STK-001 for Dravet Syndrome

Recruiting at 23 trial locations

Overseen By Kimberly Parkerson, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Stoke Therapeutics, Inc

Must be taking: Antiepileptic drugs

Must not be taking: Sodium channel blockers

Disqualifiers: Pathogenic mutation, Unstable conditions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

62 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing STK-001, a new medicine for people with Dravet syndrome. It aims to increase a protein in the brain that these patients lack, which could help reduce seizures and improve their overall health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of your epilepsy medication for at least 4 weeks before joining. You cannot participate if you are currently taking certain sodium channel blocker medications.

What makes the drug STK-001 unique for treating Dravet Syndrome?

STK-001 is unique because it is an antisense oligonucleotide, which means it is designed to target and modify the genetic mutations in the SCN1A gene 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 children and adolescents with Dravet Syndrome, who had normal development at seizure onset and have been on stable epilepsy treatments for at least 4 weeks. They must have tried at least two other epilepsy treatments without success or stopped due to side effects. Participants should not have any significant medical conditions besides epilepsy.

Inclusion Criteria

My epilepsy treatment has been the same for the last 4 weeks.

I have been on a stable dose of epilepsy medication for at least 4 weeks.

No other known cause.

Exclusion Criteria

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

I haven't had any major illnesses or symptoms, except for epilepsy, in the last 4 weeks.

I have never had brain or spinal cord diseases, bacterial meningitis, or brain malformations, except for epilepsy or DS.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive single and multiple ascending doses of STK-001

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• STK-001

Trial Overview The study by Stoke Therapeutics tests the safety of different doses of STK-001 given once or multiple times in patients with Dravet syndrome. It's an open-label study, meaning everyone knows what treatment they're getting, and it also looks at how seizures and quality of life might change.

Participant Groups

Group I: Single Ascending Doses Experimental Treatment 1 Intervention

Enrollment of patients in two age groups. A Sentinel group of 2 patients aged 13 to 18 years of age, inclusive, and an expanded group of 2 patients 2 to 12 years of age to receive single doses. There will be an option to dose up to 6 additional patients at each dose level and an option to expand the maximum tolerated dose level with 5 additional patients.

Group II: Multiple Ascending Doses Experimental Treatment 1 Intervention

Enrollment of patients in two age groups. A Sentinel group of 2 patients aged 13 to 18 years of age, inclusive, and an expanded group of 2 patients 2 to 12 years of age to receive multiple doses. There will be an option to dose up to 6 additional patients at each dose level and an option to expand the maximum tolerated dose level with 10 additional patients.

Who Is Running the Clinical Trial?

Stoke Therapeutics, Inc

Lead Sponsor

Trials

3

Recruited

270+

Findings from Research

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]

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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

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

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]