NovaDigm Therapeutics, a company developing innovative immuno-therapeutics and preventative vaccines for fungal and bacterial infections, announced the initiation of a phase 2a study evaluating NDV-3A for the reduction of Staphylococcus aureus (S. aureus) colonization in a high-risk population of military trainees. The study is being conducted with the Uniformed Services University of the Health Sciences (USU) and is enrolling US Army Infantry trainees at Fort Benning, GA. NDV-3A is the company’s lead development candidate to potentially treat antimicrobial resistant fungal and bacterial pathogens.
 
“Military recruits who are colonized with Staph aureus are at increased risk for skin infections, which can manifest in various ways including benign boils, cellulitis or more severe, invasive soft-tissue infections. The goal of this study is to reduce colonization during basic training with the NDV-3A vaccine,” said Timothy Cooke, CEO of NovaDigm. “Following on the results of this trial, a larger study would be conducted to demonstrate a reduction in skin infections. We look forward to continuing our collaboration with the Department of Defense, which plays a critical role in the support of innovative approaches to address antimicrobial-resistant pathogens.”
 
Military recruits are known to be at increased risk for S. aureus colonization and infection, attributable to a number of factors in the military training environment that may enhance the acquisition and transmission of S. aureus (e.g. limited access to hygiene during field training, crowding, etc.). The development of countermeasures to treat and prevent infections affecting medical readiness, such as those caused by S. aureus and MRSA (methicillin-resistant S. aureus), are an important focus for the military. NDV-3A has been demonstrated to be both safe and highly immunogenic in healthy human volunteers. Preclinical studies of NDV-3A have demonstrated its effectiveness in reducing the impact of bloodstream and skin infections caused by S. aureus.
 
The investigative team has initiated enrollment for the individually-randomized, double-blind, placebo-controlled clinical trial to assess the safety, immunogenicity and efficacy of NDV-3A in reducing nasal/oral acquisition of S. aureus. With a target enrollment of approximately 400 participants, infantry trainees from four classes will be recruited for the study, with receipt of NDV-3A occurring shortly after arrival at Fort Benning. Follow-up visits will occur throughout the 14-week training cycle to assess S. aureus colonization status of study participants.

NDV-3A is being developed as an immunotherapy and as a preventative vaccine for infections caused by several species of the fungus Candida, including Candida albicans, multidrug-resistant Candida auris and the bacterium Staphylococcus aureus, including MRSA. NDV-3A contains a recombinant form of the Candida albicans agglutinin-like sequence 3 (Als3) surface protein, which facilitates Candida adherence to and invasion of human endothelial cells. Als3 has been shown to have strong structural homology to surface proteins responsible for adherence of S. aureus to human endothelial cells. This finding helps to explain why NDV-3A is the first vaccine candidate to demonstrate “cross-kingdom” protection against both fungal and bacterial pathogens in preclinical studies. These studies showed that NDV-3A confers significant protection compared to placebo following bloodstream or mucocutaneous challenge with highly virulent doses of several species of Candida or several strains of Staphylococcus aureus, including MRSA strains. Two Phase 1 studies involving 200 healthy adults suggested that the vaccine is well-tolerated, safe, and induces rapid antibody and T-cell responses after a single dose, with or without alum adjuvant. A Phase 2 efficacy study of NDV-3A versus placebo in 188 patients with recurrent vulvovaginal candidiasis (RVVC) demonstrated that a single dose of NDV-3A resulted in an increase in the recurrence-free rate out to 12 months and extended the time to first recurrence for those that had a recurrence. This development program was based on research in the laboratories of NovaDigm’s scientific founders at the Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center. The work was supported in part by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (Grant Numbers AI19990, AI063382 and AI071554) and by the Department of the Army (Award Numbers JW81XWH-10-2-0035, W81XWH-11-1-0686 and W81XWH-16-C-0125).

The Uniformed Services University of the Health Sciences, founded by an act of Congress in 1972, is the nation’s federal health sciences university and the academic heart of the Military Health System. USU students are primarily active duty uniformed officers in the Army, Navy, Air Force and Public Health Service who receive specialized education in tropical and infectious diseases, TBI and PTSD, disaster response and humanitarian assistance, global health, and acute trauma care.