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).

Study Overview

• Status: Recruiting
• Conditions: Dravet Syndrome
• Intervention / Treatment: Drug: ION337

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.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ionis Pharmaceuticals, Inc.; Phone Number: (844) 867-4309; Email: IonisDravetSyndrome@clinicaltrialmedia.com

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Recruiting
      • Le Bonheur Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Single Ascending Dose (SAD): Dose Level 1; Participants aged 2 to ≤ 12 years will receive a single intrathecal bolus (ITB) injection of ION337.	Drug: ION337; ION337 will be administered by ITB injection.
Experimental: Part 1: SAD: Dose Level 2; Participants aged 2 to ≤ 12 will receive a single dose of ION337.	Drug: ION337; ION337 will be administered by ITB injection.
Experimental: Part 1: SAD: Dose Level 3; Participants aged 2 to ≤ 12 will receive a single dose of ION337.	Drug: ION337; ION337 will be administered by ITB injection.
Experimental: Part 1: SAD: Dose Level 4; Participants aged 2 to ≤ 12 will receive a single dose of ION337.	Drug: ION337; ION337 will be administered by ITB injection.
Experimental: Part 2: Multiple Ascending Dose (MAD): Dose Level 1-4; Only participants who complete Part 1 will be eligible to participate in Part 2. Participants will receive multiple doses of ION337. Participants will begin treatment at the same dose level assigned in Part 1.	Drug: ION337; ION337 will be administered by ITB injection.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Dravet syndrome
• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epilepsy; Epilepsies, Myoclonic
• Other Study ID Numbers: ION337-CS1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No