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

Sponsor
Takeda (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05163314
Collaborator
(none)
376
Enrollment
88
Locations
1
Arm
39.2
Anticipated Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

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 seizures in children and adults with Dravet Syndrome (DS) or Lennox-Gastaut Syndrome (LGS).

Participants will receive their standard anti-seizure therapy, plus tablets of soticlestat. There will be scheduled visits and follow-up phone calls throughout the study.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

The drug being tested in this study is called soticlestat (TAK-935). Soticlestat administered long-term in pediatric and adult participants who participated in either of the antecedent Phase 3 clinical studies, TAK-935-3001 [NCT04940624] (participants with DS) or TAK-935-3002 [NCT04938427] (participants with LGS) will be assessed for additional safety and tolerability data along with efficacy analysis.

The study will enroll approximately 376 participants.

All participants will receive soticlestat based on their weight in the 2-week Titration Period. Following the Titration Period, participants will continue to receive the same dose in the Maintenance Period. At the end of maintenance period, the dose will be down-tapered (unless already at the lowest dose) and then stopped. Participants not tolerating minimum dose of 100 mg twice a day (BID) will be discontinued from the study.

This multi-center trial will be conducted worldwide. The overall time to participate in the study will be approximately 4 years, or until the study is stopped at the discretion of the sponsor, or the product is approved for marketing. Participants who discontinue study drug treatment before the completion of the study, will continue to be followed per protocol and maintain a daily seizure diary until the final follow-up phone call

Study Design

Study Type:
Interventional
Anticipated Enrollment :
376 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Prospective, Open-Label, Multisite, Extension of Phase 3 Studies To Assess the Long-Term Safety and Tolerability of Soticlestat as Adjunctive Therapy in Subjects With Dravet Syndrome or Lennox-Gastaut Syndrome (ENDYMION 2)
Actual Study Start Date :
Mar 4, 2022
Anticipated Primary Completion Date :
Jun 8, 2025
Anticipated Study Completion Date :
Jun 8, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Soticlestat

Participants with DS and LGS will receive: Participants weighing <45kg: Soticlestat, mini-tablets, titrated from lower dose level (60mg to 140mg) to higher dose (100mg to 200mg) twice daily (BID), based on body weight, orally/via gastrostomy tube (G-tube) or percutaneous endoscopic gastrostomy (PEG) tube, up to 2 weeks in Titration Period. Will continue to receive dose that they are on at the end of Titration Period, for approx. 4 years in Maintenance Period. Dose will be tapered down to lower dose (not less than the lowest dose level based on weight) every 3 days until study drug is discontinued (up to 1 week) in Taper Period. Participants weighing ≥45kg or adults: Soticlestat mini-tablets or tablets with starting dose of 200 mg BID followed by 300 mg BID, up to 2 weeks in Titration Period. Will continue to receive 300 mg BID for approx. 4 years in Maintenance Period. Dose will be tapered down up to 100 mg every 3 days until study drug is discontinued (up to 1 week) in Taper Period.

Drug: Soticlestat
Soticlestat mini-tablets or tablets
Other Names:
  • TAK-935

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE) [Up to 4 years]

      An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.

    2. Change from Baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS) Categorization Based on Columbia Classification Algorithm of Suicide Assessment Categories 1, 2, 3, 4, and 5 for Participants Aged ≥6 Years [Up to 4 years]

    3. Change from Baseline in Body Weight for All Age Groups [Up to 4 years]

    4. Change from Baseline in Height for All Age Groups [Up to 4 years]

    5. Change from Baseline in Insulin-like Growth Factor 1 (IGF-1) for Children Aged 2 to 17 Years [Up to 4 years]

    6. Change from Baseline in Tanner Stage for Children Aged 6 to 17 Years [Up to 4 years]

      Tanner assessment score is used to document the stage of development of puberty by assessing the secondary sexual characteristics, rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size).

    Secondary Outcome Measures

    1. Percent Change from Baseline in Total Seizure Frequency per 28 Days for DS and LGS Participants [Up to 4 years]

      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.

    2. Percent Change from Baseline in Convulsive Seizure Frequency per 28 Days in DS Cohort [Up to 4 years]

      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 convulsive seizures per 28 days during Treatment Period - frequency of convulsive seizures per 28 days at Baseline) divided by the frequency of convulsive seizures per 28 days at Baseline multiplied by 100.

    3. Percent Change from Baseline in Major Motor Drop (MMD) Seizure Frequency per 28 Days in LGS Cohort [Up to 4 years]

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

    4. Clinical Global Impression of Improvement (CGI-I) Score [Up to 4 years]

      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.

    5. Caregiver Global Impression of Improvement (Care GI-I) Score [Up to 4 years]

      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.

    6. CGI-I Seizure Intensity and Duration Score [Up to 4 years]

      The CGI-I seizure intensity and duration instrument is used by the parent/caregiver to rate improvement in intensity and duration of convulsive seizures (DS Cohort) or MMD seizures (LGS Cohort) from Baseline. 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.

    7. CGI-I Nonseizure Symptoms Score [Up to 4 years]

      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.

    8. Change in Quality of Life Inventory-Disability (QI-Disability) Score [Up to 4 years]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 36 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Participant must have:
    • Been previously enrolled in soticlestat clinical study TAK-935-3001 (NCT04940624) or TAK-935-3002 (NCT04938427).
    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.

    2. Abnormal and clinically significant ECG abnormality at Visit 1 including QT interval with Fridericia correction method (QTcF) >450 milliseconds (ms) confirmed with a repeat ECG using manual measurement of QTcF.

    3. Participant is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property. Participants who have positive answers on item numbers 4 or 5 on the CSSRS before dosing are excluded. This scale will only be administered to participants aged ≥6 years.

    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 Colorado Children's Hospital Denver Colorado United States 80218
    5 Pediatric Neurology PA Winter Park Florida United States 32789
    6 Clinical Integrative Research Center of Atlanta Atlanta Georgia United States 30328
    7 University of Iowa Hospitals & Clinics - (CRS) Iowa City Iowa United States 52242
    8 Midatlantic Epilepsy and Sleep Center Bethesda Maryland United States 20817
    9 Minnesota Epilepsy Group PA Saint Paul Minnesota United States 55102
    10 Institute of Neurology and Neurosurgery at Saint Barnabas, LLC Livingston New Jersey United States 07039
    11 NYU Comprehensive Epilepsy Center New York New York United States 10016
    12 Oregon Health and Science University Portland Oregon United States 97239
    13 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    14 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    15 WellSpan Oncology Research York Pennsylvania United States 17403
    16 Medical University of South Carolina Children Hospital - PIN Charleston South Carolina United States 29425
    17 Cook Children's Medical Center - Jane and John Justin Neurosciences Center Fort Worth Texas United States 76104
    18 University of Utah - Primary Children's Hospital - PPDS Salt Lake City Utah United States 84113
    19 Seattle Children's Hospital Seattle Washington United States 98105
    20 MultiCare Institute for Research & Innovation (Tacoma) Tacoma Washington United States 98402
    21 Sydney Children's Hospital Randwick New South Wales Australia 2031
    22 Austin Hospital Heidelberg Victoria Australia 3084
    23 Alfred Hospital Melbourne Victoria Australia 3004
    24 UZ Antwerpen Edegem Antwerpen Belgium 2650
    25 Centre Neurologique William Lennox Ottignies-Louvain-la-Neuve Brabant Wallon Belgium 1340
    26 Hopital Universitaire des Enfants Reine Fabiola Brussel Brussels Belgium 1020
    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 Univeristy 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 of Central South University Changsha Hunan China 410008
    37 Jiangxi Provincial Children's Hospital Nanchang Jiangxi China 330006
    38 Children's Hospital of Shanghai Shanghai Shanghai China 200040
    39 Children's Hospital of Fudan University Shanghai Shanghai China 201102
    40 Hopital Roger Salengro Lille Nord France 59000
    41 Hopital Necker - Enfants Malades Paris France 75015
    42 Hopital Robert Debre Paris France 75019
    43 Childrens' Hospital of Athens 'P. and A. Kyriakou' Athens Attiki Greece 115 27
    44 Attikon University General Hospital Chaidari Attiki Greece 124 62
    45 University General Hospital of Larissa Larisa Greece 411 10
    46 Hippokration Hospital Thessaloniki Greece 546 42
    47 Pecsi Tudomanyegyetem Pecs Baranya Hungary 7623
    48 Bethesda Gyermekkorhaz Budapest Hungary 1143
    49 Orszagos Klinikai Idegtudomanyi Intezet Budapest Hungary 1145
    50 ASST di Mantova - Azienda Ospedaliera Carlo Poma Mantova Lombardia Italy 46100
    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 Vithas La Salud Granada Spain 18008
    83 Hospital Universitari i Politecnic La Fe de Valencia Valencia Spain 46026
    84 Municipal Institution Dnipropetrovsk Regional Children Clinical Hospital of DRC Dnipro Dnipropetrovs'ka Oblast Ukraine 49100
    85 Communal Non-profit Enterprise Dnipro City Children Clinical Hospital #5 of DCC Dnipro Dnipropetrovs'ka Oblast Ukraine 49101
    86 Communal Non-commercial Enterprise Iv-Frank Regional Childrens Clinical Hosp of Iv-Frank RC Ivano-Frankivsk Ukraine 76018
    87 CNPE Clinical Hospital Psychiatry of the Executive Body of the Kyiv City Council KCSA Kyiv Ukraine 4080
    88 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:
    NCT05163314
    Other Study ID Numbers:
    • TAK-935-3003
    • 2021-002482-17
    • jRCT2051210182
    First Posted:
    Dec 20, 2021
    Last Update Posted:
    Apr 12, 2022
    Last Verified:
    Apr 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
    Keywords provided by Takeda
    Drug Therapy
    Additional relevant MeSH terms:
    Epilepsies, Myoclonic
    Lennox Gastaut Syndrome
    Syndrome

    Study Results

    No Results Posted as of Apr 12, 2022