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1. Jay S. Skyler(1),Vivian A. Fonseca(2), Karen R. Sega(3), Julio Rosenstock(4),
on behalf of the MSB-DM003 Investigators
Author Affiliations
1).-Diabetes Research Institute, University of Miami, Miami, FL
2).-Tulane University Health Sciences Center, New Orleans, LA
3).-Mesoblast Inc., New York, NY
4).-Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX
Corresponding author: Jay S. Skyler, jskyler@med.miami.edu.
Abstract
OBJECTIVE To assess the safety, tolerability, and feasibility of adult allogeneic bone marrow?derived mesenchymal precursor cells (MPCs) in type 2 diabetes inadequately controlled with metformin either alone or with one additional oral antidiabetic agent.
RESEARCH DESIGN AND METHODS The study was a dose-escalating randomized placebo-controlled trial assessing one intravenous (IV) infusion of MPCs (rexlemestrocel-L; Mesoblast Inc.) 0.3 × 106/kg (n = 15), 1.0 × 106/kg (n = 15), or 2.0 × 106/kg (n = 15) or placebo (n = 16). Study duration was 12 weeks.
RESULTS Subjects (21 women, 40 men) with a mean ± SD baseline HbA1c 8.3 ± 1.0% (67 ± 10.9 mmol/mol), BMI 33.5 ± 5.5 kg/m2, and diabetes duration 10.1 ± 6.0 years were enrolled at 18 U.S. sites. No acute adverse events (AEs) were associated with infusion. No serious AEs, serious hypoglycemia AEs, or discontinuations due to AEs over 12 weeks were found. No subjects developed donor-specific anti-HLA antibodies or became sensitized. The safety profile was comparable among treatment groups. Compared with placebo, a single IV infusion of rexlemestrocel-L reduced HbA1c at all time points after week 1. The adjusted least squares mean ± SE dose-related differences in HbA1c from placebo in the rexlemestrocel-L groups ranged from ?0.1 ± 0.2% (?1.1 ± 2.2 mmol/mol) to ?0.4 ± 0.2% (4.4 ± 2.2 mmol/mol) at 8 weeks and from 0.0 ± 0.25% to ?0.3 ± 0.25% (?3.3 ± ?2.7 mmol/mol) at 12 weeks (P < 0.05 for 2.0 × 106/kg dose at 8 weeks). The clinical target HbA1c <7% (53 mmol/mol) was achieved by 33% (5 of 15) of the subjects who received the 2.0 × 106/kg dose vs. 0% of those who received placebo (P < 0.05).
CONCLUSIONS This short-term study demonstrates the safety and feasibility of up to 246 million MPCs in subjects with type 2 diabetes.
http://care.diabetesjournals.org/content/early/2015/07/01/dc14-2830.abstract
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