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

NCT ID: NCT04940624

Last Updated: 2025-01-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-28
• Study Completion Date: 2024-04-11

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.

Detailed Description

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

The study will enroll approximately 142 pediatric and young adult patients. Participants will be randomized at a 1:1 ratio to receive standard of care (SOC) plus one of the following adjunctive therapies:

• Soticlestat or
• Placebo

The total daily dose of study drug will be calculated based on body weight in the 4 weeks Titration Period. Following the Titration Period, participants will continue to receive the same dose in the 12-weeks Maintenance Period.

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 Full 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

Dravet Syndrome (DS)

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 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.

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 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.

Group Type: EXPERIMENTAL

Soticlestat

Intervention Type: DRUG

Soticlestat mini-tablets or tablets.

Interventions

Soticlestat

Soticlestat mini-tablets or tablets.

Intervention Type: DRUG

Placebo

Soticlestat placebo-matching mini-tablets or tablets.

Intervention Type: DRUG

Other Intervention Names

TAK-935

Eligibility Criteria

Inclusion Criteria

1. Has documented clinical diagnosis of DS.

2. 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.

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 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 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.

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Phoenix Childrens Hospital

Phoenix, 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

Clinical Integrative Research Center of Atlanta

Atlanta, Georgia, United States

University of Iowa Hospitals & Clinics - (CRS)

Iowa City, Iowa, United States

NYU Comprehensive Epilepsy Center

New York, New York, United States

University of Toledo

Toledo, Ohio, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Seattle Children's Hospital

Seattle, Washington, United States

Multicare Health System - Mary Bridge Pediatrics

Tacoma, Washington, United States

Queensland Childrens Hospital

South Brisbane, Queensland, Australia

Instituto de Neurologia de Curitiba (INC)

Curitiba, Paraná, Brazil

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

Porto Alegre, Rio Grande do Sul, Brazil

Universidade de Sao Paulo

São Paulo, , Brazil

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

Shenzhen Children's Hospital

Shenzhen, Guangdong, China

Wuhan Childrens hospital

Wuhan, Hubei, China

Xiangya Hospital Central South University

Changsha, Hunan, 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

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

Attikon University General Hospital

Chaïdári, Attica, Greece

Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet

Budapest, , Hungary

IRCCS Ospedale Pediatrico Bambino Gesu - INCIPIT - PIN

Rome, Lazio, 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

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

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

Hokkaido University Hospital

Chuo-Ku, Tokyo, 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

Neurosphera SP. Z O.O

Warsaw, Masovian Voivodeship, Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

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

Poznan, , Poland

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

Moscow, Moscow, Russia

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

Krasnoyarsk, , 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

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, , Spain

Hospital Regional Universitario de Malaga Hospital General

Málaga, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

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

Countries

United States; Australia; Brazil; 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/60e40858ef0b71001e743e10

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

Other Identifiers

TAK-935-3001

Identifier Type: -

Identifier Source: org_study_id

jRCT2051210074

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-002480-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id