Stavas Joseph, Diaz-Gonzalez de Ferris Maria, Johns Ashley, Jain Deepak, Bertram Tim
ProKidney, Grand Cayman, George Town, Cayman Islands,
Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Blood Purif. 2021;50(4-5):678-683. doi: 10.1159/000512586. Epub 2021 Mar 1.
Advanced cell therapies with autologous, homologous cells show promise to affect reparative and restorative changes in the chronic kidney disease (CKD) nephron. We present our protocol and preliminary analysis of an IRB-approved, phase I single-group, open-label trial that tests the safety and efficacy of Renal Autologous Cell Therapy (REACT; NCT04115345) in adults with congenital anomalies of the kidney and urinary tract (CAKUT).
Adults with surgically corrected CAKUT and CKD stages 3 and 4 signed an informed consent and served as their "own" baseline control. REACT is an active biological ingredient acquired from a percutaneous tissue acquisition from the patient's kidney cortex. The specimen undergoes a GMP-compliant manufacturing process that harvests the selected renal cells composed of progenitors for renal repair, followed by image-guided locoregional reinjection into the patient's renal cortex. Participants receive 2 doses at 6-month intervals. Primary outcomes are stable renal function and stable/improved quality of life. Additional exploratory endpoints include the impact of REACT on blood pressure, vitamin D levels, hemoglobin, hematocrit and kidney volume by MRI analysis.
Four men and 1 woman were enrolled and underwent 5 cell injections. Their characteristics were as follows: mean 52.8 years (SD 17.7 years), 1 Hispanic, 4 non-Hispanic, and 5 white. There were no renal tissue acquisition, cell injection, or cell product-related complications at baseline.
REACT is demonstrating feasibility and patient safety in preliminary analysis. Autologous cell therapy treatment has the potential to stabilize or improve renal function in CAKUT-associated CKD to delay or avert dialysis. Patient enrollment and follow-up are underway.
采用自体、同源细胞的先进细胞疗法有望在慢性肾脏病(CKD)肾单位中引发修复和恢复性变化。我们介绍了一项经机构审查委员会(IRB)批准的I期单组开放标签试验的方案及初步分析,该试验旨在测试肾自体细胞疗法(REACT;NCT04115345)对患有先天性肾脏和尿路异常(CAKUT)的成人的安全性和有效性。
患有经手术矫正的CAKUT且处于CKD 3期和4期的成人签署知情同意书,并作为他们自己的“基线”对照。REACT是一种从患者肾皮质经皮组织采集获得的活性生物成分。该标本经过符合药品生产质量管理规范(GMP)的制造过程,收获由用于肾脏修复的祖细胞组成的选定肾细胞,然后在影像引导下将其局部重新注入患者的肾皮质。参与者每隔6个月接受2剂治疗。主要结局是肾功能稳定和生活质量稳定/改善。其他探索性终点包括通过MRI分析REACT对血压、维生素D水平、血红蛋白、血细胞比容和肾脏体积的影响。
招募了4名男性和1名女性并进行了5次细胞注射。他们的特征如下:平均年龄52.8岁(标准差17.7岁),1名西班牙裔,4名非西班牙裔,5名白人。在基线时未出现肾组织采集、细胞注射或细胞产品相关并发症。
REACT在初步分析中显示出可行性和患者安全性。自体细胞疗法有可能稳定或改善CAKUT相关CKD的肾功能,以延迟或避免透析。患者招募和随访正在进行中。