Epilepsy, Rare Diseases
Conditions
Keywords
drug resistant epilepsy, rare epilepsy, cannabidiol
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.
Interventions
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.
Sponsors
Meyer Children's Hospital IRCCS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 25 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Incidence of adverse events | 24 weeks | Adverse events reporting according to Common Terminology Criteria for Adverse Events (CTCAE) from 1 (mild) to 5 (death) |
| Changes from baseline in number of inpatient hospitalizations due to epilepsy | 24 weeks | Changes from baseline in number of inpatient hospitalizations due to epilepsy |
| 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 |
| 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 |
| Body weight | 24 weeks | Measurement of body weight for tolerability monitoring |
Contacts
Primary ContactRenzo Guerrini, MD, FRCP, FAES
Backup ContactSimona Balestrini, MD, PhD
Outcome results
None listed