CLINICAL TRIAL: NOVEL THERAPY FOR RESISTANT FOCAL SEGMENTAL GLOMERULOSCLEROSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 原发性局灶性节段性肾小球硬化(FSGS)是一种严重的肾脏疾病，占所有需要慢性透析或移植的儿童和成人患者的近10%-15%。不仅这种疾病的发病率在上升。FSGS的病因尚不清楚，也没有得到证实的治疗方法。在缺乏明确的治疗目标和候选治疗的情况下，这项提案将评估三种新型药物的安全性和有效性，这些药物可能能够减少肾纤维化并减缓耐药FSGS患者的疾病恶化速度。阶段性创新奖申请由两个截然不同的部分组成。在R21阶段的初始阶段，将测试两种新疗法-肿瘤坏死因子-α拮抗剂和PPARg激动剂-的安全性、耐受性和药代动力学特征。在第二阶段，R33阶段，将进行混合排名和选择阶段II研究，以评估这两种治疗和抗转化生长因子-b抗体的疗效，并与最佳保守药物治疗进行比较。这项研究的结果将指导正式的第三阶段随机临床试验的设计。为执行R21/R33项目而建立的基础设施应有助于对未来将出现的其他新疗法进行有效评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Primary focal segmental glomerulosclerosis (FSGS) is a serious renal disease, accounting for nearly 10-15% of all pediatric and adult patients requiring chronic dialysis or transplantation. Not only is the incidence of this disease rising. The etiology of FSGS remains obscure and there is no proven therapy. In the absence of a well-defined therapeutic target and a candidate treatment, this proposal will evaluate the safety and efficacy of three novel agents that may have the capacity to reduce renal fibrosis and slow the rate of deterioration of disease in patients with resistant FSGS. The Phased Innovation Award application is composed of two distinct portions. During the initial stage, the R21 Phase, the safety, tolerance, and pharmacokinetic profile of two novel therapies - a TNF-a antagonist and a PPARg agonist -- will be tested. In the second stage, the R33 phase, a hybrid ranking and selection Phase II study will be performed to assess the efficacy of these two treatments and an anti-TGF-b antibody compared to optimal conservative medical therapy. The outcome of this study will guide the design of a formal Phase III randomized clinical trial. The infrastructure that is established for the performance of this R21/R33 project should prove useful for the efficient assessment of additional novel therapies that will to arise in the future.