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

NCT04938427 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: TAK-935-30022021-002481-40jRCT2051210073
• Study Type: interventional
• Target: 270
• Locations: 18 countries
• Sites: 98

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.

Conditions

Lennox Gastaut Syndrome (LGS)

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days During the Full Treatment Period

  MMD seizure frequency per 28 days was defined as the total number of MMD seizures reported during the period divided by the number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during the full Treatment Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100.

  Baseline; Full Treatment Period: Weeks 1 to 16

• Percent Change From Baseline in Major Motor Drop (MMD) Seizure Frequency Per 28 Days During the Maintenance Period

  MMD seizure frequency per 28 days was defined as the total number of MMD seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline was defined as (frequency of seizures per 28 days during the Maintenance Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100.

  Baseline; Maintenance Period: Weeks 5 to 16

Secondary Outcomes (13)

• Percentage of Responders During the Maintenance Period

  Maintenance Period: Weeks 5 to 16

• Percentage of Responders During the Full Treatment Period

  Full Treatment Period: Weeks 1 to 16

• Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, >75% to ≤100% Reduction in MMD Seizure During the Full Treatment Period

  Full Treatment Period: Weeks 1 to 16

• Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16

  Week 16

• Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16

  Week 16

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Soticlestat

EXPERIMENTAL

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.

Drug: Soticlestat

Interventions

Placebo DRUG

Soticlestat placebo-matching mini-tablets or tablets.

Placebo

Soticlestat DRUG

Soticlestat mini-tablets or tablets.

Also known as: TAK-935

Soticlestat

Eligibility Criteria

• Age: 2 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Has documented clinical diagnosis of LGS.
• 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.
• Weighs ≥10 kg at the Screening Visit (Visit 1).
• 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).
• 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.)
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (98)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Center For Neurosciences

Tucson, Arizona, 85718, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

University of California Benioff Children's Hospital

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado.

Denver, Colorado, 80218, United States

Location

Pediatric Neurology PA

Winter Park, Florida, 32789, United States

Location

Clinical Integrative Research Center of Atlanta

Atlanta, Georgia, 30328, United States

Location

University of Iowa Hospitals & Clinics - (CRS)

Iowa City, Iowa, 52242, United States

Location

Midatlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Minnesota Epilepsy Group PA

Roseville, Minnesota, 55113, United States

Location

Institute of Neurology and Neurosurgery at Saint Barnabas, LLC

Livingston, New Jersey, 07039, United States

Location

Premier Healthcare Inc.

New York, New York, 10001, United States

Location

NYU Comprehensive Epilepsy Center

New York, New York, 10016, United States

Location

Northwell Health Physician Partners - Neurology at Lenox Hill

New York, New York, 10075, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

WellSpan Oncology Research

York, Pennsylvania, 17403, United States

Location

Medical University of South Carolina Children Hospital - PIN

Charleston, South Carolina, 29425, United States

Location

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

Fort Worth, Texas, 76104, United States

Location

University of Utah - Primary Children's Hospital - PPDS

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MultiCare Institute for Research & Innovation (Tacoma)

Tacoma, Washington, 98402, United States

Location

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

Location

Queensland Childrens Hospital

South Brisbane, Queensland, 4101, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

UZ Antwerpen PIN

Edegem, Antwerpen, 2650, Belgium

Location

Centre Neurologique William Lennox

Ottignies-Louvain-la-Neuve, Brabant Wallon, 1340, Belgium

Location

Hopital Universitaire des Enfants Reine Fabiola

Brussels, Belgium

Location

Alberta Childrens Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Child and Family Research Institute

Vancouver, British Columbia, V5Z 4H4, Canada

Location

Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Beijing Children's Hospital,Capital Medical University

Beijing, Beijing Municipality, 100045, China

Location

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400014, China

Location

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510260, China

Location

Guangzhou Women And Children's Medical Center

Guangzhou, Guangdong, 510623, China

Location

Shenzhen Children's Hospital

Shenzhen, Guangdong, 518026, China

Location

Wuhan Childrens hospital

Wuhan, Hubei, 430010, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

Location

Jiangxi Provincial Children's Hospital

Nanchang, Jiangxi, 330006, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Children's Hospital of Shanghai

Shanghai, Shanghai Municipality, 200040, China

Location

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

Location

CHRU Dijon Hopital General

Dijon, Cote-d'Or, 21079, France

Location

Hopital Roger Salengro

Lille, Nord, 59000, France

Location

Hopitaux de La Timone

Marseille, 13386, France

Location

Hopital Necker - Enfants Malades

Paris, 75015, France

Location

Hopital Robert Debre

Paris, 75019, France

Location

Schon Klinik Vogtareuth

Vogtareuth, Bavaria, 83569, Germany

Location

Klinikum der Johann-Wolfgang Goethe-Universitat

Frankfurt am Main, Hesse, 60528, Germany

Location

Krankenhaus Mara gGmbH - Epilepsiezentrum Bethel

Bielefeld, North Rhine-Westphalia, 33617, Germany

Location

Kleinwachau Sachsisches Epilepsiezentrum Radeberg Gemeinnutzige Gmbh

Radeberg, Sachse, 1454, Germany

Location

Attikon University General Hospital

Chaïdári, Attica, 124 62, Greece

Location

University General Hospital of Larissa

Larissa, 411 10, Greece

Location

Hippokration Hospital

Thessaloniki, 546 42, Greece

Location

Pecsi Tudomanyegyetem

Pécs, Baranya, 7623, Hungary

Location

Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak

Budapest, 1023, Hungary

Location

Bethesda Gyermekkorhaz

Budapest, 1143, Hungary

Location

Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet

Budapest, 1145, Hungary

Location

Ospedale Bellaria

Bologna, Emilia-Romagna, 40139, Italy

Location

Fondazione Policlinico Universitario A Gemelli

Rome, Lazio, 168, Italy

Location

ASST di Pavia - Fondazione Istituto Neurologico Mondino IRCCS

Pavia, Lombardy, 27100, Italy

Location

Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN

Florence, Tuscany, 50139, Italy

Location

Aichi Medical University Hospital

Nagakute-Shi, Aiti, 480-1195, Japan

Location

Fukuoka Children's Hospital

Fukuoka, Hukuoka, 813-0017, Japan

Location

Kumamoto-Ezuko Medical Center for The Severely Disabled

Kumamoto, Kumamoto, 862-0947, Japan

Location

National Hospital Organization Nagasaki Medical Center

Omura-Shi, Nagasaki, 856-0835, Japan

Location

National Hospital Organization Nishi-Niigata Chuo National Hospital

Niigata, Niigata, 950-2074, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Yasuhara Childrens Clinic

Neyagawa, Osaka, 572-0085, Japan

Location

Osaka City General Hospital

Osaka, Osaka, 534-0021, Japan

Location

Osaka University Hospital

Suita-Shi, Osaka, 565-0871, Japan

Location

National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders

Shizuoka, Shizuoka, 420-0953, Japan

Location

National Center of Neurology and Psychiatry

Kodaira-Shi, Tokyo, 187-0031, Japan

Location

Childrens University Hospital

Riga, LV-1004, Latvia

Location

Kempenhaeghe - PPDS

Heeze, North Brabant, 5591 VE, Netherlands

Location

Stichting Epilepsie Instellingen Nederland

Zwolle, Overijssel, 8025 BV, Netherlands

Location

Centrum Medyczne Plejady

Krakow, Lesser Poland Voivodeship, 30-363, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

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

Poznan, 60-355, Poland

Location

UGMK-Zdorojie, LLC

Yekaterinburg, 620144, Russia

Location

Clinic for Neurology and Psychiatry for Children and Youth

Belgrade, 11000, Serbia

Location

Mother and Child Health Care Institute of Serbia Dr Vukan Cupic

Belgrade, 11000, Serbia

Location

University Clinical Center Nis

Niš, 18 000, Serbia

Location

Children and Youth Health Care Institute of Vojvodina

Novi Sad, 21 000, Serbia

Location

Clinica Universidad Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, 8035, Spain

Location

Hospital Regional Universitario de Malaga Hospital General

Málaga, 29010, Spain

Location

Centro de Neurologia Avanzada

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Municipal Institution Dnipropetrovsk Regional Children Clinical Hospital of DRC

Dnipro, Dnipropetrovsk Oblast, 49100, Ukraine

Location

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

Dnipro, Dnipropetrovsk Oblast, 49101, Ukraine

Location

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

Ivano-Frankivsk, 76018, Ukraine

Location

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

Kyiv, 4080, Ukraine

Location

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

Kyiv, 4209, Ukraine

Location

Related Links

• Related Info

MeSH Terms

Conditions

Lennox Gastaut Syndrome

Interventions

soticlestat

Condition Hierarchy (Ancestors)

Epileptic Syndromes; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2021
• First Posted: June 24, 2021
• Study Start: November 8, 2021
• Primary Completion: January 25, 2024
• Study Completion: January 25, 2024
• Last Updated: August 21, 2024
• Results First Posted: August 21, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

CA (3); CN (12); JP (11); UA (5); DE (4); ES (5); GR (3); BE (3); NL (2); AU (4); HU (4); RU (1); LA (1); PL (3); IT (4); SE (4); FR (5); US (24)