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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
zorevunersen drug product is an antisense oligonucleotide administered as an intrathecal injection.
University of California San Francisco Medical Center
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Safety of multiple doses of zorevunersen
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.
Time frame: Screening (Day -1) until 6 months after multiple drug dosing
Pharmacokinetic (PK) Parameters
Analysis of plasma concentrations of zorevunersen
Time frame: Dosing (Day 1) until 6 months after multiple drug dosing
Exposure of zorevunersen in Cerebrospinal Fluid (CSF)
Measurement of zorevunersen concentrations
Time frame: Dosing (Day 1) and every 4 months until last study drug dosing day
Measurement of Seizure Frequency
Measurement of Seizure Frequency (by paper diary)
Time frame: Screening (Day -1) until 6 months after multiple drug dosing
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)
Time frame: Screening (Day -1) until 6 months after multiple drug dosing
Change in Quality of Life
Change in quality of life as measured by the EuroQoL-five dimensions, youth version (EQ-5D-Y) instrument
Time frame: Screening (Day -1) until 6 months after multiple drug dosing
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Children's National Medical Center
Washington D.C., District of Columbia, United States
Nicklaus Children's Hospital
Miami, Florida, United States
Florida Hospital for Children
Orlando, Florida, 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
Massachusetts General Hospital
Boston, Massachusetts, United States
Michigan Medicine
Ann Arbor, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
...and 7 more locations