Background: Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full- Term human placenta, is a new approach in the treatment of patients with multiple sclerosis. Objective: This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis. Methods: This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2- dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis. The study was conducted at 6 sites in the United States and 2 sites in Canada. Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 (150 x 106 cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600 x 106 cells) or placebo. Monthly brain magnetic resonance imaging scans were performed. The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity. This was monitored using Cutter's rule (> 5 new gadolinium lesions on 2 consecutive scans) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse. Results: Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment: 6 to low-dose PDA-001, 6 to high-dose PDA-001, and A to placebo. No patient met Cutter s rule. One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001. No other patient had an increase in Expanded Disability Status Scale score >0.5, and most had stable or decreasing Expanded Disability Status Scale scores. With high-dose PDA-001, 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis. Other adverse events were mild to moderate and included headache, fatigue, infusion site reactions, and urinary tract infection. Conclusion: PDA-001 infusions were safe and well tolerated in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis patients. No paradoxical worsening of lesion counts was noted with either dose.
Bibliographical noteFunding Information:
Drs Lubin, Bowen, Huddlestone, Kremenchutzky, Carpenter, Corboy, Freedman, and Krupp have received grant support from Celgene Corporation. Drs Lublin, Corboy, and Freedman have served as remunerated members of a Celgene advisory committee. Ms Paulo, Dr Hariri, and Dr Fischkoff are full-time employees of Celgene Corporation with stock and stock options.
This study was supported by Celgene Cellular Therapeutics , Warren, NJ. The authors received editorial support in the preparation of this report from Christine H. Blood, PhD, of Peloton Advantage, funded by Celgene Cellular Therapeutics. The authors, however, directed and are fully responsible for all content and editorial decisions for this report.
© 2014 Elsevier B.V. All rights reserved.
Copyright 2017 Elsevier B.V., All rights reserved.
- Cell therapy
- Clinical trial
- Mesenchymal stromal cells
- Multiple sclerosis