TY - JOUR
T1 - Safety and tolerability of human placenta-derived cells (PDA001) in treatment-resistant crohn's disease
T2 - A phase 1 study
AU - Mayer, Lloyd
AU - Pandak, William M.
AU - Melmed, Gil Y.
AU - Hanauer, Stephen B.
AU - Johnson, Kristine
AU - Payne, Denise
AU - Faleck, Herbert
AU - Hariri, Robert J.
AU - Fischkoff, Steven A.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/3
Y1 - 2013/3
N2 - Background: The clinical utility of cellular therapies is being investigated in a broad range of therapeutic areas. This phase 1 study represents the first exploration of PDA001, a preparation of cells cultured from human placental tissue, in subjects with Crohn's disease. Methods: Twelve subjects with active, moderate-to-severe Crohn's disease unresponsive to previous therapy were given 2 intravenous infusions of PDA001 1 week apart, monitored weekly for 5 weeks, and assessed at 6 months, 1 year, and 2 years after infusion. Six subjects received 2 infusions of 2 · 108 cells (low dose), and 6 subjects received 2 infusions of 8 · 108 cells (high dose). Results: Mean baseline Crohn's Disease Activity Index in the low-dose and high-dose groups was 305 and 364, respectively, and mean C-reactive protein was 8 mg/L and 49 mg/L, respectively. All subjects in the low-dose group achieved a clinical response (a Crohn's Disease Activity Index decrease of $70 points versus baseline), and 3 achieved remission (a Crohn's Disease Activity Index decrease of $100 to ,150 points). Two subjects in the high-dose group achieved response, and none met remission criteria. Most adverse events were mild to moderate in severity and included headache, nausea, fever, and infusion site reactions. Conclusions: PDA001 infusions appear safe and well-tolerated in subjects with treatment-resistant Crohn's disease. A response was seen in all subjects in the low-dose group. The high-dose group, with a higher baseline disease activity, had only 2 responders, suggesting a more treatment-resistant population. A phase 2 study in this patient population is ongoing.
AB - Background: The clinical utility of cellular therapies is being investigated in a broad range of therapeutic areas. This phase 1 study represents the first exploration of PDA001, a preparation of cells cultured from human placental tissue, in subjects with Crohn's disease. Methods: Twelve subjects with active, moderate-to-severe Crohn's disease unresponsive to previous therapy were given 2 intravenous infusions of PDA001 1 week apart, monitored weekly for 5 weeks, and assessed at 6 months, 1 year, and 2 years after infusion. Six subjects received 2 infusions of 2 · 108 cells (low dose), and 6 subjects received 2 infusions of 8 · 108 cells (high dose). Results: Mean baseline Crohn's Disease Activity Index in the low-dose and high-dose groups was 305 and 364, respectively, and mean C-reactive protein was 8 mg/L and 49 mg/L, respectively. All subjects in the low-dose group achieved a clinical response (a Crohn's Disease Activity Index decrease of $70 points versus baseline), and 3 achieved remission (a Crohn's Disease Activity Index decrease of $100 to ,150 points). Two subjects in the high-dose group achieved response, and none met remission criteria. Most adverse events were mild to moderate in severity and included headache, nausea, fever, and infusion site reactions. Conclusions: PDA001 infusions appear safe and well-tolerated in subjects with treatment-resistant Crohn's disease. A response was seen in all subjects in the low-dose group. The high-dose group, with a higher baseline disease activity, had only 2 responders, suggesting a more treatment-resistant population. A phase 2 study in this patient population is ongoing.
KW - Biologic therapies
KW - Cellular therapies
KW - Crohn's disease
KW - Immunomodulators
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U2 - 10.1097/MIB.0b013e31827f27df
DO - 10.1097/MIB.0b013e31827f27df
M3 - Article
C2 - 23429460
AN - SCOPUS:84876367679
SN - 1078-0998
VL - 19
SP - 754
EP - 760
JO - Inflammatory bowel diseases
JF - Inflammatory bowel diseases
IS - 4
ER -