STK-001 for Dravet Syndrome

Recruiting at 16 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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing the safety of STK-001, a new treatment for Dravet syndrome. It aims to help patients by increasing a brain protein that is usually low in this condition. The study focuses on patients who have already tried this treatment in earlier studies.

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.

How is the drug STK-001 different from other treatments for Dravet Syndrome?

STK-001 is unique because it is an antisense oligonucleotide, which means it is designed to target and modify the genetic instructions that cause Dravet Syndrome, potentially addressing the root cause of the condition rather than just managing symptoms like other treatments. ^{1 2 3 4 5}

Research Team

Ann Dandurand, MD

Principal Investigator

Medical Director

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Stiripentol open study in Japanese patients with Dravet syndrome. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Dravet syndrome in Sweden: a population-based study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Development of an antiseizure drug screening platform for Dravet syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Myoclonic Absence Seizures in Dravet Syndrome. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Advances in the design and discovery of novel small molecule drugs for the treatment of Dravet Syndrome. [2021]