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

NCT07531745 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ION337-CS1
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Dravet Syndrome

Keywords

Dravet syndrome

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• 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

Study Arms (5)

Part 1: Single Ascending Dose (SAD): Dose Level 1

EXPERIMENTAL

Participants aged 2 to ≤ 12 years will receive a single intrathecal bolus (ITB) injection of ION337.

Drug: ION337

Part 1: SAD: Dose Level 2

EXPERIMENTAL

Participants aged 2 to ≤ 12 will receive a single dose of ION337.

Drug: ION337

Part 1: SAD: Dose Level 3

EXPERIMENTAL

Participants aged 2 to ≤ 12 will receive a single dose of ION337.

Drug: ION337

Part 1: SAD: Dose Level 4

EXPERIMENTAL

Participants aged 2 to ≤ 12 will receive a single dose of ION337.

Drug: ION337

Part 2: Multiple Ascending Dose (MAD): Dose Level 1-4

EXPERIMENTAL

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

Interventions

ION337 DRUG

ION337 will be administered by ITB injection.

Part 1: SAD: Dose Level 2; Part 1: SAD: Dose Level 3; Part 1: SAD: Dose Level 4; Part 1: Single Ascending Dose (SAD): Dose Level 1; Part 2: Multiple Ascending Dose (MAD): Dose Level 1-4

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant is aged ≥ 2 to ≤ 12 years old at the time of informed consent.
• 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.
• 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).
• Has confirmation of a pathogenic or likely pathogenic SCN1A variant.
• Must be currently receiving ≥ 1 concomitant ASM at a stable dose/regimen for ≥ 4 weeks prior to informed consent.
• 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.
• Experiences the required number of major motor seizures during the Screening Period.

You may not qualify if:

• 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.
• Pathogenic or likely pathogenic variant in another gene that causes epilepsy.
• 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.
• 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.
• Current treatment with an anti-seizure medication (ASM) acting primarily as a sodium channel blocker, as maintenance treatment.
• Prior brain surgeries including: corpus callosotomy, implantation of device for deep brain stimulation or any other palliative brain surgery intended to reduce seizure burden.

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (2)

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

RECRUITING

Le Bonheur Children's Hospital

Memphis, Tennessee, 38103, United States

RECRUITING

MeSH Terms

Conditions

Epilepsies, Myoclonic

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Central Study Contacts

Ionis Pharmaceuticals, Inc.

CONTACT

(844) 867-4309; IonisDravetSyndrome@clinicaltrialmedia.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2026
• First Posted: April 15, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (2)