NCT01905683已完成3 期
Open-label, Non-controlled, Multicenter Long-term Study to Investigate the Safety and Efficacy of Xeomin® (Incobotulinumtoxin A, NT 201) for the Treatment of Spasticity of the Lower Limb(s) or of Combined Spasticity of Upper and Lower Limb in Children and Adolescents (Age 2 - 17 Years) With Cerebral Palsy
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 370
- 试验地点
- 43
- 主要终点
- Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
研究概览
简要总结
The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the leg(s) or of leg(s) and one arm are safe in treating children/adolescents (age 2-17 years) long-term with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main clinical inclusion criteria for completers of study MRZ60201_3070_1:
- •Subject with lower limb [LL] spasticity who completed lead-in study MRZ60201_3070_1 in any of the three dose groups with duration of both injection cycles between 12 and 16 weeks.
- •Ashworth scale [AS] score ≥2 in plantar flexors (at least unilaterally). For subjects with an AS score of 1, the investigator has to decide on the clinical need for reinjection.
- •Clinical need for spasticity treatment with NT 201 according to the clinical judgment of the investigator for:
- •Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus and need for additional 8 U/kg BW NT 201 (maximum of 200 U) for treatment of clinical pattern flexed knee or adducted thigh (ipsilateral) or bilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus on each side.
- •No treatment of other clinical patterns is allowed.
- •Main clinical inclusion criteria for subjects who did not participate in MRZ60201_3070_1:
- •Female or male subject of 2 to 17 years age (inclusive).
- •Uni- or bilateral CP with clinical need for BoNT injection to treat limb spasticity.
- •AS score ≥ 2 in plantar flexors (at least unilaterally).
- •Clinical need according to the clinical judgment of the investigator in one out of four treatment combinations:
- •For LL(s) treatment only (Gross Motor Function Classification System [GMFCS] levels IV): Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus, and 8 U/kg BW NT 201 (maximum of 200 U) into flexed knee or adducted thigh or bilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into each pes equinus (AS score ≥ 2 on both sides).
- •For combined unilateral UL and unilateral LL, (GMFCS levels I-III): Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus, and 8 U/kg BW NT 201 (maximum of 200 U) into flexed knee or adducted thigh plus Unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum of 100 U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or pronated forearm.
- •For combined unilateral UL and unilateral LL (GMFCS level IV-V): Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum 200 U) into pes equinus, and 4 U/kg BW NT201 (maximum 100 U) into flexed knee or adducted thigh plus unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum of 100 U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or pronated forearm.
- •For combined unilateral UL and bilateral LL (GMFCS levels I-III): Bilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into each pes equinus (AS score ≥ 2 on both sides) plus unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum of 100 U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or pronated forearm.
排除标准
- •Exclusion Criteria for subjects who completed MRZ60201_3070_1:
- •Infection and/or inflammation in the area of the planned injection points.
- •Pregnancy for female with history of menarche.
- •Clinically relevant pathological findings indicating active disease of vital organs.
- •Exclusion Criteria for subjects who did not participate in MRZ60201_3070_1:
- •Fixed contracture defined as severe restriction of the range of joint movement on passive stretch in the target clinical pattern(s) or predominant forms of muscle hypertonia other than spasticity (e.g., dystonia) in the target limb(s).
- •Surgery in the pes equinus on side(s) intended to treat with BoNT injections within 12 months prior to Screening Visit (V1), within the screening period or planned for the time of participation in this study.
- •Hip flexion requiring BoNT injection.
- •Limitation of hip abduction to less than 40° or pre-diagnosed migrational percentage greater than
- •Vaccination within 2 weeks prior to Screening Visit (V1) and/or within the screening period.
- •Non-resolved fractures of the treated limb.
- •Ventilator dependency.
- •Severe neurological diagnosis and comorbidity outside the spectrum of cerebral palsy.
- •Pure dyskinetic CP or mixed CP with predominantly dyskinetic movements.
- •Treatment with BoNT (other than study drug in this study) for any body region within 14 weeks prior to Screening Visit (V1), within the screening period and/or intended to be administered during the study period.
- •Treatment with phenol or alcohol of any muscle within 6 months prior to Screening Visit (V1), within the screening period, and/or intended to be administered during the study period.
- •Treatment with
- •drugs acting as peripheral muscle relaxants
- •intrathecal baclofen, or
- •oral anticoagulants administered within 2 weeks prior to Screening Visit (V1), within the screening period, and/or intended to be administered during the study period.
研究组 & 干预措施
16-20 Units per kg body weight incobotulinumtoxinA
Experimental
干预措施: IncobotulinumtoxinA (16-20 Units per kg body weight) (Drug)
结局指标
主要结局
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
时间窗: From the timepoint of first injection up to end of study visit (Week 50-66)
TEAEs are events observed from the time point of first injection until end of study visit (Week 50-66). Values reported here refer to the number of participants affected.
Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle
时间窗: From the timepoint of first injection until end of study visit (Week 50-66)
TEAEs occurring after treatment that were thought to possibly indicate toxin spread throughout the trial conduct are defined as TEAESI. Values reported here refer to the number of participants affected.
Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle
时间窗: From the timepoint of first injection until end of study visit (Week 50-66)
TESAEs are events observed from the time point of first injection until end of study visit (Week 50-66). Values reported here refer to the number of participants affected.
次要结局
- Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle(Baseline (Day 1, Visit [V] 2) to all other visits (V3, V4, V5, V6, V7, V8, V9, V10, and V11); From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC cycle only) and Day 99 (Week 14) of the respective IC)
- Changes in Gross Motor Function Measure (GMFM)-66 Score From Baseline to All Injection Visits and End of Study(Baseline to Day 1 of 2nd (V5), 3rd (V7), 4th (V9) IC and End of study (Week 44-68) (V11))
- Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle(Day 99 (Week 14) of 1st, 2nd, 3rd and 4th injection cycle)
- Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle(Baseline (Day 1, Visit [V] 2) to all other visits (V3, V4, V5, V6, V7, V8, V9, V10, and V11); From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle only) and Day 99 (Week 14) of the respective Injection Cycle)
- Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle(Day 29 (Week 4) of 1st, 2nd, 3rd and 4th injection cycle)
- Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle(Day 29 (Week 4) of 1st, 2nd, 3rd and 4th injection cycle)
- Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection(Baseline (Day 1, Visit [V] 2) to all other visits (V3, V4, V5, V6, V7, V8, V9, V10, and V11); From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC cycle only) and Day 99 (Week 14) of the respective IC)
研究者
研究点 (43)
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