Long-Term Safety and Efficacy of Repeat Treatments of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia (ASPEN-OLS)
- Conditions
- Cervical Dystonia
- Interventions
- Biological: daxibotulinumtoxinA for injection
- Registration Number
- NCT03617367
- Lead Sponsor
- Revance Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 357
-
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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description daxibotulinumtoxinA (DAXI) for injection daxibotulinumtoxinA for injection DAXI for injection
- Primary Outcome Measures
Name Time Method Long Term Safety of patients determined by the incidence of treatment-emergent adverse events Up to 52 Weeks Evaluation of adverse events and serious adverse events, from multiple continuous treatments of DAXI for injection, over the course of the study.
- Secondary Outcome Measures
Name Time Method 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 Weeks 4 and 6 of treatment cycles 1, 2, 3, and 4 (12 - 52 weeks duration each) 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.
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)] 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).
Trial Locations
- Locations (65)
The University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
QUEST Research Institute
🇺🇸Farmington, Michigan, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Mount Sinai Movement Disorders Center
🇺🇸New York, New York, United States
Ki Health Partners LLC DBA New England Institute for Clinical Research
🇺🇸Stamford, Connecticut, United States
Parkinson's Disease and Movement Disorders Center of Boca Raton
🇺🇸Boca Raton, Florida, United States
Movement Disorders Center of Arizona
🇺🇸Scottsdale, Arizona, United States
Michigan State University
🇺🇸East Lansing, Michigan, United States
Neurologisches Studienzentrum Universitätsklinik für Neurologie Innsbruck
🇦🇹Innsbruck, Austria
The Parkinsons and Movement Disorder Institute
🇺🇸Fountain Valley, California, United States
Hôpital Neurologique Pierre Wertheimer
🇫🇷Bron, France
Infinity Clinical research
🇺🇸Hollywood, Florida, United States
Intrafusion Research Network - Wesley Neurology Clinic
🇺🇸Cordova, Tennessee, United States
Nemocnice Pardubickeho kraje, a.s.; Pardubicka nemocnice
🇨🇿Pardubice, Czechia
Hospital Universitario Burgos
🇪🇸Burgos, Spain
Veracity Neuroscience LLC
🇺🇸Memphis, Tennessee, United States
Marta Dagmara BANACH Marta Banach Specjalistyczny Gabinet Neurologiczny
🇵🇱Kraków, Poland
Suncoast Neuroscience Associates
🇺🇸Saint Petersburg, Florida, United States
Loma Linda University
🇺🇸Loma Linda, California, United States
St Louis University
🇺🇸Saint Louis, Missouri, United States
Universitaetsklinikum Duesseldorf
🇩🇪Düsseldorf, Germany
Rocky Mountain Movement Disorders Center
🇺🇸Englewood, Colorado, United States
Coastal Neurology
🇺🇸Port Royal, South Carolina, United States
Szpital sw. Wojciecha Podmiot Leczniczy Copernicus Sp. Z o.o.
🇵🇱Gdansk, Poland
Centrum Medyczne Pratia Warszawa
🇵🇱Warsaw, Poland
GFO Kliniken Troisdorf, Betriebsstätte St. Johannes Sieglar
🇩🇪Troisdorf, Germany
Central Texas Neurology Consultants
🇺🇸Round Rock, Texas, United States
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Fakultní nemocnice Ostrava
🇨🇿Ostrava-Poruba, Czechia
CHU de Grenoble
🇫🇷Grenoble cedex 9, France
Texas Neurology. P.A.
🇺🇸Dallas, Texas, United States
Klinikum rechts der Isar der TUM
🇩🇪Muenchen, Germany
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Neurologicka klinika 1. LF UK a VFN v Praze
🇨🇿Praha, Czechia
Vestra Clinics s.r.o.
🇨🇿Rychnov nad Kneznou, Czechia
University Health Network, Toronto Western Hospital
🇨🇦Toronto, Ontario, Canada
Krakowska Akademia Neurologii Sp. z o.o.
🇵🇱Kraków, Poland
Wojewodzki Szpital Specjalistyczny w Olsztynie
🇵🇱Olsztyn, Poland
Mazovian Brodno Hospital
🇵🇱Warsaw, Poland
Hôpital Roger Salengro
🇫🇷Lille Cedex, France
CHU Caremeau
🇫🇷Nîmes, France
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Hospital Universitario de La Princesa
🇪🇸Madrid, Spain
University of Miami
🇺🇸Miami, Florida, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Houston Methodist Neurological Institute
🇺🇸Houston, Texas, United States
Kansas Institute of Research
🇺🇸Overland Park, Kansas, United States
Care Access Research LLC
🇺🇸Pasadena, California, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Henry Ford West Bloomfield Hospital
🇺🇸West Bloomfield, Michigan, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
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 Kingdom
University of Rochester
🇺🇸Rochester, New York, United States
HOPE Research Institute
🇺🇸Phoenix, Arizona, United States
USF Parkinson's Disease and Movement Disorders Center
🇺🇸Tampa, Florida, United States
Duke University
🇺🇸Durham, North Carolina, United States
Wake Forest Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
USC Keck School of Medicine
🇺🇸Los Angeles, California, United States
University of Florida Center for Movement Disorders and Neurorestoration
🇺🇸Gainesville, Florida, United States