## Protocol Section
### Identification Module
**NCT ID:** NCT06422377

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

**Official Title:** 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

#### Organization Study ID Info
**ID:** TAK-935-3004
#### Organization
**Class:** INDUSTRY
**Full Name:** Takeda
#### Secondary ID Infos
**Domain:** EU CTIS
**ID:** 2023-504104-29
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2027-01-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-21

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-15

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2027-01-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-04-25

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-21
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-15
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Takeda

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** False

### Description Module

**Brief Summary:** 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.

**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 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.

### Conditions Module

**Conditions:**

- Dravet Syndrome (DS)

- Lennox-Gastaut Syndrome (LGS)

**Keywords:**

- Drug Therapy

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 45

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants with DS or LGS will receive soticlestat, mini-tablets, at the starting dose of 100 mg to 300 mg, administered orally with or without food (oral or enteral feeds), twice daily (BID) based on body weight up to 4 weeks in Titration Period. Participants will continue to receive the dose that they are on at the end of the titration period, for first 12 weeks in the Maintenance Period. The dose can be adjusted in the maintenance period as per the body weight after the initial 12 weeks. Dose will be tapered down if participants decide to discontinue the treatment. Total duration of the treatment will be up to approximately 52 weeks.

**Intervention Names:**

- Drug: Soticlestat

**Label:** Soticlestat

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Soticlestat

**Description:** Soticlestat tablets or mini-tablets

**Name:** Soticlestat

**Other Names:**

- TAK-935

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Percent Change from Baseline in Convulsive Seizure Frequency per 28 days During First 12 Weeks of Maintenance Period for DS Participants

**Time Frame:** Baseline to Week 12 of Maintenance Period

**Measure:** Percent Change from Baseline in Major Motor Drop (MMD) Seizure Frequency per 28 days During First 12 Weeks of Maintenance Period for LGS Participants

**Time Frame:** Baseline to Week 12 of Maintenance Period

### Eligibility Module

**Eligibility Criteria:** 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.

**Maximum Age:** 65 Years

**Minimum Age:** 2 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** medinfoUS@takeda.com

**Name:** Takeda Contact

**Phone:** +1-877-825-3327

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Dianalund

**Contacts:**

***Contact 1:***

- **Email:** fil-ctu@filadelfia.dk

- **Name:** Site Contact

- **Phone:** +4558264200

- **Role:** CONTACT

***Contact 2:***

- **Name:** Cathrine Elisabeth Gjerulfsen

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** Denmark

**Facility:** Epilepsihospitalet Filadelfia

**State:** Zealand

**Status:** RECRUITING

**Zip:** 4293

**Location 2:**

**City:** Cardiff

**Contacts:**

***Contact 1:***

- **Email:** hamandik@cardiff.ac.uk

- **Name:** Site Contact

- **Phone:** +442920715434

- **Role:** CONTACT

***Contact 2:***

- **Name:** Khalid Hamandi

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United Kingdom

**Facility:** University Hospital of Wales

**State:** Wales

**Status:** RECRUITING

**Zip:** CF14 4XW

#### Overall Officials

**Official 1:**

**Affiliation:** Takeda

**Name:** Study Director

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**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.

**Description:** Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

**IPD Sharing:** YES

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- ID: D000004829

- Term: Epilepsy, Generalized

- ID: D000004827

- Term: Epilepsy

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000073376

- Term: Epileptic Syndromes

- ID: D000030342

- Term: Genetic Diseases, Inborn

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- ID: M30593

- Name: Lennox Gastaut Syndrome

- Relevance: HIGH

- As Found: Lennox-Gastaut Syndrome

- ID: M7983

- Name: Epilepsy

- Relevance: LOW

- As Found: Unknown

- ID: M7987

- Name: Epilepsies, Myoclonic

- Relevance: HIGH

- As Found: Dravet Syndrome

- ID: M7985

- Name: Epilepsy, Generalized

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M1165

- Name: Epileptic Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: T1938

- Name: Dravet Syndrome

- Relevance: HIGH

- As Found: Dravet Syndrome

- ID: T1024

- Name: CDKL5 Deficiency Disorder

- Relevance: HIGH

- As Found: Dravet Syndrome

- ID: T3371

- Name: Lennox-Gastaut Syndrome

- Relevance: HIGH

- As Found: Lennox-Gastaut Syndrome

### Condition Browse Module - Meshes

- ID: D000004831

- Term: Epilepsies, Myoclonic

- ID: D000065768

- Term: Lennox Gastaut Syndrome

- ID: D000013577

- Term: Syndrome

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M8414

- Name: Fenfluramine

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
