The Mellen Center in Cleveland and the Lou Ruvo Center for Brain Health in Las Vegas have very active experimental therapeutics programs. Dr. Cohen directs the overall program, but all Mellen Center professional staff and fellows participate in clinical trials in various roles. Clinical trials have investigated disease modifying therapies, overall treatment approaches, neuroprotective strategies, and repair-promoting strategies (including cell-based therapies) in relapsing and progressive multiple sclerosis, pediatric multiple sclerosis, and neuromyelitis optica spectrum disorders. These trials have included Phase 1 safety studies, Phase 2 proof-of-concept trials, pivotal Phase 3 trials, long-term extension studies, and post-marketing studies.
The Mellen Center Academic Coordinating Center provides academic administrative for multicenter trials, including trial design, core laboratories, data management, and statistical analysis. Mellen Center staff have been involved in varying capacities in the development of nearly every medication approved to treat multiple sclerosis and have served as the Coordinating Principal Investigator of multinational industry-sponsored pivotal Phase 3 trials, including IMPACT (interferon beta-1a), SENTINEL (natalizumab), TRANSFORMS (fingolimod), FORTE (glatiramer acetate), CONFIRM (dimethyl fumarate), GATE (generic glatiramer acetate), and RADIANCE (ozanimod). In addition, Mellen staff have served on numerous study steering committees, data safety monitoring boards, eligibility or endpoint adjudication committees, advisory committees, and grant peer-review committees.
The Mellen Center is involved not only in industry-sponsored studies but staff also have directed several large, grant-funded trials, including a Phase 1/2 trial of mesenchymal stem cell transplantation supported by Department of Defense (DOD) and National Institutes of Health (NIH), a multicenter Phase 2 trial of ibudilast funded by NIH and conducted through the NeuroNext network, an international pragmatic trial of escalation versus early highly efficacious therapeutic strategies supported by Patient-Centered Outcomes Research Institute (PCORI), and a randomized trial of immunoablation followed by autologous hematopoietic stem cell transplantation (NIH).
Contracts for industry-sponsored clinical trials from Acorda, Adamas, Athena, Atlas5D, Avanir, Biogen, Elan, Genentech, Immunex, Mallinckrodt, MedDay, Medimmune, Novartis, Pharmacia, Receptos/Celgene, Sanofi/Genzyme, Synthon, Teva, and TG Therapeutics.
DOD W81XWH-10-1-0270, A phase I assessment of mesenchymal stem cells for the treatment of multiple sclerosis, Cohen (PI), 05/2010 – 05//2014.
NIH 1 RO1 NS074787, Immunobiology of mesenchymal stem cell transplantation in multiple sclerosis, Cohen (PI), 02/2011 – 11/2014.
NIH 1U01NS082329-01A1, Ibudilast phase II trial in progressive MS, Fox (PI), 07/2013 – 06/2018.
NIH 1U01NS082329-01A1S1, Supplement to ibudilast phase II trial in progressive MS, Fox (PI), 07/2013 – 06/2018.
National MS Society RG 4778-A-6, Ibudilast phase II trial in progressive MS, Fox (PI), 10/2013 – 09/2018.
PCORI R-1610-37047, Determining the effectiveness of early Intensive versus escalation approaches for the treatment of relapsing-remitting multiple sclerosis (DELIVER-MS), Ontaneda (PI) 02/2018 – 01/2023
Benefit of intramuscular interferon beta-1a on MSFC progression in secondary progressive MS.Cohen JA, Cutter GR, Fischer JS, Goodman AD, Heidenreich FR, Kooijmans MF, Rudick RA, Sandrok AW, Simon JH, Simonian NA, Tsao EC, Whitaker JN, for the IMPACT Investigators. Neurology 2002;59:679-687. PMID: 12221157
Results of the Avonex Combination Trial (ACT) in relapsing-remitting MS. Cohen JA, Imrey PB, Calabresi PA, Edwards KR, Eickenhorst T, Felton WL, Fisher E, Fox RJ, Goodman AD, Hara-Cleaver C, Hutton GJ, Mandell BF, Scott TF, Zhang H Apperson-Hansen C, Beck GJ, Houghtaling PL, Karafa MT, Stadtler M for the ACT Investigators.Neurology 2009;72:535-541. PMID: 19204263
Intramuscular interferon beta-1a therapy in patients with relapsing-remitting multiple sclerosis: a 15-year follow-up study. RA, Weinstock-Guttman B, Bourdette D, Foulds P, You X, Rudick RA. Mult Scler. 2010;16(5):588-96. PMID: 20167591
Oral fingolimod or intramuscular interferon in relapsing multiple sclerosis. Cohen JA, Barkhof F, Comi G, Hartung H-P, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G, Tiel-Wilck K, de Vera A, Jin J, Stites T, Wu S, Aradhye S, Kappos L, for the TRANSFORMS Study Group. N Engl J Med 2010;362:402-415. PMID: 20089954
Alemtuzumab versus interferon beta as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara M, Compston DAS, for the CARE-MS I investigators. Lancet 2012;380:1819-1828. PMID: 23122652
Disability outcomes in multiple sclerosis clinical trials: current status and future prospects.Cohen JA, Reingold SC, Polman CH, Wolinsky JS, on behalf of the International Advisory Committee on Clinical Trials in Multiple Sclerosis. Lancet Neurol 2012;11:467-476. PMID: 22516081.
Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT; CONFIRM Study Investigators.N Engl J Med. 2012;367(12):1087-97. PMID: 22992072
Equivalence of generic glatiramer acetate in multiple sclerosis. Cohen JA, Belova A, Selmaj K, Wolf C, Oberyé J, van den Tweel E, PhD, Mulder R, Koper N, Voortman G, Barkhof F, for the GATE Study Group. JAMA Neurol 2015;72:1433-1441. PMID: 26458034
MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study. Fox RJ, Cree BA, De Sèze J, Gold R, Hartung HP, Jeffery D, Kappos L, Kaufman M, Montalbán X, Weinstock-Guttman B, Anderson B, Natarajan A, Ticho B, Duda P.Neurology. 2014;82(17):1491-8. PMID: 24682966
Clinical trials in progressive multiple sclerosis: Lessons learned and future perspectives. D, Fox RJ, Chataway J.Lancet Neurol. 2015;14(2):208-223. PMID: 25772899.
Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomized, placebo-controlled, phase 2 trial. Cohen JA, Arnold DL, Comi G, Bar-Or A, Gujrathi S, Hartung JP, Cravets M, Olson A, Frohna PA, and Selmaj KW, for the RADIANCE Study Group. Lancet Neurol 2016;15:373-381. PMID: 26879276.
Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis. Fox RJ, Coffey CS, Cudkowicz ME, Gleason T, Goodman A, Klawiter EC, Matsuda K, McGovern M, Conwit R, Naismith R, Ashokkumar A, Bermel R, Ecklund D, Koepp M, Long J, Natarajan S, Ramachandran S, Skaramagas T, Thornell B, Yankey J, Agius M, Bashir K, Cohen B, Coyle P, Delgado S, Dewitt D, Flores A, Giesser B, Goldman M, Jubelt B, Lava N, Lynch S, Miravalle A, Moses H, Ontaneda D, Perumal J, Racke M, Repovic P, Riley C, Severson C, Shinnar S, Suski V, Weinstock-Gutman B, Yadav V, Zabeti A. Clin Trials. 2016;50:166-77. PMID: 27521810.
Clinical outcome measures for progressive MS trials. D, Cohen JA, Amato MP. Mult Scler J 2017;23(12):1627-1635. PMID: 29041863.
Progressive multiple sclerosis: Prospects for disease therapy, repair, and restoration of function. D, Thompson AJ, Fox RJ, Cohen JA. Lancet. 2017;389(10076):1357-1366. PMID: 27889191.
Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis. Cohen JA, Imrey PB, Planchon SM, Bermel RA, Fisher E, Fox RJ, Bar-Or A, Sharp SL, Skaramagas TT, Jagodnik P, Karafa M, Morrison S, Reese Koc J, Gerson SL, Lazarus HM. Mult Scler J published online 06 April 2017. PMID: 28381130
Safety and efficacy of ADS-5102 (amantadine) extended release capsules to improve walking in multiple sclerosis: a randomized, placebo-controlled, phase 2 trial.Cohen JA, Hunter SF, Brown TR, Gudesblatt M, Thrower BW, Llorens L, Souza-Prien CJ, Ruby AE, Chernoff DN, Patni R. Mult Scler J Epub ahead of print 25 January 2018. PMID: 29368539.
Members & Collaborations
- Charlene Belsole
- Robert A Bermel, MD
- Francois Bethoux, MD
- Jesse Ray Brillhart
- Jeffrey A Cohen, MD
- Devon S Conway, MD MSc
- Robert J Fox, MD MSc
- Kalyani Gonuguntla
- Carrie M Hersh, DO MSc
- Le Hua, MD
- Timothy Hudec
- Peter B Imrey, PhD
- Dee Ivancic, CCRP
- Hong Li, MS
- John Mays, CCRP
- Marisa P McGinley, DO
- Stephanie Moore
- Brandon P Moss, MD
- Sneha Natarajan, PhD
- Daniel Ontaneda, MD MSc
- Sarah M Planchon-Pope, PhD
- Alexander Rae-Grant, MD
- Mary R Rensel, MD
- Jennifer Sedlak, RN BSN MSCN
- Susan Sharp, RN BSN MSCN CCRP
- Tammy Skaramagas, CCRP
- Darlene Stough RN MSCN CCRP
- Malory Weber, MBA
- M Alissa Willis, MD
- Cassie Zimmerman, MPH CCRP