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Clinical Trial Details — Status: Enrolling by invitation

Administrative data

NCT number NCT05604170
Other study ID # 1042-TSC-3002
Secondary ID
Status Enrolling by invitation
Phase Phase 3
First received
Last updated
Start date May 16, 2022
Est. completion date June 2027

Study information

Verified date May 2024
Source Marinus Pharmaceuticals
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


Recruitment information / eligibility

Status Enrolling by invitation
Enrollment 132
Est. completion date June 2027
Est. primary completion date June 2027
Accepts healthy volunteers No
Gender All
Age group 1 Year to 65 Years
Eligibility 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 (ß-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 Design


Intervention

Drug:
Ganaxolone
GNX will be administered.

Locations

Country Name City State
Australia Austin Health Heidelberg
Australia Alfred Health Melbourne
Australia Royal Melbourne Hospital Parkville
Australia The Royal Children's Hospital Melbourne Parkville
Canada CHU Sainte-Justine Montréal
Canada Hôtel Dieu de Montréal - CHUM Montréal
Canada The Hospital for Sick Children Toronto
Canada Toronto Western Hospital Toronto
Canada BC Children's Hospital Vancouver
China Beijing Children Hospital, Capital Medical University Beijing
China Chinese PLA General Hospital Beijing
China Peking University First Hospital Beijing
China The Affiliated Hospital of Guizhou Medical University Beijing
China First Hospital of Jilin University Jilin
China Chengdu's Women and Children's Central Hospital Qingyang
France University Hospital of Lyon Bron
France Hôpital de la Pitié-Salpêtrière Paris
France Robert-Debré Hospital Paris
France University Hospital of Rennes Rennes
France University of Strasbourg Strasbourg
Germany Epilepsie-Zentrum Bethel - Krankenhaus Mara Bielefeld
Germany University Hospital Bonn Bonn
Germany ZNN - Epilepsiezentrum Frankfurt am Main Frankfurt
Germany Universitäts Krankenhaus Freiburg Freiburg
Germany Gemeinschaftskrankenhaus Herdecke Herdecke
Germany Epilepsiezentrum Kleinwachau gGmbH Radeberg
Israel Soroka University Medical Center Be'er Sheva
Israel Schneider Children´s Medical Center Petah Tikva
Israel Tel-Aviv Sourasky Medical Center Tel Aviv
Italy Azienda Ospedaliero-Universitaria Meyer Firenze
Italy Pediatric Neurology and Muscular Diseases Unit - University of Genoa Genova
Italy Policlinico Umberto I Rome
Spain Hospital de la Santa Creu i Sant Pau Barcelona
Spain Hospital Sant Joan de Déu Barcelona
Spain Hospital Universitari Vall d'Hebron Barcelona
Spain Hospital Infantil Universitario Niño Jesús Madrid
Spain Hospital Ruber International Madrid
Spain Hospital Regional Universitario de Málaga Málaga
Spain Hospital Universitario y Politécnico La Fe Valencia
United Kingdom 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 States Children's Hospital Colorado Aurora Colorado
United States Child Neurology Consultants of Austin (CNCA) Austin Texas
United States Mid-Atlantic Epilepsy and Sleep Center Bethesda Maryland
United States University of North Carolina at Chapel Hill Chapel Hill North Carolina
United States Medical University of South Carolina Charleston South Carolina
United States Atrium Health/Levine Children's Hospital Charlotte North Carolina
United States Duke University Medical Center Durham North Carolina
United States Penn State Children's Hospital Hershey Pennsylvania
United States McGovern Medical School at the University of Texas Health Science Center Houston Texas
United States Arkansas Children's Research Institute Little Rock Arkansas
United States UCLA Mattel Children's Hospital, TSC Center Los Angeles California
United States Le Bonheur Children's Hospital Memphis Tennessee
United States Children's Hospital of Orange County Orange California
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Mayo Clinic - Rochester Rochester Minnesota
United States University of Rochester Medical Center Rochester New York

Sponsors (1)

Lead Sponsor Collaborator
Marinus Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  France,  Germany,  Israel,  Italy,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of participants with adverse events (AEs), serious adverse events (SAEs) and withdrawals and dose-reductions due to AEs Week 1 through Week 160
Primary Number of participants with abnormal vital signs Week 1 through Week 160
Primary Number of participants with abnormal physical, neurological and developmental examination Week 1 through Week 160
Primary Number of participants with abnormal 12-lead electrocardiogram (ECG) findings Week 1 through Week 160
Primary Number of participants with abnormal clinical laboratory tests Week 1 through Week 156
Primary Number of participants 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. Higher scores indicate worse symptoms. Week 1 through Week 160
Secondary 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. Baseline (Day 1) and Week 1 through Week 52
Secondary Percent change from Baseline in 28-day seizure frequency during the long-term treatment Baseline (Day 1) and Week 1 through Week 52
Secondary Number of participants who will be considered as Treatment Responders Treatment responders are defined as those participants with = 50% reduction from Baseline in seizure frequency during open-label treatment. Week 1 through Week 52
Secondary Number of Participants with Clinical Global Impression of Improvement (CGI-I) 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. Week 1 through Week 156
Secondary Change from Baseline in quality-of-life scale Short Form-36 (SF-36) 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. Baseline (Day 1) and Week 1 through Week 52
Secondary Change from Baseline in percentage of Seizure-Free Days during treatment, based on seizure type Baseline (Day 1) and Week 1 through Week 52
Secondary Change from Baseline in Caregiver Global Impression of Change in Seizure Intensity/Duration (CGI-CSID) 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. Baseline (Day 1) and Week 1 through Week 156
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