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.
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.
Authors: Patricia A Zuk; Min Zhu; Peter Ashjian; Daniel A De Ugarte; Jerry I Huang; Hiroshi Mizuno; Zeni C Alfonso; John K Fraser; Prosper Benhaim; Marc H Hedrick Journal: Mol Biol Cell Date: 2002-12 Impact factor: 4.138
Authors: E J Irvine; G R Greenberg; B G Feagan; F Martin; L R Sutherland; A B Thomson; L G Nilsson; T Persson Journal: Inflamm Bowel Dis Date: 2000-08 Impact factor: 5.325
Authors: Stephen B Hanauer; William J Sandborn; Paul Rutgeerts; Richard N Fedorak; Milan Lukas; Donald MacIntosh; Remo Panaccione; Douglas Wolf; Paul Pollack Journal: Gastroenterology Date: 2006-02 Impact factor: 22.682
Authors: Carmela Rita Balistreri; Elena De Falco; Antonella Bordin; Olga Maslova; Alexander Koliada; Alexander Vaiserman Journal: Mol Biol Rep Date: 2020-03-03 Impact factor: 2.316
Authors: Hong-Jung Chen; Chien-Hsi Chen; Ming-Yao Chang; Da-Ching Tsai; Ellen Z Baum; Robert Hariri; Uri Herzberg; Patrick C H Hsieh Journal: Stem Cells Transl Med Date: 2015-02-11 Impact factor: 6.940
Authors: Rachele Ciccocioppo; Claudia C Dos Santos; Daniel C Baumgart; Giuseppina C Cangemi; Vincenzo Cardinale; Carolina Ciacci; Paolo De Coppi; Debashis Haldar; Catherine Klersy; M Cristina Nostro; Michael Ott; Lorenzo Piemonti; Alice A Tomei; Basak Uygun; Stefania Vetrano; Giuseppe Orlando Journal: Cytotherapy Date: 2018-02-15 Impact factor: 5.414
Authors: Devlin T Boyt; Lauren K Boland; Anthony J Burand; Alex J Brown; James A Ankrum Journal: J R Soc Interface Date: 2020-06-17 Impact factor: 4.118