmaniasis in the Americas. A Phase III study is planned to start in the second half of 2020 to compare the non-inferiority of the combination against the current recommended systemic treatments, sodium stibogluconate or miltefosine.

Recruitment of patients was completed in Peru (65 patients) and in Colombia (65 patients). The last patient six-month follow-up is expected in early 2019. Interim results supported the preparation of a Phase III study in the Americas comparing the combination therapy (thermotherapy and miltefosine) against the standard treatment (meglumine antimoniate) which comes with risks of potential toxicity. The study is being planned in four countries in Latin America.

Recruitment of patients continued in Peru with the inclusion of 41 patients, and started in Colombia with the inclusion of 21 patients (out of 130 patients in total). An interim analysis is planned in early 2018 once 65 patients have completed the day 90 follow-up visit.

At the end of 2016, official approvals were obtained, a site initiation visit conducted and the first patients were enrolled in Peru, while final approvals are expected by early 2017 for a second site in Colombia.