ENGAGE: Study to Evaluate Effects of DYSPORT® Injected in Lower and Upper Limb Combined With Guided Self-Rehabilitation Contract (GSC)

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02969356
• Collaborator: (none)
• Enrollment: 157
• Locations: 19
• Arm: 1
• Duration (Months): 18.4
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this clinical study is to assess whether AbobotulinumtoxinA (Dysport®) injections in upper and lower limbs accompanied with a personal exercise plan called "Guided Self-rehabilitation Contract" (GSC) can improve voluntary movements in subjects with hemiparesis.

Condition or Disease	Intervention/Treatment	Phase
Spastic Hemiparesis	Biological: Botulinum toxin type A; Other: GSC	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 157 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An International, Multicentre, Prospective, Single-Arm Study to Assess the Effect on Voluntary Movements of AbobotulinumtoxinA 1500 U Administered in Both Upper and Lower Limbs in Conjunction With a Guided Self-Rehabilitation Contract in Adult Subjects With Spastic Hemiparesis
• Study Start Date: Dec 18, 2016
• Actual Primary Completion Date: Apr 26, 2018
• Actual Study Completion Date: Jul 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Dysport Each subject will undergo two intramuscular injection (treatment) cycles, receiving AbobotulinumtoxinA (Dysport®) 1500 U on Day 1 of each cycle; the two dosing occasions will be separated by at least 12 weeks (maximum 20 weeks). Subjects will also receive daily GSC therapy. The main focus of GSC will be on the primary treatment target (TT) limb (as determined at the Baseline Visit) and then the other limb. All muscle groups requiring active training and/or stretching should be trained. Subjects will be be given a diary to record each day whether they have performed the GSC therapy.

Biological: Botulinum toxin type A; Dysport® administered in both upper and lower limbs (total dose of 1500 U per injection split between the 2 limbs).; Other Names: AbobotulinumtoxinA (Dysport®) ; Other: GSC; The GSC is a motivational tool. The physiotherapist will teach each subject the stretching postures and exercises to perform on a daily basis throughout the study. These will be tailored to the individual subject's needs and will form the GSC therapy.

Outcome Measures

Primary Outcome Measures

1. Percentage of Responder Participants at Week 6 After the Second Injection, According to Composite Active Range of Motion (AROM) in the Primary TT Limb [At Week 6, Cycle 2]

   Percentage of responder participants according to AROM was measured by goniometer in the primary TT limb, using zero as the theoretical position of minimal stretch for the muscle assessed. Participants were asked to perform the active movement as far as possible against that muscle and the angle was measured. A participant was considered a responder if he/she achieved at least the predefined improvement threshold - larger or equal to 35 degrees in UL or 5 degrees in LL - in the primary TT limb (based on the composite AROM individual change from baseline to Week 6 after the second injection).

Secondary Outcome Measures

1. Percentage of Responder Participants at Week 6 After the First Injection, According to Composite AROM in the Primary TT Limb [At Week 6, Cycle 1]

   Percentage of responder participants according to composite AROM was measured by goniometer in the primary TT limb, using zero as the theoretical position of minimal stretch for the muscle assessed. Participants were asked to perform the active movement as far as possible against that muscle and the angle was measured. A participant was considered a responder if he/she achieved at least the predefined improvement threshold - larger or equal to 35 degrees in UL or 5 degrees in LL - in the primary TT limb (based on the composite AROM individual change from baseline to Week 6 after the first injection).

2. Mean Change From Baseline in AROM Against 10 Prespecified Muscle Groups at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit [Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit]

   The AROM was measured by goniometer in the primary TT limb, using zero as the theoretical position of minimal stretch for the muscle assessed. Participants were asked to perform the active movement as far as possible against that muscle and the angle was measured. The angle of joint movement was measured in 10 prespecified muscle groups (injected or noninjected); UL: shoulder extensors (SE), elbow flexors (EF), wrist flexors (WF), extrinsic finger flexors (FF) and pronator teres (PT), LL: soleus (Sol), gastrocnemius (GN), gluteus maximus (GM), hamstrings (HS) and rectus femoris (RF). The reinjection cycle visit corresponds to Week 12, 16 or 20 of injection Cycle 1. The last study visit corresponds to the last post-baseline visit performed by the participant (including the early withdrawal visit).

3. Mean Change From Baseline in Composite AROM Against Injected Muscle Groups (Any of the 10 Prespecified Muscles) at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit [Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit]

   Composite AROM (XA) was measured by goniometer in the primary TT limb (either UL or LL, depending on which one has been selected as the primary TT limb), composite AROM in the UL injected muscle groups was calculated as the sum of the AROM in the EF, WF and FF. Composite AROM in the LL injected muscle groups was calculated as the sum of the AROM in Sol and GN.

4. Mean Change From Baseline in Full Composite AROM Against 5 UL or 5 LL Muscle Groups, Regardless of Whether the Muscle Groups Were Injected or Not at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit [Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit]

   Full composite AROM, regardless of whether the muscle groups was injected or not was measured by goniometer in the primary TT limb. Full Composite AROM in the UL was calculated as the sum of the AROM in the 5 UL muscle groups (SE+EF+WF+FF+PT). Full Composite AROM in the LL was calculated as the sum of the AROM in the 5 LL muscle groups (Sol+GN+GM+HS+RF).

5. Mean Change From Baseline in Modified Frenchay Scale (MFS) Overall Score Evaluated Locally and Centrally at Week 12 of Each Treatment Cycle and Last Study Visit [Week 12 of each treatment cycle and last study visit]

   The MFS was used to measure active function in the UL. The MFS consists of 10 tasks, each of which was evaluated locally by the site investigator and centrally by a blinded central reviewer at the coordinating investigators' site, on a 10-point visual analogue scale (VAS) ranging from "No movement" to "Normal". Higher score indicates a better outcome. The MFS overall scores were obtained by averaging all individual task scores, provided that at least 8 out of the 10 were not missing. The mean change from baseline was calculated for the local and central assessments and a positive change from baseline indicates an improvement in active function.

6. Mean Change From Baseline in Maximal Walking Speed Barefoot at Week 12 of Each Treatment Cycle and at Last Study Visit [Week 12 of each treatment cycle and last study visit]

   The 10-meter walking speed test (WST) was used to measure active function in the LL. The participant performed the WST barefoot without a walking aid. If it was absolutely necessary that the participant used a cane, this may have been permitted provided that the same cane was used at baseline and all other walking speed assessments for that participant. The participant was given instructions to walk at his/her maximum speed. The time taken for the participant to walk from the start to the end of the 10 meters was recorded.

7. Participant Satisfaction With the GSC at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit [At baseline (for participants who had GSC previously only), Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit]

   Each participant received a personalised rehabilitation programme. The physiotherapist taught each participant the stretching postures and exercises to perform on a daily basis throughout the study. These were tailored to the individual participant's needs and formed the GSC therapy. The main focus was on the primary TT limb and then the other limb. Participant satisfaction was determined by asking the question "How satisfied are you TODAY regarding the GSC?" Responses were recorded using a 5-level Likert scale, as follows: completely satisfied (+2), rather satisfied (+1), neither satisfied nor dissatisfied (0), rather dissatisfied (-1), and completely dissatisfied (-2).

8. Change From Baseline in Participant's Beliefs That the GSC Will Help to Improve Functional Capacity at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit [Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit]

   Participants were asked the following question: "Do you believe that GSC will help to improve your arm and leg function?" Responses were recorded on a 5-level Likert scale, as follows: very true of what I believe (+2), somewhat true of what I believe (+1), no opinion/don't know (0), somewhat untrue of what I believe (-1), and very untrue of what I believe (-2).

9. Change From Baseline in Physiotherapist's Beliefs That the GSC Will Help to Improve Functional Capacity at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit [Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit]

   Physiotherapists were asked the following question: "Do you believe that GSC will help to improve your patient's arm and leg function?" Responses were recorded on a 5-level Likert scale, as follows: very true of what I believe (+2), somewhat true of what I believe (+1), no opinion/don't know (0), somewhat untrue of what I believe (-1), and very untrue of what I believe (-2).

10. Percentage of Days Over Study Period When GSC Therapy Was Performed [From baseline to end of the study, up to 280 days]

    The investigator counted the number of days when GSC therapy was not performed since the last visit. Using the total number of study days and the total number of days when GSC therapy was not performed, the number of days when GSC was performed was calculated.

11. Global Assessment of Benefits of the Study Therapy [At reinjection cycle visit (Week 12, 16 or 20) and last study visit (Week 24 or 40)]

    A global assessment of the benefits of the study therapy was made by the investigator and the participant (or the caregiver). The participant's caregiver performed the global assessment only in those cases when the participant was not capable to do this. Participants were asked the following question: "How would you rate the overall response to study therapy since baseline?" Responses on the global assessment were recorded on a 5-level Likert scale, as follows: much better (+2), a bit better (+1), the same (0), a bit worse (-1), and much worse (-2).

12. Number of Participants Satisfied With a Longer Interval Between 2 Treatment Cycles [At reinjection cycle visit (Week 16 or 20) and last study visit (Week 24 or 40)]

    Participants who were not reinjected at Week 12 of a given cycle, recorded their satisfaction with a longer interval between 2 injections collected at the corresponding reinjection visit or the last cycle visit (Week 16 or Week 20 for each cycle). To assess this, the participants were asked the following question: "Are you satisfied with a longer interval between 2 injections?". The possible answers were: Yes, No or No opinion.

13. Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Scores at Last Study Visit [At last study visit (Week 24 or 40)]

    Participants were asked to complete EQ-5D-5L questionnaire to assess their current health status. The EQ-5D-5L was a generic, preference-based measure of health-related quality of life (QoL). Questions were answered based on how the participant was feeling "Today". The EQ-5D-5L consists of 2 parts: EQ-5D descriptive system and EQ VAS. The EQ-5D descriptive system included questions for each of the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The VAS recorded participant's self-rated health on a vertical 20-centimeter VAS where the endpoints were labelled "The best health you can imagine" and "The worst health you can imagine". The EQ-5D-5L questionnaire scores range from 0-100, where 0= worst self-perceived health and 100= best self-perceived health. Positive change from baseline indicates an improvement in QoL.

14. Change From Baseline in Short Form 12 (SF-12) Scales at Last Study Visit [At last study visit (Week 24 or 40)]

    The SF-12 was a short form questionnaire survey consisting of 12 questions, which were a subset of the SF-36 health survey. Most of the questions were answered based on how the participant had felt over the previous 4 weeks. The SF-12 covers 8 domains, including physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotional and mental health. The SF-12 questionnaire survey scale ranges from 0-100, where 0= lowest level of health and 100= highest level of health. Positive change from baseline indicates an improvement in QoL.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects aged at least the national legal adult age.

• Subjects with hemiparesis due to acquired brain injury (ABI) presenting with muscle overactivity impeding motor function based on investigator's judgement including, but not limited to, at least one of the following requiring botulinum neurotoxin (BoNT) treatment: typical clenched fist; flexed wrist; flexed elbow; or plantar flexed foot pattern.

• At least 12 months since the ABI (i.e. stroke or traumatic brain injury (TBI)).

• Naïve or non-naïve to BoNT treatment; if non-naïve, at least 4 months after the last BoNT injection, of any serotype.

• Upper limb active function with an overall score between 2 and 7, as assessed by Modified Frenchay Scale (MFS), if the primary TT limb is the upper limb (UL).

• A 10-metre maximal WS barefoot between 0.2 and 1.4 m/s, if the primary TT limb is the lower limb (LL). Maximal WS barefoot will be performed without walking aids. However, a cane may be permitted if absolutely necessary (although this may prevent detection of treatment-induced improvements). In this case, the same aid will have to be used for all WS assessments during the study.

• Subjects must provide written informed consent to participate in the study prior to any study-related procedures.

• Female subjects of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study until the last visit of the subjects and for at least 12 weeks post injection. Acceptable methods of contraception include total abstinence, male partner has had a vasectomy, double barrier method (e.g. male condom plus spermicide, or female diaphragm plus spermicide), intrauterine device, or hormonal contraceptive (oral, transdermal, implanted and injected).

• Subjects must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow-up evaluation as specified in the protocol

Exclusion Criteria:

• Inability to understand protocol procedures and requirements, which, in the opinion of the investigator, could negatively impact on protocol compliance, in particularly inability to exercise according to the GSC.

• Previous surgery on the affected muscles and ligaments, tendons, nerve trunks, or bones of the treated upper or lower limb.

• Previous treatment with phenol and/or alcohol in any of the treated limbs any time before the study.

• Any medical condition (including severe dysphagia or breathing difficulties) that may increase, in the opinion of the investigator, the likelihood of adverse events (AEs) related to BoNT A treatment.

• Current, planned or received within the last 4 weeks prior to study treatment, treatment with any drug that interferes either directly or indirectly with neuromuscular function (for example, aminoglycosides).

• Major neurological impairment other than spastic paresis (including major proprioceptive ataxia or apraxia on the paretic side) that could negatively impact on the functional performance of the subject.

• Known disease of the neuromuscular junction (such as Lambert-Eaton myasthenic syndrome or myasthenia gravis).

• Known sensitivity to BoNT-A or any excipient of Dysport.

• Infection at the injection site(s).

• Current pregnancy or lactation. A pregnancy test will be performed at the start of the study for all female subjects of childbearing potential (i.e. not surgically sterile or 2 years postmenopausal).

• Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.

• Abnormal baseline findings or any other medical condition(s) that, in the opinion of the investigator, might jeopardise the subject's safety.

• Subjects treated, or likely to be treated, with intrathecal baclofen during the course of the study or during the 4 weeks before study entry.

• Subjects who have participated in any therapeutic clinical study/received any investigational agent within 30 days of enrolment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kansas Institute of Research, Kansas City Bone & Joint Clinic, Division of Signature Medical Group of KC	Kansas City	Kansas	United States	66211
2	University of Pittsburgh Medical Center, Physical Medicine and Rehabilitation	Pittsburgh	Pennsylvania	United States	15213
3	Medical University of South Carolina	Charleston	South Carolina	United States	29425
4	Department of Neurology, Division of Movement Disorders, Vanderbilt University	Nashville	Tennessee	United States	37240-7915
5	UT Southwestern Medical Center	Dallas	Texas	United States	75390
6	UT Health Physical Medicine & Rehabilitation Department, TIRR Memorial Hermann	Houston	Texas	United States	77030
7	Fakultní nemocnice Královské Vinohrady, Neurologická klinika	Brno		Czechia	100 34
8	Neurology and Physiotherapy Outpatient Clinic	Brno		Czechia	615 00
9	Fakultní nemocnice Brno Neurologická klinika	Brno		Czechia	625 00
10	Neurology Department - Regional Hospital Pardubice	Pardubice		Czechia	532 03
11	Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague	Praha		Czechia	120 00
12	Service de Médecine Physique et Réadaptation, Hôpital Albert-Chenevier	Créteil	Cedex	France	94010
13	Service de Médecine Physique et de Réadaptation, Bâtiment Tastet-Girard, Groupe Hospitalier Pellegrin	Bordeaux		France	33000
14	Service de Médecine Physique et Réadaptation, Hôpital Sébastopol - CHU de Reims	Reims		France	51100
15	Service de Médecine Physique et Réadaptation, CHU Saint Etienne - Hôpital Bellevue	Saint-Étienne		France	42055
16	Federal Siberian Scientific Clinical Center	Krasnoyarsk		Russian Federation	660049
17	Medical Rehabilitation Center	Moscow		Russian Federation	125367
18	Saint-Petersburg Bekhterev Psychoneurological Research Institute	Saint-Petersburg		Russian Federation	192019
19	Samara Regional Clinical Hospital n.a. V.D.Seredavin	Samara		Russian Federation	443035

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

• Study Protocol - Jan 24, 2018
• Statistical Analysis Plan - Oct 5, 2018

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT02969356
• Other Study ID Numbers: F-FR-52120-228; 2016-001989-29
• First Posted: Nov 21, 2016
• Last Update Posted: Jul 13, 2020
• Last Verified: Jun 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Muscle Spasticity; Paresis; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Recruitment Details	This multicenter, single-arm study was conducted in 18 centers in 4 countries between 22 December 2016 and 18 July 2018 in participants with spastic hemiparesis due to acquired brain injury. Study had 2 treatment cycles separated by at least 12 (maximum 20) weeks and combined with Guided Self-Rehabilitation Contract (GSC) for whole study duration.
Pre-assignment Detail	A total of 157 participants were treated in this study. At baseline (Cycle 1, Day 1), the primary treatment target (TT) limb (upper limb [UL] or lower limb [LL]) was defined by the investigator, following discussion with the participant. If the primary TT limb was the UL, the secondary TT limb was the LL (and vice versa).

Arm/Group Title	Dysport
Arm/Group Description	Dysport (AbobotulinumtoxinA) 1500 units (U) intramuscular (IM) injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Period Title: Overall Study
STARTED	157
Intent-to-Treat (ITT) Population	153
COMPLETED	134
NOT COMPLETED	23

Baseline Characteristics

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Overall Participants	153
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	122 79.7%
>=65 years	31 20.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.9 (12.6)
Sex: Female, Male (Count of Participants)
Female	53 34.6%
Male	100 65.4%
Race/Ethnicity, Customized (Count of Participants)
Race: White	126 82.4%
Race: Black or African American	7 4.6%
Race: Asian	2 1.3%
Race: Missing	18 11.8%
Ethnicity: Not Hispanic/Latino	135 88.2%
Ethnicity: Missing	18 11.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Responder Participants at Week 6 After the Second Injection, According to Composite Active Range of Motion (AROM) in the Primary TT Limb
Description	Percentage of responder participants according to AROM was measured by goniometer in the primary TT limb, using zero as the theoretical position of minimal stretch for the muscle assessed. Participants were asked to perform the active movement as far as possible against that muscle and the angle was measured. A participant was considered a responder if he/she achieved at least the predefined improvement threshold - larger or equal to 35 degrees in UL or 5 degrees in LL - in the primary TT limb (based on the composite AROM individual change from baseline to Week 6 after the second injection).
Time Frame	At Week 6, Cycle 2

Outcome Measure Data

Analysis Population Description

The modified ITT (mITT) population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study, for whom a primary TT limb had been defined and who had the primary efficacy outcome assessed at Week 6, Cycle 2.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	136
Number (95% Confidence Interval) [percentage of participants]	72.1 47.1%

2. Secondary Outcome

Title	Percentage of Responder Participants at Week 6 After the First Injection, According to Composite AROM in the Primary TT Limb
Description	Percentage of responder participants according to composite AROM was measured by goniometer in the primary TT limb, using zero as the theoretical position of minimal stretch for the muscle assessed. Participants were asked to perform the active movement as far as possible against that muscle and the angle was measured. A participant was considered a responder if he/she achieved at least the predefined improvement threshold - larger or equal to 35 degrees in UL or 5 degrees in LL - in the primary TT limb (based on the composite AROM individual change from baseline to Week 6 after the first injection).
Time Frame	At Week 6, Cycle 1

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Number (95% Confidence Interval) [percentage of participants]	58.2 38%

3. Secondary Outcome

Title	Mean Change From Baseline in AROM Against 10 Prespecified Muscle Groups at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
Description	The AROM was measured by goniometer in the primary TT limb, using zero as the theoretical position of minimal stretch for the muscle assessed. Participants were asked to perform the active movement as far as possible against that muscle and the angle was measured. The angle of joint movement was measured in 10 prespecified muscle groups (injected or noninjected); UL: shoulder extensors (SE), elbow flexors (EF), wrist flexors (WF), extrinsic finger flexors (FF) and pronator teres (PT), LL: soleus (Sol), gastrocnemius (GN), gluteus maximus (GM), hamstrings (HS) and rectus femoris (RF). The reinjection cycle visit corresponds to Week 12, 16 or 20 of injection Cycle 1. The last study visit corresponds to the last post-baseline visit performed by the participant (including the early withdrawal visit).
Time Frame	Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
UL SE: Week 6, Cycle 1	8.9 (16.4)
UL SE: Week 12, Cycle 1	15.8 (22.9)
UL SE: Reinjection cycle visit	13.4 (22.5)
UL SE: Week 6, Cycle 2	19.3 (25.1)
UL SE: Week 12, Cycle 2	21.1 (27.7)
UL SE: Last study visit	19.0 (24.9)
UL EF: Week 6, Cycle 1	8.7 (25.5)
UL EF: Week 12, Cycle 1	12.0 (27.3)
UL EF: Reinjection cycle visit	10.9 (28.3)
UL EF: Week 6, Cycle 2	14.9 (26.2)
UL EF: Week 12, Cycle 2	15.4 (28.1)
UL EF: Last study visit	13.0 (28.2)
UL WF: Week 6, Cycle 1	11.0 (16.3)
UL WF: Week 12, Cycle 1	10.9 (20.1)
UL WF: Reinjection cycle visit	9.6 (20.4)
UL WF: Week 6, Cycle 2	15.6 (24.3)
UL WF: Week 12, Cycle 2	13.6 (22.4)
UL WF: Last study visit	12.4 (22.3)
UL FF: Week 6, Cycle 1	24.1 (37.1)
UL FF: Week 12, Cycle 1	20.7 (36.0)
UL FF: Reinjection cycle visit	14.5 (36.7)
UL FF: Week 6, Cycle 2	29.5 (43.7)
UL FF: Week 12, Cycle 2	27.9 (49.1)
UL FF: Last study visit	24.5 (44.9)
UL PT: Week 6, Cycle 1	9.0 (32.6)
UL PT: Week 12, Cycle 1	8.0 (38.0)
UL PT: Reinjection cycle visit	7.4 (37.9)
UL PT: Week 6, Cycle 2	11.0 (38.6)
UL PT: Week 12, Cycle 2	9.4 (38.4)
UL PT: Last study visit	8.7 (41.0)
LL Sol: Week 6, Cycle 1	4.7 (9.6)
LL Sol: Week 12, Cycle 1	5.2 (13.8)
LL Sol: Reinjection cycle visit	4.5 (15.4)
LL Sol: Week 6, Cycle 2	9.3 (17.9)
LL Sol: Week 12, Cycle 2	9.0 (17.0)
LL Sol: Last study visit	8.2 (16.4)
LL GN: Week 6, Cycle 1	9.0 (14.8)
LL GN: Week 12, Cycle 1	9.9 (14.6)
LL GN: Reinjection cycle visit	7.5 (15.0)
LL GN: Week 6, Cycle 2	12.6 (16.8)
LL GN: Week 12, Cycle 2	11.8 (17.1)
LL GN: Last study visit	11.9 (17.4)
LL GM: Week 6, Cycle 1	5.1 (15.9)
LL GM: Week 12, Cycle 1	5.2 (15.2)
LL GM: Reinjection cycle visit	5.1 (14.7)
LL GM: Week 6, Cycle 2	6.1 (15.9)
LL GM: Week 12, Cycle 2	7.3 (15.2)
LL GM: Last study visit	6.6 (16.5)
LL HS: Week 6, Cycle 1	0.9 (34.2)
LL HS: Week 12, Cycle 1	4.0 (34.7)
LL HS: Reinjection cycle visit	5.6 (30.7)
LL HS: Week 6, Cycle 2	8.2 (25.1)
LL HS: Week 12, Cycle 2	10.3 (26.3)
LL HS: Last study visit	6.8 (31.1)
LL RF: Week 6, Cycle 1	4.5 (15.0)
LL RF: Week 12, Cycle 1	4.4 (23.1)
LL RF: Reinjection cycle visit	5.1 (25.3)
LL RF: Week 6, Cycle 2	8.9 (24.7)
LL RF: Week 12, Cycle 2	9.6 (23.4)
LL RF: Last study visit	8.6 (23.0)

4. Secondary Outcome

Title	Mean Change From Baseline in Composite AROM Against Injected Muscle Groups (Any of the 10 Prespecified Muscles) at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
Description	Composite AROM (XA) was measured by goniometer in the primary TT limb (either UL or LL, depending on which one has been selected as the primary TT limb), composite AROM in the UL injected muscle groups was calculated as the sum of the AROM in the EF, WF and FF. Composite AROM in the LL injected muscle groups was calculated as the sum of the AROM in Sol and GN.
Time Frame	Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
UL: Week 6, Cycle 1	43.1 (49.9)
UL: Week 12, Cycle 1	42.8 (56.7)
UL: Reinjection cycle visit	34.1 (52.8)
UL: Week 6, Cycle 2	59.5 (64.4)
UL: Week 12, Cycle 2	56.3 (66.7)
UL: Last study visit	49.3 (63.4)
LL: Week 6, Cycle 1	13.7 (18.3)
LL: Week 12, Cycle 1	15.1 (23.4)
LL: Reinjection cycle visit	12.0 (24.5)
LL: Week 6, Cycle 2	21.9 (28.8)
LL: Week 12, Cycle 2	20.8 (28.8)
LL: Last study visit	20.1 (27.6)

5. Secondary Outcome

Title	Mean Change From Baseline in Full Composite AROM Against 5 UL or 5 LL Muscle Groups, Regardless of Whether the Muscle Groups Were Injected or Not at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
Description	Full composite AROM, regardless of whether the muscle groups was injected or not was measured by goniometer in the primary TT limb. Full Composite AROM in the UL was calculated as the sum of the AROM in the 5 UL muscle groups (SE+EF+WF+FF+PT). Full Composite AROM in the LL was calculated as the sum of the AROM in the 5 LL muscle groups (Sol+GN+GM+HS+RF).
Time Frame	Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
UL: Week 6, Cycle 1	60.6 (68.4)
UL: Week 12, Cycle 1	66.3 (75.7)
UL: Reinjection cycle visit	53.9 (69.9)
UL: Week 6, Cycle 2	90.5 (90.1)
UL: Week 12, Cycle 2	87.6 (94.8)
UL: Last study visit	77.8 (89.6)
LL: Week 6, Cycle 1	24.4 (42.7)
LL: Week 12, Cycle 1	28.7 (55.9)
LL: Reinjection cycle visit	28.0 (56.2)
LL: Week 6, Cycle 2	45.1 (58.2)
LL: Week 12, Cycle 2	48.1 (60.4)
LL: Last study visit	42.2 (61.7)

6. Secondary Outcome

Title	Mean Change From Baseline in Modified Frenchay Scale (MFS) Overall Score Evaluated Locally and Centrally at Week 12 of Each Treatment Cycle and Last Study Visit
Description	The MFS was used to measure active function in the UL. The MFS consists of 10 tasks, each of which was evaluated locally by the site investigator and centrally by a blinded central reviewer at the coordinating investigators' site, on a 10-point visual analogue scale (VAS) ranging from "No movement" to "Normal". Higher score indicates a better outcome. The MFS overall scores were obtained by averaging all individual task scores, provided that at least 8 out of the 10 were not missing. The mean change from baseline was calculated for the local and central assessments and a positive change from baseline indicates an improvement in active function.
Time Frame	Week 12 of each treatment cycle and last study visit

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Local assessment: Week 12, Cycle 1	0.44 (0.56)
Local assessment: Week 12, Cycle 2	0.55 (0.65)
Local assessment: Last study visit	0.53 (0.63)
Central assessment: Week 12, Cycle 1	0.08 (0.49)
Central assessment: Week 12, Cycle 2	0.18 (0.61)
Central assessment: Last study visit	0.14 (0.59)

7. Secondary Outcome

Title	Mean Change From Baseline in Maximal Walking Speed Barefoot at Week 12 of Each Treatment Cycle and at Last Study Visit
Description	The 10-meter walking speed test (WST) was used to measure active function in the LL. The participant performed the WST barefoot without a walking aid. If it was absolutely necessary that the participant used a cane, this may have been permitted provided that the same cane was used at baseline and all other walking speed assessments for that participant. The participant was given instructions to walk at his/her maximum speed. The time taken for the participant to walk from the start to the end of the 10 meters was recorded.
Time Frame	Week 12 of each treatment cycle and last study visit

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Week 12, Cycle 1	0.081 (0.161)
Week 12, Cycle 2	0.116 (0.159)
Last study visit	0.097 (0.187)

8. Secondary Outcome

Title	Participant Satisfaction With the GSC at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
Description	Each participant received a personalised rehabilitation programme. The physiotherapist taught each participant the stretching postures and exercises to perform on a daily basis throughout the study. These were tailored to the individual participant's needs and formed the GSC therapy. The main focus was on the primary TT limb and then the other limb. Participant satisfaction was determined by asking the question "How satisfied are you TODAY regarding the GSC?" Responses were recorded using a 5-level Likert scale, as follows: completely satisfied (+2), rather satisfied (+1), neither satisfied nor dissatisfied (0), rather dissatisfied (-1), and completely dissatisfied (-2).
Time Frame	At baseline (for participants who had GSC previously only), Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Baseline for non-naïve participants to GSC only	1.8 (0.5)
Week 6, Cycle 1	1.3 (0.9)
Week 12, Cycle 1	1.4 (0.8)
Reinjection cycle visit	1.4 (0.7)
Week 6, Cycle 2	1.4 (0.7)
Week 12, Cycle 2	1.4 (0.8)
Last study visit	1.4 (0.8)

9. Secondary Outcome

Title	Change From Baseline in Participant's Beliefs That the GSC Will Help to Improve Functional Capacity at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
Description	Participants were asked the following question: "Do you believe that GSC will help to improve your arm and leg function?" Responses were recorded on a 5-level Likert scale, as follows: very true of what I believe (+2), somewhat true of what I believe (+1), no opinion/don't know (0), somewhat untrue of what I believe (-1), and very untrue of what I believe (-2).
Time Frame	Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Week 6, Cycle 1	-0.2 (0.9)
Week 12, Cycle 1	-0.1 (0.8)
Reinjection cycle visit	-0.2 (0.8)
Week 6, Cycle 2	-0.1 (0.7)
Week 12, Cycle 2	-0.3 (0.8)
Last study visit	-0.2 (0.8)

10. Secondary Outcome

Title	Change From Baseline in Physiotherapist's Beliefs That the GSC Will Help to Improve Functional Capacity at Week 6 and Week 12 of Each Treatment Cycle, Reinjection Cycle Visit and Last Study Visit
Description	Physiotherapists were asked the following question: "Do you believe that GSC will help to improve your patient's arm and leg function?" Responses were recorded on a 5-level Likert scale, as follows: very true of what I believe (+2), somewhat true of what I believe (+1), no opinion/don't know (0), somewhat untrue of what I believe (-1), and very untrue of what I believe (-2).
Time Frame	Week 6 and Week 12 of each treatment cycle, reinjection cycle visit and last study visit

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Week 6, Cycle 1	-0.2 (0.6)
Week 12, Cycle 1	-0.2 (0.6)
Reinjection cycle visit	-0.1 (0.6)
Week 6, Cycle 2	-0.2 (0.6)
Week 12, Cycle 2	-0.2 (0.6)
Last study visit	-0.2 (0.7)

11. Secondary Outcome

Title	Percentage of Days Over Study Period When GSC Therapy Was Performed
Description	The investigator counted the number of days when GSC therapy was not performed since the last visit. Using the total number of study days and the total number of days when GSC therapy was not performed, the number of days when GSC was performed was calculated.
Time Frame	From baseline to end of the study, up to 280 days

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Mean (Standard Deviation) [percentage of study days]	92.80 (9.85)

12. Secondary Outcome

Title	Global Assessment of Benefits of the Study Therapy
Description	A global assessment of the benefits of the study therapy was made by the investigator and the participant (or the caregiver). The participant's caregiver performed the global assessment only in those cases when the participant was not capable to do this. Participants were asked the following question: "How would you rate the overall response to study therapy since baseline?" Responses on the global assessment were recorded on a 5-level Likert scale, as follows: much better (+2), a bit better (+1), the same (0), a bit worse (-1), and much worse (-2).
Time Frame	At reinjection cycle visit (Week 12, 16 or 20) and last study visit (Week 24 or 40)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Investigator: Reinjection cycle visit	1.4 (0.6)
Investigator: Last study visit	1.3 (0.7)
Participant: Reinjection cycle visit	1.4 (0.6)
Participant: Last study visit	1.4 (0.7)

13. Secondary Outcome

Title	Number of Participants Satisfied With a Longer Interval Between 2 Treatment Cycles
Description	Participants who were not reinjected at Week 12 of a given cycle, recorded their satisfaction with a longer interval between 2 injections collected at the corresponding reinjection visit or the last cycle visit (Week 16 or Week 20 for each cycle). To assess this, the participants were asked the following question: "Are you satisfied with a longer interval between 2 injections?". The possible answers were: Yes, No or No opinion.
Time Frame	At reinjection cycle visit (Week 16 or 20) and last study visit (Week 24 or 40)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Results are presented for participants who were not reinjected at Week 12 of the given cycle.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Yes	52 34%
No	6 3.9%
No opinion	12 7.8%
Missing	0 0%
Yes	42 27.5%
No	14 9.2%
No opinion	12 7.8%
Missing	6 3.9%

14. Secondary Outcome

Title	Change From Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Scores at Last Study Visit
Description	Participants were asked to complete EQ-5D-5L questionnaire to assess their current health status. The EQ-5D-5L was a generic, preference-based measure of health-related quality of life (QoL). Questions were answered based on how the participant was feeling "Today". The EQ-5D-5L consists of 2 parts: EQ-5D descriptive system and EQ VAS. The EQ-5D descriptive system included questions for each of the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The VAS recorded participant's self-rated health on a vertical 20-centimeter VAS where the endpoints were labelled "The best health you can imagine" and "The worst health you can imagine". The EQ-5D-5L questionnaire scores range from 0-100, where 0= worst self-perceived health and 100= best self-perceived health. Positive change from baseline indicates an improvement in QoL.
Time Frame	At last study visit (Week 24 or 40)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Mobility: Last study visit	-0.3 (0.8)
Self-care: Last study visit	-0.0 (0.8)
Usual activities: Last study visit	-0.3 (1.0)
Pain/discomfort: Last study visit	-0.3 (0.9)
Anxiety/depression: Last study visit	-0.1 (0.9)
EQ VAS: Last study visit	4.27 (18.71)

15. Secondary Outcome

Title	Change From Baseline in Short Form 12 (SF-12) Scales at Last Study Visit
Description	The SF-12 was a short form questionnaire survey consisting of 12 questions, which were a subset of the SF-36 health survey. Most of the questions were answered based on how the participant had felt over the previous 4 weeks. The SF-12 covers 8 domains, including physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotional and mental health. The SF-12 questionnaire survey scale ranges from 0-100, where 0= lowest level of health and 100= highest level of health. Positive change from baseline indicates an improvement in QoL.
Time Frame	At last study visit (Week 24 or 40)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were injected at least once with the study treatment, who received at least 1 day of GSC therapy during the study and for whom a primary TT limb had been defined. Only participants with data available at each time point are presented.

Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
Measure Participants	153
Physical score: Last study visit	3.985 (7.358)
Mental score: Last study visit	-0.008 (9.631)

Adverse Events

Time Frame	From first injection of study treatment up to end of the study or early withdrawal, approximately 40 weeks.
Adverse Event Reporting Description	The safety population included all participants who were injected at least once with the study treatment.
Arm/Group Title	Dysport
Arm/Group Description	Dysport 1500 U IM injection, was administered as a split dose, in both the UL and LL on Day 1 of each treatment cycle. The dose given in each limb was based on which was considered the primary TT limb at baseline. At least half the total dose must have been injected in the primary TT limb and a maximum of 1000 U could be injected in an UL (even if it was the primary TT limb). There was no maximum dose that could have been injected in a LL, provided that some out of the 1500 U total was used for the UL injection. The second Dysport injection (Cycle 2) may have been given in a different split to the first injection (Cycle 1), at the discretion of the investigator. However, the same minimal/maximal rules applied. The primary TT remained the same for both Dysport injections. Participants were also asked to perform daily GSC therapy throughout the study.
All Cause Mortality
	Dysport
	Affected / at Risk (%)	# Events
Total	1/157 (0.6%)
Serious Adverse Events
	Dysport
	Affected / at Risk (%)	# Events
Total	19/157 (12.1%)
Cardiac disorders
Myocardial infarction	2/157 (1.3%)	2
Ventricular extrasystoles	1/157 (0.6%)	1
General disorders
Fatigue	1/157 (0.6%)	1
Pyrexia	1/157 (0.6%)	1
Hepatobiliary disorders
Cholelithiasis	1/157 (0.6%)	1
Infections and infestations
Pneumonia	2/157 (1.3%)	2
Intervertebral discitis	1/157 (0.6%)	1
Tracheobronchitis	1/157 (0.6%)	1
Injury, poisoning and procedural complications
Fall	1/157 (0.6%)	1
Rib fracture	1/157 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric	1/157 (0.6%)	1
Squamous cell carcinoma of lung	1/157 (0.6%)	1
Nervous system disorders
Epilepsy	2/157 (1.3%)	2
Brain stem stroke	1/157 (0.6%)	1
Dysarthria	1/157 (0.6%)	1
Ischaemic stroke	1/157 (0.6%)	1
Myasthenic syndrome	1/157 (0.6%)	1
Vith nerve paralysis	1/157 (0.6%)	1
Psychiatric disorders
Depression	1/157 (0.6%)	1
Mental status changes	1/157 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/157 (0.6%)	1
Haemoptysis	1/157 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Dysport
	Affected / at Risk (%)	# Events
Total	72/157 (45.9%)
Cardiac disorders
Cardiac failure	1/157 (0.6%)	1
Intracardiac thrombus	1/157 (0.6%)	1
Myocardial ischaemia	1/157 (0.6%)	1
Ear and labyrinth disorders
Hypoacusis	1/157 (0.6%)	1
Vertigo	1/157 (0.6%)	1
Endocrine disorders
Thyroid disorder	1/157 (0.6%)	1
Eye disorders
Diplopia	2/157 (1.3%)	2
Photopsia	2/157 (1.3%)	2
Vision blurred	2/157 (1.3%)	3
Gastrointestinal disorders
Dyspepsia	3/157 (1.9%)	3
Diarrhoea	1/157 (0.6%)	1
Dry mouth	1/157 (0.6%)	1
Dysphagia	1/157 (0.6%)	2
Gastritis	1/157 (0.6%)	1
Nausea	1/157 (0.6%)	1
Toothache	1/157 (0.6%)	1
General disorders
Fatigue	5/157 (3.2%)	5
Asthenia	3/157 (1.9%)	3
Oedema peripheral	3/157 (1.9%)	3
Injection site haematoma	2/157 (1.3%)	2
Pyrexia	1/157 (0.6%)	1
Gait disturbance	1/157 (0.6%)	1
Influenza like illness	1/157 (0.6%)	1
Injection site rash	1/157 (0.6%)	1
Pain	1/157 (0.6%)	1
Peripheral swelling	1/157 (0.6%)	1
Therapeutic product ineffective	1/157 (0.6%)	1
Hepatobiliary disorders
Liver disorder	1/157 (0.6%)	1
Infections and infestations
Bronchitis	3/157 (1.9%)	3
Respiratory tract infection	3/157 (1.9%)	3
Urinary tract infection	3/157 (1.9%)	3
Viral infection	3/157 (1.9%)	3
Viral upper respiratory tract infection	3/157 (1.9%)	3
Influenza	2/157 (1.3%)	2
Gastroenteritis	1/157 (0.6%)	1
Respiratory tract infection viral	1/157 (0.6%)	1
Rhinitis	1/157 (0.6%)	2
Tooth infection	1/157 (0.6%)	1
Upper respiratory tract infection	1/157 (0.6%)	1
Injury, poisoning and procedural complications
Fall	10/157 (6.4%)	12
Contusion	4/157 (2.5%)	9
Joint injury	2/157 (1.3%)	2
Ligament sprain	2/157 (1.3%)	2
Arthropod bite	1/157 (0.6%)	1
Lip injury	1/157 (0.6%)	1
Tooth injury	1/157 (0.6%)	1
Traumatic haematoma	1/157 (0.6%)	2
Investigations
Weight decreased	2/157 (1.3%)	2
Angiogram abnormal	1/157 (0.6%)	1
ECG signs of myocardial ischaemia	1/157 (0.6%)	1
Transaminases increased	1/157 (0.6%)	1
Metabolism and nutrition disorders
Hypochloraemia	1/157 (0.6%)	1
Hyponatraemia	1/157 (0.6%)	1
Iron deficiency	1/157 (0.6%)	1
Musculoskeletal and connective tissue disorders
Back pain	11/157 (7%)	13
Pain in extremity	5/157 (3.2%)	6
Muscular weakness	4/157 (2.5%)	4
Musculoskeletal pain	3/157 (1.9%)	3
Arthralgia	2/157 (1.3%)	2
Neck pain	2/157 (1.3%)	2
Myalgia	1/157 (0.6%)	1
Osteoporosis	1/157 (0.6%)	1
Tenosynovitis	1/157 (0.6%)	1
Nervous system disorders
Dizziness	4/157 (2.5%)	4
Headache	3/157 (1.9%)	3
Clonic convulsion	1/157 (0.6%)	1
Monoparesis	1/157 (0.6%)	1
Seizure	1/157 (0.6%)	1
Slow speech	1/157 (0.6%)	1
Syncope	1/157 (0.6%)	1
Tension headache	1/157 (0.6%)	1
Transient ischaemic attack	1/157 (0.6%)	1
Vocal cord paralysis	1/157 (0.6%)	1
Vocal cord paresis	1/157 (0.6%)	1
Psychiatric disorders
Depression	4/157 (2.5%)	4
Insomnia	2/157 (1.3%)	2
Agitation	1/157 (0.6%)	1
Anxiety	1/157 (0.6%)	1
Depressed mood	1/157 (0.6%)	1
Mental status changes	1/157 (0.6%)	1
Renal and urinary disorders
Renal colic	1/157 (0.6%)	1
Urinary incontinence	1/157 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/157 (0.6%)	1
Dyspnoea	2/157 (1.3%)	2
Cough	1/157 (0.6%)	1
Nocturnal dyspnoea	1/157 (0.6%)	1
Pulmonary embolism	1/157 (0.6%)	1
Skin and subcutaneous tissue disorders
Erythema	1/157 (0.6%)	1
Surgical and medical procedures
Abscess drainage	1/157 (0.6%)	1
Dental implantation	1/157 (0.6%)	1
Sinus operation	1/157 (0.6%)	1
Vascular disorders
Hypertension	2/157 (1.3%)	2
Haematoma	1/157 (0.6%)	1
Hypotension	1/157 (0.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.