A double-blind, randomized, placebo-controlled trial of adjunctive ganaxolone treatment in female children with protocadherin 19 (PCDH19)-related epilepsy followed by long-term open-label treatment

Phase 3

Completed

• Conditions: PCDH19-related epilepsy; PCDH19 female epilepsy; 10029299

• Registration Number: NL-OMON55218
• Lead Sponsor: Marinus Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 8

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 an 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 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 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 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.

Exclusion Criteria

1. Previous exposure to 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 10cumulative 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 d

Study & Design

• Study Type: Interventional
• Study Design: Not specified