Allogeneic Mesenchymal Precursor Cells (MPC) in Diabetic Nephropathy: A Randomized, Placebo-controlled, Dose Escalation Study

作者：David Packham, Ian R. Fraser, Peter G. Kerr, Karen R. Segal · 发表于：EBioMedicine · 年份：2016 · DOI：10.1016/j.ebiom.2016.09.011 · 被引用次数：181 · 研究领域：Mesenchymal stem cell research、Advanced Glycation End Products research、Chronic Kidney Disease and Diabetes

Background Diabetic nephropathy is the most common cause of end stage renal failure. We assessed the safety, tolerability, and explored therapeutic effects of adult allogeneic bone-marrow derived mesenchymal precursor cells (MPC) in patients with moderate to severe diabetic nephropathy. Methods Multicenter, randomized, double-blind, dose-escalating, sequential, placebo-controlled trial assessing a single intravenous (IV) infusion of allogeneic MPC (United States adopted name: rexlemestrocel-L) 150×10 6 (n=10), 300×10 6 (n=10) or placebo (n=10) in adults with diabetic nephropathy with an estimated glomerular filtration rate (eGFR) 20–50ml/min/1.73m 2 . Thirty patients at three Australian centers were enrolled between July 2013 and June 2014 and randomized 2:1, in two sequential dose cohorts, to receive rexlemestrocel-L or placebo. Study duration was 60weeks. Primary endpoint was safety and tolerability. Primary exploratory efficacy endpoint was change from baseline in eGFR and directly measured GFR by 99 Tc-DTPA plasma clearance (mGFR) at 12weeks post-infusion. The trial was registered on ClinicalTrials.gov (NCT01843387). Findings All patients completed the study and were included in analyses applied to the intention to treat population. There were no acute adverse events (AEs) associated with infusion and no treatment-related AEs or serious AEs were deemed treatment-related by investigators. No patients developed persistent donor specific anti-HLA antibodies. Relative to plac...