Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04442295
Other study ID # STK-001-DS-101
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date June 3, 2020
Est. completion date April 3, 2024

Study information

Verified date April 2024
Source Stoke Therapeutics, Inc
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Stoke Therapeutics is evaluating the safety and tolerability of single and multiple ascending doses of STK-001 in patients with Dravet syndrome. Change in seizure frequency, overall clinical status, and quality of life will be measured as secondary endpoints in this open-label study.


Description:

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 Completed
Enrollment 62
Est. completion date April 3, 2024
Est. primary completion date December 13, 2023
Accepts healthy volunteers No
Gender All
Age group 2 Years to 18 Years
Eligibility Inclusion Criteria: - Diagnosis of Dravet Syndrome (DS) with onset of recurrent focal motor or hemiconvulsive or generalized tonic-clonic seizures prior to 12 months of age, which are often prolonged and triggered by hyperthermia. - No history of causal MRI lesion - No other known etiology - Normal development at seizure onset. - Documented pathogenic, likely pathogenic variant, or variant of uncertain significance in the SCN1A gene associated with DS. - Use of at least 2 prior treatments for epilepsy that either had lack of adequate seizure control (requiring an additional AED) or had to be discontinued due to an AE(s). - Currently taking at least one AED at a dose which has been stable for at least 4 weeks prior to Screening. - Stable epilepsy medications or interventions for epilepsy (including ketogenic diet or vagal nerve stimulator) for at least 4 weeks prior to Screening. Exclusion Criteria: - Known pathogenic mutation in another gene that causes epilepsy - Currently treated with an AED acting primarily as a sodium channel blocker, as maintenance treatment, including: phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide. - Clinically significant unstable medical conditions other than epilepsy. - Clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to Screening or prior to dosing on Day 1, other than epilepsy. - History of brain or spinal cord disease (other than epilepsy or DS), or history of bacterial meningitis or brain malformation - Spinal deformity or other condition that may alter the free flow of cerebrospinal fluid (CSF) or has an implanted CSF drainage shunt. - Any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, may influence the results of the study, or may affect the patient's ability to participate in the study.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
STK-001 - Single Ascending Doses
Experimental : Single Ascending Doses - STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Four dose levels will be evaluated ( 10mg, 20mg,30mg, 45mg and 70mg ).
STK-001 - Multiple Ascending Doses
Experimental : Multiple Ascending Doses - STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Three dose levels will be evaluated ( 20mg,30mg and 45mg ).

Locations

Country Name City State
United States University of Michigan - Mott Children's Hospital Ann Arbor Michigan
United States Children's Hospital Colorado Aurora Colorado
United States Massachusetts General Hospital - Pediatric Epilepsy Program Boston Massachusetts
United States Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois
United States Cook Children's Health Care System Fort Worth Texas
United States University of Iowa Hospitals and Clinics; Pediatric Specialty Clinic Iowa City Iowa
United States Le Bonheur Children's Hospital Memphis Tennessee
United States Nicklaus Children's Hospital Miami Florida
United States NYU Comprehensive Epilepsy Center New York New York
United States AdventHealth Orlando 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 Primary Children's Hospital Salt Lake City Utah
United States UCSF Benioff Children's Hospital San Francisco California
United States Seattle Children's Hospital Seattle Washington
United States Multicare 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 and Tolerability of single and multiple doses of STK-001 with respect to: Incidence of adverse events
incidence of abnormal vital signs
Abnormal physical examination findings
Abnormal 12-lead electrocardiogram (ECG)
Abnormal laboratory parameters
Screening (Day -28) until 6 months after single and multiple drug dosing
Primary Pharmacokinetic (PK) Parameters Analysis of plasma concentrations of STK-001 Day 1 (Dosing) until 6 months after single and multiple drug dosing
Primary Exposure of STK-001 in Cerebrospinal Fluid (CSF) Measurement of STK-001 concentrations Day 1 (Dosing) until 6 months after single and multiple drug dosing
Secondary Measurement of seizure frequency Measured by paper diary Screening (Day -28) until 6 months after single and multiple drug dosing
Secondary Change in Caregiver Global Impression of Change Scale Change from baseline in overall clinical status as measured by the Clinical Global Impression of Change (CGIC).
Values of scales:
Very much improved
Much improved
Minimally improved
No change
Minimally worse
Much worse
Very much worse
Baseline (Day -1) until 6 months after single and multiple drug dosing
Secondary Change in Clinician-assessed Global Impression of Change Scale Change from baseline in overall clinical status as measured by the Caregiver Global Impression of Change (CaGIC)
Values of scales:
Very much improved
Much improved
Minimally improved
No change
Minimally worse
Much worse
Very much worse
Baseline (Day -1) until 6 months after single and multiple drug dosing
Secondary Measurement of Quality of Life Change in quality of life as measured by the EuroQoL-five dimensions, youth version (EQ-5D-Y) instrument. The scale is scored from 0-100. The reference to a high score indicates a better outcome of quality of life. Baseline (Day -1) until 6 months after single and multiple drug dosing
See also
  Status Clinical Trial Phase
Recruiting NCT05651204 - GABA Biomarkers in Dravet Syndrome
Withdrawn NCT02910297 - The Pharmacokinetics of Cannabidiol (CBD) and Its Effects in Children With Severe Epilepsy
Recruiting NCT04462770 - EPX-100 (Clemizole Hydrochloride) as Add-on Therapy to Control Convulsive Seizures in Patients With Dravet Syndrome Phase 2
Completed NCT02896608 - Neuronal Excitability of HCN1 Channel Mutations in Dravet Syndrome
Withdrawn NCT05140122 - LEONIDaS Caregivers Study
Recruiting NCT05635266 - Tissue Repository Providing Annotated Biospecimens for Approved Investigator-directed Biomedical Research Initiatives
Completed NCT02091206 - A Dose-ranging Pharmacokinetics and Safety Study of GWP42003-P in Children With Dravet Syndrome (GWPCARE1) Phase 2
Enrolling by invitation NCT03655223 - Early Check: Expanded Screening in Newborns
Recruiting NCT05472389 - Neurodevelopmental Impact of Epilepsy on Autonomic Function in Dravet Syndrome N/A
Active, not recruiting NCT05626634 - Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy Phase 2
Recruiting NCT01858285 - Genetics of Epilepsy and Related Disorders
Recruiting NCT04614506 - Transcranial Magnetic Stimulation to Measure Cortical Excitability in Dravet Syndrome
Recruiting NCT06118255 - A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Fenfluramine (Hydrochloride) in Infants 1 Year to Less Than 2 Years of Age With Dravet Syndrome Phase 3
Recruiting NCT04611438 - Research on Cognitive Effect of Cannabidiol on Dravet Syndrome and Lennox-Gastaut SyndromeGastaut Syndrome Phase 3
Completed NCT02091375 - Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1) Phase 3
Completed NCT05364021 - Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies Phase 1/Phase 2
Recruiting NCT06112275 - A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome (Australia Only) Phase 1/Phase 2
Withdrawn NCT03254680 - Turmeric as Treatment in Epilepsy N/A
Terminated NCT02187809 - Safety and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome Phase 3
Withdrawn NCT02174094 - Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome Phase 3