Autoimmune EpilepsyCENSUSNCT07474285
Cenobamate Efficacy in Individuals With Autoimmune Epilepsy
An observational study of Autoimmune Epilepsy, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
Over the last decades, multiple neuronal autoantibodies directed against intracellular or cell-surface antigens have been identified in association with epilepsy and encephalopathy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Epilepsy
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 1 Feb 2026to Aug 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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.
Read more
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.
Read the detailed description
In recent decades, multiple neuronal autoantibodies directed against cell-surface or intracellular antigens associated with epilepsy and/or encephalopathy have been discovered [2]. Some patients with immune-mediated brain diseases experience seizures that become chronic and are resistant to both antiseizure medications (ASMs) and immunotherapy. This occurs more frequently in patients with antibodies directed against glutamic acid decarboxylase 65 (GAD65) and against onconeural proteins (e.g., Hu, Ma2, collapsing response mediator protein 5/CV2). In this context, the persistence of seizures despite immunotherapy suggests a lasting predisposition, consistent with the current conceptual definition of epilepsy [4].
Cenobamate (CNB) is an antiseizure medication (ASM) recently approved for the treatment of focal-onset seizures, with or without secondary generalization, in adult patients with epilepsy inadequately controlled despite a history of treatment with at least two ASMs [5].
CNB has demonstrated broad-spectrum efficacy, exerting its antiseizure effect through a dual mechanism of action. In addition to inhibiting the persistent component of voltage-gated sodium currents, CNB also acts as a non-benzodiazepine positive allosteric modulator of GABAA channels [6].
The efficacy of CNB in the treatment of patients with anti-GAD65 encephalitis has been suggested by a recent retrospective study, hypothetically compensating for the deficit in GABAergic neurotransmission observed in autoimmune encephalitis associated with anti-GAD65 antibodies [7].
Furthermore, other studies have indicated that ASMs that enhance GABA transmission, such as benzodiazepines and barbiturates, may be beneficial in patients with anti-GABAAR encephalitis, whereas sodium channel blockers have demonstrated efficacy in the treatment of LGI1/CASPR2 antibody-associated encephalitis, reducing repetitive neuronal firing through interaction with voltage-gated sodium channels [8].
Primary objective:
To determine the percentage of patients achieving a ≥50% reduction in seizure frequency during the 24 weeks following initiation of cenobamate treatment compared with the pre-treatment baseline.
Secondary objectives:
- To evaluate the proportion of patients achieving a ≥75% and 100% reduction in seizure frequency compared with baseline.
- To evaluate the safety and tolerability of CNB by documenting the frequency and severity of adverse events.
- To analyze the impact of CNB treatment on patients' quality of life using validated scales such as the Clinical Global Impression (CGI) and the Hospital Anxiety and Depression Scale (HADS).
- To examine the efficacy of CNB according to the specific type of antibody associated with autoimmune epilepsy.
- Conditions
- Autoimmune Epilepsy
- Keywords
- cenobamate, autoimmune epilepsy, epilepsy
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| patients treated with Cenobamate (CNB) | Patients affected by confirmed autoimmune epilepsy undergoing treatment with cenobamate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seizure frequency at week 24
Proportion of patients achieving a ≥50% reduction in seizure frequency at 24 weeks compared with the pre-treatment baseline.
Measured: "From therapy-start to week 24 of treatment"
Secondary outcomes (6)
Seizure frequency at week 24
Proportion of patients achieving a ≥75% reduction in monthly seizure frequency compared with the pre-treatment baseline over 24 weeks.
Measured: From therapy start to week 24 of treatment
Seizure frequency at week 24
Description: Proportion of patients achieving a ≥90% reduction in monthly seizure frequency compared with the pre-treatment baseline over 24 weeks.
Measured: From therapy start to week 24 of treatment
Seizure frequency at week 24
Proportion of patients achieving a 100% reduction in monthly seizure frequency compared with the pre-treatment baseline over 24 weeks.
Measured: From therapy start to week 24 of treatment
Safety assessment
Description of the frequency and severity of adverse events
Measured: From enrollment to the end of the observation period (Aug 2027)
Overall functioning, at week 24
Assessment of the overall functioning in patients undergoing treatment with CNB using the Clinical Global Impression (CGI) evaluated at baseline and at 24 weeks after treatment
Measured: From therapy start to week 24
Mood disorders assessment
Assessment of anxiety, and depression before and after 24 weeks of CNB treatment using the Hospital Anxiety and Depression Scale (HADS), evaluated at baseline and at 24 weeks after treatment initiation.
Measured: from baseline (therapy-start) to week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2026
- Study start1 Feb 2026
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Autoimmune EpilepsyStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Aziende Chimiche Riunite Angelini Francesco S.p.A
- Responsible party
- Sponsor
- Investigators
- Paolo Calabresi, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07474285
- Sponsor's protocol ID
- CENSUS_ID 7735
- Other IDs
- 153(A)IM24351
- Acronym
- CENSUS
- Status last verified
- Mar 2026
- First submitted
- 11 Mar 2026
- Last updated
- 16 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Husari KS, Dubey D. Autoimmune Epilepsy. Neurotherapeutics. 2019 Jul;16(3):685-702. doi: 10.1007/s13311-019-00750-3.
PubMed 31240596Beghi E. The Epidemiology of Epilepsy. Neuroepidemiology. 2020;54(2):185-191. doi: 10.1159/000503831. Epub 2019 Dec 18.
PubMed 31852003
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy and Safety of Cenobamate in Individuals With Autoimmune Epilepsy: a Real-world Study
- ClinicalTrials.gov ID
- NCT07474285
- Acronym / sponsor ID
- CENSUS / CENSUS_ID 7735
- Conditions
- Autoimmune Epilepsy
- Keywords
- cenobamate, autoimmune epilepsy, epilepsy
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Collaborators
- Aziende Chimiche Riunite Angelini Francesco S.p.A
- Study start
- 1 Feb 2026 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 16 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In recent decades, multiple neuronal autoantibodies directed against cell-surface or intracellular antigens associated with epilepsy and/or encephalopathy have been discovered [2]. Some patients with immune-mediated brain diseases experience seizures that become chronic and are resistant to both antiseizure medications (ASMs) and immunotherapy. This occurs more frequently in patients with antibodies directed against glutamic acid decarboxylase 65 (GAD65) and against onconeural proteins (e.g., Hu, Ma2, collapsing response mediator protein 5/CV2). In this context, the persistence of seizures despite immunotherapy suggests a lasting predisposition, consistent with the current conceptual definition of epilepsy [4].
Cenobamate (CNB) is an antiseizure medication (ASM) recently approved for the treatment of focal-onset seizures, with or without secondary generalization, in adult patients with epilepsy inadequately controlled despite a history of treatment with at least two ASMs [5].
CNB has demonstrated broad-spectrum efficacy, exerting its antiseizure effect through a dual mechanism of action. In addition to inhibiting the persistent component of voltage-gated sodium currents, CNB also acts as a non-benzodiazepine positive allosteric modulator of GABAA channels [6].
The efficacy of CNB in the treatment of patients with anti-GAD65 encephalitis has been suggested by a recent retrospective study, hypothetically compensating for the deficit in GABAergic neurotransmission observed in autoimmune encephalitis associated with anti-GAD65 antibodies [7].
Furthermore, other studies have indicated that ASMs that enhance GABA transmission, such as benzodiazepines and barbiturates, may be beneficial in patients with anti-GABAAR encephalitis, whereas sodium channel blockers have demonstrated efficacy in the treatment of LGI1/CASPR2 antibody-associated encephalitis, reducing repetitive neuronal firing through interaction with voltage-gated sodium channels [8].
Primary objective:
To determine the percentage of patients achieving a ≥50% reduction in seizure frequency during the 24 weeks following initiation of cenobamate treatment compared with the pre-treatment baseline.
Secondary objectives:
- To evaluate the proportion of patients achieving a ≥75% and 100% reduction in seizure frequency compared with baseline.
- To evaluate the safety and tolerability of CNB by documenting the frequency and severity of adverse events.
- To analyze the impact of CNB treatment on patients' quality of life using validated scales such as the Clinical Global Impression (CGI) and the Hospital Anxiety and Depression Scale (HADS).
- To examine the efficacy of CNB according to the specific type of antibody associated with autoimmune epilepsy.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patients treated with Cenobamate (CNB) | – | –Patients affected by confirmed autoimmune epilepsy undergoing treatment with cenobamate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Seizure frequency at week 24
Time frame: "From therapy-start to week 24 of treatment"
Proportion of patients achieving a ≥50% reduction in seizure frequency at 24 weeks compared with the pre-treatment baseline.
6 secondary outcomes
Seizure frequency at week 24
Time frame: From therapy start to week 24 of treatment
Seizure frequency at week 24
Time frame: From therapy start to week 24 of treatment
Seizure frequency at week 24
Time frame: From therapy start to week 24 of treatment
Safety assessment
Time frame: From enrollment to the end of the observation period (Aug 2027)
Overall functioning, at week 24
Time frame: From therapy start to week 24
Mood disorders assessment
Time frame: from baseline (therapy-start) to week 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2026.
- Results publication: PubMed 31240596Husari KS, Dubey D. Autoimmune Epilepsy. Neurotherapeutics. 2019 Jul;16(3):685-702. doi: 10.1007/s13311-019-00750-3.
- Results publication: PubMed 31852003Beghi E. The Epidemiology of Epilepsy. Neuroepidemiology. 2020;54(2):185-191. doi: 10.1159/000503831. Epub 2019 Dec 18.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paolo Calabresi principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autoimmune Epilepsy, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 16 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seizure frequency at week 24 (time frame: "From therapy-start to week 24 of treatment"). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07474285, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2026.