Efficacy and Safety of DaxibotulinumtoxinA for Injection for the Treatment of Adult Upper Limb Spasticity
Condition: Upper Limb Spasticity
MeSH terms: Muscle Spasticity
Intervention: DAXI for injection 250 U; DAXI for injection 375 U; DAXI for injection 500 U; Placebo
Intervention description: 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; 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.; 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; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double Blinded. The subject, Sponsor, and study site research personnel will be blinded to the identity of the subject's assigned treatment.
Enrollment: 83.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: ULS; JUNIPER; DAXI for injection; Botulinum toxin

Summary:

      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.
    

Eligibility criteria:

        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)