search
Back to results

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

Primary Purpose

PCDH19-Related Epilepsy

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ganaxolone
Placebo
Sponsored by
Marinus Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PCDH19-Related Epilepsy focused on measuring refractory seizures, epilepsy in children, seizure disorder

Eligibility Criteria

1 Year - 17 Years (Child)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Marinus Research Site
  • Marinus Research Site
  • Marinus Research Site
  • Marinus Research Site
  • Marinus Research Site
  • Marinus Research Site
  • Marinus Research Site
  • Marinus Research Site
  • Marinus Research Site
  • Marinus Research Site
  • Marinus Research Site
  • Marinus Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Ganaxolone

Arm Description

placebo suspension 3x's /day for 17 weeks

ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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)
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

Full Information

First Posted
March 5, 2019
Last Updated
June 20, 2023
Sponsor
Marinus Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT03865732
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
May 17, 2019 (Actual)
Primary Completion Date
January 19, 2021 (Actual)
Study Completion Date
June 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Marinus Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PCDH19-Related Epilepsy
Keywords
refractory seizures, epilepsy in children, seizure disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo suspension 3x's /day for 17 weeks
Arm Title
Ganaxolone
Arm Type
Experimental
Arm Description
ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks
Intervention Type
Drug
Intervention Name(s)
Ganaxolone
Intervention Description
active drug
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo (for ganaxolone)
Intervention Description
inactive
Primary Outcome Measure Information:
Title
Summary of 28-day Seizure Frequency Through 17 Week Post-Baseline Phase (Median Percent Change)
Description
Summary of 28-Day Seizure Frequency for Seizure Types through 17 week Post-Baseline Phase (Median Percent Change)
Time Frame
End of the double-blind 17 week treatment period
Secondary Outcome Measure Information:
Title
Summary of 28-day Seizure Frequency for Subjects in the Biomarker-positive Stratum (Median Percent Change)
Description
Summary of 28-day Seizure Frequency for Seizure Types for Subjects in the Biomarker-positive Stratum through 17 weeks (Median Percent Change)
Time Frame
[Time Frame: End of the double-blind 17 week treatment period]
Title
50% Primary Seizure Reduction
Description
Percent of subjects experiencing a greater than or equal to 50% reduction in 28-day primary seizure frequency relative to the 12-week baseline
Time Frame
End of the double-blind 17 week treatment period

10. Eligibility

Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maciej Gasior, M.D., Ph.D
Organizational Affiliation
Marinus Pharmaceuticals, Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Paula Bokesk, M.D., FAAP
Organizational Affiliation
Marinus Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Marinus Research Site
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Marinus Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Marinus Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Marinus Research Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Marinus Research Site
City
York
State/Province
Pennsylvania
ZIP/Postal Code
17403
Country
United States
Facility Name
Marinus Research Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Marinus Research Site
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Marinus Research Site
City
Firenze
ZIP/Postal Code
50139
Country
Italy
Facility Name
Marinus Research Site
City
Rome
ZIP/Postal Code
00165
Country
Italy
Facility Name
Marinus Research Site
City
Heeze
ZIP/Postal Code
5591
Country
Netherlands
Facility Name
Marinus Research Site
City
Zwolle
ZIP/Postal Code
8025
Country
Netherlands
Facility Name
Marinus Research Site
City
Krakow
ZIP/Postal Code
30-363
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs