A Multicenter, Open-label, Pilot Study of Soticlestat (TAK-935/OV935) in Participants With 15Q Duplication Syndrome (Dup 15q) or Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency Disorder (ARCADE STUDY)

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of soticlestat on the frequency of motor seizures for participants with Dup15q or CDD during the Maintenance Period.

Detailed Description
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The drug being tested in this study is called soticlestat. Soticlestat is being tested to treat people with Dup 15q or CDD. This study will assess the effects of TAK-935 on seizure frequency, safety. The study will enroll approximately 30 participants. Participants will be enrolled into 2 groups based on their diagnosis as: Dup 15q or CDD. All participants will be asked to take soticlestat tablets twice daily with or without food. The study comprises of 2 periods: Screening/Baseline Period and Treatment Period (Dose Optimization and Maintenance). The overall time to participate in this study is approximately 30 weeks, including 4 to 6 weeks Screening/Baseline Period, 20 weeks Treatment Period, 2 weeks Taper, and 2 weeks safety follow up period. Participants completing this study will have an option to enroll in the open-label extension (OLE) study, under a separate protocol.

Official Title
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A Multicenter, Open-label, Pilot Study of TAK-935 (OV935) in Patients With 15Q Duplication Syndrome or CDKL5 Deficiency Disorder (ARCADE Study)

Conditions
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15q Duplication Syndrome, CDKL5 Deficiency Disease

Intervention / Treatment
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* Drug: Soticlestat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Dup 15q or CDKL5 deficiency disorder. Currently taking 1 to 6 antiepileptic drugs (AEDs) at a stable dose. Exclusion Criteria: Two or more episodes of convulsive status epilepticus per 3 months requiring hospitalization and intubation. Currently receiving a study drug or participated in a clinical study involving another investigational product in the previous month.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Soticlestat Dup 15q<br>Soticlestat tablets twice daily (BID) orally or via gastrostomy tube (G-tube)/ percutaneous endoscopic gastrostomy (PEG) tube, BID. Participants with Dup 15q weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Drug: Soticlestat<br>* TAK-935 tablets<br>* Other names: TAK-935;|
| Experimental: Soticlestat CDD<br>Soticlestat tablets BID orally or via G-tube/ PEG tube, BID. Participants with CDD weighing <60 kg at Baseline received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20. | Drug: Soticlestat<br>* TAK-935 tablets<br>* Other names: TAK-935;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Maintenance Period | Seizure frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period 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. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease. | Maintenance Period: Weeks 9 to 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Treatment Period | Seizure frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during the treatment period - frequency of seizures per 28 days at Baseline) divided by frequency of seizures per 28 days at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease. | Treatment Period: Weeks 0 to 20 | 
| Percentage of Participants Considered as Treatment Responders During the Maintenance Period | Responders are defined as having over 50% motor seizure reduction compared to Baseline. Percent reduction from Baseline (%) is defined as [(Maintenance Period motor Seizure Frequency - Baseline Period motor Seizure Frequency) divided by Baseline motor Seizure Frequency] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in motor seizures from Baseline. | Maintenance Period: Weeks 9 to 20 | 
| Percent Change From Baseline in Frequency of Motor Seizures Longer Than 5 Minutes in Participants With CDD | Seizure frequency is defined as total number of Seizures reported during the period divided by number of days with no missing seizure count during the period. Percent Change from Baseline is defined as (frequency of seizures during Treatment period - frequency of seizures at Baseline) divided by frequency of seizures at Baseline multiplied by 100. Positive percent change from Baseline indicates seizure increase and negative percent change from Baseline indicates seizure decrease. The data is reported only for CDD participants. | Treatment Period: Weeks 0 to 20 | 
| Proportion of Motor Seizure-free Days in Participants During the Maintenance Period | Seizure-free days is defined as number of days with zero motor seizure during the period the Maintenance Period divided by number of days participant was in the Maintenance Period. | Maintenance Period: Weeks 9 to 20 | 
| Change From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator | The CGI-S focuses on clinician's observations of the participant's cognitive, functional, and behavioral performance since the beginning of the study. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses where, 1= normal, not at all ill, 2= borderline mentally ill, 3= mildly ill, 4= moderately ill, 5= markedly ill, 6= severely ill and 7=amongst the most extremely ill participants. Negative change from Baseline indicates improvement. | Baseline to Week 20 | 
| Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression | CGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 5-point scale, where, 0 = marked improvement and no side-effects, 1 = marked improvement and minimal side-effects, 2 = no change, 3 = minimal improvement and marked side-effects and 4 = unchanged or worse and side-effects outweigh the therapeutic effect. Lower scores indicated improvement. | Week 20 | 
| Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family | CGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 7-point scale where, 1 = very much improved, 2 = much improved, 3 = slightly improved, 4= no change, 5= slightly worse, 6= much worse and 7= very much worse and marked side-effects. Lower scores indicated improvement. | Week 20 | 
| Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels |  | Baseline to Week 20 | 
| Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy | Seizure Frequency per 28 days is defined as total number of Seizures reported during the period divided by number of days with no missing seizure during the period seizures were assessed multiplied by 28. Positive change from Baseline indicates seizure increase and negative change from Baseline indicates seizure decrease. | Baseline to Week 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy, 15q Duplication Syndrome (Dup15q), CDKL5 Deficiency Disorder (CDD), Brain Diseases, Epilepsy, Central Nervous System Diseases, Autism, Cholesterol 24S-hydroxylase inhibitor, Anti-epilepsy drug, Anticonvulsants