Single Treatment of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia (ASPEN-1) (ASPEN-1)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Trial to Evaluate the Efficacy and Safety of a Single Treatment of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia (ASPEN-1)

This is a randomized, double-blind, placebo-controlled, parallel group, multi-center trial of two doses of daxibotulinumtoxinA (DAXI) for injection (high-dose; low-dose in adult subjects with isolated (primary) cervical dystonia (CD).

Study Overview

• Status: Completed
• Conditions: Cervical Dystonia
• Intervention / Treatment: Biological: DaxibotulinumtoxinA for injection; Biological: Placebo

Detailed Description

Approximately 300 subjects, recruited from approximately 80 study centers in the United States (US), Canada, and Europe will be randomized to DAXI for injection high dose, DAXI for injection low dose, or placebo group, respectively. Subjects will be stratified by treatment center and history of prior treatment with botulinum neurotoxin (BoNT).

• Study Type: Interventional
• Enrollment (Actual): 301
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Medical University Innsbruck
  • Wien, Austria, 1090
    • Universitaetsklinik fuer Neurologie
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T2S8
      • University Health Network, Toronto Western Hospital
• Czechia
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc, Neurologicka klinika
  • Ostrava-Poruba, Czechia, 70852
    • Fakultni nemocnice Ostrava, Neurologická klinika
  • Pardubice, Czechia, 53203
    • Lekarna Pardubicke nemocnice
  • Praha, Czechia, 12821
    • Neurologicka klinika 1. LF UK a VFN v Praze
  • Rychnov Nad Kněžnou, Czechia, 51601
    • Vestra Clinics s.r.o.
• France
  • Bron, France, 69500
    • Hôpital Neurologique Pierre Wertheimer
  • Grenoble cedex 09, France, 38043
    • CHU Grenoble Alpes
  • Lille, France, 59037
    • Hôpital Roger Salengro - CHRU de Lille
  • Nimes cedex 09, France, 30029
    • CHU Caremeau, Service de Neurologie
• Germany
  • Berlin, Germany, 10627
    • Praxis fuer Neurologie im Bismark Karrée
  • Duesseldorf, Germany, 40225
    • Universitaetsklinikum Duesseldorf
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Muenchen, Germany, 81675
    • Klinikum rechts der Isar der TUM
  • Troisdorf, Germany, 53844
    • GFO Kliniken Troisdorf, Betriebsstätte St. Johannes Sieglar
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
• Poland
  • Gdansk, Poland, 80462
    • Szpital sw. Wojciecha Podmiot Leczniczy Copernicus Sp. Z o.o.
  • Krakow, Poland, 30539
    • Marta Dagmara BANACH Marta Banach Specjalistyczny Gabinet Neurologiczny
  • Kraków, Poland, 31505
    • Krakowska Akademia Neurologii
  • Olsztyn, Poland, 10-561
    • Wojewodzki Szpital Specjalistyczny w Olsztynie
  • Warsaw, Poland, 01868
    • Centrum Medyczne Pratia Warszawa
  • Warszaw, Poland, 03-242
    • Mazowiecki Szpital Bródnowski Sp. z o.o.
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Burgos, Spain, 09006
    • Hospital Universitario Burgos
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
• United Kingdom
  • Exeter, United Kingdom, EX25DW
    • Royal Devon and Exeter Foundation Trust Hospital
  • Liverpool, United Kingdom, L97LJ
    • The Walton Centre NHS Foundation Trust
  • Salford, United Kingdom, M55AP
    • Salford Royal NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Hope Research Institute
    • Scottsdale, Arizona, United States, 85258-4581
      • Movement Disorders Center of Arizona
  • California
    • Fountain Valley, California, United States, 92708
      • The Parkinsons and Movement Disorder Institute
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • Loma Linda, California, United States, 92354
      • Loma Linda University
    • Los Angeles, California, United States, 90033
      • USC Keck School of Medicine
    • Pasadena, California, United States, 91101
      • Care Access Research
    • Sacramento, California, United States, 95816
      • Sutter Institute for Medical Research
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Associated Neurologist, P.C.
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Clinical Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease And Movement Disorders Center of Boca Raton
    • Doral, Florida, United States, 33172
      • Design Neuroscience Center
    • Gainesville, Florida, United States, 32607
      • University of Florida Center for Movement Disorders and Neurorestoration
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Science Center Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami
    • Saint Petersburg, Florida, United States, 33713-8844
      • Suncoast Neuroscience Associates
    • Tampa, Florida, United States, 33613
      • USF Parkinson's Disease and Movement Disorders Center
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Kansas
    • Overland Park, Kansas, United States, 66211-1358
      • Kansas Institute of Reseach
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
    • Farmington, Michigan, United States, 48334
      • Quest Research Institute
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
    • Saint Louis, Missouri, United States, 63105
      • St Louis University
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Movement Disorders Center
    • Rochester, New York, United States, 14618
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Health Sciences
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19107
      • University of Pennsylvania, Department of Neurology
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Port Royal, South Carolina, United States, 29935
      • Coastal Neurology
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Wesley Neurology Clinic
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 37232
      • Texas Neurology. P.A.
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults, 18 to 80 years of age
• 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 3 on the TWSTRS-Disability subscale, and at least 1 on the TWSTRS-Pain subscale

Exclusion Criteria:

• Cervical dystonia attributable to an underlying etiology, (e.g., traumatic torticollis or tardive torticollis)
• Predominant retrocollis or anterocollis CD
• Significant dystonia in other body areas, or is currently being treated with BoNT for dystonia in areas other than those associated with isolated CD
• Severe dysphagia (Grade 3 or 4 on the Dysphagia Severity Scale) at Screening or Baseline (prior to study treatment)
• Any neuromuscular neurological conditions that may place the subject at increased risk of morbidity with exposure to BoNT, including peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis and motor neuropathy, and neuromuscular junctional disorders such as Lambert-Eaton syndrome and myasthenia gravis)
• Previous treatment with any BoNT product for any condition within the 14 weeks prior to Screening
• Botulinum Neurotoxin Type A (BoNTA), except the investigational daxibotulinumtoxinA, treatment-experienced subjects who had suboptimal or no treatment response to the most recent BoNTA injection for CD, as determined by the investigator, or history of primary or secondary non-response to BoNTA injections, known to have neutralizing antibodies to BoNTA; or have a history of botulinum toxin type B (rimabotulinumtoxinB [Myobloc/Neurobloc]) injection for CD due to non-response or suboptimal response to BoNTA

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo Group	Biological: 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 for injection low dose; Low Dose Group	Biological: DaxibotulinumtoxinA for injection; 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 for injection high dose; High Dose Group	Biological: DaxibotulinumtoxinA for injection; 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 Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-total score	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).	Week 4 and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline TWSTRS-total score	Change from baseline in TWSTRS-total score (all post-treatment time points)	Up to 36 Weeks
Duration of effect	Duration of effect based on target TWSTRS score	Up to 36 Weeks
Patient Global Impression of Change (PGIC) Improvement	Percentage responders at Week 4 or 6	Week 4 or Week 6
Incidence of treatment-emergent adverse events (Safety)	Evaluation of adverse events and serious adverse events over the course of the study.	Up to 36 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in TWSTRS subscale scores	Change from baseline in TWSTRS subscale scores (TWSTRS-Severity, TWSTRS-Disability, and TWSTRS-Pain) (all post-treatment time points)	Up to 36 Weeks
Clinical Global Impression of Change (CGIC)	CGIC at all post-treatment time points	Up to 36 Weeks
Patient Global Impression of Change (PGIC)	PGIC at all post-treatment time points	Up to 36 Weeks

Collaborators and Investigators

• Sponsor: Revance Therapeutics, Inc.
• Collaborators: Syneos Health

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2018
• Primary Completion (Actual): December 3, 2019
• Study Completion (Actual): June 16, 2020

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): December 5, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Cervical Dystonia; DAXI; TWSTRS; Toxin
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Dystonia; Dystonic Disorders; Torticollis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 1720302

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