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

PCDH19-Related Epilepsy Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03865732
• Other study ID #: 1042-PCDH19-3002
• Secondary ID: 2018-004496-12
• Status: Completed
• Phase: Phase 2
• Start date: May 17, 2019
• Est. completion date: June 20, 2022

Study information

• Verified date: June 2023
• Source: Marinus Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: June 20, 2022
• Est. primary completion date: January 19, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 1 Year to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Epilepsy
• PCDH19-Related Epilepsy

Intervention

Drug:
• Ganaxolone
active drug
• Placebo
inactive

Locations

Country	Name	City	State
Hungary	Marinus Research Site	Budapest
Italy	Marinus Research Site	Firenze
Italy	Marinus Research Site	Rome
Netherlands	Marinus Research Site	Heeze
Netherlands	Marinus Research Site	Zwolle
Poland	Marinus Research Site	Krakow
United States	Marinus Research Site	Durham	North Carolina
United States	Marinus Research Site	Little Rock	Arkansas
United States	Marinus Research Site	Los Angeles	California
United States	Marinus Research Site	Salt Lake City	Utah
United States	Marinus Research Site	San Francisco	California
United States	Marinus Research Site	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Marinus Pharmaceuticals

Countries where clinical trial is conducted

United States,  Hungary,  Italy,  Netherlands,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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]
Secondary	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