Phase 3
N=144
A Study of Soticlestat as an Add-on Therapy in Children and Young Adults With Dravet Syndrome
Dravet Syndrome (DS)
Bottom Line
View on ClinicalTrials.gov: NCT04940624 ↗Enrolled (actual)
144
Serious AEs
11.8%
Results posted
Jan 2025
Primary outcome: Primary: Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Full Treatment Period — -8.64; -22.16 percent change — p==0.061
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Soticlestat (Drug); Placebo (Drug)
- Age
- Pediatric, Adult · 2+ yrs
- Sex
- All
- Sponsor
- Takeda
- Primary completion
- Apr 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Full Treatment Period |
-8.64; -22.16 | =0.061 |
| PRIMARY Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Maintenance Period |
-11.99; -23.29 | =0.089 |
| SECONDARY Percentage of Responders During Maintenance Period |
11.8; 30.4 | =0.010 sig |
| SECONDARY Percentage of Responders During the Full Treatment Period |
9.9; 27.4 | =0.008 sig |
| SECONDARY Percentage of Participants With ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% Reduction in Convulsive Seizures During the Full Treatment Period |
39.4; 31.5; 32.4; 20.5; 18.3; 20.5 | — |
| SECONDARY Percentage of Participants With Caregiver Global Impression of Improvement (Care GI-I) Scale Responses as Per the Parent/Caregiver Reported Impression at Week 16 |
1.5; 4.5; 11.8; 27.3; 22.1; 28.8 | =0.004 sig |
| SECONDARY Percentage of Participants With Clinical Global Impression of Improvement (CGI-I) Scale Responses as Per the Investigator Reported Impression at Week 16 |
2.8; 7.0; 8.5; 25.4; 15.5; 19.7 | =0.003 sig |
| SECONDARY Percentage of Participants With CGI-I Nonseizure Symptoms Instrument Responses for Each Domain as Per the Investigator Reported Impression at Week 16 |
2.8; 7.0; 8.5; 4.2; 14.1; 14.1 | =0.741 |
| SECONDARY Change From Baseline in Quality of Life Inventory-Disability (QI-Disability) Total Score at Week 16 |
2.81; -1.23 | =0.189 |
| SECONDARY Percentage of Participants With CGI-I Seizure Intensity and Duration Instrument Responses as Per the Parent/Caregiver Reported Impression at Week 16 |
4.3; 10.8; 4.3; 24.6; 15.9; 23.1 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Maintenance Period |
-11.89; -17.24 | =0.565 |
| SECONDARY Percent Change From Baseline in Frequency of All Seizures Per 28 Days During the Full Treatment Period |
-7.46; -9.27 | =0.637 |
| SECONDARY Change From Baseline in Percentage of Convulsive Seizure-free Days During the Full Treatment Period |
2.74; 3.54 | — |
| SECONDARY Longest Convulsive Seizure-free Interval During the Full Treatment Period |
16.7; 22.3 | — |
| SECONDARY Number of Days When Rescue Antiseizure Medication (ASM) is Used During the Full Treatment Period |
4.0; 2.9 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Has documented clinical diagnosis of DS.
- 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.
- Weighs ≥10 kg at the screening visit (Visit 1).
- 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.
- 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.).
- 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.
Data sourced from ClinicalTrials.gov (NCT04940624). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.