Immunomodulatory Device for Treatment of Pediatric Acute Renal Failure Patients

用于治疗小儿急性肾衰竭患者的免疫调节装置

• 批准号: 8453029
• 负责人: DEBORAH Ann BUFFINGTON
• 金额: $ 36.47万
• 依托单位: INNOVATIVE BIOTHERAPIES, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-20 至 2015-07-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8453029
• 关键词: Acute; Acute Kidney Failure; Acute Renal Failure with Renal Papillary Necrosis; Adult; Affect; Anticoagulation; Area; Binding; Biocompatible; Biological Response Modifier Therapy; Biomedical Engineering; Biomimetics; Blood; Blood Volume; Blood capillaries; Cells; Characteristics; Childhood; Chronic; Citrates; Clinical; Clinical Trials; Complication; Computer Simulation; Critical Illness; Data; Development; Device Designs; Devices; Disease; Dose; Environment; Evaluation; Extracorporeal Dialysis; Extravasation; Family suidae; Fiber; Functional disorder; Goals; Imagery; In Vitro; Inflammatory; Inflammatory Response; Injury; Institute of Medicine (U.S.); Kidney; Knowledge; Laws; Leukocytes; Lung; Medical Device; Medical Device Safety; Membrane; Michigan; Modeling; Morbidity - disease rate; Organ failure; Outcome; Patients; Phase; Phase II Clinical Trials; Process; Public Health; Relative (related person); Renal Replacement Therapy; Replacement Therapy; Safety; Secondary to; Sepsis Syndrome; Septic Shock; Surface; System; Technology; Testing; Therapeutic; Time; Tissues; Treatment Efficacy; Universities; base; capillary; clinical efficacy; design; hemodynamics; improved; indexing; innovation; mortality; multiorgan damage; novel; novel therapeutics; phase 2 study; polysulphone; pre-clinical; prospective; prototype; public health relevance; simulation; success

DESCRIPTION (provided by applicant): The Problem: The lack of devices specifically designed for pediatric applications has been recognized by directives in the Pediatric Medical Device Safety and Improvement Act of 2007, included in Public Law 110-85, and the Institutes of Medicine, which has recommended pediatric studies to begin at the end of Phase II clinical trials involving adults. Acute kidney injury (AKI) and septic shock associated AKI (SSAKI) requiring renal replacement therapy (RTT) are significant complications in ICU patients with an associated mortality rate exceeding 50 percent. As with so many therapeutics, even the available sub-optimal treatment improvements for AKI and SSAKI have been predominantly targeted for use in adult AKI/SSAKI-RRT patients, with little consideration given to any adaption that would be required for pediatric application. The need for novel therapeutics that are specifically developed for pediatric AKI/SSAKI-RRT use is driven by the nearly 50% mortality rates of pediatric patients with MOD receiving RRT. The Product: The cSCD is a novel compact Selective Cytopheretic Device containing bundled biomimetic polysulfone fibers which selectively bind/sequester and deactivate leukocytes (LE) in a dialysis extracorporeal blood circuit, resulting in an immunomodulatory effect in the systemic inflammatory response associated with AKI and SSAKI. The cSCD is targeted to treat pediatric AKI/SSAKI-RRT patients Innovation: The SCD, combined with regional citrate anticoagulation, is a novel therapeutic application utilizing biocompatible membranes that allow LE attachment in a [iCa]low environment resulting in a diminution in the LE activated state. The SCD has demonstrated, in clinical trials of AKI, to be effective in reducing mortality rate from the historcal matched control of 63% to 31%. i. Long Term Goal: To develop a cSCD with optimal flow characteristics, an effective surface area (SA) and a blood fill volume that is easily tolerated by pediatric AKI/SSAKI-RRT patients. Expected Outcome: SSAKI pigs treated with cSCD+RRT will demonstrate therapeutic efficacy when compared to SSAKI pigs treated with RTT alone. The following aims will guide this study plan: Specific Aim 1. Evaluate cSCD prototype designs in silico and via flow visualization system studies. Specific Aim 2. In Vitro Blood Circuit testing of cSCD to assess hemocompatibility and determine impact of SA on LE sequestration/modulation. Specific Aim 3. Assess cSCD efficacy using a 10kg porcine model of SSAKI. Phase II objective: Completion of the Phase I aims will demonstrate proof-of-concept for use of the cSCD in the treatment of pediatric AKI-RRT patients. The Phase II plan will treat additional SSAKI pigs with the cSCD to increase the preclinical data and to further define optimization of cSCD dose, for inclusion of regulatory submissions. With successful completion of the Phase II studies, IBT plans to apply for an IDE approval from the FDA to initiate a clinical trial for the evaluation of cSCD therapy in pediatric patients with AKI- RRT. IBT would seek either a corporate partner or private equity investors to undertake these clinical trials.

描述（由申请人提供）：问题：缺乏专门为儿科应用设计的设备已被2007年儿科医疗设备安全和改善法中的指令所认识到，其中包括110 - 85年公共法110-85中的医学研究所，建议在涉及II期临床试验的成年阶段的医学研究所开始。需要肾脏替代疗法（RTT）的急性肾脏损伤（AKI）和脓毒症相关的AKI（SSAKI）是ICU患者的显着并发症，相关死亡率超过50％。与如此多的治疗药物一样，即使是AKI和SSAKI的可用亚最佳治疗改进，主要针对成人AKI/SSAKI-RRT患者，几乎没有考虑到儿科应用所需的任何适应性。专门针对小儿AKI/SSAKI-RRT使用专门开发的新型治疗剂的需求是由MOD接受RRT的儿科患者的近50％死亡率驱动的。产品：CSCD是一种新型紧凑的选择性细胞植物装置，含有捆绑的仿生多硫酮纤维，可在透析外体外血回路中选择性结合/隔离和停用白细胞（LE），从而导致与Akki和Ssaki相关的系统性炎症反应，从而导致免疫炎症效应。 CSCD旨在治疗小儿AKI/SSAKI-RRT患者的创新：SCD与柠檬酸盐区域抗凝作用相结合，是一种新型的治疗应用，利用生物相容性的膜，该膜利用允许在LE较低环境中le附着的生物相容性膜，导致LE激活状态减少。在AKI的临床试验中，SCD证明了从历史悠久的匹配控制率降低63％至31％的死亡率有效。我。长期目标：开发具有最佳流动特征的CSCD，有效的表面积（SA）和一个容易被耐受的血液填充体积 小儿Aki/Ssaki-RRT患者。预期的结果：与单独使用RTT治疗的ssaki猪相比，用CSCD+RRT处理的Ssaki猪将表现出治疗功效。以下目的将指导该研究计划：特定目的1。在计算机和流动可视化系统研究中评估CSCD原型设计。特定目标2。体外血回路测试 CSCD评估血流相容性并确定SA对LE固相/调制的影响。特定目标3。使用Ssaki的10kg猪模型评估CSCD功效。 II阶段目标：I阶段目标的完成将证明使用CSCD在治疗小儿AKI-RRT患者中的概念证明。 II期计划将使用CSCD处理其他SSAKI猪，以增加临床前数据并进一步定义CSCD剂量的优化，以包括调节性提交。随着第二阶段研究的成功完成，IBT计划申请FDA的IDE批准以启动临床 在儿科患者中评估CSCD治疗的试验。 IBT将寻求公司合作伙伴或私募股权投资者进行这些临床试验。