A clinical study with an investigational drug called ganaxolone in female children with protocadherin 19 (PCDH19)-related epilepsy
- Conditions
- protocadherin 19 (PCDH19)-related epilepsyMedDRA version: 20.0Level: LLTClassification code 10032061Term: Other forms of epilepsySystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2018-004496-12-NL
- Lead Sponsor
- Marinus Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 30
Inclusion Criteria:
1. Molecular confirmation of a pathogenic or likely pathogenic PCDH19 variant. Genetic mutations will be confirmed by the sponsor’s chosen central laboratory.
2. Female subjects aged 1 through 17 years, inclusive.
3. Subject/parent or LAR willing to give written informed consent/assent, after being properly informed of the nature and risks of the study and prior to engaging in any study-related procedures.
4. Failure to control seizures despite appropriate trial of 2 or more anti-seizure mediations at therapeutic doses.
5. Have at least 12 countable/witnessed primary seizures over a 84 day (12 week) period prior to the screening visit (pre-baseline
screening).The primary seizure types are defined as countable focal seizures that include progressive hypotonia and impaired awareness, or any countable focal or generalized seizure with a clear motor component. Focal and generalized nonmotor seizures and myoclonic seizures do not count as the primary seizure types.
6. Subject must be approved to participate by sponsor or its designee (eg, Epilepsy Consortium) after review of medical history, genetic testing, seizure classification video (if available), and historical seizure calendars.
7. Ketogenic diets and modified Atkins diets should be unchanged for 3 months prior to screening and must remain stable throughout baseline and the DB phase.
8. Subjects with surgically implanted VNS will be allowed to enter the study provided that all of the following conditions are met:
• The VNS has been in place for = 1 year prior to the screening visit.
• The settings must have remained constant for 3 months prior to the screening visit and remain constant throughout baseline and the DB phase.
• The battery is expected to last for the duration of baseline and the DB phase.
9. Parent/caregiver is able and willing to maintain an accurate and complete daily electronic seizure diary for the duration of the study.
10. Able and willing to take investigational product (suspension) with food 3 times daily. Ganaxolone must be administered with food.
11. Sexually active female of childbearing potential must be using a medically acceptable method of birth control and have a negative quantitative serum ß-human chorionic growth hormone (ß-HCG) test collected at the initial screening visit. Childbearing potential is defined as a female who is biologically capable of becoming pregnant. A medically acceptable method of birth control includes intrauterine devices in place for at least 3 months prior to the screening visit, surgical sterilization, or adequate barrier methods (eg, diaphragm or condom and foam). An oral contraceptive alone is not considered adequate for the purpose of this study. Use of oral contraceptives in combination with another method (eg, a spermicidal cream) is acceptable. In subjects who are not sexually active, abstinence is an acceptable form
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Exclusion Criteria:
1. Previous exposure to Ganaxolone (GNX).
2. Pregnant or breastfeeding.
3. Subjects with > 8 consecutive weeks (56 consecutive days) of primary seizure freedom during the 12- week pre-baseline screening period.
4. Subjects with = 3 primary seizures during the 12-week baseline period.
5. Concurrent use of strong inducers or inhibitors of CYP3A4/5/7 is not permitted. Any strong inhibitor or inducer of CYP3A4/5/7 must be discontinued at least 28 days before Baseline/Randomization Visit. This does not include approved AEDs.
6. Subjects with a positive result on tetrahydrocannabinol (THC) or non-approved cannabidiol (CBD) test (via plasma drug screen) Tetrahydrocannabinol and/or non-approved CBD will be allowed in the OL phase.
7. Chronic use of oral steroid medications, ketoconazole (except for topical formulations), St. John’s Wort, or other investigational products is not permitted. Intermittent (<5 consecutive days/month or 10 cumulative days per month) use of corticosteroids as a rescue medication for breakthrough seizures may be allowed after sponsor approval.
8. Changes in any chronic AED medications (i.e., changes in dose or starting a new chronic AED) within the last month prior to the screening visit (Visit 1) and during the 12 week baseline period (i.e., between Visit 1 and Visit 2). Changes in rescue AED medications to treat acute breakthrough seizures may be permitted with Sponsor’s approval. Changes in other (i.e., non-AED) chronic medications may be permitted with Sponsor’s approval.
9. Have an active CNS infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive as evaluated by brain imaging (magnetic resonance imaging [MRI]).
10. Have any disease or condition (medical or surgical; other than PCDH19 - related epilepsy) at the screening visit that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk.
11. An aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT/serum glutamic pyruvic transaminase [SGPT]) > 3 × the upper limit of normal (ULN) at screening and if applicable, confirmed by a repeat test. If the subject has another reason to be excluded, repeated liver enzymes are not required.
12. Total bilirubin levels > 1.5 × ULN at screening and if applicable confirmed by a repeat test. In cases of documented, stable medical condition (ie, Gilbert’s Syndrome) resulting in levels of total bilirubin > ULN, the medical monitor can determine if a protocol exception can be made.
13. Subjects with significant renal insufficiency, estimated glomerular filtration rate (eGFR) < 30 mL/min (calculated using the Cockcroft-Gault formula or Pediatric GFR calculator or Bedside Schwartz), will be excluded from study entry or will be discontinued if the criterion is met post baseline.
14. Have been exposed to any other investigational drug within 30 days or fewer than 5 half-lives prior to the screening visit.
15. Unwillingness to withhold grapefruit, Seville oranges, star fruit or grapefruit containing products from diet 14 days prior to 1st dose and for the duration of the study.
16. Unwillingness to withhold alcohol throughout the entire clinical trial.
17. Have active suicidal plan/intent or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method