title: Safety and efficacy of intramuscular human placenta-derived mesenchymal stromal-like cells (cenplacel [PDA-002]) in patients who have a diabetic foot ulcer with peripheral arterial disease.
abstract: The objective of this study was to examine the safety of cenplacel (PDA-002) in patients with peripheral arterial disease (PAD) and a diabetic foot ulcer (DFU). Cenplacel is a mesenchymal-like cell population derived from full-term human placenta. This phase 1, dose-escalation study investigated cenplacel in diabetic patients with chronic DFUs (Wagner grade 1 or grade 2) and PAD [ankle-brachial index (ABI) >0·5 and ≤0·9], enrolled sequentially into each of four dose cohorts (3 × 106, 10 × 106, 30 × 106and 100 × 106cells; administered intramuscularly on study days 1 and 8 in combination with standard of care). Overall, cenplacel was well tolerated in all 15 patients in the study. Before enrollment, nine patients had an ulcer for ≥6 months and 11 had an ABI of 0·7-0·85. No patient met dose-limiting toxicity criteria and no treatment-related serious adverse events were reported. There was preliminary evidence of ulcer healing in seven patients (five complete; two partial) within 3 months of cenplacel treatment, and circulating endothelial cell levels (a biomarker of vascular injury in PAD) were decreased within 1 month. Cenplacel was generally safe and well tolerated in patients with chronic DFUs and PAD. Outcomes from this study informed the doses, endpoints, biomarkers and patient population for an ongoing phase 2 trial.
authors.affiliation: Rosalind Franklin University, North Chicago, IL, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Wu
authors.affiliation: Endeavor Clinical Trials PA, San Antonio, TX, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Pollak
authors.affiliation: Phoenix VA Health Care System, Phoenix, AZ, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Frykberg
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Maha
authors.initials: M
authors.lastname: Karnoub
authors.affiliation: Celgene Cellular Therapeutics, Warren, NJ, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Jankovic
authors.affiliation: Celgene Cellular Therapeutics, Warren, NJ, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Fischkoff
authors.affiliation: Celgene Cellular Therapeutics, Warren, NJ, USA.
authors.forename: Denesh
authors.initials: D
authors.lastname: Chitkara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D017719:Diabetic Foot / Q000503:physiopathology* / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000503:physiopathology*; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D014945:Wound Healing / Q000502:physiology*; D055815:Young Adult
keywords: Cenplacel; Diabetic foot ulcer; Mesenchymal-like cells; Peripheral arterial disease; Placenta-derived cell population