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

NCT05323734 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 1042-TSC-3001
• Study Type: interventional
• Target: 129
• Locations: 10 countries
• Sites: 63

Brief Summary

This is a Phase 3, global, double-blind, randomized, placebo-controlled study of adjunctive GNX treatment in children and adults with TSC-related epilepsy. The study consists of a 4-week prospective Baseline phase, defined as the first 28 days following screening, followed by a double-blind phase consisting of a 4-week titration period (Day 1 to Day 28) and a 12-week maintenance period (Day 29 to Week 16).

Conditions

Tuberous Sclerosis Complex

Keywords

Tuberous Sclerosis Complex-Related Epilepsy; Ganaxolone; Adjunctive

Outcome Measures

Primary Outcomes (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.

  Baseline (Day 1), Day 28

Secondary Outcomes (3)

• Number of Participants Who Were Considered as Treatment Responders During Double Blind Period

  Up to 16 weeks

• Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Parent/Caregiver

  Baseline (Day 1) through 16 weeks

• Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Clinician

  Baseline (Day 1) through 16 weeks

Study Arms (2)

Ganaxolone (GNX)

EXPERIMENTAL

oral suspension, 3 times a day (TID)

Drug: Ganaxolone

Placebo matching GNX

PLACEBO COMPARATOR

oral suspension, TID

Drug: Placebo

Interventions

Ganaxolone DRUG

GNX will be administered

Ganaxolone (GNX)

Placebo DRUG

Placebo will be administered

Placebo matching GNX

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:

• Clinical or mutational diagnosis of TSC consistent with:
• 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
• Clinical diagnosis of definite TSC which includes 2 major features or 1 major feature with ≥ 2 minor features.
• 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.
• 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.
• 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.
• 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.)
• 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.
• 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:
• focal motor seizures without impairment of consciousness or awareness
• focal seizures with impairment of consciousness or awareness with motor features
• focal seizures evolving to bilateral, tonic-clonic seizures
• generalized motor seizures including tonic-clonic, bilateral tonic, bilateral clonic, or atonic/drop seizures.
• Seizures that do not count towards the primary endpoint include:

You may not qualify if:

• Previous exposure to GNX.
• Pregnant or breastfeeding.
• Participants who have been taking felbamate for less than 1 year prior to screening.
• Participants taking cannabidiol (CBD) preparations other than Epidiolex.
• 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).
• 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:
• Use of concomitant intranasal or pro re nata (PRN) topical steroids for dermatologic reactions and allergic rhinitis are allowed during the study.
• 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.
• Participants who have epilepsy surgery planned during the study or who have undergone surgery for epilepsy within the 6 months prior to screening.
• 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.
• 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.
• 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.
• 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
• 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.

Sponsors & Collaborators

• Marinus Pharmaceuticals: lead

Study Sites (63)

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

University of California, San Diego

San Diego, California, 92123, United States

Location

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours Children's Hospital - Delaware Valley

Wilmington, Delaware, 19803, United States

Location

University of Florida Gainesville

Gainesville, Florida, 32608, United States

Location

Nemours Children's Health

Jacksonville, Florida, 32207, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Children's Mercy Hosptial

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

Penn State Children's Hospital

Hershey, Pennsylvania, 17033, 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

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Austin Health

Heidelberg, 3084, Australia

Location

Alfred Health

Melbourne, 3004, Australia

Location

Royal Melbourne Hospital

Parkville, 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

First Hospital of Jilin University

Changchun, Jilin, 130028, China

Location

Jiangxi Provincial Children's Hospital

Jiangxi, Nanchang City, 330000, China

Location

Beijing Children Hospital, Capital Medical University

Beijing, Xicheng District, 100045, China

Location

The Affiliated Hospital of Guizhou Medical University

Guiyang, Yunyan District, 550004, China

Location

Peking University First Hospital

Beijing, 100034, China

Location

Chinese PLA General Hospital

Beijing, 100080, China

Location

Chengdu's Women and Children's Central Hospital

Chengdu, 610000, China

Location

University Hospital of Lyon

Bron, 69229, France

Location

University Hospital of Rennes

Rennes, 35033, 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, 01454, Germany

Location

Schneider Children´s Medical Center

Petah Tikva, 4920235, Israel

Location

Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Department of Neurology and Sense Organs, AOU Policlinico di Bari

Bari, 1170124, Italy

Location

Pediatric Neurology and Muscular Diseases Unit - University of Genoa

Genova, 16147, Italy

Location

Policlinico Umberto I

Rome, 00185, Italy

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Sant Joan de Déu

Barcelona, 08950, 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

NHS acute tertiary referral centre, John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Salford Royal Hospital

Salford, M6 8HD, 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: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2022
• First Posted: April 12, 2022
• Study Start: April 1, 2022
• Primary Completion: September 9, 2024
• Study Completion: October 14, 2024
• Last Updated: July 11, 2025
• Results First Posted: July 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (7); DE (6); IL (2); ES (6); FR (3); IT (3); US (23); CA (5); GB (4); AU (4)