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

Tuberous Sclerosis Complex Clinical Trial

Official title:

A Phase 3, Open-label Study of Adjunctive Ganaxolone (GNX) Treatment in Children and Adults With Tuberous Sclerosis Complex (TSC)-Related Epilepsy (TrustTSC OLE)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

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

Study information

• Verified date: December 2023
• Source: Marinus Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• 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.

Related Conditions & MeSH terms

• Epilepsy
• Sclerosis
• Tuberous Sclerosis
• Tuberous Sclerosis Complex

Intervention

Drug:
• Ganaxolone
GNX will be administered.

Locations

Country	Name	City	State
Australia	Queensland Health	Brisbane
Australia	Austin Health	Heidelberg
Australia	Royal Brisbane and Women's Hospital	Herston
Australia	Alfred Health	Melbourne
Australia	Western Sydney Local health District	North Parramatta
Australia	Royal Melbourne Hospital	Parkville
Australia	The Royal Children's Hospital Melbourne	Parkville
Australia	Prince of Wales Hospital	Randwick
Belgium	Antwerp University Hospital (UZA)	Edegem
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	Peking University First Hospital	Beijing
China	The Affiliated Hospital of Guizhou Medical University	Beijing
France	University Hospital of Lyon	Bron
France	University Hospital of Lille	Lille
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	Petach Tikva
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Israel	Sheba Medical Center	Tel HaShomer
Italy	Department of Neurology and Sense Organs, AOU Policlinico di Bari	Bari
Italy	Azienda Ospedaliero-Universitaria Meyer	Firenze
Italy	Pediatric Neurology and Muscular Diseases Unit - University of Genoa	Genova
Italy	Children's Hospital Bambino Gesù	Rome
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	Royal Aberdeen Children's Hospital, NHS Grampian	Aberdeen
United Kingdom	Bristol Royal Hospital for Children	Bristol
United Kingdom	Leeds General Infirmary	Leeds
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 Healthcare of Atlanta	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Child Neurology Consultants of Austin (CNCA)	Austin	Texas
United States	Mid-Atlantic Epilepsy & Sleep Center	Bethesda	Maryland
United States	Boston Children's Hospital, Harvard Medical School	Boston	Massachusetts
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	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Children's Hospital of Michigan Central Michigan University	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida Gainsville	Gainesville	Florida
United States	NW FL Clinical Research Group, LLC	Gulf Breeze	Florida
United States	TSC Clinic at Northeast Regional Epilepsy Group	Hackensack	New Jersey
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	Children's Mercy Hospital	Kansas City	Missouri
United States	Arkansas Children's Research Institute	Little Rock	Arkansas
United States	Institute of Neurology and Neurosurgery at Saint Barnabas	Livingston	New Jersey
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	UCLA Mattel Children's Hospital, TSC Center	Los Angeles	California
United States	Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute at Phoenix Children's Hospital	Phoenix	Arizona
United States	Virginia Commonwealth University (VCU) Health System	Richmond	Virginia
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	University of Utah Health Care-Pediatric Neurology	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	Nemours Children's Hospital - Delaware Valley	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Marinus Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  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