An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome
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| ClinicalTrials.gov Identifier: NCT04442295 |
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Recruitment Status :
Recruiting
First Posted : June 22, 2020
Last Update Posted : March 28, 2023
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Sponsor:
Stoke Therapeutics, Inc
Information provided by (Responsible Party):
Stoke Therapeutics, Inc
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Dravet Syndrome | Drug: STK-001 - Single Ascending Doses Drug: STK-001 - Multiple Ascending Doses | Phase 1 Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 78 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 and Multiple 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 22, 2024 |
| Estimated Study Completion Date : | May 4, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Pyridoxal 5'-phosphate-dependent epilepsy
CDKL5 deficiency disorder
Genetic epilepsy with febrile seizures plus
CHD2 myoclonic encephalopathy
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: STK-001 - Single Ascending Doses
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 ). |
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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.
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Drug: STK-001 - Multiple Ascending Doses
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 ). |
Primary Outcome Measures :
- 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 ]
- Incidence of adverse events
- incidence of abnormal vital signs
- Abnormal physical examination findings
- Abnormal 12-lead electrocardiogram (ECG)
- Abnormal laboratory parameters
- Pharmacokinetic (PK) Parameters [ Time Frame: Day 1 (Dosing) until 6 months after single and multiple drug dosing ]Analysis of plasma concentrations of STK-001
- 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
Secondary Outcome Measures :
- Measurement of seizure frequency [ Time Frame: Screening (Day -28) until 6 months after single and multiple drug dosing ]Measured by paper diary
- 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:
- Very much improved
- Much improved
- Minimally improved
- No change
- Minimally worse
- Much worse
- Very much worse
- 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:
- Very much improved
- Much improved
- Minimally improved
- No change
- Minimally worse
- Much worse
- Very much worse
- 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.
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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:
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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.
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
| Contact: Javier Avendaño, MD | (781) 430-8200 | clinicaltrials@stoketherapeutics.com | |
| Contact: Kimberly Parkerson, MD, PhD | (781) 430-8200 | clinicaltrials@stoketherapeutics.com |
Locations
Show 18 study locations
Sponsors and Collaborators
Stoke Therapeutics, Inc
Investigators
| Study Director: | Javier Avendaño, MD | Medical Director |
| 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: | March 28, 2023 |
| Last Verified: | February 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Stoke Therapeutics, Inc:
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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 |