Adjunctive GNX Treatment Compared With Placebo in Children and Adults With TSC-related Epilepsy

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified May 2025 by Marinus Pharmaceuticals
Sponsor
Marinus Pharmaceuticals
Information Provided by (Responsible Party)
Marinus Pharmaceuticals
Clinicaltrials.gov Identifier
NCT05323734
Other Study ID Numbers:
1042-TSC-3001
First Submitted
March 20, 2022
First Posted
April 11, 2022
Results First Posted
June 23, 2025
Last Update Posted
July 10, 2025
Last Verified
May 2025

ClinicalTrials.gov processed this data on June 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Tuberous Sclerosis Complex
Drug: GanaxoloneDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment129 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingTriple
Primary PurposeTreatment
Official TitleA Phase 3, Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone (GNX) Treatment in Children and Adults With Tuberous Sclerosis Complex (TSC)-Related Epilepsy (TrustTSC)
Study Start DateMarch 31, 2022
Actual Primary Completion DateSeptember 8, 2024
Actual Study Completion DateOctober 13, 2024

Groups and Cohorts

Group/CohortIntervention/Treatment
Ganaxolone (GNX)
oral suspension, 3 times a day (TID)
Drug: Ganaxolone
GNX will be administered
Placebo matching GNX
oral suspension, TID
Drug: Placebo
Placebo will be administered

Outcome Measures

Primary Outcome Measures
  1. Percent Change From Baseline in 28-day Seizure Frequency for Primary Seizure Type During Double Blind Period
    Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor with altered awareness, focal motor with intact awareness, focal to bilateral tonic-clonic seizures, focal with hypotonia impaired awareness, and generalized tonic-clonic. Seizure frequency was calculated as the total number of seizures divided by the number of days with seizure data in the period, multiplied by 28. Percent change from Baseline in 28-day seizure frequency was calculated as follows for each participant: post-baseline 28-day seizure frequency minus baseline 28-day seizure frequency whole divided by baseline 28-day seizure frequency and multiplied by 100.
Secondary Outcome Measures
  1. Number of Participants Who Were Considered as Treatment Responders During Double Blind Period
    Treatment responders are defined as those participants with ≥ 50% reduction from Baseline in primary seizure type frequency during the given period.
  2. Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Parent/Caregiver
    The CGI-I is a 7-point Likert scale that the parent(s)/caregiver(s)/ legally authorized representative (LAR) and clinician uses to rate the change in overall seizure control, behavior, safety, and tolerability after initiation of the IP relative to baseline (prior to treatment with the IP). The participant was rated as follows: 1 - very much improved, 2 - much improved, 3 - minimally improved, 4 - no change, 5 - minimally worse, 6 - much worse, and 7 - very much worse. Higher scores indicated worse condition. Number of responders to each score on the scale has been presented.
  3. Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Clinician
    The CGI-I is a 7-point Likert scale that the parent(s)/caregiver(s)/ LAR and clinician uses to rate the change in overall seizure control, behavior, safety, and tolerability after initiation of the IP relative to baseline (prior to treatment with the IP). The participant was rated as follows: 1 - very much improved, 2 - much improved, 3 - minimally improved, 4 - no change, 5 - minimally worse, 6 - much worse, and 7 - very much worse. Number of responders to each score on the scale has been presented.

Eligibility Criteria

Ages Eligible for Study(Child, Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. Clinical or mutational diagnosis of TSC consistent with: 1. Molecular confirmation of a pathogenic mutation in TSC1 or TSC2. A pathogenic mutation is defined as a mutation that clearly prevents protein synthesis and/or inactivates the function of the TSC1 or TSC2 proteins (eg, nonsense mutation or frameshift mutations, large genomic deletions) or is a missense mutation whose effect on protein function has been established by functional assessment. The Principal investigator (PI) or designee must review the results of the genetic analysis and confirm that the causal relationship to the epilepsy syndrome is likely. OR 2. Clinical diagnosis of definite TSC which includes 2 major features or 1 major feature with ≥ 2 minor features. 2. Male or female participants aged 1 through 65 years, inclusive. For Europe (EU), Middle East and North Africa (MENA), and Oceania (OC) Male or Female participants aged 2 through 65 years, inclusive. 3. Participant/parent(s) or LAR(s) 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. If the participant is not qualified nor able to provide written informed consent based on age, developmental stage, intellectual capacity, or other factors, parent(s)/LAR(s) must provide consent for study participation, if appropriate. 4. Failure to control seizures despite appropriate trial of 2 or more Anti-seizure medication (ASMs) at therapeutic doses and for adequate duration of treatment per PI judgment. 5. Participants should be on a stable regimen of ASMs (including moderate or strong inducer or inhibitor ASM eg, carbamazepine, phenytoin, etc.) at therapeutic doses for ≥ 28 days prior to the screening visit, and without a foreseeable change in dosing for the duration of the study. (Note: Minor dose adjustment to address tolerability and safety events may be allowed on case-by-case basis and it should be discussed with the study medical monitor.) 6. A history of at least 8 countable seizures per month in the 2 months prior to screening with no more than 1 seizure free week in each month. This includes seizures of any kind. 7. Have at least 8 primary endpoint seizures in the first 28 days following the screening visit. The primary endpoint seizure types are defined as the following: 1. focal motor seizures without impairment of consciousness or awareness 2. focal seizures with impairment of consciousness or awareness with motor features 3. focal seizures evolving to bilateral, tonic-clonic seizures 4. generalized motor seizures including tonic-clonic, bilateral tonic, bilateral clonic, or atonic/drop seizures. Seizures that do not count towards the primary endpoint include: 1. Focal or generalized nonmotor seizures (eg, absence seizures or focal nonmotor seizures with or without impairment of awareness) 2. Infantile or epileptic spasms 3. Myoclonic seizures. 8. Participants with surgically implanted vagal nerve stimulator (VNS) will be allowed to enter the study provided that all of the following conditions are met: 1. The VNS has been in place for ≥ 6 months prior to the screening visit. 2. The settings must have remained constant for 3 months prior to the screening visit and are expected to remain constant throughout the study. 3. The battery is expected to last for the duration of the study. 9. Parent(s)/caregiver(s)/LAR(s) or the participant, as appropriate, is (are) willing and able to maintain an accurate and complete daily seizure eDiary for the duration of the study. 10. Willing and able to take IP (suspension) as directed with food (TID). 11. Women of childbearing potential (WOCBP) must be using a medically acceptable method of birth control and have a negative quantitative serum beta-human chorionic growth hormone (β-HCG) test collected at the initial screening and Baseline visits.Childbearing potential is defined as a female who is biologically capable of becoming pregnant. A medically acceptable method of birth control includes intrauterine devices (that have been in place for at least 1 month prior to the screening visit), hormonal contraceptives (eg, combined oral contraceptives, patch, vaginal ring, injectables, and implants), and surgical sterilization (such as oophorectomy or tubal ligation. When used consistently and correctly, "double-barrier" methods of contraception can be used as an effective alternative to highly effective contraception methods. Contraceptive measures such as Plan B™, sold for emergency use after unprotected sex, are not acceptable methods for routine use. 12. Male participants must agree to use highly effective contraceptive methods during the study and for 30 days after the last dose of IP. Highly effective methods of contraception include surgical sterilization (such as a vasectomy) and adequate "double-barrier" methods.
Exclusion Criteria
1. Previous exposure to GNX. 2. Pregnant or breastfeeding. 3. Participants who have been taking felbamate for less than 1 year prior to screening. 4. Participants taking cannabidiol (CBD) preparations other than Epidiolex. 5. A positive result on plasma drug screen for CBD or tetrahydrocannabinol (THC) at Visit 1 (screening), with the exception of results that are fully explained by Epidiolex, which can be adjusted by the investigator in the event of any Adverse events (AEs). 6. Concurrent use of adrenocorticotropic hormone (ACTH), prednisone or other glucocorticoid is not permitted, nor use of the strong inducers of cytochrome P450 3A4 (CYP3A4), rifampin and St John's Wort. Participants on ACTH, prednisone, or other systemically (non-inhaled or topical) administered steroids should be off the product \> 28 days prior to screening. Rifampin and St John's Wort must be discontinued at least 28 days before Visit 2, study drug initiation. Note: 1. Use of concomitant intranasal or pro re nata (PRN) topical steroids for dermatologic reactions and allergic rhinitis are allowed during the study. 2. This exclusion criterion does not prohibit the use of approved ASMs. 7. Changes in any chronic medications within the 4 weeks prior to the screening visit. All chronic concomitant medications must be relatively stable in dose for at least 4 weeks prior to the screening visit unless otherwise noted. Small dose adjustment to manage tolerability and safety events is permitted and should be discussed with the study medical monitor. 8. Participants who have epilepsy surgery planned during the study or who have undergone surgery for epilepsy within the 6 months prior to screening. 9. An active central nervous system (CNS) infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive as evaluated by brain magnetic resonance imaging (MRI). This includes tumor growth which in the opinion of the investigator could affect primary endpoint seizure control. 10. Any disease or condition (medical or surgical; other than TSC) at the screening visit that might compromise the hematologic, cardiovascular (including any cardiac conduction defect), pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the IP, or would place the participant at increased risk or interfere with the assessment of safety/efficacy. This may include any illness in the past 4 weeks which in the opinion of the investigator may affect seizure frequency. 11. Hepatic impairment sufficient to affect participant safety, or 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 or Baseline visits and confirmed by a repeat test. 12. Biliary impairment sufficient to affect participant safety, or total bilirubin levels \> 1.5 × ULN at screening or Baseline visit and confirmed by a repeat test. In cases of Gilbert's Syndrome, resulting in stable levels of total bilirubin greater than ULN, the medical monitor can determine if a protocol exception can be made 13. Renal impairment sufficient to affect participant safety, or estimated glomerular filtration rate (eGFR) \< 30 milliliter per minute (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. Cases of temporary renal insufficiency should be discussed with the medical monitor to determine the participant's study continuation. 14. Exposed to any other investigational drug or investigational device within 30 days or fewer than 5 half-lives prior to the screening visit. For therapies in which half-life cannot be readily established, the Sponsor's Medical Monitor should be consulted. 15. Unwillingness to avoid excessive alcohol use throughout the study. 16. Have active suicidal plan/intent, active suicidal thoughts or a suicide attempt in the past 6 months. 17. Known sensitivity or allergy to any component in the IP(s), progesterone, or other related steroid compounds. 18. Participants deprived of their liberty by a judicial or administrative decision, or for psychiatric treatment, or participants admitted to a health or social services facility for purposes other than research. 19. Participants receiving traditional Chinese medicine therapies within the prior 28 days of the screening.

Contacts and Locations

Sponsors and CollaboratorsMarinus Pharmaceuticals
Locations
Arkansas Children's Research Institute | Little Rock Arkansas, United States, 72202UCLA Mattel Children's Hospital, TSC Center | Los Angeles California, United States, 90095Children's Hospital of Orange County | Orange California, United States, 92868University of California, San Diego | San Diego California, United States, 92123Childrens Hospital Colorado | Aurora Colorado, United States, 80045Nemours Children's Hospital - Delaware Valley | Wilmington Delaware, United States, 19803University of Florida Gainesville | Gainesville Florida, United States, 32608Nemours Children's Health | Jacksonville Florida, United States, 32207Mid-Atlantic Epilepsy and Sleep Center | Bethesda Maryland, United States, 20817Mayo Clinic - Rochester | Rochester Minnesota, United States, 55905Children's Mercy Hosptial | Kansas City Missouri, United States, 64108University of Rochester Medical Center | Rochester New York, United States, 14642University of North Carolina at Chapel Hill | Chapel Hill North Carolina, United States, 27599Atrium Health/Levine Children's Hospital | Charlotte North Carolina, United States, 28207Duke University Medical Center | Durham North Carolina, United States, 27712Cincinnati Children's Hospital Medical Center | Cincinnati Ohio, United States, 45229Penn State Children's Hospital | Hershey Pennsylvania, United States, 17033Le Bonheur Children's Hospital | Memphis Tennessee, United States, 38103Child Neurology Consultants of Austin (CNCA) | Austin Texas, United States, 78757University of Texas Southwestern Medical Center | Dallas Texas, United States, 75207McGovern Medical School at the University of Texas Health Science Center | Houston Texas, United States, 77030University of Utah Health Care-Pediatric Neurology | Salt Lake City Utah, United States, 84108Seattle Children's Hospital | Seattle Washington, United States, 98105Royal Brisbane and Women's Hospital | Herston Queensland, Australia, 4029Austin Health | Heidelberg , Australia, 3084Alfred Health | Melbourne , Australia, 3004Royal Melbourne Hospital | Parkville , Australia, 3050Hôtel Dieu de Montréal - CHUM | Montreal , Canada, H2X 0C2CHU Sainte-Justine | Montreal , Canada, H3T 1C5The Hospital for Sick Children | Toronto , Canada, M5G 1X8Toronto Western Hospital | Toronto , Canada, M5T 2S8BC Children's Hospital | Vancouver , Canada, V6H 3V4First Hospital of Jilin University | Changchun Jilin, China, 130028Jiangxi Provincial Children's Hospital | Jiangxi Nanchang City, China, 330000Beijing Children Hospital, Capital Medical University | Beijing Xicheng District, China, 100045The Affiliated Hospital of Guizhou Medical University | Guiyang Yunyan District, China, 550004Peking University First Hospital | Beijing , China, 100034Chinese PLA General Hospital | Beijing , China, 100080Chengdu's Women and Children's Central Hospital | Chengdu , China, 610000University Hospital of Lyon | Bron , France, 69229University Hospital of Rennes | Rennes , France, 35033University of Strasbourg | Strasbourg , France, 67084Epilepsie-Zentrum Bethel - Krankenhaus Mara | Bielefeld , Germany, 33617University Hospital Bonn | Bonn , Germany, 53127ZNN - Epilepsiezentrum Frankfurt am Main | Frankfurt , Germany, 60528Universitäts Krankenhaus Freiburg | Freiburg im Breisgau , Germany, 79106Gemeinschaftskrankenhaus Herdecke | Herdecke , Germany, 58313Epilepsiezentrum Kleinwachau gGmbH | Radeberg , Germany, 01454Schneider Children´s Medical Center | Petah Tikva , Israel, 4920235Sheba Medical Center | Tel Litwinsky , Israel, 52621Department of Neurology and Sense Organs, AOU Policlinico di Bari | Bari , Italy, 1170124Pediatric Neurology and Muscular Diseases Unit - University of Genoa | Genova , Italy, 16147Policlinico Umberto I | Rome , Italy, 00185Hospital Universitari Vall d'Hebron | Barcelona , Spain, 08035Hospital Sant Joan de Déu | Barcelona , Spain, 08950Hospital Infantil Universitario Niño Jesús | Madrid , Spain, 28009Hospital Ruber International | Madrid , Spain, 28034Hospital Regional Universitario de Málaga | Málaga , Spain, 29010Hospital Universitario y Politécnico La Fe | Valencia , Spain, 46026Bristol Royal Hospital for Children | Bristol , United Kingdom, BS2 8AENHS acute tertiary referral centre, John Radcliffe Hospital | Oxford , United Kingdom, OX3 9DUSalford Royal Hospital | Salford , United Kingdom, M6 8HDSheffield Children's Hospital | Sheffield , United Kingdom, S10 2TH
Study Documents (Full Text)
Documents provided by Marinus Pharmaceuticals: Study Protocol  September 12, 2023Documents provided by Marinus Pharmaceuticals: Statistical Analysis Plan  August 20, 2024