Treating eumycetoma is a challenge. Currently, the antifungals ketoconazole and itraconazole are the only therapies available but these are expensive, ineffective, and have serious side effects. Patients often have to undergo amputation, and often more than once, sometimes resulting in death. Safe, effective antifungal agents that are appropriate for use in rural settings are urgently needed.

In 2017, the Mycetoma Research Centre (MRC), a WHO Collaborating Centre, in Khartoum, Sudan, began enrolling patients in the first-ever double-blind, randomized clinical trial for eumycetoma (fungal mycetoma). The trial is studying the efficacy, in moderate-sized lesions over 12 months, of weekly treatment with fosravuconazole, versus the current standard of care, daily treatment with itraconazole.

Fosravuconazole, an orally bioavailable azole developed for onychomycosis by Eisai Ltd (Japan) that is also under development by DNDi for Chagas disease, could be an effective and affordable treatment for eumycetoma. Its pharmacokinetic properties are favourable, and its toxicity is low. Fosravuconazole, a prodrug, is rapidly converted to ravuconazole, which has been shown to have potent in vitro activity against one of the causative agents of eumycetoma, Madurella mycetomatis.

Project updates

2019

The first-ever double-blind study to determine whether the new chemical entity fosravuconazole could be an effective and affordable treatment for eumycetoma is ongoing. By January 2020, 101 patients had been enrolled in the study, which should reach the targeted enrollment of 165 patients by the end of 2020. A Data and Safety Monitoring Board (DSMB) meeting was held in 2019 after the study reached the threshold for interim analysis (84 participants). The DSMB reviewed study data and decided to continue with all three treatment arms (200 mg vs 300 mg of fosravuconazole weekly vs daily itraconazole).

2018

Following slower than anticipated recruitment, a protocol review and amendment was conducted in 2018 to extend the inclusion criteria in relation to lesion size and site, and age range of participants. By January 2019, 84 patients had been enrolled, reaching the threshold for interim analysis. This analysis will determine which of two treatment arms will be retained for the remainder of the trial (200mg vs 300mg of fosravuconazole weekly). 

2017

After receiving regulatory and ethical approval in March 2017, the Mycetoma Research Centre, a WHO Collaborating Centre, began recruiting patients into the first-ever double-blind, randomized Phase II/III clinical trial for eumycetoma. The clinical trial, which plans to recruit 138 patients, evaluates the efficacy of the anti-fungal fosravuconazole in moderate lesions in comparison with the current treatment, itraconazole.

The primary objective of this single-centre study conducted in Sudan is to demonstrate the superiority of fosravuconazole over itraconazole after 12 months’ treatment. By the end of 2017, 20 patients had been enrolled into the trial, a pace of enrolment that was slower than anticipated. In 2018, a satellite site will be established to screen more patients and refer them for treatment and care

2016

Protocols of the phase II/III aiming at assessing the comparative efficacy, safety, and tolerability of fosravuconazole in patients with eumycetoma caused by Madurella mycetomatis.were finalized in 2016 and recruitment of patients (with a target of 136 participants) should start early 2017. An interim analysis will be conducted at three months.

2015

DNDi is currently preparing for a Phase II/III randomized controlled trial that will be conducted with the WHO Collaborating Centre on Mycetoma in Khartoum to study the efficacy of fosravuconazole in moderate lesions in comparison with the current treatment, itraconazole. The primary objective of this double-blind, randomized, single-centre study will be to demonstrate superiority of fosravuconazole over itraconazole after 12 months’ treatment in patients with eumycetoma caused by Madurella mycetomatis.