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

Phase 3

Terminated

Conditions: Tuberous Sclerosis Complex

Interventions: Drug: Ganaxolone

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: TERMINATED

Sex: All

Target Recruitment: 117

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.

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 Reporting Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Withdrawals and Dose-Reductions Due to AEs	Up to 150 Weeks	An adverse event (AE) was any untoward medical occurrence in a clinical study patient, temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event was any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other event that requires scientific judgment.
Number of Participants With Clinically Significant Changes in Vital Parameters	Up to 150 Weeks	Vital parameters including heart rate, respiration rate, blood pressure, and body temperature were measured in seated position for at least 5 minutes.
Number of Participants With Clinically Significant Changes in Physical Examinations	Up to 150 Weeks	Physical examinations included a full physical evaluation of body systems including: General appearance, head (eyes, ears, nose, and throat), cardiovascular, respiratory, gastrointestinal, genitourinary, musculoskeletal, endocrine/metabolic, hematologic/lymphatic, skin, and other systems as appropriate.
Number of Participants With Clinically Significant Changes in Neurological Examinations	Up to 150 Weeks	Neurological examinations included an evaluation of: Cranial nerves, motor exam, sensory exam, reflexes, coordination/cerebellar
Number of Participants With Clinically Significant Changes in Developmental Examinations	Up to 150 Weeks	Developmental examinations (applicable only to pediatric participants 1 to 17 years of age, inclusive) included an evaluation of speech/language, motor skills, and social skills
Number of Participants With Clinically Significant 12-lead Electrocardiogram (ECG) Findings	Up to 150 Weeks	Twelve-lead ECGs were performed by the physician using an ECG machine that automatically calculates the heart rate and measure PR, QRS, QT and QTc intervals.
Number of Participants With Clinically Significant Changes in Hematology Parameters	Week 1 through Week 150	Blood samples were collected for the analysis of hematology parameters: hemoglobin, hematocrit, erythrocytes, thrombocytes (platelet count). Differential blood counts, including basophils, eosinophils, neutrophils, lymphocytes, and monocytes
Number of Participants With Clinically Significant Changes in Chemistry Parameters	Up to 150 Weeks	Blood samples were collected for the analysis of chemistry parameters: blood urea nitrogen (BUN), potassium, alanine aminotransferase (ALT), alkaline phosphatase (ALP)/serum glutamic pyruvic transaminase (SGPT), total bilirubin, creatinine, sodium, aspartate aminotransferase (AST)/serum glutamic oxaloacetic (SGOT), total protein, fasting blood glucose, calcium, carbon dioxide, estimated glomerular filtration rate (eGFR), and chloride
Number of Participants (Age Greater Than 17 Years) With Abnormal Columbia-Suicide Severity Rating Scale (C-SSRS)	Up to Week 52	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. The score ranges from 1 to 5 and higher scores indicate worse symptoms.
Number of Participants With Clinically Significant Changes in Urinalysis	Up to 150 Weeks	Urine samples were collected for the analysis of urinalysis parameters: Specific gravity, color, clarity, pH, glucose, protein, blood, nitrite, protein, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick, and microscopic examination (if blood or protein was abnormal)

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in 28-day Seizure Frequency During Open Label Extension	Baseline (Day 1), 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. Percent change from baseline in 28-day frequency was calculated for each participant by subtracting Baseline 28-day seizure frequency from post-Baseline 28-day seizure frequency, whole divided by Baseline 28-day seizure frequency and multiplied by 100.

Trial Locations

Locations (54): Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
Nemours Children's Hospital - Delaware Valley
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Wilmington, Delaware, United States
Boston Children's Hospital, Harvard Medical School
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Boston, Massachusetts, United States
Children's Mercy Hospital
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Kansas City, Missouri, United States
Cincinnati Children's Hospital Medical Center
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Cincinnati, Ohio, United States
University of Texas Southwestern Medical Center
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Dallas, Texas, United States
University of Utah Health Care-Pediatric Neurology
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Salt Lake City, Utah, United States
Seattle Children's Hospital
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Seattle, Washington, United States
Royal Brisbane and Women's Hospital
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Herston, Australia
Hôpital Sud
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Rennes, France
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Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States