Cannabidiol in refractory childhood epilepsy, a personalized high-quality approach

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Utrecht

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

24 Jan 2025 → ongoing

Decision date (initial)

2024-08-05

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacogenetic

To study efficacy of add-on CBD compared to placebo in individuals with refractory epilepsy.

Secondary objectives 3

1. To assess the effect of add-on CBD on the patient’s and caregivers’ quality of life and other patient-centered outcomes (PCOMs).
2. To assess personalized biomarkers, ultimately improving the selection of patients who may benefit from and tolerate add-on CBD.
3. To assess cost effectiveness of individualized CBD use compared to usual care in individuals with refractory epilepsy.

Conditions and MedDRA coding

Refractory Epilepsy

Regulatory references

Plan to share IPD

Yes

IPD plan description

Deidentified participant data will contain general patient characteristics, including demographic data, gender, age, relevant medical history and other characteristics that may be of importance. These data will be presented anonymously in the form of an table, graph or appendix in a reviewed article. For further details on data sharing, please recommend the study protocol.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Minimum age of 1 year old and maximum age of 18 years old.
2. Confirmed diagnosis of refractory epilepsy according to ILAE criteria.
3. At least 4 countable seizures (not all on one day) during the 4-week baseline period while receiving at least 1 ASM.
4. All medications or interventions for epilepsy must have been stable dosed for one month prior to screening and the participant is willing to maintain the current ASM regimen throughout the trial.
5. Informed consent/assent of legal representative/ parents.
6. Presence of a consistently available patient caregiver for proxy-reports.

Exclusion criteria 12

1. Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP).
2. History or current symptoms of significantly impaired liver function, such as bilirubin level ≥ 2 x upper limit of normal; or presence of liver damage as indicated by levels of alanine aminotransferase and/or aspartate aminotransferase ≥ 3 x upper limit of normal.
3. Pregnancy, breastfeeding, or intention to become pregnant throughout the trial or within 3 months of completing treatment.
4. Structural heart disease.
5. Glaucoma.
6. Ongoing evaluation for epilepsy surgery.
7. Implementation of vagal nerve stimulation within 3 months prior to screening and unwillingness to delay inclusion until stable settings of vagal nerve stimulation are reached.
8. Starting a ketogenic diet within 3 months prior to screening and unwillingness to delay inclusion until a stable ketogenic diet is reached.
9. Unstable medical condition(s), other than refractory epilepsy, that are of significant influence on participation in the trial; significance to be determined with the treating physician/pediatric neurologist.
10. History of recreational or medicinal cannabis, or cannabinoid-based medications, within three months prior to screening and the patient is unwilling to abstain for the duration of the study.
11. Planned intervention under general anesthesia interfering with the baseline period; or any planned major surgery within the duration of the trial.
12. Expected inability to undergo blood sampling due to anxiety or resistance.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in daily seizure frequency during placebo periods compared to the change from baseline in daily seizure frequency during active treatment periods.

Secondary endpoints 6

1. Change in score from baseline during placebo versus CBD treatment of: Quality of Life in Childhood Epilepsy (QoLCE-55); Global Assessment of Severity of Epilepsy (GASE); Clinical Global Impression of Change (CGI-C); Aberrant Behavior Checklist (ABC); Vineland Adaptive Behavior Score III (VABS-III); Sleep Disturbances Scale for Children (SDSC); Goal attainment scaling (GAS).
2. Number of (serious) adverse events
3. Clinical characteristics including: age; gender; epilepsy characteristics; etiology; comorbidity; co-medication.
4. Measurements of neuronal excitability, measured on EEG and TMS-EMG: assessment of epileptic discharges on EEG; assessment of background activity on EEG; measurement of resting motor threshold on TMS-EMG; measurement of cortical silent period (CSP) on TMS-EMG.
5. Pharmacogenetic assessment of CYP-enzymes such as CYP2C19, CYP2C9, and CYP3A4.
6. Change in productivity loss measured by iMTA Productivity Cost Questionnaire; change in healthcare resources used measured by iMTA Treatment Inventory of Costs in Patients with psychiatric disorders for Children; change in health related quality of life measured by EuroQol Five-Dimensional Questionnaire, Youth version

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Utrecht

Sponsor organisation

Universitair Medisch Centrum Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Secretary for Pediatric Neurology

Public contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Secretary for Pediatric Neurology

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications