CLINICAL TRIAL: NOVEL THERAPY FOR RESISTANT FOCAL SEGMENTAL GLOMERULOSCLEROSIS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 原发性局灶节段性肾小球硬化（FSGS）是一种严重的肾脏疾病，占所有需要长期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的病因仍然不清楚，没有经过证实的治疗方法。在缺乏明确的治疗靶点和候选治疗的情况下，该提案将评估三种新型药物的安全性和有效性，这些药物可能具有减少肾纤维化和减缓耐药FSGS患者疾病恶化速度的能力。分阶段创新奖申请由两个不同的部分组成。在初始阶段，R21期，将测试两种新疗法-TNF-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期，将进行混合排序和选择II期研究，以评估这两种治疗和抗TGF-B抗体与最佳保守药物治疗相比的疗效。本研究的结果将指导正式III期随机临床试验的设计。为执行该R21/R33项目而建立的基础设施应证明对未来将出现的其他新疗法的有效评估有用。

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.