Dravet Syndrome
Conditions
Keywords
Pediatric epilepsy, Epileptic Encephalopathies, Refractory Myoclonic Epilepsy, Severe Myoclonic Epilepsy in Infancy
Brief summary
Stoke Therapeutics is evaluating the long-term safety & tolerability of repeated doses of zorevunersen (STK-001) in patients with Dravet syndrome who previously participated in studies of zorevunersen. 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 zorevunersen and meet study eligibility criteria. zorevunersen is an investigational new medicine for the treatment of Dravet syndrome. Zorevunersen 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). Zorevunersen 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 zorevunersen.
Interventions
DRUGzorevunersen (STK-001)
zorevunersen drug product is an antisense oligonucleotide administered as an intrathecal injection.
Sponsors
Stoke Therapeutics, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Completed dosing with zorevunersen 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 or rufinamide (with the exception of cenobamate, which is permitted). * 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 zorevunersen) 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of multiple doses of zorevunersen | 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameters | Dosing (Day 1) until 6 months after multiple drug dosing | Analysis of plasma concentrations of zorevunersen |
| Exposure of zorevunersen in Cerebrospinal Fluid (CSF) | Dosing (Day 1) and every 4 months until last study drug dosing day | Measurement of zorevunersen 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 |
Countries
United States
Contacts
STUDY_DIRECTORAnn Dandurand, MD
Medical Director
Outcome results
None listed