A Phase 3, Open-label Study of Adjunctive Ganaxolone (GNX) Treatment in Children and Adults With Tuberous Sclerosis Complex (TSC)-Related Epilepsy (TrustTSC OLE)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 117
- 试验地点
- 54
- 主要终点
- Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Withdrawals and Dose-Reductions Due to AEs
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label, single arm study with no blinding as all participants will receive adjunctive GNX
入排标准
- 年龄范围
- 1 Year 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completion of Study 1042-TSC-3001 or participants who continue to meet study requirements in Study 1042-TSC-
- •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.
排除标准
- •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.
研究组 & 干预措施
Ganaxolone (GNX) oral suspension, 3 times a day (TID)
干预措施: Ganaxolone (Drug)
结局指标
主要结局
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Withdrawals and Dose-Reductions Due to AEs
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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)
次要结局
- Percent Change From Baseline in 28-day Seizure Frequency During Open Label Extension(Baseline (Day 1), Week 52)