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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DAXI 250 U | Experimental | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 250 U dose |
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| DAXI 375 U | Experimental | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 375 U |
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| DAXI 500 U | Experimental | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 500 U |
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| Placebo | Placebo Comparator | Placebo group |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DAXI for injection 250 U | Biological | 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 |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rancho Research Institute at Rancho Los Amigos National Rehab Center | Downey | California | 90242 | United States | ||
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| ID | Title | Description |
|---|---|---|
| FG000 | DAXI 250 U | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 250 U |
| FG001 | DAXI 375 U | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 375 U |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 29, 2020 | Jun 1, 2023 |
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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).
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Double Blinded. The subject, Sponsor, and study site research personnel will be blinded to the identity of the subject's assigned treatment.
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| DAXI for injection 375 U | Biological | 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. |
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| DAXI for injection 500 U | Biological | 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 |
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| Placebo | Other | 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. |
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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 |
| The Parkinsons and Movement Disorder Institute |
| Fountain Valley |
| California |
| 92708-5153 |
| United States |
| Collaborative Neuroscience Network LLC | Long Beach | California | 90806 | United States |
| SC3 Research | Pasadena | California | 91105 | United States |
| Yale University | Fairfield | Connecticut | 06824-5340 | United States |
| Waterbury Neurologists | Middlebury | Connecticut | 06762 | United States |
| Ki Health Partners LLC DBA New England Institute for Clinical Research | Stamford | Connecticut | 06905-1206 | United States |
| MedStar National Rehabilitation Hospital | Washington D.C. | District of Columbia | 20010 | United States |
| Parkinsons Disease and Movement Disorders Center | Boca Raton | Florida | 33486 | United States |
| NW FL Clinical Research Group, LLC | Gulf Breeze | Florida | 32561-4458 | United States |
| Infinity Clinical Research | Hollywood | Florida | 33024 | United States |
| Parkinsons Disease Treatment Center of Southwest Florida | Port Charlotte | Florida | 33980-8421 | United States |
| Shirley Ryan AbilityLab | Chicago | Illinois | 60611-2654 | United States |
| Kansas Institute of Research | Overland Park | Kansas | 66211-1358 | United States |
| William Beaumont Hospital | Royal Oak | Michigan | 48073 | United States |
| Rusk Rehabilitation Hospital | Columbia | Missouri | 65203 | United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| Weill Cornell Medical College | New York | New York | 10065-4870 | United States |
| Carolinas Rehabilitation | Charlotte | North Carolina | 28203 | United States |
| Wake Forest University School of Medicine | Salem | North Carolina | 27157 | United States |
| MossRehab | Elkins Park | Pennsylvania | 19027-2220 | United States |
| University of Pittsburgh School of Medicine | Pittsburgh | Pennsylvania | 15213 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| North Texas Institute of Neurology and Headache | Frisco | Texas | 75034 | United States |
| University of Texas Health Science Center at Houston | Houston | Texas | 77030 | United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
| FG002 | DAXI 500 U | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 500 U |
| FG003 | Placebo | Placebo group |
| COMPLETED |
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| NOT COMPLETED |
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Safety population
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| ID | Title | Description |
|---|---|---|
| BG000 | DAXI 250 U | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 250 U |
| BG001 | DAXI 375 U | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 375 U |
| BG002 | DAXI 500 U | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 500 U |
| BG003 | Placebo | Placebo group |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | Intent to treat population | Posted | Least Squares Mean | Standard Error | score on a scale | Week 6 |
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| 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). | Intent to treat population | Posted | Least Squares Mean | Standard Error | score on a scale | Week 6 |
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| 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) | Intent to treat population | Posted | Count of Participants | Participants | Weeks 6 and 12 |
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| 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. | Intent to treat population | Posted | Count of Participants | Participants | Weeks 6 and 12 |
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| 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). | Intent to treat population | Posted | Least Squares Mean | Standard Error | score on a scale | Weeks 6 and 12 |
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| 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. | Intent to treat population | Posted | Median | 95% Confidence Interval | weeks | Up to 36 weeks |
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| Post-Hoc | Change From Baseline at Week 4 in the Suprahypertonic Muscle Group (SMG) Score | Mean change from baseline at Week 4 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). | Intent to treat population | Posted | Least Squares Mean | Standard Error | score on a scale | Week 4 |
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| Post-Hoc | Change From Baseline at Week 4 in the Physician Global Impression of Change (PGIC) Score | Change from Baseline at Week 4 in the Physician Global Impression of Change (PGIC). Score range: -4 (Markedly worse) to +4 (Markedly improved). | Intent to treat population | Posted | Least Squares Mean | Standard Error | score on a scale | Week 4 |
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The adverse events were collected throughout the entire study, up to 36 weeks.
The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DAXI 250 U | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 250 U | 0 | 22 | 2 | 22 | 4 | 22 |
| EG001 | DAXI 375 U | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 375 U | 0 | 19 | 0 | 19 | 12 | 19 |
| EG002 | DAXI 500 U | DAXI for injection for the treatment of Upper Limb Spasticity (ULS) in Adults with 500 U | 0 | 18 | 1 | 18 | 6 | 18 |
| EG003 | Placebo | Placebo group | 0 | 24 | 2 | 24 | 4 | 24 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | Systematic Assessment |
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| Coronavirus infection | Infections and infestations | Systematic Assessment |
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| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | Systematic Assessment |
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| Seizure | Nervous system disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Muscular weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | Systematic Assessment |
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| Vision blurred | Eye disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Influenza like illness | General disorders | Systematic Assessment |
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| Injection site bruising | General disorders | Systematic Assessment |
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| Injection site erythema | General disorders | Systematic Assessment |
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| Injection site hematoma | General disorders | Systematic Assessment |
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| Injection site induration | General disorders | Systematic Assessment |
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| Injection site swelling | General disorders | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | Systematic Assessment |
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| Nail infection | Infections and infestations | Systematic Assessment |
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| Pharyngitis | Infections and infestations | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
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| Heat stroke | Injury, poisoning and procedural complications | Systematic Assessment |
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| Limb injury | Injury, poisoning and procedural complications | Systematic Assessment |
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| Meniscus injury | Injury, poisoning and procedural complications | Systematic Assessment |
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| Skin laceration | Injury, poisoning and procedural complications | Systematic Assessment |
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| Urine analysis abnormal | Investigations | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Myofascial pain syndrome | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Trigger finger | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Cervical radiculopathy | Nervous system disorders | Systematic Assessment |
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| Nocturia | Renal and urinary disorders | Systematic Assessment |
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| Blood blister | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Tooth extraction | Surgical and medical procedures | Systematic Assessment |
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The Study Center and/or Investigator shall submit to Revance a copy of the proposed publication at least sixty (60) days prior to the submission thereof for publication or disclosure to a third party: (i)to provide Revance with the opportunity to review and comment on the contents thereof, (ii)to identify any Confidential Information to be deleted from the proposed publication or disclosure, and (iii)or delay the publication or disclosure 90 days to allow Revance to pursue patent protections.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Todd Gross, PhD, VP, Clinical Development & Data Science | Revance Therapeutics, Inc. | 510-742-3400 | tgross@revance.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 11, 2020 | Jun 1, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D007267 | Injections |
| ID | Term |
|---|---|
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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| > 50 years |
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| Male |
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| Black |
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| Asian |
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| American Indian or Alaska Native |
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| Native Hawaiian or Other Pacific Islander |
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| Other |
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| Not provided |
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| Superiority |
| ANCOVA | 0.0488 | Superiority |
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