Epidiolex for ESES

Overseen By Aaqil Ali

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Northwell Health

Disqualifiers: Cannabidiol, Pregnancy, Allergic reactions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Epidiolex, a cannabidiol (CBD) solution, can reduce seizures in children with ESES, a rare epilepsy disorder characterized by frequent spikes in brain activity during sleep. Researchers will compare Epidiolex to a placebo to determine its effectiveness in reducing seizure activity. Children aged 2 to 17 with ESES who do not require immediate hospital care for seizures might be suitable candidates. This study aims to determine if CBD can provide a new treatment option for those with this condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that several anti-epileptic drugs have been tried with mixed benefits, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that Epidiolex is likely to be safe for humans?

Research has shown that Epidiolex, a type of cannabidiol (CBD), has been studied for its safety in treating epilepsy. In several studies, some patients experienced side effects, usually mild to moderate. One study found that about 9.7% of patients using CBD reported side effects like tiredness or diarrhea, compared to 4% in the group not using CBD.

The FDA has already approved Epidiolex for treating certain types of epilepsy, indicating its safety for those conditions. However, the current study is in the early stages and examines the safety of Epidiolex for ESES, a type of epilepsy with sleep-related spikes. While some safety information is available, more research is needed for this specific condition. ^{1 2 3 4 5}

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

Researchers are excited about Epidiolex for treating ESES because it leverages cannabidiol, a compound derived from cannabis, which offers a new mechanism of action compared to standard treatments like steroids or antiepileptic drugs. Unlike these conventional therapies that often focus on suppressing electrical activity in the brain, Epidiolex targets and modulates the endocannabinoid system, which might provide a more balanced approach to reducing seizures. Additionally, Epidiolex is an oral solution, making it easier to administer and adjust dosages compared to some other treatments that might require injections or more complex regimens. This novel approach could potentially offer a more effective and manageable treatment option for patients with ESES.

What evidence suggests that Epidiolex might be an effective treatment for ESES?

Research has shown that Epidiolex, which contains cannabidiol, can help reduce seizures in people with epilepsy. In studies, many patients experienced fewer seizures when they included cannabidiol in their treatment. For instance, one study found that 86% of children had fewer seizures over 12 to 32 months. Cannabidiol works by affecting the brain's communication systems to lower seizure activity. In this trial, participants will receive either Epidiolex or a placebo to evaluate its effectiveness specifically for ESES. Although data on ESES is limited, positive results in other types of epilepsy suggest that Epidiolex might also be effective for ESES. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children and teens aged 2-17 with ESES, a type of seizure disorder worsened by sleep. Participants must be in stable health, able to take oral medication, and use effective contraception if applicable. They can't join if they've used CBD recently, are pregnant or breastfeeding, have had a recent feverish illness, taken experimental drugs within the last 6 months, or are allergic to Epidiolex ingredients.

Inclusion Criteria

I am a man who can father children and will use contraception.

I am between 2 and 17 years old.

In good general health as evidenced by medical history or diagnosed with ESES. 'Good health' in relation to this study is understood as stable without current seizures requiring immediate hospitalization

Exclusion Criteria

I have used cannabidiol in the last 4 months.

I have not had a fever or febrile illness in the last month.

You have smoked or used tobacco in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Epidiolex or placebo in a double-blind, placebo-controlled crossover design to assess efficacy in reducing seizure frequency and intensity

20 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 Epidiolex's effectiveness against ESES compared to a placebo. It's double-blind (neither doctors nor patients know who gets what) and crossover (patients switch from drug to placebo at some point), aiming to see if CBD can help where other treatments have had mixed results.

How Is the Trial Designed?

Group I: IP Active Control 1 Intervention

Epidiolex (Cannabidiol) is a colorless to yellow solution in a 100mL vial that is to be administered with a 5mL syringe.The starting dosage is 2.5 mg/kg twice daily, or 5 mg/kg/day. After one week, the dosage can be increased to a maintenance dosage of 5mg/kg twice daily, or 10 mg/kg/day. Patients who are tolerating Epidiolex at 10mg/kg per day and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance. Dosage of 10mg/kg twice daily (20mg/kg/day), in weekly increments of 2.5 mg/kg twice daily(5mg/kg/day), as tolerated. For patients in whom a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased to no more frequently than every other day administration of the 20 mg/kg/day. Dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions.

Group II: Placebo Placebo Group 1 Intervention

Placebo is a colorless to yellow solution in a 100mL vial that is to be administered with a 5mL syringe. The starting dosage is 2.5 mg/kg twice daily, or 5 mg/kg/day. After one week, the dosage can be increased to a maintenance dosage of 5mg/kg twice daily, or 10 mg/kg/day. Patients who are tolerating Placebo at 10mg/kg per day and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance. Dosage of 10mg/kg twice daily (20mg/kg/day), in weekly increments of 2.5 mg/kg twice daily(5mg/kg/day), as tolerated. For patients in whom a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased to no more frequently than every other day administration of the 20 mg/kg/day. Dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions.

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?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Greenwich Biosciences

Industry Sponsor

Trials

3

Recruited

150+

Published Research Related to This Trial

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]

Epidiolex, a 99% pure oral CBD extract, has been shown to significantly reduce seizure frequency in patients with medically refractory epilepsy, leading to its FDA approval.

The review highlights the safety profile of Epidiolex, noting that while it is effective, understanding its adverse effects is crucial for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects. Sekar, K., Pack, A.[2020]

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 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]

In a study of 139 participants with treatment-resistant epilepsy, the use of highly purified cannabidiol (CBD; Epidiolex®) led to significant reductions in adverse events, seizure severity, and seizure frequency over 12 weeks, with improvements sustained for up to 48 weeks.

The study demonstrated that CBD was well-tolerated, with a decrease in adverse events from 40.8 to 33.2 and a reduction in seizure severity scores from 80.7 to 39.2, indicating its efficacy as a treatment option for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study. Szaflarski, JP., Bebin, EM., Cutter, G., et al.[2019]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04721691

Efficacy of Epidiolex in Patients With Electrical Status ... This study aims to assess the efficacy of Epidiolex in patients with ESES. ESES is characterized by sleep potentiated spikes with a spike index greater than ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04721691/efficacy-of-epidiolex-in-patients-with-electrical-status-epilepticus-of-sleep-eses

Efficacy of Epidiolex in Patients With Electrical Status ... This study aims to assess the efficacy of Epidiolex in patients with ESES. ESES is characterized by sleep potentiated spikes with a spike ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7023903/

Prospects of Cannabidiol for Easing Status Epilepticus ... In this review, we confer the promise of cannabidiol, an active ingredient of Cannabis sativa, for preventing or easing SE-induced neurodegeneration.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11775975/

The use of cannabidiol as adjunctive therapy in adult ... One study reported the three most common adverse events: diarrhea, sedation, and decreased appetite. Regarding patient outcomes, two studies ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1059131122000012#!

Long-term use of cannabidiol-enriched medical cannabis ... At the last visit after a follow-up ranging from 12 to 32 months, 51/59 children (86%) had responded to treatment with a decrease in seizure frequency. Overall, ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK605531/

Clinical Review - Cannabidiol (Epidiolex) - NCBI - NIH Out of all patients with DS, 70.1% experienced a 25% or greater reduction in total seizure frequency, 39.7% experienced a 75% or greater reduction in total ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S152550502100799X

Effects of Epidiolex® (Cannabidiol) on seizure-related ... Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. ...

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2803957

Adverse Events of Cannabidiol Use in Patients With Epilepsy Results Nine studies were included. Overall incidences of 9.7% in the CBD group and 4.0% in the control group were found for any grade AEs.