An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome

NCT ID: NCT04442295

Last Updated: 2025-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-29
• Study Completion Date: 2023-11-14

Brief Summary

Stoke Therapeutics is evaluating the safety and tolerability of single and multiple ascending doses of STK-001 in patients with Dravet syndrome. Change in seizure frequency, overall clinical status, and quality of life will be measured as secondary endpoints in this open-label study.

Detailed Description

STK-001 is an investigational new medicine for the treatment of Dravet syndrome. STK-001 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).

STK-001 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 STK-001.

Conditions

Dravet Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Ascending Doses

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 Type: EXPERIMENTAL

STK-001 - Single Ascending Doses

Intervention Type: DRUG

Experimental : Single Ascending Doses - STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Four dose levels will be evaluated ( 10mg, 20mg,30mg, 45mg and 70mg ).

Multiple Ascending Doses

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.

Group Type: EXPERIMENTAL

STK-001 - Multiple Ascending Doses

Intervention Type: DRUG

Experimental : Multiple Ascending Doses - STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Three dose levels will be evaluated ( 20mg,30mg and 45mg ).

Interventions

STK-001 - Single Ascending Doses

Experimental : Single Ascending Doses - STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Four dose levels will be evaluated ( 10mg, 20mg,30mg, 45mg and 70mg ).

Intervention Type: DRUG

STK-001 - Multiple Ascending Doses

Experimental : Multiple Ascending Doses - STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Three dose levels will be evaluated ( 20mg,30mg and 45mg ).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Dravet Syndrome (DS) with onset of recurrent focal motor or hemiconvulsive or generalized tonic-clonic seizures prior to 12 months of age, which are often prolonged and triggered by hyperthermia.

• No history of causal MRI lesion
• No other known etiology
• Normal development at seizure onset.
• Documented pathogenic, likely pathogenic variant, or variant of uncertain significance in the SCN1A gene associated with DS.
• Use of at least 2 prior treatments for epilepsy that either had lack of adequate seizure control (requiring an additional AED) or had to be discontinued due to an AE(s).
• Currently taking at least one AED at a dose which has been stable for at least 4 weeks prior to Screening.
• Stable epilepsy medications or interventions for epilepsy (including ketogenic diet or vagal nerve stimulator) for at least 4 weeks prior to Screening.

Exclusion Criteria

• Known pathogenic mutation in another gene that causes epilepsy
• Currently treated with an AED acting primarily as a sodium channel blocker, as maintenance treatment, including: phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide.
• Clinically significant unstable medical conditions other than epilepsy.
• Clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to Screening or prior to dosing on Day 1, other than epilepsy.
• History of brain or spinal cord disease (other than epilepsy or DS), or history of bacterial meningitis or brain malformation
• Spinal deformity or other condition that may alter the free flow of cerebrospinal fluid (CSF) or has an implanted CSF drainage shunt.
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, may influence the results of the study, or may affect the patient's ability to participate in the study.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stoke Therapeutics, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ann Dandurand, MD

Role: STUDY_DIRECTOR

Medical Director

Locations

UCSF Benioff Children's Hospital

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Nicklaus Children's Hospital

Miami, Florida, United States

AdventHealth Orlando

Orlando, Florida, United States

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

Chicago, Illinois, United States

University of Iowa Hospitals and Clinics; Pediatric Specialty Clinic

Iowa City, Iowa, United States

Massachusetts General Hospital - Pediatric Epilepsy Program

Boston, Massachusetts, United States

University of Michigan - Mott Children's Hospital

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

NYU Comprehensive Epilepsy Center

New York, New York, United States

Oregon Health & Science University

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Le Bonheur Children's Hospital

Memphis, Tennessee, United States

Cook Children's Health Care System

Fort Worth, Texas, United States

Primary Children's Hospital

Salt Lake City, Utah, United States

Seattle Children's Hospital

Seattle, Washington, United States

Multicare Institute for Research and Innovation

Tacoma, Washington, United States

Countries

United States

Other Identifiers

STK-001-DS-101

Identifier Type: -

Identifier Source: org_study_id