A Study of Soticlestat as an Add-on Therapy in Children and Young Adults With Dravet Syndrome

NCT04940624 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: TAK-935-3001jRCT20512100742021-002480-22
• Study Type: interventional
• Target: 144
• Locations: 18 countries
• Sites: 66

Brief Summary

The main aim of the study is to learn if soticlestat, when given as an add-on therapy, reduces the number of convulsive seizures in children and young adults with DS. Participants will receive their standard antiseizure therapy, plus either a tablet of soticlestat or placebo for 16 weeks. A placebo looks just like soticlestat but will not have any medicine in it. Participants may continue treatment in an extension study, based on the extension study's entry criteria. Those that want to stop treatment will have a gradual dose reduction during 1 week and then be followed up for 2 weeks.

Conditions

Dravet Syndrome (DS)

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Full Treatment Period

  Convulsive seizure frequency per 28 days was defined as the total number of convulsive 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 Convulsive Seizure Frequency Per 28 Days During the Maintenance Period

  Convulsive seizure frequency per 28 days was defined as the total number of convulsive 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 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 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%, and >75% to ≤100% Reduction in Convulsive Seizures 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 gastrostomy tube (G-tube) or low-profile gastric tube (MIC-KEY) button or jejunostomy tube (J-tube), twice daily (BID), up to 4 weeks during titration. Participants continued to receive the 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 the 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 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 dose tapered down if participants decided to discontinue the treatment.

Drug: Soticlestat

Interventions

Soticlestat DRUG

Soticlestat mini-tablets or tablets.

Also known as: TAK-935

Soticlestat

Placebo DRUG

Soticlestat placebo-matching mini-tablets or tablets.

Placebo

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Has documented clinical diagnosis of DS.
• Had ≥12 convulsive seizures over 12 weeks before screening based on the historical information and has had ≥4 convulsive 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 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 4 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. Fenfluramine and cannabidiol (Epidiolex) are allowed where available and should be 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (66)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016-7710, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095-3075, United States

Location

University of California Benioff Children's Hospital

San Francisco, California, 94143-2350, United States

Location

Clinical Integrative Research Center of Atlanta

Atlanta, Georgia, 30328, United States

Location

University of Iowa Hospitals & Clinics - (CRS)

Iowa City, Iowa, 52242-1009, United States

Location

NYU Comprehensive Epilepsy Center

New York, New York, 10016, United States

Location

University of Toledo

Toledo, Ohio, 43606-3818, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105-3901, United States

Location

Multicare Health System - Mary Bridge Pediatrics

Tacoma, Washington, 98405, United States

Location

Queensland Childrens Hospital

South Brisbane, Queensland, 4101, Australia

Location

Instituto de Neurologia de Curitiba (INC)

Curitiba, Paraná, 81210-310, Brazil

Location

Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Universidade de Sao Paulo

São Paulo, 04039-032, Brazil

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

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

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

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

Attikon University General Hospital

Chaïdári, Attica, 124 62, Greece

Location

Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet

Budapest, 1145, Hungary

Location

IRCCS Ospedale Pediatrico Bambino Gesu - INCIPIT - PIN

Rome, Lazio, 164, 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

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

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

Hokkaido University Hospital

Chuo-Ku, Tokyo, 104-0045, 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

Neurosphera SP. Z O.O

Warsaw, Masovian Voivodeship, 02-952, 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

Russian National Research Medical University n.a. N.I.Pirogov

Moscow, Moscow, 117437, Russia

Location

Krasnoyarsk State Medical University n.a. V.F. Voyno-Ysenetskiy

Krasnoyarsk, 660022, 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

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, 8035, Spain

Location

Hospital Regional Universitario de Malaga Hospital General

Málaga, 29010, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

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

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Epilepsies, Myoclonic

Interventions

soticlestat

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study 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 16, 2021
• First Posted: June 25, 2021
• Study Start: October 28, 2021
• Primary Completion: April 11, 2024
• Study Completion: April 11, 2024
• Last Updated: January 1, 2025
• Results First Posted: January 1, 2025

Record last verified: 2024-12

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

UA (3); LA (1); US (10); HU (1); JP (9); BR (3); CA (3); CN (10); IT (4); NL (2); PL (4); GR (1); RU (2); SE (3); ES (3); FR (3); AU (1); DE (3)