Dysport® Adult Upper Limb Spasticity Extension Study

A Phase III, Multicentre, Prospective, Open Label Extension Study to Assess the Long Term Safety and Efficacy of Repeated Treatment 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 long term safety of Dysport® in hemiparetic subjects with upper limb spasticity due to stroke or traumatic brain injury over repeated treatment cycles.

Study Overview

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

Detailed Description

This was a phase III, multicentre, prospective, open label, repeat treatment cycles, extension to the double study Y-52-52120-145 (Study 145) . The study included both rollover subjects from Study 145 and de novo subjects. The primary study objective was to assess the long term safety of Dysport® in hemiparetic subjects with upper limb spasticity due to stroke or traumatic brain injury over repeated treatment cycles. The secondary study objective was to assess the long term efficacy of repeated treatment with Dysport®.

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Université catholique de Louvain av Hippocrate 10
  • Yvoir, Belgium
    • Clinique Universitaire
• Czechia
  • Praha 2, Czechia
    • Charles University in Prague
• France
  • 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
    • Hopital Rangueil
• Hungary
  • Budapest, Hungary
    • National Institute for Medical Rehabilitation
  • Budapest
    • Gyor, Budapest, Hungary
      • Petz Aladar County Hospital
• 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
    • 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, 33143
      • 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 University of Texas
    • Fort Worth, Texas, United States, 76104
      • University of North Texas HSC at Ben Hogan Center
  • 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:

• Completion of the double blind study, Y-52-52120-145

Exclusion Criteria:

• Major limitation in the passive range of motion in upper limb

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Total Dysport®; A total of 254 subjects in the open label study received between 1 and 5 intramuscular (i.m) injections of Dysport® according to their individual needs, for a period of up to 12 months. All subjects were administered an appropriate dosage of Dysport® (1000 Units [U] or 500 U) on Day 1 of treatment Cycle 1. At each study visit from Week 12 onwards, subjects were assessed to determine whether a subsequent treatment cycle was required and treatment cycles were administered at intervals of a minimum of 12 weeks apart depending on the subject's safety and efficacy response. From Cycle 2 onwards, a total dose of 1500 U could be administered in subjects requiring treatment with Dysport® in their shoulder and other upper limb muscles. Subjects who showed improvement in their upper limb during the first two treatment cycles were able to receive concomitant injections of Dysport® 500 U into at least one calf muscle, from Cycle 3 onwards as long as the total dose did not exceed 1500 U.

Biological: Botulinum toxin type A; Dysport® was supplied to the study centres in vials containing 500 U of botulinum toxin type A (BTX-A). Depending on the dose administered up to 3 vials were required for the injection. Each vial was reconstituted with sodium chloride for injection (0.9%). A total volume of 5.0 mL of the reconstituted product was injected for Dysport® 500 U and 1000 U, and 7.5 mL was injected for Dysport® 1500 U.; Other Names: AbobotulinumtoxinA (Dysport®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the Long-term Safety of Dysport® Through the Collection of Treatment Emergent Adverse Events (TEAEs)	A TEAE was reported as emergent if it arose (i.e. started or worsened in severity) in the treatment phase after the subject received study medication. Adverse events of special interest (AESIs) were identified as those assessed as being due to remote spread of effect of Dysport®, or any adverse event (AE) that was assessed as a hypersensitivity reaction. TEAEs, AESIs, severe TEAEs, serious adverse events (SAEs), treatment related TEAEs, TEAEs leading to withdrawal and fatal SAEs are summarised by treatment cycle.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in Diastolic and Systolic Blood Pressure (BP)	Systolic and diastolic BP were recorded at screening, baseline and at each post baseline visit. Vital signs were measured with the subject in a sitting position after resting for 3 minutes. Outcome measure is reported for number of subjects with data available for analysis.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in Heart Rate (HR)	HR was recorded at screening, baseline and at each post baseline visit. Vital signs were measured with the subject in a sitting position after resting for 3 minutes. Outcome measure is reported for number of subjects with data available for analysis.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in Red Blood Cell (RBC) Count	Blood samples for RBC count were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in Haemoglobin and Mean Corpuscular Haemoglobin Concentration (MCHC)	Blood samples for haemoglobin and MCHC were taken at baseline, at post treatment follow up visit Week 4, and at the end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in Haematocrit	Blood samples for haematocrit were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in Mean Corpuscular Haemoglobin (MCH)	Blood samples for MCH were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in Mean Corpuscular Volume (MCV)	Blood samples for MCV were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in White Blood Cell (WBC) Count, Neutrophils, Lymphocytes and Platelets	Blood samples for WBC count with differentials (neutrophils, lymphocytes) and platelet count were taken at baseline, at post treatment follow up visit Week 4, and at end of study or early withdrawal.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in 12-Lead Electrocardiogram (ECG)	12-lead ECG tracing was performed at baseline, post treatment at Week 4 and at the end of study/early withdrawal visit. The 12-lead ECG recordings were performed at a paper speed of 25 mm/s, recorded with the subject in a supine position after 5 minutes rest. The ECG parameters reported were QRS duration, PR duration, QT duration, QTcB (QT interval corrected for HR according to Bazett), and QTcF (QT interval corrected for HR according to Fridericia) at baseline and the change to end of study/early withdrawal visit (EOS).	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT)	Blood samples for analysis of the following clinical chemistry parameters: ALP, GGT, SGOT and SGPT were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in Total Bilirubin and Creatinine	Blood samples for clinical chemistry analysis of total bilirubin and creatinine were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal. Outcome measure is reported for number of subjects with data available for analysis.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in Blood Urea Nitrogen (BUN) and Fasting Blood Glucose	Blood samples for analysis of BUN and fasting blood glucose levels were taken at baseline, at post treatment follow up visit Week 4, and at end of study/early withdrawal.	Up to Week 52
Mean Change From Baseline to End of Study/Early Withdrawal in 12 Lead ECG - HR	HR was measured by 12-lead ECG tracing, performed at baseline, at post treatment follow up visit Week 4, and at the end of study or early withdrawal visit. The 12-lead ECG recordings were performed at a paper speed of 25 mm/s, recorded with the subject in a supine position after 5 minutes rest.	Up to Week 52
Number of Subjects With Botulinum Toxin A Binding and Neutralising Putative Antibodies	Blood samples were collected at baseline, Week 4 of each cycle, and at the end of study/early withdrawal to test for the presence of Botulinum Toxin A Binding antibodies. Samples positive for the presence of binding antibodies were then analysed for the presence of neutralising putative antibodies. The number of subjects who were either positive (+ve) or negative (-ve) at baseline and then positive post baseline for binding or neutralising antibodies were reported.	Up to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline Modified Ashworth Scale (MAS) in the Overall Primary Targeted Muscle Group (PTMG) for Upper Limb at Week 4	The clinical assessment of muscle tone was performed using the MAS. The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The mean changes from baseline to Week 4 in MAS in the overall PTMG (finger, wrist or elbow flexors) are reported.	At Week 4
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Overall PTMG	The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The percentage of subjects with at least a 1 grade reduction and at least a 2 grades reduction from baseline in mean MAS in the overall PTMG at Week 4 are reported.	At Week 4
Mean Change From Baseline MAS in the Extrinsic Finger Flexors at Week 4	The clinical assessment of muscle tone was performed using the MAS. The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The mean changes from baseline to Week 4 in MAS in the extrinsic finger flexors are reported.	At Week 4
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Extrinsic Finger Flexors at Week 4	The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The percentage of subjects with at least a 1 grade reduction and at least a 2 grades reduction from baseline in mean MAS in the extrinsic finger flexors at Week 4 are reported.	At Week 4
Mean Change From Baseline MAS in the Wrist Flexors at Week 4	The clinical assessment of muscle tone was performed using the MAS. The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The mean changes from baseline to Week 4 in MAS in the wrist flexors are reported.	At Week 4
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Wrist Flexors at Week 4	The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The percentage of subjects with at least a 1 grade reduction and at least a 2 grades reduction in mean MAS in the wrist flexors at Week 4 are reported.	At Week 4
Mean Change From Baseline MAS in the Elbow Flexors at Week 4	The clinical assessment of muscle tone was performed using the MAS. The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The mean changes from baseline to Week 4 in MAS in the elbow flexors are reported.	At Week 4
Percentage of Subjects With at Least 1 or 2 Grade Reduction in MAS for Elbow Flexors at Week 4	The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The percentage of subjects at least a 1 grade reduction and at least a 2 grades reduction from baseline in mean MAS in the elbow flexors at Week 4 are reported.	At Week 4
Mean Change From Baseline MAS in the Shoulder Extensors at Week 4	The clinical assessment of muscle tone was performed using the MAS. The MAS consists of 6 grades: 0, 1, 1+, 2, 3, or 4 that can be applied to muscles of both the upper and lower limbs. The MAS was applied by the rater by stretching the joint through its full available range over 1 second. The mean changes from baseline to Week 4 in MAS in the shoulder extensors are reported.	At Week 4
Physician's Global Assessment (PGA) of Treatment Response at Week 4	The PGA is a 9-point rating scale: -4=markedly worse, -3=much worse, -2=worse, -1=slightly worse, 0=no change, +1=slightly improved, +2=improved, +3=much improved, +4=markedly improved. An assessment of overall treatment response was conducted by the investigator and the mean PGA scores during long-term open label treatment with Dysport were reported.	At Week 4
Mean Change From Baseline in Disability Assessment Scale (DAS) Score for the Principal Target of Treatment (PTT) at Week 4	At baseline the subject and investigator together selected one of the four DAS domains as the PTT. The selected domain was required to have a rating of moderate or severe (≥2) at baseline. The DAS is a 4-point scale, the extent of functional impairment in 4 functional domains (dressing, hygiene, limb position and pain) was rated as follows: 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). The mean changes in DAS at Week 4 are reported.	At Week 4
Percentage of Subjects With at Least 1 Grade Reduction in DAS for PTT at Week 4	At baseline the subject and investigator together selected one of the four DAS domains as the PTT. The selected domain was required to have a rating of moderate or severe (≥2) at baseline. The DAS is a 4-point scale, the extent of functional impairment in 4 functional domains (dressing, hygiene, limb position and pain) was rated as follows: 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). The percentage of subjects with at least 1 grade reduction from baseline in DAS for PTT at Week 4 are reported.	At Week 4
Percentage of Subjects With at Least One Grade Reduction in DAS for Individual Domains at Week 4	The DAS is a 4-point scale. The extent of functional impairment in 4 functional domains (dressing, hygiene, limb position and pain) was rated as follows: 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). The percentage of subjects with at least one grade reduction in DAS for each of the individual domains at Week 4 is reported.	At Week 4
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Extrinsic Finger Flexors as PTMG	The Tardieu Scale (TS) was used to measure spasticity in extrinsic finger flexors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.	At Week 4
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Extrinsic Finger Flexors as PTMG	The TS was used to measure spasticity in extrinsic finger flexors. The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.	At Week 4
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Elbow Flexors as PTMG	The TS was used to measure spasticity in elbow flexors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.	At Week 4
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Elbow Flexors as PTMG	The TS was used to measure spasticity in elbow flexors.The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.	At Week 4
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Wrist Flexors as PTMG	The TS was used to measure spasticity in wrist flexors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.	At Week 4
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Wrist Flexors as PTMG	The TS was used to measure spasticity in wrist flexors. The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.	At Week 4
Mean Change From Baseline to Week 4 for Angle of Arrest (XV1), Angle of Catch (XV3) and Angle of Spasticity (X) in Shoulder Extensors	The TS was used to measure spasticity in shoulder extensors. The TS is administered by applying passive stretch to a muscle group at two velocities. Slow speed of muscle stretch measures the range of passive motion. During a slow stretching movement, the examiner determines the angle of movement arrest, either due to subject discomfort or a mechanical resistance. The same movement is repeated at high velocity (as fast as possible) to determine the angle of catch and release. The angle of movement arrest at slow velocity (XV1) and the angle of catch at fast speed (XV3) were recorded. The spasticity angle (X) was calculated as the difference between XV1 and XV3. Mean changes in Angles XV1, XV3 and X from baseline to Week 4 are reported.	At Week 4
Mean Change From Baseline to Week 4 for Spasticity Grade (Y) in Shoulder Extensors	The TS was used to measure spasticity in shoulder extensors. The TS is administered by applying passive stretch to a muscle group. The spasticity grade (Y) assesses quality of muscle reaction on a 5-point scale (measured at fast speed): 0 =No resistance throughout passive movement, 1=slight resistance throughout passive movement, 2=clear catch at precise angle, interrupting passive movement, followed by release, 3=fatigable clonus (less than 10 seconds when maintaining pressure) occurring at a precise angle, followed by release. 4=unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at precise angle. Mean changes in spasticity grade (Y) from baseline to Week 4 are reported.	At Week 4
Mean Change From Baseline in Active Range of Motion (AROM) at Week 4 in the 3 Possible PTMGs	The AROM was assessed by the range of extension achieved by the subject moving each joint in the PTMGs (extrinsic finger flexors, elbow flexors and wrist flexors) without assistance. A goniometer was used for measurements in the elbow and wrist flexors but not for measurements in the extrinsic finger flexors. Mean changes in AROM in the 3 possible PTMGs from baseline to Week 4 are reported.	At Week 4
Mean Change From Baseline at Week 4 in Ease of Applying a Splint	The ease of applying a splint was evaluated on a 6-point scale (0= no splint needed, -1= splint needed and applied with no difficulty, -2= splint needed and applied with mild difficulty, -3= splint needed and applied with moderate difficulty, -4= splint needed and applied with severe difficulty, -5= splint needed,but unable to apply). Mean change in ease of applying a splint from baseline to Week 4 was reported.	At Week 4
Mean Change From Baseline in Modified Frenchay Scale (MFS) at Week 4	The MFS was used to measure upper limb active function. Each subject was video taped while performing specific tasks. The videos were sent to a central provider and were read and scored by two independent readers blinded to the timing of the video and to treatment. These central assessments were used for the analysis of efficacy endpoints. The MFS consists of 10 tasks asking the subject to reach, grasp, carry and release different objects of different sizes which subjects are likely to use in their daily life. Each of these tasks was rated on a 10 point scale ranging from no movement to normal movement; for each task, the score 5 is used to rate a task barely accomplished. Mean change in MFS from baseline to Week 4 was reported.	At Week 4
Mean Change From Baseline in Short Form (36) Health Survey (SF-36) Quality of Life (QoL) at End of Study/Early Withdrawal Visit	Subjects were asked to complete the SF-36 questionnaires prior to the study treatment at baseline and at the end of study/early withdrawal visit. The SF-36 is a generic non-preference based health status measure. This instrument assessed subject health across 8 variable dimensions, which are specific health domains such as physical functioning, social functioning and vitality. Each variable item score is coded and turned into a 0-100 scale where 0 indicates the worst and 100 indicates the best possible health state for both the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the questionnaire. Baseline results and the change from baseline to end of study/early withdrawal for the PCS and MCS are reported.	Up to Week 52
Mean Change From Baseline in European 5 Dimensions, 5 Level (EQ-5D-5L) QoL at End of Study/Early Withdrawal Visit	Subjects were asked to complete the EQ-5D-5L QoL questionnaires prior to the study treatment at baseline and at the end of study/early withdrawal visit. The EQ-5D-5L index is a generic preference based measure of health related QoL producing utility scores that represent subject preferences for particular health states. This instrument rated subject health state looking at 5 specific dimensions such as mobility, self-care, usual activity, pain/discomfort and anxiety/depression and scored their general health state. Each dimension has 5 levels of severity (no problems, slight problems,moderate problems, severe problems and extreme problems). In addition, a visual analogue scale (VAS) ranging from 0 to 100 was also included for the patients to summarize their overall health status, where 0 is the worst and 100 the best possible health state. The mean values for each dimension and the VAS scores at baseline and at the end of-study /early withdrawal are reported.	Up to Week 52

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.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

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-52-52120-148; 2010-019162-83 (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/).