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

• ClinicalTrials.gov Identifier: NCT03865732
• Recruitment Status: Active, not recruiting
• First Posted: March 7, 2019
• Last Update Posted: February 23, 2021
• Sponsor: Marinus Pharmaceuticals
• Information provided by (Responsible Party): Marinus Pharmaceuticals

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.

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.

Study Design

• 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

Arms and Interventions

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; inactive; Other Name: Placebo (for ganaxolone)

Outcome Measures

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

Eligibility Criteria

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

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

Contacts and Locations

Locations

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

Hungary

Marinus Research Site

Budapest, Hungary, 1083

Italy

Marinus Research Site

Firenze, Italy, 50139

Marinus Research Site

Rome, Italy, 00165

Netherlands

Marinus Research Site

Heeze, Netherlands, 5591

Marinus Research Site

Zwolle, Netherlands, 8025

Poland

Marinus Research Site

Krakow, Poland, 30-363

Sponsors and Collaborators

Marinus Pharmaceuticals

Investigators

• Study Director: Maciej Gasior, M.D., Ph.D; Marinus Pharmaceuticals, Inc.
• Study Director: Paula Bokesk, M.D., FAAP; Marinus Pharmaceuticals, Inc.

More Information

• Responsible Party: Marinus Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03865732
• Other Study ID Numbers: 1042-PCDH19-3002; 2018-004496-12 ( EudraCT Number )
• First Posted: March 7, 2019
• Last Update Posted: February 23, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pregnanolone; Ganaxolone; Neurosteroids; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; GABA Modulators; GABA Agents; Anesthetics; Central Nervous System Depressants