Efficacy and Safety of DYSPORT® Using 2mL Dilution in Adults With Cervical Dystonia.

A Phase 3b, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of DYSPORT® Using 2mL Dilution in Adults With Cervical Dystonia.

The purpose of the protocol is to evaluate the efficacy and safety of Dysport® using 2 mL dilution compared with placebo for the treatment of Cervical Dystonia.

Study Overview

• Status: Completed
• Conditions: Cervical Dystonia
• Intervention / Treatment: Biological: Botulinum toxin type A; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Movement Disorders Center of Arizona, LLC
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Berkeley, California, United States, 94705
      • East Bay Physician's Group
    • Fountain Valley, California, United States, 92708
      • Parkinson's and Movement Disorder Institute
    • Loma Linda, California, United States, 92354
      • Loma Linda University Healthcare, Department of Neurology
    • Los Angeles, California, United States, 90033
      • USC Keck School of Medicine
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado at Denver Health Sciences
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurosciences Research
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologists of Southern Connecticut
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's & Movement Disorders Center of Boca Raton
    • Gainesville, Florida, United States, 32607
      • University of Florida Center for Movement Disorders and Neurorestoration
    • Pensacola, Florida, United States, 32514
      • Emerald Coast Center for Neurological Disorders
    • Port Charlotte, Florida, United States, 33980
      • PD Treatment Center of SW FL
    • Tampa, Florida, United States, 33606
      • University of South Florida
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute at Palm Beach Neurology
    • West Palm Beach, Florida, United States, 33407
      • Guilford Neurologic Associates
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research Inc.
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66211
      • Kansas City Bone & Joint Clinic
    • Overland Park, Kansas, United States, 66210
      • International Clinical Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Minnesota
    • Eagan, Minnesota, United States, 55122
      • Rehabilitation Consultants PA
  • New Jersey
    • Stratford, New Jersey, United States, 08084
      • University of Medicine and Dentistry of New Jersey
    • Summit, New Jersey, United States, 07901
      • Atlantic Neuroscience Institute
  • New York
    • Kingston, New York, United States, 12401
      • Kingston Neurological Associates
    • New York, New York, United States, 10029
      • The Ichan School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • Fazzini Parkinson's Disease & Dystonia Center
    • Plainview, New York, United States, 11803
      • Island Neurological Associates
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Guilford Neurologic Associates; Cone Health Medical Group
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Physicians Company, LLC
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Center for Health and Healing
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Neurology
  • South Carolina
    • Port Royal, South Carolina, United States, 29935
      • Coastal Neurology
  • Texas
    • Bedford, Texas, United States, 76201
      • North Texas Movement Disorders Institute
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Washington
    • Tacoma, Washington, United States, 98409
      • Puget Sound Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary diagnosis of Cervical Dystonia at least 9 months since onset and either previously untreated with botulinum toxin or currently treated with Botox at a total dosing range of 100-200 U and ≤60 U in the sternocleidomastoid muscle at the last injection cycle, and having had a satisfactory treatment response in the principal investigator's judgment during the last two sequential Botox treatment cycles.
• TWSTRS total score≥ 20; TWSTRS-severity subscale score> 10;

Exclusion Criteria:

• In apparent remission from Cervical Dystonia
• Diagnosis of pure retrocollis or pure anterocollis
• For non-naïve subjects, previous poor response to either of the last two Botox treatments
• Known requirement of <100U or >200U of Botox injected into the neck muscles

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dysport®; Dysport® (intramuscular injection), between 250 and 500 units (U)/vial using 2mL dilution, 1 cycle only	Biological: Botulinum toxin type A; Intramuscular injection, between 250 and 500 units (U)/vial using 2mL dilution, 1 cycle only; Other Names: AbobotulinumtoxinA (Dysport®)
Placebo Comparator: Placebo; Placebo, up to 2mL	Drug: Placebo; Up to 2mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score at Week 4.	The change from baseline in the TWSTRS total score at Week 4 was determined for the subjects who received a single dose of Dysport® or placebo by intramuscular injection at the baseline visit (Day 1), and is expressed as weighted overall treatment difference. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The score was assessed by the investigator prior to study treatment at baseline and at all post-treatment visits.	4 weeks post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in TWSTRS Total Score at Week 2.	The change from baseline in the TWSTRS total score at Week 2 was determined for the subjects who received a single dose of Dysport® or placebo by intramuscular injection at the baseline visit (Day 1), and is expressed as weighted overall treatment difference. The TWSTRS is an assessment scale used to measure the impact of CD on subjects, and comprises 3 subscales: severity, disability and pain, each of which is scored independently. The total score from the 3 subscales gives the TWSTRS total score with a value from 0 to 85 (best to worst). The score was assessed by the investigator prior to study treatment at baseline and at all post-treatment visits.	2 weeks post-treatment
Change From Baseline in Clinical Global Impression of Change (CGIC) in CD at Week 2.	The CGIC is an investigator-reported assessment of the global clinical change in CD since study treatment administration. The CGIC uses a seven-point Likert scale ranging from +3 (very much improved) to -3 (very much worse), and was assessed by the investigator at the Week 2 and Week 4 visits.	2 weeks post-treatment
TWSTRS Responders at Week 2.	Treatment response was determined as the number of responders at Week 2 relative to the baseline TWSTRS total score. A treatment responder is defined as a subject who had at least a 30% reduction in the TWSTRS total score after treatment. This was calculated as ([Week 2 score - baseline score]/baseline score) * 100.	2 weeks post-treatment
Change From Baseline in CGIC in CD at Week 4.	The CGIC is an investigator-reported assessment of the global clinical change in CD since study treatment administration. The CGIC uses a seven-point Likert scale ranging from +3 (very much improved) to -3 (very much worse), and was assessed by the investigator at the Week 2 and Week 4 visits.	4 weeks post-treatment
TWSTRS Responders at Week 4.	Treatment response was determined as the number of responders at Week 4 relative to the baseline TWSTRS total score. A treatment responder is defined as a subject who had at least a 30% reduction in the TWSTRS total score after treatment. This was calculated as ([Week 4 score - baseline score]/baseline score) * 100.	4 weeks post-treatment
Change From Baseline in Cervical Dystonia Impact Profile-58 (CDIP-58) Total Score at Week 4.	The CDIP-58 scale is a subject-based rating scale measuring the health impact of CD measured in 8 health dimensions including head and neck symptoms, pain and discomfort, upper limb activities, walking, sleep, annoyance, mood and psychosocial functioning. Subscale scores were transformed to a common theoretical range of 0 (no impact) to 100 (most impact). Negative changes from the baseline total score indicate improvement in the impact of CD on health whereas postive changes indicate worsening.	4 weeks post-treatment
Change From Baseline in CDIP-58 Total Score at Week 2.	The CDIP-58 scale is a subject-based rating scale measuring the health impact of CD measured in 8 health dimensions including head and neck symptoms, pain and discomfort, upper limb activities, walking, sleep, annoyance, mood and psychosocial functioning. Subscale scores were transformed to a common theoretical range of 0 (no impact) to 100 (most impact). Negative changes from the baseline total score indicate improvement in the impact of CD on health whereas postive changes indicate worsening. The hierarchical testing procedure would only be conducted if the previous secondary efficacy endpoint (change from baseline in CDIP-58 total score at Week 4) reached a statistically significant treatment effect. This secondary efficacy endpoint (change from baseline in CDIP-58 total score at Week 2) was performed to characterise the full clinical effect.	2 weeks post-treatment

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Medical Director, Neurology, M.D., Ipsen

Publications and helpful links

General Publications

• Patel AT, Lew MF, Dashtipour K, Isaacson S, Hauser RA, Ondo W, Maisonobe P, Wietek S, Rubin B, Brashear A. Sustained functional benefits after a single set of injections with abobotulinumtoxinA using a 2-mL injection volume in adults with cervical dystonia: 12-week results from a randomized, double-blind, placebo-controlled phase 3b study. PLoS One. 2021 Feb 1;16(2):e0245827. doi: 10.1371/journal.pone.0245827. eCollection 2021. Erratum In: PLoS One. 2021 Apr 14;16(4):e0250475.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: December 17, 2012
• First Submitted That Met QC Criteria: December 17, 2012
• First Posted (Estimate): December 20, 2012

Study Record Updates

• Last Update Posted (Actual): August 7, 2019
• Last Update Submitted That Met QC Criteria: July 25, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Dystonia; Dystonic Disorders; Torticollis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: A-TL-52120-169