Randomized, Placebo-Controlled Study of AbobotulinumtoxinA (Dysport®) for the Treatment of Cervical Dystonia

A Phase III Multicentre, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Dysport® for the Treatment of Cervical Dystonia

The aim of this study is to demonstrate the effectiveness and safety of 500 units of Dysport manufactured at a new manufacturing facility in Europe.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 123367
    • Scientific Research Institute of Neurology, RAMS
  • Moscow, Russian Federation, 125047
    • Clinic "Cecil Plus"
  • St Petersburg, Russian Federation, 194354
    • Municipal Multi-Speciality Hospital #2
  • St Petersburg, Russian Federation, 197022
    • St Petersburg Pavlov State Medical University
• United States
  • Arizona
    • Phoenix, Arizona, United States
      • St. Joseph's Hospital and Medical Center
  • California
    • Fountain Valley, California, United States
      • Parkinson's and Movement Disorder Institute
    • Los Angeles, California, United States, 90033
      • Usc School Of Medicine
  • Florida
    • Gainesville, Florida, United States
      • University of Florida
    • Miami, Florida, United States
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States
      • Emory University
  • Illinois
    • Chicago, Illinois, United States
      • Rush University Medical Center
  • Iowa
    • Iowa City, Iowa, United States
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States
      • University of Maryland Medical Center
  • Michigan
    • Southfield, Michigan, United States
      • Wayne State University Medical Center
  • New York
    • Albany, New York, United States
      • Albany Medical Center
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States
      • Columbia University
  • North Carolina
    • Winston-Salem, North Carolina, United States
      • Wake Forest University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • Allegeheny General
  • Texas
    • Dallas, Texas, United States
      • University of Texas Southwest
    • Houston, Texas, United States
      • Baylor College of Medicine
  • Washington
    • Seattle, Washington, United States
      • Swedish Neuroscience

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cervical dystonia with at least 18 months since onset, and previously untreated with botulinum toxin or previously treated with botulinum toxin type A or B with a minimum interval of 16 weeks since the last injection and having returned at least to their usual pre-treatment status
• TWSTRS severity, disability and total scores meeting the defined criteria at baseline

Exclusion Criteria:

• Pure anterocollis or pure retrocollis
• In apparent remission from cervical dystonia
• Previous poor response to the last two botulinum toxin type A or type B treatments
• Being treated with type B toxin due to lack of efficacy to type A toxin or have known neutralizing antibodies to type A toxin

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
Placebo Comparator: 2; Placebo	Drug: Placebo; 500 units
Experimental: 1; Drug: abobotulinumtoxinA (Dysport®)	Biological: Botulinum toxin type A; 500 units; Other Names: AbobotulinumtoxinA (Dysport®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)	TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for each is the following: for severity from 0 (absence of severity) to 35 (max severity), for disability from 0 (no disability) to 30 (max disability) and for pain from 0 (no pain) to 20 (max pain). TWSTRS total score is the sum of the 3 component scores, with a range from 0 to a maximum of 85. The change in TWSTRS total score is the score at week 4 minus the score at baseline.	Baseline and Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)	TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for each is the following: for severity from 0 (absence of severity) to 35 (max severity), for disability from 0 (no disability) to 30 (max disability) and for pain from 0 (no pain) to 20 (max pain). TWSTRS total score is the sum of the 3 component scores, with a range from 0 to a maximum of 85. The change in TWSTRS total score is the score at week 4 minus the score at baseline.	Baseline and Week 8
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score	TWSTRS is comprised of three different components which are severity, disability & pain. There is an ordinal scale for each component and the score range for each is the following: for severity from 0 (absence of severity) to 35 (max severity), for disability from 0 (no disability) to 30 (max disability) and for pain from 0 (no pain) to 20 (max pain). TWSTRS total score is the sum of the 3 component scores, with a range from 0 to a maximum of 85. The change in TWSTRS total score is the score at week 4 minus the score at baseline.	Baseline and Week 12
Subject Visual Analogue Score (VAS) for Cervical Dystonia (CD) Symptom Assessment	The assessment was a continuous 100 mm horizonal line with a scale of 0 mm (no symptoms)to 100 mm (worst possible symptoms).	Baseline and Week 4
Investigator VAS for CD Symptom Assessment	The assessment was a continuous 100 mm horizonal line with a scale of 0 mm (no symptoms)to 100 mm (worst possible symptoms).	Baseline and Week 4
Subject VAS for CD Symptom Assessment	The assessment was a continuous 100 mm horizonal line with a scale of 0 mm (no symptoms)to 100mm (worst possible symptoms).	Baseline and Week 8
Investigator's VAS for CD Symptom Assessment	The assessment was a continuous 100 mm horizonal line with a scale of 0 mm (no symptoms)to 100 mm (worst possible symptoms).	Baseline and week 8
Subject VAS for CD Symptom Assessment	The assessment was a continuous 100 mm horizonal line with a scale of 0 mm (no symptoms)to 100 mm (worst possible symptoms).	Baseline and week 12
Investigator's VAS for CD Symptom Assessment	The assessment was a continuous 100 mm horizonal line with a scale of 0 mm (no symptoms) to 100 mm (worst possible symptoms).	Baseline and week 12
SF-36 Mental Health Summary Score	SF-36 is a Quality of Life scale comprising eight individual domains. The QoL score for each domain is on a scale from 0 (worst health possible) to 100 (best health possible). SF-36 Mental Health Summary Score is derived from four individual domains (vitality, social functioning, role limitations due to emotional problems and mental health).	Week 8
SF-36 Physical Health Summary Score	SF-36 is a Quality of Life scale comprising eight individual domains. The QoL score for each domain is on a scale from 0 (worst health possible) to 100 (best health possible). SF-36 Physical Health Summary Score is derived from four individual domains (physical functioning, role physical, bodily pain and general health).	Week 8
Number of Participants Considered by the Investigator to be Overall Treatment Successes	The number of participants considered to be overall treatment successes by the investigator at week 12 was assessed.	Week 12

Collaborators and Investigators

• Sponsor: Ipsen

Publications and helpful links

General Publications

• Truong D, Brodsky M, Lew M, Brashear A, Jankovic J, Molho E, Orlova O, Timerbaeva S; Global Dysport Cervical Dystonia Study Group. Long-term efficacy and safety of botulinum toxin type A (Dysport) in cervical dystonia. Parkinsonism Relat Disord. 2010 Jun;16(5):316-23. doi: 10.1016/j.parkreldis.2010.03.002. Epub 2010 Mar 31.
• Mordin M, Masaquel C, Abbott C, Copley-Merriman C. Factors affecting the health-related quality of life of patients with cervical dystonia and impact of treatment with abobotulinumtoxinA (Dysport): results from a randomised, double-blind, placebo-controlled study. BMJ Open. 2014 Oct 16;4(10):e005150. doi: 10.1136/bmjopen-2014-005150.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2005
• Primary Completion (Actual): September 1, 2006
• Study Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: November 22, 2005
• First Submitted That Met QC Criteria: November 22, 2005
• First Posted (Estimate): November 23, 2005

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

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: Y-47-52120-051; 2005-000709-70 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).