An open-label phase 3 study of Isavuconazole (VITAL): focus on patients with mixed fungal infections

G. Rahav, I. Oren, K. M. Mullane, R. Maher, M. Lee, B. Zeiher, A.-H. Schmitt-Hoffmann, M. Giladi

Abstract: 

Objective: Isavuconazole (ISA) is a water-soluble, broad-spectrum triazole antifungal developed for the treatment of invasive fungal disease (IFD). We present outcomes and safety in ISA-treated patients from the Phase 3 VITAL trial with IFD caused by multiple (>1) fungal pathogens.
Methods: VITAL (NCT00634049) was a multi-centre, open-label, single-arm trial that evaluated safety and efficacy of ISA treatment of IA in patients with renal impairment, or in patients with IFD caused by emerging moulds, yeasts, and dimorphic fungi. Patients received ISA 200 mg (IV/oral) TID for 2 days followed by 200 mg QD (IV/oral) to end of treatment (EOT; ≤180 days). Proven/probable/possible IFD (EORTC/MSG criteria) were determined by an independent data-review committee (DRC). DRC-assessed overall response at EOT was reported.
Results: Of 146 patients in VITAL receiving ISA, 134 patients had various IFDs, and only 15 patients had proven/probable IFD caused by multiple fungal pathogens (refractory to previous antifungal therapy, n=10; primary ISA therapy, n=5) (Table). Pathogens identified included: Aspergillus, Rhizopus, Fusarium, Mucormycetes, Absidia, Scedosporium, Mucor, Verticillium, Phaeoacremonium, Fonsecaea, Candida, Alternaria, Cladosporium, and Trichosporon. Median (range) ISA treatment duration was 97 (6–544) days. Eight (53%) patients survived beyond Day 180 and 8 (53%) patients had partial or stable response to ISA. Four (27%) patients experienced SAEs attributed by the investigator to ISA.
Conclusions: Successful outcomes were observed in patients receiving ISA as salvage or primary therapy for IFD involving multiple fungal pathogens. No new ISA-related safety issues were observed.

Tables: 

abstract No: 

P0230
    • ECCMID 25th (2015)