Prospective, Double-blind, Placebo-controlled, Randomized, Parallel-group, Multi-center Study With an Open-label Extension Period to Investigate the Efficacy and Safety of Two Different Doses of NT 201 in Botulinum Toxin Treatment-naïve Subjects With Blepharospasm
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 11
- 主要终点
- Double-blind MP: Change From Baseline in JRS Severity Subscore at Day 43 (Visit 4)
研究概览
简要总结
This phase 3 study will serve to collect efficacy and safety data of two different doses of NT 201 in subjects suffering from Bilateral Blepharospasm (BEB) who are BTX treatment-naïve.
In this study, BTX treatment-naïve subjects are defined as those who have not received BTX treatment within the last 12 months for the treatment of BEB. This definition aims to avoid bias by comparison of treatment effects in the subject's assessments. Furthermore, this study will substantiate the existing efficacy and safety database for the indication BEB.
详细描述
Subjects to receive one injection with NT 201 or placebo at baseline of the placebo-controlled first cycle. Thereafter, all subjects entering the Open-Label Extension Period (OLEX) to receive a second injection of NT 201 (second injection cycle).
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female out-patients age ≥ 18 and ≤ 80 years.
- •A clinical diagnosis of bilateral BEB characterized by spontaneous, spasmodic, intermittent or persistent involuntary contractions of orbicular oculi muscles.
- •A need for injection of BTX defined as a Jankovic Rating Scale [JRS] severity subscore ≥
- •Treatment-naïve subject defined as at least 12 months without BTX of any serotype for the treatment of BEB before administration of IP.
排除标准
- •Subject with any previous unsuccessful treatment with BTX of any serotype for the treatment of BEB.
- •Atypical variant of BEB (e.g., apraxia of the eyelid opening) caused by inhibition of levator palpebrae muscle.
- •Neuroleptic-induced blepharospasm.
- •Myotomy or denervation surgery in the affected muscles (e.g., peripheral denervation, spinal cord stimulation) and surgery in the upper face.
- •Generalized disorders of muscles activity (e.g., myasthenia gravis in particular ocularis, Lambert-Eaton-Syndrome, amyotrophic lateral sclerosis) or any other significant neuromuscular dysfunction which might interfere with the study.
研究组 & 干预措施
IncobotulinumtoxinA (Xeomin) 25U per eye
Main Period: one injection session, 25 Units per eye. Open-Label Extension: one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
干预措施: IncobulinumtoxinA (Xeomin), 25 Units (Drug)
IncobotulinumtoxinA (Xeomin) 25U per eye
Main Period: one injection session, 25 Units per eye. Open-Label Extension: one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
干预措施: IncobotulinumtoxinA (Xeomin), 35 Units (Drug)
IncobotulinumtoxinA (Xeomin) 12.5U per eye
Main Period: one injection session, 12.5 Units per eye. Open-Label Extension Period: one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
干预措施: IncobotulinumtoxinA (Xeomin), 12.5 Units (Drug)
IncobotulinumtoxinA (Xeomin) 12.5U per eye
Main Period: one injection session, 12.5 Units per eye. Open-Label Extension Period: one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
干预措施: IncobotulinumtoxinA (Xeomin), 35 Units (Drug)
Placebo
Main Period: Placebo to IncobotulinumtoxinA (Xeomin)(12.5 or 25U/eye), one injection session.
Open-Label Extension: IncobotulinumtoxinA (Xeomin), one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
干预措施: Placebo (Drug)
Placebo
Main Period: Placebo to IncobotulinumtoxinA (Xeomin)(12.5 or 25U/eye), one injection session.
Open-Label Extension: IncobotulinumtoxinA (Xeomin), one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
干预措施: IncobotulinumtoxinA (Xeomin), 35 Units (Drug)
结局指标
主要结局
Double-blind MP: Change From Baseline in JRS Severity Subscore at Day 43 (Visit 4)
时间窗: Baseline, Day 43 (Visit 4)
JRS severity subscore was used to classify individual symptoms of blepharospasm and to determine therapeutic efficacy. JRS severity subscore ranges from 0 to 4, where 0: None; 1: increased blinking present with external stimuli; 2: Mild but spontaneous eyelid fluttering, definitely noticeable, possibly embarrassing, but not functionally disabling, 3: Moderate, very noticeable spasm of eyelids only, mildly incapacitating, 4: Severe, incapacitating spasm of eyelids and possibly other facial muscles. Values represent least square (LS) mean differences between baseline and visit 4 resulting from analysis of covariance (ANCOVA) with treatment group, pooled site, and gender as fixed factors and baseline JRS severity subscore and age as covariates and missings replaced using the last observation carried forward (LOCF) method. Negative values denote improvement, while positive values denote deterioration vs. baseline.
次要结局
- Double-blind MP: Patient Evaluation of Global Response (PEGR) at Final Visit (Day 43-Day 141)(Baseline, Final Visit (Day 43-Day 141))
- Double-blind MP: Change From Baseline in Blepharospasm Disability Index (BSDI) at Day 43 (Visit 4)(Baseline, Day 43 (Visit 4))