Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of NT 201 in the Treatment of Lower Limb Spasticity Caused by Stroke or Traumatic Brain Injury in Adult Subjects, Followed by an Open Label Extension With or Without Combined Upper Limb Treatment
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 603
- 试验地点
- 132
- 主要终点
- Change from baseline in derived Modified Ashworth Scale-Bohannon (MAS) ankle score (knee extended) at weeks 4 to 6
研究概览
简要总结
The purpose of this study is to determine whether a single treatment with administration of 400 Units NT 201 (botulinum toxin) is superior to placebo (no medicine) for the treatment of lower limb spasticity caused by stroke or traumatic brain injury (Main Period). Participants will be assigned to the treatment groups by chance and neither the participants nor the research staff who interact with them will know the allocation.
The following 4 to 5 treatment cycles will investigate the safety and tolerability of treatment with NT 201 (botulinum toxin) when administered in doses between 400 and 800 Units (Open Label Extension Period). All participants will receive the treatment and the dose will depend on whether only lower limb spasticity or combined upper and lower limb spasticity are treated.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female or male subject ≥ 18 years and ≤ 85 years at screening
- •Diagnosis of lower limb spasticity with or without upper limb spasticity of the same body side caused by stroke or traumatic brain injury
- •Disabling ankle flexor spasticity presenting as pes equinus or pes equinovarus
- •Modified Ashworth Scale-Bohannon [MAS] score of 2 or 3 points in the ankle plantar flexor of the target lower limb (supine position, knee extended)
- •Minimum passive range of motion in ankle of the target lower limb (supine position, knee extended): 10°dorsiflexion and 20°plantarflexion
- •At least 4 months since last botulinum neurotoxin [BoNT] injection for treatment of spasticity or any other condition
- •For subjects receiving anticoagulation therapy, the investigator confirms and documents that the subject has an:
- •Activated partial thromboplastin time [aPTT] ≤ 80 seconds (subjects on dabigatran or other direct thrombin inhibitors) or
- •International normalized ratio [INR] value of ≤ 2.5 (subjects on coumarins or other anticoagulants monitored by INR)
排除标准
- •Generalized disorders of muscle activity (e.g. myasthenia gravis, Lambert Eaton syndrome, amyotrophic lateral sclerosis) or any other significant peripheral neuromuscular dysfunction which might interfere with the study
- •Bilateral lower limb paresis/paralysis/spasticity or tetraparesis/paralysis/spasticity
- •Body weight < 50 kg
- •Severe atrophy of the target limb muscles
- •Previous, ongoing or planned treatments of spasticity with intrathecal baclofen
- •Previous, ongoing, or planned treatments of spasticity in the target lower limb with any of the following procedures: Surgical Intervention; Alcohol or phenol block; Muscle afferent block
- •Physiotherapy or use of orthoses or splints at the target limb initiated less than 4 weeks before screening or expected to change during the double blind phase of the study
- •Current or planned treatment with parenterally administered drugs that interfere with neuromuscular transmission (e.g. intrathecal baclofen, tubocurarine type muscle relaxants used in anesthesia), or local anesthetics in the treated region within 2 weeks prior to screening
- •Infection or inflammation at the injection sites
- •Subjects with presence or history of aspiration pneumonia, recurrent lower respiratory tract infections, or compromised respiratory function as per investigator's clinical judgment
- •Pregnancy (as verified by a positive pregnancy test) or breast feeding
研究组 & 干预措施
Placebo
Main Period (1 treatment cycle): subjects to receive intramuscular placebo injection into muscles of the lower limb.
Open Label Extension Period (4-5 treatment cycles): subjects to receive intramuscular injection of NT 201 (up to 800 units) into muscles of the lower limb and upper limb, if indicated.
干预措施: NT 201 (Drug)
Placebo
Main Period (1 treatment cycle): subjects to receive intramuscular placebo injection into muscles of the lower limb.
Open Label Extension Period (4-5 treatment cycles): subjects to receive intramuscular injection of NT 201 (up to 800 units) into muscles of the lower limb and upper limb, if indicated.
干预措施: Placebo (Drug)
NT 201 (IncobotulinumtoxinA, Xeomin)
Main Period (1 treatment cycle): subjects to receive intramuscular injection of NT 201 (400 units) into muscles of the lower limb.
Open Label Extension Period (4-5 treatment cycles): subjects to receive intramuscular injection of NT 201 (up to 800 units) into muscles of the lower limb and upper limb, if indicated.
干预措施: NT 201 (Drug)
结局指标
主要结局
Change from baseline in derived Modified Ashworth Scale-Bohannon (MAS) ankle score (knee extended) at weeks 4 to 6
时间窗: Baseline to week 4-6
The MAS is a 6-grade scale
Co-Primary: Global Impression of Change Scale (GICS) assessed by physician at Week 4 to 6
时间窗: Week 4-6
The GICS s a 9-grade scale
Occurrence of treatment emergent adverse events [TEAEs] in the Main Period
时间窗: Baseline to week 12
次要结局
- Global Impression of Change Scale (GICS) assessed by the study subject at Week 4 to 6(Week 4-6)
- Global Impression of Change Scale (GICS) assessed by the caregiver at Week 4 to 6(Week 4-6)
- Change from Study Baseline in Goal Attainment Scale [GAS] at Week 6(Baseline to week 6)