Oral Cladribine Capsules for Generalized Myasthenia Gravis: Design of the Actively Recruiting Phase 3 MyClad Study
Konrad Rejdak1, James F. Howard Jr.2, Gary Cutter3, Kevin O'Connor4, Mazen Dimachkie5, Jacqueline Palace6, Andreas Meisel7, Renato Mantegazza8, Axel Nolting9, Sathej Gopalakrishnan9, Claire Le Bolay10, Andrija Javor11, Nektaria Alexandri9, Dominic Jack12, Henry Kaminski13
1Department of Neurology, Medical University of Lublin, 2Department of Neurology, University of North Carolina at Chapel Hill, 3School of Public Health – Biostatistics, University of Alabama at Birmingham, 4Departments of Neurology and Immunobiology, Yale School of Medicine, Yale University, 5Department of Neurology, University of Kansas Medical Center, 6Nuffield Department of Clinical Neurosciences, University of Oxford, 7Department of Neurology with Experimental Neurology, Charité – Universitätsmedizin Berlin, 8Neuroimmunology and Neuromuscular Diseases, IRCCS Carlo Besta, 9The healthcare business of Merck KGaA, Darmstadt, Germany, 10Merck Santé S.A.S., an affiliate of the healthcare business of Merck KGaA, Darmstadt, Germany, 11Ares Trading SA, an affiliate of the healthcare business of Merck KGaA, Darmstadt, Germany, 12Merck Serono Ltd., an affiliate of the healthcare business of Merck KGaA, Darmstadt, Germany, 13Department of Neurology and Rehabilitation Medicine, School of Medicine and Health Sciences, George Washington University
Objective:
To evaluate the efficacy and safety of a new oral formulation of cladribine versus placebo in generalized myasthenia gravis (gMG).
Background:
Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disorder of neuromuscular junction transmission characterized by fluctuating muscle weakness, often beginning in ocular muscles and progressing to gMG. Cladribine is a B and T cell targeting immune reconstitution therapy designed to address the source of autoantibodies in gMG. Cladribine has shown efficacy in a pilot study of participants with gMG. We present the design of MyClad, an actively recruiting Phase 3 trial of a new oral formulation of cladribine in gMG (NCT06463587; funded by the healthcare business of Merck KGaA, Darmstadt, Germany).
Design/Methods:
MyClad is a 3-year Phase 3 trial that aims to recruit 240 participants with gMG (MG Foundation of America Class II–IVa). In the first double-blind, placebo-controlled period of 24 weeks, participants will be randomized in a 1:1:1 ratio to two short courses of placebo or one of two oral cladribine doses. In the following blinded extension period of 24 weeks, placebo recipients will be re-randomized to one of two oral cladribine doses. During this period and a third double-blind follow-up period of 96 weeks, any participant may be re-treated with oral cladribine if clinically needed. The primary endpoint is change from baseline to Week 24 in MG Activities of Daily Living scores for each oral cladribine dose versus placebo. Secondary endpoints include change from baseline to Week 24 in Quantitative MG, MG Composite, and MG 15-Item Quality of Life Scale-Revised scores; time from oral cladribine full dose to retreatment or rescue treatment; safety; and oral cladribine pharmacokinetics.
Conclusions:
MyClad is actively recruiting and seeks to establish meaningful clinical benefits with oral cladribine capsules in gMG by targeting B and T cell mediated autoimmunity.
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