Human placenta-derived cells (PDA-001) for the treatment of moderate-to-severe Crohn's disease: A phase 1b/2a study

Gil Y. Melmed*, William M. Pandak, Kevin Casey, Bincy Abraham, John Valentine, David Schwartz, Dahlia Awais, Issac Bassan, Simon Lichtiger, Bruce Sands, Stephen Hanauer, Robert Richards, Ioannis Oikonomou, Nimisha Parekh, Stephen Targan, Kristine Johnson, Robert Hariri, Steven Fischkoff

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Scopus citations

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 × 108 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.

Original languageEnglish (US)
Pages (from-to)1809-1816
Number of pages8
JournalInflammatory bowel diseases
Volume21
Issue number8
DOIs
StatePublished - Apr 29 2015

Keywords

  • Cell therapy
  • Crohn's disease
  • Immunomodulation
  • PDA-001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Fingerprint Dive into the research topics of 'Human placenta-derived cells (PDA-001) for the treatment of moderate-to-severe Crohn's disease: A phase 1b/2a study'. Together they form a unique fingerprint.

  • Cite this

    Melmed, G. Y., Pandak, W. M., Casey, K., Abraham, B., Valentine, J., Schwartz, D., Awais, D., Bassan, I., Lichtiger, S., Sands, B., Hanauer, S., Richards, R., Oikonomou, I., Parekh, N., Targan, S., Johnson, K., Hariri, R., & Fischkoff, S. (2015). Human placenta-derived cells (PDA-001) for the treatment of moderate-to-severe Crohn's disease: A phase 1b/2a study. Inflammatory bowel diseases, 21(8), 1809-1816. https://doi.org/10.1097/MIB.0000000000000441