Current therapies for onychomycosis are inadequate due to the low efficacy of topical products or poor safety profile of oral therapies, which often require monitoring of liver transaminases. VT-1161 is a novel inhibitor of cytochrome P51 (CYP51), with nearly 2000-fold greater selectivity for fungal CYP51, and minimal activity against off-target human CYPs. It exhibits favorable oral pharmacokinetics with sustained plasma and nail concentrations combined with an excellent safety profile. VT-1161 has demonstrated potent activity against Trichophyton rubrum, T. mentagrophytes, and yeast.
We report the final results of RENOVATE, a Phase. 2b study to evaluate the efficacy and safety of oral VT-1161 in patients with toenail onychomycosis
The study enrolled 259 patients (18-70 years) with a clinical diagnosis of moderate to severe distal lateral subungual onychomycosis (DLSO) defined as having 25% to 75% nail involvement at baseline and positive KOH and culture for dermatophytes, performed at a central laboratory. Patients had at least 2 mm clear nail measured from the proximal nail fold and a nail thickness of no greater than 3 mm measured at the distal end. Patients who were breast feeding, pregnant or intended to become pregnant were excluded. Those who received systemic antifungal therapy for 3 months, or a topical applied to their toenail or feet for 1 month prior to entry were also excluded.
Patients received 300 or 600 mg oral VT-1161 or matching placebo once-weekly for either 10 or 22 weeks, following 14-days of a daily loading dose.
The percent nail involvement of the target toenail was assessed by the Principal Investigator (PI) at each clinic visit.
Dermatophyte infection was assessed by KOH wet mount microscopy and culture of the subungual debris in the target toenail; both conducted at the central mycology Lab.
Efficacy Endpoints and Assessments:
The primary efficacy endpoint was the proportion of patients with complete cure at Week 48, defined as both clinical cure (0% nail involvement) and mycological cure (negative KOH stain and negative culture). The secondary endpoints were complete cure at Week 60, mycological and clinical cure at Week 48 and/or 60. Efficacy assessment are presented for 259 patients in the intent to treat (ITT) population defined as all patients who were randomized.
Adverse events (AE) were collected as reported by patients as well as by any clinically significant changes in blood chemistry. ECGs performed at each visit.
Study was designed to provide >90% power to show a treatment difference of 25% between active treatment and placebo in complete cure rates at Week 48 (Fisher's exact test, two-sided alpha=0.05; assuming 5% of placebo patients are completely cured)