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

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.

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.

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.

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