NCT04244175已完成2 期
A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Trial of CVL-865 as Adjunctive Therapy in Adults With Drug-Resistant Focal Onset Seizures (REALIZE Trial)
AbbVie72 个研究点 分布在 4 个国家目标入组 154 人开始时间: 2020年1月27日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 154
- 试验地点
- 72
- 主要终点
- Response Ratio (RRatio)
研究概览
简要总结
The goal of this clinical trial is to learn if CVL-865, when taken regularly with other anti-seizure medicines, works to prevent seizures in adults with drug-resistant focal onset seizures. It will also learn about the safety of CVL-865.
The main question it aims to answer is whether CVL-865, when taken regularly with other anti-seizure medicines, lowers the number of seizures in those with a diagnosis of epilepsy with drug-resistant focal onset seizures.
This study has an 8-week Screening/Baseline Period, a 13-week Treatment Period (including a 2-week Titration Phase, an 8-week Maintenance Phase, and a 3-week Taper Phase), and a 4-week Safety Follow-Up Period.
Participants will take CVL-865 or a placebo twice a day during the 10-13 week Treatment Period, visit the clinic every few weeks for checkups, tests, and surveys, and fill out an e-Diary.
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
- Double (Participant, Investigator)
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
- •Participants with a diagnosis of epilepsy with focal onset, as defined in the International League Against Epilepsy (ILAE) Classification of Seizures, focal aware (except participants with only focal aware seizures without a motor component), focal impaired awareness, and focal to bilateral tonic-clonic seizures for at least 2 years prior to signing the Informed Consent Form (ICF)
- •Participants must have history of an average of 4 or more spontaneous and observable focal onset, as defined in the ILAE Classification of Seizures, focal aware (except participants with only focal aware seizures without a motor component), focal impaired awareness, and focal to bilateral tonic-clonic seizures per 28-day period for at least 3 months (84 days) prior to signing the ICF
- •Participants who have tried and failed at least 2 appropriate Anti- epileptic drugs (AEDs) in the past and also currently taking 1 to 3 permitted AEDs at a stable dose for 4 Weeks prior to the Screening Visit
- •Participants with a minimum of 8 focal onset, focal aware, focal impaired awareness, or focal to bilateral tonic-clonic seizures during the 8 week baseline period with no 21-day period free of any of these seizure types
- •Participants must have had magnetic resonance imaging or contrast enhance computed tomography scan of the brain that demonstrated no progressive structural central nervous system abnormality at the time of the diagnosis of epilepsy
- •Participants must have a body mass index (BMI) of 17.5 to 40.0 kilogram per meter square (kg/m^2) and a total body weight greater than (>) 50 kilograms (kg) [110 pounds (lbs)]
- •Women of childbearing potential must agree to use an effective method of contraception from signing of informed consent throughout the duration of the study and for 30 days post last dose
- •Male must agree to use condom during treatment and until the end of relevant systemic exposure in the male participant for 94 days following the last dose with Investigational Manufacturing Product (IMP)
排除标准
- •Participants with (genetic) idiopathic generalized epilepsies or combined generalized and focal epilepsies, including a history of Lennox-Gastaut Syndrome
- •Participants with a history of seizures over the past 12 months that occur at such a high frequency they cannot be counted (eg, repetitive seizures, cluster seizures)
- •Participants with a history of psychogenic non-epileptic seizures within the year prior to signing the ICF
- •Participants with a history of status epilepticus within 5 years prior to signing the ICF
- •Participants with a history of neurosurgery for seizures less than 1 year prior to signing the ICF, or radiosurgery less than 2 years prior to signing the ICF
- •Participants with a current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or neurological (excluding focal onset epilepsy) disease
- •Participants who test positive for human immunodeficiency virus (HIV), hepatitis B and/or or hepatitis C infection
- •Participants with a 12-lead ECG demonstrating : QT interval corrected for heart rate using Fridericia's formula >450 milliseconds (msec) (average of 3 ECGs obtained at the Screening Visit); QRS interval >120 msec at the Screening Visit assessed by central reader
- •Participants with abnormal laboratory test results which includes (Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) elevated to >2 × Upper limit of normal range (ULN); Total bilirubin greater than or equal to (>=)1.5 × ULN; Females: Hemoglobin <11 gram per deciliter (g/dL); Males: hemoglobin <12 g/dL; White blood cell (WBC) count <3.0 x 10 power 9 per liter (10^9/L); Neutrophil count <2.0 x 10^9/L; Platelet count <150 × 10^9/L
- •Use of prohibited medications as listed in the protocol in the absence of appropriate washout phase or the likelihood of requiring treatment during the study period with drugs not permitted by the study protocol
- •Participants taking any drug that is a sensitive P-glycoprotein (P-gp) and Breast cancer resistance protein (BCRP) substrate
- •Female participants who are breastfeeding and/or who have a positive pregnancy test result prior to receiving IMP
- •Participants who are known to be allergic or hypersensitive to the IMP or any of its components
- •Participants who have participated in any clinical trial within 60 days prior to signing the ICF or who have participated in more than 2 clinical trials within the year prior to signing the ICF
- •Participants with difficulty swallowing
- •Participants who answer "Yes" on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria for this CSSRS Item 5 occurred within the last 6 months OR Subjects who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred in the last 2 years
研究组 & 干预措施
Placebo
Placebo Comparator
Participants received a placebo matched to CVL-865 tablets orally twice a day (BID) during the 2-week Titration Phase, the 8-week Maintenance Phase, and the 3-week Taper Phase.
干预措施: Placebo (Drug)
CVL-865 7.5 mg BID
Experimental
CVL-865 tablets were administered orally as 2.5 mg twice a day (BID) for 1 week followed by 5 mg BID for another week during the Titration Phase, and then 7.5 mg BID during the 8-week Maintenance Phase. For participants not enrolling into the open-label extension trial, following the Maintenance Phase the dose was gradually decreased over a 3-week Taper Phase.
干预措施: CVL-865 (Drug)
CVL-865 25 mg BID
Experimental
CVL-865 tablets were administered orally as 5 mg twice a day (BID) for 1 week followed by 12.5 mg for another week during the Titration Phase, and then 25 mg BID during the 8-week Maintenance Phase. For participants not enrolling into the open-label extension trial, following the Maintenance Phase the dose was gradually decreased over a 3-week Taper Phase.
干预措施: CVL-865 (Drug)
结局指标
主要结局
Response Ratio (RRatio)
时间窗: Baseline Period; Maintenance Phase Days 15 through 71
Response Ratio (RRatio) is calculated as RRatio=(T-B)/(T+B) ×100, where T represents the focal onset seizure frequency rate per week in the Maintenance Phase and B represents the focal onset seizure frequency rate per week in the Baseline Period. The Response Ratio ranges between -100 and 100; negative values indicate reduction in seizure rate and positive values indicate increase in seizure rate during treatment.
次要结局
- Percentage Change From Baseline in Focal Onset Seizure Frequency Per Week Over the Maintenance Phase(Baseline Period; Maintenance Phase Days 15 through 71)
- Percentage of Participants With 50 Percent (%) Responder Rate(Baseline Period; Maintenance Phase Days 15 through 71)
- Percentage of Seizure-free Participants During the Maintenance Phase(Maintenance Phase Days 15 through 71)
- Weekly Seizure Rate During the Maintenance Phase(Maintenance Phase Weeks 1, 2, 3, 4, 5, 6, 7, 8)
- Patient's Global Impression of Change (PGI-C) Score at Maintenance Phase Days 15, 43, and 71(Maintenance Phase Days 15, 43, and 71)
- Change From Baseline in Clinical Global Impression-Severity of Symptoms Scale (CGI-S) Score at Maintenance Phase Days 15, 43, and 71(Baseline, Maintenance Phase Days 15, 43, and 71)
- Clinical Global Impression-Improvement Scale (CGI-I) Score at Maintenance Phase Days 15, 43, and 71(Baseline, Maintenance Phase Days 15, 43, and 71)
- Change From Baseline in Quality of Life in Epilepsy-31 (QOLIE-31) Overall Score at Maintenance Phase Day 71(Baseline, Maintenance Phase Day 71)
- Change From Baseline in Health Utilities Index (HUI) Utility Score at Maintenance Phase Day 71(Baseline, Maintenance Phase Day 71)
- Number of Participants With Treatment Emergent Adverse Event (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)(From first dose of study drug until 30 days following last dose of study drug (up to Day 120))
- Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs)(Baseline; From first dose of study drug until 30 days following last dose of study drug (up to Day 120))
- Number of Participants With Clinically Significant Changes in Vital Sign Measurements(From first dose of study drug until 30 days following last dose of study drug (up to Day 120))
- Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results(Baseline; From first dose of study drug until 30 days following last dose of study drug (up to Day 120))
- Number of Participants With Positive Response to Columbia Suicide-Severity Rating Scale (C-SSRS)(From first dose of study drug until 30 days following last dose of study drug (up to Day 120))
- Change in Modified Clinical Institute Withdrawal Assessment - Benzodiazepines (mCIWA-B) From Last On-treatment Assessment(Maintenance Phase Day 71, Taper Phase Days 78, 85, and 92, and Safety Follow-up Days 99 and 120)
- Number of Participants With Adverse Events That Are Abuse-related or Involve Medication Handling Irregularities (MHI)(From first dose of study drug until 30 days following last dose of study drug (up to Day 120))
- Plasma Concentrations of CVL-865 on Maintenance Phase Days 15, 43, and 71, and Taper Phase Day 92(Maintenance Phase Days 15, 43, and 71, and Taper Phase Day 92)
研究者
研究点 (72)
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