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

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

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.

Study Overview

• Status: Completed
• Conditions: Upper Limb Spasticity
• Intervention / Treatment: Other: Placebo; Biological: DAXI for injection 250 U; Biological: DAXI for injection 375 U; Biological: DAXI for injection 500 U

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Downey, California, United States, 90242
      • Rancho Research Institute at Rancho Los Amigos National Rehab Center
    • Fountain Valley, California, United States, 92708-5153
      • The Parkinsons and Movement Disorder Institute
    • Long Beach, California, United States, 90806
      • Collaborative NeuroScience Network LLC
    • Pasadena, California, United States, 91105
      • SC3 Research
  • Connecticut
    • Fairfield, Connecticut, United States, 06824-5340
      • Yale University
    • Middlebury, Connecticut, United States, 06762
      • Waterbury Neurologists
    • Stamford, Connecticut, United States, 06905-1206
      • Ki Health Partners LLC DBA New England Institute for Clinical Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar National Rehabilitation Hospital
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinsons Disease and Movement Disorders Center
    • Gulf Breeze, Florida, United States, 32561-4458
      • NW FL Clinical Research Group, LLC
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research
    • Port Charlotte, Florida, United States, 33980-8421
      • Parkinsons Disease Treatment Center of Southwest Florida
  • Illinois
    • Chicago, Illinois, United States, 60611-2654
      • Shirley Ryan AbilityLab
  • Kansas
    • Overland Park, Kansas, United States, 66211-1358
      • Kansas Institute of Research
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Rusk Rehabilitation Hospital
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10065-4870
      • Weill Cornell Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Rehabilitation
    • Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Pennsylvania
    • Elkins Park, Pennsylvania, United States, 19027-2220
      • MossRehab
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Frisco, Texas, United States, 75034
      • North Texas Institute of Neurology and Headache
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo group	Other: Placebo; 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.
Experimental: DAXI 250 U; DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 250 U dose	Biological: DAXI for injection 250 U; 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
Experimental: DAXI 375 U; DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 375 U	Biological: DAXI for injection 375 U; 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.
Experimental: DAXI 500 U; DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 500 U	Biological: DAXI for injection 500 U; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Revance Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): November 23, 2020
• Study Completion (Actual): November 23, 2020

Study Registration Dates

• First Submitted: January 15, 2019
• First Submitted That Met QC Criteria: January 28, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Botulinum toxin; ULS; JUNIPER; DAXI for injection
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Muscle Spasticity
• Other Study ID Numbers: 1820203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No