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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03865732
Recruitment Status : Active, not recruiting
First Posted : March 7, 2019
Last Update Posted : February 23, 2021
Information provided by (Responsible Party):
Marinus Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
PCDH19-Related Epilepsy Drug: Ganaxolone Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.
Actual Study Start Date : May 17, 2019
Actual Primary Completion Date : January 19, 2021
Estimated Study Completion Date : May 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy Seizures

Arm Intervention/treatment
Experimental: Ganaxolone
ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks
Drug: Ganaxolone
active drug

Placebo Comparator: Placebo
placebo suspension 3x's /day for 17 weeks
Drug: Placebo
Other Name: Placebo (for ganaxolone)

Primary Outcome Measures :
  1. Percent change in 28-day seizure frequency [ Time Frame: End of the double-blind 17 week treatment period ]
    Percent change in 28-day seizure frequency during the double-blind treatment period relative to the 12-week prospective baseline period

Secondary Outcome Measures :
  1. 50% Primary Seizure Reduction [ Time Frame: End of the double-blind 17 week treatment period ]
    Percent of subjects experiencing a greater than or equal to 50% reduction in 28-day primary seizure frequency relative to the 12-week baseline

  2. Behavior Rating Inventory of Executive Function [ Time Frame: End of the double-blind 17 week treatment period ]
    Behavior rating inventory of executive function during the double-blind treatment period of ganaxolone compared to placebo

  3. Aberrant Behavior Checklist - Community [ Time Frame: End of the double-blind 17 week treatment period ]
    Aberrant behavior checklist - community during the double-blind treatment period of ganaxolone compared to placebo

  4. Children's Sleep Habit Questionnaire [ Time Frame: End of the double-blind 17 week treatment period ]
    Children's sleep habit questionnaire during the double-blind treatment period of ganaxolone compared to placebo

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   1 Year to 17 Years   (Child)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03865732

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United States, Arkansas
Marinus Research Site
Little Rock, Arkansas, United States, 72202
United States, California
Marinus Research Site
Los Angeles, California, United States, 90095
Marinus Research Site
San Francisco, California, United States, 94158
United States, North Carolina
Marinus Research Site
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Marinus Research Site
York, Pennsylvania, United States, 17403
United States, Utah
Marinus Research Site
Salt Lake City, Utah, United States, 84113
Marinus Research Site
Budapest, Hungary, 1083
Marinus Research Site
Firenze, Italy, 50139
Marinus Research Site
Rome, Italy, 00165
Marinus Research Site
Heeze, Netherlands, 5591
Marinus Research Site
Zwolle, Netherlands, 8025
Marinus Research Site
Krakow, Poland, 30-363
Sponsors and Collaborators
Marinus Pharmaceuticals
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Study Director: Maciej Gasior, M.D., Ph.D Marinus Pharmaceuticals, Inc.
Study Director: Paula Bokesk, M.D., FAAP Marinus Pharmaceuticals, Inc.
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Responsible Party: Marinus Pharmaceuticals Identifier: NCT03865732    
Other Study ID Numbers: 1042-PCDH19-3002
2018-004496-12 ( EudraCT Number )
First Posted: March 7, 2019    Key Record Dates
Last Update Posted: February 23, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Marinus Pharmaceuticals:
refractory seizures
epilepsy in children
seizure disorder
Additional relevant MeSH terms:
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Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
GABA Modulators
GABA Agents
Central Nervous System Depressants