Single Treatment of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia (ASPEN-1)

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, parallel group, multi-center trial of two doses of daxibotulinumtoxinA (DAXI) for injection (high-dose; low-dose in adult subjects with isolated (primary) cervical dystonia (CD).

Detailed Description
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Approximately 300 subjects, recruited from approximately 80 study centers in the United States (US), Canada, and Europe will be randomized to DAXI for injection high dose, DAXI for injection low dose, or placebo group, respectively. Subjects will be stratified by treatment center and history of prior treatment with botulinum neurotoxin (BoNT).

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Trial to Evaluate the Efficacy and Safety of a Single Treatment of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia (ASPEN-1)

Conditions
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Cervical Dystonia

Intervention / Treatment
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* Biological: DaxibotulinumtoxinA for injection
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults, 18 to 80 years of age Meets diagnostic criteria for isolated CD (idiopathic; dystonic symptoms localized to the head, neck, shoulder areas) with at least moderate severity at Baseline (Day 1), defined as a TWSTRS-total score of at least 20, with at least 15 on the TWSTRS-Severity subscale, at least 3 on the TWSTRS-Disability subscale, and at least 1 on the TWSTRS-Pain subscale Exclusion Criteria: Cervical dystonia attributable to an underlying etiology, (e.g., traumatic torticollis or tardive torticollis) Predominant retrocollis or anterocollis CD Significant dystonia in other body areas, or is currently being treated with BoNT for dystonia in areas other than those associated with isolated CD Severe dysphagia (Grade 3 or 4 on the Dysphagia Severity Scale) at Screening or Baseline (prior to study treatment) Any neuromuscular neurological conditions that may place the subject at increased risk of morbidity with exposure to BoNT, including peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis and motor neuropathy, and neuromuscular junctional disorders such as Lambert-Eaton syndrome and myasthenia gravis) Previous treatment with any BoNT product for any condition within the 14 weeks prior to Screening Botulinum Neurotoxin Type A (BoNTA), except the investigational daxibotulinumtoxinA, treatment-experienced subjects who had suboptimal or no treatment response to the most recent BoNTA injection for CD, as determined by the investigator, or history of primary or secondary non-response to BoNTA injections, known to have neutralizing antibodies to BoNTA; or have a history of botulinum toxin type B (rimabotulinumtoxinB [Myobloc/Neurobloc]) injection for CD due to non-response or suboptimal response to BoNTA

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
Interventional Model Description: Approximately 300 subjects, recruited from study centers in the United States (US), Canada, and Europe will be randomized to DAXI high dose, DAXI low dose or placebo group.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DAXI for injection low dose<br>Low Dose Group | Biological: DaxibotulinumtoxinA for injection<br>* DaxibotulinumtoxinA for injection is a sterile, white to off-white lyophilized product containing the active ingredient, daxibotulinumtoxinA, and inactive ingredients to be reconstituted with sterile, non-preserved, 0.9% sodium chloride solution saline.<br>|
| Experimental: DAXI for injection high dose<br>High Dose Group | Biological: DaxibotulinumtoxinA for injection<br>* DaxibotulinumtoxinA for injection is a sterile, white to off-white lyophilized product containing the active ingredient, daxibotulinumtoxinA, and inactive ingredients to be reconstituted with sterile, non-preserved, 0.9% sodium chloride solution saline.<br>|
| Placebo Comparator: Placebo<br>Placebo Group | Biological: Placebo<br>* Placebo is a sterile lyophilized product consisting of inactive ingredients without the neurotoxin to be reconstituted with sterile, non-preserved 0.9% sodium chloride solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-total score | TWSTRS is used to assess the severity of cervical Dystonia and the success of its treatment. The average of the change from baseline in TWSTRS-total score at Weeks 4 and 6 will be determined. TWSTRS-total score has a minimum score of 0 and a maximum score of 85, where higher scores represent worse outcomes. It is made up of the summation of 3 subscales: the Torticollis Severity Scale (minimum score of 0, maximum score of 35), the Disability Scale (minimum score of 0, maximum score of 30), and the Pain Scale (minimum score of 0, maximum score of 20). | Week 4 and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline TWSTRS-total score | Change from baseline in TWSTRS-total score (all post-treatment time points) | Up to 36 Weeks | 
| Duration of effect | Duration of effect based on target TWSTRS score | Up to 36 Weeks | 
| Patient Global Impression of Change (PGIC) Improvement | Percentage responders at Week 4 or 6 | Week 4 or Week 6 | 
| Incidence of treatment-emergent adverse events (Safety) | Evaluation of adverse events and serious adverse events over the course of the study. | Up to 36 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DAXI, Cervical Dystonia, TWSTRS, Toxin