Study of Soticlestat as Adjunctive Therapy in Pediatric and Adult Subjects With Lennox-Gastaut Syndrome

• Register: EUCTR
• Last refreshed on: 24 June 2024
• Main ID: EUCTR2021-002481-40-HU
• Date of registration: 25/10/2021
• Prospective Registration: No
• Primary sponsor: Takeda Development Center Americas, Inc.
• Public title: Study of Soticlestat as Adjunctive Therapy in Pediatric and Adult Subjects With Lennox-Gastaut Syndrome
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Soticlestat as Adjunctive Therapy in Pediatric and Adult Subjects With Lennox-Gastaut Syndrome (LGS)
• Date of first enrolment: 22/10/2021
• Target sample size: 234
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-002481-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes 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, Canada, China, France, Germany, Greece, Hungary, Italy, Japan, Latvia, Netherlands, Poland, Russian Federation, Serbia, Spain, Ukraine, United Kingdom, 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:
1. In the opinion of the investigator, the subject and/or parent or legal guardian is capable of understanding and complying with protocol requirements including the use of digital tools, complete appropriate assessments, maintain an accurate and complete daily seizure diary and take study drug for the duration of the study.
2. The subject or the subject’s parent or legal guardian are willing and able to read, understand, and sign and date a written or an electronic informed consent form (ICF), assent form (if applicable), and any required privacy authorization before the initiation of any study procedures.
3. The subject is male or female and aged 2 to 35 years, inclusive, at the time of informed consent.
4. Documented clinical diagnosis of LGS supported by:
– Onset of seizures usually between the ages of 1 and 8 years.
– Presence of multiple seizure types: including drop seizures (eg, tonic-atonic seizures) and other seizure types including atypical absence seizures, tonic-clonic, myoclonic, and partial seizures.
– History of abnormal EEG (eg, slow spike and wave [<2.5 Hz], slow or disorganized EEG background, generalized paroxysmal fast activity).
– Developmental delay or intellectual disability consistent with LGS.
5. The participant has =8 MMD seizures each month in the 3 months prior to screening based on the historical information and has =8 MMD seizures per 28 days during the 4- to 6-week prospective baseline period.
6. Weighs =10 kg at the screening visit (Visit 1).
7. Failure to control seizures despite appropriate trials of at least 2 ASMs based on historical information and is currently on an anti-seizure therapy (eg, ASMs, vagus nerve stimulation (VNS), ketogenic/modified Atkins diet), or other treatment options considered as SOC.
8. Currently taking 0 to 3 ASMs at stable doses for at least 4 weeks before the screening visit (Visit 1); benzodiazepines used chronically (daily) to treat seizures are considered ASMs. ASM dosing regimen must remain constant throughout the study.
9. If using a VNS, the subject must have had VNS placed at least 3 months before the screening visit with stable settings for >1 month; and VNS parameters must remain constant throughout the study (VNS will not be counted as an ASM).
10. If on ketogenic diet (or any other diet used for treatment of epilepsy, such as modified Atkins diet), the subject must have started the diet at least 3 months before the screening visit (Visit 1), and the subject’s diet should be stable for 1 month before the screening visit (Visit 1); should continue this diet throughout the duration of the study (ketogenic diet, or any other diet for the treatment of epilepsy will not be counted as an ASM).
11. The use of felbamate is allowed provided that the subject does not meet the liver function test(LFT) exclusion criteria, the dose has been stable for at least 6 months before screening, and the subject has had stable liver function (as determined by serum aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels) and hematology laboratory tests during the course of treatment.
12. Approved to participate by the sponsor and/or designee (ie, TESC) after review of medical history and seizure classification.
13. Female subjects of childbearing potential (defined as first menarche) must have a negative pregnancy test and agree to use an effective method of birth control during the study and for 30 days following the last dose of study drug.
Effecti
Exclusion criteria:
1. Investigator site personnel directly affiliated with this study and/or their immediate family. Note: Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
2. Takeda employees or immediate family members.
3. Currently enrolled in a clinical study involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), 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 based on consultation with the medical monitor or
the sponsor.
4. Participated in a clinical study involving another study drug in the last 30 days (or 5 halflives of the study drug, whichever is longer) before screening (Visit 1).
5. Received soticlestat in a previous clinical study.
6. Known hypersensitivity to any component of the soticlestat formulation.
7. Admitted to a medical facility and intubated for treatment of status epilepticus 2 or more times in the 3 months immediately before screening (Visit 1). Status epilepticus is defined as continuous seizure activity lasting longer than 5 minutes or repeated seizures without return to baseline in between seizures.
8. 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.
9. Any history of alcohol, opioid, or other drug use disorder, as per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V), within the 2 years immediately before the screening Visit (Visit 1).
10. Considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or the subject has attempted suicide within 12 months before the screening visit (Visit 1). Subjects who have positive answers on item numbers 4 or 5 on the C-SSRS before randomization/dosing (Visit 2) are excluded. This scale will only be administered to subjects
aged = 6 years.
11. History of HIV infection (subject has tested positive for HIV-1 or HIV-2 antibodies), history of hepatitis B infection, or current active hepatitis C infection.
Note: Subjects who have been vaccinated against hepatitis B (hepatitis B surface antibodypositive]
and who test negative for other markers of prior hepatitis B infection (eg, negative for hepatitis B core antibody) are eligible. Also note that subjects who test positive for hepatitis C antibody are eligible if they have a negative hepatitis C viral load by quantitative polymerase chain reaction.
12. Abnormal and clinically significant ECG abnormality at screening (Visit 1) or before randomization/dosing (Visit 2), including QT interval with Fridericia correction method (QTcF) >450 ms confirmed with a repeat ECG using manual measurement of QTcF. Clinically significant ECG abnormalities should be discussed with the medical monitor.
13. Abnormal clinical laboratory test results at screening (Visit 1) that suggest a clinically significant underlyin

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

Health Condition(s) or Problem(s) studied

Lennox-Gastaut Syndrome (LGS)
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-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

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-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: - To assess the efficacy and safety of soticlestat in reducing MMD seizure frequency as add-on therapy to standard of care (SOC) as compared with placebo during the full treatment period (titration + maintenance).

For EMA registration:
- To assess the efficacy and safety of soticlestat in reducing MMD seizure frequency as add-on
therapy to SOC compared with placebo during the maintenance period only.

Primary end point(s): - Percent change from baseline in MMD seizure frequency per 28 days in subjects receiving soticlestat as compared with placebo during the full treatment period.
For EMA registration:
- Percent change from baseline in MMD seizure frequency per 28 days in subjects receiving soticlestat as compared with placebo during the maintenance period.

Secondary Objective: To assess the following in subjects taking soticlestat as compared with placebo during the full treatment period, unless otherwise noted:
- Proportion of treatment responders defined as those with =50% reduction in MMD seizures from baseline during the maintenance period and the full treatment period.
-Effect on total seizure frequency of all seizure types during the maintenance period and the full treatment period.
- Change from baseline in proportion of MMD seizure-free days.
- Longest MMD seizure-free interval.
- Number of days when rescue ASMs are used.
- Effect on the Clinical Global Impression of Improvement (CGI-I) (clinician) and Caregiver Global Impression of Improvement (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 caregiver.
- Effect on Quality of Life Inventory-Disability (QI-Disability).

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

Secondary Outcome(s)

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

Secondary end point(s): To assess the following in subjects receiving soticlestat as compared with placebo during the full treatment period, unless otherwise noted:
- Proportion of responders defined as those with =50% reduction from baseline in MMD seizures during the maintenance period and the full treatment period.
- Percent change from baseline in frequency of all seizures per 28 days during the maintenance period and the full treatment period.
- Percent change from baseline in MMD seizure frequency per 28 days during the maintenance period.
- Responder analysis of the proportion of subjects with =0%, >0% to =25%, >25% to =50%, >50% to =75%, and >75% to =100% reduction from baseline in MMD seizures in a cumulative response curve.
- Change from baseline in proportion of MMD seizure-free days.
- Longest MMD seizure-free interval.
- Number of days when rescue ASM is used.
- CGI-I (clinician).
- Care GI-I (caregiver).
- CGI-I Seizure Intensity and Duration.
- CGI-I Nonseizure Symptoms.
- Change in QI-Disability score.

Secondary ID(s)

2021-002481-40-Outside-EU/EEA

TAK-935-3002

Source(s) of Monetary Support

akeda Development Center Americas, Inc.

Ethics review

Status: Approved
Approval date: 13/10/2021
Contact: