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30,000名患者接受了造血细胞移植(HCT)。大约三分之一(10,000)的移植受者接受了异基因血细胞移植。在这些患者中，只有不到50%到70%，即5000到7000名患者会发展为急性移植物抗宿主病。发生胃肠道移植物抗宿主病的患者是这些患者的一部分。这项赠款申请要求提供资金，以继续对用于治疗GVHD的两种专利制剂倍氯米松二丙酸酯(BDP)的独特组合进行第三阶段临床评估，BDP是一种速释片和一种肠溶型胃肠耐受片。Dor BioPharma，Inc.将这种配方称为OrBec(R)。 研究设计使用诱导剂量的泼尼松来控制GI GVHD的主要表现，然后在症状对初步治疗有反应的受试者中迅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活性糖皮质激素(倍氯米松二丙酸酯，BDP)]。BDP及其代谢物17-倍氯米松单丙酸酯(17-BMP)是一种有效的糖皮质激素，在胃肠道粘膜中的滞留时间延长，全身生物利用度有限。因此，使用口服局部活性糖皮质激素来控制GVHD的胃肠道炎症过程，应将全身强的松暴露降至最低。以前的研究表明，口服BDP在治疗GI GVHD方面是安全的；这项研究旨在提供令人信服的证据，证明在泼尼松逐渐减少后，BDP在控制GVHD方面的有效性。 总共166名受试者(每组83人)将被要求在双侧显着性水平0.05的情况下达到90%的能力，以检测治疗和安慰剂之间26%的差异(65%对39%，基于之前的第三阶段数据)。当第80天GVHD治疗失败的总事件数达到约87个时，试验将终止。可能会招募更多的患者，以便在试验期间考虑到辍学。 在试验结束时，DOR打算向FDA提交文件，以便对这一未得到满足的临床需求的新疗法进行市场批准。