Dysport® Adult Upper Limb Spasticity

A Phase III, Multicentre, Prospective, Double Blind, Randomised, Placebo Controlled Study, Assessing the Efficacy and Safety of Dysport® Intramuscular Injections Used for the Treatment of Upper Limb Spasticity in Adult Subjects With Spastic Hemiparesis Due to Stroke or Traumatic Brain Injury

The purpose of this research study is to assess the efficacy of Dysport compared to placebo in improving muscle tone in hemiparetic subjects with upper limb spasticity due to stroke or traumatic brain injury.

Study Overview

• Status: Completed
• Conditions: Nervous System Disorders
• Intervention / Treatment: Biological: Botulinum toxin type A; Biological: Botulinum toxin type A; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Université catholique de Louvain av Hippocrate 10
  • Yvoir, Belgium
    • Clinique Universitaire
• Czechia
  • Olomouc, Czechia
    • Neurologicka klinika, Olomouc
  • Praha 2, Czechia
    • Charles University in Prague
• France
  • Besançon, France
    • CHU Jean Minjoz
  • Brest, France
    • Chu Brest
  • Coubert, France
    • Centre de Réadaptation de Coubert
  • Créteil, France
    • Centre Hospitalier Albert Chenevier-Hopital Henri Mondor
  • Garches, France
    • Hôpital Raymond Poincarre
  • Reims, France
    • Hôpital Sébastopol
  • Strasbourg, France
    • CHU Strasbourg
  • Toulouse, France
    • Hôpital Rangueil
• Hungary
  • Budapest, Hungary
    • National Institut for Medical Rehabilitation
  • Gyor, Hungary
    • Petz Aladar County Hospital
  • Szeged, Hungary
    • University of Szeged
• Italy
  • Catania, Italy
    • Azienda Hospedaliero
  • Roma, Italy
    • Policlinico Universitario Agostino Gemelli
• Poland
  • Krakow, Poland
    • Malopolskie Centrum Medyczne
  • Warszawa, Poland
    • Samodzielny Publiczny Centralny Szpital Kliniczny
  • Warszawa, Poland
    • Krakowska Akademia Neurologii
• Russian Federation
  • Moscow, Russian Federation
    • Medical rehabilitation center
  • Moscow, Russian Federation
    • Scientific Center of Neurology of RAMS
  • St Petersburg, Russian Federation
    • State University
• Slovakia
  • Bratislava, Slovakia
    • Univerzitna nemocnica Bratislava
  • Bratislava, Slovakia
    • Derer's Hospital
• United States
  • California
    • Downey, California, United States, 90242
      • Rancho Los Amigos National Rehabilitation Center
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologist of Southern CT, PT
  • Florida
    • Boca Raton, Florida, United States, 33488
      • Parkinson's Disease & Movement Disorders Center of Boca Raton
    • South Miami, Florida, United States, 33169
      • Design Neuroscience Miami
  • Illinois
    • Chicago, Illinois, United States, 60611
      • The Rehabilitation Institute of Chicago
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10029-6574
      • Mount Sinai School of Medicine
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Univ of North Carolina - Chapel Hill
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75390
      • Southwestern Medical Center at Dallas
    • Dallas, Texas, United States, 75080
      • University of Texas
    • Fort Worth, Texas, United States, 76104
      • University of North Texas HSC
    • Houston, Texas, United States, 77030
      • University of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients - post stroke or brain injury
• Modified Ashworth Scale ≥ 2
• Ambulatory patients

Exclusion Criteria:

• Previous treatment with botulinum toxin of any type within 4 months prior to study entry for any condition
• Physiotherapy initiated less than 4 weeks before inclusion
• Previous surgery, alcohol, phenol in upper limb
• Neurological/neuromuscular disorders which may interfere with protocol evaluations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; I.M. (in the muscle) injection on day 1 of a single treatment cycle.
EXPERIMENTAL: Dysport 500 U	Biological: Botulinum toxin type A; 500 U, I.M. (in the muscle) injection on day 1 of a single treatment cycle.; Other Names: AbobotulinumtoxinA (Dysport®); Biological: Botulinum toxin type A; 1000 U, I.M. (in the muscle) injection on day 1 of a single treatment cycle.; Other Names: AbobotulinumtoxinA (Dysport®)
EXPERIMENTAL: Dysport 1000 U	Biological: Botulinum toxin type A; 500 U, I.M. (in the muscle) injection on day 1 of a single treatment cycle.; Other Names: AbobotulinumtoxinA (Dysport®); Biological: Botulinum toxin type A; 1000 U, I.M. (in the muscle) injection on day 1 of a single treatment cycle.; Other Names: AbobotulinumtoxinA (Dysport®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in MAS Score in the Primary Targeted Muscle Group (PTMG)	MAS scale is used to assess muscle tone using a 6-point scale where: 0=No increase in muscle tone, 1=Slight increase in muscle tone manifested by a catch and release or by minimal resistance at the end of the range of motion (ROM) when the part is flexed or extended, 1±Slight increase in muscle tone manifested by a catch followed by minimal resistance throughout the remainder of the ROM, 2=Marked increase in muscle tone through most of the ROM but affected part easily moved, 3=Considerable increase in muscle tone passive movement difficult or 4=Affected part(s) rigid in flexion or extension. The MAS has been derived for analyses as follows: 0=0 ; 1=1; 1+=2; 2=3; 3=4 and 4=5.	From Baseline (Day 1) to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physician's Global Assessment (PGA) of Treatment Response	PGA is a 9-point scale used to assess global overall treatment response by the investigator (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved and +4: markedly improved).	At Week 4
Change From Baseline in DAS Score for the Principal Target of Treatment (PTT)	DAS is a 4-point scale used to determine the extent of functional impairment in 4 functional domains (dressing, hygiene, limb position and pain). DAS scale rating: 0=No disability, 1=Mild disability (noticeable but does not interfere significantly with normal activities), 2=Moderate disability (normal activities require increased effort and/or assistance) and 3=Severe disability (normal activities limited). If subject chose 'Hygiene' as PTT the score collected will be between 0 and 3.	From Baseline (Day 1) to Week 4

Collaborators and Investigators

• Sponsor: Ipsen

Publications and helpful links

General Publications

• Delafont B, Carroll K, Vilain C, Pham E. Investigation of mixed model repeated measures analyses and non-linear random coefficient models in the context of long-term efficacy data. Pharm Stat. 2018 Sep;17(5):515-526. doi: 10.1002/pst.1868. Epub 2018 May 20.
• O'Dell MW, Brashear A, Jech R, Lejeune T, Marque P, Bensmail D, Ayyoub Z, Simpson DM, Volteau M, Vilain C, Picaut P, Gracies JM. Dose-Dependent Effects of AbobotulinumtoxinA (Dysport) on Spasticity and Active Movements in Adults With Upper Limb Spasticity: Secondary Analysis of a Phase 3 Study. PM R. 2018 Jan;10(1):1-10. doi: 10.1016/j.pmrj.2017.06.008. Epub 2017 Jun 19.
• Marciniak C, McAllister P, Walker H, Brashear A, Edgley S, Deltombe T, Khatkova S, Banach M, Gul F, Vilain C, Picaut P, Grandoulier AS, Gracies JM; International AbobotulinumtoxinA Adult Upper Limb Spasticity Study Group. Efficacy and Safety of AbobotulinumtoxinA (Dysport) for the Treatment of Hemiparesis in Adults With Upper Limb Spasticity Previously Treated With Botulinum Toxin: Subanalysis From a Phase 3 Randomized Controlled Trial. PM R. 2017 Dec;9(12):1181-1190. doi: 10.1016/j.pmrj.2017.06.007. Epub 2017 Jun 16.
• Gracies JM, Brashear A, Jech R, McAllister P, Banach M, Valkovic P, Walker H, Marciniak C, Deltombe T, Skoromets A, Khatkova S, Edgley S, Gul F, Catus F, De Fer BB, Vilain C, Picaut P; International AbobotulinumtoxinA Adult Upper Limb Spasticity Study Group. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: a double-blind randomised controlled trial. Lancet Neurol. 2015 Oct;14(10):992-1001. doi: 10.1016/S1474-4422(15)00216-1. Epub 2015 Aug 26.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: March 10, 2011
• First Submitted That Met QC Criteria: March 10, 2011
• First Posted (ESTIMATE): March 11, 2011

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: Nervous System Diseases; 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-52-52120-145; 2010-019069-28 (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/).