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

Study Overview
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Brief Summary
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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

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

Conditions
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Tuberous Sclerosis Complex

Intervention / Treatment
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* Drug: Ganaxolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ganaxolone (GNX) oral suspension, 3 times a day (TID)<br> | Drug: Ganaxolone<br>* GNX will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 12-lead electrocardiogram (ECG) findings |  | Week 1 through Week 160 | 
| Number of participants with abnormal clinical laboratory tests |  | Week 1 through Week 156 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | Treatment responders are defined as those participants with ≥ 50% reduction from Baseline in seizure frequency during open-label treatment. | Week 1 through Week 52 | 
| 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 | 
| 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 | 
| 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberous Sclerosis Complex-Related Epilepsy, Ganaxolone, Adjunctive