Upper Limb Spasticity (Altered Skeletal Muscle Performance) in ChildrenPhase 3PULNCT02106351

Efficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children

A Phase 3 study testing Botulinum toxin type A in people with Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children, run by Ipsen at 31 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 2 to 17 years
Conditions the study is for: Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children
What is being tested?: Botulinum toxin type A
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 212 participants
Where: 31 sitesin 8 countries
Study dates: Apr 2014to 4 Sep 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

31 sites in 8 countries.

Country

City, postcode or hospital

31 sites in 8 countries

United States12 sites

Study site
Albuquerque, New Mexico
Study site
Aurora, Colorado
Study site
Austin, Texas
Study site
Columbus, Ohio
Study site
Dallas, Texas
Study site
New Orleans, Louisiana
Study site
New York, New York
Study site
Omaha, Nebraska
Study site
Portland, Oregon
Study site
Royal Oak, Michigan
Study site
Saint Paul, Minnesota
Study site
Washington D.C., District of Columbia

Other trials in United States

Israel5 sites

Study site
Beersheba
Study site
Jerusalem
Study site
Petah Tikva
Study site
Tel Aviv
Study site
Tel HaShomer

Other trials in Israel

Mexico3 sites

Study site
Celaya
Study site
La Paz, Baja California Sur
Study site
Monterrey

Other trials in Mexico

Poland3 sites

Study site
Gdansk
Study site
Poznan
Study site
Wiązowna

Other trials in Poland

Turkey (Türkiye)3 sites

Study site
Istanbul
Study site
Izmir
Study site
Kocaeli

Other trials in Turkey (Türkiye)

Czechia2 sites

Study site
Brno
Study site
Prague

Other trials in Czechia

Spain2 sites

Study site
Barcelona
Study site
Terrassa

Other trials in Spain

Belgium1 site

Study site
Brussels

Other trials in Belgium

About this study

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

Conditions: Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children
Being tested: Botulinum toxin type A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Botulinum toxin type ABiological
Also called AbobotulinumtoxinA (Dysport®)
Subjects randomised to receive Dysport 2 U/kg, 8 U/kg or 16 U/kg administered intramuscularly in the study limb.

Study groups in NCT02106351
Study group	Role	What they receive
Group A	Experimental	Group A - Treatments 1, 2, 3 and 4: Dysport 16 Units (U)/kg in one upper extremity (the study limb). Receives: Biological: Botulinum toxin type A
Group B	Experimental	Group B - Treatments 1, 2, 3 and 4: Dysport 8 U/kg in one upper extremity (the study limb). Receives: Biological: Botulinum toxin type A
Group C	Experimental	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). Receives: Biological: Botulinum toxin type A

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline (TC 1, Day 1) and TC 1, Week 6.

Secondary outcomes (2)

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.
Measured: TC 1, Week 6.
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.
Measured: TC 1, Week 6.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 20144 Sep 2018

First posted8 Apr 2014 (estimated)
Study startApr 2014
Primary completion21 Sep 2017
Study completion4 Sep 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Upper Limb Spasticity (Altered Skeletal Muscle Performance) in ChildrenStudies of the same condition, open and under way.
More trials run by IpsenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 212 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02106351
Sponsor's protocol ID: Y-52-52120-153
Other IDs: 2010-021817-22
Acronym: PUL
Status last verified: Sep 2022
First submitted: 3 Apr 2014
Last updated: 28 Sep 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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.

Publications

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.
PubMed 33206382
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.
PubMed 30204515

Study at a glance

From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02106351
Acronym / sponsor ID: PUL / Y-52-52120-153
Conditions: Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 212 participants (actual)
Lead sponsor: IpsenIndustry (pharma, biotech, devices)
Study start: Apr 2014 (actual)
Primary completion: 21 Sep 2017 (actual)
Study completion: 4 Sep 2018 (actual)
First posted: 8 Apr 2014 (estimated)
Results: Posted 24 Dec 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Group A	Experimental	Biological: Botulinum toxin type AGroup A - Treatments 1, 2, 3 and 4: Dysport 16 Units (U)/kg in one upper extremity (the study limb).
Group B	Experimental	Biological: Botulinum toxin type AGroup B - Treatments 1, 2, 3 and 4: Dysport 8 U/kg in one upper extremity (the study limb).
Group C	Experimental	Biological: Botulinum toxin type AGroup 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).

Who may qualify

Ages: 2 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Botulinum toxin type AAlso: AbobotulinumtoxinA (Dysport®)Subjects randomised to receive Dysport 2 U/kg, 8 U/kg or 16 U/kg administered intramuscularly in the study limb.	Biological	Group A, Group B, Group C

Primary outcome

Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG
Time frame: Baseline (TC 1, Day 1) and TC 1, Week 6.
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.

2 secondary outcomes

Mean Physician's Global Assessment (PGA) Score at TC 1, Week 6
Time frame: TC 1, Week 6.
Mean Goal Attainment Scale (GAS) Total Score at TC 1, Week 6
Time frame: TC 1, Week 6.

Results and safety

Results posted to the registry on 24 Dec 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dysport 2 U/kg	71	66
Dysport 8 U/kg	70	67
Dysport 16 U/kg	71	67

Primary outcome: Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG

Time frame: Baseline (TC 1, Day 1) and TC 1, Week 6.. Mean (Standard Deviation). Unit: score on a scale

Measure	Dysport 2 U/kg n = 69	Dysport 8 U/kg n = 69	Dysport 16 U/kg n = 70
Value	-1.5 (1.1)	-1.9 (1.0)	-2.2 (0.9)

Dysport 2 U/kg vs Dysport 8 U/kg: LS mean difference back transformed: -0.4, p = 0.0118, ANCOVA
Dysport 2 U/kg vs Dysport 16 U/kg: LS mean difference back transformed: -0.7, p <0.0001, ANCOVA

Population analysed: The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment emergent adverse events (TEAEs) were collected from the first injection of study treatment up to the end of TC 4 (up to 21 months).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TC1: Dysport 2 U/kg	4 of 70 (5.7%)	15 of 70 (21.4%)	0 of 70
TC 1: Dysport 8 U/kg	2 of 70 (2.9%)	23 of 70 (32.9%)	0 of 70
TC 1: Dysport 16 U/kg	2 of 70 (2.9%)	19 of 70 (27.1%)	0 of 70
TC 2: Dysport 8 U/kg	6 of 88 (6.8%)	18 of 88 (20.5%)	0 of 88
TC 2: Dysport 16 U/kg	1 of 90 (1.1%)	17 of 90 (18.9%)	0 of 90
TC 3: Dysport 8 U/kg	3 of 49 (6.1%)	14 of 49 (28.6%)	0 of 49
TC 3: Dysport 16 U/kg	2 of 58 (3.4%)	10 of 58 (17.2%)	0 of 58
TC 4: Dysport 8 U/kg	2 of 22 (9.1%)	14 of 22 (63.6%)	0 of 22
TC 4: Dysport 16 U/kg	1 of 33 (3%)	5 of 33 (15.2%)	0 of 33

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33206382Delgado 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.
Derived from this study: PubMed 30204515Shierk 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.
Individual participant dataSharing planned: Yes. 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ipsen Medical Director study director

Ipsen

31 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Botulinum toxin type A in people with Upper Limb Spasticity (Altered Skeletal Muscle Performance) in Children, run by Ipsen at 31 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Israel, Mexico, Poland, Turkey (Türkiye) and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG (time frame: Baseline (TC 1, Day 1) and TC 1, Week 6.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02106351, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2022.