Long-Term Safety and Efficacy of Repeat Treatments of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia (ASPEN-OLS)

Study Overview
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Brief Summary
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Phase 3, open-label, multi-center trial to evaluate the long-term safety, efficacy, and immunogenicity of up to four continuous treatment cycles of daxibotulinumtoxinA (DAXI) for injection.

Detailed Description
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Approximately 350 adult subjects will be recruited from approximately 80 study centers in the United States, Canada, and Europe who were enrolled in the ASPEN-1 Study Protocol 1720302 and de novo subjects (not previously enrolled in ASPEN-1 Study Protocol 1720302) will be treated with up to 4 different doses of daxibotulinumtoxinA for injection.

Official Title
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A Phase 3, Open-Label, Multi-Center Trial to Evaluate the Long-Term Safety and Efficacy of Repeat Treatments of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia (ASPEN-OLS)

Conditions
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Cervical Dystonia

Intervention / Treatment
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* Biological: daxibotulinumtoxinA for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 (minimum TWSTRS subscale criteria applicable only to subjects not previously enrolled in Study Protocol 1720302) Subjects who were previously enrolled in Study Protocol 1720302, and completed the study, including: Those with no reduction or have an increase from baseline in the average TWSTRS-total score at Weeks 4 and 6 (i.e., no improvement or worsened disease status), and the investigator agreed that there was a need for retreatment based on the subject's symptoms and neurologic exam findings Those who benefited from study treatment and completed follow-up study visits up to the time point of when their TWSTRS - total score reached/exceeded their target TWSTRS score Those who benefited from study treatment but subsequently experienced significant recurrence of CD symptoms (e.g. pain) during the study before their TWSTRS-total score reached their target TWSTRS score and requested retreatment, which the investigator determined was warranted based on the subject's symptoms and neurologic exam findings Those who completed study visits up to Week 36 and their TWSTRS-total score never reached their target TWSTRS score and they never requested another treatment. The investigator determined that these subjects can be followed in the OLS until their TWSTRS-total score is the same or higher than their target TWSTRS score or until they request retreatment, which the investigator determined is clinically indicated De novo subjects (not previously enrolled in Study Protocol 1720302): Naïve to BoNT treatment BoNT treatment-experienced; if previously treated with BoNTA, the subject must have demonstrated a clinically meaningful response to the last BoNTA treatment based on the clinical judgment of the investigator 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 botulinum toxin (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 (applicable only to de novo subjects) Botulinum neurotoxin 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 (rimabotulinumtoxinA [Myobloc/Neurobloc]) injection for CD due to non-response or suboptimal response to BoNTA (applicable only to de novo subjects)

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
Intervention Model: Single Group Assignment
Interventional Model Description: This is a Phase 3, open-label, multi-center trial to evaluate the long-term safety, efficacy, and immunogenicity of up to four continuous treatment cycles of daxibotulinumtoxinA (DAXI) for injection with up to four different doses in adults with isolated cervical dystonia (CD).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: daxibotulinumtoxinA (DAXI) for injection<br>DAXI for injection | 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>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long Term Safety of patients determined by the incidence of treatment-emergent adverse events | Evaluation of adverse events and serious adverse events, from multiple continuous treatments of DAXI for injection, over the course of the study. | Up to 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with at least moderate improvement on the Clinician Global Impression of Change (CGIC) at Weeks 4 or 6 for Treatment Cycles 1, 2, 3, and 4 | The CGIC is an investigator-reported assessment of the global clinical change in CD since study treatment administration. The CGIC uses a 7-point Likert scale ranging from +3 (very much improved) to -3 (very much worse), and will be assessed by the investigator at the Week 4 and Week 6 visits. | Weeks 4 and 6 of treatment cycles 1, 2, 3, and 4 (12 - 52 weeks duration each) | 
| The average of the change from Baseline in the TWSTRS Total Score at Weeks 4 and 6 for Treatment Cycles 1, 2, 3, and 4 [Time Frame: Weeks 4 and 6 of treatment cycles 1, 2, 3, and 4 (12 - 52 weeks duration each)] | The difference in TWSTRS-Total score between the Baseline and average of Weeks 4 and 6 for each treatment cycle will be determined for each subject. The TWSTRS is an assessment scale used to measure the impact of CD on subjects. 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). | Weeks 4 and 6 of treatment cycles 1, 2, 3, and 4 (12 - 52 weeks duration each) | 

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