title: Human Placenta-derived Cells (PDA-001) for the Treatment of Moderate-to-severe Crohn's Disease: A Phase 1b/2a Study.
abstract: BACKGROUND
  PDA-001 (cenplacel-L), a preparation of placenta-derived mesenchymal-like adherent cells with immunomodulatory effects, previously demonstrated safety and tolerability in an open-label Crohn's disease (CD) study. The current phase 1b/2a study evaluated the safety and efficacy of PDA-001 in subjects with moderate-to-severe CD.
  
  
  METHODS
  Subjects had active inflammation on colonoscopy or elevated fecal calprotectin and inadequate response to conventional therapy. Concomitant therapy with stable doses of immunomodulators and/or biologics was permitted. Subjects received 8 units of PDA-001 (1.5 × 10 cells per unit) in the phase 1b open-label study. In the phase 2a double-blind study, subjects were randomly assigned placebo, 1 unit, or 4 units of PDA-001 (2 infusions 1 wk apart). The primary endpoint was induction of clinical response (≥100 points and/or 25% decrease in Crohn's Disease Activity Index) at 4 and 6 weeks.
  
  
  RESULTS
  Fifty subjects were enrolled (safety analysis, 50 subjects; efficacy analysis, 48 subjects). Four subjects received 8 units of PDA-001 (phase 1b study); 46 subjects were subsequently randomized to 1 or 4 units of PDA-001 or placebo (phase 2a study). The primary endpoint was achieved in 10/28 (36%) of PDA-001 subjects compared with placebo (0%, P = 0.026). Clinical remission was achieved in 4/28 (14%) of PDA-001 subjects compared with placebo (0%, P = 0.3). One treatment-related serious adverse event occurred (systemic hypersensitivity reaction at 8 units). In the phase 2a study, serious adverse events occurred in 9/28 (32%) of PDA-001 subjects and 1/16 (7%) of placebo subjects.
  
  
  CONCLUSIONS
  A 2-infusion regimen of PDA-001 induced clinical response in subjects with moderate-to-severe CD. Additional studies are warranted.
authors.affiliation: 1Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California; 2Department of Medicine, Virginia Commonwealth University, Richmond, Virginia; 3Rochester General Health System, Rochester, New York; 4Baylor College of Medicine, Houston, Texas; 5Department of Medicine, University of Utah, Salt Lake City, Utah; 6Department of Medicine, Vanderbilt University, Nashville, Tennessee; 7Case Western Reserve University, Cleveland, Ohio; 8Innovative Medical Research, Aventura, Florida; 9Department of Medicine, Mt. Sinai Medical Center, New York, New York; 10Department of Medicine, The University of Chicago Medicine, Chicago, Illinois; 11State University of New York at Stony Brook, Stony Brook, New York; 12Section of Digestive Diseases, Yale University, New Haven, Connecticut; 13Department of Medicine, University of California, Irvine, Irvine, California; and 14Celgene Cellular Therapeutics, Warren, New Jersey.
authors.forename: Gil Y
authors.initials: GY
authors.lastname: Melmed
authors.forename: William M
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authors.lastname: Pandak
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mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D003424:Crohn Disease / Q000473:pathology* / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D011379:Prognosis; D011788:Quality of Life; D012074:Remission Induction; D012449:Safety; D055815:Young Adult