Back to resultsEfficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children (PUL)
Primary Purpose
Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Botulinum toxin type A
Sponsored by
About this trial
This is an interventional treatment trial for Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children
Eligibility Criteria
Inclusion Criteria:
- Upper limb spasticity due to cerebral palsy
- Body weight 10 kg or over
- MAS score of 2 or more in affected elbow or wrist flexors
Exclusion Criteria:
- Fixed myocontracture
- Previous phenol or alcohol injection within 1 year
- Severe athetoid or dystonic movements
- Previous or planned surgery for spasticity in elbow or wrist flexors
- Neuromuscular disorders
- Previous Rhizotomy within 6 months
- Intrathecal baclofen within 30 days
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Group A
Group B
Group C
Arm Description
Group A - Treatments 1, 2, 3 and 4: Dysport 16 Units (U)/kg in one upper extremity (the study limb).
Group B - Treatments 1, 2, 3 and 4: Dysport 8 U/kg in one upper extremity (the study limb).
Group C - Treatment 1: Dysport 2 U/kg in one upper extremity (the study limb). Group C - Treatments 2, 3 and 4: Dysport 8 or 16 U/kg in one upper extremity (the study limb).
Outcomes
Primary Outcome Measures
Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG
The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 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 ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone.
Secondary Outcome Measures
Mean Physician's Global Assessment (PGA) Score at TC 1, Week 6
The PGA of treatment response was assessed by asking the investigator the following question: 'How would you rate the response to treatment in the subject's upper limb since the start of the study?'. Answers were on 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 and +4: markedly improved). The mean scores for each treatment group at TC 1, Week 6 are presented.
Mean Goal Attainment Scale (GAS) Total Score at TC 1, Week 6
The GAS is a functional 5-point scale used to measure progress towards individual therapy goals. At start of each TC, 1 to 3 individual goals were defined for each subject by investigator and child's parents/guardians/caregivers prior to treatment. Outcome to reach each goal was rated on a 5-point scale ranging from -2 to +2 (-2: much less than expected outcome, -1: somewhat less than expected outcome, 0: expected outcome, +1: somewhat more than expected outcome, +2: much more than expected outcome). Higher score indicates a better outcome. A GAS T-score was calculated as: 50+(10∑_(i=1)^n wi xi)/√(0.7∑_(i=1)^n wi^2 +0.3(∑_(i=1)^n wi)^2) where, xi = rating of ith goal post-baseline; wi = weight of ith goal, calculated as importance * difficulty as defined at baseline; n = number of goals assessed at baseline and post-baseline. A GAS T-score of 50 indicates goals achieved as expected. Scores below 50 reflect under attainment of goals and scores above 50 reflect over attainment of goals.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02106351
Brief Title
Efficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children
Acronym
PUL
Official Title
A Phase III, Multicentre, Double Blind, Prospective, Randomised, Controlled, Multiple Treatment Study Assessing Efficacy And Safety Of DYSPORT® Used In The Treatment Of Upper Limb Spasticity In Children
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
April 2014 (Actual)
Primary Completion Date
September 21, 2017 (Actual)
Study Completion Date
September 4, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ipsen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the efficacy and safety of multiple doses of Dysport used in the treatment of upper limb spasticity (altered skeletal muscle performance) in children with cerebral palsy (CP).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
212 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Description
Group A - Treatments 1, 2, 3 and 4: Dysport 16 Units (U)/kg in one upper extremity (the study limb).
Arm Title
Group B
Arm Type
Experimental
Arm Description
Group B - Treatments 1, 2, 3 and 4: Dysport 8 U/kg in one upper extremity (the study limb).
Arm Title
Group C
Arm Type
Experimental
Arm Description
Group C - Treatment 1: Dysport 2 U/kg in one upper extremity (the study limb).
Group C - Treatments 2, 3 and 4: Dysport 8 or 16 U/kg in one upper extremity (the study limb).
Intervention Type
Biological
Intervention Name(s)
Botulinum toxin type A
Other Intervention Name(s)
AbobotulinumtoxinA (Dysport®)
Intervention Description
Subjects randomised to receive Dysport 2 U/kg, 8 U/kg or 16 U/kg administered intramuscularly in the study limb.
Primary Outcome Measure Information:
Title
Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG
Description
The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 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 ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone.
Time Frame
Baseline (TC 1, Day 1) and TC 1, Week 6.
Secondary Outcome Measure Information:
Title
Mean Physician's Global Assessment (PGA) Score at TC 1, Week 6
Description
The PGA of treatment response was assessed by asking the investigator the following question: 'How would you rate the response to treatment in the subject's upper limb since the start of the study?'. Answers were on 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 and +4: markedly improved). The mean scores for each treatment group at TC 1, Week 6 are presented.
Time Frame
TC 1, Week 6.
Title
Mean Goal Attainment Scale (GAS) Total Score at TC 1, Week 6
Description
The GAS is a functional 5-point scale used to measure progress towards individual therapy goals. At start of each TC, 1 to 3 individual goals were defined for each subject by investigator and child's parents/guardians/caregivers prior to treatment. Outcome to reach each goal was rated on a 5-point scale ranging from -2 to +2 (-2: much less than expected outcome, -1: somewhat less than expected outcome, 0: expected outcome, +1: somewhat more than expected outcome, +2: much more than expected outcome). Higher score indicates a better outcome. A GAS T-score was calculated as: 50+(10∑_(i=1)^n wi xi)/√(0.7∑_(i=1)^n wi^2 +0.3(∑_(i=1)^n wi)^2) where, xi = rating of ith goal post-baseline; wi = weight of ith goal, calculated as importance * difficulty as defined at baseline; n = number of goals assessed at baseline and post-baseline. A GAS T-score of 50 indicates goals achieved as expected. Scores below 50 reflect under attainment of goals and scores above 50 reflect over attainment of goals.
Time Frame
TC 1, Week 6.
Other Pre-specified Outcome Measures:
Title
Mean Change From Baseline to TC 1 Week 16 in MAS Score in the TC 1 PTMG
Description
The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 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 ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone.
Time Frame
Baseline (TC 1, Day 1) and TC 1, Week 16.
Title
Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Elbow Flexors of the Study Limb
Description
The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 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 ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone. Data is presented for subjects injected in the elbow flexors.
Time Frame
Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.
Title
Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Wrist Flexors of the Study Limb
Description
The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 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 ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone. Data is presented for subjects injected in the wrist flexors.
Time Frame
Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.
Title
Mean Change From Baseline to TC 1 Weeks 6 and 16 in MAS Score in the Finger Flexors of the Study Limb
Description
The MAS was used to assess muscle tone in the upper limb PTMG and consists of 6 grades: 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 ROM) when the affected part is moved in flexion or extension, 1+ (slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM), 2 (more marked increase in muscle tone), 3 (considerable increase in muscle tone) or 4 (affected part(s) rigid in flexion or extension). The original score '+1' was given a derived numeric score of '2' and the higher numeric scores were incremented by 1 so that the MAS score range was from 0 to 5 with higher scores indicating greater muscle tone. A negative change from baseline indicates a decrease in muscle tone. Data is presented for subjects injected in the finger flexors.
Time Frame
Baseline (TC 1, Day 1) and TC 1, Weeks 6 and 16.
Title
Mean PGA Score at TC 1 Week 16
Description
The PGA of treatment response was assessed by asking the investigator the following question: 'How would you rate the response to treatment in the subject's upper limb since the start of the study?'. Answers were on 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 and +4: markedly improved). The mean scores for each treatment group at TC 1 Week 16 are presented.
Time Frame
Baseline (TC 1, Day 1) and TC 1, Week 16.
Title
Mean GAS Total Score at TC 1, Week 16
Description
The GAS is a functional 5-point scale used to measure progress towards individual therapy goals. At start of each TC, 1 to 3 individual goals were defined for each subject by investigator and child's parents/guardians/caregivers prior to treatment. Outcome to reach each goal was rated on a 5-point scale ranging from -2 to +2 (-2: much less than expected outcome, -1: somewhat less than expected outcome, 0: expected outcome, +1: somewhat more than expected outcome, +2: much more than expected outcome). Higher score indicates a better outcome. A GAS T-score was calculated as: 50+(10∑_(i=1)^n wi xi)/√(0.7∑_(i=1)^n wi^2 +0.3(∑_(i=1)^n wi)^2) where, xi = rating of ith goal post-baseline; wi = weight of ith goal, calculated as importance * difficulty as defined at baseline; n = number of goals assessed at baseline and post-baseline. A GAS T-score of 50 indicates goals achieved as expected. Scores below 50 reflect under attainment of goals and scores above 50 reflect over attainment of goals.
Time Frame
Baseline (TC 1, Day 1) and TC 1, Week 16.
Title
Mean Change From Baseline to TC 1, Week 16 in the Paediatric Quality of Life (PedsQL) Scores
Description
Parents/guardians completed questionnaires on their child's quality of life. The PedsQL parent inventory measured healthcare concepts for children/adolescents aged 2-18 years. The Generic Core Scales include physical, emotional, social and school aspects. The CP module was also completed. Scores were transformed on a scale from 0 to 100 with higher scores indicating a better quality of life. Mean changes from baseline to TC 1, Week 16 are presented for the General Core Scale and for the CP module. A positive change from baseline indicates an improvement in quality of life.
Time Frame
Baseline (TC 1, Day 1) and TC 1, Week 16.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Upper limb spasticity due to cerebral palsy
Body weight 10 kg or over
MAS score of 2 or more in affected elbow or wrist flexors
Exclusion Criteria:
Fixed myocontracture
Previous phenol or alcohol injection within 1 year
Severe athetoid or dystonic movements
Previous or planned surgery for spasticity in elbow or wrist flexors
Neuromuscular disorders
Previous Rhizotomy within 6 months
Intrathecal baclofen within 30 days
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ipsen Medical Director
Organizational Affiliation
Ipsen
Official's Role
Study Director
Facility Information:
City
Aurora
State/Province
Colorado
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
New Orleans
State/Province
Louisiana
Country
United States
City
Royal Oak
State/Province
Michigan
Country
United States
City
Saint Paul
State/Province
Minnesota
Country
United States
City
Omaha
State/Province
Nebraska
Country
United States
City
Albuquerque
State/Province
New Mexico
Country
United States
City
New York
State/Province
New York
Country
United States
City
Columbus
State/Province
Ohio
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Brussels
Country
Belgium
City
Brno
Country
Czechia
City
Prague
Country
Czechia
City
Be'er Sheva
Country
Israel
City
Jerusalem
Country
Israel
City
Petaẖ Tiqwa
Country
Israel
City
Tel Aviv
Country
Israel
City
Tel Hashomer
Country
Israel
City
La Paz
State/Province
Baja California Sur
Country
Mexico
City
Celaya
Country
Mexico
City
Monterrey
Country
Mexico
City
Gdansk
Country
Poland
City
Poznan
Country
Poland
City
Wiazowna
Country
Poland
City
Barcelona
Country
Spain
City
Terrassa
Country
Spain
City
Istanbul
Country
Turkey
City
Izmir
Country
Turkey
City
Kocaeli
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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/).
IPD Sharing URL
https://vivli.org/members/ourmembers
Citations:
PubMed Identifier
33206382
Citation
Delgado MR, Tilton A, Carranza-Del Rio J, Dursun N, Bonikowski M, Aydin R, Maciag-Tymecka I, Oleszek J, Dabrowski E, Grandoulier AS, Picaut P; Dysport in PUL study group. Efficacy and safety of abobotulinumtoxinA for upper limb spasticity in children with cerebral palsy: a randomized repeat-treatment study. Dev Med Child Neurol. 2021 May;63(5):592-600. doi: 10.1111/dmcn.14733. Epub 2020 Nov 18.
Results Reference
derived
PubMed Identifier
30204515
Citation
Shierk A, Jimenez-Moreno AC, Roberts H, Ackerman-Laufer S, Backer G, Bard-Pondarre R, Cekmece C, Pyrzanowska W, Vilain C, Delgado MR. Development of a Pediatric Goal-Centered Upper Limb Spasticity Home Exercise Therapy Program for Use in a Phase-III Trial of Abobotulinumtoxina (Dysport(R)). Phys Occup Ther Pediatr. 2019;39(2):124-135. doi: 10.1080/01942638.2018.1486346. Epub 2018 Sep 11.
Results Reference
derived
Learn more about this trial
Efficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children
We'll reach out to this number within 24 hrs