Open-Label PoC Trial of Ganaxolone in Children With PCDH19 Female Pediatric Epilepsy and Other Rare Genetic Epilepsies
Primary Purpose
Epilepsy
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ganaxolone
Sponsored by
About this trial
This is an interventional prevention trial for Epilepsy focused on measuring PCDH19, ganaxolone, neurosteroid, CDKL5, LGS, CSWS
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.
Sites / Locations
- Phoenix Children's Hospital
- Sutter Institute for Medical Research
- University of California San Francisco
- Center for Rare Neurological Diseases
- JWM Neurology
- Boston Children's Hospital
- Northeast Regional Epilepsy Group
- Institute of Neurology and Neurosurgery at St. Barnabas
- Nationwide Children's Hospital
- Bambino Gesu Children's Hospital, IRCCS
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ganaxolone
Arm Description
Maximum of 1800 mg/day or 63 mg/kg/day
Outcomes
Primary Outcome Measures
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)
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)
Secondary Outcome Measures
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.
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.
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
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
Full Information
NCT ID
NCT02358538
First Posted
January 30, 2015
Last Updated
March 17, 2023
Sponsor
Marinus Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02358538
Brief Title
Open-Label PoC Trial of Ganaxolone in Children With PCDH19 Female Pediatric Epilepsy and Other Rare Genetic Epilepsies
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
November 6, 2015 (Actual)
Primary Completion Date
January 16, 2018 (Actual)
Study Completion Date
January 4, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Marinus Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
Keywords
PCDH19, ganaxolone, neurosteroid, CDKL5, LGS, CSWS
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ganaxolone
Arm Type
Experimental
Arm Description
Maximum of 1800 mg/day or 63 mg/kg/day
Intervention Type
Drug
Intervention Name(s)
Ganaxolone
Other Intervention Name(s)
CCD 1042
Intervention Description
oral suspension or capsules
Primary Outcome Measure Information:
Title
Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters for 52-week OLE Period (Mean Percent Change & Standard Deviation)
Description
Percentage change from baseline in 28-day seizure frequency at 3 months (day 91), 26 weeks, 52 week OLE (Mean Percent Change & Standard Deviation)
Time Frame
Baseline through 52 week open label period
Title
Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters Through 52-week OLE (Median Percent Change)
Description
Percentage change from baseline in 28-day seizure frequency at 3 months (day 91), 26 weeks, 52 week OLE (Median Percent Change)
Time Frame
Baseline through 52-week open- label period
Secondary Outcome Measure Information:
Title
Summary of CGII-C
Description
Clinician Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ] CGII-C scale is qualitative values and not quantitative.
Time Frame
End of Week 4, End of Week 8, End of Week 17, End of Week 26, Week 44, Week 62, Week 78
Title
Summary of CGII-P
Description
Patient Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ] CGII-P scale is qualitative values and not quantitative.
Time Frame
Patient Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ]
Title
Number of Participants With Responder Rate of Seizure Frequency
Description
Responder Rate in Terms of 28-day Seizure Frequency Based on the Sum of Individual Seizures and Clusters
Time Frame
Month 3 and Week 26
Title
Mean Percentage Change of Individual Seizure-free Days
Description
Mean Percentage Change of Individual Seizure-free days per 28-day period (through 52-week OLE) period relative to baseline
Time Frame
Baseline, Day 91, Week 26, 52-week OLE through month 6, 52-week OLE Period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Phoenix Children's Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Sutter Institute for Medical Research
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Center for Rare Neurological Diseases
City
Norcross
State/Province
Georgia
ZIP/Postal Code
30093
Country
United States
Facility Name
JWM Neurology
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46239
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Northeast Regional Epilepsy Group
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Institute of Neurology and Neurosurgery at St. Barnabas
City
Livingston
State/Province
New Jersey
ZIP/Postal Code
07039
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Bambino Gesu Children's Hospital, IRCCS
City
Rome
ZIP/Postal Code
00165
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Open-Label PoC Trial of Ganaxolone in Children With PCDH19 Female Pediatric Epilepsy and Other Rare Genetic Epilepsies
We'll reach out to this number within 24 hrs