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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04940624
Recruitment Status : Active, not recruiting
First Posted : June 25, 2021
Last Update Posted : January 19, 2024
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE June 16, 2021
First Posted Date  ICMJE June 25, 2021
Last Update Posted Date January 19, 2024
Actual Study Start Date  ICMJE October 28, 2021
Estimated Primary Completion Date April 18, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2021)
  • Percent Change From Baseline in Convulsive Seizure Frequency per 28 days During the Full Treatment Period [ Time Frame: 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) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2022)
  • Percentage of Responders During Maintenance Period [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline up to Week 16 ]
  • Caregiver Global Impression of Improvement (Care GI-I) Score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: Baseline up to Week 16 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2021)
  • Percentage of Responders During Maintenance Period [ Time Frame: 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 [ Time Frame: Baseline up to Week 16 ]
    Responders are defined as those with ≥50% reduction from baseline in convulsive seizures during the Treatment Period.
  • Percent Change From Baseline in Frequency of all Seizures per 28 Days During the Maintenance Period [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • 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 [ Time Frame: Baseline up to Week 16 ]
  • Change from Baseline in Percentage of Convulsive Seizure-free Days [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: Baseline up to Week 16 ]
  • Clinical Global Impression of Improvement (CGI-I) Score [ Time Frame: 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.
  • Caregiver Global Impression of Improvement (Care GI-I) Score [ Time Frame: 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.
  • CGI-I Seizure Intensity and Duration Score [ Time Frame: 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 duration of convulsive 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.
  • CGI-I Nonseizure Symptoms Score [ Time Frame: 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 [ Time Frame: 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Soticlestat as an Add-on Therapy in Children and Young Adults With Dravet Syndrome
Official Title  ICMJE A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Soticlestat as Adjunctive Therapy in Pediatric and Young Adult Subjects With Dravet Syndrome (DS)
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.

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:

  • Soticlestat or
  • 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Dravet Syndrome (DS)
Intervention  ICMJE
  • Drug: Soticlestat
    Soticlestat mini-tablets or tablets.
    Other Name: TAK-935
  • Drug: Placebo
    Soticlestat placebo-matching mini-tablets or tablets.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Soticlestat
  • 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.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 18, 2024)
144
Original Estimated Enrollment  ICMJE
 (submitted: June 18, 2021)
142
Estimated Study Completion Date  ICMJE April 18, 2024
Estimated Primary Completion Date April 18, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Has documented clinical diagnosis of DS.
  2. 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.
  3. Weighs ≥10 kg at the screening visit (Visit 1).
  4. 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.
  5. 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.).
  6. 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:

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Brazil,   Canada,   China,   France,   Germany,   Greece,   Hungary,   Italy,   Japan,   Latvia,   Netherlands,   Poland,   Russian Federation,   Serbia,   Spain,   Ukraine,   United States
Removed Location Countries Mexico
 
Administrative Information
NCT Number  ICMJE NCT04940624
Other Study ID Numbers  ICMJE TAK-935-3001
jRCT2051210074 ( Registry Identifier: jRCT )
2021-002480-22 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
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/
Current Responsible Party Takeda
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Takeda
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Takeda
PRS Account Takeda
Verification Date January 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP