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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04442295
Recruitment Status : Recruiting
First Posted : June 22, 2020
Last Update Posted : October 5, 2020
Sponsor:
Information provided by (Responsible Party):
Stoke Therapeutics, Inc

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

Condition or disease Intervention/treatment Phase
Dravet Syndrome Drug: STK-001 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study to Investigate the Safety and Pharmacokinetics of Single Ascending Doses of Antisense Oligonucleotide STK-001 in Children and Adolescents With Dravet Syndrome
Actual Study Start Date : June 3, 2020
Estimated Primary Completion Date : September 11, 2021
Estimated Study Completion Date : October 8, 2022


Arm Intervention/treatment
Experimental: Cohort 1: STK-001 dose level 1
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. There will be an option to dose up to 3 additional patients at the same level.
Drug: STK-001
STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Single dose levels ranging from AA to BB mg will be administered.

Experimental: Cohort 2: STK-001 dose level 2
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. There will be an option to dose up to 3 additional patients at the same level.
Drug: STK-001
STK-001 drug product is an antisense oligonucleotide administered as an intrathecal injection. Single dose levels ranging from AA to BB mg will be administered.




Primary Outcome Measures :
  1. Incidence proportion of adverse events [ Time Frame: Screening until 7 months after single drug dosing ]
    Safety of STK-001 will be evaluated by the proportion of subjects experiencing Adverse Events, Serious Adverse Events, and Adverse Events leading to drug discontinuation.

  2. Pharmacokinetic (PK) Parameters [ Time Frame: Screening until 7 months after single drug dosing ]
    Analysis of plasma concentrations of STK-001

  3. Exposure of STK-001 in Cerebrospinal Fluid (CSF) [ Time Frame: Screening until 6 months after single drug dosing ]
    Measurement of STK-001 concentrations


Secondary Outcome Measures :
  1. Measurement of seizure frequency [ Time Frame: Screening until 7 months after single drug dosing ]
    Measured by paper diary

  2. Change in clinical status [ Time Frame: Screening until 7 months after single 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

  3. Change in clinical status [ Time Frame: Screening until 7 months after single 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

  4. Measurement of Quality of Life [ Time Frame: Screening until 7 months after single drug dosing ]
    Change from baseline in the patient health is measured by the EuroQOL quality of life questionnaire, 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have DS with onset prior to 12 months of age with recurrent focal motor or hemiconvulsive or generalized tonic-clonic seizures, 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.
  • Had at least 2 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 be taking at least one AED at a dose which has been stable for at least 4 weeks prior to Screening.
  • All epilepsy medications or interventions for epilepsy (including ketogenic diet or vagal nerve stimulator) must have been stable (including product type, dose, and setting) for at least 4 weeks prior to Screening.

Exclusion Criteria:

  • Known pathogenic mutation in another gene that causes epilepsy
  • Currently being treated with an antiepileptic drug acting primarily as a sodium channel blocker including: phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide.
  • Clinically significant unstable medical conditions other than epilepsy.
  • Has had 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04442295


Contacts
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Contact: Javier Avendaño, MD (781) 430-8200 clinicaltrials@stoketherapeutics.com
Contact: Barry Ticho, MD, PhD (781) 430-8200 clinicaltrials@stoketherapeutics.com

Locations
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United States, California
University of California San Francisco Medical Center Recruiting
San Francisco, California, United States, 94158
Contact: Research Assistant         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Research Assistant         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Research Assistant         
United States, Florida
Nicklaus Children's Hospital Recruiting
Miami, Florida, United States, 33155
Contact: Research Assistant         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Research Assistant         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Research Assistant         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Research Assistant         
United States, Tennessee
Le Bonheur Children's Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Research Assistant         
United States, Texas
Cook Children's Medical Center Recruiting
Fort Worth, Texas, United States, 76104
Contact: Research Assistant         
United States, Washington
Multicare Institute for Research and Innovation Recruiting
Tacoma, Washington, United States, 98405
Contact: Research Assistant         
Sponsors and Collaborators
Stoke Therapeutics, Inc
Investigators
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Study Director: Javier Avendaño, MD Medical Director
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Responsible Party: Stoke Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT04442295    
Other Study ID Numbers: STK-001-DS-101
First Posted: June 22, 2020    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Stoke Therapeutics, Inc:
Pediatric epilepsy
Epileptic Encephalopathies
Refractory Myoclonic Epilepsy
Severe Myoclonic Epilepsy in Infancy
Additional relevant MeSH terms:
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Epilepsies, Myoclonic
Syndrome
Disease
Pathologic Processes
Epilepsy, Generalized
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Epileptic Syndromes