Study to Assess Impact of Dysport Injections Early After Stroke on Upper Limb Spasticity Progression

Study Overview
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Brief Summary
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The purpose of this study is to investigate if early administration (i.e. within 12 weeks after stroke) of Dysport® 500 U injections may delay the appearance or the progression of upper limb symptomatic spasticity.

Official Title
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Asian Multicentre, Double Blind, Randomised, Placebo Controlled Pilot Study, to Assess the Impact of Dysport® Intramuscular Injections When Administered Within the First 12 Weeks After Stroke on the Time to Spasticity Progression in Adult Subjects With Upper Limb (UL) Spasticity.

Conditions
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Stroke, Upper Limb Spasticity

Intervention / Treatment
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* Biological: Botulinum toxin type A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 2 to 12 weeks after first ever stroke according to the World Health Organisation criteria (previous transient ischaemic attack or clinically silent infarct on computerised tomography (CT)/magnetic resonance imaging (MRI) are not counted as previous stroke) Stroke confirmed by CT/MRI scan and classified as ischaemic/haemorrhagic stroke Presence of spasticity: either symptomatic, based on symptomatic spasticity criteria (i.e. at least one of the following items: impacted passive/active function, involuntary movements, or pain ≥4 on a numeric pain rating scale [NPRS]), in addition to increased muscle tone [Modified Ashworth Scale, MAS ≥2]) or only increased muscle tone (MAS≥2) Exclusion Criteria: Neuromuscular junction (NMJ) diseases, or any other neurological disorders (including prior local joint, tendon, and intrinsic muscle disorders) that could potentially interfere with assessment of spasticity in the primary targeted muscle group selected by the Investigator and in agreement with the subject Currently receiving drugs affecting NMJ transmission e.g. aminoglycosides, aminoquinolines, cyclosporine, D penicillamine Previous surgery of the affected muscles/ ligaments/tendons Severe comorbidities (e.g. congestive heart failure, myocardial infarction, multiple organ failure, hepatic renal failures, severe infections)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: Treatment group<br>Dysport® 500U intramuscular injection | Biological: Botulinum toxin type A<br>* Subjects to receive Dysport® 500U administered intramuscularly in the targeted upper limb.<br>* Other names: AbobotulinumtoxinA (Dysport®);|
| Placebo Comparator: Placebo Group<br>Placebo intramuscular injection | Drug: Placebo<br>* Placebo administered intramuscularly in the targeted upper limb.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Between the Initial Injection and the Appearance of Reinjection Criteria as Evaluated by the Modified Ashworth Scale (MAS) and Spasticity Symptoms | The appearance of increased muscle tone was assessed using the MAS (scale ranges from 0 [no increase in muscle tone] to 4 [affected part rigid in flexion or extension]). For confirmation of reinjection criteria appearance, a subject had to have a MAS score in the primary targeted muscle group of ≥2 and at least 1 of the following 4 criteria confirming signs of symptomatic spasticity in the UL: A Numeric Pain Rating Scale (NPRS) pain score ≥ 4 (NPRS ranges from 0 [no pain] to 10 [severe pain]) An impact on passive function measured by a score of ≥ 1 on the 4-point Likert scale (scale ranges from 0 [no impact] to 3 [severe impact]) An impact on active function measured by a score of ≥ 1 on the 4-point Likert scale An involuntary movements score ≥1 on the 4-point Likert scale in relevant upper limb. Results are reported overall for subjects with both symptomatic and asymptomatic spasticity. | From Week 4 up to Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in MAS of the Primary Targeted Muscle Group. | Increased muscle tone in the primary muscle group (selected by the investigator at the first visit, based on his/her clinical judgement and in agreement with the subject, in one of the following muscle groups: elbow flexors or pronators, wrist flexors, or finger flexors) was assessed using the MAS. Scale ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). Least Squares (LS) mean change from baseline to each subsequent visit (including the subject's last study visit) of the MAS score is reported. | From baseline up to Week 28 | 
| Mean Change in Fugl-Meyer Assessment for Evaluation of UL Motor Impairment. | The Fugl-Meyer assessment is a validated tool for measuring motor functioning, balance, sensation, and joint functioning in the upper or lower limbs of subjects with post-stroke hemiplegia. The assessment scale is comprised of 155 items across 5 domains: motor functioning, sensory functioning, balance, joint range of motion and joint pain. For this study, only the UL motor part was assessed using the following criteria: A. Upper Extremity (from 0 to 36) B. Wrist (from 0 to 10) C. Hand (from 0 to 14) D. Coordination / Speed (from 0 to 6) Total motor function scores (A-D [from 0 to 66]) were calculated and LS mean changes from baseline up to (but not including) the visit when the reinjection criteria were met were reported. Higher values for change from baseline indicated a better outcome. | From baseline up to Week 28 | 
| Global Assessment of Changes at Last Visit | Global assessment of changes was assessed by the investigator from Week 4 up to (but not including) the visit when the reinjection criteria were met. This endpoint was assessed by the investigator using a 5-point Likert scale to answer the following question: How does your patient feel compared to his/her condition at the first visit? Much better Better No change Worse Much worse Results are reported overall for subjects with both symptomatic and asymptomatic spasticity. | From Week 4 up to Week 28 | 
| Number of Concomitant Non-drug Therapy Sessions. | The number of non-drug therapy sessions that the subject received for UL spasticity in combination with injections of either Dysport® or placebo - up to and including the subject's last study visit - were recorded in the Electronic Case Report Form (eCRF) as part of concomitant medications and therapies evaluation at all study visits (Prior and Concomitant Non-Drug Therapies eCRF page). All concomitant therapies in the indication of Post Stroke UL Spasticity were counted by subject from first administration of Dysport® or placebo to last study visit. Concomitant non-drug therapies were defined as received any time during study (on or after the day of the first injection of Dysport® or placebo) regardless of the start or stop date. For each subject, overlapping sessions were defined as one therapy session using the earliest start date as the start date and the latest start date as the stop date. | From baseline up to Week 28 | 
| Mean Duration of Concomitant Non-drug Therapy Sessions. | The duration of non-drug therapy sessions that the subject received for UL spasticity in combination with injections of either Dysport® or placebo - up to and including the subject's last study visit - were recorded in the Electronic Case Report Form (eCRF) as part of concomitant medications and therapies evaluation at all study visits (Prior and Concomitant Non-Drug Therapies eCRF page). Overall duration of concomitant therapies in the indication of Post Stroke UL Spasticity was computed for the period from first administration of Dysport® or placebo to last study visit. Concomitant non-drug therapies were defined as received any time during study (on or after the day of the first injection of Dysport® or placebo) regardless of the start or stop date. For each subject, overlapping sessions were defined as one therapy session using the earliest start date as the start date and the latest start date as the stop date. | From baseline up to Week 28 |