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An Open-Label Extension Study of STK-001 for Patients With Dravet Syndrome

Primary Purpose

Dravet Syndrome

Status
Enrolling by invitation
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
STK-001
Sponsored by
Stoke Therapeutics, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dravet Syndrome focused on measuring Pediatric epilepsy, Epileptic Encephalopathies, Refractory Myoclonic Epilepsy, Severe Myoclonic Epilepsy in Infancy

Eligibility Criteria

30 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Completed dosing with STK-001 and the End of Study Visit in Study STK-001-DS-101, with an acceptable safety profile per Investigator judgment.
  • Had satisfactory compliance with study visits and procedures in Study STK-001-DS-101 per Investigator and Sponsor judgment.
  • Completed Study STK-001-DS-101 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.
  • 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.
  • 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 STK-001) since participating in Study STK-001-DS-101.
  • Participating in an observational study, they are excluded unless approved by the Sponsor.

Sites / Locations

  • University of California San Francisco Medical Center
  • Children's Hospital Colorado
  • Children's National Medical Center
  • Nicklaus Children's Hospital
  • Florida Hospital for Children
  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • University of Iowa Children's Hospital
  • Massachusetts General Hospital
  • Michigan Medicine
  • Mayo Clinic
  • NYU Comprehensive Epilepsy Center
  • Oregon Health & Science University
  • Children's Hospital of Philadelphia
  • UT LeBonheur Pediatric Specialists, Inc.
  • Cook Children's Medical Center
  • Seattle Children's Hospital
  • MultiCare Health System Institute for Research and Innovation

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

STK-001 multiple dose levels

Arm Description

Enrollment of patients after completion of study STK-001-DS-101 if eligible for additional dosing in this extension study. Patients will receive IT administration of study drug STK-001 at the dose level they received while participating in Study STK-001-DS-101, or at a dose level recommended by the Safety Monitoring Committee (SMC).The highest dose administered in this study may not exceed that which has already been evaluated in an STK-001 Phase 1/2 study, and doses above 30 mg/dose in this study require approval from the Food and Drug Administration (FDA). Patients will initially receive 3 doses, one every approximately 4 months (16 weeks). Patients who are tolerating treatment may continue treatment with doses approximately every 4 months, with an End of Study/Follow-up Visit 24 weeks after the last dose of study drug. Patients who do not continue treatment after the third dose will have a Follow-up Visit (V5) at Week 48 and an End of Study Visit at Week 56.

Outcomes

Primary Outcome Measures

Safety of multiple doses of STK-001
Safety variables for analysis include the incidence, type, severity, and seriousness of AEs, and changes in vital signs, ECG, laboratory, immunogenicity, physical examination, and Gillette FAQ parameters.

Secondary Outcome Measures

Pharmacokinetic (PK) Parameters
Analysis of plasma concentrations of STK-001
Exposure of STK-001 in Cerebrospinal Fluid (CSF)
Measurement of STK-001 concentrations
Measurement of Seizure Frequency
Measurement of Seizure Frequency (by paper diary)
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)
Change in Quality of Life
Change in quality of life as measured by the EuroQoL-five dimensions, youth version (EQ-5D-Y) instrument

Full Information

First Posted
February 2, 2021
Last Updated
February 8, 2023
Sponsor
Stoke Therapeutics, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT04740476
Brief Title
An Open-Label Extension Study of STK-001 for Patients With Dravet Syndrome
Official Title
An Open-Label Extension Study for Patients With Dravet Syndrome Who Previously Participated in Studies of STK-001
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
January 21, 2021 (Actual)
Primary Completion Date
February 3, 2026 (Anticipated)
Study Completion Date
March 3, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stoke Therapeutics, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Stoke Therapeutics is evaluating the long-term safety & tolerability of repeated doses of STK-001 in patients with Dravet syndrome who previously participated in studies of STK-001. 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 STK-001 and meet study eligibility criteria. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dravet Syndrome
Keywords
Pediatric epilepsy, Epileptic Encephalopathies, Refractory Myoclonic Epilepsy, Severe Myoclonic Epilepsy in Infancy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
69 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
STK-001 multiple dose levels
Arm Type
Experimental
Arm Description
Enrollment of patients after completion of study STK-001-DS-101 if eligible for additional dosing in this extension study. Patients will receive IT administration of study drug STK-001 at the dose level they received while participating in Study STK-001-DS-101, or at a dose level recommended by the Safety Monitoring Committee (SMC).The highest dose administered in this study may not exceed that which has already been evaluated in an STK-001 Phase 1/2 study, and doses above 30 mg/dose in this study require approval from the Food and Drug Administration (FDA). Patients will initially receive 3 doses, one every approximately 4 months (16 weeks). Patients who are tolerating treatment may continue treatment with doses approximately every 4 months, with an End of Study/Follow-up Visit 24 weeks after the last dose of study drug. Patients who do not continue treatment after the third dose will have a Follow-up Visit (V5) at Week 48 and an End of Study Visit at Week 56.
Intervention Type
Drug
Intervention Name(s)
STK-001
Intervention Description
STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection.
Primary Outcome Measure Information:
Title
Safety of multiple doses of STK-001
Description
Safety variables for analysis include the incidence, type, severity, and seriousness of AEs, and changes in vital signs, ECG, laboratory, immunogenicity, physical examination, and Gillette FAQ parameters.
Time Frame
Screening (Day -1) until 6 months after multiple drug dosing
Secondary Outcome Measure Information:
Title
Pharmacokinetic (PK) Parameters
Description
Analysis of plasma concentrations of STK-001
Time Frame
Dosing (Day 1) until 6 months after multiple drug dosing
Title
Exposure of STK-001 in Cerebrospinal Fluid (CSF)
Description
Measurement of STK-001 concentrations
Time Frame
Dosing (Day 1) until Week 32 (last study drug dosing day)
Title
Measurement of Seizure Frequency
Description
Measurement of Seizure Frequency (by paper diary)
Time Frame
Screening (Day -1) until 6 months after multiple drug dosing
Title
Change in overall clinical status
Description
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
Title
Change in Quality of Life
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Completed dosing with STK-001 and the End of Study Visit in Study STK-001-DS-101, with an acceptable safety profile per Investigator judgment. Had satisfactory compliance with study visits and procedures in Study STK-001-DS-101 per Investigator and Sponsor judgment. Completed Study STK-001-DS-101 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. 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. 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 STK-001) since participating in Study STK-001-DS-101. Participating in an observational study, they are excluded unless approved by the Sponsor.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Javier Avendaño, MD
Organizational Affiliation
Medical Director
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Francisco Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Nicklaus Children's Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Florida Hospital for Children
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Iowa Children's Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Michigan Medicine
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
NYU Comprehensive Epilepsy Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
UT LeBonheur Pediatric Specialists, Inc.
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
MultiCare Health System Institute for Research and Innovation
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States

12. IPD Sharing Statement

Learn more about this trial

An Open-Label Extension Study of STK-001 for Patients With Dravet Syndrome

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