Dravet SyndromePhase 1/2NCT07531745
ASCEND: Safety and Tolerability of ION337 for the Treatment of Dravet Syndrome
A Phase 1/2 study testing ION337 in people with Dravet Syndrome, run by Ionis Pharmaceuticals, Inc. at 7 sites in 2 countries.
Trial summary
The primary purpose of this study is to evaluate the safety and tolerability of ION337 in participants with Dravet syndrome (DS). Read more about this study
- Who is it for?
- Ages 2 to 12 years
- Conditions the study is for
- Dravet Syndrome
- What is being tested?
- ION337
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 21 May 2026to Dec 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
- Note: Other protocol pre-specified inclusion/exclusion criteria may apply.
Trial locations and contacts
7 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
7 sites in 2 countries
United States6 sites, 6 recruiting
- Recruiting
University of Michigan Health System
Ann Arbor, Michigan, 48109
- Recruiting
Duke University Health Systems
Durham, North Carolina, 27705
- Recruiting
Le Bonheur Children's Hospital
Memphis, Tennessee, 38103
- Recruiting
The Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Canada1 site, 1 recruiting
- Recruiting
McGill University Health Center - Research Institute
Montreal, H4A 3J1
About this study
Official title: 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).
Read the 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.
- Conditions
- Dravet Syndrome
- Being tested
- ION337
- Keywords
- Dravet syndrome
- Medical subject headings
- Epilepsies, Myoclonic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ION337Drug
ION337 will be administered by ITB injection.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: ION337 |
| Part 1: SAD: Dose Level 2 | Experimental | Participants aged 2 to ≤ 12 will receive a single dose of ION337. Receives: Drug: ION337 |
| Part 1: SAD: Dose Level 3 | Experimental | Participants aged 2 to ≤ 12 will receive a single dose of ION337. Receives: Drug: ION337 |
| Part 1: SAD: Dose Level 4 | Experimental | Participants aged 2 to ≤ 12 will receive a single dose of ION337. Receives: 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. Receives: Drug: ION337 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parts 1 and 2: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: Part 1: up to 6 months; Part 2: up to 31 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2026
- Study start21 May 2026
- Primary completionDec 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dravet SyndromeStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07531745
- Sponsor's protocol ID
- ION337-CS1
- Status last verified
- Oct 2026
- First submitted
- 8 Apr 2026
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/.
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07531745
- Acronym / sponsor ID
- ION337-CS1
- Conditions
- Dravet Syndrome
- Keywords
- Dravet syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 May 2026 (actual)
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 15 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to evaluate the safety and tolerability of ION337 in participants with Dravet syndrome (DS).
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1: Single Ascending Dose (SAD): Dose Level 1 | Experimental | Drug: ION337Participants aged 2 to ≤ 12 years will receive a single intrathecal bolus (ITB) injection of ION337. |
| Part 1: SAD: Dose Level 2 | Experimental | Drug: ION337Participants aged 2 to ≤ 12 will receive a single dose of ION337. |
| Part 1: SAD: Dose Level 3 | Experimental | Drug: ION337Participants aged 2 to ≤ 12 will receive a single dose of ION337. |
| Part 1: SAD: Dose Level 4 | Experimental | Drug: ION337Participants aged 2 to ≤ 12 will receive a single dose of ION337. |
| Part 2: Multiple Ascending Dose (MAD): Dose Level 1-4 | Experimental | Drug: ION337Only 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. |
Who may qualify
- Ages
- 2 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ION337ION337 will be administered by ITB injection. | Drug | 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 |
Primary outcome
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
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
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
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
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
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
3 secondary outcomes
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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- Individual participant dataSharing planned: Yes. 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/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ION337 in people with Dravet Syndrome, run by Ionis Pharmaceuticals, Inc. at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ionis Pharmaceuticals, Inc. ((844) 867-4309, IonisDravetSyndrome@clinicaltrialmedia.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.