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

• 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
• 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

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）是一种昂贵的危及生命的并发症，在一些接受这种挽救某些癌症生命的治疗的患者中，在同种异体造血细胞移植后。拟定的开放标签、多中心、 两部分2期临床研究旨在评估orBec（R）作为慢性胃肠道cGVHD治疗的潜力，orBec（R）是一种口服倍氯米松17，21-二丙酸酯（BDP）的新制剂。OrBec（R）由Soligenix开发，被配制成两种单独的口服药物产品，分别为速释和缓释片剂，每种片剂含有1 mg BDP，BDP是一种强效的局部作用皮质类固醇，最初开发用于预防和治疗急性胃肠道移植物抗宿主病（aGVHD）。口服BDP降低的全身生物利用度提供了优于全身性糖皮质激素如泼尼松和甲泼尼龙的主要治疗优势，后者具有公认的不良反应（例如，葡萄糖耐受不良、库欣样体质、肌无力和疲劳、骨脱矿和感染风险增加）。全身性糖皮质激素给药的不良反应可以通过使用局部活性糖皮质激素来避免。本II期临床研究的方案于2011年6月24日提交IND 20，212。迄今为止，FDA尚未注意到FDA对研究设计的其他反馈。我们将开展本II期临床研究，具体目标如下，构成本提案的具体目的：开展FDA审查并接受的II期临床研究：本研究将是一项点估计设计，旨在阐明定义未来安慰剂对照研究所需的剂量反应。安慰剂对照研究将是III期临床研究，将在II期SBIR提案中描述。本研究将估计cGVHD患者接受orBec（R）2 mg每日4次（8 mg/天）治疗长达16周时，GI 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。本研究的次要目的是确定：i.经历GI GVHD发作/恶化的受试者比例; ii.在每个剂量水平下至GI GVHD发作/恶化的时间; iii.初始治疗期间至CR的时间 16周orBec（R）治疗;和iv.研究第2部分中每次计划的orBec（R）剂量降低期间GI GVHD体征和症状的发作/恶化时间。安全性目标是评估orBec（R）在cGVHD受试者中的安全性和耐受性。在完成II期临床研究后，Soligenix将能够开始FDA审查和接受的III期临床研究的过程，从而成为首个获批用于治疗cGVHD的药物。