Epidyolex® in Lennox Gastaut and Dravet Syndrome: an Observational Study in ITALY

Study Overview
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Brief Summary
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This is a prospective, observational study on approximately 70 Real World participants affected by LGS or DS, treated with Epidyolex® as prescribed in the summary of product characteristics. The eligible participants are expected to participate in the study for a duration of 56 weeks of treatment.

Detailed Description
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This observational study evaluates a Real-World population of children and adolescent participants affected by LGS and DS and the effect of therapy with Epidyolex® administered according to clinical practice on epileptic symptoms. The study will assess specific scales, questionnaires, the QoL of the participants, and the satisfaction of the caregivers and the participants/tutors.

Official Title
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Observational, Prospective, Multicenter Study of Epidyolex® (Cannabidiol CBD 100 mg/ml) Oral Solution, as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome (LGS) and Dravet Syndrome (DS)

Conditions
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Lennox Gastaut Syndrome, Dravet Syndrome

Intervention / Treatment
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* Drug: Epidiolex 100 mg/mL Oral Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Paediatric participants aged 6-17 years, diagnosed with LGS or DS Clinical decision, taken by the physician, to initiate Epidyolex® Availability of a diary with the number and type of epileptic seizures that occurred at least 28 days before the start of the study Parents or legal representatives must be willing and able to give informed consent/assent for participation in the study. Exclusion Criteria: Participants currently using or have used recreational, medicinal cannabis, or cannabinoid-based products within the three months prior to study entry and are unwilling to abstain from these products for the duration of the study. This study will not include participants who have already been prescribed Epidyolex® before the start of the study. Any reason, according to Investigator's judgment, able to compromise compliance with procedures outlined in the study There will not be any other specific exclusion criteria; however, contraindications, special warnings, and precautions for use as detailed in the Summary of Product Characteristics (SmPC) (particularly related to raising of aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin) will have to be considered by the treating physician.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lennox Gastaut and Dravet Syndrome<br>Participants aged 6-17 years of age diagnosed with LGS and DS. | Drug: Epidiolex 100 mg/mL Oral Solution<br>* As prescribed in routine clinical practice in Italy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Study Visit in Proportion of Participants Remaining on Therapy from Enrollment | Treatment retention will be evaluated through the proportion of participants remaining on therapy from the enrollment visit (baseline, V0) to each study visit (Weeks 4 [V1], 16 [V2], 28 [V3], 40 [V4], 56 [V5]). | Baseline up to Week 56 post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change from Baseline in Frequency of LGS/DS Associated Seizures (average per 28 days) | LGS associated seizures are defined as drop seizures which include tonic-clonic, tonic or atonic seizures. DS associated seizures are defined as convulsive seizures which include tonic, clonic, atonic, tonic-clonic. | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) post-dose. | 
| Percentage Change from Baseline in Total Seizure Frequency (average per 28 days) | Total seizures are defined as all countable seizures. | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Percentage of Participants Achieving a ≥25% Reduction in Seizure Frequency from Baseline |  | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Percentage of Participants Achieving a ≥50% Reduction in Seizure Frequency from Baseline |  | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Percentage of Participants Achieving a ≥75% Reduction in Seizure Frequency from Baseline |  | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Average Number of Seizure-Free Days in the Last 28 Days |  | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Longest Duration of Seizure Free Days in the Last 28 Days |  | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Number of Events of Status Epilepticus |  | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Average Maintenance Dose of Epidyolex® |  | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Maximum Maintenance Dose of Epidyolex® |  | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Type, Dosage, and Frequency of Concomitant Anti-Seizure Medications (ASMs) |  | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Number of Participants Reducing Number/Dosage of Concomitant Medication Related to Epilepsy |  | Weeks 4 (V1), 16 (V2), 28 (V3), 40 (V4) and 56 (V5) | 
| Change from Baseline to Week 28 (V3) in the Child Behavior Check List (CBCL) | The CBCL is a standardized form that parents fill out to describe their adolescent and children's behavioral and emotional problems(e.g., anxiety, depression, social problems). The CBCL is also scored on (optional) competence scales for activities, social relations, school and total competence. The CBCL consists of 113 questions, scored on a three-point Likert scale (0=absent, 1= occurs sometimes, 2=occurs often). A higher score indicates a worse outcome. | Baseline to week 28 (v3) post-dose. | 
| Change from Baseline to Week 56 (V5) in the Child Behavior Check List (CBCL) | The CBCL is a standardized form that parents fill out to describe their adolescent and children's behavioral and emotional problems(e.g., anxiety, depression, social problems). The CBCL is also scored on (optional) competence scales for activities, social relations, school and total competence. The CBCL consists of 113 questions, scored on a three-point Likert scale (0=absent, 1= occurs sometimes, 2=occurs often). A higher score indicates a worse outcome. | Baseline to week 56 (V5) post-dose. | 
| Change from Baseline to Week 28 (V3) in the Sleep Disturbance Scale for Children (SDSC) | The SDSC assesses sleep behavior and disturbances during the previous 6 mo. The questionnaire consists of two sections: the first one is used to obtain demographic, behavioral and clinical data, information about previous illnesses and present medical status with specific questions regarding pathology that could affect sleep; the second is made up of 27 items in a Likert-type scale with values 1 (never) to 5 (always [daily]) with the wording arranged so that higher scores reflect a greater clinical severity of symptoms and indicate more acute sleep disturbances. | Baseline to week 28 (v3) post-dose. | 
| Change from Baseline to Week 56 (V5) in the Sleep Disturbance Scale for Children (SDSC) | The SDSC assesses sleep behavior and disturbances during the previous 6 mo. The questionnaire consists of two sections: the first one is used to obtain demographic, behavioral and clinical data, information about previous illnesses and present medical status with specific questions regarding pathology that could affect sleep; the second is made up of 27 items in a Likert-type scale with values 1 (never) to 5 (always [daily]) with the wording arranged so that higher scores reflect a greater clinical severity of symptoms and indicate more acute sleep disturbances. | Baseline to week 56 (v5) post-dose. | 
| Change from Baseline to Week 28 (V3) in the Social Communication Questionnaire (SCQ) | The SCQ is a parent report screening measure for autism spectrum disorders (ASDs) based on the Autism Diagnostic Interview-Revised (ADI-R). This brief instrument helps evaluate communication skills and social functioning in children who may have autism or autism spectrum disorders. It is available in two forms-Lifetime and Current-each composed of just 40 yes-or-no questions. Scores above the cutoff of 15 suggest the individual is likely to be on the autism spectrum and a more extended evaluation should be undertaken. | Baseline to week 28 (v3) post-dose. | 
| Change from Baseline to Week 56 (V5) in the Social Communication Questionnaire (SCQ) | The SCQ is a parent report screening measure for autism spectrum disorders (ASDs) based on the Autism Diagnostic Interview-Revised (ADI-R). This brief instrument helps evaluate communication skills and social functioning in children who may have autism or autism spectrum disorders. It is available in two forms-Lifetime and Current-each composed of just 40 yes-or-no questions. Scores above the cutoff of 15 suggest the individual is likely to be on the autism spectrum and a more extended evaluation should be undertaken. | Baseline to week 56 (v5) post-dose. | 
| Change from Baseline to Week 28 (V3) in the Pediatric Quality of Life (Peds-QoL) -Epilepsy | The Parent Report for Toddlers (ages 2-4) of the PedsQLTM 3.0 Epilepsy Module is composed of 22 items comprising 5 dimensions. The dimensions consist of impact (6 items), cognitive functioning (5 items), sleep/rest (2 items), executive functioning (4 items), and mood/behavior (5 items). The items are rated on a 5-point Likert scale: 0 never a problem, 1 almost never a problem, 2 sometime a problem, 3 often a problem, 4 almost always a problem. Scores are transformed to a 0 to 100 scale. Higher scores indicate lower problems and a better outcome. | Baseline to week 28 (v3) post-dose. | 
| Change from Baseline to Week 56 (V5) in the Pediatric Quality of Life (Peds-QoL) -Epilepsy | The Parent Report for Toddlers (ages 2-4) of the PedsQLTM 3.0 Epilepsy Module is composed of 22 items comprising 5 dimensions. The dimensions consist of impact (6 items), cognitive functioning (5 items), sleep/rest (2 items), executive functioning (4 items), and mood/behavior (5 items). The items are rated on a 5-point Likert scale: 0 never a problem, 1 almost never a problem, 2 sometime a problem, 3 often a problem, 4 almost always a problem. Scores are transformed to a 0 to 100 scale. Higher scores indicate lower problems and a better outcome. | Baseline to week 56 (v5) post-dose. | 
| Caregiver Global Impression of Change (CGIC) at Week 28 (V3) | The CGIC evaluates efficacy and quality of life. At enrollment the investigator will be asked to write a brief description of the patient's overall condition as a memory aid for assessment at each subsequent appointment. The CGIC comprises of the following question: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The questionnaire is rated on a seven-point scale: Very Much Improved (1); Much Improved (2);Slightly Improved (3); No Change (4); Slightly Worse (5); Much Worse (6); Very Much Worse (7). A score of 1 indicates a better outcome and a score of 7 indicates a worse outcome. | Week 28 (V3) post-dose. | 
| Caregiver Global Impression of Change (CGIC) at Week 56 (V5) | The CGIC evaluates efficacy and quality of life. At enrollment the investigator will be asked to write a brief description of the patient's overall condition as a memory aid for assessment at each subsequent appointment. The CGIC comprises of the following question: Since your child started treatment, please assess the status of your child's overall condition (comparing their condition now to their condition before treatment) using the scale below. The questionnaire is rated on a seven-point scale: Very Much Improved (1); Much Improved (2);Slightly Improved (3); No Change (4); Slightly Worse (5); Much Worse (6); Very Much Worse (7). A score of 1 indicates a better outcome and a score of 7 indicates a worse outcome. | Week 56 (V5) post-dose. | 
| Caregiver Global Impression of Change in Seizure Duration (CGICSD) at Week 28 (V3) | The CGICSD comprises the following question to be rated on a three-point scale for each seizure subtype: Since the patient started treatment, please assess the average duration of the patient's seizures (comparing their condition now to their condition before treatment) using the scale below. The scale markers are: 1=Average duration of seizures has decreased; 2=Average duration of seizures has stayed the same; 3=Average duration of seizures has increased. Higher scores indicate a worse outcome. | Week 28 post-dose. | 
| Caregiver Global Impression of Change in Seizure Duration (CGICSD) at Week 56 (V5) | The CGICSD comprises the following question to be rated on a three-point scale for each seizure subtype: Since the patient started treatment, please assess the average duration of the patient's seizures (comparing their condition now to their condition before treatment) using the scale below. The scale markers are: 1=Average duration of seizures has decreased; 2=Average duration of seizures has stayed the same; 3=Average duration of seizures has increased. Higher scores indicate a worse outcome. | Week 56 post-dose. | 
| Physician Global Impression of Change (PGIC) at Week 28 (V3) | The PGIC evaluates efficacy and quality of life. At enrollment the investigator will be asked to write a brief description of the patient's overall condition as a memory aid for assessment at each subsequent appointment. The PGIC comprises of the following question: Please assess the change in the patient's general functional abilities since enrolment. The questionnaire is rated on a seven-point scale: Very Much Improved (1); Much Improved (2);Slightly Improved (3); No Change (4); Slightly Worse (5); Much Worse (6); Very Much Worse (7). A score of 1 indicates a better outcome and a score of 7 indicates a worse outcome. | Week 28 (V3) post-dose. | 
| Physician Global Impression of Change at Week 56 (V5) | The PGIC evaluates efficacy and quality of life. At enrollment the investigator will be asked to write a brief description of the patient's overall condition as a memory aid for assessment at each subsequent appointment. The PGIC comprises of the following question: Please assess the change in the patient's general functional abilities since enrolment. The questionnaire is rated on a seven-point scale: Very Much Improved (1); Much Improved (2);Slightly Improved (3); No Change (4); Slightly Worse (5); Much Worse (6); Very Much Worse (7). A score of 1 indicates a better outcome and a score of 7 indicates a worse outcome. | Week 56 (V5) post-dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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seizures, Epidyolex, cannabidiol oral solution