Rezafungin Continues to Put Up Positive Results in Phase 1 & 2 Clinical Trials
Positive safety and efficacy results have been seen across 2 different dosing regimens as well as for any effects on QT prolongation.
Additional data recently released on the phase 2 STRIVE trial for rezafungin reveal positive safety and efficacy results on 2 dosing regimens for the drug, with both regimens providing therapeutic exposures substantially above those that are needed to eradicate Candida infections. Furthermore, results of a phase 1 QT clinical trial on rezafungin revealed that single doses of the medication—up to 1400 mg intravenously (IV) “had no significant effect on QT prolongation or on any of the other cardiac conduction parameters tested,” according to a press release on the trial results.
For the phase 2 trial, a total of 92 patients were enrolled in the microbiological intent-to-treat (mITT) population. These patients were then randomized into 1 of 2 rezafungin arms (Group 1 and Group 2), or a comparator arm (Group 3). According to the press release, “in the 2 rezafungin arms of the trial, patients received either 400 mg of rezafungin administered IV once weekly for 2 to 4 weeks (Group 1), or 400 mg for the first week followed by 200 mg once weekly for up to 4 weeks in total (Group 2).” Patients in the comparator arm received caspofungin, “IV according to the approved prescribing information, with an optional step down to oral fluconazole.”
Of note is that the intent of the trial was to provide data on dosing selection for a phase 3 study, and therefore, it was not statistically powered enough to demonstrate non-inferiority or superiority.
Previously reported topline data on the phase 2 trial showed that all primary objectives were met; once-weekly IV dosing of rezafungin was generally well tolerated and safe in patients with candidemia or invasive candidiasis. In addition, the results revealed, “evidence of the efficacy of rezafungin, which was defined in the trial by clearance of Candida from the blood or other normally sterile sites, resolution of signs related to the infection, investigator assessment of clinical response and overall survival,” according to the press release.
Because the investigators found an imbalance in the number of patients with indeterminate responses in Group 1, further evaluations were performed and these successes and failures, as well as reasons for each are available via the press release.
Peter Pappas, MD, professor of medicine in the Division of Infectious Diseases at the University of Alabama in Birmingham, and chair of the Mycoses Study Group spoke about these results in a press release, stating, “These data from STRIVE are very encouraging. What they have demonstrated is that rezafungin appears to be safe and well tolerated, and the overall response rates achieved in the 2 rezafungin dosing arms were similar as predicted. Indeterminate responses in clinical studies are not unusual, despite investigators’ best efforts to avoid them. I am very pleased that the data support advancing rezafungin into future phase 3 trials in both treatment and prophylaxis to address very real, clinical needs we experience every day.”
The additional phase 1 trial was a “single-center, randomized, comparative study of the effect of single-ascending doses of rezafungin, IV placebo, and a single oral dose of moxifloxacin (positive control) in healthy adult subjects,” according to the press release. Assessment of the effects of rezafungin on QT interval was set as the primary objective; assessment of other cardiac conduction parameters were set as secondary objectives.
A total of 60 healthy adults were enrolled in the trial. These adults were enrolled into 2 cohorts, with each group having 3 dosing groups. Cohort 1 patients received either 600 mg IV of rezafungin, or IV placebo, or oral moxifloxacin. Cohort 2 patients received either 1400 mg IV of rezafungin, or placebo, or oral moxifloxacin. According to the press release, “the rezafungin doses “were selected to achieve peak concentrations up to 2.5-fold higher than the expected peak concentration of the 400 mg dose given once-weekly for 3 weeks.”
Trial results revealed that “rezafungin in single doses up to 1400 mg IV had no significant effect on QT prolongation or on any of the other cardiac conduction parameters tested.”
Contagion® will be following upcoming trials on rezafungin and will continue to provide readers with the latest information as it is released.