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

NCT03608397 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 1720302
• Study Type: interventional
• Target: 301
• Locations: 9 countries
• Sites: 75

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).

Conditions

Cervical Dystonia

Keywords

DAXI; Cervical Dystonia; TWSTRS; Toxin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change from Baseline TWSTRS-total score

  Up to 36 Weeks

• Duration of effect

  Up to 36 Weeks

• Patient Global Impression of Change (PGIC) Improvement

  Week 4 or Week 6

• Incidence of treatment-emergent adverse events (Safety)

  Up to 36 Weeks

Other Outcomes (3)

• Change in TWSTRS subscale scores

  Up to 36 Weeks

• Clinical Global Impression of Change (CGIC)

  Up to 36 Weeks

• Patient Global Impression of Change (PGIC)

  Up to 36 Weeks

Study Arms (3)

DAXI for injection low dose

EXPERIMENTAL

Low Dose Group

Biological: DaxibotulinumtoxinA for injection

DAXI for injection high dose

EXPERIMENTAL

High Dose Group

Biological: DaxibotulinumtoxinA for injection

Placebo

PLACEBO COMPARATOR

Placebo Group

Biological: Placebo

Interventions

DaxibotulinumtoxinA for injection BIOLOGICAL

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.

DAXI for injection high dose; DAXI for injection low dose

Placebo BIOLOGICAL

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Revance Therapeutics, Inc.: lead
• Syneos Health: collaborator

Study Sites (75)

HOPE Research Institute

Phoenix, Arizona, 85018, United States

Location

Movement Disorders Center of Arizona

Scottsdale, Arizona, 85258-4581, United States

Location

The Parkinsons and Movement Disorder Institute

Fountain Valley, California, 92708, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

Loma Linda University

Loma Linda, California, 92354, United States

Location

USC Keck School of Medicine

Los Angeles, California, 90033, United States

Location

Care Access Research

Pasadena, California, 91101, United States

Location

Sutter Institute for Medical Research

Sacramento, California, 95816, United States

Location

Rocky Mountain Movement Disorders Center

Englewood, Colorado, 80113, United States

Location

Associated Neurologist, P.C.

Danbury, Connecticut, 06810, United States

Location

New England Institute for Clinical Research

Stamford, Connecticut, 06905, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Design Neuroscience Center

Doral, Florida, 33172, United States

Location

University of Florida Center for Movement Disorders and Neurorestoration

Gainesville, Florida, 32607, United States

Location

Infinity Clinical Research

Hollywood, Florida, 33024, United States

Location

University of Florida Health Science Center Jacksonville

Jacksonville, Florida, 32209, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Suncoast Neuroscience Associates

St. Petersburg, Florida, 33713-8844, United States

Location

USF Parkinson's Disease and Movement Disorders Center

Tampa, Florida, 33613, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Kansas Institute of Reseach

Overland Park, Kansas, 66211-1358, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

QUEST Research Institute

Farmington, Michigan, 48334, United States

Location

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, 48322, United States

Location

St Louis University

St Louis, Missouri, 63105, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Mount Sinai Movement Disorders Center

New York, New York, 10029, United States

Location

University of Rochester

Rochester, New York, 14618, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Wake Forest Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pennsylvania, Department of Neurology

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Coastal Neurology

Port Royal, South Carolina, 29935, United States

Location

Wesley Neurology Clinic

Cordova, Tennessee, 38018, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Neurology. P.A.

Dallas, Texas, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

Central Texas Neurology Consultants

Round Rock, Texas, 78681, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Medical University Innsbruck

Innsbruck, 6020, Austria

Location

Universitaetsklinik fuer Neurologie

Vienna, 1090, Austria

Location

University Health Network, Toronto Western Hospital

Toronto, Ontario, M5T2S8, Canada

Location

Fakultni nemocnice Olomouc, Neurologicka klinika

Olomouc, 779 00, Czechia

Location

Fakultní nemocnice Ostrava, Neurologicka klinika

Ostrava-Poruba, 70852, Czechia

Location

Lekarna Pardubicke nemocnice

Pardubice, 53203, Czechia

Location

Neurologicka klinika 1. LF UK a VFN v Praze

Prague, 12821, Czechia

Location

Vestra Clinics s.r.o.

Rychnov nad Kněžnou, 51601, Czechia

Location

Hôpital Neurologique Pierre Wertheimer

Bron, 69500, France

Location

CHU Grenoble Alpes

Grenoble, 38043, France

Location

Hôpital Roger Salengro - CHRU de Lille

Lille, 59037, France

Location

CHU Caremeau, Service de Neurologie

Nîmes, 30029, France

Location

Praxis fuer Neurologie im Bismark Karrée

Berlin, 10627, Germany

Location

Universitaetsklinikum Duesseldorf

Düsseldorf, 40225, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Klinikum rechts der Isar der TUM

München, 81675, Germany

Location

GFO Kliniken Troisdorf, Betriebsstätte St. Johannes Sieglar

Troisdorf, 53844, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Szpital sw. Wojciecha Podmiot Leczniczy Copernicus Sp. Z o.o.

Gdansk, 80462, Poland

Location

Marta Dagmara BANACH Marta Banach Specjalistyczny Gabinet Neurologiczny

Krakow, 30539, Poland

Location

Krakowska Akademia Neurologii

Krakow, 31505, Poland

Location

Wojewodzki Szpital Specjalistyczny w Olsztynie

Olsztyn, 10-561, Poland

Location

Centrum Medyczne Pratia Warszawa

Warsaw, 01868, Poland

Location

Mazowiecki Szpital Brodnowski Sp. z o.o.

Warsaw, 03-242, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario Burgos

Burgos, 09006, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Royal Devon and Exeter Foundation Trust Hospital

Exeter, EX25DW, United Kingdom

Location

The Walton Centre NHS Foundation Trust

Liverpool, L97LJ, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, M55AP, United Kingdom

Location

Related Publications (1)

• Comella CL, Jankovic J, Hauser RA, Patel AT, Banach MD, Ehler E, Vitarella D, Rubio RG, Gross TM; ASPEN-1 Study Group. Efficacy and Safety of DaxibotulinumtoxinA for Injection in Cervical Dystonia: ASPEN-1 Phase 3 Randomized Controlled Trial. Neurology. 2024 Feb 27;102(4):e208091. doi: 10.1212/WNL.0000000000208091. Epub 2024 Jan 31.

  PMID: 38295339 DERIVED

MeSH Terms

Conditions

Torticollis

Interventions

Botulinum Toxins, Type A; Injections

Condition Hierarchy (Ancestors)

Dystonia; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Approximately 300 subjects, recruited from study centers in the United States (US), Canada, and Europe will be randomized to DAXI high dose, DAXI low dose or placebo group.

Study Record Dates

• First Submitted: July 11, 2018
• First Posted: August 1, 2018
• Study Start: June 20, 2018
• Primary Completion: December 3, 2019
• Study Completion: June 16, 2020
• Last Updated: December 5, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); ES (4); FR (4); CZ (5); CA (1); AU (2); US (44); DE (6); PL (6)