Clinical trial NCT02358538: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy
Keywords: PCDH19
ganaxolone
neurosteroid
CDKL5
LGS
CSWS
Lead sponsor: Marinus Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-02-09
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters for 52-week OLE Period (Mean Percent Change & Standard Deviation)
timeFrame: Baseline through 52 week open label period
measure: Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters Through 52-week OLE (Median Percent Change)
timeFrame: Baseline through 52-week open- label period
Secondary outcomes:
measure: Summary of CGII-C
timeFrame: End of Week 4, End of Week 8, End of Week 17, End of Week 26, Week 44, Week 62, Week 78
measure: Summary of CGII-P
timeFrame: Patient Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ]
measure: Number of Participants With Responder Rate of Seizure Frequency
timeFrame: Month 3 and Week 26
measure: Mean Percentage Change of Individual Seizure-free Days
timeFrame: Baseline, Day 91, Week 26, 52-week OLE through month 6, 52-week OLE Period
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Sacramento
country: United States
facility: Sutter Institute for Medical Research
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Norcross
country: United States
facility: Center for Rare Neurological Diseases
state: Georgia
city: Indianapolis
country: United States
facility: JWM Neurology
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: Livingston
country: United States
facility: Institute of Neurology and Neurosurgery at St. Barnabas
state: New Jersey
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Rome
country: Italy
facility: Bambino Gesu Children's Hospital, IRCCS
Study officials:
References: