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)

• ClinicalTrials.gov Identifier: NCT03694275
• Recruitment Status: Completed
• First Posted: October 3, 2018
• Results First Posted: April 20, 2021
• Last Update Posted: April 20, 2021
• Sponsor: Takeda
• Collaborator: Ovid Therapeutics Inc.
• Information provided by (Responsible Party): Takeda

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
15q Duplication Syndrome; CDKL5 Deficiency Disease	Drug: Soticlestat	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label, Pilot Study of TAK-935 (OV935) in Patients With 15Q Duplication Syndrome or CDKL5 Deficiency Disorder (ARCADE Study)
• Actual Study Start Date: September 10, 2018
• Actual Primary Completion Date: July 13, 2020
• Actual Study Completion Date: July 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Soticlestat Dup 15q; 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; TAK-935 tablets; Other Name: TAK-935
Experimental: Soticlestat CDD; 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; TAK-935 tablets; Other Name: TAK-935

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Maintenance Period [ Time Frame: Maintenance Period: Weeks 9 to 20 ]
   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.

Secondary Outcome Measures :

1. Percent Change From Baseline in Motor Seizure Frequency Per 28 Days During the Treatment Period [ Time Frame: Treatment Period: Weeks 0 to 20 ]
   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.
2. Percentage of Participants Considered as Treatment Responders During the Maintenance Period [ Time Frame: Maintenance Period: Weeks 9 to 20 ]
   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.
3. Percent Change From Baseline in Frequency of Motor Seizures Longer Than 5 Minutes in Participants With CDD [ Time Frame: Treatment Period: Weeks 0 to 20 ]
   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.
4. Proportion of Motor Seizure-free Days in Participants During the Maintenance Period [ Time Frame: Maintenance Period: Weeks 9 to 20 ]
   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.
5. Change From Baseline in Clinician's Global Impression of Severity (CGI-S) Responses of Investigator [ Time Frame: Baseline to Week 20 ]
   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.
6. Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression [ Time Frame: Week 20 ]
   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.
7. Percentage of Participants With Care Clinical Global Impression of Change (CGI-C) Responses of Parent/Family [ Time Frame: Week 20 ]
   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.
8. Change From Baseline of Plasma 24S-hydroxycholesterol (24HC) Levels [ Time Frame: Baseline to Week 20 ]
9. Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy [ Time Frame: Baseline to Week 20 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 55 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Clinical diagnosis of Dup 15q or CDKL5 deficiency disorder.
2. Currently taking 1 to 6 antiepileptic drugs (AEDs) at a stable dose.

Exclusion Criteria:

1. Two or more episodes of convulsive status epilepticus per 3 months requiring hospitalization and intubation.
2. Currently receiving a study drug or participated in a clinical study involving another investigational product in the previous month.

Contacts and Locations

Locations

United States, California

UCLA

Los Angeles, California, United States, 90095

United States, Colorado

Research Institute Children's Hospital Colorado

Aurora, Colorado, United States, 80045

United States, Georgia

Center for Rare Neurological Diseases

Norcross, Georgia, United States, 30093

United States, Massachusetts

Center for Rare Neurological Diseases (CRND)--Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Boston Children's Hospital Translational Neuroscience Center

Boston, Massachusetts, United States, 02115

United States, Minnesota

Minnesota Epilepsy Group, P.A.

Saint Paul, Minnesota, United States, 55102

United States, New York

New York University (NYU)

New York, New York, United States, 10017

Columbia University Medical Center

New York, New York, United States, 10032

Sponsors and Collaborators

Takeda

Ovid Therapeutics Inc.

Investigators

• Study Director: Medical Director Clinical Science; Takeda

  Study Documents (Full-Text)

Documents provided by Takeda:

Study Protocol  [PDF] November 21, 2019

Statistical Analysis Plan  [PDF] June 25, 2020

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03694275
• Other Study ID Numbers: TAK-935-18-002 (OV935); U1111-1219-5787 ( Registry Identifier: WHO )
• First Posted: October 3, 2018
• Results First Posted: April 20, 2021
• Last Update Posted: April 20, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• URL: https://vivli.org/ourmember/takeda/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda:

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

Additional relevant MeSH terms:

Deficiency Diseases; Syndrome; Disease; Pathologic Processes; Malnutrition; Nutrition Disorders