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

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).

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).

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).

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.

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).

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.

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.

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).

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).

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).

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.

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).

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.

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.

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.