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NCT06872125PHASE3Recruiting

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

Stoke Therapeutics, Inc

Start Date

6/4/2025

Completion Date

10/1/2028

Summary

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

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.

Eligibility Criteria

Age Range: 2 years to 17 years

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.

Interventions

DRUG

zorevunersen

OTHER

Sham Comparator

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Conditions

Dravet Syndrome

Locations

Phoenix Children's Hospital

Phoenix, Arizona 85016

United States

Arkansas Children's Hospital

Little Rock, Arkansas 72202

United States

Cedars Sinai Medical Center

Los Angeles, California 90048

United States

Children's Hospital of Orange County

Orange, California 92868

United States

USCF Medical Center

San Francisco, California 94158

United States

Children's Hospital Colorado

Aurora, Colorado 80045

United States

Children's National Medical Center

Washington D.C., District of Columbia 20010

United States

Nemours Children's Health

Jacksonville, Florida 32207

United States

Nicklaus Children's Hospital

Miami, Florida 33155

United States

Advent Health Neuroscience Research Institute

Orlando, Florida 32804

United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois 60611

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Boston Children's Hospital

Boston, Massachusetts 02115

United States

CS Mott Children's Hospital

Ann Arbor, Michigan 48109

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

NYU Langone Health

New York, New York 10016

United States

Weill Cornell Medicine

New York, New York 10021

United States

University of Rochester Medical Center

Rochester, New York 14642

United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27514

United States

Duke University Health System

Durham, North Carolina 27705

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Nationwide Children's Hospital

Columbus, Ohio 43205

United States

Oregon Health & Science University (OHSU)

Portland, Oregon 97239

United States

LeBonheur Children's Hospital

Memphis, Tennessee 38103

United States

Cook Children's Medical Center

Fort Worth, Texas 76104

United States

Texas Children's Hospital

Houston, Texas 77030

United States

University of Utah Primary Children's Hospital

Salt Lake City, Utah 84113

United States

UVA Health

Charlottesville, Virginia 22903

United States

Hôpital de la Timone

Marseille,

France

Hôpital Necker - Enfants Malades

Paris,

France

Hôpital Robert Debré - Paris

Paris,

France

Charité - Campus Virchow-Klinikum

Berlin,

Germany

Universitaetsklinikum Bonn AoeR

Bonn,

Germany

Universitaetsklinikum Frankfurt Goethe-Universitaet

Frankfurt,

Germany

Universitaetsklinikum Freiburg

Friedberg,

Germany

Universitaetsklinikum Heidelberg

Heidelberg,

Germany

Integriertes Sozialpaediatrisches Zentrum

München,

Germany

Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer

Florence,

Italy

Istituto Giannina Gaslini-Ospedale Pediatrico IRCCS

Genova,

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma,

Italy

Ospedale Pediatrico Bambino Gesù

Roma,

Italy

Fukuoka Children's Hospital

Fukuoka,

Japan

Hokkaido University Hospital

Hokkaido,

Japan

Kyoto University Hospital

Kyoto,

Japan

Nagoya University Hospital

Nagoya,

Japan

National Hospital Organization Nishi Niigata Central Hospital

Niigata,

Japan

Okayama University Hospital

Okayama,

Japan

Osaka City General Hospital

Osaka,

Japan

Jichi Medical University Hospital

Shimotsuke,

Japan

NHO Shizuoka

Shizuoka,

Japan

National Center of Neurology and Psychiatry

Tokyo,

Japan

Yokohama City University Medical Center

Yokohama,

Japan

Hospital Blua Sanitas Valdebebas

Madrid,

Spain

Hospital Ruber Internacional

Madrid,

Spain

Clinica Universidad de Navarra

Pamplona,

Spain

Royal Hospital for Children

Glasgow, G51 4TF

United Kingdom

Great Ormond Street Hospital for Children

London, WC1N 3JH

United Kingdom

Sheffield Children's Hospital

Sheffield, S10 2TH

United Kingdom