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

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

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Ganaxolone

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00165
    • Bambino Gesu Children's Hospital, IRCCS
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Sacramento, California, United States, 95816
      • Sutter Institute for Medical Research
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Georgia
    • Norcross, Georgia, United States, 30093
      • Center for Rare Neurological Diseases
  • Indiana
    • Indianapolis, Indiana, United States, 46239
      • JWM Neurology
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Northeast Regional Epilepsy Group
    • Livingston, New Jersey, United States, 07039
      • Institute of Neurology and Neurosurgery at St. Barnabas
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Have parent or legal guardian available and willing to give written informed consent.
2. Male and female outpatients between 2 and 18 years of age years of age at time of consent.
3. Have any of the following epilepsy syndromes: PCDH19; CDKL5; Dravet Syndrome; Lennox Gastaut Syndrome (LGS); Continuous Spikes and Waves during Sleep (CSWS)
4. Have uncontrolled cluster seizures and/or non-clustered seizures.
5. Subjects should be on a stable regimen of anti-epileptic medication, and generally in good health.
6. Parent or guardian is able and willing to maintain an accurate and complete daily written seizure calendar.
7. Able and willing to take study medication with food, two or three times daily.

Key Exclusion Criteria

1. Have had previous exposure to ganaxolone.
2. Known sensitivity or allergy to any component in the study drug, progesterone, or other related steroid compounds.
3. 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.
4. Concurrent use of vigabatrin, tiagabine, or ezogabine is not permitted.
5. 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.
6. 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.
7. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ganaxolone; Maximum of 1800 mg/day or 63 mg/kg/day	Drug: Ganaxolone; oral suspension or capsules; 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

Collaborators and Investigators

• Sponsor: Marinus Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2015
• Primary Completion (Actual): January 16, 2018
• Study Completion (Actual): January 4, 2019

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: February 3, 2015
• First Posted (Estimate): February 9, 2015

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: March 17, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: ganaxolone; neurosteroid; PCDH19; CDKL5; LGS; CSWS
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents; Neurosteroids; Ganaxolone
• Other Study ID Numbers: 1042-900

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No