BLESS: Cenobamate in Adults With Focal-Onset Seizures

Sponsor

Aziende Chimiche Riunite Angelini Francesco S.p.A (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05859854

Collaborator

Iqvia Pty Ltd (Industry)

200

Enrollment

Locations

20.2

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The BLESS Study contributes to filling this information gap by collecting data from the Italian clinical practice and the Compassionate Use Program, to better characterize the clinical profile of cenobamate describing its effectiveness, safety and tolerability in adult patients diagnosed with uncontrolled focal epilepsy despite the use of at least two antiepileptic medicinal products.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy Focal-Onset Seizure Neurological Disorder

Detailed Description

The main objective of the study is to describe the effectiveness of adjunctive cenobamate treatment in adult patients with uncontrolled focal epilepsy in Italy, as assessed by intra-patient percent change and achievement of a ≥50% reduction in the seizure frequency from the pre-treatment baseline over a period of 52 weeks.

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

Cenobamate in Adults With Focal-Onset Seizures: a Real-World Multicenter Observational Italian

Actual Study Start Date :

Jan 24, 2023

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Sep 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Adult patients diagnosed treated with adjunctive cenobamate in Italy. Adult patients diagnosed with focal epilepsy uncontrolled despite the use of at least two antiepileptic medicinal products, treated with adjunctive cenobamate in Italy. A single cohort of patients will be involved in the study, enrolling both subjects who initiated cenobamate treatment in accordance with the current clinical practice, and subjects previously included in the cenobamate Compassionate Use Programme in Italy, provided that they fulfil all of the eligibility criteria listed below

Arm

Intervention/Treatment

Adult patients diagnosed treated with adjunctive cenobamate in Italy.

Adult patients diagnosed with focal epilepsy uncontrolled despite the use of at least two antiepileptic medicinal products, treated with adjunctive cenobamate in Italy. A single cohort of patients will be involved in the study, enrolling both subjects who initiated cenobamate treatment in accordance with the current clinical practice, and subjects previously included in the cenobamate Compassionate Use Programme in Italy, provided that they fulfil all of the eligibility criteria listed below

Outcome Measures

Primary Outcome Measures

Absolute frequency of patients achieving a 50 % or greater reduction in the seizure frequency [12, 24 and 52 weeks of cenobamate treatment initiation]
Seizure frequency during the baseline and post-baseline assessments was calculated by summing the total number of seizures (all types of seizures) reported in each considered period and dividing by the duration of that period (number of days), excluding days with no available diary data, and multiplying by 28 to normalize to a monthly rate ("monthly seizure frequency").
Relative frequency of patients achieving a ≥50% (50% or greater) reduction in the seizure frequency [12, 24 and 52 weeks of cenobamate treatment initiation]
Seizure frequency during the baseline and post-baseline assessments was calculated by summing the total number of seizures (all types of seizures) reported in each considered period and dividing by the duration of that period (number of days), excluding days with no available diary data, and multiplying by 28 to normalize to a monthly rate ("monthly seizure frequency").
Intra-patient percent change in the seizure frequency [12, 24 and 52 weeks of cenobamate treatment initiation]
Intra-patient percent change from baseline will be defined as [(monthly seizure frequency at post-baseline assessments - monthly seizure frequency at baseline), divided by the monthly seizure frequency at baseline] multiplied by 100.

Secondary Outcome Measures

Absolute frequency of patients achieving a ≥50%/≥75%/≥90%/=100% sustained reduction in the seizure frequency [24 and 52 weeks of cenobamate treatment initiation.]
Sustained seizure frequency reduction will be defined as a ≥50%/≥75%/≥90%/=100% reduction in baseline seizure frequency achieved at 12 weeks of cenobamate treatment initiation, that continues (is sustained) without interruption and without cenobamate permanent discontinuation through the observation period until 24 and 52 weeks of cenobamate treatment initiation, respectively.
Absolute frequency of patients achieving a ≥75%/≥90%/=100% reduction in the seizure frequency [12, 24 and 52 weeks of cenobamate treatment initiation.]
Seizure frequency reduction will be defined as a ≥75%/≥90%/=100% reduction in baseline seizure frequency achieved at 12, 24 and 52 weeks of cenobamate treatment initiation, respectively.
Relative frequencies of patients achieving a ≥50%/≥75%/≥90%/=100% sustained reduction in the seizure frequency [24 and 52 weeks of cenobamate treatment initiation.]
Sustained seizure frequency reduction will be defined as a ≥50%/≥75%/≥90%/=100% reduction in baseline seizure frequency achieved at 12 weeks of cenobamate treatment initiation, that continues (is sustained) without interruption and without cenobamate permanent discontinuation through the observation period until 24 and 52 weeks of cenobamate treatment initiation, respectively
Relative frequencies of patients achieving a ≥75%/≥90%/=100% reduction in the seizure frequency [12, 24 and 52 weeks of cenobamate treatment initiation.]
Seizure frequency reduction will be defined as a ≥75%/≥90%/=100% reduction in baseline seizure frequency achieved at 12, 24 and 52 weeks of cenobamate treatment initiation.
Absolute frequency of patients with at least one AE [Through study completion, an average of 1 year]
Absolute frequency of patients treated with cenobamate who experienced at least one AE during the applicable observation period
Relative frequency of patients with at least one AE [Through study completion, an average of 1 year]
Relative frequency of patients treated with cenobamate who experienced at least one AE during the applicable observation period
Absolute frequency of patients with at least one ADR [Through study completion, an average of 1 year]
Absolute frequency of patients treated with cenobamate who experienced at least one ADR during the applicable observation period
Relative frequency of patients with at least one ADR [Through study completion, an average of 1 year]
Relative frequency of patients treated with cenobamate who experienced at least one ADR during the applicable observation period
Absolute frequency of patients treated with at least one SAE [Through study completion, an average of 1 year]
Absolute frequency of patients treated with at least one SAE during the applicable observation period
Relative frequency of patients treated with at least one SAE [Through study completion, an average of 1 year]
Relative frequency of patients treated with at least one SAE during the applicable observation period
Health-Related Quality of life (HRQoL) [12, 24 and 52 weeks]
The Health-Related Quality of life (HRQoL) of patients will be assessed by means of the 31-item Quality Of Life In Epilepsy inventory (QOLIE-31). The 31-item Quality Of Life In Epilepsy inventory (QOLIE-31) is a patient self-reported instrument that contains 31 items grouped in seven multi-item scales ( "seizure worry", "overall QoL", "emotional well-being", "energy fatigue", "cognitive functioning", "medication effects" and "social functioning"). Different items in the QOLIE-31 have different ranges of precoded numeric values, so the scoring procedure requires conversion from raw, precoded numeric values to scores of 0-100 points, with higher scores reflecting better quality of life. The QOLIE-31 overall score is calculated by summing the product of each scale score times its weight and summing over all scales, according to the instructions obtained from copyright holders.
Patient Global functioning (CGI-S) [12, 24 and 52 weeks]
The patient global functioning will be assessed by means of the Clinical Global Impression (CGI) Scales. The Early Clinical Drug Evaluation Program (ECDEU) version of the CGI is a 3-item clinician rated scale that measures illness severity (CGI-S), global improvement or change (CGI-I) and treatment response (efficacy index: CGI-E). The CGI-S score ranges from 1 (normal) through to 7 (amongst the most severely ill patients). The calculation of the scores will be performed according to the instructions obtained from copyright holders.
Patient Global functioning (CGI-I) [12, 24 and 52 weeks]
The patient global functioning will be assessed by means of the Clinical Global Impression (CGI) Scales. The Early Clinical Drug Evaluation Program (ECDEU) version of the CGI is a 3-item clinician rated scale that measures illness severity (CGI-S), global improvement or change (CGI-I) and treatment response (efficacy index: CGI-E). The CGI-I score ranges from 1 (very much improved) through to 7 (very much worse). The calculation of the scores will be performed according to the instructions obtained from copyright holders.
Patient Global functioning (CGI-E) [12, 24 and 52 weeks]
The patient global functioning will be assessed by means of the Clinical Global Impression (CGI) Scales. The Early Clinical Drug Evaluation Program (ECDEU) version of the CGI is a 3-item clinician rated scale that measures illness severity (CGI-S), global improvement or change (CGI-I) and treatment response (efficacy index: CGI-E). The CGI-E score should take account of both therapeutic effect and tolerance, and ranges from 0 (marked improvement and no toxicity) and 4 (unchanged or worse and toxicity outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score. The calculation of the scores will be performed according to the instructions obtained from copyright holders.
Daytime Sleepiness [12, 24 and 52 weeks]
Daytime Sleepiness will be assessed by means of the Epworth Sleepiness Scale (ESS). The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different daily activities. The ESS score can range from 0 to 24. The higher the ESS score, the higher that person Average Sleep Propensity in Daily Life (ASP), or their daytime sleepiness across a wide range of activities in their daily lives.
Hospital Anxiety and Depression [12, 24 and 52 weeks]
Anxiety and depression symptoms will be assessed by means of the the Hospital Anxiety and Depression Scale (HADS). This is a patient self-reported instrument consisting of 14 items that provide scores on two specific subscales: "Anxiety" subscale (HADS-A, 7 items) and "Depression" subscale (HADS-D, 7 items). All items were scored on a 4-point Likert scale from 0 ("never") to 3 ("almost every day") referring to overt symptoms within the last week. Total scores range from 0 to 21 points for each subscale, with higher scores indicating higher levels of symptoms.
Retention with cenobamate [52 weeks]
Retention with cenobamate will be assessed by calculating the frequency of patients still on treatment with cenobamate at 52 weeks of treatment initiation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years at the time of cenobamate treatment initiation
Male or female patients
Patients diagnosed with focal epilepsy uncontrolled despite a history of treatment with at least two antiepileptic medicinal products at the time of cenobamate treatment initiation in agreement with the Summary of Product Characteristics (SmPC)
Patients who at enrolment had received at least 12 weeks (titration period up to the initial recommended target dose of 200 mg daily completed) but no more than 52 weeks of cenobamate as adjunctive treatment of focal-onset seizures with or without secondary generalization
Patients with available retrospective data in medical charts and seizure diaries, including information about baseline seizure frequency prior to cenobamate treatment initiation
Patients who gave written informed consent to take part into the study and personal data processing consent following local regulation.
Patients who received adjunctive cenobamate for at least 12 weeks and discontinued permanently treatment before enrolment will also be included in the study-

Exclusion Criteria:

Patients diagnosed with familial short-QT syndrome
Patients affected by hypersensitivity to the active substance cenobamate or to any of the excipients (e.g., lactose monohydrate)
Patients with history of severe drug-induced hypersensitivity reaction, including (but not limited to) drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens Johnson syndrome
Patients enrolled in a clinical trial in which treatments for epilepsy are managed through a study protocol
Patient unable to read and write in Italian language and to autonomously fill in questionnaires and scales
Patients with a known pregnancy or who are breast-feeding from cenobamate treatment initiation till enrolment visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IRCCS Neuromed	Pozzilli	Isernia	Italy	86077
2	Associazione La Nostra Famiglia - IRCCS Eugenio Medea	Conegliano	Treviso	Italy	31015
3	Policlinico di Bari	Bari		Italy	70124
4	Università degli Studi di Catanzaro "Magna Graecia"	Catanzaro		Italy	88100
5	Fondazione Istituto Neurologico Casimiro Mondino	Pavia		Italy	27100
6	Campus Bio-Medico	Roma		Italy	00128
7	Policlinico Umberto I	Roma		Italy	00161
8	Humanitas Gradenigo	Torino		Italy	10153
9	Azienda Sanitaria Universitaria (A.O.U.) Integrata	Udine		Italy	33100
10	Ospedale San Bortolo	Vicenza		Italy	36100