Research Project
7659687
DESCRIPTION (provided by applicant): The long-term objective of the proposed development is to improve the standard of care and quality of life in patients with the skin-disruptive disease, Epidermolysis Bullosa (EB). To begin to accomplish this task, a proof-of-principle (pilot) study has been designed and will be implemented to assess the safety and clinical activity of TB4 in promoting wound healing in patients with EB. TB4 is a synthetically- produced copy of a naturally occurring and ubiquitous 43-amino acid peptide, which has wound healing and anti-inflammatory properties. It is thought to exert its therapeutic effect through an ability to regulate the cell-building protein, actin, a vital component of cellular structure, upregulate the expression of the adhesion protein, Iaminin-5, stimulate keratinocyte and endothelial cell migration, increase collagen recruitment and deposition, and promote angiogenesis. In particular, Iaminin-5, integral to the integrity of the epithelial subepithelial junction and one of the best ligands for keratinocyte adhesion and migration, is defective in certain patients with EB. Its up-regulation by TB4 could not only benefit those patients but all EB patients as well. This early Phase 2 clinical trial will be a double-blind, placebo-controlled, dose-response study using 3 concentrations of TB4. Because enrollment of this orphan population will be challenging and the dropout rate likely high, 42 patients will be screened to enroll 36 eligible patients to yield at least 24 evaluable patients. The study will enroll 9 patients at each of 3 concentrations of TB4 plus 3 patients in the placebo group parallel to each dose group. Patients within each group will be randomized to TB4 or placebo in a 3:1 ratio. The study population will comprise male and female outpatients between the ages of 2 and 30 years with a diagnosis of junctional or dystrophic EB. Because the ratio of junctional to dystrophic patients is approximately 1:6, an enrollment imbalance will most likely occur. As this is a pilot study of short duration, no attempts will be made to adjust enrollment between these two types of patients.
