NCT06924827 - A Study to Investigate the Transition of Children From 'Artisanal" Cannabidiol (CBD) to Epidiolex | Crick

Eligibility

Sex: ALLMin age: 2 YearsMax age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female aged 2 through 18 years, inclusive. * Clinical diagnosis of Dravet or Lennox Gastaut Syndrome: Clinical diagnosis of Dravet Syndrome supported by: 1. Onset of seizures within the first year of life. 2. Initial seizures present as fever-induced or fever-triggered seizures, hemi-clonic, generalized tonic-clonic, prolonged seizures (more than 15 minutes). 3. Emergence of other seizure types after 1 year of age. 4. Normal development within the first year of age, then emergence of neurodevelopmental difficulties or delay. Clinical diagnosis of Lennox Gastaut Syndrome supported by: a. History of an EEG with slow/disorganized background and slow (\<2.5 Hz or less) spike and wave activity or generalized paroxysmal fast activity (GPFA). b. History of more than 1 type of generalized seizures, including drop seizures (tonic, atonic or tonic-clonic). * Participant must be willing and able to give written informed consent for participation. If the participant is not qualified or unable to provide written consent based on age, development, intellectual capacity or other factors, the parent or legally authorized representative must provide written informed consent on their behalf. * Must be on a stable dose of a licensed artisanal cannabidiol (CBD) product as maintenance therapy for seizure control for a minimum of 3 months prior to screening (visit 1). * 'Artisanal' CBD dose must be between 5 mg/kg/day and 20mg/kg/day. * 'Artisanal' CBD preparation must be a high CBD to THC formulation defined as a minimum CBD:THC ratio of 20:1. * Must be taking a minimum of 1 other anti-seizure medication (ASM) in addition to an 'artisanal' form of CBD. * Must be on a stable dose of ASMs for a minimum of 28 days prior to screening (visit 1) and remain on a stable dose throughout the entire study unless medically necessary change(s) are required for safety events. * Participants with a vagal nerve stimulator (VNS) must have the following conditions met: 1. The VNS has been in place for a minimum of 3 months prior to screening (visit 1). 2. The settings have remained constant for 28 days prior to screening (visit 1) and are expected to remain constant throughout the entire study. 3. The battery is expected to last for the duration of the study. * Participants on the ketogenic diet must be on a stable regime for a minimum of 28 days prior to screening (visit 1) and expected to remain stable throughout the entire study. * Participant and/or caregiver must be willing to maintain a seizure diary throughout the duration of the study. Exclusion Criteria: * Previous or current exposure to Epidiolex. * Supplemental use of cannabinoid-containing products, including but not limited to: 1. Recreational use of cannabis. 2. Use of artisanal CBD as a seizure rescue medication. 3. Use of more than one formulation of 'artisanal' CBD (e.g. THC supplementation). * Pregnant or breastfeeding. * Any clinically significant, unstable medical condition other than epilepsy that, in the opinion of the investigator, could place the participant at increased risk or interfere with the results of the study. * Hepatic impairment at screening (visit 1) defined as either of the following conditions: 1. ALT or AST \> 5x upper limit of normal (ULN). 2. ALT or AST \> 3x ULN and total bilirubin \>2x ULN (or international normalized ratio \>1.5). * Known sensitivity to any ingredient in Epidiolex, including sesame and sesame oil. * Unwillingness to refrain from alcohol consumption throughout the duration of the study. * Unwillingness of females of childbearing potential to use a highly effective form of birth control. Acceptable methods include: hormonal contraceptives, intra-uterine devices, bilateral tube occlusion, vasectomized partner and sexual abstinence. * Currently enrolled in another clinical trial. * Have suicidal plan/intent, active suicidal thoughts, or a suicide attempt in the past 6 month prior to screening.

Outcomes

Primary Outcomes

The success rate of transition of children from 'artisanal' CBD to Epidiolex.

Participants successfully transitioned from 'artisanal' CBD to Epidiolex if they complete the transition protocol and continue treatment with Epidiolex at visit 2 following the two-week transition phase of the study. The success rate will be determined as the percentage of participants that complete the two-week transition phase.

Time frame: Baseline (visit 2, Day 1) through visit 4 (Day 15), the two-week transition phase.

Secondary Outcomes

The acceptability rate of Epidiolex in children previously treated with 'artisanal' CBD.

Participants accepted transition to Epidiolex if they continued treatment with Epidiolex after the last scheduled visit of the maintenance period (visit 7). The acceptability rate will be determined as the percentage of participants that continue treatment with Epidiolex after the last scheduled visit of the maintenance period (visit 7, Day 85).

Time frame: Baseline (visit 2, Day 15) to end of treatment (visit 7, Day 85).

The change in seizure frequency following transition of children from 'artisanal' CBD to Epidiolex.

The percent change (increase or decrease) from baseline in 28-day seizure frequency during the maintenance period. Seizure frequency will be calculated as the total number of seizures divided by the number of days with seizure data, multiplied by 28.

Time frame: Baseline (visit 2, Day 1) through the end of treatment (visit 7, Day 85).

Change in reported Pediatric Epilepsy Side-Effects Questionnaire (PESQ) score.

The Pediatric Epilepsy Side Effects Questionnaire (PESQ) is a rating scale to assess pediatric participant-reported side effects associated with anti-seizure medication treatment. Each side-effect is rated on a 6-point Likert scale as follows: (1) - "Not present", (2) - "Low severity", (3) - "Low-moderate severity", (4) - "Moderate severity", (5) - "Moderate-high severity", (6) - "High severity". Higher scores indicated worse side-effects.

Time frame: Baseline (visit 2, Day 1) through visit 4 (Day 15), visit 5 (Day 29) and end of treatment (visit 7, Day 85).

Change Clinical Global Impression of Improvement (CGI-I) score.

The Clinical Global Impression of Improvement (CGI-I) is a 7-point Likert scale used to rate the overall change in seizure control, behaviour, safety and tolerability after transitioning to Epidiolex relative to baseline. The participant's overall improvement is rated by the clinician and caregiver as: 1- "very much improved", 2- "much improved', 3- "minimally improved", 4- "no change", 5- "minimally worse", 6- "much worse", and 7- "very much worse". Higher scores indicate worse condition.

Time frame: Baseline (visit 2, Day 1) through visit 5 (Day 29) and end of treatment (visit 7, Day 85).

Change in Clinical Global Impression of Seizure Intensity/Duration (CGI-CSID) score.

The Clinical Global Impression of Change in Seizure Intensity/Duration (CGI-CSID) is a 7-point Likert scale used to rate the overall change in seizure intensity and/or duration after transitioning to Epidiolex relative to baseline. The participant's overall improvement is rated by the clinician and caregiver as: 1- "very much improved", 2- "much improved', 3- "minimally improved", 4- "no change", 5- "minimally worse", 6- "much worse", and 7- "very much worse". Higher scores indicate worse condition.

Time frame: Baseline (visit 2, Day 1) through visit 5 (Day 29) and end of treatment (visit 7, Day 85).

Change in Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) score.

The Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) is a caregiver-reported questionnaire that evaluates quality of life in epileptic children. It contains 55 questions that measure quality of life in 4 areas: cognitive functioning, emotional functioning, social functioning, and physical functioning. Each question is rated on a 5-point Likert scale, with the option to answer "not applicable" as follows: (1) - "All of the time", (2) - "Most of the time", (3) - "Some of the time", (4) - "A little of the time", (5) - "None of the time", (6) - Not applicable. Higher scores indicate higher health-related quality of life.

Time frame: Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85).

Change in Measure Yourself Medical Outcome Profile 2 (MYMOP2) score.

The Measure Yourself Medical Outcome Profile 2 (MYMOP2) questionnaire is a scale that allows participants or caregivers to identify the problem(s) that are most important to them/the participant, and rate the severity of the problem (s) on a 7-point Likert scale ranging from 0 (as good as it can be) to 6 (as bad as it could be). Higher scores indicate worse problems.

Time frame: Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85)

Change in Children's Sleep Habit Questionnaire (CSHQ) score.

The Children's Sleep Habit Questionnaire (CSHQ) is a caregiver-reported questionnaire to measure sleep behaviours in children. The questionnaire has 45 questions about bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. Each question is rated on a 3-point Likert scale as follows: (1) - "Usually (5 or more times in a week)", (2) - "Sometimes (2-4 times in a week)", (3) - Rarely (never or 1 time during a week). A higher score indicates more sleep problems.

Time frame: Baseline (visit 2, Day 1) through visit 5 (Day 29) and end of treatment (visit 7, Day 85).

Number of dose increases in anti-seizure medications (ASMs) after starting Epidiolex.

The number of dose increases in anti-seizure medications (ASMs), including Epidiolex, due to worsening seizure burden or other factors.

Time frame: Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85).

Number of dose decreases in anti-seizure medications (ASMs) after starting Epidiolex.

The number of dose increases in anti-seizure medications (ASMs), including Epidiolex, due to adverse events or other factors.

Time frame: Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85).

Frequency of adverse events of special interest (AESIs) after starting Epidiolex.

Adverse events of special interest (AESIs) include: somnolence, sedation, appetite changes, gastro-intestinal upset (including diarrhea and vomiting), and transaminase elevations. Frequency of AESIs will be measured by determining the total number of AESIs experienced throughout the treatment period of the study.

Time frame: Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85).

Severity of adverse events of special interest (AESIs) after starting Epidiolex.

Adverse events of special interest (AESIs) include: somnolence, sedation, appetite changes, gastro-intestinal upset (including diarrhea and vomiting), and transaminase elevations. The severity of AESIs will be assessed as: "Mild - Events require minimal or no treatment and do not interfere with the participant's daily activities", "Moderate - Events result in a low level of inconvenience or concern", or "Severe - Events interrupt a participant's usual daily activity and may require therapy or other treatment". The total number of mild, moderate and severe AESIs experienced throughout the treatment period of the study will be determined.

Time frame: Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85).

Duration of adverse events of special interest (AESIs) after starting Epidiolex.

Adverse events of special interest (AESIs) include: somnolence, sedation, appetite changes, gastro-intestinal upset (including diarrhea and vomiting), and transaminase elevations. The duration of AESIs will be measured by calculating the length of individual AESIs experienced throughout the treatment period of the study.

Time frame: Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85).

Withdrawal rate due to adverse events after starting Epidiolex.

The withdrawal rate will be determined as the percentage of participants who withdraw from the study and discontinue Epidiolex due to adverse events.

Time frame: Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85).

The change in frequency of seizure rescue medication use following transition from 'artisanal' CBD to Epidiolex.

The percent change (increase or decrease) from baseline in 28-day seizure rescue medication use during the maintenance period. Rescue medication frequency will be calculated as the total number of doses of rescue medication administered divided by the number of days with diary data, multiplied by 28.

Time frame: Baseline (visit 2, Day 1) through end of treatment (visit 7, Day 85).

Change in Columbia-Suicide Severity Rating Scale (C-SSRS) score.

The Columbia-Suicide Severity Rating Scale (C-SSRS) assess the risk of suicidal ideation and behaviour. The questions are divided into categories related to ideation (thoughts) and behaviour (actions). Higher scores indicate more serious/worse suicidal ideation or behaviors.

Time frame: Baseline (visit 1, Day -28) through end of treatment (visit 7, Day 85).

A Study to Investigate the Transition of Children From 'Artisanal" Cannabidiol (CBD) to Epidiolex

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts