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

Upper Limb Spasticity Clinical Trial

— JUNIPER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03821402
• Other study ID #: 1820203
• Status: Completed
• Phase: Phase 2
• Start date: December 12, 2018
• Est. completion date: November 23, 2020

Study information

• Verified date: August 2023
• Source: Revance Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: November 23, 2020
• Est. primary completion date: November 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Muscle Spasticity
• Upper Limb Spasticity

Intervention

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
• 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.
• 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

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.

Locations

Country	Name	City	State
United States	Parkinsons Disease and Movement Disorders Center	Boca Raton	Florida
United States	Carolinas Rehabilitation	Charlotte	North Carolina
United States	Shirley Ryan AbilityLab	Chicago	Illinois
United States	Rusk Rehabilitation Hospital	Columbia	Missouri
United States	Rancho Research Institute at Rancho Los Amigos National Rehab Center	Downey	California
United States	MossRehab	Elkins Park	Pennsylvania
United States	Yale University	Fairfield	Connecticut
United States	The Parkinsons and Movement Disorder Institute	Fountain Valley	California
United States	North Texas Institute of Neurology and Headache	Frisco	Texas
United States	NW FL Clinical Research Group, LLC	Gulf Breeze	Florida
United States	Infinity Clinical Research	Hollywood	Florida
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Collaborative Neuroscience Network LLC	Long Beach	California
United States	Waterbury Neurologists	Middlebury	Connecticut
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Kansas Institute of Research	Overland Park	Kansas
United States	SC3 Research	Pasadena	California
United States	University of Pittsburgh School of Medicine	Pittsburgh	Pennsylvania
United States	Parkinsons Disease Treatment Center of Southwest Florida	Port Charlotte	Florida
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Wake Forest University School of Medicine	Salem	North Carolina
United States	University of Utah	Salt Lake City	Utah
United States	Ki Health Partners LLC DBA New England Institute for Clinical Research	Stamford	Connecticut
United States	MedStar National Rehabilitation Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Revance Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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