A Study to Compare the Safety and Efficacy of Dysport® and Botox® in Adults With Upper Limb Spasticity.

Study Overview
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Brief Summary
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This study is aiming to demonstrate the non-inferiority of AbobotulinumtoxinA (aboBoNT-A) versus OnabotulinumtoxinA (onaBoNT-A) as the primary safety endpoint, and the superiority of aboBoNT-A over onaBoNT-A with respect to duration of response as the key secondary efficacy endpoint when used at optimal doses according to approved prescribing information of each product.

Official Title
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A Multicentre, Interventional, Post-marketing, Randomised, Double-blind, Crossover Study to Evaluate the Clinical Safety and Efficacy of AbobotulinumtoxinA (Dysport®) in Comparison With OnabotulinumtoxinA (Botox®) When Treating Adults With Upper Limb Spasticity

Conditions
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Upper Limb Spasticity

Intervention / Treatment
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* Biological: AboBoNT-A
* Biological: OnaBoNT-A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent 2a. [US/France] Participants with stable Upper Limb Spasticity (ULS) for at least 3 months, in whom treatment of only one upper limb is necessary for the duration of the study; 2b. [Canada] Participants with stable post-stroke ULS for at least 3 months, in whom treatment of only one upper limb is necessary for the duration of the study Participants who are either naïve to Botulinum toxin type A (BoNT-A) for ULS or who have been previously treated with BoNT-A for ULS; Participants with MAS score of at least 2 at two muscle groups (one of these two muscles groups should be the PTMG) and at least 1 in the remaining muscle group. Participants with DAS score of at least 2 on the Principal Target of Treatment (PTT) (one of four functional domains: dressing, hygiene, limb position and pain); Participants who require BoNT-A injection in all of the following muscles: flexor carpi radialis, flexor carpi ulnaris, flexor digitorum profundus, flexor digitorum superficialis and biceps brachii; Participants for whom injection of a total dose of 900 Units aboBoNT-A or 360 Units onaBoNT-A is considered by the investigator to be clinically appropriate; Participants who have been stable for at least 3 months prior to study entry in terms of oral antispasticity, anticoagulant and/or anticholinergic medication if treated are considered by the investigator likely to remain stable for the duration of the study; Exclusion Criteria: Major limitations in the passive range of motion in the paretic upper limb; Major neurological impairment (other than limb paresis) that could negatively affect functional performance; Participants clinically requiring injection into any upper limb muscles other than the five muscles of one arm listed in Section 5.1, or requiring injection into both arms or any lower limb within the timeframe of the study; Hypersensitivity to any BoNT product or excipients; Hypersensitivity to cow's milk protein (casein); Infection at the proposed injection site(s); Known peripheral motor neuropathic diseases, amyotrophic lateral sclerosis or neuromuscular junction disorders (e.g. myasthenia gravis or Lambert-Eaton syndrome); Any medical condition (including dysphagia or breathing difficulties/compromised respiratory function) that in the opinion of the investigator, might jeopardize the participant's safety; Women who are pregnant or lactating Participants treated with BoNT of any type for any indication (e.g. bladder injection, headache or cosmetic) within the previous 12 weeks or planned/likely to be treated during the course of the study; Prior history of non-responsiveness to BoNT treatment; Previous surgery, or administration of alcohol or phenol in the study limb 6 months or earlier from study enrolment or planned/likely to be treated during the course of the study; Participants treated with intrathecal baclofen (except if treatment has reached a stable dose for >4 weeks and is likely to remain stable throughout the study), aminoglycosides or other agents interfering with neuromuscular transmission (e.g. curare-like agents) within the 4 weeks prior to study enrolment or planned/likely to be treated during the course of the study BoNT naïve participants with a history of facial neurogenic disorder (facial paralysis, polyradiculoneuropathy) (only for France). Participants receiving concomitant medication treatment with the following PT/OT interventions on the study limb: new splinting/orthotics/casting, serial casting, shockwave therapy, dry needling and needle tenotomies. However, PT/OT interventions not intended to reduce study limb spasticity (e.g. functional training exercises) or with a transient (<1 day) reduction of study limb spasticity (e.g. stretching, weight bearing) are allowed.

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sequence 1<br>Participants will receive one cycle of aboBoNT-A followed by one cycle of onaBoNT-A in the selected overactive upper limb muscles | Biological: AboBoNT-A<br>* AbobotulinumtoxinA for injection: 500 Unit vial. Dose: 900 Units (3.6 mL)<br>* Other names: Dysport®;Biological: OnaBoNT-A<br>* OnabotulinumtoxinA for injection: 200 Unit vial. Dose: 360 Units (3.6 mL)<br>* Other names: Botox®;|
| Other: Sequence 2<br>Participants will receive one cycle of onaBoNT-A followed by one cycle of aboBoNT-A in the selected overactive upper limb muscles | Biological: AboBoNT-A<br>* AbobotulinumtoxinA for injection: 500 Unit vial. Dose: 900 Units (3.6 mL)<br>* Other names: Dysport®;Biological: OnaBoNT-A<br>* OnabotulinumtoxinA for injection: 200 Unit vial. Dose: 360 Units (3.6 mL)<br>* Other names: Botox®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Treatment-emergent Adverse Events (TEAEs) |  | from baseline (injection) to 12 weeks (injection cycle 1 and 2, each cycle is a maximum 24 weeks)) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) |  | from baseline (injection) to 12 weeks (injection cycle 1 and 2, each cycle is a maximum 24 weeks)) | 
| Duration of response |  | baseline (injection) to retreatment criteria met, from week 10 up to week 24 (for each cycle, 1&2) or baseline to withdrawal or end of study if retreatment criteria not met, up to 24 weeks (for each cycle,1&2, each cycle is a maximum 24 weeks) | 
| Muscle tone assessed by Modified Ashworth scale (MAS) total score | MAS is a scale which represents improvement in spasticity. This tool assesses muscle tone using a six-point scale from 0 = no change to 4 = considerable increase of affected/rigid region. | at baseline (injection), 1 week, 4 weeks, 10 weeks, 12 weeks and additional visits at 16 weeks, 20 weeks, 24 weeks (injection cycle 1 and 2; each cycle is a maximum 24 weeks) | 
| Perceived function and pain assessed by the Disability Assessment Scale (DAS) total score | DAS scale to determine the extent of functional impairment in four domains: hygiene, dressing, limb position and pain. Impairment will be assessed on a four-point scale (range 0 to 3, where 0 indicates no disability and 3 indicates severe disability). The four domain ratings will be added to give an overall score between 0 and 12. | at baseline (injection), 1 week, 4 weeks, 10 weeks, 12 weeks and additional visits at 16 weeks, 20 weeks, 24 weeks (injection cycle 1 and 2; each cycle is a maximum 24 weeks) | 
| Physician global assessment (PGA) of treatment response | PGA answers will be made on a nine-point rating scale (from -4 = markedly worse, to +4 = markedly improved). | at baseline (injection), 1 week, 4 weeks, 10 weeks, 12 weeks and additional visits at 16 weeks, 20 weeks, 24 weeks (injection cycle 1 and 2; each cycle is a maximum 24 weeks) | 
| Change in Quality of Life (QoL) using the SF-12 perceived health score | 12-Item Short-form Health Survey (SF-12) is a health survey that will assess general health and wellbeing. The SF-12 summary score is between 0 and 100, with higher scores indicating better self-reported health. | at baseline (injection), 4 weeks, 12 weeks and at end of each cycle (injection cycle 1 and 2; each cycle is a maximum 24 weeks) | 
| Change in Quality of Life (QoL) using SQoL-6D | Spasticity-related Quality of Life Tool (SQoL-6D) is a brief questionnaire in six domains (pain/discomfort, involuntary movements or spasms, restricted range of movement, caring for the affected limb, using the affected limb and mobility/balance) using a five-level scale ranging from 0 to 4, with higher scores meaning worse condition. | at baseline (injection), 4 weeks, 12 weeks and at end of each cycle (injection cycle 1 and 2; each cycle is a maximum 24 weeks) |