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

NCT04442295 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: STK-001-DS-101
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 18

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.

Conditions

Dravet Syndrome

Keywords

Pediatric epilepsy; Epileptic Encephalopathies; Refractory Myoclonic Epilepsy; Severe Myoclonic Epilepsy in Infancy

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability of single and multiple doses of STK-001 with respect to:

  1. Incidence of adverse events 2. incidence of abnormal vital signs 3. Abnormal physical examination findings 4. Abnormal 12-lead electrocardiogram (ECG) 5. Abnormal laboratory parameters

  Screening (Day -28) until 6 months after single and multiple drug dosing

• Pharmacokinetic (PK) Parameters

  Analysis of plasma concentrations of STK-001

  Day 1 (Dosing) until 6 months after single and multiple drug dosing

• Exposure of STK-001 in Cerebrospinal Fluid (CSF)

  Measurement of STK-001 concentrations

  Day 1 (Dosing) until 6 months after single and multiple drug dosing

Secondary Outcomes (4)

• Measurement of seizure frequency

  Screening (Day -28) until 6 months after single and multiple drug dosing

• Change in Caregiver Global Impression of Change Scale

  Baseline (Day -1) until 6 months after single and multiple drug dosing

• Change in Clinician-assessed Global Impression of Change Scale

  Baseline (Day -1) until 6 months after single and multiple drug dosing

• Measurement of Quality of Life

  Baseline (Day -1) until 6 months after single and multiple drug dosing

Study Arms (2)

Single Ascending Doses

EXPERIMENTAL

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.

Drug: STK-001 - Single Ascending Doses

Multiple Ascending Doses

EXPERIMENTAL

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.

Drug: STK-001 - Multiple Ascending Doses

Interventions

STK-001 - Single Ascending Doses 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 ).

Single Ascending Doses

STK-001 - Multiple Ascending Doses 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 ).

Multiple Ascending Doses

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stoke Therapeutics, Inc: lead

Study Sites (18)

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

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

Chicago, Illinois, 60611, United States

Location

University of Iowa Hospitals and Clinics; Pediatric Specialty Clinic

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital - Pediatric Epilepsy Program

Boston, Massachusetts, 02114, United States

Location

University of Michigan - Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

NYU Comprehensive Epilepsy Center

New York, New York, 10016, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Le Bonheur Children's Hospital

Memphis, Tennessee, 38105, United States

Location

Cook Children's Health Care System

Fort Worth, Texas, 76104, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84108, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Multicare Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

MeSH Terms

Conditions

Epilepsies, Myoclonic

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• Ann Dandurand, MD

  Medical Director

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 22, 2020
• Study Start: June 29, 2020
• Primary Completion: November 14, 2023
• Study Completion: November 14, 2023
• Last Updated: May 18, 2025

Record last verified: 2025-05

Locations

US (18)