Immunomodulatory Device for Treatment of Pediatric Acute Renal Failure Patients

描述（由申请人提供）：问题：2007年儿科医疗器械安全和改进法案（包括公法110-85）和医学研究所的指令已经认识到缺乏专门为儿科应用设计的器械，医学研究所建议在涉及成人的II期临床试验结束时开始儿科研究。急性肾损伤（AKI）和需要肾脏替代治疗（RTT）的感染性休克相关AKI （SSAKI）是ICU患者的重要并发症，相关死亡率超过50%。与许多治疗方法一样，即使是AKI和SSAKI可用的次优治疗改进也主要针对成人AKI/SSAKI- rrt患者，很少考虑儿科应用所需的任何适应。由于接受RRT的儿童MOD患者的死亡率接近50%，因此需要专门开发用于儿科AKI/SSAKI-RRT的新疗法。产品：cSCD是一种新型紧凑的选择性细胞移植装置，包含捆绑的仿生聚砜纤维，可选择性地结合/隔离和使透析体外血液循环中的白细胞（LE）失活，从而在与AKI和SSAKI相关的全身炎症反应中产生免疫调节作用。创新：SCD结合局部柠檬酸抗凝，是一种新的治疗应用，利用生物相容性膜，允许LE附着在[iCa]低环境中，从而减少LE激活状态。在AKI的临床试验中，SCD已被证明可以有效地将死亡率从历史匹配对照的63%降低到31%。i.长期目标：开发具有最佳流动特性，有效表面积（SA）和易于耐受的血填充量的cSCD

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.