- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04442295
An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome
An Open-Label Study to Investigate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Antisense Oligonucleotide STK-001 in Children and Adolescents With Dravet Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Javier Avendaño, MD
- Phone Number: (781) 430-8200
- Email: clinicaltrials@stoketherapeutics.com
Study Contact Backup
- Name: Kimberly Parkerson, MD, PhD
- Phone Number: (781) 430-8200
- Email: clinicaltrials@stoketherapeutics.com
Study Locations
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California
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San Francisco, California, United States, 94158
- UCSF Benioff Children's Hospital
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Colorado
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Aurora, Colorado, United States, 80045
- Children's Hospital Colorado
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Children's National Medical Center
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Florida
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Miami, Florida, United States, 33155
- Nicklaus Children's Hospital
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Orlando, Florida, United States, 32803
- AdventHealth Orlando
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Illinois
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Chicago, Illinois, United States, 60611
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Iowa
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Iowa City, Iowa, United States, 52242
- University of Iowa Hospitals and Clinics; Pediatric Specialty Clinic
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital - Pediatric Epilepsy Program
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan - Mott Children's Hospital
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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New York
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New York, New York, United States, 10016
- NYU Comprehensive Epilepsy Center
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health & Science University
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
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Tennessee
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Memphis, Tennessee, United States, 38105
- Le Bonheur Children's Hospital
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Texas
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Fort Worth, Texas, United States, 76104
- Cook Children's Health Care System
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Utah
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Salt Lake City, Utah, United States, 84108
- Primary Children's Hospital
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Washington
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Seattle, Washington, United States, 98105
- Seattle Children's Hospital
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Tacoma, Washington, United States, 98405
- MultiCare Institute for Research and Innovation
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Single Ascending Doses
Enrollment of patients in two age groups.
A Sentinel group of 2 patients aged 13 to 18 years of age, inclusive, and an expanded group of 2 patients 2 to 12 years of age to receive single doses.
There will be an option to dose up to 6 additional patients at each dose level and an option to expand the maximum tolerated dose level with 5 additional patients.
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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 ).
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Experimental: Multiple Ascending Doses
Enrollment of patients in two age groups.
A Sentinel group of 2 patients aged 13 to 18 years of age, inclusive, and an expanded group of 2 patients 2 to 12 years of age to receive multiple doses.
There will be an option to dose up to 6 additional patients at each dose level and an option to expand the maximum tolerated dose level with 10 additional patients.
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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 ).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and Tolerability of single and multiple doses of STK-001 with respect to:
Time Frame: Screening (Day -28) until 6 months after single and multiple drug dosing
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Screening (Day -28) until 6 months after single and multiple drug dosing
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Pharmacokinetic (PK) Parameters
Time Frame: Day 1 (Dosing) until 6 months after single and multiple drug dosing
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Analysis of plasma concentrations of STK-001
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Day 1 (Dosing) until 6 months after single and multiple drug dosing
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Exposure of STK-001 in Cerebrospinal Fluid (CSF)
Time Frame: Day 1 (Dosing) until 6 months after single and multiple drug dosing
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Measurement of STK-001 concentrations
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Day 1 (Dosing) until 6 months after single and multiple drug dosing
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measurement of seizure frequency
Time Frame: Screening (Day -28) until 6 months after single and multiple drug dosing
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Measured by paper diary
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Screening (Day -28) until 6 months after single and multiple drug dosing
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Change in Caregiver Global Impression of Change Scale
Time Frame: Baseline (Day -1) until 6 months after single and multiple drug dosing
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Change from baseline in overall clinical status as measured by the Clinical Global Impression of Change (CGIC). Values of scales:
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Baseline (Day -1) until 6 months after single and multiple drug dosing
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Change in Clinician-assessed Global Impression of Change Scale
Time Frame: Baseline (Day -1) until 6 months after single and multiple drug dosing
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Change from baseline in overall clinical status as measured by the Caregiver Global Impression of Change (CaGIC) Values of scales:
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Baseline (Day -1) until 6 months after single and multiple drug dosing
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Measurement of Quality of Life
Time Frame: Baseline (Day -1) until 6 months after single and multiple drug dosing
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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.
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Baseline (Day -1) until 6 months after single and multiple drug dosing
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Ann Dandurand, MD, Medical Director
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- STK-001-DS-101
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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