Gil Y Melmed1, 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. 1. 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.
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.
RCT Entities:
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: Henry Caplan; Scott D Olson; Akshita Kumar; Mitchell George; Karthik S Prabhakara; Pamela Wenzel; Supinder Bedi; Naama E Toledano-Furman; Fabio Triolo; Julian Kamhieh-Milz; Guido Moll; Charles S Cox Journal: Front Immunol Date: 2019-07-31 Impact factor: 7.561