Human Placenta-Derived Cells (PDA001) for the Treatment of Moderate-to-Severe Crohnʼs Disease: Results of a Phase 1b/2a Study (2012)

Purpose: PDA001 is a preparation of placenta-derived cells with immunomodulatory effects in animal models. An open label trial demonstrated safety and tolerability of PDA001 at 1 unit (200 × 106 cells) and 4 units (800 × 106 cells) in patients with Crohn's disease. Methods: We evaluated the safety and efficacy of PDA001 using an adaptive 1b/2a trial design in patients with moderate-to-severe Crohn's disease (CDAI 220-450). All subjects had active inflammation on colonoscopy or elevated fecal calprotectin, and an inadequate response to conventional therapy. Concomitant therapy with stable doses of immunomodulators and biologics was permitted. Subjects received 8 units (1.6 × 107 cells) of PDA001 in the phase 1b study. For the phase 2a study, subjects were randomly assigned to receive placebo, 1 unit, or 4 units of PDA001 in a double-blinded fashion. For each arm, two infusions were administered 1 week apart. The primary endpoint was induction of clinical response (100 points or >25% decrease in CDAI) at both week 4 and week 6. Secondary endpoints included clinical remission (CDAI<150) at weeks 4 and 6 and improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) scores, CRP and stool calprotectin. Results: Fifty patients were enrolled; 48 were included in the safety analysis, and 44 randomized subjects were assessed for efficacy in a modified intention-to-treat analysis. Four subjects received 8 units PDA001 after which subsequent patients were randomized to 1 unit or 4 units of PDA001, or placebo. Baseline demographics and disease activity were similar across treatment groups. In the randomized 2a study, the primary endpoint was achieved in 10/28 (36%) among those treated with PDA001 and in 0/16 (0%) among those treated with placebo. Response was greater for both the 1 unit (33%, p=0.04) and 4 unit (39%, p=0.013) doses relative to placebo (0%). Clinical remission at weeks 4 and 6 was achieved in 4/28 (13%) among those treated with PDA001, and 0% in those treated with placebo. At week 6, mean improvement in IBDQ was greater with PDA001 (16.3 points) compared to placebo (3.9 points). No consistent changes in CRP or calprotectin were observed. Two serious adverse events (SAE) occurred at the 8 unit dose including a suspected systemic hypersensitivity reaction. Thus, this dose was not used in the 2a study. SAEs occurred in 9 of 28 (32%) of those treated with PDA001 and in 1 of 16 (7%) of those treated with placebo. Pneumonia occurred in one patient 77 days after infusion and colon cancer was diagnosed in another at 74 days after infusion. Conclusion: A two-infusion regimen of PDA001 can induce clinical response in patients with moderate-to-severe Crohn's disease. Additional studies to optimize efficacy and safety are warranted. Disclosure: Dr. Steven Fischkoff, Dr. Robert Hariri, Kristine Johnson - Full time employee, Celgene. All other authors have received research support as investigators on this study except Dr. Targan who does not have a direct relationship with Celgene. This research was supported by an industry grant from The study was funded in total by Celgene Corporation.