Cannabidiol (Epidiolex) for neurobehavioral symptoms in Sanfilippo syndrome

Randomized, Double-Blind, Placebo-Controlled Cross-Over Study to Evaluate the Effects of Cannabidiol on Neurobehavioral and Function Outcomes in Sanfilippo Syndrome

This trial will test whether Epidiolex (a pharmaceutical cannabidiol) is safe and can help children and young people with Sanfilippo syndrome reduce neurobehavioral problems and improve daily functioning.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 4 Years and up
• Sex: All
• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (other)
• Locations: 1 site (Torrance, California)
• Trial ID: NCT06333041 on ClinicalTrials.gov

What this trial studies

Approximately 35 participants with genetically confirmed Mucopolysaccharidosis type III (Sanfilippo) aged 4 years and older will be enrolled to collect safety and parent-reported neurobehavioral and functional outcomes. The first five participants form a sentinel safety cohort all receiving Epidiolex, and the next ~30 are randomized 1:1 in a controlled crossover design to receive Epidiolex or placebo for 16 weeks, then an 8-week washout, followed by the opposite treatment for 16 weeks. Caregivers will complete periodic surveys on behavior, mood, sleep, stooling, pain, and caregiver stress to capture changes during each treatment period. Epidiolex is an FDA-approved cannabidiol formulation for severe pediatric epilepsy and has shown behavioral benefits in other pediatric neurodevelopmental conditions, but its use in Sanfilippo is novel.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 4 years or older with genetically confirmed MPS III who meet the study's functional or prior gene-therapy participation criteria and whose caregivers can complete study visits and questionnaires.

Not a fit: Patients with mutations known to cause a slowly progressive form of the disease or who meet the study's exclusion criteria (or who cannot attend the single-site visits) are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this treatment could reduce disruptive neurobehavioral symptoms and improve quality of life for patients and families.

How similar studies have performed: Pharmaceutical-grade cannabidiol (Epidiolex) is proven safe and effective for certain pediatric epilepsies and has shown behavioral improvements in some autism studies, but applying it to Sanfilippo syndrome is novel and unproven.

Eligibility criteria

Inclusion Criteria:

* MPS III diagnosis confirmed by genetic testing
* ≥ 4 years of age
* Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 16 years of age, assent must also be provided when cognitively possible.
* If taking any of the following, no dose changes for the last 8 weeks:

  1. Anakinra
  2. Fluoxetine
  3. Probiotic supplement
* One of the following criteria are met:

  1. Previous participation in a gene/cell therapy or enzyme restorative clinical trial.
  2. Previously ineligible to participate in a gene/cell therapy or enzyme restorative clinical trial due to advanced disease state.
  3. Functional age, as measured by the Vineland, is ≤ 0.5 chronological age

Exclusion Criteria:

Equitable selection will be used when choosing participants. An individual who meets any of the following criteria will be excluded from participation in this study:

* Mutation known to cause slowly progressive disease
* Taken any form of cannabis, including cannabidiol, in the last 8 weeks
* Currently enrolled in another ongoing clinical trial
* Concomitant use of any of the following therapies:

  * Rifampin
  * Diazepam (except for intermittent use as needed for treatment of a prolonged seizure episode)
  * Clobazam
  * Stiripentol
  * Everolimus, sirolimus, tacrolimus
  * Digoxin
  * Valproate
  * Recreational or medical Tetrahydrocannabinol (THC) or synthetic cannabinoid medications (including Sativex) within the last three months
  * Felbamate (if taking for less than one year)
* Non-pharmacological therapies (e.g. ketogenic diet) must be stable for up to four weeks prior to enrollment
* Clinical evidence of liver disease or liver injury as indicated by the presence of abnormal tests (AST or ALT \> 2 x ULN; Bilirubin \> 2 x ULN)
* Known hypersensitivity to any components of Epidiolex (cannabidiol)
* Pregnant or lactating women
* Any other social or medical condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or be detrimental to the study

Where this trial is running

Torrance, California

• The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center — Torrance, California, United States (RECRUITING)

Study contacts

• Study coordinator: Jonathan Acevedo, BS

Conditions: Sanfilippo Syndrome, Mucopolysaccharidosis III, Cannabidiol, Epidiolex