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

Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02358538
• Other study ID #: 1042-900
• Status: Completed
• Phase: Phase 2
• Start date: November 6, 2015
• Est. completion date: January 4, 2019

Study information

• Verified date: March 2023
• Source: Marinus Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 4, 2019
• Est. primary completion date: January 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• Ganaxolone
oral suspension or capsules

Locations

Country	Name	City	State
Italy	Bambino Gesu Children's Hospital, IRCCS	Rome
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Northeast Regional Epilepsy Group	Hackensack	New Jersey
United States	JWM Neurology	Indianapolis	Indiana
United States	Institute of Neurology and Neurosurgery at St. Barnabas	Livingston	New Jersey
United States	Center for Rare Neurological Diseases	Norcross	Georgia
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Sutter Institute for Medical Research	Sacramento	California
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Marinus Pharmaceuticals

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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 ]
Secondary	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
Secondary	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