IND 20212 (03-25-99) PHASE 2: ORBEC (ORAL BDP)-PATIENTS WITH CHRONIC GVHD

IND 20212 (03-25-99) 第 2 阶段：ORBEC（口服 BDP）-慢性 GVHD 患者

基本信息

批准号：
8537391
负责人：
Christopher Joseph Schaber
金额：
$ 14.42万
依托单位：
SOLIGENIX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8537391
关键词：
Acute Adrenal Cortex Hormones Adverse effects Allogenic Applications Grants Beclomethasone Biological Availability Cancer Survivor Chronic Clinical Clinical Research Colon Complication Consensus Cushingoid habitus Data Development Disease Dose Drug Formulations Enrollment Enteral Enteric-Coated Tablets FDA approved Feedback Flare Funding Future Glucocorticoids Glucose Intolerance Goals Hematologic Neoplasms In complete remission Infection Label Life Malignant Neoplasms Medical Methylprednisolone Muscle Fatigue Muscle Weakness Oral Oral Administration Patients Pharmaceutical Preparations Pharmacology Phase Placebo Control Positioning Attribute Prednisone Prevention Prevention therapy Process Protocols documentation Quality of life Reporting Request for Applications Research Design Risk Safety Schedule Signs and Symptoms Small Business Innovation Research Grant Small Intestines Symptoms System Tablets Therapeutic Time United States National Institutes of Health base bone chronic graft versus host disease demineralization design experience follow-up gastrointestinal gastrointestinal sign gastrointestinal symptom graft vs host disease hematopoietic cell transplantation improved mortality novel open label partial response phase 2 study placebo controlled study programs research clinical testing response treatment duration

项目摘要

DESCRIPTION (provided by applicant): Graft vs. Host Disease (GVHD) is an expensive life-threatening complication following allogeneic hematopoietic cell transplantation in some patients that receive this life-saving treatment for certain cancers. The proposed open-label, multi-center, two-part Phase 2 clinical study is designed to evaluate the potential of orBec(R), a novel formulation of oral beclomethasone 17,21- dipropionate (BDP), as a treatment for chronic gastrointestinal cGVHD. OrBec(R), as developed by Soligenix, is formulated as two separate drug products for oral administration as an immediate release and delayed release tablet, each containing 1 mg of BDP, a potent, locally-acting corticosteroid originally developed primarily for the prevention and treatment of acute gastrointestinal graft versus host disease (aGVHD). The reduced systemic bioavailability of oral BDP offers a major therapeutic advantage over systemic glucocorticoids such as prednisone and methylprednisolone, which have well-recognized adverse effects (e.g., development of glucose intolerance, Cushingoid habitus, muscle weakness and fatigue, bone demineralization, and increased risks of infections). Adverse effects of systemic glucocorticoid administration can be avoided by use of topically active glucocorticoids. The protocol for this Phase 2 CLINICAL STUDY was submitted to IND 20,212 June 24, 2011. To date, no additional FDA feedback on the study design has been noted by the FDA. We will conduct this Phase 2 clinical study with the following specific goals, which form the Specific Aims of this proposal: To conduct a FDA reviewed and accepted Phase 2 clinical study: the study will be a point estimate design aimed at elucidating the dose response needed to define future placebo-controlled studies. The placebo-controlled study will be the Phase 3 clinical study that will be described in the Phase II SBIR proposal. This study will estimate the proportion of subjects who achieve a complete response (CR), partial response (PR) and overall response (OR) of GI GVHD signs and symptoms when treated with orBec(R), 2 mg four times a day (8 mg/day) for up to 16 weeks, in patients with cGVHD. The secondary objectives of this study are to determine the: i. proportion of subjects who experience a flare/worsening of GI GVHD; ii. time to flare/worsening of GI GVHD at each dose-level; iii. time to CR during the initial 16 weeks of orBec(R) treatment; and iv. time to flare/worsening of GI GVHD signs and symptoms during each of the planned orBec(R) dose reductions in Part 2 of the study. The safety objectives are to evaluate safety and tolerability of orBec(R) in subjects with cGVHD. Upon completion of the Phase 2 clinical study, Soligenix will be in a position to begin the process for a Phase 3 FDA reviewed and accepted clinical study, on the road to the first drug to be approved for treatment for cGVHD.

描述（由申请人提供）：移植物抗宿主病（GVHD）是一些接受这种针对某些癌症的挽救生命的治疗的患者进行同种异体造血细胞移植后出现的一种昂贵的危及生命的并发症。拟议的开放标签、多中心、分为两部分的 2 期临床研究旨在评估 orBec(R) 的潜力，orBec(R) 是一种新型口服倍氯米松 17,21-二丙酸酯 (BDP) 制剂，用于治疗慢性胃肠道 cGVHD。 OrBec(R) 由 Soligenix 开发，被配制为两种单独的口服药物产品，分别为立即释放和延迟释放片剂，每种含有 1 毫克 BDP，一种有效的局部作用皮质类固醇，最初主要用于预防和治疗治疗急性胃肠移植物抗宿主病（aGVHD）。口服 BDP 的全身生物利用度降低，与全身性糖皮质激素（例如泼尼松和甲泼尼龙）相比具有主要的治疗优势，后者具有众所周知的不良反应（例如，出现葡萄糖耐受不良、库欣样习惯、肌肉无力和疲劳、骨骼脱矿质和风险增加）感染）。通过使用局部活性糖皮质激素可以避免全身糖皮质激素的不良反应。该 2 期临床研究的方案已于 2011 年 6 月 24 日提交给 IND 20,212。迄今为止，FDA 尚未注意到有关该研究设计的其他 FDA 反馈。我们将按照以下具体目标进行这项 2 期临床研究，这些目标构成了本提案的具体目标：进行 FDA 审查和接受的 2 期临床研究：该研究将是一项点估计设计，旨在阐明所需的剂量反应定义未来的安慰剂对照研究。安慰剂对照研究将是第 3 期临床研究，将在第 2 期 SBIR 提案中进行描述。本研究将估计接受 orBec(R) 2 mg 每天四次治疗时，胃肠道 GVHD 体征和症状达到完全缓解 (CR)、部分缓解 (PR) 和总体缓解 (OR) 的受试者比例（8毫克/天），对于患有 cGVHD 的患者，持续长达 16 周。本研究的次要目标是确定：经历胃肠道 GVHD 发作/恶化的受试者比例；二.每个剂量水平下胃肠道 GVHD 发作/恶化的时间；三.初始阶段达到 CR 的时间 16 周的 orBec(R) 治疗；和四。在研究第 2 部分中每次计划的 orBec(R) 剂量减少期间，胃肠道 GVHD 体征和症状发作/恶化的时间。安全性目标是评估 orBec(R) 在 cGVHD 受试者中的安全性和耐受性。完成 2 期临床研究后，Soligenix 将能够开始 FDA 审查和接受的 3 期临床研究流程，迈向第一个被批准用于治疗 cGVHD 的药物。