A Study of Soticlestat as an Add-on Therapy in Children, Teenagers, and Adults With Lennox-Gastaut Syndrome

NCT ID: NCT04938427

Last Updated: 2024-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 270 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-08
• Study Completion Date: 2024-01-25

Brief Summary

The aims of the study are:

• to learn if soticlestat, when given as add-on therapy, reduces the number of major motor drop seizures in children, teenagers, and adults with Lennox-Gastaut Syndrome.
• to assess the safety profile of soticlestat when given in combination with other therapies.

Participants will receive their standard antiseizure therapy, plus either tablets of soticlestat or placebo. A placebo looks just like soticlestat but will not have any medicine in it. Participants will take soticlestat or placebo for 16 weeks, followed by a gradual dose reduction for 1 week. Then, participants will be followed up for 2 weeks.

Detailed Description

The drug being tested in this study is called soticlestat (TAK-935). Soticlestat will be assessed for efficacy, safety, and tolerability in pediatric and adult participants with LGS.

The study will enroll approximately 234 patients. Participants will be randomly assigned (by chance, like flipping a coin) in a 1:1 ratio to receive standard of care (SOC) plus one of the following adjunctive therapies which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

1. Soticlestat

2. Placebo (dummy inactive pill - this is a tablet/mini-tablet that looks like the study drug but has no active ingredient)

Participants will receive soticlestat or matching placebo based on their weight in the 4-week Titration Period. Following the Titration Period, participants will continue to receive the same dose in the 12-week Maintenance Period. The dose will then be down-tapered if participants decide to discontinue the treatment and/or are not deemed eligible to continue in Open-label extension (OLE).

This multi-center trial will be conducted worldwide. The overall time to participate in the study will be from 22-25 weeks. At the end of the treatment period, participants have the option to either complete the study and taper off the investigational product or to enter the OLE if they meet eligibility requirements. If participants discontinue, they will be followed-up on phone call approximately 14 days after the last dose of study drug for safety.

Conditions

Lennox Gastaut Syndrome (LGS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Soticlestat placebo-matching mini-tablets or tablets, orally or via G-tube or MIC-KEY button or J-tube, BID, up to 4 weeks during titration. Participants continued to receive soticlestat placebo-matching mini-tablets or tablets for 12 weeks during maintenance. The total duration of the treatment was up to 16 weeks (Full Treatment Period). Soticlestat matching tapering was done to maintain the blind if participants decided to discontinue the treatment.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Soticlestat placebo-matching mini-tablets or tablets.

Soticlestat

Participants weighing <45 kg: Soticlestat, mini-tablets, at the dose of 40 mg to 200 mg, orally or via G-tube or MIC-KEY button or J-tube, BID based on body weight up to 4 weeks during titration. Participants continued to receive the dose that they were on at the end of the titration, for 12 weeks during maintenance. The total duration of the treatment was up to 16 weeks (Full Treatment Period) with the dose tapered down if participants decided to discontinue the treatment.

Participants weighing ≥45 kg: Soticlestat mini-tablets or tablets with a starting dose of 100 mg BID followed by 200 mg BID and, then 300 mg BID, up to 4 weeks during titration. Participants continued to receive 300 mg BID for 12 weeks during maintenance. The total duration of the treatment was up to 16 weeks (Full Treatment Period) with the dose tapered down if participants decided to discontinue the treatment.

Group Type: EXPERIMENTAL

Soticlestat

Intervention Type: DRUG

Soticlestat mini-tablets or tablets.

Interventions

Placebo

Soticlestat placebo-matching mini-tablets or tablets.

Intervention Type: DRUG

Soticlestat

Soticlestat mini-tablets or tablets.

Intervention Type: DRUG

Other Intervention Names

TAK-935

Eligibility Criteria

Inclusion Criteria

1. Has documented clinical diagnosis of LGS.

2. Has had ≥8 MMD seizures each month in the 3 months prior to Screening based on the historical information and has had ≥8 MMD seizures per 28 days during the 4 to 6 week prospective Baseline Period.

3. Weighs ≥10 kg at the Screening Visit (Visit 1).

4. Failure to control seizures despite appropriate trials of at least 1 ASM based on historical information, and is currently on an antiseizure therapy or other treatment options considered as standard of care (SOC).

5. Artisanal cannabidiols are allowed at a stable dose for at least 4 weeks before the screening visit (Visit 1); the dosing regimen and manufacturer should remain constant throughout the study. (Artisanal cannabidiols will not be counted as ASMs.)

6. Currently taking 0 to 3 ASMs at stable doses for at least 4 weeks before the Screening Visit (Visit 1); Fenfluramine and cannabidiol (Epidiolex) are allowed where available and counted as an ASM. ASM dosing regimen must remain constant throughout the study.

Exclusion Criteria

1. 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). For the purpose of this exclusion criterion, status is defined as continuous seizure activity lasting longer than 5 minutes or repeated seizures without return to Baseline in between seizures.

2. 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.

3. Considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or the participant has attempted suicide within 12 months before the Screening Visit (Visit 1). Participants who have positive answers on item numbers 4 or 5 on the Columbia suicide severity rating scale (C-SSRS) before dosing (Visit 2) are excluded. This scale will only be administered to participants aged ≥6 years.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Center For Neurosciences

Tucson, Arizona, United States

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

University of California Benioff Children's Hospital

San Francisco, California, United States

Children's Hospital Colorado.

Denver, Colorado, United States

Pediatric Neurology PA

Winter Park, Florida, United States

Clinical Integrative Research Center of Atlanta

Atlanta, Georgia, United States

University of Iowa Hospitals & Clinics - (CRS)

Iowa City, Iowa, United States

Midatlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Minnesota Epilepsy Group PA

Roseville, Minnesota, United States

Institute of Neurology and Neurosurgery at Saint Barnabas, LLC

Livingston, New Jersey, United States

Premier Healthcare Inc.

New York, New York, United States

NYU Comprehensive Epilepsy Center

New York, New York, United States

Northwell Health Physician Partners - Neurology at Lenox Hill

New York, New York, United States

Oregon Health and Science University

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

WellSpan Oncology Research

York, Pennsylvania, United States

Medical University of South Carolina Children Hospital - PIN

Charleston, South Carolina, United States

Cook Children's Medical Center - Jane and John Justin Neurosciences Center

Fort Worth, Texas, United States

University of Utah - Primary Children's Hospital - PPDS

Salt Lake City, Utah, United States

Seattle Children's Hospital

Seattle, Washington, United States

MultiCare Institute for Research & Innovation (Tacoma)

Tacoma, Washington, United States

Sydney Children's Hospital

Randwick, New South Wales, Australia

Queensland Childrens Hospital

South Brisbane, Queensland, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Alfred Hospital

Melbourne, Victoria, Australia

UZ Antwerpen PIN

Edegem, Antwerpen, Belgium

Centre Neurologique William Lennox

Ottignies-Louvain-la-Neuve, Brabant Wallon, Belgium

Hopital Universitaire des Enfants Reine Fabiola

Brussels, , Belgium

Alberta Childrens Hospital

Calgary, Alberta, Canada

Child and Family Research Institute

Vancouver, British Columbia, Canada

Hospital For Sick Children

Toronto, Ontario, Canada

Peking University First Hospital

Beijing, Beijing Municipality, China

Beijing Children's Hospital,Capital Medical University

Beijing, Beijing Municipality, China

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Guangzhou Women And Children's Medical Center

Guangzhou, Guangdong, China

Shenzhen Children's Hospital

Shenzhen, Guangdong, China

Wuhan Childrens hospital

Wuhan, Hubei, China

Xiangya Hospital Central South University

Changsha, Hunan, China

Jiangxi Provincial Children's Hospital

Nanchang, Jiangxi, China

The First Hospital of Jilin University

Changchun, Jilin, China

Children's Hospital of Shanghai

Shanghai, Shanghai Municipality, China

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, China

CHRU Dijon Hopital General

Dijon, Cote-d'Or, France

Hopital Roger Salengro

Lille, Nord, France

Hopitaux de La Timone

Marseille, , France

Hopital Necker - Enfants Malades

Paris, , France

Hopital Robert Debre

Paris, , France

Schon Klinik Vogtareuth

Vogtareuth, Bavaria, Germany

Klinikum der Johann-Wolfgang Goethe-Universitat

Frankfurt am Main, Hesse, Germany

Krankenhaus Mara gGmbH - Epilepsiezentrum Bethel

Bielefeld, North Rhine-Westphalia, Germany

Kleinwachau Sachsisches Epilepsiezentrum Radeberg Gemeinnutzige Gmbh

Radeberg, Sachse, Germany

Attikon University General Hospital

Chaïdári, Attica, Greece

University General Hospital of Larissa

Larissa, , Greece

Hippokration Hospital

Thessaloniki, , Greece

Pecsi Tudomanyegyetem

Pécs, Baranya, Hungary

Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak

Budapest, , Hungary

Bethesda Gyermekkorhaz

Budapest, , Hungary

Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet

Budapest, , Hungary

Ospedale Bellaria

Bologna, Emilia-Romagna, Italy

Fondazione Policlinico Universitario A Gemelli

Rome, Lazio, Italy

ASST di Pavia - Fondazione Istituto Neurologico Mondino IRCCS

Pavia, Lombardy, Italy

Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN

Florence, Tuscany, Italy

Aichi Medical University Hospital

Nagakute-Shi, Aiti, Japan

Fukuoka Children's Hospital

Fukuoka, Hukuoka, Japan

Kumamoto-Ezuko Medical Center for The Severely Disabled

Kumamoto, Kumamoto, Japan

National Hospital Organization Nagasaki Medical Center

Omura-Shi, Nagasaki, Japan

National Hospital Organization Nishi-Niigata Chuo National Hospital

Niigata, Niigata, Japan

Okayama University Hospital

Okayama, Okayama-ken, Japan

Yasuhara Childrens Clinic

Neyagawa, Osaka, Japan

Osaka City General Hospital

Osaka, Osaka, Japan

Osaka University Hospital

Suita-Shi, Osaka, Japan

National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders

Shizuoka, Shizuoka, Japan

National Center of Neurology and Psychiatry

Kodaira-Shi, Tokyo, Japan

Childrens University Hospital

Riga, , Latvia

Kempenhaeghe - PPDS

Heeze, North Brabant, Netherlands

Stichting Epilepsie Instellingen Nederland

Zwolle, Overijssel, Netherlands

Centrum Medyczne Plejady

Krakow, Lesser Poland Voivodeship, Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

Poznan, , Poland

UGMK-Zdorojie, LLC

Yekaterinburg, , Russia

Clinic for Neurology and Psychiatry for Children and Youth

Belgrade, , Serbia

Mother and Child Health Care Institute of Serbia Dr Vukan Cupic

Belgrade, , Serbia

University Clinical Center Nis

Niš, , Serbia

Children and Youth Health Care Institute of Vojvodina

Novi Sad, , Serbia

Clinica Universidad Navarra

Pamplona, Navarre, Spain

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, , Spain

Hospital Regional Universitario de Malaga Hospital General

Málaga, , Spain

Centro de Neurologia Avanzada

Seville, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Municipal Institution Dnipropetrovsk Regional Children Clinical Hospital of DRC

Dnipro, Dnipropetrovsk Oblast, Ukraine

Communal Non-profit Enterprise City Childrens Clinical Hospital #6 of DCC

Dnipro, Dnipropetrovsk Oblast, Ukraine

Communal Non-commercial Enterprise Iv-Frank Regional Childrens Clinical Hosp of Iv-Frank RC

Ivano-Frankivsk, , Ukraine

CNPE Clinical Hospital Psychiatry of the Executive Body of the Kyiv City Council KCSA

Kyiv, , Ukraine

SI Ukr. Med. Rehabilitation Center For Children With Organic Injury of Nervous System of MoH of Ukr

Kyiv, , Ukraine

Countries

United States; Australia; Belgium; Canada; China; France; Germany; Greece; Hungary; Italy; Japan; Latvia; Netherlands; Poland; Russia; Serbia; Spain; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/60e30ebd1f1122001e30a940

Related Info

Other Identifiers

2021-002481-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

jRCT2051210073

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-935-3002

Identifier Type: -

Identifier Source: org_study_id