Zorevunersen (STK-001) in Patients With Dravet Syndrome

What is the Purpose of this Study?

The purpose of this study is to determine whether an experimental drug called zorevunersen (STK-001) works to reduce the number of seizures for children and adolescents with Dravet syndrome. Dravet syndrome is a severe form of epilepsy (a brain disorder that causes seizures). The study will evaluate whether zorevunersen affects the damage caused by Dravet syndrome, including behavioral and developmental delays. In addition, researchers will assess how long the drug may reduce the frequency of seizures in these patients, as well as examine its safety and tolerability. Zorevunersen is designed to make more of a specific protein in the brain called Nav1.1, which is important for the nerves in the brain to work properly. However, children and adolescents with Dravet syndrome have low levels of this protein, which can lead to seizures and other symptoms of Dravet syndrome. It is hoped that zorevunersen will help to reduce the number of seizures, prevent seizures from happening, and improve other symptoms of the disease. Participants will be randomly assigned to receive either zorevunersen or placebo (inactive substance); participants in both groups will have a lumbar puncture.

Eligibility

1. Patients must be ≥2 and \<18 years of age.
2. Patients must have a clinical diagnosis of DS confirmed by the Epilepsy Study Consortium, Inc. (ESCI) and as defined by:
Onset, prior to 12 months (inclusive, \<13 months), of age, of recurrent focal with motor signs, hemiclonic, or generalized tonic-clonic seizures. No other known etiology causing clinical DS manifestations..

Key Inclusion Criteria:

1. Patients must be ≥2 and \<18 years of age.
2. Patients must have a clinical diagnosis of DS confirmed by the Epilepsy Study Consortium, Inc. (ESCI) and as defined by:
Onset, prior to 12 months (inclusive, \<13 months), of age, of recurrent focal with motor signs, hemiclonic, or generalized tonic-clonic seizures. No other known etiology causing clinical DS manifestations..
3. Patient must have a documented pathogenic, likely pathogenic variant, or variant of uncertain significance in the sodium voltage-gated channel type 1 alpha subunit (SCN1A) gene. Patients who have SCN1A testing results of Negative (no variants identified) cannot be randomized.
4. Patient must experience the required number of major motor seizures during the 6-week Observation Period. Major motor seizure types included are Seizure types included in counts are Hemiclonic, Focal with Motor Signs, Focal to Bilateral Tonic-Clonic, Generalized Tonic-Clonic, Tonic, Tonic/Atonic (Drop Attacks with fall or risk of fall), and Bilateral Clonic.
5. Patient must have used at least 2 prior interventions for seizures. These can include anti-seizure medications (ASMs), ketogenic diet and/or vagus nerve stimulation (VNS) with either lack of adequate seizure control or discontinued due to an AE(s). These interventions can be ongoing therapies.
6. Patient must be taking at least one ASM. Benzodiazepines or ASMs used on a standing basis (i.e., not as needed \[PRN\]) for any indication will be considered an ASM.
7. Patients' maintenance ASMs and interventions for seizures (i.e., ketogenic diet or VNS), as well as any marijuana- or cannabinoid-based products, must have been stable (unless adjusted for weight) during the Baseline Period.

Key Exclusion Criteria:

1. Patient has documented variant in the SCN1A gene associated with gain-of-function
2. Patient is currently treated with a maintenance ASM acting primarily as a sodium channel blocker, including but not limited to phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, rufinamide, or cenobamate, given the mechanism of action of zorevunersen.
3. Patient is currently treated with neuromodulation techniques (e.g., responsive neurostimulation, deep brain stimulation, or transcranial magnetic stimulation), with the exception of VNS.
4. Patient has emergence of a new seizure type or reemergence of a past seizure type (seizure types that last occurred more than 12 months before Screening Visit A) during the Baseline Period, or has more than 1 hospitalization for seizures during the Baseline Period.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

EMPEROR: A Multicenter, Randomized, Double-blind, Sham-controlled, Parallel Group, Phase 3 Study Evaluating the Efficacy, Safety, and Tolerability of zorevunersen in Patients with Dravet Syndrome

Study Details

Disease Type/Condition

Other

Principal Investigator

Holder, Deborah

Co-Investigators

Catherine Stanecki, Cesar Ochoa-Lubinoff, Jeffrey Swarz, Michele VanHirtum-Das, Michelle Allen-Sharpley

Age Group

Children

Phase

III

IRB Number

STUDY00004145

ClinicalTrials.gov ID

NCT06872125

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org