A Study Evaluating Soticlestat in Participants With Dravet Syndrome or Lennox-Gastaut Syndrome Who Have Been Exposed to Fenfluramine

An Open-label, Nonrandomized, Phase 3 Study to Evaluate the Efficacy and Safety of Soticlestat in Participants With Dravet Syndrome or Lennox-Gastaut Syndrome Who Have Been Exposed to Fenfluramine

The purpose of this study is to check how soticlestat impacts symptoms of Dravet syndrome [DS] and Lennox-Gastaut syndrome [LGS] in participants who have been exposed to fenfluramine.

Study Overview

• Status: Terminated
• Conditions: Dravet Syndrome (DS); Lennox-Gastaut Syndrome (LGS)
• Intervention / Treatment: Drug: Soticlestat

Detailed Description

The drug being tested in this study is called soticlestat. Soticlestat is being tested to treat people who have DS or LGS and have been exposed to fenfluramine. This study will assess the efficacy and safety of soticlestat in addition to standard care in the treatment of DS or LGS.

The study will enroll approximately 45 patients. This study comprises a screening period of up to 6 weeks, a 4-week titration period, a 48-week maintenance period, a taper period of up to 1 week and a follow-up safety visit. Participants will be enrolled to receive soticlestat along with the standard of care:

• Soticlestat 100-300 milligrams (mg)

Participants will receive oral administration of soticlestat Dose 1 (days 1 to 7), Dose 2 (days 8 to 14), and Dose 3 (Days 15 to 28) with a minimum dose of 100 mg to a maximum dose of 300 mg depending on participant's body weight in the titration period followed by maintenance period up to end of treatment (up to approximately 52 weeks). Percent change from baseline in convulsive in participants with DS and major motor drop (MMD) in participants with LGS seizure frequency per 28 days during the initial 12 weeks of the maintenance period will be assessed.

This multi-center trial will be conducted in the United Kingdom and Europe. The overall time to participate in this study is approximately 60 weeks. Participants will make multiple visits to the clinic and will be followed up for safety by visiting the clinic or by telephone approximately 2 weeks after the last dose of the study drug.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Zealand
    • Dianalund, Zealand, Denmark, 4293
      • Epilepsihospitalet Filadelfia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The participant has been exposed to fenfluramine (currently on or used previously).
2. The participant has a clinical diagnosis of LGS and a history of, on average, ≥12 MMD seizures in the last 90 days immediately before screening based on historical information, and the participant has ≥4 MMD seizures during a minimum of 4 weeks of seizure data collection during the prospective baseline period.
3. The participant is currently taking 0 to 5 antiseizure treatments (eg. antiseizure medications [ASMs], vagus nerve stimulation [VNS], ketogenic diet) at stable doses.

Exclusion Criteria:

1. The participant is currently enrolled in a clinical study involving an investigational product or treatment device (ie, not approved in that country, other than soticlestat), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Note: Compatibility will be determined on the basis of consultation with the sponsor/designee.
2. The participant has a known hypersensitivity to any component of the soticlestat formulation.
3. Participants aged ≥6 years who have positive answers on item numbers 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) before dosing are excluded. This scale will only be administered to participants aged ≥6 years at the time of enrollment or participants who turn 6 after enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Soticlestat; Participant received soticlestat at a starting dose of 100 mg to 200 mg in the 4-week titration. As a part of maintenance (initially planned for 48 weeks per protocol), participant remained on the 200 mg BID dose for 9 days followed by a 1-week taper to receive soticlestat 100 mg BID.	Drug: Soticlestat; Soticlestat tablets or mini-tablets; Other Names: TAK-935

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During First 12 Weeks of Maintenance Period for DS Participants	Baseline to Week 12 of Maintenance Period
Percent Change From Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days During First 12 Weeks of Maintenance Period for LGS Participants	Baseline to Week 12 of Maintenance Period

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Medical Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click this link.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2024
• Primary Completion (Actual): August 14, 2024
• Study Completion (Actual): August 14, 2024

Study Registration Dates

• First Submitted: May 15, 2024
• First Submitted That Met QC Criteria: May 15, 2024
• First Posted (Actual): May 21, 2024

Study Record Updates

• Last Update Posted (Actual): July 29, 2025
• Last Update Submitted That Met QC Criteria: July 16, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Genetic Diseases, Inborn; Disease; Epilepsy, Generalized; Epilepsy; Syndrome; Epilepsies, Myoclonic; Lennox Gastaut Syndrome
• Other Study ID Numbers: TAK-935-3004; 2023-504104-29-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites, …).
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No