A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Background. Recurrent vulvovaginal candidiasis (RVVC) is a problematic form of mucosal Candida infection, characterized by repeated episodes per year. Candida albicans is the most common cause of RVVC. Currently, there are no immunotherapeutic treatments for RVVC. Methods. Tis exploratory randomized, double-blind, placebo-controlled trial evaluated an immunotherapeutic vaccine (NDV-3A) containing a recombinant C. albicans adhesin/invasin protein for prevention of RVVC. Results. Te study in 188 women with RVVC (n = 178 evaluable) showed that 1 intramuscular dose of NDV-3A was safe and generated rapid and robust B- A nd T-cell immune responses. Post hoc exploratory analyses revealed a statistically signifcant increase in the percentage of symptom-free patients at 12 months afer vaccination (42% vaccinated vs 22% placebo; P = .03) and a doubling in median time to frst symptomatic episode (210 days vaccinated vs 105 days placebo) for the subset of patients aged <40 years (n = 137). Te analysis of evaluable patients, which combined patients aged <40 years (77%) and =40 years (23%), trended toward a positive impact of NDV-3A versus placebo (P = .099). Conclusions. In this unprecedented study of the effectiveness of a fungal vaccine in humans, NDV-3A administered to women with RVVC was safe and highly immunogenic and reduced the frequency of symptomatic episodes of vulvovaginal candidiasis for up to 12 months in women aged <40 years. Tese results support further development of NDV-3A vaccine and provide guidance for meaningful clinical endpoints for immunotherapeutic management of RVVC.