Long-Term Safety and Efficacy of Repeat Treatments of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia (ASPEN-OLS)

Cervical Dystonia Clinical Trial

— ASPEN-OLS  

Official title:

A Phase 3, Open-Label, Multi-Center Trial to Evaluate the Long-Term Safety and Efficacy of Repeat Treatments of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia (ASPEN-OLS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03617367
• Other study ID #: 1720304
• Status: Completed
• Phase: Phase 3
• Start date: September 5, 2018
• Est. completion date: May 25, 2021

Study information

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

Clinical Trial Summary

Phase 3, open-label, multi-center trial to evaluate the long-term safety, efficacy, and immunogenicity of up to four continuous treatment cycles of daxibotulinumtoxinA (DAXI) for injection.

Description:

Approximately 350 adult subjects will be recruited from approximately 80 study centers in the United States, Canada, and Europe who were enrolled in the ASPEN-1 Study Protocol 1720302 and de novo subjects (not previously enrolled in ASPEN-1 Study Protocol 1720302) will be treated with up to 4 different doses of daxibotulinumtoxinA for injection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 357
• Est. completion date: May 25, 2021
• Est. primary completion date: May 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 3 on the TWSTRS-Disability subscale, and at least 1 on the TWSTRS-Pain subscale (minimum TWSTRS subscale criteria applicable only to subjects not previously enrolled in Study Protocol 1720302)

• Subjects who were previously enrolled in Study Protocol 1720302, and completed the study, including:

• Those with no reduction or have an increase from baseline in the average TWSTRS-total score at Weeks 4 and 6 (i.e., no improvement or worsened disease status), and the investigator agreed that there was a need for retreatment based on the subject's symptoms and neurologic exam findings

• Those who benefited from study treatment and completed follow-up study visits up to the time point of when their TWSTRS - total score reached/exceeded their target TWSTRS score

• Those who benefited from study treatment but subsequently experienced significant recurrence of CD symptoms (e.g. pain) during the study before their TWSTRS-total score reached their target TWSTRS score and requested retreatment, which the investigator determined was warranted based on the subject's symptoms and neurologic exam findings

• Those who completed study visits up to Week 36 and their TWSTRS-total score never reached their target TWSTRS score and they never requested another treatment. The investigator determined that these subjects can be followed in the OLS until their TWSTRS-total score is the same or higher than their target TWSTRS score or until they request retreatment, which the investigator determined is clinically indicated

• De novo subjects (not previously enrolled in Study Protocol 1720302):

• Naïve to BoNT treatment

• BoNT treatment-experienced; if previously treated with BoNTA, the subject must have demonstrated a clinically meaningful response to the last BoNTA treatment based on the clinical judgment of the investigator

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 botulinum toxin (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 (applicable only to de novo subjects)

• Botulinum neurotoxin 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 (rimabotulinumtoxinA [Myobloc/Neurobloc]) injection for CD due to non-response or suboptimal response to BoNTA (applicable only to de novo subjects)

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.

Locations

Country	Name	City	State
Austria	Neurologisches Studienzentrum Universitätsklinik für Neurologie Innsbruck	Innsbruck
Canada	University Health Network, Toronto Western Hospital	Toronto	Ontario
Czechia	Fakultní nemocnice Ostrava	Ostrava-Poruba
Czechia	Nemocnice Pardubickeho kraje, a.s.; Pardubicka nemocnice	Pardubice
Czechia	Neurologicka klinika 1. LF UK a VFN v Praze	Praha
Czechia	Vestra Clinics s.r.o.	Rychnov nad Kneznou
France	Hôpital Neurologique Pierre Wertheimer	Bron
France	CHU de Grenoble	Grenoble cedex 9
France	Hôpital Roger Salengro	Lille Cedex
France	CHU Caremeau	Nîmes
Germany	Universitaetsklinikum Duesseldorf	Düsseldorf
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	Krakowska Akademia Neurologii Sp. z o.o.	Kraków
Poland	Marta Dagmara BANACH Marta Banach Specjalistyczny Gabinet Neurologiczny	Kraków
Poland	Wojewodzki Szpital Specjalistyczny w Olsztynie	Olsztyn
Poland	Centrum Medyczne Pratia Warszawa	Warsaw
Poland	Mazovian Brodno Hospital	Warsaw
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, Neuroscience Research Centre	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	The University of Vermont Medical Center	Burlington	Vermont
United States	Rush University Medical Center	Chicago	Illinois
United States	Intrafusion Research Network - Wesley Neurology Clinic	Cordova	Tennessee
United States	Texas Neurology. P.A.	Dallas	Texas
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	Loma Linda University	Loma Linda	California
United States	USC Keck School of Medicine	Los Angeles	California
United States	Veracity Neuroscience LLC	Memphis	Tennessee
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 Research	Overland Park	Kansas
United States	Care Access Research LLC	Pasadena	California
United States	University of Pennsylvania	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	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	Ki Health Partners LLC DBA New England Institute for Clinical Research	Stamford	Connecticut
United States	USF Parkinson's Disease and Movement Disorders Center	Tampa	Florida
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
Primary	Long Term Safety of patients determined by the incidence of treatment-emergent adverse events	Evaluation of adverse events and serious adverse events, from multiple continuous treatments of DAXI for injection, over the course of the study.	Up to 52 Weeks
Secondary	The proportion of subjects with at least moderate improvement on the Clinician Global Impression of Change (CGIC) at Weeks 4 or 6 for Treatment Cycles 1, 2, 3, and 4	The CGIC is an investigator-reported assessment of the global clinical change in CD since study treatment administration. The CGIC uses a 7-point Likert scale ranging from +3 (very much improved) to -3 (very much worse), and will be assessed by the investigator at the Week 4 and Week 6 visits.	Weeks 4 and 6 of treatment cycles 1, 2, 3, and 4 (12 - 52 weeks duration each)
Secondary	The average of the change from Baseline in the TWSTRS Total Score at Weeks 4 and 6 for Treatment Cycles 1, 2, 3, and 4 [Time Frame: Weeks 4 and 6 of treatment cycles 1, 2, 3, and 4 (12 - 52 weeks duration each)]	The difference in TWSTRS-Total score between the Baseline and average of Weeks 4 and 6 for each treatment cycle will be determined for each subject. The TWSTRS is an assessment scale used to measure the impact of CD on subjects. 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).	Weeks 4 and 6 of treatment cycles 1, 2, 3, and 4 (12 - 52 weeks duration each)