Open-label Study of Adjunctive GNX Treatment in Children and Adults With TSC-related Epilepsy
- Registration Number
- NCT05604170
- Lead Sponsor
- Marinus Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 132
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ganaxolone (GNX) oral suspension, 3 times a day (TID) Ganaxolone -
- Primary Outcome Measures
Name Time Method Number of participants with abnormal vital signs Week 1 through Week 160 Number of participants with abnormal physical, neurological and developmental examination Week 1 through Week 160 Number of participants with abnormal clinical laboratory tests Week 1 through Week 156 Number of participants with adverse events (AEs), serious adverse events (SAEs) and withdrawals and dose-reductions due to AEs Week 1 through Week 160 Number of participants with abnormal 12-lead electrocardiogram (ECG) findings Week 1 through Week 160 Number of participants with abnormal Columbia-Suicide Severity Rating Scale (C-SSRS) Week 1 through Week 160 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. Higher scores indicate worse symptoms.
- Secondary Outcome Measures
Name Time Method Percent change from Baseline in 28-day seizure frequency during the long-term treatment Baseline (Day 1) and Week 1 through Week 52 Number of participants who will be considered as Treatment Responders Week 1 through Week 52 Treatment responders are defined as those participants with ≥ 50% reduction from Baseline in seizure frequency during open-label treatment.
Change from Baseline in Caregiver Global Impression of Change in Seizure Intensity/Duration (CGI-CSID) Baseline (Day 1) and Week 1 through Week 156 The CGI-CSID is a 7-point Likert scale in which the parent(s)/caregiver(s)/LAR(s) assesses change in seizure intensity and/or duration after initiation of investigational product relative to Baseline (prior to treatment with investigational product). The scale ranges from 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 indicate worse condition.
Percent change from Baseline in 28-day seizure frequency during open label extension Baseline (Day 1) and Week 1 through Week 52 Seizure frequency will be calculated as the total number of seizures divided by the number of days with seizure data, multiplied by 28.
Change from Baseline in percentage of Seizure-Free Days during treatment, based on seizure type Baseline (Day 1) and Week 1 through Week 52 Change from Baseline in quality-of-life scale Short Form-36 (SF-36) Baseline (Day 1) and Week 1 through Week 52 The SF-36 is a multi-purpose survey designed to capture participant or parent(s)/caregiver(s)/LAR(s) perceptions of own health and well-being. The SF-36 has 36 items grouped in 8 dimensions: physical functioning, physical and emotional limitations, social functioning, bodily pain, general, and mental health, which are the weighted sums of the questions in each section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. Higher scores represent better health-related quality-of-life.
Number of Participants with Clinical Global Impression of Improvement (CGI-I) Week 1 through Week 156 The CGI-I is a 7-point Likert scale that the parent(s)/caregiver(s)/legally authorized representative (LAR)(s) and clinician uses to rate the change in overall seizure control, behavior, safety, and tolerability after initiation of the Investigational product (IP) relative to Baseline (prior to treatment with the IP). It was rated as: 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.
Trial Locations
- Locations (59)
UCLA Mattel Children's Hospital, TSC Center
🇺🇸Los Angeles, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Atrium Health/Levine Children's Hospital
🇺🇸Charlotte, North Carolina, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Child Neurology Consultants of Austin (CNCA)
🇺🇸Austin, Texas, United States
McGovern Medical School at the University of Texas Health Science Center
🇺🇸Houston, Texas, United States
Le Bonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
BC Children's Hospital
🇨🇦Vancouver, Canada
Peking University First Hospital
🇨🇳Beijing, China
The Affiliated Hospital of Guizhou Medical University
🇨🇳Beijing, China
Beijing Children Hospital, Capital Medical University
🇨🇳Beijing, China
Chinese PLA General Hospital
🇨🇳Beijing, China
Chengdu's Women and Children's Central Hospital
🇨🇳Qingyang, China
First Hospital of Jilin University
🇨🇳Jilin, China
University Hospital of Rennes
🇫🇷Rennes, France
Pediatric Neurology and Muscular Diseases Unit - University of Genoa
🇮🇹Genova, Italy
Soroka University Medical Center
🇮🇱Be'er Sheva, Israel
Tel-Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Ruber International
🇪🇸Madrid, Spain
Hospital Sant Joan de Déu
🇪🇸Barcelona, Spain
Hospital Infantil Universitario Niño Jesús
🇪🇸Madrid, Spain
Hospital Regional Universitario de Málaga
🇪🇸Málaga, Spain
Hospital Universitario y Politécnico La Fe
🇪🇸Valencia, Spain
Bristol Royal Hospital for Children
🇬🇧Bristol, United Kingdom
NHS acute tertiary referral centre, John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Salford Royal Hospital
🇬🇧Salford, United Kingdom
Sheffield Children's Hospital
🇬🇧Sheffield, United Kingdom
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Mid-Atlantic Epilepsy and Sleep Center
🇺🇸Bethesda, Maryland, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Alfred Health
🇦🇺Melbourne, Australia
Austin Health
🇦🇺Heidelberg, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Australia
The Royal Children's Hospital Melbourne
🇦🇺Parkville, Australia
ZNN - Epilepsiezentrum Frankfurt am Main
🇩🇪Frankfurt, Germany
Arkansas Children's Research Institute
🇺🇸Little Rock, Arkansas, United States
University of Strasbourg
🇫🇷Strasbourg, France
Azienda Ospedaliero-Universitaria Meyer
🇮🇹Firenze, Italy
Policlinico Umberto I
🇮🇹Rome, Italy
University Hospital of Lyon
🇫🇷Bron, France
University Hospital Bonn
🇩🇪Bonn, Germany
Gemeinschaftskrankenhaus Herdecke
🇩🇪Herdecke, Germany
Schneider Children´s Medical Center
🇮🇱Petah Tikva, Israel
CHU Sainte-Justine
🇨🇦Montréal, Canada
Epilepsiezentrum Kleinwachau gGmbH
🇩🇪Radeberg, Germany
The Hospital for Sick Children
🇨🇦Toronto, Canada
Toronto Western Hospital
🇨🇦Toronto, Canada
Universitäts Krankenhaus Freiburg
🇩🇪Freiburg, Germany
Robert-Debré Hospital
🇫🇷Paris, France
Hôpital de la Pitié-Salpêtrière
🇫🇷Paris, France
Hôtel Dieu de Montréal - CHUM
🇨🇦Montréal, Canada
Epilepsie-Zentrum Bethel - Krankenhaus Mara
🇩🇪Bielefeld, Germany
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States