Clinical trial NCT03865732: Study of Adjunctive Ganaxolone Treatment in Female Children With Protocadherin 19 (PCDH19)-Related Epilepsy (Violet Study)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: PCDH19-Related Epilepsy
Keywords: refractory seizures
epilepsy in children
seizure disorder
Lead sponsor: Marinus Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-03-07
Enrollment: 29
Sex: FEMALE
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Summary of 28-day Seizure Frequency Through 17 Week Post-Baseline Phase (Median Percent Change)
timeFrame: End of the double-blind 17 week treatment period
Secondary outcomes:
measure: Summary of 28-day Seizure Frequency for Subjects in the Biomarker-positive Stratum (Median Percent Change)
timeFrame: [Time Frame: End of the double-blind 17 week treatment period]
measure: 50% Primary Seizure Reduction
timeFrame: End of the double-blind 17 week treatment period
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Marinus Research Site
state: Arkansas
city: Los Angeles
country: United States
facility: Marinus Research Site
state: California
city: San Francisco
country: United States
facility: Marinus Research Site
state: California
city: Durham
country: United States
facility: Marinus Research Site
state: North Carolina
city: York
country: United States
facility: Marinus Research Site
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Marinus Research Site
state: Utah
city: Budapest
country: Hungary
facility: Marinus Research Site
city: Firenze
country: Italy
facility: Marinus Research Site
city: Rome
country: Italy
facility: Marinus Research Site
city: Heeze
country: Netherlands
facility: Marinus Research Site
city: Zwolle
country: Netherlands
facility: Marinus Research Site
city: Krakow
country: Poland
facility: Marinus Research Site
Study officials:
affiliation: Marinus Pharmaceuticals, Inc.
name: Maciej Gasior, M.D., Ph.D
role: STUDY_DIRECTOR
affiliation: Marinus Pharmaceuticals, Inc.
name: Paula Bokesk, M.D., FAAP
role: STUDY_DIRECTOR
References: