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

Sponsor
Takeda (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04940624
Collaborator
(none)
142
87
2
16.2
1.6
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
142 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official 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 Young Adult Subjects With Dravet Syndrome (DS)
Actual Study Start Date :
Oct 28, 2021
Anticipated Primary Completion Date :
Mar 5, 2023
Anticipated Study Completion Date :
Mar 5, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Soticlestat

Participants weighing <45kg: Soticlestat, mini-tablets, at the dose of 40mg to 200mg, orally or via gastrostomy tube (G-tube) or low-profile gastric tube (MIC-KEY button) or jejunostomy tube (J-tube), twice daily (BID) based on the body weight up to 4 weeks in Titration Period. Participants will continue to receive dose that they are on at the end of Titration Period, for 12 weeks in Maintenance Period. The total duration of the treatment will be up to 16 weeks (Treatment Period). The dose will be tapered down if participants decide to discontinue the treatment. Participants weighing ≥45kg: Soticlestat mini-tablets or tablets with a starting dose of 100mg BID followed by 200 mg BID and, then 300mg BID, up to 4 weeks in Titration Period. Participants will continue to receive 300mg BID for 12 weeks in the Maintenance Period. The total duration of the treatment will be up to 16 weeks (Treatment Period). The dose will be tapered down if participants decide to discontinue the treatment.

Drug: Soticlestat
Soticlestat mini-tablets or tablets.
Other Names:
  • TAK-935
  • Placebo Comparator: 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 in the Titration Period. Participants will continue to receive the soticlestat placebo-matching mini-tablets or tablets for 12 weeks in the Maintenance Period. The total duration of the treatment will be up to 16 weeks. Soticlestat matching tapering will be done to maintain the blind if participants decide to discontinue the treatment.

    Drug: Placebo
    Soticlestat placebo-matching mini-tablets or tablets.

    Outcome Measures

    Primary Outcome Measures

    1. Percent Change From Baseline in Convulsive Seizure Frequency per 28 days During the Full Treatment Period [Baseline up to Week 16]

      Convulsive seizure frequency per 28 days is defined as 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 will be defined as (frequency of seizures per 28 days during Treatment Period - frequency of seizures per 28 days at Baseline) divided by the frequency of seizures per 28 days at Baseline multiplied by 100.

    2. Percent Change From Baseline in Convulsive Seizure Frequency per 28 days During the Maintenance Period (EMA Region Specific) [Baseline up to Week 16]

      Convulsive seizure frequency per 28 days is defined as 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 will be 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. This outcome measure is European Medicines Agency (EMA) specific.

    Secondary Outcome Measures

    1. Percentage of Responders During Maintenance Period [Baseline up to Week 16]

      Responders are defined as those with ≥50% reduction from baseline in convulsive seizures during the Maintenance Period.

    2. Percentage of Responders During the Full Treatment Period [Baseline up to Week 16]

      Responders are defined as those with ≥50% reduction from baseline in convulsive seizures during the full Treatment Period.

    3. Percentage of Participants with ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures in a Cumulative Response Curve [Baseline up to Week 16]

    4. Caregiver Global Impression of Improvement (Care GI-I) Score [Baseline up to Week 16]

      The Care GI-I is a 7-point Likert scale that the caregiver uses to rate improvement in overall seizure control, behavior, safety and tolerability after the initiation of study drug relative to Baseline (before treatment with study drug). The participant will be rated as follows: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), and 7 (very much worse). The parent/caregiver will complete the Care GI-I via interview. Higher score will indicate worse symptoms.

    5. Clinical Global Impression of Improvement (CGI-I) Score [Baseline up to Week 16]

      The CGI-I Clinician is a 7-point Likert scale that the investigator uses to rate a participant's change (improvement) in overall seizure control, behavior, safety and tolerability, after the initiation of study drug relative to Baseline (before treatment with study drug). The participant will be rated as follows: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), and 7 (very much worse). Higher score will indicate worse symptoms.

    6. CGI-I Nonseizure Symptoms Score [Baseline up to Week 16]

      The CGI-I nonseizure symptoms instrument is a series of single-item assessments that the investigator uses to rate improvement in the symptoms and impacts in select nonseizure domains since initiating the study drug. The participant will be rated on 7-point scale by the investigator as follows: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), and 7 (very much worse). At baseline, a symptoms form is completed by the clinician in collaboration with the primary caregiver to assess the participants status based on the presence of any nonseizure symptoms. Higher score will indicate worse symptoms.

    7. Change in Quality of Life Inventory-Disability (QI-Disability) Score [Baseline up to Week 16]

      The QI-Disability tool is a parent/caregiver-reported questionnaire that evaluates quality of life in children with intellectual disabilities. It contains 32 items covering 6 domains of quality of life: physical health, positive emotions, negative emotions, social interaction, leisure and the outdoors, and independence. Scores are from a 5-point Likert scale and then are transformed to a scale of 0 to 100. Possible scores range from 0-100, with higher scores indicating better quality of life.

    8. CGI-I Seizure Intensity and Duration Score [Baseline up to Week 16]

      The CGI-I seizure Intensity and duration instrument is used by the parent/caregiver to rate improvement in intensity and/or duration of the most impactful seizures from the first assessment. The participant's symptoms will be rated on 7-point scale as follows: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), and 7 (very much worse). Higher score will indicate worse symptoms.

    9. Percent Change From Baseline in Frequency of all Seizures per 28 Days During the Maintenance Period [Baseline up to Week 16]

      Seizure frequency per 28 days is defined as total number of seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline is 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.

    10. Percent Change From Baseline in Frequency of all Seizures per 28 Days During the Full Treatment Period [Baseline up to Week 16]

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

    11. Percent Change From Baseline in Convulsive Seizure Frequency per 28 days During the Maintenance Period [Baseline up to Week 16]

      Convulsive seizure frequency per 28 days is defined as 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 is defined as (frequency of seizures per 28 days during Maintenance Period - frequency of seizures per 28 days at Baseline) divided by frequency of seizures per 28 days at Baseline multiplied by 100.

    12. Change from Baseline in Percentage of Convulsive Seizure-free Days [Baseline up to Week 16]

      Convulsive seizure-free days will be defined as number of days a participant remained convulsive seizure free after initiation of the treatment.

    13. Longest Convulsive Seizure-free Interval. [Baseline up to Week 16]

      Longest convulsive seizure-free interval will be defined as the longest time period that the participant remained convulsive seizure free after initiation of the treatment.

    14. Number of Days When Rescue Antiseizure Medication (ASM) is Used [Baseline up to Week 16]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 21 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Phoenix Childrens Hospital Phoenix Arizona United States 85016
    2 David Geffen School of Medicine at UCLA Los Angeles California United States 90095
    3 University of California Benioff Children's Hospital San Francisco California United States 94143
    4 NW FL Clinical Research Group, LLC - ClinEdge - PPDS Gulf Breeze Florida United States 32561
    5 Pediatric Neurology PA Winter Park Florida United States 32789
    6 Clinical Integrative Research Center of Atlanta Atlanta Georgia United States 30328
    7 Sunrise Pediatric Neurology Marietta Georgia United States 30066
    8 University of Iowa Hospitals & Clinics - (CRS) Iowa City Iowa United States 52242
    9 NYU Comprehensive Epilepsy Center New York New York United States 10016
    10 Nationwide Children's Hospital Columbus Ohio United States 43205
    11 University of Toledo Toledo Ohio United States 43606
    12 Oregon Health and Science University Portland Oregon United States 97239
    13 Medical University of South Carolina Charleston South Carolina United States 29403
    14 Cook Children's Medical Center Fort Worth Texas United States 76104
    15 Childrens National Medical Center - Fairfax Fairfax Virginia United States 22031
    16 Seattle Children's Hospital Seattle Washington United States 98105
    17 Multicare Health System - Mary Bridge Pediatrics Tacoma Washington United States 98405
    18 Sydney Children's Hospital Randwick New South Wales Australia 2031
    19 Austin Hospital Heidelberg Victoria Australia 3084
    20 Alfred Hospital Melbourne Victoria Australia 3004
    21 UZ Antwerpen PIN Edegem Antwerpen Belgium 2650
    22 Hopital Universitaire des Enfants Reine Fabiola Brussels Belgium
    23 Hospital das Clinicas - UNICAMP Campinas Sao Paulo Brazil 13083-888
    24 Universidade Federal de Sao Paulo Vila Clementino Sao Paulo Brazil 04023-062
    25 Universidade de Sao Paulo Sao Paulo Brazil 04039-032
    26 Alberta Childrens Hospital Calgary Alberta Canada T3B 6A8
    27 Child and Family Research Institute Vancouver British Columbia Canada V5Z 4H4
    28 Hospital For Sick Children Toronto Ontario Canada M5G 1X8
    29 Peking University First Hospital Beijing Beijing China 100034
    30 Beijing Children's Hospital,Capital Medical University Beijing Beijing China 100045
    31 Children's Hospital of Chongqing Medical University Chongqing Chongqing China 400014
    32 The Second Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong China 510260
    33 Guangzhou Women And Children's Medical Center Guangzhou Guangdong China 510623
    34 Shenzhen Children's Hospital Shenzhen Guangdong China 518026
    35 Wuhan Childrens hospital Wuhan Hubei China 430010
    36 Xiangya Hospital Central South University Changsha Hunan China 410008
    37 The First Hospital of Jilin University Changchun Jilin China 130021
    38 Children's Hospital of Shanghai Shanghai Shanghai China 200040
    39 Children's Hospital of Fudan University Shanghai Shanghai China 201102
    40 CHRU Dijon Hopital General Dijon Cote-d'Or France 21079
    41 Hopital Roger Salengro Lille Nord France 59000
    42 Hopitaux de La Timone Marseilles France 13386
    43 Hopital Necker - Enfants Malades Paris France 75015
    44 Hopital Robert Debre Paris France 75019
    45 Childrens' Hospital of Athens 'P. and A. Kyriakou' Athens Attiki Greece 115 27
    46 Attikon University General Hospital Chaidari Attiki Greece 124 62
    47 University General Hospital of Larissa Larisa Greece 411 10
    48 Hippokration Hospital Thessaloniki Greece 546 42
    49 Szent Janos Korhaz es Eszak-Budai Egyesitett Korhazak Budapest Hungary 1023
    50 Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet Budapest Hungary 1145
    51 ASST di Pavia - Fondazione Istituto Neurologico Mondino IRCCS Pavia Lombardia Italy 27100
    52 Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN Firenze Toscana Italy 50139
    53 Aichi Medical University Hospital Nagakute-Shi Aiti Japan 480-1195
    54 Fukuoka Children's Hospital Fukuoka-Shi Hukuoka Japan 813-0017
    55 Kumamoto-Ezuko Medical Center for The Severely Disabled Kumamoto-Shi Kumamoto Japan 862-0947
    56 National Hospital Organization Nagasaki Medical Center Omura-Shi Nagasaki Japan 856-0835
    57 National Hospital Organization Nishi-Niigata Chuo National Hospital Niigata-Shi Niigata Japan 950-2074
    58 Okayama University Hospital Okayama-city Okayama Japan 700-8558
    59 Yasuhara Childrens Clinic Neyagawa-Shi Osaka Japan 572-0085
    60 Osaka City General Hospital Osaka-Shi Osaka Japan 534-0021
    61 Osaka University Hospital Suita-Shi Osaka Japan 565-0871
    62 National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders Shizuoka-Shi Sizuoka Japan 420-0953
    63 National Center of Neurology and Psychiatry Kodaira-Shi Tokyo Japan 187-0031
    64 Childrens University Hospital Riga Latvia LV-1004
    65 Kempenhaeghe - PPDS Heeze Noord-Brabant Netherlands 5591 VE
    66 Stichting Epilepsie Instellingen Nederland Zwolle Overijssel Netherlands 8025 BV
    67 Centrum Medyczne Plejady Krakow Malopolskie Poland 30-363
    68 Dzieciecy Szpital Kliniczny im. Jozefa Polikarpa Brudzinskiego w Warszawie Warszawa Mazowieckie Poland 02-091
    69 Uniwersyteckie Centrum Kliniczne Gdansk Poland 80-952
    70 Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu Poznan Poland 60-355
    71 Russian National Research Medical University n.a. N.I.Pirogov Moscow Moskva Russian Federation 117437
    72 UGMK-Zdorojie, LLC Ekaterinburg Russian Federation 620144
    73 Krasnoyarsk State Medical University n.a. V.F. Voyno-Ysenetskiy Krasnoyarsk Russian Federation 660022
    74 Russian National Research Medical University n.a. N.I.Pirogov Moscow Russian Federation 125412
    75 Tyumen State Medical Academy Tyumen' Russian Federation 625023
    76 Clinic for Neurology and Psychiatry for Children and Youth Beograd Belgrade Serbia 11000
    77 Mother and Child Health Care Institute of Serbia Dr Vukan Cupic Belgrade Serbia 11000
    78 University Clinical Center Nis Nis Serbia 18 000
    79 Children and Youth Health Care Institute of Vojvodina Novi Sad Serbia 21 000
    80 Clinica Universidad Navarra Pamplona Navarra Spain 31008
    81 Hospital Universitario Vall d'Hebron - PPDS Barcelona Spain 8035
    82 Hospital Universitari i Politecnic La Fe de Valencia Valencia Spain 46026
    83 Municipal Institution Dnipropetrovsk Regional Children Clinical Hospital of DRC Dnipro Dnipropetrovs'ka Oblast Ukraine 49100
    84 Communal Non-profit Enterprise City Childrens Clinical Hospital #6 of DCC Dnipro Dnipropetrovs'ka Oblast Ukraine 49101
    85 Communal Non-commercial Enterprise Iv-Frank Regional Childrens Clinical Hosp of Iv-Frank RC Ivano-Frankivsk Ukraine 76018
    86 CNPE Clinical Hospital Psychiatry of the Executive Body of the Kyiv City Council KCSA Kyiv Ukraine 4080
    87 SI Ukr. Med. Rehabilitation Center For Children With Organic Injury of Nervous System of MoH of Ukr Kyiv Ukraine 4209

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT04940624
    Other Study ID Numbers:
    • TAK-935-3001
    • jRCT2051210074
    • 2021-002480-22
    First Posted:
    Jun 25, 2021
    Last Update Posted:
    Aug 10, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Takeda
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 10, 2022