Open-Label PoC Trial of Ganaxolone in Children With PCDH19 Female Pediatric Epilepsy and Other Rare Genetic Epilepsies

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy of open-label ganaxolone as adjunctive therapy for uncontrolled seizures in female children with PCDH19 mutation and other rare genetic epilepsies in an open-label proof-of-concept study.

Detailed Description
-----------------
The purpose of this proof-of-concept study is to evaluate ganaxolone as adjunctive therapy for uncontrolled seizures in female children with PCDH19 mutations and other rare genetic epilepsies. After establishing baseline seizure frequency, qualifying subjects will enter the study and be treated with open-label ganaxolone for up to six months.

Official Title
-----------------
A Multicenter, Open-Label Proof-of-Concept Trial of Ganaxolone in Children With PCDH19 Female Pediatric Epilepsy and Other Rare Genetic Epilepsies Followed by 52 Week Open-Label Treatment

Conditions
-----------------
Epilepsy

Intervention / Treatment
-----------------
* Drug: Ganaxolone


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Have parent or legal guardian available and willing to give written informed consent. Male and female outpatients between 2 and 18 years of age years of age at time of consent. Have any of the following epilepsy syndromes: PCDH19; CDKL5; Dravet Syndrome; Lennox Gastaut Syndrome (LGS); Continuous Spikes and Waves during Sleep (CSWS) Have uncontrolled cluster seizures and/or non-clustered seizures. Subjects should be on a stable regimen of anti-epileptic medication, and generally in good health. Parent or guardian is able and willing to maintain an accurate and complete daily written seizure calendar. Able and willing to take study medication with food, two or three times daily. Key Exclusion Criteria Have had previous exposure to ganaxolone. Known sensitivity or allergy to any component in the study drug, progesterone, or other related steroid compounds. Exposure to any investigational drug or device < 90 days prior to screening, or plans to participate in another drug or device trial at any time during the study. Concurrent use of vigabatrin, tiagabine, or ezogabine is not permitted. Have any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome, including but not limited to: clinically significant cardiac, renal, pulmonary, gastrointestinal, hematologic or hepatic conditions; or a condition that affects the absorption, distribution, metabolism or excretion of drugs. Have active suicidal plan/intent, or have had active suicidal thoughts in the past 6 months or a suicide attempt in the past 3 years. Have Alanine transferase (ALT; SGPT) or Aspartate transferase (AST; SGOT) levels > 3 times upper limits of normal (ULN), or total bilirubin >1.5 time ULN at the screening and baseline visits.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ganaxolone<br>Maximum of 1800 mg/day or 63 mg/kg/day | Drug: Ganaxolone<br>* oral suspension or capsules<br>* Other names: CCD 1042;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters for 52-week OLE Period (Mean Percent Change & Standard Deviation) | Percentage change from baseline in 28-day seizure frequency at 3 months (day 91), 26 weeks, 52 week OLE (Mean Percent Change & Standard Deviation) | Baseline through 52 week open label period | 
| Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters Through 52-week OLE (Median Percent Change) | Percentage change from baseline in 28-day seizure frequency at 3 months (day 91), 26 weeks, 52 week OLE (Median Percent Change) | Baseline through 52-week open- label period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of CGII-C | Clinician Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ] CGII-C scale is qualitative values and not quantitative. | End of Week 4, End of Week 8, End of Week 17, End of Week 26, Week 44, Week 62, Week 78 | 
| Summary of CGII-P | Patient Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ] CGII-P scale is qualitative values and not quantitative. | Patient Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ] | 
| Number of Participants With Responder Rate of Seizure Frequency | Responder Rate in Terms of 28-day Seizure Frequency Based on the Sum of Individual Seizures and Clusters | Month 3 and Week 26 | 
| Mean Percentage Change of Individual Seizure-free Days | Mean Percentage Change of Individual Seizure-free days per 28-day period (through 52-week OLE) period relative to baseline | Baseline, Day 91, Week 26, 52-week OLE through month 6, 52-week OLE Period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PCDH19, ganaxolone, neurosteroid, CDKL5, LGS, CSWS