Cannabidiol in Children and Young Adults With Rare Disease-associated Severe Epilepsy

Phase 2

Not yet recruiting

• Conditions: Epilepsy; Rare Diseases
• Interventions: Drug: Cannabidiol oral solution

• Registration Number: NCT05803434
• Lead Sponsor: Meyer Children's Hospital IRCCS

Brief Summary

This is a pilot, open-label, phase II study. The main objective of the study is to demonstrate that Cannabidiol (CBD), used in addition to current anti-seizure medications (ASMs) reduces the number and/or severity of motor (generalized, focal, or both) seizures in children and young adults with rare disease-associated severe epilepsy.

Secondary objectives include assessment of safety and tolerability, changes in behaviour, cognition and sleep, pharmacokinetic interaction with concurrent ASMs.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-28
• Study First Submitted QC: 2023-03-27
• Status Verified: 2023-04
• Study First Posted: 2023-04-07
• Last Update Submitted: 2023-04-14
• Last Update Posted: 2023-04-18
• Study Start: 2023-06-01
• Primary Completion: 2025-03-01
• Study Completion: 2025-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Male or female;
2. Children (age 2-18 years) and young adults (18-25 years), as of the day of the Screening Visit;
3. Subject with rare disease-associated severe epilepsy. Subject has been certified by the National Health System as affected by a rare disease listed in https://www.malattierare.gov.it
4. Patient has severe epilepsy, with at least 4 motor (generalized, focal, or both) seizures per month during baseline period, despite 2 or more current or prior ASMs;
5. Previous treatment with at least 2 ASMs;
6. Currently taking at least 1 other ASMs or between one and four ASMs, with a stable antiseizure treatment for the previous 4 weeks (including ketogenic diet and vagal nerve stimulation);
7. Subject's parent/caregiver has been informed of the nature of the study and informed consent has been obtained from the legally responsible parent/guardian;
8. Subject's parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability in the opinion of the investigator

Exclusion Criteria

1. Age <2 years;
2. Known hypersensitivity to CBD or any of the excipients in the study formulation;
3. Progressive neurological disease;
4. Clinically significant unstable medical conditions other than epilepsy that may place patient's safety at risk;
5. Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, may influence the result of the study, or affect the patient's ability to participate in the study;
6. Impaired hepatic function at screening defined as any of the following: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal (ULN) and total bilirubin (TBL) greater than 2 times the ULN;
7. Subject taking more than four concurrent ASMs;
8. Subject has taken corticotropins in the six months prior to screening;
9. Subjects taking felbamate, and they have been taking it for less than one year prior to screening;
10. Inadequate supervision by parents and/or caregivers as judged by the investigator;
11. Subject has been part of a clinical trial involving another investigational medicinal product in the previous six months;
12. Current or past use of recreational or medicinal cannabis, or cannabinoid-based medications, within the three months prior to screening and is unwilling to abstain for the duration for the study;
13. Female patients who are pregnant;
14. Female patients of childbearing potential or male patient whose partner is of childbearing potential, unless willing to ensure that they or their partner use a highly effective method of birth control during the study and for three months thereafter.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cannabidiol treatment	Cannabidiol oral solution	-

Primary Outcome Measures

Name	Time	Method
Change in number of generalized and/or focal motor-onset seizure frequency	24 weeks	percentage change per 28 days from the 4-week baseline period in generalized and/or focal motor-onset seizure frequency during the 24-week treatment period
Change in severity of generalized and/or focal motor-onset seizure frequency	24 weeks	a score will be established for each patient, based on review and comparison of all baseline-EEG/7-weeks control-EEG and baseline-EEG/15-weeks control-EEG, with values ranging from 0 (= worsened EEG), to a maximum of 2 (= improved); 1 will be assigned if the EEG trace is unmodified

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events	24 weeks	Adverse events reporting according to Common Terminology Criteria for Adverse Events (CTCAE) from 1 (mild) to 5 (death)
Body weight	24 weeks	Measurement of body weight for tolerability monitoring
Maximum Plasma Concentraion [Cmax] of concurrent ASMs	24 weeks	blood levels of concurrent ASMs will be taken at baseline and every 4 weeks
Number of subjects considered treatment responders	24 weeks	Number of subjects with a ≥25%, ≥50% ≥75% reduction in motor (generalized, focal, or both) seizures from baseline
Changes from baseline in number of inpatient hospitalizations due to epilepsy	24 weeks	Changes from baseline in number of inpatient hospitalizations due to epilepsy
Number of subjects who are free of motor (generalized, focal, or both) seizures	24 weeks	Number of subjects who are free of motor (generalized, focal, or both) seizures
Longest period of seizure freedom	24 weeks	Longest period of seizure freedom
Number of patients experiencing a >25% worsening, -25 to +25% no change, 25-50% improvement, 50-75% improvement or >75% improvement in total seizures from baseline	24 weeks	Number of patients experiencing a \>25% worsening, -25 to +25% no change, 25-50% improvement, 50-75% improvement or \>75% improvement in total seizures from baseline
Change in severity of seizures will be assessed using a pediatric adaptation of the Chalfont Seizure Severity Scale	24 weeks	Change in severity of seizures will be assessed using a pediatric adaptation of the Chalfont Seizure Severity Scale (from 1 minimum severity to \>100 max severity)
Change from baseline to 6-months after treatment initiation in number of seizure-free days	24 weeks	Change from baseline to 6-months after treatment initiation in number of seizure-free days