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

Cervical Dystonia Clinical Trial

— ASPEN-1  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03608397
• Other study ID #: 1720302
• Status: Completed
• Phase: Phase 3
• Start date: June 20, 2018
• Est. completion date: June 16, 2020

Study information

• Verified date: November 2022
• Source: Revance Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 301
• Est. completion date: June 16, 2020
• Est. primary completion date: December 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cervical Dystonia
• Dystonia
• Dystonic Disorders
• Torticollis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Austria	Medical University Innsbruck	Innsbruck
Austria	Universitaetsklinik fuer Neurologie	Wien
Canada	University Health Network, Toronto Western Hospital	Toronto	Ontario
Czechia	Fakultni nemocnice Olomouc, Neurologicka klinika	Olomouc
Czechia	Fakultní nemocnice Ostrava, Neurologicka klinika	Ostrava-Poruba
Czechia	Lekarna Pardubicke nemocnice	Pardubice
Czechia	Neurologicka klinika 1. LF UK a VFN v Praze	Praha
Czechia	Vestra Clinics s.r.o.	Rychnov Nad Knežnou
France	Hôpital Neurologique Pierre Wertheimer	Bron
France	CHU Grenoble Alpes	Grenoble cedex 09
France	Hôpital Roger Salengro - CHRU de Lille	Lille
France	CHU Caremeau, Service de Neurologie	Nimes cedex 09
Germany	Praxis fuer Neurologie im Bismark Karrée	Berlin
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Klinikum rechts der Isar der TUM	Muenchen
Germany	GFO Kliniken Troisdorf, Betriebsstätte St. Johannes Sieglar	Troisdorf
Germany	Universitätsklinikum Tübingen	Tübingen
Poland	Szpital sw. Wojciecha Podmiot Leczniczy Copernicus Sp. Z o.o.	Gdansk
Poland	Marta Dagmara BANACH Marta Banach Specjalistyczny Gabinet Neurologiczny	Krakow
Poland	Krakowska Akademia Neurologii	Kraków
Poland	Wojewodzki Szpital Specjalistyczny w Olsztynie	Olsztyn
Poland	Centrum Medyczne Pratia Warszawa	Warsaw
Poland	Mazowiecki Szpital Brodnowski Sp. z o.o.	Warszaw
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Burgos	Burgos
Spain	Hospital Universitario de La Princesa	Madrid
United Kingdom	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 States	Emory University	Atlanta	Georgia
United States	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Wesley Neurology Clinic	Cordova	Tennessee
United States	Texas Neurology. P.A.	Dallas	Texas
United States	Associated Neurologist, P.C.	Danbury	Connecticut
United States	Design Neuroscience Center	Doral	Florida
United States	Duke University	Durham	North Carolina
United States	Michigan State University	East Lansing	Michigan
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	QUEST Research Institute	Farmington	Michigan
United States	The Parkinsons and Movement Disorder Institute	Fountain Valley	California
United States	University of Florida Center for Movement Disorders and Neurorestoration	Gainesville	Florida
United States	Infinity Clinical Research	Hollywood	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Houston Methodist Neurological Institute	Houston	Texas
United States	University of California, Irvine	Irvine	California
United States	University of Florida Health Science Center Jacksonville	Jacksonville	Florida
United States	Loma Linda University	Loma Linda	California
United States	USC Keck School of Medicine	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Mount Sinai Movement Disorders Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Kansas Institute of Reseach	Overland Park	Kansas
United States	Care Access Research	Pasadena	California
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania, Department of Neurology	Philadelphia	Pennsylvania
United States	HOPE Research Institute	Phoenix	Arizona
United States	Coastal Neurology	Port Royal	South Carolina
United States	University of Rochester	Rochester	New York
United States	Central Texas Neurology Consultants	Round Rock	Texas
United States	Sutter Institute for Medical Research	Sacramento	California
United States	St Louis University	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	Suncoast Neuroscience Associates	Saint Petersburg	Florida
United States	Movement Disorders Center of Arizona	Scottsdale	Arizona
United States	New England Institute for Clinical Research	Stamford	Connecticut
United States	USF Parkinson's Disease and Movement Disorders Center	Tampa	Florida
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Wake Forest Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Revance Therapeutics, Inc.	Syneos Health

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Czechia,  France,  Germany,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Clinical Global Impression of Change (CGIC)	CGIC at all post-treatment time points	Up to 36 Weeks
Other	Patient Global Impression of Change (PGIC)	PGIC at all post-treatment time points	Up to 36 Weeks
Primary	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	Change from Baseline TWSTRS-total score	Change from baseline in TWSTRS-total score (all post-treatment time points)	Up to 36 Weeks
Secondary	Duration of effect	Duration of effect based on target TWSTRS score	Up to 36 Weeks
Secondary	Patient Global Impression of Change (PGIC) Improvement	Percentage responders at Week 4 or 6	Week 4 or Week 6
Secondary	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