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

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Dravet Syndrome; Lennox Gastaut Syndrome
• Intervention / Treatment: Drug: Epidiolex 100 mg/mL Oral Solution

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosure & Transparency; Phone Number: 215-832-3750; Email: ClinicalTrialDisclosure@JazzPharma.com

Study Locations

• Italy
  • Roma, Italy, 00152
    • Ospedale Pediatrico Bambino Gesù (OPBG)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

The study groups will comprise of 70 male and female participants, aged 6-17 years, satisfying the inclusion and exclusion criteria and agreeing to take part in this observational study. The decision to prescribe Epidyolex® as adjunctive therapy for seizures associated with LGS or DS will be entirely independent of including the participant in the study.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Collaborators: Evidilya S.r.l.

Study record dates

Study Major Dates

• Study Start (Estimated): June 23, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: July 29, 2022
• First Submitted That Met QC Criteria: August 1, 2022
• First Posted (Actual): August 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: seizures; Epidyolex; cannabidiol oral solution
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Disease; Genetic Diseases, Inborn; Epilepsy; Epilepsies, Myoclonic; Syndrome; Lennox Gastaut Syndrome; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: GWPIT001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO