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

Brief Title

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

Official Title

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

Brief Summary

      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.
    

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 Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Safety and Tolerability of single and multiple doses of STK-001 with respect to:

Secondary Outcome

 Measurement of seizure frequency

Condition

Dravet Syndrome

Intervention

STK-001 - Single Ascending Doses

Study Arms / Comparison Groups

 Single Ascending Doses

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

78

Start Date

June 3, 2020

Completion Date

May 4, 2025

Primary Completion Date

September 22, 2024

Eligibility Criteria

        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.
      

Gender

All

Ages

2 Years - 18 Years

Accepts Healthy Volunteers

No

Contacts

Javier Avendaño, MD, (781) 430-8200, [email protected]

Location Countries

United States

Location Countries

United States

NCT ID

NCT04442295

Organization ID

STK-001-DS-101

Responsible Party

Sponsor

Study Sponsor

Stoke Therapeutics, Inc

Study Sponsor

Javier Avendaño, MD, Study Director, Medical Director

Verification Date

February 2022