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

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

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.

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.