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

Epilepsy Clinical Trial

— CBD_RE  

Official title:

Open-label Pilot Study to Assess the Efficacy and Safety of Cannabidiol Oral Solution as an Adjunctive Treatment for Children and Young Adults With Rare Disease-associated Severe Epilepsy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05803434
• Other study ID #: CBD_RE
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 1, 2023
• Est. completion date: March 1, 2025

Study information

• Verified date: April 2023
• Source: Meyer Children's Hospital IRCCS
• Contact: Renzo Guerrini, MD, FRCP, FAES
• Phone: 00390555662573
• Email: renzo.guerrini[@]meyer.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: March 1, 2025
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 25 Years

Eligibility

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.

Related Conditions & MeSH terms

• Epilepsy
• Rare Diseases

Intervention

Drug:
• Cannabidiol oral solution
Cannabidiol will be administered orally twice daily into equally divided doses. The starting dose is 2.5 mg/kg twice daily. The dose can be gradually increased to 5 mg/kg twice daily, which is the recommended maintenance dose, up to a maximum dose of 10 mg/kg twice daily, according to tolerability and clinical response. Following titration, subjects will continue treatment over a 20-week maintenance period. The total treatment duration from the beginning of the titration period till the end of the maintenance period will be 24 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Meyer Children's Hospital IRCCS

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in number of generalized and/or focal motor-onset seizure frequency	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	24 weeks
Primary	Change in severity of generalized and/or focal motor-onset seizure frequency	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	24 weeks
Secondary	Incidence of adverse events	Adverse events reporting according to Common Terminology Criteria for Adverse Events (CTCAE) from 1 (mild) to 5 (death)	24 weeks
Secondary	Body weight	Measurement of body weight for tolerability monitoring	24 weeks
Secondary	Maximum Plasma Concentraion [Cmax] of concurrent ASMs	blood levels of concurrent ASMs will be taken at baseline and every 4 weeks	24 weeks
Secondary	Number of subjects considered treatment responders	Number of subjects with a =25%, =50% =75% reduction in motor (generalized, focal, or both) seizures from baseline	24 weeks
Secondary	Number of subjects who are free of motor (generalized, focal, or both) seizures	Number of subjects who are free of motor (generalized, focal, or both) seizures	24 weeks
Secondary	Longest period of seizure freedom	Longest period of seizure freedom	24 weeks
Secondary	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	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
Secondary	Changes from baseline in number of inpatient hospitalizations due to epilepsy	Changes from baseline in number of inpatient hospitalizations due to epilepsy	24 weeks
Secondary	Change in severity of seizures will be assessed using a pediatric adaptation of the Chalfont Seizure Severity Scale	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)	24 weeks
Secondary	Change from baseline to 6-months after treatment initiation in number of seizure-free days	Change from baseline to 6-months after treatment initiation in number of seizure-free days	24 weeks