Clinical study to assess the efficacy and safety of Cannabidiol in children and young adults with rare disease-associated severe epilepsy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero Universitaria Meyer IRCCS

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 Apr 2024 → ongoing

Decision date (initial)

2023-06-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Jazz Pharmaceutical plc

External identifiers

EU CT number

2023-503709-12-00

ClinicalTrials.gov

NCT05803434

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Demonstrate that Cannabidiol, used in addition to current anti-seizure medications, 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 1

1. Assessment of safety and tolerability, changes in behaviour, cognition and sleep, pharmacokinetic interaction with concurrent anti-seizure medications.

Conditions and MedDRA coding

Epilepsy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female aged 2-25 years as of the day of the Screening Visit;
2. 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
3. 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;
4. Previous treatment with at least 2 ASMs and 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);
5. 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;
6. 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.
7. Surgical treatment for the epilepsy has failed or cannot be pursued

Exclusion criteria 12

1. Age <2 years
2. Current or past use of recreational or medicinal cannabis, or cannabinoid-based medications, within the three months prior to screening
3. Patients with previous history of suicidal behaviour and ideation or at high suicidal risk based on clinical assessment and administration of the Columbia Suicide Severity Rating Scale (for patients 6 years of age, when appropriate otherwise, clinical judgment will be used)
4. Female patients who are pregnant and female of childbearing potential unless willing to ensure the use of a highly effective method of birth control during the study and for three months thereafter
5. Known hypersensitivity to CBD or any of the excipients in the study formulation
6. Progressive neurological disease
7. Clinically significant unstable medical conditions other than epilepsy 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
8. 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
9. Subject taking more than four concurrent ASMs, corticotropins in the six months prior to screening, felbamate 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. Patients with LGS, DS or TSC

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Assess the 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;
2. Assess EEG improvement from baseline during treatment period in a blind senior epileptologists evaluation procedure; 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 endpoints 10

1. Assess the safety and tolerability of CBD as an adjunctive therapy based on safety variables (adverse events, vital signs, body weight, physical examination, neurological examination)
2. Assess pharmacokinetic interaction with concurrent ASMs (blood levels of concurrent ASMs will be taken at baseline and every 4 weeks);
3. Assess the number of subjects considered treatment responders, defined as those with a ≥25%, ≥50% ≥75% reduction in motor (generalized, focal, or both) seizures from baseline;
4. Assess the number of subjects who are free of motor (generalized, focal, or both) seizures;
5. Assess the longest period of seizure freedom;
6. Assess the 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;
7. Assess changes from baseline in number of inpatient hospitalizations due to epilepsy (6 months-period);
8. Assess change in severity of seizures will be assessed using a pediatric adaptation of the Chalfont Seizure Severity Scale (Duncan & Sander, 1991);
9. Assess the change from baseline to 6-months after treatment initiation in number of seizure-free days;
10. Assess the changes from baseline to week 24 in the following scores: cognitive, adaptative, behavioural, functional, quality of life, caregivers and investigator impressions on global severity and improvement, sleep habits.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Meyer IRCCS

Sponsor organisation

Azienda Ospedaliero Universitaria Meyer IRCCS

Address

Viale Gaetano Pieraccini 24

City

Florence

Postcode

50139

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero Universitaria Meyer IRCCS

Contact name

Clinical Trial Office

Public contact point

Organisation

Azienda Ospedaliero Universitaria Meyer IRCCS

Contact name

Clinical Trial Office

Locations

1 EU/EEA country · 1 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 18 files

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

Application history

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