Cenobamate Efficacy in Individuals With Autoimmune Epilepsy

NCT07474285 | Enrolling By Invitation

• 2 other identifiers: CENSUS_ID 7735153(A)IM24351
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Autoimmune Epilepsy

Keywords

cenobamate; autoimmune epilepsy; epilepsy

Outcome Measures

Primary Outcomes (1)

• Seizure frequency at week 24

  Proportion of patients achieving a ≥50% reduction in seizure frequency at 24 weeks compared with the pre-treatment baseline.

  "From therapy-start to week 24 of treatment"

Secondary Outcomes (6)

• Seizure frequency at week 24

  From therapy start to week 24 of treatment

• Seizure frequency at week 24

  From therapy start to week 24 of treatment

• Seizure frequency at week 24

  From therapy start to week 24 of treatment

• Safety assessment

  From enrollment to the end of the observation period (Aug 2027)

• Overall functioning, at week 24

  From therapy start to week 24

Study Arms (1)

patients treated with Cenobamate (CNB)

Patients affected by confirmed autoimmune epilepsy undergoing treatment with cenobamate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will include adult patients (\>18 years) who provide written informed consent and have a diagnosis of autoimmune epilepsy according to the ILAE 2017 criteria. Eligible participants must have been on a stable treatment regimen with immunotherapy and antiseizure medications (ASMs) for at least 3 months prior to initiating cenobamate (CNB). Patients will be excluded if they have a familial short QT syndrome, known hypersensitivity to CNB or any excipients, or a history of severe adverse drug reactions, including DRESS or Stevens-Johnson syndrome. Additional exclusion criteria include inability to read and write in Italian, as well as pregnancy or breastfeeding.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• Aziende Chimiche Riunite Angelini Francesco S.p.A: collaborator

Study Sites (1)

UOC di Neurologia

Rome, Lazio, 00168, Italy

Location

Related Publications (2)

• Husari KS, Dubey D. Autoimmune Epilepsy. Neurotherapeutics. 2019 Jul;16(3):685-702. doi: 10.1007/s13311-019-00750-3.

  PMID: 31240596 RESULT

• Beghi E. The Epidemiology of Epilepsy. Neuroepidemiology. 2020;54(2):185-191. doi: 10.1159/000503831. Epub 2019 Dec 18.

  PMID: 31852003 RESULT

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Paolo Calabresi

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: March 16, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

IT (1)