Candidemia

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called Fosmanogepix) for the potential treatment of candidemia and/or invasive candidiasis, a life-threatening fungal infection caused by several species of yeast called Candida. The study is seeking patients who have a diagnosis of candidemia and/or invasive candidiasis. Two-thirds of all patients will receive the study medication fosmanogepix Intravenous (IV) infusion followed by optional fosmanogepix tablets. One-third of all patients will receive a standard of care regimen of caspofungin Intravenous (IV) infusion followed by optional fluconazole capsules. Fosmanogepix or caspofungin will first be given as an Intravenous (IV) infusion directly into a vein in the arm each day at the study clinic. Fosmanogepix tablets or fluconazole capsules will be taken orally by mouth daily either at the study clinic, or at home if patients are well enough to be discharged from the hospital. The treatment effect in patients receiving fosmanogepix to those receiving caspofungin/ fluconazole will be compared. The primary aim is to show that fosmanogepix is not inferior (not worse) to caspofungin/ fluconazole with a noninferiority margin of 15%. The duration of study treatment and number of study visits will vary depending on how long the patient will be treated for the infection. Treatment will continue for a maximum of 6 weeks depending on when the infection is cleared and whether other symptoms related to the infection have improved. There will also be a follow-up visit 6 weeks after the study treatment was stopped.

The goal of this clinical trial is to assess whether a seven-day course of standard of care (echinocandin) antifungal therapy is non-inferior to a 14-day course of echinocandin antifungal therapy in patients with uncomplicated candidemia in terms of clinical, mycologic, adverse events and all cause mortality.

Scientific justification Candidemia is a major public health problem. In France, the 30-day mortality of candidemia varies from 30% to 50% depending on the need for intensive care and it has not decreased in 30 years. The duration of treatment for candidemia was set at a minimum of 14 days after the last positive blood culture following the Rex trial (1) comparing the efficacy of fluconazole vs amphotericin B where the minimum duration of treatment was imposed. The risk of a too short treatment is the absence of control of the candidemia with secondary dissemination, in particular cardiac and ophthalmic. A retrospective study looking at the risk of ophthalmologic complications after candidemia found among the 21/78 treated for less than 14 days, only one case of late endophthalmitis in a patient who had only been treated for 48 hours. In addition, the prolonged duration of antifungals exposes the risk of selection of more resistant strains with a modification of the flora, with the possibility of acquiring resistance as early as 8 days of treatment with caspofungin, and has a greater liver toxicity. There is no prospective study on the direct impact of antifungal agents (type of antifungal agent and duration) on the mycobiota.