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

Phase 2

Completed

• Conditions: Upper Limb Spasticity
• Interventions: Biological: DAXI for injection 500 U; Biological: DAXI for injection 250 U; Biological: DAXI for injection 375 U; Other: Placebo

• Registration Number: NCT03821402
• Lead Sponsor: Revance Therapeutics, Inc.

Brief 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.

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 Timeline

• Study Start: 2018-12-12
• Study First Submitted: 2019-01-15
• Study First Submitted QC: 2019-01-28
• Study First Posted: 2019-01-29
• Primary Completion: 2020-11-23
• Study Completion: 2020-11-23
• Disposition First Submitted: 2020-12-22
• Results First Submitted: 2023-06-02
• Status Verified: 2023-08
• Results First Submitted QC: 2023-08-25
• Last Update Submitted: 2023-08-25
• Results First Posted: 2023-09-21
• Disposition First Posted: 2023-09-21
• Last Update Posted: 2023-09-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 83

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DAXI 500 U	DAXI for injection 500 U	DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 500 U
DAXI 250 U	DAXI for injection 250 U	DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 250 U dose
DAXI 375 U	DAXI for injection 375 U	DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 375 U
Placebo	Placebo	Placebo group

Primary Outcome Measures

Name	Time	Method
Change From Baseline at Week 6 on the Modified Ashworth Scale (MAS) in the Suprahypertonic Muscle Group (SMG) Score	Week 6	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).
Physician Global Impression of Change (PGIC) Score	Week 6	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).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline at Weeks 6 and 12 on the Disability Assessment Scale (DAS) Functional Impairment	Weeks 6 and 12	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).
Duration of Effect	Up to 36 weeks	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.
Muscle Tone Improvement Responder Rate	Weeks 6 and 12	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)
Physician Global Impression of Change (PGIC) Responder Rate	Weeks 6 and 12	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.

Trial Locations

Locations (26)

Kansas Institute of Research; 🇺🇸 Overland Park, Kansas, United States

The Parkinsons and Movement Disorder Institute; 🇺🇸 Fountain Valley, California, United States

SC3 Research; 🇺🇸 Pasadena, California, United States

Wake Forest University School of Medicine; 🇺🇸 Salem, North Carolina, United States

Infinity Clinical Research; 🇺🇸 Hollywood, Florida, United States

Rusk Rehabilitation Hospital; 🇺🇸 Columbia, Missouri, United States

Collaborative Neuroscience Network LLC; 🇺🇸 Long Beach, California, United States

MossRehab; 🇺🇸 Elkins Park, Pennsylvania, United States

NW FL Clinical Research Group, LLC; 🇺🇸 Gulf Breeze, Florida, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Parkinsons Disease and Movement Disorders Center; 🇺🇸 Boca Raton, Florida, United States

North Texas Institute of Neurology and Headache; 🇺🇸 Frisco, Texas, United States

Carolinas Rehabilitation; 🇺🇸 Charlotte, North Carolina, United States

Parkinsons Disease Treatment Center of Southwest Florida; 🇺🇸 Port Charlotte, Florida, United States

William Beaumont Hospital; 🇺🇸 Royal Oak, Michigan, United States

Rancho Research Institute at Rancho Los Amigos National Rehab Center; 🇺🇸 Downey, California, United States

Yale University; 🇺🇸 Fairfield, Connecticut, United States

Shirley Ryan AbilityLab; 🇺🇸 Chicago, Illinois, United States

University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

University of Pittsburgh School of Medicine; 🇺🇸 Pittsburgh, Pennsylvania, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

Ki Health Partners LLC DBA New England Institute for Clinical Research; 🇺🇸 Stamford, Connecticut, United States

Waterbury Neurologists; 🇺🇸 Middlebury, Connecticut, United States

MedStar National Rehabilitation Hospital; 🇺🇸 Washington, District of Columbia, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States