Effectiveness of CBD on behavioural problems in patients with TSC, FXS and Sanfilippo

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Decision date (initial)

2025-10-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Jazz Pharmaceuticals

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To investigate the effectiveness of CBD on irritability and other behavioural problems in children and adults with TSC, Sanfilippo and FXS

Secondary objectives 1

1. To evaluate the impact of CBD on aspects of the behavior, functioning, wellbeing and safety of patients with TSC, FXS or Sanfilippo syndrome

Conditions and MedDRA coding

Tuberous Sclerosis Complex (TSC), Sanfilippo syndrome, Fragile X syndrome (FXS)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Subjects must be at least 6 years old and have a clinically confirmed diagnosis of FXS, TSC or Sanfilippo syndrome. Participants must also exhibit severe behavioral manifestations, defined as a minimum score of 4 on the Clinical Global Impressions (CGI) scale. All medications or interventions for epilepsy and behavioral symptoms must have been stable for at least one month prior to the screening, and participants must be willing to maintain this regimen throughout the duration of the study. Finally, a consistently available patient caregiver is required to provide proxy reports.
2. Minimum age of 6 years old
3. Clinically definite diagnosis of TSC, Sanfilippo syndrome or FXS (modified Gomez criteria or positive genetic test (such as FISH test, microarray, WES-analysis))
4. Suffering from severe behavioural manifestation with a minimum score of 4 on the CGI scale
5. All medications or interventions for epilepsy and behavioural manifestations must have been stable dosed for one month prior to screening and the participant is willing to maintain the current regimen throughout the trial
6. Presence of a consistently available patient caregiver for proxy-reports

Exclusion criteria 16

1. Use of valproate should be stable three months prior to enrolment
2. Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP), such as sesame oil
3. Participant is currently using or has in the past used recreational or medicinal cannabis, or cannabinoid-based medications, within three months prior to screening and is unwilling to abstain for the duration of the study
4. Treatment with CBD or other cannabinoid within the previous two months
5. History or current evidence of significantly impaired liver function, defined as 1) Alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) > 5 × upper limit of nor-mal (ULN); 2) ALT or AST > 3 × ULN with concomitant total bilirubin > 2.0 × ULN; or 3) ALT or AST ≥ 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia
6. Pregnancy or breastfeeding
7. Glaucoma
8. Participant has undergone general anaesthesia in the four weeks prior to randomization
9. Planned changes in use of anti-epileptics
10. Subjects who have had changes in non-exclusionary psychotropic medications within 4 weeks of initiation of trial
11. Any planned major surgery within the duration of the trial
12. Expected inability to take blood samples due to anxiety or resistance
13. Unable to swallow the study drug (or placebo)
14. The patient is unwilling or, in the investigator’s opinion, unable to adhere to the requirements of the study
15. Any condition or abnormality which may, in opinion of the investigator, compromise the safety of patients
16. Use of any interfering medication within 30 days prior to enrolment or planning to take in-terfering medication during the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The effectiveness of CBD on behavioural problems using the irritability subscale of the Aberrant Behavior Checklist (ABC) in children and adults with FXS, TSC and Sanfilippo syndrome

Secondary endpoints 10

1. Effectiveness of CBD on symptom severity, measured bij change in Clinical Global Impression (CGI)
2. Effectiveness of CBD on quality of life, measured by changes in syndrome specific outcome measures.
3. Effectiveness of CBD on anxiety, depression and mood, measured by change in Anxiety, Depression and Mood Scale (ADAMS).
4. Effectiveness of CBD on autism symptoms, measured by change in Social Communication Questionnaire / Social Responsiveness Scale (SCQ/SRS-2) score
5. Effectiveness of CBD on sensory processing, measured by change in Short Sensory Profile (SP-NL)
6. Effectiveness of CBD on parental stress, measured by change in Opvoedingsbelasting Vragenlijst (OBVL)
7. Effectiveness of CBD on personal goals, measured by change in Goal Attainment Scaling (GAS)
8. Effectiveness of CBD on focal and generalized seizure frequency, measured by keeping a seizure diary each time a seizure occurs.
9. Safety and tolerability of CBD, measured by keeping track of adverse events and side effects
10. Monitoring of hepatic enzyme levels (ALT, AST, bilirubin)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Agnies van Eeghen

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Agnies van Eeghen

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 19 files

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

Application history

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