Clinical trial NCT05604170: Open-label Study of Adjunctive GNX Treatment in Children and Adults With TSC-related Epilepsy
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)
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Tuberous Sclerosis Complex
Keywords: Tuberous Sclerosis Complex-Related Epilepsy
Ganaxolone
Adjunctive
Lead sponsor: Marinus Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-11-03
Enrollment: 132
Sex: ALL
Minimum age (years): 1
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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 (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
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.

Primary outcomes:
measure: Number of participants with adverse events (AEs), serious adverse events (SAEs) and withdrawals and dose-reductions due to AEs
timeFrame: Week 1 through Week 160
measure: Number of participants with abnormal vital signs
timeFrame: Week 1 through Week 160
measure: Number of participants with abnormal physical, neurological and developmental examination
timeFrame: Week 1 through Week 160
measure: Number of participants with abnormal 12-lead electrocardiogram (ECG) findings
timeFrame: Week 1 through Week 160
measure: Number of participants with abnormal clinical laboratory tests
timeFrame: Week 1 through Week 156
measure: Number of participants with abnormal Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Week 1 through Week 160
Secondary outcomes:
measure: Percent change from Baseline in 28-day seizure frequency during open label extension
timeFrame: Baseline (Day 1) and Week 1 through Week 52
measure: Percent change from Baseline in 28-day seizure frequency during the long-term treatment
timeFrame: Baseline (Day 1) and Week 1 through Week 52
measure: Number of participants who will be considered as Treatment Responders
timeFrame: Week 1 through Week 52
measure: Number of Participants with Clinical Global Impression of Improvement (CGI-I)
timeFrame: Week 1 through Week 156
measure: Change from Baseline in quality-of-life scale Short Form-36 (SF-36)
timeFrame: Baseline (Day 1) and Week 1 through Week 52
measure: Change from Baseline in percentage of Seizure-Free Days during treatment, based on seizure type
timeFrame: Baseline (Day 1) and Week 1 through Week 52
measure: Change from Baseline in Caregiver Global Impression of Change in Seizure Intensity/Duration (CGI-CSID)
timeFrame: Baseline (Day 1) and Week 1 through Week 156
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Research Institute
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA Mattel Children's Hospital, TSC Center
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health/Levine Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Hershey
country: United States
facility: Penn State Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Austin
country: United States
facility: Child Neurology Consultants of Austin (CNCA)
state: Texas
city: Houston
country: United States
facility: McGovern Medical School at the University of Texas Health Science Center
state: Texas
city: Heidelberg
country: Australia
facility: Austin Health
city: Melbourne
country: Australia
facility: Alfred Health
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
city: Parkville
country: Australia
facility: The Royal Children's Hospital Melbourne
city: Montréal
country: Canada
facility: Hôtel Dieu de Montréal - CHUM
city: Montréal
country: Canada
facility: CHU Sainte-Justine
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Toronto
country: Canada
facility: Toronto Western Hospital
city: Vancouver
country: Canada
facility: BC Children's Hospital
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Beijing Children Hospital, Capital Medical University
city: Beijing
country: China
facility: Chinese PLA General Hospital
city: Beijing
country: China
facility: The Affiliated Hospital of Guizhou Medical University
city: Jilin
country: China
facility: First Hospital of Jilin University
city: Qingyang
country: China
facility: Chengdu's Women and Children's Central Hospital
city: Bron
country: France
facility: University Hospital of Lyon
city: Paris
country: France
facility: Robert-Debré Hospital
city: Paris
country: France
facility: Hôpital de la Pitié-Salpêtrière
city: Rennes
country: France
facility: University Hospital of Rennes
city: Strasbourg
country: France
facility: University of Strasbourg
city: Bielefeld
country: Germany
facility: Epilepsie-Zentrum Bethel - Krankenhaus Mara
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Frankfurt
country: Germany
facility: ZNN - Epilepsiezentrum Frankfurt am Main
city: Freiburg
country: Germany
facility: Universitäts Krankenhaus Freiburg
city: Herdecke
country: Germany
facility: Gemeinschaftskrankenhaus Herdecke
city: Radeberg
country: Germany
facility: Epilepsiezentrum Kleinwachau gGmbH
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Center
city: Petah Tikva
country: Israel
facility: Schneider Children´s Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Meyer
city: Genova
country: Italy
facility: Pediatric Neurology and Muscular Diseases Unit - University of Genoa
city: Rome
country: Italy
facility: Policlinico Umberto I
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
city: Madrid
country: Spain
facility: Hospital Ruber International
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Oxford
country: United Kingdom
facility: NHS acute tertiary referral centre, John Radcliffe Hospital
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
Study officials:
References: