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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
62
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 ).
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 ).
UCSF Benioff Children's Hospital
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Safety and Tolerability of single and multiple doses of STK-001 with respect to:
1. Incidence of adverse events 2. incidence of abnormal vital signs 3. Abnormal physical examination findings 4. Abnormal 12-lead electrocardiogram (ECG) 5. Abnormal laboratory parameters
Time frame: Screening (Day -28) until 6 months after single and multiple drug dosing
Pharmacokinetic (PK) Parameters
Analysis of plasma concentrations of STK-001
Time frame: Day 1 (Dosing) until 6 months after single and multiple drug dosing
Exposure of STK-001 in Cerebrospinal Fluid (CSF)
Measurement of STK-001 concentrations
Time frame: Day 1 (Dosing) until 6 months after single and multiple drug dosing
Measurement of seizure frequency
Measured by paper diary
Time frame: Screening (Day -28) until 6 months after single and multiple drug dosing
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: 1. Very much improved 2. Much improved 3. Minimally improved 4. No change 5. Minimally worse 6. Much worse 7. Very much worse
Time frame: Baseline (Day -1) until 6 months after single and multiple drug dosing
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: 1. Very much improved 2. Much improved 3. Minimally improved 4. No change 5. Minimally worse 6. Much worse 7. Very much worse
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
AdventHealth Orlando
Orlando, Florida, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
University of Iowa Hospitals and Clinics; Pediatric Specialty Clinic
Iowa City, Iowa, United States
Massachusetts General Hospital - Pediatric Epilepsy Program
Boston, Massachusetts, United States
University of Michigan - Mott Children's Hospital
Ann Arbor, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
...and 8 more locations
Time frame: Baseline (Day -1) until 6 months after single and multiple drug dosing
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.
Time frame: Baseline (Day -1) until 6 months after single and multiple drug dosing