Efficacy and Safety of DYSPORT® Using 2mL Dilution in Adults With Cervical Dystonia.

Study Overview
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Brief Summary
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The purpose of the protocol is to evaluate the efficacy and safety of Dysport® using 2 mL dilution compared with placebo for the treatment of Cervical Dystonia.

Official Title
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A Phase 3b, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of DYSPORT® Using 2mL Dilution in Adults With Cervical Dystonia.

Conditions
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Cervical Dystonia

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: Primary diagnosis of Cervical Dystonia at least 9 months since onset and either previously untreated with botulinum toxin or currently treated with Botox at a total dosing range of 100-200 U and ≤60 U in the sternocleidomastoid muscle at the last injection cycle, and having had a satisfactory treatment response in the principal investigator's judgment during the last two sequential Botox treatment cycles. TWSTRS total score≥ 20; TWSTRS-severity subscale score> 10; Exclusion Criteria: In apparent remission from Cervical Dystonia Diagnosis of pure retrocollis or pure anterocollis For non-naïve subjects, previous poor response to either of the last two Botox treatments Known requirement of <100U or >200U of Botox injected into the neck muscles

Ages Eligible for Study
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Minimum Age: 18 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: Dysport®<br>Dysport® (intramuscular injection), between 250 and 500 units (U)/vial using 2mL dilution, 1 cycle only | Biological: Botulinum toxin type A<br>* Intramuscular injection, between 250 and 500 units (U)/vial using 2mL dilution, 1 cycle only<br>* Other names: AbobotulinumtoxinA (Dysport®);|
| Placebo Comparator: Placebo<br>Placebo, up to 2mL | Drug: Placebo<br>* Up to 2mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4. | The change from baseline in the TWSTRS total score at Week 4 was determined for the subjects who received a single dose of Dysport® or placebo by intramuscular injection at the baseline visit (Day 1), and is expressed as weighted overall treatment difference. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The score was assessed by the investigator prior to study treatment at baseline and at all post-treatment visits. | 4 weeks post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in TWSTRS Total Score at Week 2. | The change from baseline in the TWSTRS total score at Week 2 was determined for the subjects who received a single dose of Dysport® or placebo by intramuscular injection at the baseline visit (Day 1), and is expressed as weighted overall treatment difference. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The score was assessed by the investigator prior to study treatment at baseline and at all post-treatment visits. | 2 weeks post-treatment | 
| Change From Baseline in Clinical Global Impression of Change (CGIC) in CD at Week 2. | The CGIC is an investigator-reported assessment of the global clinical change in CD since study treatment administration. The CGIC uses a seven-point Likert scale ranging from +3 (very much improved) to -3 (very much worse), and was assessed by the investigator at the Week 2 and Week 4 visits. | 2 weeks post-treatment | 
| TWSTRS Responders at Week 2. | Treatment response was determined as the number of responders at Week 2 relative to the baseline TWSTRS total score. A treatment responder is defined as a subject who had at least a 30% reduction in the TWSTRS total score after treatment. This was calculated as ([Week 2 score - baseline score]/baseline score) * 100. | 2 weeks post-treatment | 
| Change From Baseline in CGIC in CD at Week 4. | The CGIC is an investigator-reported assessment of the global clinical change in CD since study treatment administration. The CGIC uses a seven-point Likert scale ranging from +3 (very much improved) to -3 (very much worse), and was assessed by the investigator at the Week 2 and Week 4 visits. | 4 weeks post-treatment | 
| TWSTRS Responders at Week 4. | Treatment response was determined as the number of responders at Week 4 relative to the baseline TWSTRS total score. A treatment responder is defined as a subject who had at least a 30% reduction in the TWSTRS total score after treatment. This was calculated as ([Week 4 score - baseline score]/baseline score) * 100. | 4 weeks post-treatment | 
| Change From Baseline in Cervical Dystonia Impact Profile-58 (CDIP-58) Total Score at Week 4. | The CDIP-58 scale is a subject-based rating scale measuring the health impact of CD measured in 8 health dimensions including head and neck symptoms, pain and discomfort, upper limb activities, walking, sleep, annoyance, mood and psychosocial functioning. Subscale scores were transformed to a common theoretical range of 0 (no impact) to 100 (most impact). Negative changes from the baseline total score indicate improvement in the impact of CD on health whereas postive changes indicate worsening. | 4 weeks post-treatment | 
| Change From Baseline in CDIP-58 Total Score at Week 2. | The CDIP-58 scale is a subject-based rating scale measuring the health impact of CD measured in 8 health dimensions including head and neck symptoms, pain and discomfort, upper limb activities, walking, sleep, annoyance, mood and psychosocial functioning. Subscale scores were transformed to a common theoretical range of 0 (no impact) to 100 (most impact). Negative changes from the baseline total score indicate improvement in the impact of CD on health whereas postive changes indicate worsening. The hierarchical testing procedure would only be conducted if the previous secondary efficacy endpoint (change from baseline in CDIP-58 total score at Week 4) reached a statistically significant treatment effect. This secondary efficacy endpoint (change from baseline in CDIP-58 total score at Week 2) was performed to characterise the full clinical effect. | 2 weeks post-treatment |