Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: A randomized, placebo-controlled, multiple-dose study

• DOI: 10.1016/j.msard.2014.08.002
• Publication Date: 2014-08-28T20:50:28Z
• Authors: Fred D. Lublin; James D. Bowen; John Huddlestone; Marcelo Kremenchu...; Adam Carpenter; John R. Corboy; Mark S. Freedman; Lauren Krupp; Corri Paulo; Robert J. Hariri; Steven A. Fischkoff
• Keywords: Adult; Male; Canada; Contrast Media; Gadolinium; Mesenchymal Stem Cell Transplantation; Severity of Illness Index; Disability Evaluation; 03 medical and health sciences; Multiple Sclerosis, Relapsing-Remitting; 0302 clinical medicine; Double-Blind Method; Recurrence; Humans; 10. No inequality; Brain; Middle Aged; Multiple Sclerosis, Chronic Progressive; Magnetic Resonance Imaging; United States; 3. Good health; Treatment Outcome; Female; Follow-Up Studies

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.This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis.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 (150×10(6) cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600×10(6) 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.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 4 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.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.