Safety and Tolerability of ION337 for the Treatment of Dravet Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ionis Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-06-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ionis Pharmaceuticals Inc.

External identifiers

EU CT number

2025-523835-20-00

WHO UTN

U1111-1332-5367

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Others, Pharmacokinetic

To evaluate the safety and tolerability of ION337

Secondary objectives 2

1. 01. To characterize the pharmacokinetics of ION337 in the CSF and plasma
2. 02. To evaluate the effects of ION337 on seizure frequency

Conditions and MedDRA coding

Dravet Syndrome

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices, Federal Agency For Medicines And Health Products, National Agency For The Safety Of Medicine And Health Products

Plan to share 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/.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 01. Participant has at least 1 authorized representative who is willing and able to give informed consent and attend all scheduled study visits.
2. 02. Males and females age ≥ 2 to ≤ 12 years old at the time of informed consent.
3. 03. Has a documented diagnosis of DS according to the ILAE criteria and as agreed by the ESCI
4. 04. Has confirmation of a pathogenic or likely pathogenic SCN1A variant.
5. 05. Must be currently receiving ≥ 1 concomitant ASM at a stable dose/regimen for ≥ 4 weeks prior to informed consent.
6. 06. 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. 07. Experiences the required number of major motor seizures during the Screening Period

Exclusion criteria 5

1. 01. 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. 02. Pathogenic or likely pathogenic variant in another gene that causes epilepsy.
3. 03. Gain-of function variant in the SCN1A gene.
4. 04. Current treatment with an ASM acting primarily as a sodium channel blocker, as maintenance treatment.
5. 05. Prior brain surgeries including: corpus callosotomy, implantation of device for deep brain stimulation or any other palliative brain surgery intended to reduce seizure burden.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of TEAEs and SAEs, and clinically significant changes from Baseline in safety laboratory values, vital signs, ECGs, physical/neurological exam measures, and C-SSRS summarized by study part (Part 1/SAD and Part 2/MAD).

Secondary endpoints 2

1. 1. - ION337 trough (pre-dose) in CSF and plasma for all doses in Part 1/SAD and Part 2/MAD. - Post-dose Cmax, AUC, and t1/2λz from plasma in Part 1/SAD - Post-dose Cmax, AUC, and t1/2λz from plasma in Part 2/MAD – first dose only
2. 2. Percent change from Baseline in 28-day normalized major motor seizure (MMS) frequency in Part 1/SAD and Part 2/MAD.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ionis Pharmaceuticals Inc.

Sponsor organisation

Ionis Pharmaceuticals Inc.

Address

2855 Gazelle Court

City

Carlsbad

Postcode

92010-6670

Country

United States

Scientific contact point

Organisation

Ionis Pharmaceuticals Inc.

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Ionis Pharmaceuticals Inc.

Contact name

Global Regulatory Affairs

Third parties 2

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications