IND 20212 (03-25-99) PHASE 3: ORBEC (ORAL BDP) -PATIENTS WITH GI GVHD-FDA-11-12-0

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DESCRIPTION (provided by applicant): In the United States, approximately 30,000 patients undergo hematopoietic cell transplantation (HCT). Approximately one-third (10,000) of transplant recipients undergo allogeneic HCT. Of these patients less than 50 to 70%, or 5,000 to 7,000 patients, will develop acute GVHD. The patients that develop GI GVHD are a subset of these patients. This grant application requests funding to continue the Phase 3 clinical evaluation of a unique combination of two patented formulations of beclomethasone dipropionate (BDP) for use in treating GVHD, an immediate release tablet and an enteric-coated gastro-resistant tablet. DOR BioPharma, Inc. calls this formulation orBec(r). The study design uses an induction dose of prednisone to control the presenting manifestations of GI GVHD, then rapidly tapers the dose of prednisone in subjects whose symptoms have responded to initial treatment, while subjects continue to take the study drug [placebo tablets or an oral topically-active glucocorticoid (beclomethasone dipropionate, BDP)]. BDP and its metabolite 17-beclomethasone monopropionate (17-BMP) are potent glucocorticoids with prolonged residence time in the GI mucosa and limited systemic bioavailability. Thus, the use of an oral topically-active glucocorticoid with limited systemic effects to control the GI inflammatory process of GVHD should minimize systemic prednisone exposure. Previous studies have shown that oral BDP is safe in the treatment of GI GVHD; this study is designed to provide compelling evidence of its efficacy in controlling GVHD following a prednisone taper. A total of 166 subjects (83 per group) will be required to achieve 90% power at a 2-sided significance level of 0.05 to detect a difference of 26% of difference between treatment and placebo (65% vs. 39% projected, based on the previous Phase 3 data). The trial will be terminated when the total events for GVHD treatment failure at Day 80 has reached approximately 87. Slightly more patients may be recruited to allow for dropouts during the trial. At the completion of the trial DOR intends to file documents with the FDA to allow for marketing approval of the new treatment for this unmet clinical need.