Adjunctive GNX Treatment Compared With Placebo in Children and Adults With TSC-related Epilepsy
Study Purpose
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).
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 1 Year - 65 Years |
Gender | All |
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.Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT05323734 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 3 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Marinus Pharmaceuticals |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
N/A |
Principal Investigator Affiliation | N/A |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
Overall Status | Recruiting |
Countries | Canada, France, Germany, Israel, Italy, Spain, United Kingdom, United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Tuberous Sclerosis Complex |
Arms
Experimental: Ganaxalone (GNX)
oral suspension, 3 times a day (TID)
Placebo Comparator: Placebo matching GNX
oral suspension, TID
Interventions
Drug: - Ganaxalone
GNX will be administered
Drug: - Placebo
Placebo will be administered
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Recruiting
Address
Barrow Neurological Institute at Phoenix Children's Hospital
Phoenix, Arizona, 85106
Status
Recruiting
Address
Arkansas Children's Research Institute
Little Rock, Arkansas, 72202
Status
Recruiting
Address
UCLA Mattel Children's Hospital, TSC Center
Los Angeles, California, 90095
Status
Recruiting
Address
Children's Hospital of Orange County
Orange, California, 92868
Status
Not yet recruiting
Address
Childrens Hospital Colorado
Aurora, Colorado, 80045
Status
Recruiting
Address
Nemours Children's Hospital - Delaware Valley
Wilmington, Delaware, 19803
Status
Recruiting
Address
University of Florida Gainesville
Gainesville, Florida, 32608
Status
Recruiting
Address
NW FL Clinical Research Group, LLC
Gulf Breeze, Florida, 32561
Status
Recruiting
Address
Nicklaus Children's Hospital
Miami, Florida, 33155
Status
Recruiting
Address
Orlando Health
Orlando, Florida, 32806
Status
Recruiting
Address
Comprehensive Neurology Clinic
Orlando, Florida, 32825
Status
Recruiting
Address
Children's Healthcare of Atlanta
Atlanta, Georgia, 30329
Status
Recruiting
Address
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Status
Recruiting
Address
Mid Atlantic Epilepsy & Sleep Center
Bethesda, Maryland, 20817
Status
Recruiting
Address
Boston Children's Hospital, Harvard Medical School
Boston, Massachusetts, 02115
Status
Recruiting
Address
Children's Hospital of Michigan Central Michigan University
Detroit, Michigan, 48201
Status
Recruiting
Address
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
Status
Not yet recruiting
Address
University of Missouri Child Health
Columbia, Missouri, 65201
Status
Recruiting
Address
Children's Mercy Hosptial
Kansas City, Missouri, 64108
Status
Recruiting
Address
TSC Clinic at Northeast Regional Epilepsy Group
Hackensack, New Jersey, 07601
Status
Recruiting
Address
Institute of Neurology and Neurosurgery at Saint Barnabas
Livingston, New Jersey, 07039
Status
Not yet recruiting
Address
University of Rochester Medical Center
Rochester, New York, 14642
Status
Recruiting
Address
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Status
Recruiting
Address
Atrium Health/Levine Children's Hospital
Charlotte, North Carolina, 28207
Status
Recruiting
Address
Duke University Medical Center
Durham, North Carolina, 27712
Status
Recruiting
Address
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Status
Recruiting
Address
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Status
Not yet recruiting
Address
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Status
Recruiting
Address
Medical University of South Carolina
Charleston, South Carolina, 29425
Status
Recruiting
Address
Le Bonheur Children's Hospital
Memphis, Tennessee, 38103
Status
Recruiting
Address
Child Neurology Consultants of Austin (CNCA)
Austin, Texas, 78757
Status
Recruiting
Address
University of Texas Southwestern Medical Center
Dallas, Texas, 75207
Status
Recruiting
Address
McGovern Medical School at the University of Texas Health Science Center
Houston, Texas, 77030
Status
Recruiting
Address
University of Utah Health Care-Pediatric Neurology
Salt Lake City, Utah, 84108
Status
Recruiting
Address
Seattle Children's Hospital
Seattle, Washington, 98105
International Sites
Status
Recruiting
Address
Hôtel Dieu de Montréal - CHUM
Montreal, , H2X 0C2
Status
Recruiting
Address
CHU Sainte-Justine
Montréal, , H3T 1C5
Status
Recruiting
Address
The Hospital for Sick Children
Toronto, , M5G 1X8
Status
Recruiting
Address
Toronto Western Hospital
Toronto, , M5T 2S8
Status
Recruiting
Address
BC Children's Hospital
Vancouver, , V6H 3V4
Status
Recruiting
Address
University Hospital of Lyon
Bron, , 69229
Status
Recruiting
Address
University Hospital of Lille
Lille, , 59037
Status
Recruiting
Address
Robert-Debré Hospital
Paris, , 75019
Status
Recruiting
Address
University Hospital of Rennes
Rennes, , 35700
Status
Recruiting
Address
University of Strasbourg
Strasbourg, , 67084
Status
Recruiting
Address
Epilepsie-Zentrum Bethel - Krankenhaus Mara
Bielefeld, , 33617
Status
Recruiting
Address
University Hospital Bonn
Bonn, , 53127
Status
Not yet recruiting
Address
ZNN - Epilepsiezentrum Frankfurt am Main
Frankfurt, , 60528
Status
Recruiting
Address
Universitäts Krankenhaus Freiburg
Freiburg, , 79106
Status
Recruiting
Address
Gemeinschaftskrankenhaus Herdecke
Herdecke, , 58313
Status
Not yet recruiting
Address
Epilepsiezentrum Kleinwachau gGmbH
Radeberg, , 01454
Status
Recruiting
Address
Soroka University Medical Center
Beer-Sheva, , 8410100
Status
Recruiting
Address
Hadassah Medical Center
Jerusalem, , 9112991
Status
Recruiting
Address
Schneider Children´s Medical Center
Petah Tikva, , 4920235
Status
Recruiting
Address
Sheba Medical Center
Tel Hashomer, , 52621
Status
Recruiting
Address
Tel-Aviv Sourasky Medical Center
Tel-Aviv, , 64239
Status
Not yet recruiting
Address
Department of Neurology and Sense Organs, AOU Policlinico di Bari
Bari, , 1170124
Status
Not yet recruiting
Address
Azienda Ospedaliero-Universitaria Meyer
Firenze, , 50139
Status
Not yet recruiting
Address
Pediatric Neurology and Muscular Diseases Unit - University of Genoa
Genova, , 16147
Status
Not yet recruiting
Address
Children's Hospital Bambino Gesù
Rome, , 00165
Status
Not yet recruiting
Address
Policlinico Umberto I
Rome, , 00185
Status
Recruiting
Address
Hospital de la Santa Creu i Sant Pau
Barcelona, , 08025
Status
Recruiting
Address
Hospital Universitari Vall d'Hebron
Barcelona, , 08035
Status
Recruiting
Address
Hospital Sant Joan de Déu
Barcelona, , 08950
Status
Recruiting
Address
Hospital Infantil Universitario Niño Jesús
Madrid, , 28009
Status
Recruiting
Address
Hospital Ruber International
Madrid, , 28034
Status
Recruiting
Address
Hospital Regional Universitario de Málaga
Málaga, , 29010
Status
Recruiting
Address
Hospital Universitario y Politécnico La Fe
Valencia, , 46026
Status
Recruiting
Address
Royal Aberdeen Children's Hospital, NHS Grampian
Aberdeen, , AB25 2ZG
Status
Recruiting
Address
Bristol Royal Hospital for Children
Bristol, , BS2 8AE
Status
Recruiting
Address
Leeds General Infirmary
Leeds, , LS1 3EX
Status
Recruiting
Address
NHS acute tertiary referral centre, John Radcliffe Hospital
Oxford, , OX3 9DU
Status
Recruiting
Address
Salford Royal Hospital
Salford, , M6 8HD
Status
Recruiting
Address
Sheffield Children's Hospital
Sheffield, , S10 2TH