A trial for children and teenagers with Cyclin-dependent Kinase-like 5 (CDKL5) Deficiency Disorder (CDD) to determine how effective Ganaxolone treatment is.
- Conditions
- Treatment of seizures in children and young adults with genetically confirmed cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD)MedDRA version: 20.0Level: LLTClassification code 10032062Term: Other forms of epilepsy, with intractable epilepsySystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-001180-23-PL
- Lead Sponsor
- Marinus Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
1. (a) Molecular confirmation of a pathogenic or likely pathogenic CDKL5 variant, early onset, difficult to control seizures, and neurodevelopmental impairment are required. The principal investigator (PI) must review the results of the genetic analysis and confirm that the gene mutation is likely to be the cause of epilepsy syndrome. If the subject has a de novo variant of unknown significance (VUS) in the kinase domain of the CDKL5, parental testing is negative and meets all other inclusion criteria, then the subject can be included.
Genetic mutations will be confirmed by the sponsor’s chosen central laboratory. In France, genetic mutations may be confirmed by an approved French organization, in compliance with French legislation prior to Screening Visit 1. Subjects must have (b) seizure onset by 1 year of age and (c) lack of independent ambulation by 2 years of age.
2. Male or female subjects aged 2 through 21 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 16 seizures of primary seizure types: bilateral tonic (sustained motor activity = 3 seconds), generalized tonic-clonic, bilateral clonic, atonic/drop or focal to bilateral tonic-clonic per 28 days in each 1-month period in the 2-month period prior to screening.
6. Subject must be approved to participate by sponsor and/or designee (i.e., Epilepsy Consortium) after review of medical history, genetic testing, seizure classification, and historical seizure calendars.
7. Participants should be on a stable regimen of 0-4 anti-seizure medications (including moderate or strong inducer or inhibitor anti-seizure medications e.g. carbamazepine, phenytoin, etc.) for = 1 month prior to the screening visit, without a foreseeable change in dosing for the duration of the double-blind phase. Vagus nerve stimulator (VNS), ketogenic diet, and modified Atkins diet do not count towards this limit but must be unchanged for 3 months prior to screening.
8. Subjects with surgically implanted VNS will be allowed to enter the study provided that all of the following conditions are met:
a. The VNS has been in place for = 1 year prior to the screening visit.
b. The settings must have remained constant for 3 months prior to the screening visit and remain constant throughout the double-blind phase.
c. The battery is expected to last for the duration of the double-blind phase.
9. Felbamate: The use of felbamate is allowed provided that the subject has been maintained on a stable dose of felbamate for > 6 months and has had stable liver function (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and hematology during the course of treatment, and is expected to remain constant throughout the double-blind phase.
10. Parent/caregiver is able and willing to maintain an accurate and complete daily electronic seizure calendar for the duration of the study.
11. Able and willing to take investigational product with food 3 times daily if dosed with oral suspension or 2 times daily if dosed with oral capsules. Ganaxolone must be administered with food.
12. Sexually active female of childbearing potential must be using a medically acceptable method of birth control and have a negative quantitative serum ß-huma
1. Previous exposure to GNX.
2. Pregnant or breastfeeding.
3. West Syndrome with hypsarrhythmia pattern on EEG or seizures predominantly of Infantile Spasms (IS) type; if EEG pattern/seizure type is uncertain, study inclusion should be reviewed and determined by the sponsor/sponsor delegate.
4. Concurrent use of adrenocorticotropic hormone (ACTH), prednisone or other glucocorticoid is not permitted, nor use of moderate or strong inducers or inhibitors of CYP3A4/5/7. A list of CYP3A4/5/7 inhibitors and inducers is included in Section 12.1. Moderate or strong inducer or inhibitor anti-epileptic drugs will be allowed (e.g., carbamazepine, phenytoin, etc.)
5. Subjects on ACTH, prednisone or other systemically (non-inhaled) administered steroids should be off the product greater than 28 days prior to screening. Concomitant PRN topical or intranasal steroids for dermatologic reactions and allergic rhinitis are allowed and do not warrant exclusion from the study.
6. Subjects with a positive result on tetrahydrocannabinol (THC) or cannabidiol (CBD) test (via urine or plasma drug screen) at the screening visit, and a positive result on THC or CBD test (via plasma) at the baseline visit without prescription for Epidiolex (may go by another name in countries outside the United States) in epilepsy will be excluded from the study. Concomitant Epidiolex (CBD) use will be allowed in the double-blind phase provided the subject has been on a stable dose for at least 1 month prior to screening and is expected to remain on a stable dose without a foreseeable change for the duration of the double-blind phase. THC and/or CBD will be allowed in the open-label phase.
7. Use of dietary supplements or herbal preparations are not permitted if subject has been using them consistently for less than 3 months prior to screening, or does not plan on remaining on stable doses for the duration of the double-blind phase. Use of St. John’s Wort is not permitted (See Section 12.1).
8. Changes in anti-epileptic drugs (AEDs) within the last month prior to screening. All concomitant medications must be stable in dose for at least 1-month prior to screening unless otherwise noted.
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 CDKL5) at screening 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 AST (serum glutamic oxaloacetic transaminase [SGOT]) or ALT (serum glutamic pyruvic transaminase [SGPT]) greater than 3 times the upper limit of normal (ULN) at study entry. If AST or ALT increases > 3 times ULN during the study, subject should be followed with weekly laboratory repeat testing and continue in study if levels trending down. Subject will be discontinued if levels do not decline to under 3 x ULN.
12. Total bilirubin levels greater than ULN at study entry. In cases of documented, stable medical condition (i.e., Gilbert’s Syndrome) resulting in levels of total bilirubin greater than ULN, the medical monitor can determine if a protocol exception can be made. If total bilirubin increases to 1.5 x ULN or more during study, t
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