Allogeneic Mesenchymal Precursor Cells (MPC) in Diabetic Nephropathy: A Randomized, Placebo-controlled, Dose Escalation Study
AuthorPackham, DK; Fraser, IR; Kerr, PG; Segal, KR
University of Melbourne Author/sPackham, David
Document TypeJournal Article
CitationsPackham, D. K., Fraser, I. R., Kerr, P. G. & Segal, K. R. (2016). Allogeneic Mesenchymal Precursor Cells (MPC) in Diabetic Nephropathy: A Randomized, Placebo-controlled, Dose Escalation Study. EBIOMEDICINE, 12, pp.263-269. https://doi.org/10.1016/j.ebiom.2016.09.011.
Access StatusOpen Access
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) 150×106 (n=10), 300×106 (n=10) or placebo (n=10) in adults with diabetic nephropathy with an estimated glomerular filtration rate (eGFR) 20-50ml/min/1.73m2. 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 99Tc-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 placebo, a single IV rexlemestrocel-L infusion showed trends of stabilizing or improving eGFR and mGFR at week 12. The adjusted least squares mean (LSM±SE) differences from placebo in changes from baseline at 12weeks in the rexlemestrocel-L groups were 4.4±2.16 and 1.6±2.15ml/min/1.73m2 for eGFR and 4.1±2.75 and 3.9±2.75 for mGFR for the 150×106 and 300×106 cell groups, respectively. INTERPRETATION: This study demonstrates the safety of rexlemestrocel-L in diabetic nephropathy with suggestive effects on renal function to be confirmed in larger, appropriately powered trials.
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