Human placenta-derived cells (PDA-001) for the treatment of moderate-to-severe Crohn's disease: A phase 1b/2a study
Department
Administration
Document Type
Article
Publication Title
Inflammatory Bowel Diseases
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.
First Page
1809
Last Page
1816
DOI
10.1097/MIB.0000000000000441
Volume
21
Issue
8
Publication Date
5-15-2015
PubMed ID
25985246
Recommended Citation
Melmed, G., Pandak, W., 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