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Also known as DaxibotulinumtoxinA
Botulinum Toxins, Type A · 11 trials · 12 indications
Evaluation of adverse events and serious adverse events, from multiple continuous treatments of DAXI for injection, over the course of the study.
TWSTRS is used to assess the severity of cervical Dystonia and the success of its treatment. The average of the change from baseline in TWSTRS-total score at Weeks 4 and 6 will be determined. TWSTRS-total score has a minimum score of 0 and a maximum score of 85, where higher scores represent worse outcomes. It is made up of the summation of 3 subscales: the Torticollis Severity Scale (minimum score of 0, maximum score of 35), the Disability Scale (minimum score of 0, maximum score of 30), and the Pain Scale (minimum score of 0, maximum score of 20).
Incidence rates based on the number and percentage of subjects treated within each cycle who report Adverse Events (AEs) at anytime following study treatment. Note that subjects could receive up to 3 consecutive treatments during the 36-week follow up period.
Percentage of subjects who achieve at least a 2-point improvement from baseline and a score of 0 or 1 (i.e., none or mild wrinkles in severity) on both Investigator and Subject Frown Wrinkle Severity (FWS) assessments
Time to retreatment (in days) with DAXI between the first and second study injection cycle.
For patients who receive 3 study injection cycles with DAXI over 12 months, a second primary endpoint will be the time to retreatment (in days) between the second-to-last and last injection cycle (i.e., between DAXI cycles 2 and 3).
The percentage of subjects achieving a score of 0 (none) or 1 (mild) in GL severity at maximum contraction (maximum frown) at Week 4 as assessed by the IGA-FWS
The percentage of subjects achieving a score of 0 (none) or 1 (mild) in FHL severity at maximum contraction (maximum eyebrow elevation) at Week 4 as assessed by the IGA-FHWS
The percentage of subjects achieving a score of 0 (none) or 1 (mild) in LCL severity at maximum contraction (maximum smile effort) at Week 4 as assessed by the IGA-LCWS
Percentage of subjects achieving a score or 0 or 1 (none or mild) in LCL severity at maximum smile at Week 4 after LCL treatment on the Investigator Global Assessment Lateral Canthal Wrinkle Severity (IGA-LCWS) scale
The primary efficacy endpoint, as identified in the Statistical Analysis Plan (SAP) was the change from baseline in the visual analog scale (VAS) for pain for the affected foot at Week 8. The outcome was measured by means of a 100 mm VAS (0= no pain, 100= maximum pain) and higher reduction from baseline VAS pain scores means a better outcome.
| Arm | Type | Description |
|---|---|---|
| daxibotulinumtoxinA (DAXI) for injection | EXPERIMENTAL | DAXI for injection |
| DAXI for injection low dose | EXPERIMENTAL | Low Dose Group |
| DAXI for injection high dose | EXPERIMENTAL | High Dose Group |
| Placebo | PLACEBO_COMPARATOR | Placebo Group |
| DaxibotulinumtoxinA 40 units | EXPERIMENTAL | Biological/Vaccine: Botulinum Toxins, Type A Intramuscular injection |
| Open label arm | EXPERIMENTAL | The study cohort will consist of adults with blepharospasm who previously received onabotulinumtoxinA or incobotulinumtoxinA and will transition to DAXI 12 weeks after their last botulinum toxin treatment. Each participant will receive a DAXI dose equivalent to their prior therapy, using a 1:1 conversion for onabotulinumtoxinA or a 1.5:1 conversion for incobotulinumtoxinA, adjusted if prior treatment caused excessive weakness or other side effects. Injections will be limited to muscles directly involved in blepharospasm (the orbicularis oculi, corrugators, procerus, and nasalis) and will use a dilution of 10 units per 0.1 mL. Subjects may use topical anesthetics to reduce injection pain, and efforts will ensure the same injector administers all treatments to maintain consistency. |
| DAXI 40 U GL / 32 U FHL / 48 U LCL | EXPERIMENTAL | DaxibotulinumtoxinA for injection for the treatment of moderate to severe Glabellar Lines (GL), Forehead Lines (FHL), \& Lateral Canthal Lines (LCL) |
| Cohort 1: DAXI 12 U | EXPERIMENTAL | DAXI for injection for the treatment of moderate to severe Lateral Canthal Lines (LCL) |
| Cohort 2: DAXI 24 U | EXPERIMENTAL | DAXI for injection for the treatment of moderate to severe Lateral Canthal Lines (LCL) |
| Cohort 3: DAXI 36 U | EXPERIMENTAL | DAXI for injection for the treatment of moderate to severe Lateral Canthal Lines (LCL) |
| Cohort 4: DAXI 48 U | EXPERIMENTAL | DAXI for injection for the treatment of moderate to severe Lateral Canthal Lines (LCL) |
| Cohort 1: Dose A | EXPERIMENTAL | DAXI for injection for the treatment of Forehead Lines (FHL) and Glabellar Lines (GL) |
| Cohort 2: Dose B | EXPERIMENTAL | DAXI for injection for the treatment of Forehead Lines (FHL) and Glabellar Lines (GL) |
| Cohort 3: Dose C | EXPERIMENTAL | DAXI for injection for the treatment of Forehead Lines (FHL) and Glabellar Lines (GL) |
| Cohort 4: Dose D | EXPERIMENTAL | DAXI for injection for the treatment of Forehead Lines (FHL) and Glabellar Lines (GL) |
| DAXI 240 U | EXPERIMENTAL | DaxibotulinumtoxinA for injection for the treatment of plantar fasciitis (PF) with 240 U |
| Name | Type | Description |
|---|---|---|
| daxibotulinumtoxinA for injection | 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. |
| Placebo | BIOLOGICAL | 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. |
| Botulinum Toxins, Type A | BIOLOGICAL | Intramuscular Injection |
| Placebos | BIOLOGICAL | Intramuscular injection |
| Botulinum Neurotoxin Type A | DRUG | DaxibotulinumtoxinA (DAXI) for injection is a sterile, lyophilized powder containing 100 units of active daxibotulinumtoxinA per vial, along with inactive ingredients including RTP004, trehalose dihydrate, L-histidine, L-histidine hydrochloride, and polysorbate 20. It is reconstituted with Bacteriostatic Sodium Chloride Injection 0.9% (Pfizer) and stored at 2-8°C. DAXI will be prepared by trained injectors or staff, with all preparations documented. Experienced movement disorder neurologists will administer injections, primarily from UPenn's Parkinson's Disease and Movement Disorders Center. Dosing will follow prior treatment patterns using a 1:1 conversion from onabotulinumtoxinA or 1.5:1 from incobotulinumtoxinA, adjusted for prior adverse effects. Injection sites will be selected based on clinical presentation, with optional EMG or imaging guidance. |
| DaxibotulinumtoxinA | BIOLOGICAL | Low, mid, and high dose sequential treatments of daxibotulinumtoxinA in dose-escalation safety and efficacy study |
Inclusion Criteria: * Meets diagnostic criteria for isolated CD (idiopathic; dystonic symptoms localized to the head, neck, shoulder areas) with at least moderate severity at Baseline (Day 1), defined as a TWSTRS-total score of at least 20, with at least 15 on the TWSTRS-Severity subscale, at least...
Botulinum toxins, type A is being developed by Revance Therapeutics for two indications: moderate to severe glabellar frown lines, the vertical lines between the eyebrows, and plantar fasciitis, a painful inflammation of the tissue along the bottom of the foot. Both programs are in clinical development.
Botulinum toxins, type A targets SNAP25, a hydrolytic enzyme protein involved in the release of neurotransmitters from nerve terminals. By acting on SNAP25, the therapy is designed to interfere with nerve signaling to the targeted muscle, which underlies its use in smoothing glabellar frown lines and in treating plantar fasciitis.
Revance Therapeutics, Inc., which trades on the Nasdaq under the ticker RVNC, is developing botulinum toxins, type A. The company is running the clinical program for the asset across dermatology and musculoskeletal indications, including glabellar frown lines and plantar fasciitis.
Botulinum toxins, type A is in Phase 3 clinical development and is investigational. It has not been established as approved. The program includes completed Phase 3 trials in glabellar frown lines and a completed Phase 2 trial in plantar fasciitis, with no trials currently listed as active.
Four completed trials are registered for botulinum toxins, type A. NCT03014635 and NCT03014622 were Phase 3 studies in moderate to severe glabellar lines, NCT03004248 was a Phase 3 safety study of single and repeat treatments in glabellar lines, and NCT03137407 was a Phase 2 study in plantar fasciitis.
Across the registered trials, total enrollment was about 3,300 participants. The glabellar line studies enrolled 306, 303, and 2,691 patients respectively, and the plantar fasciitis study enrolled 59. The trials were randomized, double blind, and placebo controlled, and enrolled adults 18 years and older.