Americans suffer from chronic wounds associated with diabetic, pressure and venous stasis ulcers. In many cases, chronic wounds can take years to heal, have a high recurrence rate and will result in amputations for 54,000 patients annually. It is estimated that 2.2 million patients in the United States have chronic ulcers that don't respond to conventional therapies. Angiotensin peptides have been shown to effectively promote wound healing in preclinical studies undertaken at US Biotest, Inc. in collaboration with scientists at USC KECK School of Medicine. In a Phase II SBIR grant, US Biotest developed USB001 (NorLeu3-A(1-7) in 2% HEC and preservatives), an angiotensin peptide formulation appropriate for clinical study. USB001 was found to be stable, safe for topical use and more effective than Regranex in facilitating wound healing in diabetic mice. Much of this data was reviewed during a pre-IND meeting with the FDA when US Biotest's clinical development plan was approved for IND filing. In addition, US Biotest identified treatment responsive genes and two potential molecular mechanisms of action for NorLeu3-A(1-7) in wound healing. Building upon the foundation established in our Phase II SBIR grant and our IND (approved by FDA on July 11, 2006), US Biotest is submitting a competing continuation to initiate clinical trials for evaluation of USB001's safety and efficacy sufficient to establish proof of concept.
In Specific Aim 1, we will conduct a Phase I safety study in normal volunteers (N=9) and measure toxicokinetic and pharmacokinetic samples in our LC/MS/MS assay for NorLeu3-A(1- 7).
In Specific Aim 2, we will manufacture sterile USB001 and conduct a Phase II dose response study in diabetic patients with chronic ulcers (3 groups of 25 study subjects per group).
In Specific Aim 3, we will complete preclinical safety studies required to initiate Phase III clinical studies. Angiotensin Analogs to Treat Wound Healing Diabetes is an illness that plagues an estimated 20 million individuals in the United States (National Diabetes Information Clearinghouse, 2005). Complications of diabetes include chronic skin ulcers that often lead to amputation and loss of life due to persistent wound infection. US Biotest's lead compound, NorLeu3-A(1-7), has been shown in pre-clinical studies to be significantly more effective than Regranex, the only FDA-approved drug for healing diabetic ulcers. This competing continuation of our Phase II SBIR will allow US Biotest to conduct Phase I and II studies of clinical efficacy. Development of a successful treatment for diabetic ulcers will preserve and improve quality of life as well as reduce health care costs. ? ? ?
| Balingit, Peter P; Armstrong, David G; Reyzelman, Alexander M et al. (2012) NorLeu3-A(1-7) stimulation of diabetic foot ulcer healing: results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial. Wound Repair Regen 20:482-90 |
| Rodgers, Kathleen; Verco, Shelagh; Bolton, Laura et al. (2011) Accelerated healing of diabetic wounds by NorLeu(3)-angiotensin (1-7). Expert Opin Investig Drugs 20:1575-81 |
