Study of Adjunctive Ganaxolone Treatment in Female Children With Protocadherin 19 (PCDH19)-Related Epilepsy (Violet Study)

Study Overview
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Brief Summary
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A clinical study to evaluate the efficacy, safety, and tolerability of adjunctive ganaxolone therapy compared to placebo for the treatment of seizures in female children and young adults with genetically confirmed PCDH19 gene mutation.

Detailed Description
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The Violet Study is a global, double-blind, placebo-controlled, Phase 2 clinical trial that plans to enroll approximately 25 female patients between the ages of 1 and 17 with a confirmed disease-related PCDH19 gene variant. Patients will undergo a baseline period before being randomized to receive, in addition to their existing anti-seizure treatment, either ganaxolone or placebo for 17 weeks. Following the treatment period, all patients that meet certain eligibility requirements will have the opportunity to receive ganaxolone in the open label phase of the study. The study's primary efficacy endpoint is percent reduction in seizures. Secondary outcome measures will include non-seizure-related endpoints to capture certain behavioral and sleep disturbances that have been seen in previous clinical studies with ganaxolone.

Official Title
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A Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone Treatment in Female Children With Protocadherin 19 (PCDH19)-Related Epilepsy Followed by Long-term Open-label Treatment.

Conditions
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PCDH19-Related Epilepsy

Intervention / Treatment
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* Drug: Ganaxolone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Molecular confirmation of a pathogenic or likely pathogenic PCDH19 variant Failure to control seizures despite 2 or more anti-seizure medications 12 seizures over a 12-week period of primary seizure types prior to screening On a stable regimen of concomitant AEDs, Ketogenic diets, and modified Atkins diet should be unchanged for 3 months prior to screening) Exclusion Criteria: Previous exposure to ganaxolone > 8 consecutive weeks of seizure freedom during the 12 weeks prior to screening Concurrent use of strong inducers or inhibitors of CYP3A4/5/7 is not permitted Use of tetrahydrocannabinol (THC) or non-approved cannabidiol (CBD) is prohibited during the double-blind phase Exposure to any other investigational drug within 30 days or fewer than 5 half-lives prior to screening

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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Female

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo suspension 3x's /day for 17 weeks | Drug: Placebo<br>* inactive<br>* Other names: Placebo (for ganaxolone);|
| Experimental: Ganaxolone<br>ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks | Drug: Ganaxolone<br>* active drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of 28-day Seizure Frequency Through 17 Week Post-Baseline Phase (Median Percent Change) | Summary of 28-Day Seizure Frequency for Seizure Types through 17 week Post-Baseline Phase (Median Percent Change) | End of the double-blind 17 week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of 28-day Seizure Frequency for Subjects in the Biomarker-positive Stratum (Median Percent Change) | Summary of 28-day Seizure Frequency for Seizure Types for Subjects in the Biomarker-positive Stratum through 17 weeks (Median Percent Change) | [Time Frame: End of the double-blind 17 week treatment period] | 
| 50% Primary Seizure Reduction | Percent of subjects experiencing a greater than or equal to 50% reduction in 28-day primary seizure frequency relative to the 12-week baseline | End of the double-blind 17 week treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory seizures, epilepsy in children, seizure disorder