title: Safety and tolerability of human placenta-derived cells (PDA001) in treatment-resistant crohn's disease: a phase 1 study.
abstract: 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 × 10 cells (low dose), and 6 subjects received 2 infusions of 8 × 10 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.
authors: Mount Sinai School of Medicine, New York, NY 10029, USA. lloyd.mayer@mssm.edu
authors: Lloyd
authors: L
authors: Mayer
authors: William M
authors: WM
authors: Pandak
authors: Gil Y
authors: GY
authors: Melmed
authors: Stephen B
authors: SB
authors: Hanauer
authors: Kristine
authors: K
authors: Johnson
authors: Denise
authors: D
authors: Payne
authors: Herbert
authors: H
authors: Faleck
authors: Robert J
authors: RJ
authors: Hariri
authors: Steven A
authors: SA
authors: Fischkoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D003424:Crohn Disease / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D012074:Remission Induction; D016879:Salvage Therapy; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult