Efficacy and Safety of DaxibotulinumtoxinA for Injection for the Treatment of Adult Upper Limb Spasticity

Study Overview
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Brief Summary
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This is a randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Ranging, trial to Evaluate the Efficacy and Safety of DaxibotulinumtoxinA for Injection for the Treatment of Upper Limb Spasticity in Adults After Stroke or Traumatic Brain Injury. The study will be conducted in the U.S.A., approximately 128 adult subjects from approximately 30 study centers will be randomly assigned (1:1:1:1) to one of four treatment groups. The study consists of a 21-day screening period, a treatment visit and follow-up visits. The protocol was amended and the study was completed with fewer subjects than described in the initial protocol due to impact of COVID-19 on enrollment.

Detailed Description
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Subjects will be randomly assigned to DAXI for Injection 250 U, DAXI for Injection 375 U, DAXI for Injection 500 U, or placebo group, respectively. Eligible subjects will have ULS characterized by a primary aggregate posture

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Ranging, Multi-Center Trial to Evaluate the Efficacy and Safety of DaxibotulinumtoxinA for Injection for the Treatment of Upper Limb Spasticity in Adults After Stroke or Traumatic Brain Injury

Conditions
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Upper Limb Spasticity

Intervention / Treatment
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* Biological: DAXI for injection 250 U
* Biological: DAXI for injection 375 U
* Biological: DAXI for injection 500 U
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 75 years of age Written informed consent including authorization to release health information Focal upper limb spasticity (ULS) after a stroke (as defined by WHO criteria) or traumatic brain injury (TBI), last stroke or TBI > 24 weeks prior to Screening ULS with the primary aggregate posture Moderate to severe ULS with a MAS score ≥ 2 at the elbow, wrist, and finger flexors Moderate to severe functional disability (Disability Assessment Score [DAS] score ≥2) on the principal target of treatment Has sufficient cognitive and communication ability to be able to give informed consent Exclusion Criteria: Upper limb spasticity attributable to an etiology other than stroke or TBI. Bilateral upper limb paresis or quadriplegia. Initiated in physiotherapy of the upper extremities ≤ 30 days prior to Screening or planned to start physiotherapy of the upper extremities during the course of the study. Previous or planned treatment of the spastic upper limb with phenol, alcohol injection, or surgery Profound muscular atrophy or fixed contracture leading to marked limitation on range of motion Prior treatment with intrathecal baclofen Any neuromuscular neurologic conditions (amyotrophic lateral sclerosis, Lambert- Eaton, myasthenia gravis)

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible subjects will be randomized (1:1:1:1) to one of four treatment groups: Group 1: DAXI 250 U (N=32); Group 2: DAXI 375 U (N=32); Group 3: DAXI 500 U (N=32); Group 4: Placebo (N=32).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DAXI 250 U<br>DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 250 U dose | Biological: DAXI for injection 250 U<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 375 U<br>DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 375 U | Biological: DAXI for injection 375 U<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 500 U<br>DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 500 U | Biological: DAXI for injection 500 U<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 | Other: 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 at Week 6 on the Modified Ashworth Scale (MAS) in the Suprahypertonic Muscle Group (SMG) Score | Mean change from baseline at Week 6 in muscle tone measured with the Modified Ashworth Scale (MAS) in the Suprahypertonic Muscle Group (SMG) in one of the following: elbow, wrist, or finger flexors. Score range: 0 (Normal tone, no in tone) to 4 (Affected part{s} rigid in flexion or extension). | Week 6 | 
| Physician Global Impression of Change (PGIC) Score | Mean score on the Physician Global Impression of Change (PGIC) score at week 6. The PGIC is a single-item, 9-point scale that measures the physician's impression of improvement following treatment. Score range: -4 (Markedly worse) to +4 (Markedly improved). | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Tone Improvement Responder Rate | Percentage of subjects who improve by a full point on the Modified Ashworth Scale (MAS) in the Suprahypertonic Muscle Group (SMG). Score range: 0 (Normal tone, no increase in tone) to 4 (Affected part(s) rigid in flexion or extension) | Weeks 6 and 12 | 
| Physician Global Impression of Change (PGIC) Responder Rate | Percentage of subjects with improvement (i.e., a score of 1 to 4) on the Physician Global Impression of Change (PGIC). The PGIC is a single-item, 9-point scale that measures the physician's impression of improvement following treatment. Score range: -4 (Markedly worse) to +4 (Markedly improved). Scores of 1 or more indicate improvement following treatment. | Weeks 6 and 12 | 
| Change From Baseline at Weeks 6 and 12 on the Disability Assessment Scale (DAS) Functional Impairment | Change from Baseline at Weeks 6 and 12 in functional impairment as measured by the Disability Assessment Scale (DAS) for the principal treatment target (PTT). DAS score range: 0 (No disability) to 3 (Severe disability - normal activities limited). | Weeks 6 and 12 | 
| Duration of Effect | Duration of effect is defined as time from injection (in weeks) until loss of muscle tone improvement in the SMG, as indicated by a reduction from baseline in MAS score of < 1-point and PGIC score is ≤ 0. | Up to 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ULS, JUNIPER, DAXI for injection, Botulinum toxin