Dataset Information

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.

SUBMITTER: Thompson GR

PROVIDER: S-EPMC8662762 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract Background Rezafungin (RZF) is a novel echinocandin in Phase 3 development for treatment of candidemia and invasive candidiasis (IC) and for prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis in blood and marrow transplant recipients. This analysis of the completed Phase 2 STRIVE trial (NCT02734862) of RZF treatment was conducted to evaluate outcomes based on baseline pathogen and susceptibility. Methods In STRIVE, adults (≥ 18 y) with systemic signs and mycological evidence of candidemia and/or IC were randomized to either RZF once weekly or caspofungin (CAS) once daily for ≥ 14 days (Fig. 1). The primary efficacy endpoint was Overall Response (resolution of clinical signs of infection + mycological eradication) at Day 14. For this analysis, outcomes by treatment group were stratified by Candida species and by its in vitro susceptibility (CLSI broth microdilution MIC values; M27-Ed4). Figure 1. Treatment Groups of the Phase 2 STRIVE Trial Results A total of 196 Candida isolates were recovered from 183 patients across all treatment groups (Fig. 2). C. albicans was the most common species, followed by C. glabrata, C. parapsilosis, and C. tropicalis; non-albicans Candida comprised 54% of all baseline isolates (Fig. 2). Among all clinical isolates, MIC distributions and ranges for RZF were generally lower than or comparable to those for CAS (Table 1). The rate of Overall Response (as defined above) against C. parapsilosis was lower for CAS than for RZF (Table 2). Overall, outcomes by Candida species and MIC did not appear to be affected by MIC values for either RZF or CAS (Table 1). Figure 2. Candida Species Distribution and MIC ranges in the Phase 2 STRIVE Trial (mITT) Table 1. Overall Response Rates (%) for Most Frequently Isolated Candida Species at Baseline by Treatment Group and MIC Values (mITT) Table 2. Overall Response Rates (%) for Most Frequently Isolated Candida Species at Baseline by Treatment Group (mITT) Conclusion This analysis demonstrated RZF efficacy across multiple Candida species. RZF outcomes were similar to or better than those for CAS regardless of species identified. There was no clear correlation between increased MICs and clinical outcomes although, based on MICs, all isolates exhibited a wild-type in vitro susceptibility profile. These findings from STRIVE, together with future analyses from the ongoing Phase 3 trial of RZF treatment of candidemia and IC (ReSTORE; NCT03667690), will further our understanding of the relationships between MIC values and clinical outcomes in patients with candidemia or IC. Disclosures Jeffrey B. Locke, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Rolando Viani, MD, Cidara Therapeutics, Inc. (Employee, Shareholder) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Mahmoud Ghannoum, PhD, Amplyx (Grant/Research Support)Cidara (Grant/Research Support)Scynexis (Consultant, Grant/Research Support) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder)

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