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

IND 20212 (03-25-99) 第 3 阶段：ORBEC（口服 BDP）-胃肠道 GVHD-FDA-11-12-0 患者

• 批准号: 7980077
• 负责人: Kevin James Horgan
• 金额: $ 40万
• 依托单位: SOLIGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7980077
• 关键词: IND; 20212; 03; 25; 99

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.

描述（由申请人提供）： 在美国，大约有 30,000 名患者接受造血细胞移植 (HCT)。 大约三分之一 (10,000) 的移植受者接受同种异体 HCT。这些患者中，不到 50% 至 70%，即 5,000 至 7,000 名患者会发生急性 GVHD。发生胃肠道 GVHD 的患者是这些患者的一部分。 该拨款申请要求提供资金，以继续对用于治疗 GVHD 的二丙酸倍氯米松 (BDP) 两种专利配方（一种速释片和一种肠溶胃抗药片）的独特组合进行 3 期临床评估。 DOR BioPharma, Inc. 将此配方称为“Bec(r)”。 研究设计使用诱导剂量的泼尼松来控制胃肠道 GVHD 的表现，然后在症状对初始治疗有反应的受试者中快速减少泼尼松的剂量，同时受试者继续服用研究药物 [安慰剂片剂或口服局部用药] -活性糖皮质激素（二丙酸倍氯米松，BDP）]。 BDP 及其代谢物 17-丙酸倍氯米松 (17-BMP) 是强效糖皮质激素，在胃肠道粘膜中的停留时间较长，但全身生物利用度有限。因此，使用全身作用有限的口服局部活性糖皮质激素来控制 GVHD 的胃肠道炎症过程应尽量减少全身泼尼松暴露。既往研究表明口服BDP治疗胃肠道GVHD是安全的；这项研究旨在提供令人信服的证据，证明其在泼尼松逐渐减量后控制 GVHD 的功效。 总共 166 名受试者（每组 83 名）需要在 0.05 的双侧显着性水平下达到 90% 的功效，才能检测到治疗组与安慰剂组之间 26% 的差异（根据预测，65% 与 39% 相比）之前的第 3 阶段数据）。当第 80 天 GVHD 治疗失败的总事件达到约 87 例时，试验将终止。可能会招募稍多的患者，以允许试验期间退出。 试验完成后，DOR 打算向 FDA 提交文件，以便批准新疗法的上市，以满足这一未满足的临床需求。