Abstract
Objective To evaluate efficacy and safety of rozanolixizumab for treatment of leucine-rich glioma inactivated 1 (LGI1) autoimmune encephalitis (AIE).
Background LGI1 AIE is a clinically homogeneous syndrome mediated by autoantibodies, predominantly of the IgG4 subclass, characterized by seizures, cognitive impairment and neuropsychiatric symptoms. No approved treatment options are available, and current treatment paradigms are variable. Rozanolixizumab is a fully humanized monoclonal antibody that can be delivered subcutaneously and inhibits the IgG binding region of the neonatal Fc receptor (FcRn), reducing the concentration of circulating IgG-antibodies, including pathogenic IgG-autoantibodies.
Design/Methods This multicenter, randomized, double-blind, placebo-controlled LEGIONE study (NCT04875975) is the first Phase 2 study to evaluate efficacy and safety of FcRn inhibition as treatment for LGI1 AIE. The study is recruiting adults with serum LGI1-autoantibodies, considered for intravenous methylprednisolone treatment, with new-onset disease (0-12 months prior to study entry). At screening, patients with prior diagnosis of epilepsy unrelated to LGI1 AIE, IgG level =5.5 g/L, clinically relevant infection or history of neoplastic disease will be excluded. Alongside a typical steroid taper, ∼68 patients will be randomized 1:1 to subcutaneous infusion of rozanolixizumab or placebo for 24 weeks, stratified by time from disease onset and cognitive function (measured by the Repeatable Battery for the Assessment of Neuropsychological Status) at randomization. Primary endpoint is measured by seizure freedom (28 consecutive days of no seizures maintained until the end of the treatment period). Secondary endpoints are change in cognitive function, use of rescue medication, time to onset of seizure freedom and safety and tolerability of rozanolixizumab. Exploratory pharmacokinetic/pharmacodynamic and biomarker-based endpoints are anticipated.
Results Study background, rationale and design will be presented.
Conclusions The LEGIONE study is the first randomized, double-blind, placebo-controlled Phase 2 study to evaluate the efficacy and safety of an FcRn inhibitor, rozanolixizumab, in patients with leucine-rich glioma-inactivated 1 autoimmune encephalitis and is enrolling patients.
Footnotes
Disclosure: The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. The institution of Dr. Dubey has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for AGRIMS. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Advances in Neurology. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Moffit Cancer Center. Dr. Dubey has received research support from Department of Defense. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Titulaer has received research support from Dutch Epilepsy Foundations (NEF 14-18 and 19-08). The institution of Dr. Titulaer has received research support from CSL Behring. The institution of Dr. Titulaer has received research support from UCB. The institution of Dr. Titulaer has received research support from Netherlands Organisation for Scientific Research (ZonMW, Memorabel initiative and E-RARE UltraAIE). The institution of Dr. Titulaer has received research support from Horizon Therapeutics. The institution of Dr. Titulaer has received research support from Dioraphte (charity). The institution of Dr. Titulaer has received research support from Guidepoint Global LLC. Dr. Koul has stock in UCB. An immediate family member of Dr. Koul has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Koul has received personal compensation in the range of $0-$499 for serving as a Scientific advisory board member with CSIR. Dr. Yates has received personal compensation for serving as an employee of UCB Biosciences, Inc. Dr. Yates has stock in UCB Biosciences, Inc. Dr. Irani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Irani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Irani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Irani has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Brain. Dr. Irani has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for kinmi. The institution of Dr. Irani has received research support from UCB / CSL. Dr. Irani has received intellectual property interests from a discovery or technology relating to health care.
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