Cannabidiol for Sanfilippo Syndrome

Overseen By Adolfo Morales, BA

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Must not be taking: Cannabis, Diazepam, Valproate, others

Disqualifiers: Slow disease, Liver disease, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 40 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of cannabidiol, specifically Epidiolex, to determine its safety and effectiveness in treating Sanfilippo syndrome. Sanfilippo syndrome is a rare genetic condition that can cause neurobehavioral issues and affect daily life. Caregivers will monitor changes in behavior, mood, sleep, and other areas throughout the study. Participants must have a confirmed diagnosis of Sanfilippo syndrome and should not have recently used cannabis products. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, giving participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain drugs like Rifampin, Diazepam, or Valproate. If you're on Anakinra, Fluoxetine, or a probiotic, you must keep the same dose for 8 weeks before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Epidiolex (cannabidiol) is safe for humans. The FDA has already approved it to treat certain types of epilepsy, indicating it is generally well-tolerated. Earlier studies identified common side effects such as sleepiness and diarrhea. Importantly, these studies did not reveal any serious safety concerns. While mild side effects may occur, past research considers the treatment safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Sanfilippo syndrome?

Unlike the standard treatments for Sanfilippo Syndrome, which mainly focus on managing symptoms with supportive care and enzyme replacement therapies, Epidiolex offers a novel approach by using cannabidiol (CBD) as its active ingredient. CBD is thought to have neuroprotective and anti-inflammatory properties, which could address the underlying mechanisms of the disease rather than just alleviating symptoms. Researchers are excited about Epidiolex because it represents a potential shift towards a treatment that might modify the disease course, offering hope for improved outcomes in a condition that currently lacks effective therapies.

What evidence suggests that cannabidiol might be an effective treatment for Sanfilippo syndrome?

Research has shown that cannabidiol (CBD) may improve behavior in children with certain conditions, such as autism. In studies of severe behavioral issues related to genetic disorders, CBD proved effective. For example, one study of children with hard-to-treat epilepsy found that CBD reduced major seizures by 54-72%. Although Sanfilippo syndrome differs, these results suggest CBD might help with neurobehavioral symptoms. In this trial, participants will receive Epidiolex, a specific type of CBD known for its high quality and reliability. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals with Sanfilippo syndrome, a rare genetic condition. Participants will be selected based on their order of enrollment and must have caregivers able to complete various surveys about the patient's behavior and health throughout the study.

Inclusion Criteria

My MPS III diagnosis was confirmed through genetic testing.

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

I haven't changed my dose of Anakinra, Fluoxetine, or probiotics in the last 8 weeks.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Epidiolex or placebo for 16 weeks, followed by an 8-week washout, then switch to the opposite treatment for another 16 weeks

40 weeks

Regular visits for safety labs and questionnaires

Open-label extension

All participants receive Epidiolex for 52 weeks to measure long-term safety and efficacy

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epidiolex

Trial Overview The study tests cannabidiol (Epidiolex) against a placebo to assess its safety and effectiveness in treating neurobehavioral symptoms of Sanfilippo syndrome. It includes an initial safety cohort followed by a controlled group that switches between Epidiolex and placebo.

How Is the Trial Designed?

Group I: Epidiolex (cannabidiol) Experimental Treatment 1 Intervention

Oral Epidiolex (cannabidiol) administered twice daily (BID) Week 1: 5 mg/kg/day BID Weeks 2-8: 10 mg/kg/day BID Weeks 9-16: 20 mg/kg/day BID 8-week washout; cross-over to placebo comparator starting on Week 24.

Group II: Placebo (PBO) Placebo Group 1 Intervention

Week 1: Dose escalate to maximum tolerated placebo dose Weeks 2-16: Maximum tolerated placebo dose 8-week washout; cross-over to Experimental group starting at week 24, following the same dose-escalation as the Experimental arm.

Epidiolex is already approved in United States, European Union for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidyolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Lead Sponsor

Trials

105

Recruited

46,600+

Published Research Related to This Trial

A single oral dose of 750 mg of cannabidiol (CBD) showed significantly increased exposure when taken with a high-fat/calorie meal, with a 3.8-fold increase in overall exposure (AUC0-∞) and a 5.2-fold increase in maximum concentration (Cmax) compared to fasting.

CBD was well-tolerated with no severe adverse events reported, indicating its safety in healthy adults, while its absorption was also enhanced by low-fat meals, whole milk, and alcohol, albeit to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. Crockett, J., Critchley, D., Tayo, B., et al.[2021]

In a study involving 45 children with treatment-resistant epilepsy, cannabidiol (CBD) significantly reduced major seizure frequency by 54-72% and increased seizure-free days by an average of 7.52 days over 36 months, demonstrating its efficacy as an adjunctive treatment.

CBD was well tolerated at doses up to 50 mg/kg/day, although children who increased their dose beyond 25 mg/kg/day initially reported more adverse events; however, the overall rate of adverse events decreased after transitioning to higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. Park, YD., Linder, DF., Pope, J., et al.[2021]

Pure, plant-derived cannabidiol (CBD; Epidiolex) has been shown to significantly reduce seizure frequencies in patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) by 17% to 23% compared to placebo, making it an effective adjunctive therapy for treatment-resistant epilepsy.

CBD is generally well tolerated, with common side effects including somnolence, diarrhea, and elevated liver enzymes, and it is the first cannabis-derived medication approved by the FDA for these conditions, providing a new treatment option for patients aged 2 years and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes. Chen, JW., Borgelt, LM., Blackmer, AB.[2020]

Epidiolex® (cannabidiol) is an FDA-approved medication for treating epilepsy associated with Lennox-Gastaut and Dravet syndromes, showing promise for treatment-resistant epilepsy.

A case study of a 23-year-old female revealed a delayed skin rash related to Epidiolex®, highlighting the need to monitor for potential side effects even when they are rare in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidiolex-induced skin rash. Singh, J., Antimisiaris, MF.[2021]

In a study of 107 patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), cannabidiol (CBD) was found to be effective as an add-on therapy, with a notable 30% of LGS patients and 21% of DS patients achieving a 50% reduction in seizure frequency after 12 months.

The treatment was well-tolerated, with a retention rate of 63% at 12 months, although 31% of patients experienced adverse events, primarily somnolence and gastrointestinal issues, indicating that while CBD is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective chart review study of use of cannabidiol (CBD) independent of concomitant clobazam use in patients with Lennox-Gastaut syndrome or Dravet syndrome. Nabbout, R., Arzimanoglou, A., Auvin, S., et al.[2023]

Epidiolex® (CBD) is effective for treating epilepsy in patients over 2 years old, but it can interact with other medications, as seen in a case where it contributed to lithium toxicity in a patient with Lennox-Gastaut syndrome.

After discontinuing lithium due to toxicity, the patient improved and remained seizure-free on CBD and two other antiseizure medications, highlighting the importance of monitoring drug interactions when adding CBD to treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-Drug Interactions Between Cannabidiol and Lithium. Singh, RK., Dillon, B., Tatum, DA., et al.[2020]

In a study of 108 patients with refractory epilepsy taking Epidiolex®, 75% remained on the treatment at the final evaluation, indicating that it is generally well-tolerated and effective for long-term use.

However, 46.3% of patients experienced treatment-emergent adverse effects, with 14.5% discontinuing due to these effects, highlighting the need for further research on managing side effects and drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy. Georgieva, D., Langley, J., Hartkopf, K., et al.[2023]

In a study of 47 patients with refractory epilepsy, highly purified cannabidiol (CBD) was found to be effective in reducing seizure frequency, regardless of whether it was used with clobazam (CLB) or not.

Patients taking CBD alongside CLB had a significantly higher responder rate (more than 50% reduction in seizures) at the point of best seizure control within the first year, indicating that combining these treatments may enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. Savage, TE., Sourbron, J., Bruno, PL., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06333041?intr=CANNABIDIOL&aggFilters=studyType:int&viewType=Table&rank=7

Study of Cannabidiol in Sanfilippo Syndrome Studies have shown that CBD improves behavior in children with autism. This study will use Epidiolex, a pharmaceutical-grade purified oral solution of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10768432/

Cannabidiol (Epidyolex®) for severe behavioral ... Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex ( ...

3. ctv.veeva.com ctv.veeva.com/study/study-of-cannabidiol-in-sanfilippo-syndrome

Study of Cannabidiol in Sanfilippo Syndrome The goal of this clinical trial is to test cannabidiol in Sanfilippo syndrome. The main questions it aims to answer are: 1) determine the safety of cannabidiol ...

4. curesanfilippofoundation.org curesanfilippofoundation.org/wp-content/uploads/2025/08/Clinical-Studies-Info-CureSanfilippoFoundation-081125.pdf

Clinical Studies in Sanfilippo syndromes This study is a first in human clinical trial to explore the safety, tolerability and clinical efficacy of ex vivo gene therapy (autologous ...

5. withpower.com withpower.com/trial/phase-2-and-3-mucopolysaccharidosis-iii-4-2024-b5db1

Cannabidiol for Sanfilippo Syndrome · Info for Participants In a study involving 45 children with treatment-resistant epilepsy, cannabidiol (CBD) significantly reduced major seizure frequency by 54-72% and increased ...

6. epidiolexhcp.com epidiolexhcp.com/efficacy-and-safety/safety

Safety and Tolerability | EPIDIOLEX® (cannabidiol) EPIDIOLEX was found to have a consistent safety profile in children and adults. Pneumonia was observed more frequently with concomitant use of EPIDIOLEX and ...