A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Exploring the Efficacy, Safety, and Tolerability of Natalizumab (BG00002) as Adjunctive Therapy in Adult Subjects With Drug-Resistant Focal Epilepsy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment
研究概览
简要总结
The primary efficacy objective of the study is to determine if adjunctive therapy of natalizumab 300 mg intravenous (IV) every 4 weeks reduces the frequency of seizures in adult participants with drug-resistant focal epilepsy. The secondary efficacy objective is to assess the effects of natalizumab versus placebo in drug-resistant focal epilepsy on additional measures of seizure frequency.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Double-blind
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
- •Must have focal epilepsy diagnosed on clinical grounds and as applicable supported by electroencephalogram findings [Scheffer 2017] and brain imaging. Participants with multifocal epilepsy may be included if all other entry criteria are met.
- •Must have a drug-resistant epilepsy defined as failure of adequate trials of 2 (or more) tolerated and appropriately chosen and used AEDs (whether as monotherapies or in combination) [Kwan 2010].
- •Experiences 6 or more seizures during the 6-week prospective baseline period and is not seizure free for more than 21 consecutive days during the prospective baseline period
排除标准
- •Focal aware seizures without motor signs are the only seizure type.
- •Diagnosis of generalized, combined generalized and focal, or unknown epilepsy
- •Known progressive structural CNS lesion.
- •History of seizures occurring in predominantly clustered patterns, as determined by the Investigator, over the 12 months prior to the Screening Visit (Week -6) or during the 6-week prospective baseline period, where individual seizures cannot be counted.
- •History of status epilepticus within the previous 6 months.
- •Known history or presence of non-epileptic seizures.
- •NOTE; Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Natalizumab 300 mg
Participants will undergo a prospective baseline period of 6 weeks (Weeks -6 to 0) followed by placebo controlled phase to receive natalizumab 300 mg intravenous (IV) infusion every 4 weeks from Week 0 to Week 24. Participants will continue to receive natalizumab 300 mg IV infusion every 4 weeks for up to an additional 24 weeks in open label phase.
干预措施: Natalizumab (Drug)
Placebo
Participants will undergo a prospective baseline period of 6 weeks (Weeks -6 to 0) followed by placebo controlled phase to receive natalizumab matching placebo intravenous (IV) infusion every 4 weeks from Week 0 to Week 24. Participants will then receive natalizumab 300 mg IV infusion every 4 weeks for 24 weeks in open label phase.
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment
时间窗: Baseline, Week 8 to Week 24
Seizures included were focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizure. Focal aware seizures without motor signs were not included. Seizure clusters (where individual seizures cannot be distinguished) were counted as 1 seizure per cluster on each day that they are present. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participant's seizure diary data during prospective baseline phase. Seizure frequency (SF) at post baseline visit was calculated based on sum of the seizures reported in participant seizure diary and the number of days with non-missing SF data in participant seizure diary on or after the previous visit date. Change from Baseline are based on natural log transformation of baseline SF or SF at post baseline visit correspondingly. For log-transformation, the quantity 0.2 {ln(x+0.2)} was added to the SF at post baseline visit to account for 0 seizure count.
次要结局
- Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment(Week 8 to Week 24)
- Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment(Baseline, Week 8, Week 12, Week 16, Week 20, Week 24)
- Percentage of Responders During Weeks 8 to 24 of Treatment(Week 8 to Week 24)
- Percentage of Participants With Inadequate Treatment Response During Weeks 8 to 24 of Treatment(Week 8 to Week 24)