Fred D Lublin1, James D Bowen2, John Huddlestone3, Marcelo Kremenchutzky4, Adam Carpenter5, John R Corboy6, Mark S Freedman7, Lauren Krupp8, Corri Paulo9, Robert J Hariri10, Steven A Fischkoff11. 1. Icahn School of Medicine at Mount Sinai, 5 East 98th Street, Box 1138, New York, NY 10029, United States. Electronic address: fred.lublin@mssm.edu. 2. Swedish Neuroscience Institute, 1600 East Jefferson, Suite 205, Seattle, WA 98122, United States. Electronic address: James.Bowen@swedish.org. 3. MultiCare Health System-Neuroscience Center of Washington, 915 6th Avenue, Suite 101 and 200, Tacoma, WA 98405, United States. Electronic address: John.Huddlestone@multicare.org. 4. London Health Sciences Centre, University Hospital, Multiple Sclerosis Clinic, 7th Floor, 339 Windermere Road, PO Box 5339, London, ON, Canada N6A 5A5. Electronic address: Marcelo.Kremenchutzky@lhsc.on.ca. 5. University of Minnesota, Clinical Neuroscience Research Unit, 717 Delaware Street SE, Suite 246, Minneapolis, MN 55414, United States. Electronic address: carpe004@umn.edu. 6. University of Colorado Denver, 12631 E. 17th Avenue, Mail Stop B185, Room 5506, Aurora, CO 80045, United States. Electronic address: John.Corboy@ucdenver.edu. 7. The Ottawa Hospital Multiple Sclerosis Clinic, 501 Smyth Road, Box 607, Ottawa, Ontario, Canada K1H 8L6. Electronic address: mfreedman@ottawahospital.on.ca. 8. MS Comprehensive Care Center, MSC T12-020 SUNY, Stony Brook, NY 11794, United States. Electronic address: Lauren.Krupp@stonybrook.edu. 9. Celgene Cellular Therapeutics, 7 Powderhorn Road, Warren, NJ 07059, United States. Electronic address: cpaulo@celgene.com. 10. Celgene Cellular Therapeutics, 7 Powderhorn Road, Warren, NJ 07059, United States. Electronic address: rhariri@celgene.com. 11. Celgene Cellular Therapeutics, 7 Powderhorn Road, Warren, NJ 07059, United States. Electronic address: sfischkoff@celgene.com.
Abstract
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 (150×10(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. 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 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. 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.
RCT Entities:
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 (150×10(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. 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 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. CONCLUSION:PDA-001 infusions were safe and well tolerated in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosispatients. No paradoxical worsening of lesion counts was noted with either dose.
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: Jayden A Smith; Alexandra M Nicaise; Rosana-Bristena Ionescu; Regan Hamel; Luca Peruzzotti-Jametti; Stefano Pluchino Journal: Front Cell Dev Biol Date: 2021-07-09