A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen in Patients With Dravet Syndrome

May 29, 2026 updated by: Stoke Therapeutics, Inc

EMPEROR: A Multicenter, Randomized, Double-blind, Sham-controlled, Parallel Group, Phase 3 Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen (STK-001) in Patients With Dravet Syndrome

The purpose of the study is to evaluate the efficacy, safety, and tolerability of zorevunersen in Patients with Dravet syndrome.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Zorevunersen is an investigational new medicine for the treatment of Dravet syndrome. It 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.

This is a global, multicenter, randomized, double-blind, sham-controlled, parallel group Phase 3 study to assess the efficacy, safety, and tolerability of zorevunersen in patients with Dravet syndrome. The study duration and endpoints are designed to evaluate the potential of zorevunersen for disease modification. The study consists of two parts, Treatment Period 1 and Treatment Period 2. The primary and secondary endpoints will be assessed at the conclusion of Treatment Period 1. These endpoints will be assessed again at the end of Treatment Period 2. The primary endpoint is the change from baseline in major motor seizure frequency. Secondary endpoints include the change in behavior and cognition, clinical status, and health-related quality of life in patients with Dravet syndrome.

Patients will have the opportunity to enroll in an open label extension study and receive zorevunersen if they meet eligibility criteria at the end of the study.

Study Type

Interventional

Enrollment (Estimated)

170

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Marseille, France
        • Recruiting
        • Hopital de la Timone
        • Contact:
          • Study Coordinator
      • Paris, France
        • Recruiting
        • Hôpital Necker - Enfants Malades
        • Contact:
          • Study Coordinator
      • Paris, France
        • Recruiting
        • Hôpital Robert Debré - Paris
        • Contact:
          • Study Coordinator
  • Germany
      • Berlin, Germany
        • Recruiting
        • Charité - Campus Virchow-Klinikum
        • Contact:
          • Study Coordinator
      • Bonn, Germany
        • Recruiting
        • Universitaetsklinikum Bonn AoeR
        • Contact:
          • Study Coordinator Study Coordinator
      • Frankfurt, Germany
        • Recruiting
        • Universitaetsklinikum Frankfurt Goethe-Universitaet
        • Contact:
          • Study Coordinator
      • Friedberg, Germany
        • Recruiting
        • Universitaetsklinikum Freiburg
        • Contact:
          • Study Coordinator
      • Heidelberg, Germany
        • Recruiting
        • Universitaetsklinikum Heidelberg
        • Contact:
          • Study Coordinator
      • München, Germany
        • Recruiting
        • Integriertes Sozialpaediatrisches Zentrum
        • Contact:
          • Study Coordinator
  • Italy
      • Florence, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
        • Contact:
          • Study Coordinator
      • Genova, Italy
        • Recruiting
        • Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS
        • Contact:
          • Study Coordinator
      • Roma, Italy
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Contact:
          • Study Coordinator
      • Roma, Italy
        • Recruiting
        • Ospedale Pediatrico Bambino Gesu
        • Contact:
          • Study Coordinator
  • Japan
      • Fukuoka, Japan
        • Recruiting
        • Fukuoka Children's Hospital
        • Contact:
          • Research Assistant
      • Hokkaido, Japan
        • Recruiting
        • Hokkaido University Hospital
        • Contact:
          • Research Assistant
      • Kyoto, Japan
        • Recruiting
        • Kyoto University Hospital
        • Contact:
          • Research Assistant
      • Nagoya, Japan
        • Recruiting
        • Nagoya University Hospital
        • Contact:
          • Research Assistant
      • Niigata, Japan
        • Recruiting
        • National Hospital Organization Nishi Niigata Central Hospital
        • Contact:
          • Research Assistant
      • Okayama, Japan
        • Recruiting
        • Okayama University Hospital
        • Contact:
          • Research Assistant
      • Osaka, Japan
        • Recruiting
        • Osaka City General Hospital
      • Shimotsuke, Japan
        • Recruiting
        • Jichi Medical University Hospital
        • Contact:
          • Research Assistant
      • Shizuoka, Japan
        • Recruiting
        • NHO Shizuoka
      • Tokyo, Japan
        • Recruiting
        • National Center of Neurology and Psychiatry
        • Contact:
          • Research Assistant
      • Yokohama, Japan
        • Recruiting
        • Yokohama City University Medical Center
        • Contact:
          • Research Assistant
  • Spain
      • Madrid, Spain
        • Recruiting
        • Hospital Ruber Internacional
        • Contact:
          • Study Coordinator
      • Madrid, Spain
        • Recruiting
        • Hospital Blua Sanitas Valdebebas
        • Contact:
          • Study Coordinator
      • Pamplona, Spain
        • Recruiting
        • Clinica Universidad de Navarra
        • Contact:
          • Study Coordinator
  • United Kingdom
      • Glasgow, United Kingdom, G51 4TF
        • Recruiting
        • Royal Hospital For Children
        • Contact:
      • London, United Kingdom, WC1N 3JH
        • Recruiting
        • Great Ormond Street Hospital for Children
        • Contact:
      • Sheffield, United Kingdom, S10 2TH
        • Recruiting
        • Sheffield Children's Hospital
        • Contact:
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Recruiting
        • Phoenix Children's Hospital
        • Contact:
          • Angus Wilfong, MD
        • Contact:
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Recruiting
        • Arkansas Children's Hospital
        • Contact:
        • Contact:
          • Andrea Sellew
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars Sinai Medical Center
        • Contact:
          • Research Assistant
      • Orange, California, United States, 92868
        • Recruiting
        • Children's Hospital of Orange County
        • Contact:
      • San Francisco, California, United States, 94158
    • Colorado
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Recruiting
        • Nemours Children's Health
        • Contact:
      • Miami, Florida, United States, 33155
      • Orlando, Florida, United States, 32804
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Not yet recruiting
        • University of Iowa Hospital and Clinics
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • CS Mott Children's Hospital
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Not yet recruiting
        • Washington University in St. Louis School of Medicine
        • Contact:
    • New York
      • New York, New York, United States, 10016
      • New York, New York, United States, 10021
        • Recruiting
        • Weill Cornell Medicine
        • Contact:
      • Rochester, New York, United States, 14642
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University Health System
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Not yet recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
      • Columbus, Ohio, United States, 43205
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University (OHSU)
        • Contact:
    • Tennessee
      • Memphis, Tennessee, United States, 38103
        • Recruiting
        • LeBonheur Children's Hospital
        • Contact:
    • Texas
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Recruiting
        • University of Utah Primary Children's Hospital
        • Contact:
          • Ryan Kennington
          • Phone Number: 801-587-0833
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • UVA Health
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Sham Comparator
Eligible patients will be randomly assigned in a 1:1 ratio to zorevunersen:sham
Other: Sham Comparator

Treatment Period 1: Sham group will not have drug administered. Sham group will have a procedure intended to mimic the drug administration.

Treatment Period 2: Group assigned to sham in Treatment Period 1 will receive 70 mg of zorevunersen on Day 393 (Week 56) and on Day 477 (Week 68), and 45 mg of zorevunersen Day 589 (Week 84).
Experimental: Zorevunersen
Eligible patients will be randomly assigned in a 1:1 ratio to zorevunersen:sham in Treatment Period 1 (approximately 52 weeks). Upon the completion of Treatment Period 1 all eligible patients, will enter Treatment Period 2 and receive zorevunersen, regardless of initial treatment assignment.
Drug: zorevunersen

Treatment Period 1: Zorevunersen group will receive study drug by intrathecal (IT) administration on Day 1 (after the 8-week Baseline Period), Day 57 (Week 8), Day 169 (Week 24), and Day 281 (Week 40) at a dose level of 70 mg on Day 1 and Day 57, and 45 mg on Day 169 and Day 281.

Treatment Period 2: Group assigned to zorevunersen in Treatment Period 1 will receive 45 mg of zorevunersen on Day 393 (Week 56), Day 477 (Week 68), and Day 589 (Week 84).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of Seizure Change
Time Frame: Week 28
Measured by daily seizure diary
Week 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of Seizure Change
Time Frame: Week 52
Measured by daily seizure diary
Week 52
Multi-component Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Outcome Score
Time Frame: Week 52
Measurement of change from baseline for multi-component score. Scoring is non-parametric and based on rank between treatment and sham groups. Individual items are scored on a scale of 0, 1, or 2, indicating never, sometimes, or usually or often, or on a scale of 0 or 2, indicating no or yes, with higher scores indicating greater performance
Week 52
Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Subdomain Score
Time Frame: Week 52
Measurement of change from baseline for individual subdomains. Scoring is point-based on a scale that varies, depending on subdomain, Individual items are scored on a scale of 0, 1, or 2, indicating never, sometimes, or usually or often, or on a scale of 0 or 2, indicating no or yes, with higher scores indicating greater performance.
Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stoke Therapeutics, Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 4, 2025

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

March 6, 2025

First Submitted That Met QC Criteria

March 6, 2025

First Posted (Actual)

March 12, 2025

Study Record Updates

Last Update Posted (Actual)

June 2, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STK-001-DS-301
  • 2024-519555-28 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Dravet Syndrome

Clinical Trials on zorevunersen

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Azerbaijan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe