NanoDOX^® 1% Doxycycline Monohydrate Hydrogel - Dermal Ulcers and Trauma Wounds

NanoDOX^® 1% Doxycycline Monohydrate Hydrogel (NanoDOX^®) is a topical gel that is intended for direct contact with the wound and is applied to the entire surface of the wound bed. A secondary dressing, such as gauze or non-adhering dressing, will be applied to cover NanoDOX^® and wound tissue allowing NanoDOX^® to provide a moist, wound healing environment.

 

The molecular environment of chronic inflammatory diseases, like diabetic foot ulcers, contains abnormally high levels of pro-inflammatory cytokines (TNF-α and IL-1β) and abnormally high levels of proteases (matrix metalloproteinase (MMPs) and neutrophil elastase), which are theorized to prevent normal wound healing. Doxycycline is an antibiotic that is an inhibitor of high levels of active proteases, including MPMs. Topical treatment of diabetic ulcers with a molecule that reduces inflammation and proteases activity could promote healing by reducing the destruction of endogenous growth factors, receptors, and extra cellular matrix proteins that are essential for wound healing.  Doxycycline is an inexpensive, FDA approved antibiotic that also inhibits MMPs and TNF-α converting enzyme (TACE) activity. Its therapeutic benefit in animal models and clinical studies of ulcerative diseases is due to its ability to inhibit MMPs, not from its antibiotic effect. A published clinical study by Chin has demonstrated that topically applied doxycycline (not NanoDOX^®) is successful in treating diabetic foot ulcers. If these characteristics also apply to the proposed clinical trials then NanoDOX^® would constitute an important new therapeutic tool for the treatment of partial and full thickness diabetic, chronic cutaneous (dermal) ulcers that have adequate blood supply.

 

Nanotherapeutics entered into a Cooperative Research and Development Agreement (CRADA) with the North Florida/South Georgia Veterans Health System to conduct the Phase 2a clinical trial, "A Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of NanoDOX^® 1.0% Doxycycline Monohydrate Hydrogel in Diabetic Adult Subjects with Lower Extremity Ulcers Compared to Placebo Hydrogel," at the Malcom Randall VA Medical Center in Gainesville, Florida. Recruitment began in February 2009 and the trial has been completed.

The 20-week Phase 2a double-blind, one center, two-arm study with a two (2) week run-in, evaluating the safety and efficacy of a once-daily administration of NanoDOX^® topically applied to diabetic ulcers in concert with professionally administered Standard of Care (SoC) procedures as described by Standard Operating Procedure(s) of the Department of Veterans Administration Hospitals has been completed. Patients with infected wounds received oral antibiotics and were not included in the topical portion of the study until the infection was shown by wound biopsy analysis to have been resolved. Following a two (2) week run-in of all patients receiving SoC treatment for diabetic ulcers, patients received either the investigational material or the placebo applied as a part of their wound care. Each patient received 2cc packets of either the test article or the placebo for a once-daily home treatment accompanied by a dressing change. Results indicated no safety concerns and an encouraging exploratory efficacy signal. 

A pilot study using NanoDOX^® to treat dehisced surgical wounds is being developed through an agreement with The Henry M. Jackson Foundation. The study, "Double-Blinded, Single-Site, Pilot Study of NanoDOX^® versus Placebo Hydrogel for Dehisced Surgical Wounds," is expected to begin 4Q 2011 at Walter Reed Army Medical Center and is supported by funding through the Department of Defense Appropriations Act.

An additional 24 subject prospective, randomized, open label Phase 2 study will evaluate the efficacy of NanoDOX^® Hydrogel topically applied to orthopedic traumatic wounds receiving vacuum assisted closure therapy versus vacuum assisted closure therapy alone.  This trial is set to begin 4Q 2011 with the University of Missouri and Walter Reed Army Medical Center.