A Study of Soticlestat as an Add-on Therapy in Children and Young Adults With Dravet Syndrome
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 |
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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:
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Soticlestat or
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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
Arms and Interventions
Arm | Intervention/Treatment |
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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:
|
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
- 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.
- 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
- 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.
- 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.
- 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]
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Number of Days When Rescue Antiseizure Medication (ASM) is Used [Baseline up to Week 16]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Has documented clinical diagnosis of DS.
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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.
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Weighs ≥10 kg at the screening visit (Visit 1).
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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.
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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.).
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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:
- 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 | |
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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.- TAK-935-3001
- jRCT2051210074
- 2021-002480-22