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: This 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: The 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- and T-cell immune responses. Post hoc exploratory analyses revealed a statistically significant increase in the percentage of symptom-free patients at 12 months after vaccination (42% vaccinated vs 22% placebo; P = .03) and a doubling in median time to first symptomatic episode (210 days vaccinated vs 105 days placebo) for the subset of patients aged <40 years (n = 137). The 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. These results support further development of NDV-3A vaccine and provide guidance for meaningful clinical endpoints for immunotherapeutic management of RVVC.

Clinical trials registration: NCT01926028.

Figure 1.

Flow chart for patient participation in study NDV3A-006. Abbreviation: C. albicans, Candida albicans.

Figure 2.

Evaluation of patient and physician scores. A, Percentage of patient office visits at each patient symptom score for scheduled and unscheduled visits. B, Physician sign scores versus patient symptom scores.

Figure 3.

A, Kaplan-Meier survival plot of percentage of vulvovaginal candidiasis (VVC) recurrence-free patients, with VVC recurrence defined by a patient-reported symptom score ≥3, versus time after day 17, for per protocol population aged <40 years. For NDV-3A, n = 65; for placebo, n = 62. B, Median time to first VVC recurrence, defined by patient-reported symptom score ≥3, for each age group. Error bars reflect 1st and 3rd quartile values.