A Phase III, multicentre prospective, double blind, randomised, placebo controlled study, assessing the efficacy and safety of Dysport intramuscular injections used for the treatment of upper limb spasticity in adult subjects with spastic hemiparesis due to stroke or traumatic brain injury (TBI).
This is a phase III, multicentre, prospective, double blind, randomised, placebo controlled, single treatment cycle study.
All subjects are planned to have a single treatment cycle. All subjects receiving treatment after signing an informed consent are expected to be followed up for a minimum of 12 weeks and a maximum of 24 weeks in this study. All subjects who have had a minimum of 12 weeks follow up will be considered to have completed the study.
At study entry, subjects will be randomised into one of three treatment groups (Dysport 500 U, Dysport 1000 U, or placebo) in a ratio of 1:1:1. Stratification will be performed between BTX naive and non-naive subjects. For the purpose of this protocol, a naive subject is defined as a subject who has never received any BTX in the affected upper limb.
Following treatment administration, all subjects will attend follow up visits at Week 1, Week 4, and Week 12. Three discretionary visits are planned for the study, one at Week 16 (for subjects not requiring retreatment at Week 12), one at Week 20 (for those not requiring retreatment at Week 16), and one at Week 24 (for those not requiring retreatment at Week 20). Subjects who have completed the Week 12, Week 16, Week 20, or Week 24 follow up visit will be offered entry into an open label extension study. At the Week 24 follow up visit, if the subject still does not require retreatment, he/she will be offered entry into the observational phase of the open label extension study until he/she requires retreatment or until he/she has undergone a minimum of one year follow up.
Primary efficacy endpoint
* Mean change from baseline in muscle tone measured on the Modified Ashworth Scale (MAS), in the primary targeted muscle group at Week 4.
Secondary efficacy endpoints
* Mean PGA Score at Week 4.
* Mean change from baseline in the Principal Target of Treatment (PTT) of the Disability Assessment Scale (DAS) at Week 4.
Tertiary efficacy endpoints
* Mean change from baseline in the MAS in the primary targeted muscle group.
* Mean change from baseline in the MAS in each of the following muscle groups: shoulder extensors, elbow flexors, wrist flexors and extrinsic finger flexors for subjects injected in these muscle groups and having a MAS baseline score >=2.
* Proportion of subjects with at least one grade decrease from baseline on the MAS in the primary targeted muscle group over the treatment cycle.
* Mean Physicians Global Assessment (PGA) Score.
* Mean change from baseline in the PTT of the DAS.
* Mean change from baseline in the Modified Frenchay Scale (MFS) overall score.
* Proportion of subjects with a decrease from baseline of at least one grade in the PTT and in each domain of disability of the DAS for subjects having a baseline score >=2 in the considered domain at each study visit.
* Mean change from baseline in the Tardiue Scale (TS) in the primary targeted muscle group (spasticity angle, angle of catch and grade).
* Mean change from baseline in the TS in the shoulder extensors, elbow flexors and, wrist flexors and extrinsic finger flexors in subjects injected in these muscle groups and with a baseline spasticity angle and amp;gt;10[Degrees].
* Mean change from baseline in the active range of motion (ROM) against the primary targeted muscle group at each study visit.
* Mean change from baseline in the ease of applying a splint.
* Mean change from baseline in QoL measured on the Short Form (36) Health Survey (SF-36) and European Quality of Life x 5 Dimensions (EQ-5D) scales will be analysed at the end of study or early withdrawal visit.
All subjects must satisfy the following inclusion criteria to be eligible for the study:
* Provision of written informed consent prior to any study related procedures.
* Between 18 and 80 years of age, inclusive.
* Only one clinically defined stroke episode (as defined by the World Health Organization (WHO) criteria) or one traumatic brain injury, or subjects who had a nonevolutive lesion diagnosed prior to the stroke and in the same hemisphere as shown by brain imaging (i.e. scan or MRI).
* At least 6 months post-stroke or traumatic brain injury with hemiparesis..
* Modified Ashworth Scale (MAS) score >=2 in the primary targeted muscle group for toxin naive subjects or MAS score >=3 in the primary targeted muscle group for toxin non-naive subjects at least 4 months after the last BTX injection, of any serotype.
* Disability Assessment Scale (DAS) score >=2 on the PTT.
* Spasticity angle (measured on the TS) >= 10[Degrees] in the primary targeted muscle group.
* Modified Frenchay Scale (MFS) overall score (average of all task scores) between 1 and 8 (including limit values).