Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B)
Study Details
Study Description
Brief Summary
To assess preliminary safety and efficacy of ganaxolone as adjunctive therapy for the treatment of primary seizure types in patients with genetically- or clinically-confirmed TSC-related epilepsy through the end of the 12 week treatment period.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This is an OL proof of concept study of adjunctive GNX treatment in patients with a confirmed clinical diagnosis of TSC and/or a mutation in either the TSC1 or TSC2 gene. The trial consists of two parts: Part A consists of a 4-week baseline period followed by a 12-week treatment period (4-week titration and 8-week maintenance). For patients not continuing in the 24-week OLE period (Part B), a 2-week taper period followed by a 2-week safety period would follow. The main difference between Part A and Part B is the length of treatment, less frequent assessments, and the ability to alter drug doses (both GNX and other antiepileptic drug [AED] treatments which includes initiating and stopping other medications) based on investigator evaluation of the patient's clinical course during Part B. Patients with a seizure frequency reduction during the 12-week treatment period in Part A compared to baseline may continue into Part B ("OLE eligible"), to assess long-term safety, efficacy and tolerability in patients with TSC-related Epilepsy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Open-label ganaxolone suspension (50 mg/ml) TID for 12 weeks with 24 week extension |
Drug: Ganaxolone
titration followed by maintenance and extension period
|
Outcome Measures
Primary Outcome Measures
- Percent Change in 28-day Seizure Frequency [End of Open-label 12 weeks treatment period]
Percent change in 28-day seizure frequency during 12 weeks Open-label treatment period relative to the 4 week baseline period
Secondary Outcome Measures
- Percentage of patients [up to 24 weeks after end of Part A]
Percentage of patients experiencing a greater than or equal to 50% reduction in 28-day primary seizure frequency through the end of the 12-weeks treatment period compared to the 4-week Baseline Period.
Eligibility Criteria
Criteria
Inclusion Criteria (Part A):
-
Clinical or mutational diagnosis of TSC
-
Failure to control seizures despite appropriate trial of 2 or more ASMs at therapeutic doses.
-
Have at least 8 countable/witnessed primary seizures during the 4-week baseline period with at least 1 primary seizure occurring in at least 3 of the 4 weeks of baseline.
Inclusion Criteria (Part B)
• Patients have experienced ≥ 35% reduction in primary seizure frequency during the Part A treatment period compared to the 4-week Baseline Period.
Exclusion Criteria (Part A):
-
Previous exposure to GNX
-
Pregnant or breastfeeding
-
Concurrent use of strong inducers or inhibitors of cytochrome P450 (CYP)3A4/5/7. Any strong inhibitor or inducer of CYP3A4/5/7 must be discontinued at least 28 days before Visit 2, study drug initiation. This does not include approved ASMs.
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Patients who have been taking felbamate for less than 1 year prior to screening
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Patients who test positive for tetrahydrocannabinol (THC) or non-approved cannabidiol (CBD) via plasma drug screen
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Chronic use of oral steroid medications, ketoconazole (except for topical formulations), St. John's Wort, or other IPs is not permitted
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Have an active CNS infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive. This includes tumor growth which in the opinion of the investigator could affect primary seizure control
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Patients 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
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Have been exposed to any other investigational drug within 30 days or fewer than 5 half lives (whichever is shorter) prior to the screening visit
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Marinus Research Site | Los Angeles | California | United States | 90095 |
| 2 | Marinus Research Site | Palo Alto | California | United States | 94304 |
| 3 | Marinus Research Site | Boston | Massachusetts | United States | 02115 |
| 4 | Marinus Research Site | Livingston | New Jersey | United States | 07039 |
| 5 | Marinus Research Site | Durham | North Carolina | United States | 27710 |
| 6 | Marinus Research Site | Cincinnati | Ohio | United States | 45229 |
| 7 | Marinus Research Site | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Marinus Pharmaceuticals
Investigators
- Study Director: Maciej Gasior, MD, Marinus Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1042-TSC-2001