Efficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of multiple doses of Dysport used in the treatment of upper limb spasticity (altered skeletal muscle performance) in children with cerebral palsy (CP).

Official Title
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A Phase III, Multicentre, Double Blind, Prospective, Randomised, Controlled, Multiple Treatment Study Assessing Efficacy And Safety Of DYSPORT® Used In The Treatment Of Upper Limb Spasticity In Children

Conditions
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Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children

Intervention / Treatment
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* Biological: Botulinum toxin type A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Upper limb spasticity due to cerebral palsy Body weight 10 kg or over MAS score of 2 or more in affected elbow or wrist flexors Exclusion Criteria: Fixed myocontracture Previous phenol or alcohol injection within 1 year Severe athetoid or dystonic movements Previous or planned surgery for spasticity in elbow or wrist flexors Neuromuscular disorders Previous Rhizotomy within 6 months Intrathecal baclofen within 30 days

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Group A - Treatments 1, 2, 3 and 4: Dysport 16 Units (U)/kg in one upper extremity (the study limb). | Biological: Botulinum toxin type A<br>* Subjects randomised to receive Dysport 2 U/kg, 8 U/kg or 16 U/kg administered intramuscularly in the study limb.<br>* Other names: AbobotulinumtoxinA (Dysport®);|
| Experimental: Group B<br>Group B - Treatments 1, 2, 3 and 4: Dysport 8 U/kg in one upper extremity (the study limb). | Biological: Botulinum toxin type A<br>* Subjects randomised to receive Dysport 2 U/kg, 8 U/kg or 16 U/kg administered intramuscularly in the study limb.<br>* Other names: AbobotulinumtoxinA (Dysport®);|
| Experimental: Group C<br>Group C - Treatment 1: Dysport 2 U/kg in one upper extremity (the study limb). Group C - Treatments 2, 3 and 4: Dysport 8 or 16 U/kg in one upper extremity (the study limb). | Biological: Botulinum toxin type A<br>* Subjects randomised to receive Dysport 2 U/kg, 8 U/kg or 16 U/kg administered intramuscularly in the study limb.<br>* Other names: AbobotulinumtoxinA (Dysport®);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG | The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 0 (no increase in muscle tone), 1 (slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone. | Baseline (TC 1, Day 1) and TC 1, Week 6. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Physician's Global Assessment (PGA) Score at TC 1, Week 6 | The PGA of treatment response was assessed by asking the investigator the following question: 'How would you rate the response to treatment in the subject's upper limb since the start of the study?'. Answers were on a 9-point rating scale (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved). The mean scores for each treatment group at TC 1, Week 6 are presented. | TC 1, Week 6. | 
| Mean Goal Attainment Scale (GAS) Total Score at TC 1, Week 6 | The GAS is a functional 5-point scale used to measure progress towards individual therapy goals. At start of each TC, 1 to 3 individual goals were defined for each subject by investigator and child's parents/guardians/caregivers prior to treatment. Outcome to reach each goal was rated on a 5-point scale ranging from -2 to +2 (-2: much less than expected outcome, -1: somewhat less than expected outcome, 0: expected outcome, +1: somewhat more than expected outcome, +2: much more than expected outcome). Higher score indicates a better outcome. A GAS T-score was calculated as: 50+(10∑_(i=1)^n wi xi)/√(0.7∑_(i=1)^n wi^2 +0.3(∑_(i=1)^n wi)^2) where, xi = rating of ith goal post-baseline; wi = weight of ith goal, calculated as importance * difficulty as defined at baseline; n = number of goals assessed at baseline and post-baseline. A GAS T-score of 50 indicates goals achieved as expected. Scores below 50 reflect under attainment of goals and scores above 50 reflect over attainment of goals. | TC 1, Week 6. |