STK-001 for Dravet Syndrome

No longer recruiting at 24 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called STK-001 for individuals with Dravet syndrome, a severe form of epilepsy that begins before 12 months of age and is characterized by prolonged seizures often triggered by fever. The trial primarily aims to determine if STK-001 is safe and well-tolerated, with a secondary focus on changes in seizure frequency and overall quality of life. Participants will receive either single or multiple doses of the treatment. It is suitable for those diagnosed with Dravet syndrome who began having seizures before 12 months, have tried at least two other epilepsy treatments without success, and are currently using a stable epilepsy medication. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering a chance to be among the first to benefit from this potential new therapy.

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.

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

Research has shown that STK-001 was generally well-tolerated in earlier studies. In trials with 74 patients, both single and multiple doses proved safe, as most patients did not experience serious side effects. The treatment was tested at doses up to 70 mg, and the results support its continued development. These findings suggest that STK-001 is safe enough for further study in people with Dravet syndrome, a severe form of epilepsy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for Dravet syndrome?

Researchers are excited about STK-001 for Dravet Syndrome because it offers a novel approach compared to existing treatments like antiepileptic drugs and dietary therapies. Unlike these standard treatments, which primarily focus on managing symptoms, STK-001 targets the underlying genetic cause of Dravet Syndrome. It works by using antisense oligonucleotides to increase the production of a protein that is deficient in patients with this condition. This new mechanism of action has the potential to significantly improve outcomes by addressing the root cause rather than just alleviating symptoms.

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

Research shows that STK-001 has promising results for treating Dravet syndrome. In earlier studies, a single 70 mg dose led to a noticeable drop in seizures—43% fewer at three months and 57% fewer at six months. In this trial, participants will join different treatment arms. Some will receive single ascending doses, while others will receive multiple ascending doses. Patients who received two to three doses in previous studies experienced even greater benefits, with seizures reduced by 85% at three months and 74% at six months. These results suggest that STK-001 could effectively lower seizure frequency and improve overall health. Additionally, improvements in thinking and behavior have been observed, which are important for quality of life. ^{2 3 6 7 8}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. 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 ... STK-001-treated patients in the OLE studies had durable reductions in convulsive SF (Fig 1) and clinically meaningful improvements in multiple measures of ...

2. 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 ...

3. 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 ...

4. 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 ...

5. neurologylive.com neurologylive.com/view/stoke-announces-phase-3-emperor-registrational-study-zorevunersen-dravet-syndrome

Stoke Announces Phase 3 EMPEROR Registrational Study ... Notably, patients who received 2 or 3 doses of 70 mg of STK-001 achieved median seizure reductions of 85% at 3 months and 74% at 6 months post- ...

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

Press Release Details – MONARCH & ADMIRAL Study Safety Data: STK-001 has been generally well-tolerated among 74 patients treated with single and multiple doses of ...

7. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04740476

STK-001 for Patients With Dravet Syndrome 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 ...

8. aesnet.org aesnet.org/abstractslisting/zorevunersen-stk-001-demonstrates-potential-for-disease-modification-including-reductions-in-seizures-and-improvements-in-cognition-and-behavior-in-children-and-adolescents-with-dravet-syndrome-ds

zorevunersen stk-001 demonstrates potential for disease ... Conclusions: STK-001 benefit-risk profile appears favorable in single and multiple doses up to 70mg/dose, supporting continued development as ...