This is a Retrospective Study on the Use of CENOBAMATE as Adjunctive Treatment in Patients Suffering From Epilepsy in Early Access Program in Germany, France and UK (CENOR)

Retrospective Study on the Use of CENOBAMATE as Adjunctive Treatment in a Cohort of Patients Suffering From Epilepsy With Focal Onset Seizure (FOS) and Enrolled Into the Early Access Program (EAP) in Germany, France and UK

Cenobamate is a newly-FDA and EMA approved drug used to treat -focal-onset seizures in adult patients.

The aim of the current study is to analyse retrospectively the overall effectiveness and tolerability of cenobamate from real-world data collected in patients who partecipated in the Early Access Program (EAP) and were treated with cenobamate as adjunctive ASM.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Focal Onset Seizure

Detailed Description

Cenobamate is a new approved drug used to treat -focal-onset seizures in adult patients. This novel tetrazole-derived carbamate seems to act primarily by two mechanisms that are commonly associated with epilepsy: cenobamate acts as a positive allosteric modulator of the GABAA ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown.

In clinical trials, cenobamate showed also low toxicity and adverse drug reaction profile.

In European Union (EU), cenobamate received the marketing authorisation, valid throughout the EU, in March 2021. Starting from September 2020 an EAP was initiated with cenobamate as adjunctive ASM in several EU Countries such as Germany, France, and UK.

Real-world data are of importance to understand and confirm the efficacy and safety profile of drugs outside of the clinical trial setting. The aim of the current study is to analyse the overall effectiveness and tolerability of cenobamate from real-world data in a large series of patients treated with cenobamate as adjunctive ASM.

As a consequence, a retrospective collection and analysis of the data of the patients who participated in the EAP, according to the authorization received from the local regulatory or ethic authorities, was conducted.

• Study Type: Observational
• Enrollment (Actual): 319

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Hôpital Pierre Wertheimer - Hopsices Civils de Lyon
  • Lille Cedex, France, 59037
    • CHRU de Lille - Hôpital Roger Salengro (LILLE)
  • Marseille, France, 13005
    • Centre Hospitalier Universitaire (CHU) de Marseille - Hopital de la Timone
  • Nancy, France, 54000
    • CHRU de Nancy -Hopital Central, Service de Neurologie
  • Paris, France, 75013
    • Hôpital de la Pitié-Salpêtrière
  • Rennes, France, 35000
    • CHU Rennes - Pontchaillou Hospital
  • Rouen, France, 76000
    • CHU de Rouen Hôpital Charles-NicolleService de Neurophysiologie
  • Strasbourg, France, 67098
    • CHU de Strasbourg - Hôpital de Hautepierre
• Germany
  • Berlin-Reinickendorf, Germany, 13509
    • Neurologie - Stroke Unit - Zentrum für Epilepsie
  • Bernau bei Berlin, Germany, 16321
    • Epilepsieklinik Tabor
  • Bielefeld, Germany, 33617
    • Epilepsy Center Bethel hospital Mara
  • Bonn, Germany, 53127
    • Klinik und Poliklinik für Epileptologie, Universitätsklinikum Bonn
  • Erlangen, Germany, 91054
    • Neurologische Klinik
  • Frankfurt am main, Germany, 60528
    • Epilepsy Center Frankfurt Rhine-Main Neurocenter
  • Freiburg, Germany, 79106
    • Klinik für Neurochirurgie Uniklinik Freiburg -
  • Hamburg, Germany, 22297
    • Evangelische Krankenhaus Alsterdorf
  • Kehl, Germany, 77694
    • Diakonie Kork Epilepsiezentrum
  • Marburg, Germany, 35043
    • Epilepsiezentrum Hessen, Klinik für Neurologie, Philipps Universität Marburg - Standort Marburg
  • Radeberg, Germany, 01454
    • Epilepsiezentrum Kleinwachau gGmbH
  • Tübingen, Germany, 72016
    • Universitatsklinikum Tubingen
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom, WC1N 3BG
    • UCLH NHS Trust Epilepsy Department
  • Newcastle, United Kingdom, NE1 4LP
    • The Newcastle Upon Tyne Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population includes adult patients suffering from epilepsy with FOS who have been treated with cenobamate as adjunctive Anti-seizure medication (ASM) during the EAP in Germany, France and UK.

Description

Inclusion Criteria:

• Data from adult patients diagnosed with epilepsy with FOS participating in the EAP with cenobamate as adjunctive treatment, according to the authorization received from the local regulatory or ethic authorities will be collected and analyzed.
• Available data will be collected after obtaining consent from patient/legal representative to the processing of personal data according to the General Data Protection Regulation (GDPR) and applicable local regulation

Exclusion Criteria:

• Patient enrolled in other clinical trial during the EAP.
• Patient aged less than 18 years old.
• Patient with specific syndrome (e.g. LGS and Dravet)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Cohort 1; Cohort of patients suffering from epilepsy with Focal Onset Seizure (FOS) and enrolled into the Early Access Program (EAP) in Germany, France and UK

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder rate (%) at 3 months from the start of maintenance	Percentage of responder rate (defined as a ≥50% reduction from screening/baseline in focal onset seizure frequency) after 3 months of maintenance phase.	3 months from the start of maintenance

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Portion of responders	Portion of responders (defined as a ≥50% and <100% reduction from screening/baseline in focal onset seizure frequency) at 1 and 3 months after start of cenobamate therapy	1 and 3 months after start of cenobamate therapy
Portion of responders	Portion of responders (defined as a ≥50% and <100% reduction from screening/baseline in focal onset seizure frequency) at 3, 6 and 12 months after the completion of the titration and its relation with the dosage.	3, 6 and 12 months after the completion of the titration and its relation with the dosage.
Portion of seizure free	Portion of seizure free (100% reduction from screening/baseline) 1 and 3 months after start of cenobamate therapy	1 and 3 months after start of cenobamate therapy
Portion of seizure free	Portion of seizure free (100% reduction from screening/baseline)3, 6 and 12 months after the completion of the titration and its relation with the dosage.	3, 6 and 12 months after the completion of the titration and its relation with the dosage.
Retention rate	Retention rate measured as percentage of patients remaining in the study and on adjunctive therapy at: 1 and 3 months after start of cenobamate therapy	1 and 3 months after start of cenobamate therapy
Retention rate	Retention rate measured as percentage of patients remaining in the study and on adjunctive therapy at 3, 6 and 12 months after the completion of the titration and its relation with the dosage.	3, 6 and 12 months after the completion of the titration
No. of Adverse Reactions (ADRs),	Adverse Reactions (ADRs), including DRESS, rash/hypersensitivity occurred during the EAP.	Through study completion, an average of 2 years
Change in Seizures Frequency	Change in Seizures Frequency at 1 and 3 months after start of cenobamate therapy,	1 and 3 months after start of cenobamate therapy
Change in Seizures Frequency	Change in Seizures Frequency at 3, 6 and 12 months after the completion of the titration	3, 6 and 12 months after the completion of the titration
Assessment of quality of life	The quality of life was assessed through the Questionnaire Quality of Life in Epilepsy Inventory - 31 items	1 and 3 months after start of cenobamate therapy
Assessment of quality of life	The quality of life was assessed through the Questionnaire Quality of Life in Epilepsy Inventory - 31 items	3, 6 and 12 months after the completion of the titration

Collaborators and Investigators

• Sponsor: Aziende Chimiche Riunite Angelini Francesco S.p.A
• Collaborators: Hippocrates Research
• Investigators: Principal Investigator: Sylvain Rheims, Hôpital Neurologique Pierre Wertheimer - Hospices Civils de Lyon; Principal Investigator: Rhys Thoma, The Newcastle upon Tyne Hospitals NHS Trust Victoria Road, Newcastle, NE1 4LP; Principal Investigator: Felix Rosenow, Epilepsy Center Frankfurt Rhine-Main Neurocenter Schleusenweg 2 - 16 (Haus 95) 60528 Frankfurt am Main

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2023
• Primary Completion (Actual): September 30, 2023
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): February 28, 2023

Study Record Updates

• Last Update Posted (Actual): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: epilepsy; Europe; retrospective; FOS; cenobamate; Early Access Program
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures
• Other Study ID Numbers: 169(A)MD21350

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No