Dravet Syndrome
Conditions
Keywords
Dravet syndrome
Brief summary
The primary purpose of this study is to evaluate the safety and tolerability of ION337 in participants with Dravet syndrome (DS).
Detailed description
This is an open-label study of ION337 in people with DS between the ages of 2 and 12 years old (inclusive). The study consists of 2 parts: Part 1) 6-month single ascending dose (SAD) and Part 2) 24-month multiple ascending dose (MAD), followed by a 7-month safety follow up.
Interventions
DRUGION337
ION337 will be administered by ITB injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participant is aged ≥ 2 to ≤ 12 years old at the time of informed consent. 2. Participant has at least 1 parent or caregiver ≥ 18 years old who is willing and able to provide informed consent (signed and dated) and attend all scheduled study visits. 3. Has a documented diagnosis of DS according to the International League Against Epilepsy (ILAE) criteria and as agreed by the Epilepsy Study Consortium, Inc (ESCI). 4. Has confirmation of a pathogenic or likely pathogenic SCN1A variant. 5. Must be currently receiving ≥ 1 concomitant ASM at a stable dose/regimen for ≥ 4 weeks prior to informed consent. 6. Must have all other interventions for epilepsy (including ketogenic diet or VNS) as well as any other concomitant medications including medications for behavioral management, sleep, and supplements or nutritional support stable for ≥ 4 weeks prior to informed consent. Vagus nerve stimulator implantation must have occurred ≥ 6 months prior to informed consent. 7. Experiences the required number of major motor seizures during the Screening Period. Key
Exclusion criteria
1. Known brain or spinal disease that would interfere with the LP procedure or CSF circulation, or presence of other factors that would affect the safety of the LP procedure. 2. Pathogenic or likely pathogenic variant in another gene that causes epilepsy. 3. Has had prior treatment with or is currently enrolled in an interventional clinical trial for a gene therapy or for another antisense oligonucleotide (ASO) for the treatment of DS. 4. Has had treatment with or is currently enrolled in an interventional clinical trial of any other investigational drug, biological agent, or device within 30 days prior to Screening, or 5 half-lives of investigational agent, whichever is longer. 5. Current treatment with an anti-seizure medication (ASM) acting primarily as a sodium channel blocker, as maintenance treatment. 6. Prior brain surgeries including: corpus callosotomy, implantation of device for deep brain stimulation or any other palliative brain surgery intended to reduce seizure burden. Note: Other protocol pre-specified inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Parts 1 and 2: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Part 1: up to 6 months; Part 2: up to 31 months |
| Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Values | Part 1: up to 6 months; Part 2: up to 31 months |
| Parts 1 and 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Part 1: up to 6 months; Part 2: up to 31 months |
| Parts 1 and 2: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) | Part 1: up to 6 months; Part 2: up to 31 months |
| Parts 1 and 2: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings | Part 1: up to 6 months; Part 2: up to 31 months |
| Parts 1 and 2: Number of Participants with Change in Columbia Suicidality Severity Rating Scale (C-SSRS) | Part 1: up to 6 months; Part 2: up to 31 months |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) Parameters Measure Description: Analysis of plasma concentrations of ION337 | Pre-Dose Day 1 (Dosing) until 6 months after dosing in Part 1 and up to 31 months in Part 2 |
| Exposure of ION337 in Cerebrospinal Fluid (CSF) Measure Description: Measurement of ION337 concentrations | Pre-dose Day 1 (Dosing) until 6 months after dosing in Part 1 and up to 31 months in Part 2 |
| Parts 1 and 2: Percent Change From Baseline in 28-day Normalized Major Motor Seizure (MMS) Frequency | Part 1: up to 6 months; Part 2: up to 31 months |
Countries
Canada, United States
Contacts
CONTACTIonis Pharmaceuticals, Inc.
Outcome results
None listed