Open-label Study of Adjunctive GNX Treatment in Children and Adults With TSC-related Epilepsy

A Phase 3, Open-label Study of Adjunctive Ganaxolone (GNX) Treatment in Children and Adults With Tuberous Sclerosis Complex (TSC)-Related Epilepsy (TrustTSC OLE)

This is a Phase 3, global, open-label extension (OLE) study of adjunctive GNX treatment in children and adults with TSC who previously participated in either Study 1042-TSC-3001 or Study 1042-TSC-2001

Study Overview

• Status: Terminated
• Conditions: Tuberous Sclerosis Complex
• Intervention / Treatment: Drug: Ganaxolone

Detailed Description

This is a Phase 3, OLE study of adjunctive GNX treatment in children and adults with TSC-related epilepsy. Children and adults with TSC-related epilepsy are included in the study as this is one of the patient populations that may benefit from GNX treatment being

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Heidelberg, Australia, VIC 3084
    • Austin Health
  • Herston, Australia, QLD 4029
    • Royal Brisbane and Women's Hospital
  • Melbourne, Australia, VIC 3004
    • Alfred Health
  • Parkville, Australia, VIC 3050
    • Royal Melbourne Hospital
• Canada
  • Montreal, Canada, H2X 0C2
    • Hôtel Dieu de Montréal - CHUM
  • Montreal, Canada, H3T 1C5
    • CHU Sainte-Justine
  • Toronto, Canada, M5G 1X8
    • The Hospital for Sick Children
  • Toronto, Canada, M5T 2S8
    • Toronto Western Hospital
  • Vancouver, Canada, V6H 3V4
    • BC Children's Hospital
• China
  • Beijing, China, 100853
    • Chinese PLA General Hospital
  • Beijing, China, 100034
    • Peking University First Hospital
  • Beijing, China, 550004
    • The Affiliated Hospital of Guizhou Medical University
  • Beijing, China, 100045
    • Beijing Children Hospital, Capital Medical University
  • Jilin, China, 130021
    • First Hospital of Jilin University
• France
  • Bron, France, 69229
    • University Hospital of Lyon
  • Rennes, France, 35000
    • Hopital Sud
  • Strasbourg, France, 67084
    • University of Strasbourg
• Germany
  • Bielefeld, Germany, 33617
    • Epilepsie-Zentrum Bethel - Krankenhaus Mara
  • Bonn, Germany, 53127
    • University Hospital Bonn
  • Frankfurt, Germany, 60528
    • ZNN - Epilepsiezentrum Frankfurt am Main
  • Freiburg im Breisgau, Germany, 79106
    • Universitäts Krankenhaus Freiburg
  • Herdecke, Germany, 58313
    • Gemeinschaftskrankenhaus Herdecke
  • Radeberg, Germany, 1454
    • Epilepsiezentrum Kleinwachau gGmbH
• Israel
  • Petah Tikva, Israel, 4920235
    • Schneider Children´s Medical Center
• Italy
  • Genova, Italy, 16147
    • Pediatric Neurology and Muscular Diseases Unit - University of Genoa
  • Rome, Italy, 00185
    • Policlinico Umberto I
• Spain
  • Barcelona, Spain, 8025
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain, 8950
    • Hospital Sant Joan de Déu
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus
  • Madrid, Spain, 28034
    • Hospital Ruber International
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La Fe
• United Kingdom
  • Bristol, United Kingdom, BS2 8AE
    • Bristol Royal Hospital for Children
  • Sheffield, United Kingdom, S10 2TH
    • Sheffield Children's Hospital
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Research Institute
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Mattel Children's Hospital, TSC Center
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Diego, California, United States, 92123
      • Rady Children's Hospital - San Diego
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Children's Hospital - Delaware Valley
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital, Harvard Medical School
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28207
      • Atrium Health/Levine Children's Hospital
    • Durham, North Carolina, United States, 27712
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Le Bonheur Children's Hospital
  • Texas
    • Austin, Texas, United States, 78757
      • Child Neurology Consultants of Austin (CNCA)
    • Dallas, Texas, United States, 75207
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • McGovern Medical School at the University of Texas Health Science Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health Care-Pediatric Neurology
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Completion of Study 1042-TSC-3001 or participants who continue to meet study requirements in Study 1042-TSC-2001.
2. Participant/parent(s)/LAR(s) willing and able 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 or able to provide written informed consent based on age, developmental stage, intellectual capacity, or other factors, parent(s)/LAR(s) must provide assent for study participation, if appropriate.
3. Parent(s)/caregiver(s) is (are) willing and able to maintain an accurate and complete daily seizure diary for the duration of the study.
4. Willing and able to take Investigational product (IP) (suspension) as directed with food TID.
5. 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 visit. Childbearing potential is defined as a female who is biologically capable of becoming pregnant. Medically acceptable methods of birth control include 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
6. 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. Pregnant or breastfeeding.
2. An active Central nervous system (CNS) infection, demyelinating disease, or degenerative neurological disease.
3. History of psychogenic nonepileptic seizures.
4. Any disease or condition (other than TSC) at the initial visit that could 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.
5. Unwillingness to avoid excessive alcohol use or cannabis use throughout the study.
6. Have active suicidal plan/intent or have had active suicidal thoughts in the past 6 months or a suicide attempt in the past 6 months.
7. Known sensitivity or allergy to any component in the IP(s), progesterone, or other related steroid compounds.
8. Exposed to any other investigational drug (except for GNX in Study 1042-TSC-2001 or Study 1042-TSC-3001) or investigational device within 30 days or fewer than 5 half-lives prior to Visit 1 (first visit of the OLE). For therapies in which half-life cannot be readily established, the Sponsor's medical monitor should be consulted.

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
Experimental: Ganaxolone (GNX) oral suspension, 3 times a day (TID)	Drug: Ganaxolone; GNX will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Withdrawals and Dose-Reductions Due to AEs	An adverse event (AE) was any untoward medical occurrence in a clinical study patient, temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event was any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other event that requires scientific judgment.	Up to 150 Weeks
Number of Participants With Clinically Significant Changes in Vital Parameters	Vital parameters including heart rate, respiration rate, blood pressure, and body temperature were measured in seated position for at least 5 minutes.	Up to 150 Weeks
Number of Participants With Clinically Significant Changes in Physical Examinations	Physical examinations included a full physical evaluation of body systems including: General appearance, head (eyes, ears, nose, and throat), cardiovascular, respiratory, gastrointestinal, genitourinary, musculoskeletal, endocrine/metabolic, hematologic/lymphatic, skin, and other systems as appropriate.	Up to 150 Weeks
Number of Participants With Clinically Significant Changes in Neurological Examinations	Neurological examinations included an evaluation of: Cranial nerves, motor exam, sensory exam, reflexes, coordination/cerebellar	Up to 150 Weeks
Number of Participants With Clinically Significant Changes in Developmental Examinations	Developmental examinations (applicable only to pediatric participants 1 to 17 years of age, inclusive) included an evaluation of speech/language, motor skills, and social skills	Up to 150 Weeks
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings	Twelve-lead ECGs were performed by the physician using an ECG machine that automatically calculates the heart rate and measure PR, QRS, QT and QTc intervals.	Up to 150 Weeks
Number of Participants With Clinically Significant Changes in Hematology Parameters	Blood samples were collected for the analysis of hematology parameters: hemoglobin, hematocrit, erythrocytes, thrombocytes (platelet count). Differential blood counts, including basophils, eosinophils, neutrophils, lymphocytes, and monocytes	Week 1 through Week 150
Number of Participants With Clinically Significant Changes in Chemistry Parameters	Blood samples were collected for the analysis of chemistry parameters: blood urea nitrogen (BUN), potassium, alanine aminotransferase (ALT), alkaline phosphatase (ALP)/serum glutamic pyruvic transaminase (SGPT), total bilirubin, creatinine, sodium, aspartate aminotransferase (AST)/serum glutamic oxaloacetic (SGOT), total protein, fasting blood glucose, calcium, carbon dioxide, estimated glomerular filtration rate (eGFR), and chloride	Up to 150 Weeks
Number of Participants With Clinically Significant Changes in Urinalysis	Urine samples were collected for the analysis of urinalysis parameters: Specific gravity, color, clarity, pH, glucose, protein, blood, nitrite, protein, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick, and microscopic examination (if blood or protein was abnormal)	Up to 150 Weeks
Number of Participants (Age Greater Than 17 Years) With Abnormal Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a clinician administered assessment tool that evaluates suicidal ideation and behavior. Number of participants that have an affirmative response to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) will be reported. The score ranges from 1 to 5 and higher scores indicate worse symptoms.	Up to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in 28-day Seizure Frequency During Open Label Extension	Seizure frequency will be calculated as the total number of seizures divided by the number of days with seizure data, multiplied by 28. Percent change from baseline in 28-day frequency was calculated for each participant by subtracting Baseline 28-day seizure frequency from post-Baseline 28-day seizure frequency, whole divided by Baseline 28-day seizure frequency and multiplied by 100.	Baseline (Day 1), Week 52

Collaborators and Investigators

• Sponsor: Marinus Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2022
• Primary Completion (Actual): April 2, 2025
• Study Completion (Actual): April 2, 2025

Study Registration Dates

• First Submitted: October 5, 2022
• First Submitted That Met QC Criteria: October 27, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Adjunctive; Ganaxolone; Tuberous Sclerosis Complex-Related Epilepsy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Genetic Diseases, Inborn; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Hamartoma; Neoplasms, Multiple Primary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; 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-3002

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