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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44DK080567-04A1
Application #
8646302
Study Section
Special Emphasis Panel (ZRG1-MOSS-T (12))
Program Officer
Arreaza-Rubin, Guillermo
Project Start
2007-09-15
Project End
2017-04-30
Budget Start
2014-05-05
Budget End
2015-04-30
Support Year
4
Fiscal Year
2014
Total Cost
$999,289
Indirect Cost
Name
Firststring Research, LLC
Department
Type
DUNS #
602545654
City
MT. Pleasant
State
SC
Country
United States
Zip Code
29464
Grek, Christina L; Rhett, J Matthew; Ghatnekar, Gautam S (2014) Cardiac to cancer: connecting connexins to clinical opportunity. FEBS Lett 588:1349-64