Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B) (TSC)
Primary Purpose
Tuberous Sclerosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ganaxolone
Sponsored by
About this trial
This is an interventional treatment trial for Tuberous Sclerosis
Eligibility 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.
- Patients who have been taking felbamate for less than 1 year prior to screening
- Patients who test positive for tetrahydrocannabinol (THC) or non-approved cannabidiol (CBD) via plasma drug screen
- Chronic use of oral steroid medications, ketoconazole (except for topical formulations), St. John's Wort, or other IPs is not permitted
- 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
- 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
- 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
Sites / Locations
- Marinus Research Site
- Marinus Research Site
- Marinus Research Site
- Marinus Research Site
- Marinus Research Site
- Marinus Research Site
- Marinus Research Site
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Open-label
Arm Description
ganaxolone suspension (50 mg/ml) TID for 12 weeks with 24 week extension
Outcomes
Primary Outcome Measures
Percent Change From Baseline in 28-day Seizure Frequency Through the End of 12-Week Treatment Period
Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor without impairment of consciousness or awareness, focal (motor or non-motor) with impairment of consciousness or awareness, focal to bilateral tonic-clonic, generalized tonic-clonic. Baseline 28-day seizure frequency was calculated as the total number of primary seizures in the Baseline period divided by the number of days with non-missing seizure data in the Baseline period, multiplied by 28. The Baseline Visit was defined as Week 0. Percent change from Baseline in 28-day seizure frequent was calculated as the difference in post-Baseline 28-day seizure frequency and Baseline 28-day seizure frequency, divided by Baseline 28-day seizure frequency, multiplied by 100.
Secondary Outcome Measures
Percentage of Participants Experiencing a >=50 Percent Reduction in 28-day Primary Seizure Frequency Through the End of the 12-week Treatment Period Compared to the Baseline Period
Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor without impairment of consciousness or awareness, focal (motor or non-motor) with impairment of consciousness or awareness, focal to bilateral tonic-clonic, generalized tonic-clonic. Percentage of participants reporting >=50 percent reduction in seizure frequency has been presented.
Full Information
NCT ID
NCT04285346
First Posted
February 18, 2020
Last Updated
March 8, 2023
Sponsor
Marinus Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04285346
Brief Title
Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B)
Acronym
TSC
Official Title
A Phase 2 Open-label 12-Week Trial of Adjunctive Ganaxolone Treatment (Part A) in Tuberous Sclerosis Complex-related Epilepsy Followed by Long-term Treatment (Part B)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
April 8, 2020 (Actual)
Primary Completion Date
June 25, 2021 (Actual)
Study Completion Date
August 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Marinus Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberous Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Open-label
Arm Type
Other
Arm Description
ganaxolone suspension (50 mg/ml) TID for 12 weeks with 24 week extension
Intervention Type
Drug
Intervention Name(s)
Ganaxolone
Intervention Description
titration followed by maintenance and extension period
Primary Outcome Measure Information:
Title
Percent Change From Baseline in 28-day Seizure Frequency Through the End of 12-Week Treatment Period
Description
Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor without impairment of consciousness or awareness, focal (motor or non-motor) with impairment of consciousness or awareness, focal to bilateral tonic-clonic, generalized tonic-clonic. Baseline 28-day seizure frequency was calculated as the total number of primary seizures in the Baseline period divided by the number of days with non-missing seizure data in the Baseline period, multiplied by 28. The Baseline Visit was defined as Week 0. Percent change from Baseline in 28-day seizure frequent was calculated as the difference in post-Baseline 28-day seizure frequency and Baseline 28-day seizure frequency, divided by Baseline 28-day seizure frequency, multiplied by 100.
Time Frame
Baseline and Up to Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants Experiencing a >=50 Percent Reduction in 28-day Primary Seizure Frequency Through the End of the 12-week Treatment Period Compared to the Baseline Period
Description
Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor without impairment of consciousness or awareness, focal (motor or non-motor) with impairment of consciousness or awareness, focal to bilateral tonic-clonic, generalized tonic-clonic. Percentage of participants reporting >=50 percent reduction in seizure frequency has been presented.
Time Frame
Baseline and up to 12 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Patients who have been taking felbamate for less than 1 year prior to screening
Patients who test positive for tetrahydrocannabinol (THC) or non-approved cannabidiol (CBD) via plasma drug screen
Chronic use of oral steroid medications, ketoconazole (except for topical formulations), St. John's Wort, or other IPs is not permitted
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
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
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
Facility Information:
Facility Name
Marinus Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Marinus Research Site
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Marinus Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Marinus Research Site
City
Livingston
State/Province
New Jersey
ZIP/Postal Code
07039
Country
United States
Facility Name
Marinus Research Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Marinus Research Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Marinus Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B)
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