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JRCT ID: jRCT2051210182

Registered date:02/03/2022

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

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Dravet Syndrome (DS), Lennox Gastaut Syndrome (LGS)
Date of first enrollment	04/03/2022
Target sample size	400
Countries of recruitment	Australia,Japan,Belgium,Japan,Canada,Japan,China,Japan,Spain,Japan,France,Japan,United Kingdom,Japan,Greece,Japan,Hungary,Japan,Italy,Japan,Latvia,Japan,Netherlands,Japan,Poland,Japan,Serbia,Japan,Russia,Japan,Ukraine,Japan,USA,Japan
Study type	Interventional
Intervention(s)	Participants with DS and LGS will receive: Participants weighing <45 kg: 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 enteral feeding tubes including but not limited to nasogastric(NG)-tube, gastrostomy tube (G-tube),MIC-KEY button, up to 2 weeks in Titration Period. Will continue to receive dose they are on at end of Titration Period, for approximately 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/ adults: Soticlestat mini-tablets/ 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 approximately 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.

TO Original Data: JRCT

Outcome(s)

Primary Outcome	1.Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE) Time Frame: 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) Score Time Frame: Up to 4 years C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) to 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation. 3.Change from Baseline in Body Weight for All Age Groups Time Frame: Up to 4 years 4.Change from Baseline in Height for All Age Groups Time Frame: Up to 4 years 5.Absolute Value for Tanner Stage for Children 6 to 17 Years of Age During the Study Time Frame: 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). 6.Absolute Value for Insulin-like Growth Factor 1 (IGF-1) for Children 2 to 17 Years of Age During the Study Time Frame: Up to 4 years
Secondary Outcome	1.Percent Change from Baseline in Total Seizure Frequency per 28 Days for DS and LGS Participants Time Frame: 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 Time Frame: 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 Time Frame: 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 Time Frame: 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 Time Frame: 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 Time Frame: 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 Time Frame: 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 Time Frame: 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.

Primary Outcome

1.Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE) Time Frame: 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) Score Time Frame: Up to 4 years C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) to 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation. 3.Change from Baseline in Body Weight for All Age Groups Time Frame: Up to 4 years 4.Change from Baseline in Height for All Age Groups Time Frame: Up to 4 years 5.Absolute Value for Tanner Stage for Children 6 to 17 Years of Age During the Study Time Frame: 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). 6.Absolute Value for Insulin-like Growth Factor 1 (IGF-1) for Children 2 to 17 Years of Age During the Study Time Frame: Up to 4 years

Secondary Outcome

1.Percent Change from Baseline in Total Seizure Frequency per 28 Days for DS and LGS Participants Time Frame: 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 Time Frame: 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 Time Frame: 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 Time Frame: 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 Time Frame: 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 Time Frame: 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 Time Frame: 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 Time Frame: 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.

Key inclusion & exclusion criteria

Age minimum	>= 2age old
Age maximum	<= 56age old
Gender	Both
Include criteria	1. Participant must have: Been previously enrolled in a phase 3 soticlestat clinical study.
Exclude 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 Columbia-Suicide Severity Rating Scale (C-SSRS) before dosing are excluded. This scale will only be administered to participants aged >=6 years.

Related Information

Primary Sponsor	Nonomura Hidenori
Secondary Sponsor
Source(s) of Monetary Support
Secondary ID(s)	NCT05163314,2021-002482-17,2022-502802-34-00

Contact

Public contact
Name	Trial Information Contact for Clinical
Address	1-1, Doshomachi 4-chome, Chuo-ku, Osaka Osaka Japan 540-8645
Telephone	+81-6-6204-2111
E-mail	smb.Japanclinicalstudydisclosure@takeda.com
Affiliation	Takeda Pharmaceutical Company Limited
Scientific contact
Name	Hidenori Nonomura
Address	1-1, Doshomachi 4-chome, Chuo-ku, Osaka Osaka Japan 540-8645
Telephone	+81-6-6204-2111
E-mail	smb.Japanclinicalstudydisclosure@takeda.com
Affiliation	Takeda Pharmaceutical Company Limited

TO Original Data: JRCT