According to the ADA, 25.8 million children and adults have diabetes. Diabetics have an increased risk of complications such as heart disease and are prone to impaired wound healing. A major cause of morbidity and hospitalization is diabetic foot ulceration (DFUs) that may result in infection, gangrene, amputations requiring prolonged hospitalization, costly treatments, and can significantly impair a patient's quality of life. The cost of DFU's to the US healthcare system is over $10 Billion annually. Diabetic wounds tend to remain stalled in the initial inflammatory phase of wound healing and are generally unresponsive to conventional treatments. Current treatment approaches including debridement, pressure off-loading, infection control, negative pressure, and skin substitutes tend to have marginal efficacy and high cost. A large unmet need exists for an easier and more effective treatment. FirstString Research, Inc. (FSR), a clinical stage biotech company, is advancing the development of novel bioengineered peptides based on the c-terminus of connexin proteins;a protein with important roles in multiple aspects of the wound healing process. A lead peptide ?CT1 (25 amino acids) based on connexin 43 (Cx43) has demonstrated a unique capability of switching the body's own healing response from inflammation and scarring to a healthy regenerative stage. FSR, with the assistance of Phase I and II SBIR/STTR grants, has developed ACT1 in a topical product called Granexin" Gel;obtained IND approval;and demonstrated its MOA, safety, and efficacy in a Phase I (N=48) and two (2) Phase II (N=92 per trial) clinical trials. Granexin" Gel has been shown to be safe and efficacious with no evidence of immunogenicity. FSR proposes to conduct a Phase 2b human (N=180) clinical trial to evaluate safe and efficacy of Granexin" Gel for treating DFUs. This trial will involve 3 groups to receive: Granexin" Gel (100 ?M ?CT1) + Standard of Care (SOC);Granexin" Gel (200 ?M ?CT1) + SOC;or Vehicle Gel + SOC. Due to ?CT1's unique MOA, we hypothesize that Granexin" Gel will significantly accelerate wound closure in DFU patients, when compared to Vehicle + SOC. The hypothesis will be tested through the following specific aims: To evaluate the safety and efficacy of Granexin" Gel administered topically to Diabetic Foot Ulcer. The primary endpoint will be the incidence of 100% wound closure from Baseline to Week 12. The secondary endpoints will include mean percent wound closure at 4 weeks, subject self-assessment of intensity of pain (till Week 12), time to 50% and 100% wound closure. The safety variable will be the incidence of treatment related Adverse Events. Further clinical success achieved with this project will enable the advancement Granexin" Gel toward pivotal Phase 3 trials, obtaining FDA's approval, and subsequent product commercialization, thus laying the foundation for a novel therapeutic for patients suffering from DFUs.
Diabetics have an increased risk of complications such as heart disease and prone to impaired wound healing. A major cause of morbidity and hospitalization is diabetic foot ulceration (DFUs) that may result in infection, gangrene, amputations requiring prolonged hospitalization, costly treatments, and can significantly impair a patient's quality of life. FSR proposes to conduct a Phase 2b human clinical trial to evaluate safety and efficacy of Granexin Gel for treating DFUs whereby clinical success will lay a foundation for a new treatment option for patients suffering from DFUs.
|Grek, Christina L; Rhett, J Matthew; Ghatnekar, Gautam S (2014) Cardiac to cancer: connecting connexins to clinical opportunity. FEBS Lett 588:1349-64|