Clinical trial NCT04740476: 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
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Dravet Syndrome
Keywords: Pediatric epilepsy
Epileptic Encephalopathies
Refractory Myoclonic Epilepsy
Severe Myoclonic Epilepsy in Infancy
Lead sponsor: Stoke Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2021-02-05
Enrollment: 60
Sex: ALL
Minimum age (years): 30
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Completed dosing with STK-001 and the End of Study Visit in Study STK-001-DS-101 or Study STK-001-DS-102, with an acceptable safety profile per Investigator judgment.
* Had satisfactory compliance with study visits and procedures in Study STK-001-DS-101 or Study STK-001-DS-102 per Investigator and Sponsor judgment.
* Completed Study STK-001-DS-101 or STK-001-DS-102 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 or STK-001-DS-102.
* Currently treated with an antiepileptic drug (AED) acting primarily as a sodium channel blocker, as maintenance therapy, including phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, rufinamide or cenobamate.
* 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 or STK-001-DS-102.
* Participating in an observational study, they are excluded unless approved by the Sponsor.

Primary outcomes:
measure: Safety of multiple doses of STK-001
timeFrame: Screening (Day -1) until 6 months after multiple drug dosing
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameters
timeFrame: Dosing (Day 1) until 6 months after multiple drug dosing
measure: Exposure of STK-001 in Cerebrospinal Fluid (CSF)
timeFrame: Dosing (Day 1) and every 4 months until last study drug dosing day
measure: Measurement of Seizure Frequency
timeFrame: Screening (Day -1) until 6 months after multiple drug dosing
measure: Change in overall clinical status
timeFrame: Screening (Day -1) until 6 months after multiple drug dosing
measure: Change in Quality of Life
timeFrame: Screening (Day -1) until 6 months after multiple drug dosing
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Florida Hospital for Children
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Children's Hospital
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: NYU Comprehensive Epilepsy Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: UT LeBonheur Pediatric Specialists, Inc.
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: MultiCare Health System Institute for Research and Innovation
state: Washington
Study officials:
affiliation: Medical Director
name: Ann Dandurand, MD
role: STUDY_DIRECTOR
References: