An Open-Label Extension Study of STK-001 for Patients With Dravet Syndrome

An Open-Label Extension Study for Patients With Dravet Syndrome Who Previously Participated in Studies of STK-001

Stoke Therapeutics is evaluating the long-term safety & tolerability of repeated doses of zorevunersen (STK-001) in patients with Dravet syndrome who previously participated in studies of zorevunersen. Change in seizure frequency and overall clinical status, and quality of life will be measured as secondary endpoints in this open-label study.

Study Overview

• Status: Active, not recruiting
• Conditions: Dravet Syndrome
• Intervention / Treatment: Drug: zorevunersen (STK-001)

Detailed Description

This study is a multi-center, open-label, multiple-dose, safety extension study for patients who have completed another study of zorevunersen and meet study eligibility criteria. zorevunersen is an investigational new medicine for the treatment of Dravet syndrome. Zorevunersen is an antisense oligonucleotide (ASO) that is intended to increase the level of productive SCN1A messenger RNA (mRNA) and consequently increase the expression of the sodium channel Nav1.1 protein. This RNA-based approach is not gene therapy, but rather RNA modulation, as it does not manipulate nor insert genetic deoxyribonucleic acid (DNA).

Zorevunersen is designed to upregulate Nav1.1 protein expression from the nonmutant (wild-type) copy of the SCN1A gene to restore physiological Nav1.1 levels. Nav1.1 levels are reduced in people with Dravet syndrome. Stoke has generated preclinical data demonstrating proof-of-mechanism for zorevunersen.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California San Francisco Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
    • Orlando, Florida, United States, 32803
      • Florida Hospital for Children
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10016
      • NYU Comprehensive Epilepsy Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • UT LeBonheur Pediatric Specialists, Inc.
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Completed dosing with zorevunersen and the End of Study Visit in Study STK-001-DS-101 or Study STK-001-DS-102, with an acceptable safety profile per Investigator judgment.
• Had satisfactory compliance with study visits and procedures in Study STK-001-DS-101 or Study STK-001-DS-102 per Investigator and Sponsor judgment.
• Completed Study STK-001-DS-101 or STK-001-DS-102 within 4 weeks of the start of their participation in Study STK-001-DS-501 unless approved by sponsor.

Exclusion Criteria:

• Met any withdrawal criteria from Study STK-001-DS-101 or STK-001-DS-102.
• Currently treated with an antiepileptic drug (AED) acting primarily as a sodium channel blocker, as maintenance therapy, including phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide or rufinamide (with the exception of cenobamate, which is permitted).
• Clinically significant unstable medical conditions other than epilepsy.
• Clinically relevant symptoms or a clinically significant illness (in the judgment of the Investigator) at Screening or prior to dosing on Day 1, other than epilepsy.
• Spinal deformity or other condition that may alter the free flow of CSF or has an implanted CSF drainage shunt.
• Treated (or is being treated) with an investigational product (other than zorevunersen) since participating in Study STK-001-DS-101 or STK-001-DS-102.
• Participating in an observational study, they are excluded unless approved by the Sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: zorevunersen (STK-001) multiple dose levels; 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 zorevunersen 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 zorevunersen 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.

Drug: zorevunersen (STK-001); zorevunersen drug product is an antisense oligonucleotide administered as an intrathecal injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of multiple doses of zorevunersen	Safety variables for analysis include the incidence, type, severity, and seriousness of AEs, and changes in vital signs, ECG, laboratory, immunogenicity, physical examination, and outcomes on the cerebellar function clinical screening battery.	Screening (Day -1) until 6 months after multiple drug dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Seizure Frequency	Measurement of Seizure Frequency (by paper diary)	Screening (Day -1) until 6 months after multiple drug dosing
Change in overall clinical status	Change in overall clinical status as measured by the Clinical Global Impression of Change (CGIC) and the Caregiver Global Impression of Change (CaGIC)	Screening (Day -1) until 6 months after multiple drug dosing
Change in Quality of Life	Change in quality of life as measured by the EuroQoL-five dimensions, youth version (EQ-5D-Y) instrument	Screening (Day -1) until 6 months after multiple drug dosing
Pharmacokinetic (PK) Parameters	Analysis of plasma concentrations of zorevunersen	Dosing (Day 1) until 6 months after multiple drug dosing
Exposure of zorevunersen in Cerebrospinal Fluid (CSF)	Measurement of zorevunersen concentrations	Dosing (Day 1) and every 4 months until last study drug dosing day

Collaborators and Investigators

• Sponsor: Stoke Therapeutics, Inc
• Investigators: Study Director: Ann Dandurand, MD, Medical director

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2021
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: February 2, 2021
• First Submitted That Met QC Criteria: February 2, 2021
• First Posted (Actual): February 5, 2021

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Pediatric epilepsy; Epileptic Encephalopathies; Refractory Myoclonic Epilepsy; Severe Myoclonic Epilepsy in Infancy
• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epilepsy; Epilepsies, Myoclonic
• Other Study ID Numbers: STK-001-DS-501

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No