A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 as Adjunctive Therapy in Focal-onset Epilepsy, With an Open-label Extension
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 325
- 试验地点
- 94
- 主要终点
- Median Percent Change in Focal Seizure Frequency
研究概览
简要总结
The XEN1101 Phase 2 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of increasing doses of XEN1101 administered as adjunctive treatment in adult patients diagnosed with focal epilepsy, followed by an optional open-label extension (OLE).
详细描述
The XEN1101 Phase 2 clinical trial is designed as a randomized, double-blind, placebo-controlled, multicenter study with an optional open-label extension (OLE) to evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive treatment in adult patients aged 18 to 75 years diagnosed with focal epilepsy. Approximately 300 patients will be randomized in a blinded manner to one of three active treatment groups or placebo in a 2:1:1:2 fashion (XEN1101 25 mg : 20 mg : 10 mg : Placebo). After screening, patients will have 8 weeks of baseline to assess frequency of seizures, followed by 8 weeks of treatment and a 6-week post treatment follow-up period. In order to be included in the study, patients must already be treated with a stable dose of 1 to 3 allowable current anti-epileptic drugs for at least one month prior to screening, during baseline, and throughout the double-blind portion (DBP) of the study. During the treatment period, patients will be given XEN1101 or placebo once daily in the evening. An OLE will be available to eligible patients who complete the DBP. All patients will receive a 20 mg daily dose of XEN1101 during this extension period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study
- •BMI ≤40 kg/m2
- •Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy [ILAE] Classification of Epilepsy (2017)
- •Prior neuroimaging within the last 10 years and documentation is available
- •Treatment with a stable dose of 1 to 3 allowable current AEDs for at least one month prior to screening, during baseline, and throughout the duration of the DBP
- •Must be willing to comply with the contraception requirements
- •Males must agree not to donate sperm from the time of the first administration of study drug until 6 months after the last dose. Females must agree not to donate ova from the time of the first administration of study drug until 6 months after the last dose.
- •Able to keep accurate seizure diaries
排除标准
- •History of pseudoseizures, psychogenic seizures, primary generalized seizure, or focal aware non-motor seizures only
- •Presence or previous history of Lennox-Gastaut syndrome
- •Seizures secondary to other diseases or conditions
- •History of repetitive seizures within the last 12 months where the individual seizures cannot be counted
- •History of neurosurgery for seizures <1 year prior to enrollment, or radiosurgery <2 years prior to enrollment
- •Schizophrenia and other psychotic disorders, or active suicidal plan/intent in the past 6 months, or a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt
- •History or presence of any significant medical or surgical condition or uncontrolled medical illness at screening, or history of cancer within the past 2 years, with the exception of appropriately treated basal cell or squamous cell carcinoma
- •Any clinically significant abnormalities on pre-study physical examination, vital signs, laboratory values or ECG indicating a medical problem that would preclude study participation including but not limited to:
- •History of presence of long QT syndrome; QTcF > 450 msec at baseline; family history of sudden death of unknown cause
- •History of skin or retinal pigment epithelium abnormalities caused by ezogabine
- •Past use of vigabatrin without stable visual fields tested twice over the 12 months after the last dose of vigabatrin (concomitant use of vigabatrin is not allowed)
- •If felbamate is used as a concomitant AED, patients must be taking it for at least 2 years, with a stable dose for 2 months (or no less than 49 days) and acceptable hematology and LFT history and values prior to Screening. If received in the past, felbamate must have been discontinued 2 months (or no less than 49 days) prior to Screening.
- •Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity reactions
- •Current use of a ketogenic diet
研究组 & 干预措施
25 mg XEN1101
Capsule filled with 25 mg XEN1101
干预措施: XEN1101 (Drug)
20 mg XEN1101
Capsule filled with 20 mg XEN1101
干预措施: XEN1101 (Drug)
10 mg XEN1101
Capsule filled with 10 mg XEN1101
干预措施: XEN1101 (Drug)
Placebo
Placebo capsule
干预措施: XEN1101 (Drug)
结局指标
主要结局
Median Percent Change in Focal Seizure Frequency
时间窗: From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56)
Median percent change in monthly (28 days) focal seizure frequency from baseline to DBP for XEN1101 versus placebo
次要结局
- 50% XEN1101 Response Rate(From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56))
- Percent Change in Focal Seizure Frequency Over Time(From baseline (8 weeks prior to Day 0) through to the final dose (up to Day 56))