Background: The clinical utility of cellular therapies is being investigated in a broad range of therapeutic areas. This phase 1 study represents the first exploration of PDA001, a preparation of cells cultured from human placental tissue, in subjects with Crohn’s disease.
Methods: Twelve subjects with active, moderate-to-severe Crohn’s disease unresponsive to previous therapy were given 2 intravenous infusions of PDA001 1 week apart, monitored weekly for 5 weeks, and assessed at 6 months, 1 year, and 2 years after infusion. Six subjects received 2 infusions of 2 × 108 cells (low dose), and 6 subjects received 2 infusions of 8 × 108 cells (high dose).
Results: Mean baseline Crohn’s Disease Activity Index in the low-dose and high-dose groups was 305 and 364, respectively, and mean C-reactive protein was 8 mg/L and 49 mg/L, respectively. All subjects in the low-dose group achieved a clinical response (a Crohn’s Disease Activity Index decrease of ≥70 points versus baseline), and 3 achieved remission (a Crohn’s Disease Activity Index decrease of ≥100 to <150 points). Two subjects in the high-dose group achieved response, and none met remission criteria. Most adverse events were mild to moderate in severity and included headache, nausea, fever, and infusion site reactions.
Conclusions: PDA001 infusions appear safe and well-tolerated in subjects with treatment-resistant Crohn’s disease. A response was seen in all subjects in the low-dose group. The high-dose group, with a higher baseline disease activity, had only 2 responders, suggesting a more treatment-resistant population. A phase 2 study in this patient population is ongoing.
Article first published online 20 February 2013
*Mount Sinai School of Medicine, New York, New York
†Virginia Commonwealth University, Richmond, Virginia
‡Cedars Sinai Medical Center, Los Angeles, California
§University of Chicago Medical Center, Chicago, Illinois
‖Celgene Cellular Therapeutics, Warren, New Jersey.
Reprints: Lloyd Mayer, MD, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box #1089, New York, NY 10029 (e-mail: email@example.com).
This study was funded by Celgene Cellular Therapeutics, Warren, NJ. Writing support (funded by CCT) was provided by Watermeadow Medical USA. The authors have had full access to the study data and take full responsibility for the contents of this manuscript.
Received June 20, 2012
Accepted June 21, 2012