Allogeneic Mesenchymal Precursor Cells (MPC) in Diabetic Nephropathy: A Randomized, Placebo-controlled, Dose Escalation Study.
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.
['Packham|David K|DK|', 'Fraser|Ian R|IR|', 'Kerr|Peter G|PG|', 'Segal|Karen R|KR|']
D000368:Aged D003928:Diabetic Nephropathies D005260:Female D005919:Glomerular Filtration Rate D006801:Humans D008297:Male D045164:Mesenchymal Stem Cell Transplantation D059630:Mesenchymal Stem Cells D008875:Middle Aged D014184:Transplantation, Homologous D016896:Treatment Outcome D016482:Urinalysis
Mesenchymal precursor cells Diabetic nephropathy Glomerular filtration rate Inflammation Stem cell