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

NCT05604170 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 1042-TSC-3002
• Study Type: interventional
• Target: 117
• Locations: 10 countries
• Sites: 54

Brief Summary

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

Conditions

Tuberous Sclerosis Complex

Keywords

Tuberous Sclerosis Complex-Related Epilepsy; Ganaxolone; Adjunctive

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (1)

• Percent Change From Baseline in 28-day Seizure Frequency During Open Label Extension

  Baseline (Day 1), Week 52

Study Arms (1)

Ganaxolone (GNX) oral suspension, 3 times a day (TID)

EXPERIMENTAL

Drug: Ganaxolone

Interventions

Ganaxolone DRUG

GNX will be administered.

Ganaxolone (GNX) oral suspension, 3 times a day (TID)

Eligibility Criteria

• Age: 1 Year - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Completion of Study 1042-TSC-3001 or participants who continue to meet study requirements in Study 1042-TSC-2001.
• 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.
• Parent(s)/caregiver(s) is (are) willing and able to maintain an accurate and complete daily seizure diary for the duration of the study.
• Willing and able to take Investigational product (IP) (suspension) as directed with food TID.
• 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
• 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.

You may not qualify if:

• Pregnant or breastfeeding.
• An active Central nervous system (CNS) infection, demyelinating disease, or degenerative neurological disease.
• History of psychogenic nonepileptic seizures.
• 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.
• Unwillingness to avoid excessive alcohol use or cannabis use throughout the study.
• 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.
• Known sensitivity or allergy to any component in the IP(s), progesterone, or other related steroid compounds.
• 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.

Sponsors & Collaborators

• Marinus Pharmaceuticals: lead

Study Sites (54)

Arkansas Children's Research Institute

Little Rock, Arkansas, 72202, United States

Location

UCLA Mattel Children's Hospital, TSC Center

Los Angeles, California, 90095, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours Children's Hospital - Delaware Valley

Wilmington, Delaware, 19803, United States

Location

Boston Children's Hospital, Harvard Medical School

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Atrium Health/Levine Children's Hospital

Charlotte, North Carolina, 28207, United States

Location

Duke University Medical Center

Durham, North Carolina, 27712, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Le Bonheur Children's Hospital

Memphis, Tennessee, 38103, United States

Location

Child Neurology Consultants of Austin (CNCA)

Austin, Texas, 78757, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75207, United States

Location

McGovern Medical School at the University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

University of Utah Health Care-Pediatric Neurology

Salt Lake City, Utah, 84108, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Austin Health

Heidelberg, VIC 3084, Australia

Location

Royal Brisbane and Women's Hospital

Herston, QLD 4029, Australia

Location

Alfred Health

Melbourne, VIC 3004, Australia

Location

Royal Melbourne Hospital

Parkville, VIC 3050, Australia

Location

Hôtel Dieu de Montréal - CHUM

Montreal, H2X 0C2, Canada

Location

CHU Sainte-Justine

Montreal, H3T 1C5, Canada

Location

The Hospital for Sick Children

Toronto, M5G 1X8, Canada

Location

Toronto Western Hospital

Toronto, M5T 2S8, Canada

Location

BC Children's Hospital

Vancouver, V6H 3V4, Canada

Location

Peking University First Hospital

Beijing, 100034, China

Location

Beijing Children Hospital, Capital Medical University

Beijing, 100045, China

Location

Chinese PLA General Hospital

Beijing, 100853, China

Location

The Affiliated Hospital of Guizhou Medical University

Beijing, 550004, China

Location

First Hospital of Jilin University

Jilin, 130021, China

Location

University Hospital of Lyon

Bron, 69229, France

Location

Hôpital Sud

Rennes, 35000, France

Location

University of Strasbourg

Strasbourg, 67084, France

Location

Epilepsie-Zentrum Bethel - Krankenhaus Mara

Bielefeld, 33617, Germany

Location

University Hospital Bonn

Bonn, 53127, Germany

Location

ZNN - Epilepsiezentrum Frankfurt am Main

Frankfurt, 60528, Germany

Location

Universitäts Krankenhaus Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Gemeinschaftskrankenhaus Herdecke

Herdecke, 58313, Germany

Location

Epilepsiezentrum Kleinwachau gGmbH

Radeberg, 1454, Germany

Location

Schneider Children´s Medical Center

Petah Tikva, 4920235, Israel

Location

Pediatric Neurology and Muscular Diseases Unit - University of Genoa

Genova, 16147, Italy

Location

Policlinico Umberto I

Rome, 00185, Italy

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 8025, Spain

Location

Hospital Sant Joan de Déu

Barcelona, 8950, Spain

Location

Hospital Infantil Universitario Niño Jesús

Madrid, 28009, Spain

Location

Hospital Ruber International

Madrid, 28034, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Bristol Royal Hospital for Children

Bristol, BS2 8AE, United Kingdom

Location

Sheffield Children's Hospital

Sheffield, S10 2TH, United Kingdom

Location

MeSH Terms

Conditions

Tuberous Sclerosis

Interventions

ganaxolone

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Results Point of Contact

• Title: Marinus Clinical Trials Submission Manager
• Organization: Marinus Pharmaceuticals, Inc.

clinicaltrials@marinuspharma.com

484-801-4670

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label, single arm study with no blinding as all participants will receive adjunctive GNX
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: November 3, 2022
• Study Start: May 16, 2022
• Primary Completion: April 2, 2025
• Study Completion: April 2, 2025
• Last Updated: October 1, 2025
• Results First Posted: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1); GB (2); FR (3); US (20); CN (5); CA (5); AU (4); DE (6); ES (6); IT (2)