Dose-escalating Safety and Preliminary Efficacy of DaxibotulinumtoxinA for Injection in Cervical Dystonia

Study Overview
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Brief Summary
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This is an open-label, dose-escalation study to assess the safety and preliminary efficacy of daxibotulinumtoxinA in subjects with isolated cervical dystonia (CD).

Conditions
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Torticollis (Spasmodic)

Intervention / Treatment
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* Biological: DaxibotulinumtoxinA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets diagnostic criteria for isolated cervical dystonia Has moderate severity with a baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) - Total score of at least 20 and a TWSTRS-Severity subscale score or at least 15 Has been using stable doses of focal dystonia medications for at least 3 months and willing to continue through end of study Exclusion Criteria: Cervical dystonia attributable to an underlying etiology, such as traumatic torticollis or tardive torticollis; predominant retrocollis or anterocollis cervical dystonia Significant dystonia in other body areas, or is currently being treated with botulinum toxin for dystonia in other areas than isolated cervical dystonia Neurological abnormalities other than cervical dystonia History of severe dysphagia or aspiration, or current clinically significant swallowing disorder Previous neck surgery, phenol injection to the neck muscles, myotomy or denervation surgery in the neck/shoulder region, or intrathecal baclofen Marked limitation on passive range of motion that suggests contractures or other structural abnormality, e.g. cervical contractures or cervical spinal deformity Profound atrophy of cervical musculature Any neurological condition that may place the subject at increased risk with exposure to botulinum toxin type A, including peripheral motor neuropathic diseases such as amyotrophic lateral sclerosis and motor neuropathy, and neuromuscular junctional disorders such as Lambert-Eaton syndrome and myasthenia gravis Suboptimal efficacy response to any prior botulinum toxin type A product, when a previous treatment produced more optimal therapeutic response, as judged subjectively by the Investigator Previous treatment with any botulinum toxin product for any condition within the 6 months prior to Screening and during the study; presence of any blood coagulation disorder; or on anticoagulation treatment with international normalized ratio (INR) > 3.5

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: daxibotulinumtoxinA (DAXI) for injection<br>DAXI for injection | Biological: DaxibotulinumtoxinA<br>* Low, mid, and high dose sequential treatments of daxibotulinumtoxinA in dose-escalation safety and efficacy study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of dystonia as measured by change from baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) - Total Score |  | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Toronto Western Spasmodic Torticollis Rating Scale(TWSTRS) - Total Score |  | Post-treatment: Weeks 2, 4, 6, 9, 12, 16, 20, 24 | 
| Change from baseline in TWSTRS subscale scores (Severity, Disability and Pain) |  | Post-treatment: Weeks 2, 4, 6, 9, 12, 16, 20, 24 | 
| Duration of effect based on number of weeks from treatment until return of symptoms that warrant treatment |  | Post-treatment: Weeks 2, 4, 6, 9, 12, 16, 20, 24 | 
| Percentage of treatment responders with at least a 20% reduction in the TWSTRS - Total score post-treatment |  | Weeks 2, 4, 6, 9, 12, 16, 20, 24 | 
| Patient-rated quality of life measurement based upon change from baseline of the Cervical Dystonia Impact Profile Scale (CDIP-58) |  | Post-treatment: Weeks 4, 6, 12, 16, 20, 24 | 
| Percentage of responders showing improvement on Clinical Global Impression of Change (CGIC) |  | Post-treatment: Weeks 2, 4, 6, 9, 12, 16, 20, 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical dystonia, Spasmodic torticollis