An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome

November 8, 2023 updated by: Stoke Therapeutics, Inc

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

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.

Study Overview

Status

Active, not recruiting

Conditions

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

Interventional

Enrollment (Estimated)

78

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • California
      • San Francisco, California, United States, 94158
        • UCSF Benioff Children's Hospital
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Florida
      • Miami, Florida, United States, 33155
        • Nicklaus Children's Hospital
      • Orlando, Florida, United States, 32803
        • AdventHealth Orlando
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics; Pediatric Specialty Clinic
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital - Pediatric Epilepsy Program
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan - Mott Children's Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10016
        • NYU Comprehensive Epilepsy Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Le Bonheur Children's Hospital
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Health Care System
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • Primary Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
      • Tacoma, Washington, United States, 98405
        • MultiCare Institute for Research and Innovation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
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.
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
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.
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 ).

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
  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
Screening (Day -28) until 6 months after single and multiple drug dosing
Pharmacokinetic (PK) Parameters
Time Frame: Day 1 (Dosing) until 6 months after single and multiple drug dosing
Analysis of plasma concentrations of STK-001
Day 1 (Dosing) until 6 months after single and multiple drug dosing
Exposure of STK-001 in Cerebrospinal Fluid (CSF)
Time Frame: Day 1 (Dosing) until 6 months after single and multiple drug dosing
Measurement of STK-001 concentrations
Day 1 (Dosing) until 6 months after single and multiple drug dosing

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
Measured by paper diary
Screening (Day -28) until 6 months after single and multiple drug dosing
Change in Caregiver Global Impression of Change Scale
Time Frame: Baseline (Day -1) until 6 months after single and multiple drug dosing

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
Baseline (Day -1) until 6 months after single and multiple drug dosing
Change in Clinician-assessed Global Impression of Change Scale
Time Frame: Baseline (Day -1) until 6 months after single and multiple drug dosing

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
Baseline (Day -1) until 6 months after single and multiple drug dosing
Measurement of Quality of Life
Time Frame: Baseline (Day -1) until 6 months after single and multiple drug dosing
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Ann Dandurand, MD, Medical Director

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 3, 2020

Primary Completion (Estimated)

September 22, 2024

Study Completion (Estimated)

May 4, 2025

Study Registration Dates

First Submitted

June 8, 2020

First Submitted That Met QC Criteria

June 19, 2020

First Posted (Actual)

June 22, 2020

Study Record Updates

Last Update Posted (Estimated)

November 9, 2023

Last Update Submitted That Met QC Criteria

November 8, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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