Study design and patient demographics of the ULTIMATE phase III trials evaluating Ublituximab (UTX), a novel glycoengineered anti-CD20 monoclonal antibody (mAb), in patients with relapsing multiple sclerosis (RMS)
ECTRIMS Online Library. Steinman L. Sep 12, 2019; 279351; P991
Lawrence Steinman
Lawrence Steinman

Abstract: P991

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

L. Steinman1, E. Fox2, H.-P. Hartung3, E. Alvarez4, P. Qian5, S. Wray6, D. Robertson7, D. Huang8, K. Selmaj9, D. Wynn10, M. Weiss11, S. Power11, J. Bosco11, K. Mok11, B. Cree12

1Stanford University, Stanford, CA, 2Central Texas Neurology Consultants, Round Rock, TX, United States, 3Heinrich Heine University, Dusseldorf, Germany, 4University of Colorado, Aurora, CO, 5Swedish Medical Center, Seattle, WA, 6Hope Neurology, Knoxville, TN, 7University of South Florida, Tampa, FL, 8Center for Multiple Sclerosis, Mount Carmel Health System, Westerville, OH, United States, 9Department of Neurology, Medical Academy of Lodz, Lodz, Poland, 10Consultants in Neurology, Northbrook, IL, 11TG Therapeutics, New York, NY, 12UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, United States

Objective: To present the study design and patient demographics of the ULTIMATE I and II Phase III trials.
Background: UTX is a novel mAb targeting a unique epitope on the CD20 antigen and glyco-engineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). The greater ADCC potency may offer a benefit over currently available anti-CD20s in terms of lower doses and shorter infusion times. A 52 week multicenter Phase 2 study designed to assess the optimal dose and infusion time of UTX in RMS subjects has been completed with UTX demonstrating robust efficacy while being well tolerated. Two Phase III trials, ULTIMATE I and II, are fully enrolled and are investigating the efficacy and safety of UTX compared with oral teriflunomide in patients with RMS.
Methods: ULTIMATE I and II are two identical, global, randomized, double-blinded, double-dummy, active-controlled studies investigating the efficacy of 450mg UTX administered by intravenous infusion as a one-hour infusion every 24 weeks compared to 14mg oral teriflunomide, given once daily. Subjects in each study were randomized 1:1 to UTX plus oral placebo or teriflunomide plus placebo infusions. Eligible patients had a diagnosis of RMS (McDonald Criteria 2010), an Expanded Disability Status Scale (EDSS) score of 0-5.5, and age of 18-55 years. Subjects were required to have had at least 2 documented relapses within the past two years, one relapse in the past year, and/or 1 or more Gd-enhancing lesions in the year prior to screening. The primary endpoint is annualized relapse rate (ARR) at Week 96.
Results: As of September 2018, both ULTIMATE I and II studies had reached the target enrollment of 500 subjects per study. At completion of enrollment, a total of 549 and 545 patients were randomized to ULTIMATE I and II, respectively, across 10 countries. Median baseline age was 36 and 35 years, respectively in ULTIMATE I and II; 63% and 65% of patients were female in ULTIMATE I and II, respectively. At date of presentation, trial design and patient demographics will be reported.
Conclusions: The ULTIMATE I and II trials enrolled a total of 1,094 patients and will provide information on the efficacy and safety of ublituximab compared to teriflunomide in patients with RMS, with final results expected in 2020.
Disclosure: Dr. Lawrence Steinman has received compensation from TG Therapeutics, Tolerion, Novartis, Celgene, Atreca and Katexco. Dr. Edward Fox has received compensation for research, Consulting, Speakers' Bureau, and/or Advisory work from Biogen, Celgene, Chugai, EMD Serono, Genentech/Roche, MedDay, Novartis, Sanofi, Genzyme, Teva, and TG Therapeutics. Professor Hans-Peter Hartung received fees for consulting, serving on steering and data monitoring committees and adboards from BayerHealthcare, Biogen, GeNeuro, MedImmune, Merck, Novartis, Receptos Celgene, Roche, Safi Genzyme, Teva, TG Therapeutics. In the past 36 months, Bruce Cree has received personal compensation for consulting from Abbvie, Akili, Alexion, Biogen, EMD Serono, GeNeuro, Novartis, Sanofi Genzyme and TG Therapeutics. Dr. Enrique Alvarez has received Research grants/studies: Acorda, Biogen, Genentech, Novartis, TG Therapeutics, and Rocky Mountain MS Center; and has consulted for: Actelion, Biogen, Celgene, EMD Serono, Genentech, Genzyme, Novartis, Teva, and TG Therapeutics. Dr. Peiqing Qian has received speaking and consulting honoraria from Biogen, Teva and Genzyme. Dr. Sibyl Wray has conducted research and has been a consultant and speaker for Abbvie, Biogen, EMD Serono, Genentech/Roche, and Genzyme/Sanofi; has conducted research and been a consultant for Novartis; and has conducted research for Celgene and TG Therapeutics. Dr. Derrick Robertson, MD, has received consultancy fees from Alexion, Biogen, Celgene, EMD Serono, Genentech, Novartis, Sanofi Genzyme, and Teva Neuroscience; has received honoraria or speaker fees from Acorda, Alexion, Biogen, Celgene, EMD Serono, Genentech, Mallinckrodt, Novartis, Sanofi Genzyme, and Teva Neuroscience; and has received research grant support from Actelion, Biogen, EMD Serono, Genentech, Mallinckrodt, MedDay, Novartis, PCORI, Sanofi Genzyme, and TG Therapeutics. DeRen Huang, MD, PhD, served as a consultant for Biogen, Celgene and Novartis; and received speaker honoraria from Biogen, Genentech, Novartis and Teva Neuroscience. Professor Krzysztof Selmaj has received honoraria for speaking, consulting and serving for advisory boards for Merck, Novartis, Roche, Biogen, Celgene, Synthon and TG Therapeutics. Daniel Wynn, MD, has received speaking and/or consulting fees from Acorda Therapeutics, Avanir Pharmaceuticals, Biogen, EMD Serono, Hope Biosciences, Mallinckrodt, MAPI Pharma, Novartis, Roche/Genentech, Sanofi Genzyme, and Teva; has received research support from Acorda Therapeutics, Actelion, Adamas Pharma, Avanir Pharmaceuticals, Biogen, Chugai Pharma, EMD Serono, Eisai, Genentech/Roche, Mallinckrodt, Novartis,Osmotica, Receptos/Celgene, SanBio, Sunovion, Sanofi Genzyme, Teva, TG Therapeutics, and the National MS Society. Michael S. Weiss, Sean Power, Jenna Bosco, and Koby Mok: Employed by TG Therapeutics.

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