A Study of Adjunctive Ganaxolone Treatment in Children and Young Adults with CDKL5 Deficiency Disorder


About this study

A clinical study to evaluate the effectiveness, safety, and tolerability of adjunctive ganaxolone therapy compared to placebo for the treatment of seizures in children and young adults with genetically confirmed CDKL5 gene mutation.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.


The subject will not be considered eligible for the study without meeting all the criteria below.
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 gene mutation is likely to be the cause of the epilepsy syndrome. If the patient 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. Patients 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 patients 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 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. 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 β-human chorionic growth hormone (β-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 screening, surgical sterilization, or adequate barrier methods (e.g., diaphragm and foam). An oral contraceptive alone is not considered adequate for the purpose of this study. Hormonal oral contraceptives must also be used when a condom is used. In subjects who are not sexually active, abstinence is an acceptable form.

Exclusion Criteria:

1. Previous exposure to GNX.
2. Pregnant or breastfeeding.
3. West Syndrome with hypsarrhythmia pattern on EEG or seizures predominantly of Infantile Spasm (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. Patients 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 AEDs 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, the subject will be discontinued.
13. Subjects with significant renal insufficiency, estimated glomerular filtration rate (eGFR) < 30 mL/min (calculated using the Cockcroft-Gault formula, Pediatric GFR calculator or Bedside Schwartz), will be excluded from study entry or will be discontinued if the criteria is met post baseline.
14. Have been exposed to any other investigational drug within 30 days or less than 5 half-lives prior to screening.
15. Unwillingness to withhold grapefruit, Seville oranges or star fruit from diet during the entire clinical trial.
16. Unwillingness to withhold alcohol throughout the entire clinical trial.
17. 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.
18. Known sensitivity or allergy to any component in the investigational product(s), progesterone or other related steroid compounds.
19. Plasma allopregnanolone – sulfate (Allo-S) levels ≥ 6.0 ng/ml at the screening visit.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Elaine Wirrell, M.D.

Closed for enrollment

More information


Publications are currently not available

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