Open-Label Extension Study of Soticlestat in Dravet and Lennox-Gastaut Syndromes

• Register: EUCTR
• Last refreshed on: 15 April 2024
• Main ID: EUCTR2021-002482-17-NL
• Date of registration: 27/12/2021
• Prospective Registration: Yes
• Primary sponsor: Takeda Development Center Americas, Inc
• Public title: Open-Label Extension Study of Soticlestat in Dravet and Lennox-Gastaut Syndromes
• Scientific title: A Phase 3, Prospective, Open-Label, Multisite, Extension of Phase 3 Studies To Assess the Long-Term Safety and Tolerability of Soticlestat as Adjunctive Therapy in Subjects With Dravet Syndrome or Lennox-Gastaut Syndrome (ENDYMION 2).
• Date of first enrolment: 17/03/2022
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-002482-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Canada, China, France, Germany, Greece, Hungary, Italy, Japan, Latvia, Mexico, Netherlands, Poland, Russian Federation, Serbia, Spain, Ukraine, United States

Contacts

• Name: Medical Director
• Affiliation: Takeda Development Center Americas, Inc.

• Name: Medical Director
• Affiliation: Takeda Development Center Americas, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Subject must have:
Been previously enrolled in a phase 3 soticlestat clinical study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 282
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 118
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Unstable, clinically significant neurologic (other than the disease being studied), psychiatric, cardiovascular, ophthalmologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, endocrine disease, malignancy including progressive tumors, or other abnormality that may impact the ability to participate in the study or that may potentially confound the study results. It is the responsibility of the investigator to assess the clinical significance; however, consultation with the medical monitor may be warranted.
2. Abnormal and clinically significant ECG abnormality at Visit 1 including QT interval with Fridericia correction method (QTcF) >450 milliseconds (ms) confirmed with a repeat ECG using manual measurement of QTcF.
3. Participant is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property. Participants who have positive answers on item numbers 4 or 5 on the CSSRS before dosing are excluded. This scale will only be administered to participants aged =6 years.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Dravet Syndrome (DS) Lennox-Gastaut Syndrome (LGS)
MedDRA version: 20.0 Level: LLT Classification code 10073682 Term: Dravet syndrome System Organ Class: 100000004850
MedDRA version: 20.1 Level: PT Classification code 10048816 Term: Lennox-Gastaut syndrome System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: soticlestat
Product Code: TAK-935
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SOTICLESTAT
CAS Number: 1429505-03-2
Current Sponsor code: TAK-935
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: soticlestat
Product Code: TAK-935
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SOTICLESTAT
CAS Number: 1429505-03-2
Current Sponsor code: TAK-935
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Primary end points will be assessed throughout the study.

Secondary Objective: - To assess the effect of soticlestat on seizure frequency (convulsive seizures for the DS cohort, MMD seizures for the LGS cohort, and total seizure count for each cohort).
- To assess the effect of soticlestat on the Clinical Global Impression of Improvement (CGI-I) (clinician) and Caregiver Global Impression of Improvement (Care GI-I).
- To assess the effect of soticlestat on CGI-I Seizure Intensity and Duration.
- To assess the effect of soticlestat on the CGI-I Nonseizure Symptoms completed by clinician with input from the caregiver.
- To assess the effect on Quality of Life Inventory-Disability (QI-Disability).

Primary end point(s): - Incidence of TEAEs.
- Incidence of abnormal values for clinical laboratory tests and electrocardiogram (ECG) evaluations.
- Change from baseline in clinical laboratory test values, vital signs and Columbia-Suicide Severity Rating Scale (C-SSRS), and ECG parameters.
- Change from baseline in height and weight for all age groups.
- Absolute value for Tanner stage for children 6 to 17 years of age during the study.
- Absolute values for IGF-1 for children 2 to 17 years of age during the study.

Main Objective: - To assess the long-term safety and tolerability of soticlestat when administered as adjunctive therapy to SOC (eg, ASMs, vagus nerve stimulation, ketogenic diet, modified Atkins diet) in subjects with DS or LGS.

Secondary Outcome(s)

Secondary end point(s): - Percent change from baseline in total seizure frequency per 28 days for each (DS and LGS) cohort.
- Percent change from baseline in convulsive seizure frequency (DS) per 28 days.
- Percent change from baseline in MMD seizure frequency (LGS) per 28 days.
- Effect on the CGI-I and Care GI-I.
- Effect on CGI-I Seizure Intensity and Duration.
- Effect on the CGI-I Nonseizure Symptoms completed by clinician with input from the caregivers.
- Effect on QI-Disability.

Timepoint(s) of evaluation of this end point: Secondary end points will be assessed throughout the study.

Secondary ID(s)

TAK-935-3003

2021-002482-17-BE

Source(s) of Monetary Support

Takeda Development Center Americas, Inc.

Ethics review

Status: Approved
Approval date: 17/03/2022
Contact: