Title | Safety and tolerability of human placenta-derived cells (PDA001) in treatment-resistant crohn's disease: a phase 1 study. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Mayer L, Pandak WM, Melmed GY, Hanauer SB, Johnson K, Payne D, Faleck H, Hariri RJ, Fischkoff SA |
Journal | Inflamm Bowel Dis |
Volume | 19 |
Issue | 4 |
Pagination | 754-60 |
Date Published | 2013 Mar-Apr |
ISSN | 1536-4844 |
Keywords | Adolescent, Adult, Aged, Aged, 80 and over, Cell- and Tissue-Based Therapy, Cells, Cultured, Crohn Disease, Female, Humans, Male, Maximum Tolerated Dose, Middle Aged, Placenta, Pregnancy, Remission Induction, Salvage Therapy, Surveys and Questionnaires, Treatment Outcome, Young Adult |
Abstract | 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 × 10 cells (low dose), and 6 subjects received 2 infusions of 8 × 10 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. |
DOI | 10.1097/MIB.0b013e31827f27df |
Alternate Journal | Inflamm. Bowel Dis. |
PubMed ID | 23429460 |
PubMed Central ID | PMC4272923 |
Grant List | P01 DK072201 / DK / NIDDK NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm