ASCEND: Safety and Tolerability of ION337 for the Treatment of Dravet Syndrome

Phase 1-2, Open-Label, Single and Multiple Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION337 in Patients With Dravet Syndrome

The primary purpose of this study is to evaluate the safety and tolerability of ION337 in participants with Dravet syndrome (DS).

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.

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/exclusion criteria may apply.