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

Phase 2

• Conditions: Dravet Syndrome
• Interventions: Drug: STK-001

• Registration Number: NCT04740476
• Lead Sponsor: Stoke Therapeutics, Inc

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2021-01-21
• Study First Submitted: 2021-02-02
• Study First Submitted QC: 2021-02-02
• Study First Posted: 2021-02-05
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-07
• Last Update Posted: 2024-05-10
• Primary Completion: 2026-02-03
• Study Completion: 2027-03-03

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 60

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
STK-001 multiple dose levels	STK-001	Enrollment of patients after completion of Study STK-001-DS-101 or Study STK-001-DS-102 if eligible. Patients will receive IT administration of study drug STK-001 at the dose level they received while participating in Study STK-001-DS-101 or STK-001-DS-102, or at a dose level recommended by the Safety Monitoring Committee (SMC).The highest dose administered in this study may not exceed that which has already been evaluated in an STK-001 Phase 1/2 study, and doses above 45 mg/dose in this study require approval from the Food and Drug Administration (FDA). Patients will initially receive 3 doses, one every approximately 4 months (16 weeks). Patients who are tolerating treatment may continue treatment with doses approximately every 4 months, with an End of Study/Follow-up Visit 24 weeks after the last dose of study drug. Patients who do not continue treatment after the third dose will have a Follow-up Visit (V5) at Week 48 and an End of Study Visit at Week 56.

Primary Outcome Measures

Name	Time	Method
Safety of multiple doses of STK-001	Screening (Day -1) until 6 months after multiple drug dosing	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.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Parameters	Dosing (Day 1) until 6 months after multiple drug dosing	Analysis of plasma concentrations of STK-001
Exposure of STK-001 in Cerebrospinal Fluid (CSF)	Dosing (Day 1) and every 4 months until last study drug dosing day	Measurement of STK-001 concentrations
Measurement of Seizure Frequency	Screening (Day -1) until 6 months after multiple drug dosing	Measurement of Seizure Frequency (by paper diary)
Change in Quality of Life	Screening (Day -1) until 6 months after multiple drug dosing	Change in quality of life as measured by the EuroQoL-five dimensions, youth version (EQ-5D-Y) instrument
Change in overall clinical status	Screening (Day -1) until 6 months after multiple drug dosing	Change in overall clinical status as measured by the Clinical Global Impression of Change (CGIC) and the Caregiver Global Impression of Change (CaGIC)

Trial Locations

Locations (17)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

MultiCare Health System Institute for Research and Innovation; 🇺🇸 Tacoma, Washington, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

University of California San Francisco Medical Center; 🇺🇸 San Francisco, California, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Nicklaus Children's Hospital; 🇺🇸 Miami, Florida, United States

Cook Children's Medical Center; 🇺🇸 Fort Worth, Texas, United States

NYU Comprehensive Epilepsy Center; 🇺🇸 New York, New York, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Ann & Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Iowa Children's Hospital; 🇺🇸 Iowa City, Iowa, United States

UT LeBonheur Pediatric Specialists, Inc.; 🇺🇸 Memphis, Tennessee, United States

Michigan Medicine; 🇺🇸 Ann Arbor, Michigan, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Florida Hospital for Children; 🇺🇸 Orlando, Florida, United States