Cenobamate Efficacy in Individuals With Autoimmune Epilepsy

Trial details

Who runs it

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Trial code

NCT07474285

Record updated

16 March 2026

Original description

Over the last decades, multiple neuronal autoantibodies directed against intracellular or cell-surface antigens have been identified in association with epilepsy and encephalopathy. In some patients with immune-mediated brain disorders, seizures persist and become chronic despite treatment with antiseizure medications (ASMs) and immunotherapy. This condition is particularly common in patients with antibodies against glutamic acid decarboxylase 65 (GAD65) or onconeural antigens (e.g., Hu, Ma2, and CRMP5/CV2). The persistence of seizures despite immunotherapy suggests the development of a sustained epileptogenic predisposition, consistent with the current conceptual definition of epilepsy.Read full original descriptionShow less

Evaluation of the Efficacy and Safety of Cenobamate in Individuals With Autoimmune Epilepsy: a Real-world Study

Over the last decades, multiple neuronal autoantibodies directed against intracellular or cell-surface antigens have been identified in association with epilepsy and encephalopathy. In some patients with immune-mediated brain disorders, seizures persist and become chronic despite treatment with antiseizure medications (ASMs) and immunotherapy. This condition is particularly common in patients with antibodies against glutamic acid decarboxylase 65 (GAD65) or onconeural antigens (e.g., Hu, Ma2, and CRMP5/CV2). The persistence of seizures despite immunotherapy suggests the development of a sustained epileptogenic predisposition, consistent with the current conceptual definition of epilepsy.

Cenobamate (CNB) is a recently approved antiseizure medication for the treatment of focal-onset seizures, with or without secondary generalization, in adults whose epilepsy remains uncontrolled despite prior treatment with at least two ASMs. CNB has demonstrated broad antiseizure efficacy, likely due to its dual mechanism of action: inhibition of the persistent component of voltage-gated sodium currents and positive allosteric modulation of GABAA receptors through a non-benzodiazepine mechanism.

Recent retrospective data suggest that CNB may be effective in patients with anti-GAD65 autoimmune encephalitis, potentially compensating for impaired GABAergic neurotransmission associated with these antibodies. Other studies have also suggested that GABA-enhancing ASMs, such as benzodiazepines and barbiturates, may be beneficial in anti-GABAAR encephalitis, whereas sodium channel blockers may be effective in LGI1/CASPR2 antibody-associated encephalitis by reducing repetitive neuronal firing through interactions with voltage-gated sodium channels.

The primary objective of this study is to determine the proportion of patients achieving a ≥50% reduction in seizure frequency during the 24 weeks following initiation of cenobamate compared with baseline seizure frequency.

Secondary objectives include:

evaluating the proportion of patients achieving ≥75% and 100% seizure reduction,

assessing the safety and tolerability of cenobamate by documenting the frequency and severity of adverse events,

analyzing the impact of CNB treatment on quality of life using validated scales such as the Clinical Global Impression (CGI) and the Hospital Anxiety and Depression Scale (HADS),

exploring treatment efficacy according to the specific autoantibody subtype associated with autoimmune epilepsy.

Inclusion: Age >18 years; Signed informed consent; Diagnosis of autoimmune epilepsy according to the ILAE 2017 criteria; Stable treatment regimen with immunotherapy and antiseizure medications (ASMs) during the 3 months preceding the initiation of CNB treatment.

Exclusion: Hypersensitivity to CNB or any of its excipients; History of severe adverse drug reactions, including DRESS and Stevens-Johnson syndrome; Diagnosis of familial short QT syndrome; Inability to read and write in Italian; Pregnant or breastfeeding patients.

ClinicalTrials.gov NCT07474285