STK-001 for Dravet Syndrome

Not currently recruiting at 17 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Stoke Therapeutics, Inc

Must not be taking: Sodium channel blockers

Disqualifiers: Unstable medical conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 5

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety of a treatment called STK-001 for individuals with Dravet syndrome, a condition causing frequent and severe seizures. Researchers aim to determine if repeated doses of STK-001 are safe and if they improve seizure control and quality of life. The study is open to those who have previously tried STK-001 in earlier trials and completed them successfully. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

If you are currently taking an antiepileptic drug that acts mainly as a sodium channel blocker, you will need to stop it to participate in this trial. This includes medications like phenytoin, carbamazepine, and lamotrigine.

Is there any evidence suggesting that STK-001 is likely to be safe for humans?

Research has shown that STK-001 is generally well-tolerated by people with Dravet syndrome. In studies such as MONARCH and ADMIRAL, 74 patients received one or more doses of STK-001, and the treatment proved safe for these individuals. Patients received up to 9 doses, with amounts ranging from 10 to 45 mg, every four months. These studies did not identify any major safety issues. Additionally, the treatment demonstrated potential in reducing the number of seizures, a significant challenge for those with Dravet syndrome. This suggests that STK-001 is not only safe but might also improve life for those affected. ^{1 2 3 4 5}

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

Unlike the standard treatments for Dravet Syndrome, which typically include antiepileptic drugs like valproate and clobazam, STK-001 takes a novel approach by targeting the root genetic cause of the condition. STK-001 is designed to increase the production of a protein called Nav1.1, which is often deficient in individuals with Dravet Syndrome due to mutations in the SCN1A gene. This treatment offers hope for more directly addressing the underlying cause of seizures rather than just managing symptoms. Researchers are excited about STK-001 because it represents a potential breakthrough in precision medicine for Dravet Syndrome, aiming for more effective and long-lasting seizure control.

What evidence suggests that STK-001 might be an effective treatment for Dravet syndrome?

Research has shown that STK-001 may help reduce seizures in people with Dravet syndrome. Studies found that a single 70mg dose lowered seizure frequency by 43% after three months and by 57% after six months. In previous studies, multiple doses of STK-001 led to ongoing improvements in reducing seizures and enhancing thinking and behavior. Researchers are exploring STK-001 as a treatment that might change the disease itself, not just the symptoms. These findings suggest that STK-001 could greatly enhance the quality of life for those with Dravet syndrome. ^{1 2 3 6 7}

Who Is on the Research Team?

Ann Dandurand, MD

Principal Investigator

Medical Director

Are You a Good Fit for This Trial?

This trial is for patients with Dravet syndrome who completed the STK-001 study STK-001-DS-101, showed a good safety profile, and were compliant with that study's procedures. They shouldn't be on certain antiepileptic drugs like sodium channel blockers or have unstable medical conditions besides epilepsy.

Inclusion Criteria

Had satisfactory compliance with study visits and procedures in Study STK-001-DS-101 per Investigator and Sponsor judgment.

I finished my STK-001 treatment and was deemed safe to proceed by my doctor.

Completed Study STK-001-DS-101 within 4 weeks of the start of their participation in Study STK-001-DS-501 unless approved by sponsor.

Exclusion Criteria

I do not have any unstable health conditions except for epilepsy.

You are currently using or have used an experimental drug other than STK-001 after joining Study STK-001-DS-101.

I am currently on medication for epilepsy that includes drugs like phenytoin or carbamazepine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

Treatment

Participants receive IT administration of STK-001 at the dose level they received in previous studies or as recommended by the Safety Monitoring Committee. Initial treatment includes 3 doses, one every approximately 4 months.

48 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with an End of Study/Follow-up Visit 24 weeks after the last dose of study drug.

24 weeks

2 visits (in-person)

Open-label extension (optional)

Participants may continue treatment with doses approximately every 4 months if they are tolerating the treatment.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• STK-001

Trial Overview The trial tests the long-term safety of repeated doses of STK-001 in those previously treated for Dravet syndrome. It's an open-label extension where changes in seizure frequency, overall health status, and quality of life are also monitored.

How Is the Trial Designed?

Group I: STK-001 multiple dose levels Experimental Treatment 1 Intervention

Enrollment of patients after completion of Study STK-001-DS-101 or Study STK-001-DS-102 if eligible. Patients will receive IT administration of study drug STK-001 at the dose level they received while participating in Study STK-001-DS-101 or STK-001-DS-102, or at a dose level recommended by the Safety Monitoring Committee (SMC).The highest dose administered in this study may not exceed that which has already been evaluated in an STK-001 Phase 1/2 study, and doses above 45 mg/dose in this study require approval from the Food and Drug Administration (FDA). Patients will initially receive 3 doses, one every approximately 4 months (16 weeks). Patients who are tolerating treatment may continue treatment with doses approximately every 4 months, with an End of Study/Follow-up Visit 24 weeks after the last dose of study drug. Patients who do not continue treatment after the third dose will have a Follow-up Visit (V5) at Week 48 and an End of Study Visit at Week 56.

Who Is Running the Clinical Trial?

Stoke Therapeutics, Inc

Lead Sponsor

Trials

3

Recruited

270+

Published Research Related to This Trial

In a study of 112 patients with Dravet syndrome, only 15% of trials with conventional antiepileptic drugs (AEDs) were effective in reducing seizures by more than 50%, highlighting the challenges in managing this condition.

In contrast, stiripentol (STP) add-on therapy resulted in over 50% reduction in generalized tonic-clonic seizures (GTCS) for 61% of patients, with some achieving seizure freedom, indicating its potential as a beneficial treatment option for Dravet syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stiripentol open study in Japanese patients with Dravet syndrome. Inoue, Y., Ohtsuka, Y., Oguni, H., et al.[2018]

The estimated incidence of Dravet syndrome in Sweden is approximately 1 in 33,000 live births, with a prevalence of 1 in 45,700 children under 18 years, based on a study of 42 children diagnosed between 2007 and 2011.

A significant majority (88%) of the patients had mutations in the SCN1A gene, and treatment with the add-on medication Stiripentol showed that 23% of patients became seizure-free, indicating potential efficacy in managing this severe genetic epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dravet syndrome in Sweden: a population-based study. Rosander, C., Hallböök, T.[2022]

A 20-year-old man with Dravet syndrome exhibited a rare seizure type called photosensitive myoclonic absence seizures, which had not been previously reported, highlighting the complexity of this condition.

Despite treatment with multiple antiepileptic medications and a vagus nerve stimulator, the seizures remained refractory, indicating the challenges in managing Dravet syndrome and the need for careful monitoring to identify all seizure types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myoclonic Absence Seizures in Dravet Syndrome. Myers, KA., Scheffer, IE.[2018]

Dravet syndrome, a severe form of epilepsy that begins in infancy, is often linked to mutations in the SCN1A gene, affecting about 85% of patients, and leads to various stages of seizure activity and developmental challenges.

Several potential treatments are being explored, including fenfluramine and STK-001, which target different mechanisms of action, showing promise in early clinical evaluations and animal models for managing the symptoms of Dravet syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the design and discovery of novel small molecule drugs for the treatment of Dravet Syndrome. Miziak, B., Czuczwar, S.[2021]

Citations

1. dravetfoundation.org dravetfoundation.org/updates-on-stk-001-a-possible-disease-modifying-therapy-for-dravet-syndrome/

Updates on STK-001: A Possible Disease-Modifying ... While a single dose of 70mg led to significant seizure reductions (43% at 3 months and 57% at 6 months), two to three doses at 70mg resulted in ...

2. investor.stoketherapeutics.com investor.stoketherapeutics.com/news-releases/news-release-details/stoke-therapeutics-announces-landmark-new-data-support-potential

Stoke Therapeutics Announces Landmark New Data That ... STK-001 is the first medicine in development to demonstrate substantial and durable reductions in seizure frequency and improvements in multiple measures of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04740476

An Open-Label Extension Study of STK-001 for Patients ... This study is a multi-center, open-label, multiple-dose, safety extension study for patients who have completed another study of STK-001 and meet study ...

4. investor.stoketherapeutics.com investor.stoketherapeutics.com/news-releases/news-release-details/stoke-therapeutics-announces-positive-new-safety-efficacy-data

Press Release Details – OLE Study Data STK-001 (30mg, 45mg): Sustained reductions in convulsive seizure frequency and improvements in cognition and behavior –. – ...

5. neurologylive.com neurologylive.com/view/neurovoices-barry-ticho-disease-modifying-potential-stk-001-treating-dravet-syndrome

NeuroVoices: Barry Ticho, MD, PhD, on the Disease- ... In the future, STK-001 could become a cornerstone therapy for Dravet syndrome. Our Phase 3 study will focus on children aged 2 to 18 who ...

6. aesnet.org aesnet.org/abstractslisting/patients-with-dravet-syndrome-in-open-label-extension-studies-of-zorevunersen-stk-001-have-durable-reductions-in-seizure-frequency-and-clinically-meaningful-improvements-in-cognition-and-behavior

patients with dravet syndrome in open-label extension studies ... Patients have received up to a total of 9 STK-001 doses given every four months (10-45 mg/dose) in the OLE studies. All patients are currently ...

7. isrctn.com isrctn.com/ISRCTN99651026

Admiral: a study of the safety of multiple increasing doses ... Administration of multiple ascending doses of STK-001 is safe and well-tolerated in patients with Dravet syndrome between the ages of 2 and <18 years.