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

Dravet Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04740476
• Other study ID #: STK-001-DS-501
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: January 21, 2021
• Est. completion date: March 3, 2027

Study information

• Verified date: May 2024
• Source: Stoke Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

This study is a multi-center, open-label, multiple-dose, safety extension study for patients who have completed another study of STK-001 and meet study eligibility criteria. 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 60
• Est. completion date: March 3, 2027
• Est. primary completion date: February 3, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Months and older

Eligibility

Inclusion Criteria:

• Completed dosing with STK-001 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, rufinamide or cenobamate.

• 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 STK-001) 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.

Related Conditions & MeSH terms

• Dravet Syndrome
• Epilepsies, Myoclonic
• Syndrome

Intervention

Drug:
• STK-001
STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection.

Locations

Country	Name	City	State
United States	Michigan Medicine	Ann Arbor	Michigan
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Iowa Children's Hospital	Iowa City	Iowa
United States	UT LeBonheur Pediatric Specialists, Inc.	Memphis	Tennessee
United States	Nicklaus Children's Hospital	Miami	Florida
United States	NYU Comprehensive Epilepsy Center	New York	New York
United States	Florida Hospital for Children	Orlando	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California San Francisco Medical Center	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Stoke Therapeutics, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of multiple doses of STK-001	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	Pharmacokinetic (PK) Parameters	Analysis of plasma concentrations of STK-001	Dosing (Day 1) until 6 months after multiple drug dosing
Secondary	Exposure of STK-001 in Cerebrospinal Fluid (CSF)	Measurement of STK-001 concentrations	Dosing (Day 1) and every 4 months until last study drug dosing day
Secondary	Measurement of Seizure Frequency	Measurement of Seizure Frequency (by paper diary)	Screening (Day -1) until 6 months after multiple drug dosing
Secondary	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
Secondary	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