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
Overview
- Phase
- Phase 2
- Intervention
- Cannabidiol oral solution
- Conditions
- Epilepsy
- Sponsor
- Meyer Children's Hospital IRCCS
- Enrollment
- 30
- Primary Endpoint
- Change in number of generalized and/or focal motor-onset seizure frequency
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
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.
Investigators
Renzo Guerrini
Director, Head of Child Neurology Department, Principal Investigator, Clinical Professor
Meyer Children's Hospital IRCCS
Eligibility Criteria
Inclusion Criteria
- •Male or female;
- •Children (age 2-18 years) and young adults (18-25 years), as of the day of the Screening Visit;
- •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
- •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;
- •Previous treatment with at least 2 ASMs;
- •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);
- •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;
- •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
- •Age \<2 years;
- •Known hypersensitivity to CBD or any of the excipients in the study formulation;
- •Progressive neurological disease;
- •Clinically significant unstable medical conditions other than epilepsy that may place patient's safety at risk;
- •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;
- •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;
- •Subject taking more than four concurrent ASMs;
- •Subject has taken corticotropins in the six months prior to screening;
- •Subjects taking felbamate, and they have been taking it for less than one year prior to screening;
- •Inadequate supervision by parents and/or caregivers as judged by the investigator;
Arms & Interventions
Cannabidiol treatment
Intervention: Cannabidiol oral solution
Outcomes
Primary Outcomes
Change in number of generalized and/or focal motor-onset seizure frequency
Time Frame: 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
Time Frame: 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 Outcomes
- Incidence of adverse events(24 weeks)
- Body weight(24 weeks)
- Maximum Plasma Concentraion [Cmax] of concurrent ASMs(24 weeks)
- Number of subjects considered treatment responders(24 weeks)
- Changes from baseline in number of inpatient hospitalizations due to epilepsy(24 weeks)
- Number of subjects who are free of motor (generalized, focal, or both) seizures(24 weeks)
- Longest period of seizure freedom(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(24 weeks)
- Change in severity of seizures will be assessed using a pediatric adaptation of the Chalfont Seizure Severity Scale(24 weeks)
- Change from baseline to 6-months after treatment initiation in number of seizure-free days(24 weeks)