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

September 2, 2026 updated by: Ionis Pharmaceuticals, Inc.

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
      • Montreal, Canada, H4A 3J1
        • Recruiting
        • McGill University Health Center - Research Institute
  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Health System
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University Health Systems
    • Tennessee
      • Memphis, Tennessee, United States, 38103
        • Recruiting
        • Le Bonheur Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Parts 1 and 2: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Time Frame: Part 1: up to 6 months; Part 2: up to 31 months
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
Time Frame: Part 1: up to 6 months; Part 2: up to 31 months
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
Time Frame: Part 1: up to 6 months; Part 2: up to 31 months
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)
Time Frame: Part 1: up to 6 months; Part 2: up to 31 months
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
Time Frame: Part 1: up to 6 months; Part 2: up to 31 months
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)
Time Frame: Part 1: up to 6 months; Part 2: up to 31 months
Part 1: up to 6 months; Part 2: up to 31 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Pharmacokinetic (PK) Parameters Measure Description: Analysis of plasma concentrations of ION337
Time Frame: Pre-Dose Day 1 (Dosing) until 6 months after dosing in Part 1 and up to 31 months in Part 2
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
Time Frame: Pre-dose Day 1 (Dosing) until 6 months after dosing in Part 1 and up to 31 months in Part 2
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
Time Frame: Part 1: up to 6 months; Part 2: up to 31 months
Part 1: up to 6 months; Part 2: up to 31 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ionis Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 21, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 8, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 15, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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