Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B) (TSC)

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)

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.

Study Overview

• Status: Completed
• Conditions: Tuberous Sclerosis
• Intervention / Treatment: Drug: Ganaxolone

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 Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Marinus Research Site
    • Palo Alto, California, United States, 94304
      • Marinus Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Marinus Research Site
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Marinus Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Marinus Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Marinus Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Marinus Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and up to 12 Weeks

Collaborators and Investigators

• Sponsor: Marinus Pharmaceuticals
• Investigators: Study Director: Maciej Gasior, MD, Marinus Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2020
• Primary Completion (Actual): June 25, 2021
• Study Completion (Actual): August 30, 2022

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (Actual): February 26, 2020

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms; Congenital Abnormalities; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Hamartoma; Neoplasms, Multiple Primary; Sclerosis; Tuberous Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents; Neurosteroids; Ganaxolone
• Other Study ID Numbers: 1042-TSC-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No