Clinical trial NCT03617367: Long-Term Safety and Efficacy of Repeat Treatments of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia (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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Dystonia
Keywords: DAXI
Cervical Dystonia
TWSTRS
Toxin
multiple treatment
Lead sponsor: Revance Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2018-08-06
Enrollment: 357
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a 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 with up to four different doses in adults with isolated cervical dystonia (CD).
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Long Term Safety of patients determined by the incidence of treatment-emergent adverse events
timeFrame: Up to 52 Weeks
Secondary outcomes:
measure: 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
timeFrame: Weeks 4 and 6 of treatment cycles 1, 2, 3, and 4 (12 - 52 weeks duration each)
measure: 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)]
timeFrame: Weeks 4 and 6 of treatment cycles 1, 2, 3, and 4 (12 - 52 weeks duration each)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Scottsdale
country: United States
facility: Movement Disorders Center of Arizona
state: Arizona
city: Fountain Valley
country: United States
facility: The Parkinsons and Movement Disorder Institute
state: California
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Los Angeles
country: United States
facility: USC Keck School of Medicine
state: California
city: Pasadena
country: United States
facility: Care Access Research LLC
state: California
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center
state: Colorado
city: Stamford
country: United States
facility: Ki Health Partners LLC DBA New England Institute for Clinical Research
state: Connecticut
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Gainesville
country: United States
facility: University of Florida Center for Movement Disorders and Neurorestoration
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical research
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Saint Petersburg
country: United States
facility: Suncoast Neuroscience Associates
state: Florida
city: Tampa
country: United States
facility: USF Parkinson's Disease and Movement Disorders Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Overland Park
country: United States
facility: Kansas Institute of Research
state: Kansas
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Farmington
country: United States
facility: QUEST Research Institute
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford West Bloomfield Hospital
state: Michigan
city: Saint Louis
country: United States
facility: St Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Mount Sinai Movement Disorders Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Health Sciences
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Port Royal
country: United States
facility: Coastal Neurology
state: South Carolina
city: Cordova
country: United States
facility: Intrafusion Research Network - Wesley Neurology Clinic
state: Tennessee
city: Memphis
country: United States
facility: Veracity Neuroscience LLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Neurology. P.A.
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
city: Innsbruck
country: Austria
facility: Neurologisches Studienzentrum Universitätsklinik für Neurologie Innsbruck
city: Toronto
country: Canada
facility: University Health Network, Toronto Western Hospital
state: Ontario
city: Ostrava-Poruba
country: Czechia
facility: Fakultní nemocnice Ostrava
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s.; Pardubicka nemocnice
city: Praha
country: Czechia
facility: Neurologicka klinika 1. LF UK a VFN v Praze
city: Rychnov nad Kneznou
country: Czechia
facility: Vestra Clinics s.r.o.
city: Bron
country: France
facility: Hôpital Neurologique Pierre Wertheimer
city: Grenoble cedex 9
country: France
facility: CHU de Grenoble
city: Lille Cedex
country: France
facility: Hôpital Roger Salengro
city: Nîmes
country: France
facility: CHU Caremeau
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TUM
city: Troisdorf
country: Germany
facility: GFO Kliniken Troisdorf, Betriebsstätte St. Johannes Sieglar
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Gdansk
country: Poland
facility: Szpital sw. Wojciecha Podmiot Leczniczy Copernicus Sp. Z o.o.
city: Kraków
country: Poland
facility: Marta Dagmara BANACH Marta Banach Specjalistyczny Gabinet Neurologiczny
city: Kraków
country: Poland
facility: Krakowska Akademia Neurologii Sp. z o.o.
city: Olsztyn
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Olsztynie
city: Warsaw
country: Poland
facility: Centrum Medyczne Pratia Warszawa
city: Warsaw
country: Poland
facility: Mazovian Brodno Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Burgos
country: Spain
facility: Hospital Universitario Burgos
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Foundation Trust Hospital
city: Liverpool
country: United Kingdom
facility: The Walton Centre NHS Foundation Trust, Neuroscience Research Centre
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
Study officials:
References: