ION337 safety and tolerability in children with 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

This will test whether ION337 is safe and well tolerated in children ages 2 to 12 with Dravet syndrome.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 2 Years to 12 Years
• Sex: All
• Sponsor: Ionis Pharmaceuticals, Inc. (Industry-sponsored)
• Locations: 2 sites (Ann Arbor, Michigan and 1 other locations)
• Trial ID: NCT07531745 on ClinicalTrials.gov

What this trial studies

This open-label, phase 1/2 trial enrolls children aged 2–12 with genetically confirmed Dravet syndrome and a pathogenic or likely pathogenic SCN1A variant. Part 1 uses a 6-month single ascending dose (SAD) design and Part 2 uses a 24-month multiple ascending dose (MAD) period, followed by a 7-month safety follow-up. Participants must be on a stable antiseizure medication regimen and have stable non-drug epilepsy interventions before enrollment. Safety, tolerability, and dosing will be monitored through scheduled clinic visits, neurological assessments, and laboratory testing.

Who should consider this trial

Good fit: Ideal candidates are children aged 2 to 12 with a confirmed diagnosis of Dravet syndrome and a pathogenic or likely pathogenic SCN1A variant who have a caregiver able to attend visits and are on a stable antiseizure medication regimen.

Not a fit: Children outside the 2–12 age range, those without a pathogenic SCN1A variant, or those with unstable antiseizure therapy or recent neuromodulation procedures are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If safe and well tolerated, ION337 could become a new targeted option that reduces seizures or improves daily functioning for children with SCN1A-related Dravet syndrome.

How similar studies have performed: Gene-directed therapies targeting SCN1A have shown promise in animal models and early-phase human work, but robust clinical success in large trials has not yet been established.

Eligibility 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/exclusion criteria may apply.

Where this trial is running

Ann Arbor, Michigan and 1 other locations

• University of Michigan Health System — Ann Arbor, Michigan, United States (Recruiting)
• Le Bonheur Children's Hospital — Memphis, Tennessee, United States (Recruiting)

Study contacts

• Study coordinator: Ionis Pharmaceuticals, Inc.

Conditions Dravet Syndrome; Dravet syndrome