用于治疗中重度克罗恩病的人胎盘源细胞（PDA - 001）：一项1b/2a期研究。

Human Placenta-derived Cells (PDA-001) for the Treatment of Moderate-to-severe Crohn's Disease: A Phase 1b/2a Study.

作者信息

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

机构信息

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.

出版信息

Inflamm Bowel Dis. 2015 Aug;21(8):1809-16. doi: 10.1097/MIB.0000000000000441.

DOI:10.1097/MIB.0000000000000441

PMID:25985246

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.

摘要

背景

PDA - 001（cenplacel - L）是一种具有免疫调节作用的胎盘来源的间充质样贴壁细胞制剂，先前在一项开放标签的克罗恩病（CD）研究中已证明其安全性和耐受性。当前的1b/2a期研究评估了PDA - 001在中重度CD患者中的安全性和疗效。

方法

受试者在结肠镜检查时存在活动性炎症或粪便钙卫蛋白升高，且对传统治疗反应不佳。允许同时使用稳定剂量的免疫调节剂和/或生物制剂进行治疗。在1b期开放标签研究中，受试者接受8个单位的PDA - 001（每单位1.5×10⁶个细胞）。在2a期双盲研究中，受试者被随机分配接受安慰剂、1个单位或4个单位的PDA - 001（分2次输注，间隔1周）。主要终点是在4周和6周时诱导临床反应（克罗恩病活动指数降低≥100分和/或降低25%）。

结果

共纳入50名受试者（安全性分析，50名受试者；疗效分析，48名受试者）。4名受试者接受了8个单位的PDA - 001（1b期研究）；随后46名受试者被随机分配接受1个单位或4个单位的PDA - 001或安慰剂（2a期研究）。与安慰剂组（0%，P = 0.026）相比，PDA - 001组中10/28（36%）的受试者达到了主要终点。与安慰剂组（0%，P = 0.3）相比，PDA - 001组中4/28（14%）的受试者实现了临床缓解。发生了1例与治疗相关的严重不良事件（8个单位时出现全身性过敏反应）。在2a期研究中，PDA - 001组9/28（32%）的受试者和安慰剂组1/16（7%）的受试者发生了严重不良事件。