NCT04737174撤回2 期
Adjunctive ES-481 for Uncontrolled Glioma-Associated Epilepsy and Assessment for Potential Anti-Tumorigenic Effect in Patients With Isocitrate Dehydrogenase 1 (IDH1) Mutant Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Electroencephalogram Monitoring of epileptiform interictal and seizure discharge
研究概览
简要总结
Phase 2A single-arm exploratory clinical study in up to 12 adult subjects aged 18 and older with primary glioma, IDH1 mutation, and uncontrolled focal-onset seizure activity to determine the potential efficacy, safety and pharmacokinetics of ES-481 as adjunctive therapy in glioma-associated epilepsy and to assess for potential anti-tumorigenic effects.
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
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects greater than 18 years of age
- •Subjects with brain tumour-related epilepsy
- •Subjects with a history of uncontrolled seizures (at least three focal-onset seizure per month over the last 28 days)
- •Subjects currently being treated with at least one appropriate AED
- •Subjects who have had a brain MRI performed in the last three months preceding the signing of informed consent
- •Subjects with primary brain tumour with an IDH1 mutation (to be determined during the screening period)
- •Subjects with satisfactory hematologic, renal and liver function, as assessed by the Principal Investigator
- •Subject with a Karnofsky performance scale index (KPD) of > 70%
- •An expected survival time > 6 months
- •A female subject is eligible to participate if she is not pregnant by serum pregnancy test, not breastfeeding, and at least 1 of the following conditions applies:
- •Not of childbearing potential, defined as surgically sterile (documented hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient)
- •Of childbearing potential and agrees to use a highly effective method of contraception consistently during the 4-week dose escalation, 16-week treatment, and 4-week washout periods; and for at least 30 days after the last dose of study treatment
- •A male patient with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception during 4-week dose escalation, 16-week treatment, and 4-week washout periods; and for at least 30 days after the last dose of study treatment and refrains from donating sperm during this period
- •Willing to participate in the study and willing to provide written signed informed consent.
排除标准
- •Urgent need for surgical intervention
- •Alanine aminotransferase or aspartate aminotransferase > 10 times the upper reference limit at the screening visit
- •Estimated glomerular filtration rate < 60 mL/min (calculated using the using the Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation) at the screening visit
- •Any haematological National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 Grade ≥ 3 (with the exception of alopecia) at the screening visit
- •Factors that significantly affect oral drug absorption, such as inability to swallow, chronic diarrhoea, short bowel syndrome, and/or intestinal obstruction
- •Hypertension that cannot be reduced to normal range with antihypertensive medication (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg)
- •Concurrent active cancer that requires non-surgical treatment (e.g., chemotherapy, radiotherapy, adjuvant therapy)
- •History of severe cardiovascular disease: myocardial ischemia or myocardial infarction of Grade 2 or above, poorly controlled arrhythmia (including QTc interval ≥450 ms for men, ≥470 ms for women); according to New York Heart Association standards, Grade 3 or 4 cardiac insufficiency, or colour doppler ultrasound examination of the left ventricular ejection fraction < 50% as assessed at the screening visit
- •In the Investigators opinion, the subject's involvement may affect the progress of the clinical study and/or the determination of the research results, and/or considers them unsuitable for inclusion
- •Previously suffered severe cardiovascular disease: myocardial ischemia or myocardial infarction of Grade 2 or above, poorly controlled arrhythmia (including QTc interval ≥450 ms for men, ≥470 ms for women); according to New York Heart Association standards, Grade 3 or 4 cardiac insufficiency, or color doppler ultrasound examination of the left ventricular ejection fraction < 50%.
- •Investigator judges that may affect the progress of the clinical study and/or the determination of the research results, and/or considers them unsuitable for inclusion.
研究组 & 干预措施
ES-481
Experimental
Administered as 25 mg oral gelatin capsules
干预措施: ES-481 (Drug)
结局指标
主要结局
Electroencephalogram Monitoring of epileptiform interictal and seizure discharge
时间窗: Continual 24 hours
Subject Captured Seizure Activity
时间窗: Continual 24 hour
Subjects will keep daily diary of seizure activity
次要结局
未报告次要终点
研究者
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