The fungal immunotherapeutic vaccine NDV-3A may be safe and highly effective when administered to women with recurrent vulvovaginal candidiasis (RVVC), according to a study recently published in Clinical Infectious Diseases.1
At this time, RVVC is treated with repeated or prolonged antifungal therapy, which has variable efficacy, adds selective pressure for antifungal resistance, and poses specific safety concerns.2,3 Therefore, the management of RVVC would be substantially improved with a safe and effective vaccine. This randomized, double-blind study (ClinicalTrials.gov identifier: NCT01926028) evaluated the immunotherapeutic vaccine NDV-3A containing a recombinant Candida albicans adhesion/invasion protein for prevention of RVVC.
From July 2013 to May 2016, 188 women (aged 18-55 years) using an approved method of birth control and presenting with a clinically diagnosed active VVC episode at time of enrollment were included among 20 study sites in the United States. An active VVC episode was defined as having a composite sign and symptom score of 3 (range, 0-18), a vaginal swab culture-positive for C albicans, and at least 2 episodes of vaginitis during the 12 months before the current episode, 1 of which was documented by a diagnostic test specific for Candida.
Patients received 3 doses of 150 mg oral fluconazole taken on days −14, −11, and −8. Those with sign/symptom scores of 3 at day 0 left the study and were treated by their physician; those with combined sign/symptom scores of <3 were randomly assigned to a single intramuscular dose of either vaccine or placebo and were given 3 additional 150-mg doses for near-maximum immune response to the vaccine with minimal chance of influence of an active Candida colonization on days 0, 7, and 14.
Results suggested that 1 intramuscular NDV-3A dose was safe and generated rapid B- and T-cell immune responses. In addition, post hoc exploratory analyses showed an increase of symptom-free patients at 12 months after vaccination compared with placebo (42% vs 22%; P =.03). Among patients aged <40 years (n=137), analyses showed a doubling in median time to first symptomatic episode (210 days vaccinated vs 105 days placebo). Furthermore, the analysis of evaluable patients, which combined patients aged 40 years (23%) and <40 years (77%), suggested a positive effect of NDV-3A compared with placebo (P =.099).
NDV-3A showed comparable adverse events compared with placebo. NDV-3A recipients showed slightly higher frequency in specific injection site reactions, which resolved in a few days, than placebo recipients, but these results were not statistically significant, although it did suggest elevated reactogenicity of NDV-3A.
Overall, the study authors conclude that because results showed NDV-3A to be safe and highly immunogenic in women with RVVC, while it reduced the frequency of symptomatic episodes for up to 12 months, “these results support further development of NDV-3A vaccine and provide guidance for meaningful clinical endpoints for immunotherapeutic management of RVVC.”
Disclosures: Several authors reported being employees and shareholders of NovaDigm Therapeutics.
1. Edwards JE Jr, Schwartz MM, Schmidt CS, et al. A fungal immunotherapeutic vaccine (ndv-3a) for treatment of recurrent vulvovaginal candidiasis-a phase 2 randomized, double-blind, placebo-controlled trial [published online April 25, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy185
2. Howley MM, Carter TC, Browne ML, Romitti PA, Cunniff CM, Druschel CM; National Birth Defects Prevention Study. Fluconazole use and birth defects in the National Birth Defects Prevention Study. Am J Obstet Gynecol. 2016;214:657.e1-657.e9.
3. Marchaim D, Lemanek L, Bheemreddy S, Kaye KS, Sobel JD. Fluconazole-resistant Candida albicans vulvovaginitis. Obstet Gynecol. 2012;120:1407-1414.