An Open-Label Extension Study of STK-001 for Patients With Dravet Syndrome
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: STK-001 multiple dose levels Enrollment of patients after completion of study STK-001-DS-101 if eligible for additional dosing in this extension study. Patients will be administered the same dose level they received in study STK-001- DS-101 and will initially receive 3 doses, one every approximately 4 months (16 weeks). Patients who are tolerating treatment may continue treatment with doses 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 5 |
Drug: STK-001
STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection.
|
Outcome Measures
Primary Outcome Measures
- Safety of multiple doses of STK-001 [Screening (Day -1) until 6 months after multiple drug dosing]
Analysis of incidence, type, severity, and seriousness of adverse events, vital signs, physical examination, electrocardiogram (ECG), and laboratory parameters
Secondary Outcome Measures
- 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) until Week 32 (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 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)
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Completed dosing with STK-001 and the End of Study Visit in Study STK-001-DS-101, with an acceptable safety profile per Investigator judgment.
-
Had satisfactory compliance with study visits and procedures in Study STK-001-DS-101 per Investigator and Sponsor judgment.
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Completed Study STK-001-DS-101 within 4 weeks of the start of their participation in Study STK-001-DS-501 unless approved by sponsor.
Exclusion Criteria:
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Met any withdrawal criteria from Study STK-001-DS-101.
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Currently treated with an antiepileptic drug (AED) acting primarily as a sodium channel blocker, as maintenance therapy, including phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide.
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Clinically significant unstable medical conditions other than epilepsy.
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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.
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Spinal deformity or other condition that may alter the free flow of CSF or has an implanted CSF drainage shunt.
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Treated (or is being treated) with an investigational product (other than STK-001) since participating in Study STK-001-DS-101.
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Participating in an observational study, they are excluded unless approved by the Sponsor.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California San Francisco Medical Center | San Francisco | California | United States | 94158 |
| 2 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
| 3 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
| 4 | Nicklaus Children's Hospital | Miami | Florida | United States | 33155 |
| 5 | Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois | United States | 60611 |
| 6 | NYU Comprehensive Epilepsy Center | New York | New York | United States | 10016 |
| 7 | Oregon Health & Science University | Portland | Oregon | United States | 97239 |
| 8 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
| 9 | MultiCare Health System Institute for Research and Innovation | Tacoma | Washington | United States | 98405 |
Sponsors and Collaborators
- Stoke Therapeutics, Inc
Investigators
- Study Director: Javier Avendaño, MD, Medical Director
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STK-001-DS-501