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

Phase 3

Completed

• Conditions: Cervical Dystonia
• Interventions: Biological: Placebo; Biological: DaxibotulinumtoxinA for injection

• Registration Number: NCT03608397
• Lead Sponsor: Revance Therapeutics, Inc.

Brief Summary

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).

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 Timeline

• Study Start: 2018-06-20
• Study First Submitted: 2018-07-11
• Study First Submitted QC: 2018-07-23
• Study First Posted: 2018-08-01
• Primary Completion: 2019-12-03
• Study Completion: 2020-06-16
• Disposition First Submitted: 2020-12-22
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-29
• Last Update Posted: 2022-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 301

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo Group
DAXI for injection low dose	DaxibotulinumtoxinA for injection	Low Dose Group
DAXI for injection high dose	DaxibotulinumtoxinA for injection	High Dose Group

Primary Outcome Measures

Name	Time	Method
Change from Baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-total score	Week 4 and Week 6	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).

Secondary Outcome Measures

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

Trial Locations

Locations (75)

Medical University Innsbruck; 🇦🇹 Innsbruck, Austria

Centrum Medyczne Pratia Warszawa; 🇵🇱 Warsaw, Poland

New England Institute for Clinical Research; 🇺🇸 Stamford, Connecticut, United States

University Health Network, Toronto Western Hospital; 🇨🇦 Toronto, Ontario, Canada

Care Access Research; 🇺🇸 Pasadena, California, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Houston Methodist Neurological Institute; 🇺🇸 Houston, Texas, United States

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

Movement Disorders Center of Arizona; 🇺🇸 Scottsdale, Arizona, United States

Loma Linda University; 🇺🇸 Loma Linda, California, United States

University of California, Irvine; 🇺🇸 Irvine, California, United States

USC Keck School of Medicine; 🇺🇸 Los Angeles, California, United States

Rocky Mountain Movement Disorders Center; 🇺🇸 Englewood, Colorado, United States

Associated Neurologist, P.C.; 🇺🇸 Danbury, Connecticut, United States

Design Neuroscience Center; 🇺🇸 Doral, Florida, United States

Parkinson's Disease and Movement Disorders Center of Boca Raton; 🇺🇸 Boca Raton, Florida, United States

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

University of Florida Center for Movement Disorders and Neurorestoration; 🇺🇸 Gainesville, Florida, United States

University of Florida Health Science Center Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Suncoast Neuroscience Associates; 🇺🇸 Saint Petersburg, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

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

Michigan State University; 🇺🇸 East Lansing, Michigan, United States

QUEST Research Institute; 🇺🇸 Farmington, Michigan, United States

Henry Ford West Bloomfield Hospital; 🇺🇸 West Bloomfield, Michigan, United States

St Louis University; 🇺🇸 Saint Louis, Missouri, United States

Mount Sinai Movement Disorders Center; 🇺🇸 New York, New York, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

University of Pennsylvania, Department of Neurology; 🇺🇸 Philadelphia, Pennsylvania, United States

Wesley Neurology Clinic; 🇺🇸 Cordova, Tennessee, United States

Coastal Neurology; 🇺🇸 Port Royal, South Carolina, United States

Texas Neurology. P.A.; 🇺🇸 Dallas, Texas, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Central Texas Neurology Consultants; 🇺🇸 Round Rock, Texas, United States

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

Lekarna Pardubicke nemocnice; 🇨🇿 Pardubice, Czechia

Universitaetsklinik fuer Neurologie; 🇦🇹 Wien, Austria

Fakultni nemocnice Olomouc, Neurologicka klinika; 🇨🇿 Olomouc, Czechia

Fakultní nemocnice Ostrava, Neurologicka klinika; 🇨🇿 Ostrava-Poruba, Czechia

Neurologicka klinika 1. LF UK a VFN v Praze; 🇨🇿 Praha, Czechia

Vestra Clinics s.r.o.; 🇨🇿 Rychnov Nad Kněžnou, Czechia

Hôpital Neurologique Pierre Wertheimer; 🇫🇷 Bron, France

Hôpital Roger Salengro - CHRU de Lille; 🇫🇷 Lille, France

Praxis fuer Neurologie im Bismark Karrée; 🇩🇪 Berlin, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Universitaetsklinikum Duesseldorf; 🇩🇪 Duesseldorf, Germany

GFO Kliniken Troisdorf, Betriebsstätte St. Johannes Sieglar; 🇩🇪 Troisdorf, Germany

Universitätsklinikum Tübingen; 🇩🇪 Tübingen, Germany

Szpital sw. Wojciecha Podmiot Leczniczy Copernicus Sp. Z o.o.; 🇵🇱 Gdansk, Poland

Krakowska Akademia Neurologii; 🇵🇱 Kraków, Poland

Marta Dagmara BANACH Marta Banach Specjalistyczny Gabinet Neurologiczny; 🇵🇱 Krakow, Poland

Wojewodzki Szpital Specjalistyczny w Olsztynie; 🇵🇱 Olsztyn, Poland

Mazowiecki Szpital Brodnowski Sp. z o.o.; 🇵🇱 Warszaw, Poland

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitario de La Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario Burgos; 🇪🇸 Burgos, Spain

Royal Devon and Exeter Foundation Trust Hospital; 🇬🇧 Exeter, United Kingdom

The Walton Centre NHS Foundation Trust; 🇬🇧 Liverpool, United Kingdom

Salford Royal NHS Foundation Trust; 🇬🇧 Salford, United Kingdom

CHU Grenoble Alpes; 🇫🇷 Grenoble cedex 09, France

CHU Caremeau, Service de Neurologie; 🇫🇷 Nimes cedex 09, France

Klinikum rechts der Isar der TUM; 🇩🇪 Muenchen, Germany

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

HOPE Research Institute; 🇺🇸 Phoenix, Arizona, United States

Sutter Institute for Medical Research; 🇺🇸 Sacramento, California, United States

USF Parkinson's Disease and Movement Disorders Center; 🇺🇸 Tampa, Florida, United States

Wake Forest Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

MedStar Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

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

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States