Rezafungin Versus Caspofungin in a Phase 2, Randomized, Double-blind Study for the Treatment of Candidemia and Invasive Candidiasis: The STRIVE Trial

Abstract

Background: Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC).

Methods: Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤4 weeks. Efficacy assessments included overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14 (primary endpoint), investigator-assessed clinical response at day 14, and 30-day all-cause mortality (ACM) (secondary endpoints), and time to negative blood culture. Safety was evaluated by adverse events and ACM through follow-up.

Results: Of 207 patients enrolled, 183 were in the microbiological intent-to-treat population (~21% IC). Overall cure rates were 60.5% (46/76) for RZF 400 mg, 76.1% (35/46) for RZF 400/200 mg, and 67.2% (41/61) for CAS; investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. In total, 30-day ACM was 15.8% for RZF 400 mg, 4.4% for RZF 400/200 mg, and 13.1% for CAS. Candidemia was cleared in 19.5 and 22.8 hours in RZF and CAS patients, respectively. No concerning safety trends were observed; ACM through follow-up was 15.2% (21/138) for RZF and 18.8% (13/69) for CAS.

Conclusions: RZF was safe and efficacious in the treatment of candidemia and/or IC.

Clinical trials registration: NCT02734862.

Keywords: candidemia; echinocandins; rezafungin; systemic antifungal therapy.

Figure 1.

Patient flow. ITT population included all consented and randomized patients. Safety population included all patients who received any amount of study drug. The mITT population included all patients in the safety population with documented Candida infection. *Two patients who were randomized to Group 2 received caspofungin and were included in safety analyses of Group 3. Abbreviations: ITT, intent-to-treat; MITT, microbiological intent-to-treat; OD, once daily; QWk, once weekly.

Figure 2.

Time to negative blood culture following treatment with RZF versus caspofungin (P = .02; log-rank test, post hoc analysis). Abbreviations: IV, intravenous; RZF, rezafungin.