A Phase III, multicentre prospective, open label, extension study to assess the long term safety and efficacy of repeated treatment 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.

Study ID
STU 052011-156

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Cynthia Dolezal
214-648-2735
cindy.dolezal@utsouthwestern.edu

Principal Investigator
Fatma Gul

Summary

all subjects are planned to have a minimum of 6 months of follow up in this open label extension study. Subjects requiring treatment at the end of the double blind study will receive a maximum of four treatment cycles. The first open label treatment cycle should start on the same day as the end of study visit of the double blind study. The last treatment cycle will end once the total follow up duration reaches 12 months, and not before the Week 4 visit of the last treatment cycle in this open label extension study. Subjects who do not require treatment at the Week 24 follow up visit of the double blind study, will enter an observational phase of this open label extension study wherein they will have follow up visits every 4 weeks until they require retreatment or until they have completed at least 12 months of follow up. When the retreatment criteria are met, subjects will receive Treatment Cycle 1 in this open label extension study.

at Treatment Cycle 1 of this open label extension study, all subjects will receive 1000 u of Dysport. Subjects, who have experienced an ae in the double blind study which, in the opinion of the investigator, would pose an unacceptable risk, were they to receive Dysport 1000 u, will receive the Dysport 500 u dose or be withdrawn from the study.

From Treatment Cycle 2 onwards, subjects will receive Dysport injections as described the study treatment section. at each treatment cycle in this open label extension study, all subjects will attend follow up visits at Week 4 and Week 12 and potentially at Week 16, Week 20 and Week 24.

if physical therapy (PT) was ongoing prior to study entry, every effort should be made to maintain the same therapy regimen until the end of the study. However, in case of medical need, PT may be initiated or modified after the Week 4 visit of any treatment cycle.

Safety endpoints
* adverse events (aes) at each study visit.
* Vital signs at Day 1 of Treatment Cycle 1 and at each study visit.
* Clinical laboratory parameters at Day 1 of Treatment Cycle 1, Week 4 of each treatment cycle and at the end of study or early withdrawal.
* Presence of BTX-a-abs at Day 1 of Treatment Cycle 1, Week 4 of each treatment cycle and at the end of study or early withdrawal.
* a 12-lead electrocardiogram (eCG) at Day 1 of Treatment Cycle 1, Week 4 of each treatment cycle and at the end of study or early withdrawal.

efficacy endpoints
* Mean change from baseline in the Modified ashworth Scale (MaS) in the primary targeted muscle group.
* Mean change from baseline in the MaS in the following muscle groups: shoulder extensors, elbow flexors, wrist flexors and extrinsic finger flexors in subjects injected in these muscle groups and having a baseline MaS score [GreaterThanorequalTo]2.
* Proportion of subjects with at least one grade decrease from baseline on the MaS in the primary targeted muscle group.
* Mean Physicians Global assessment score.
* Mean change from baseline in the Principal Target of Treatment of the Disability assessment Scale (DaS).
* 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 [GreaterThanorequalTo]2 in the considered domain.
* Mean change from baseline in the Modified Frenchay Scale total score.
* Mean change from baseline in the Tardieu Scale in the primary targeted muscle group.
* Mean change from baseline in the TS in the shoulder extensors, elbow flexors, wrist flexors and extrinsic finger flexors in subjects injected in these muscle groups and with a baseline spasticity angle [Greater Than]10o.
* Mean change from baseline in the active Range of Motion against the primary targeted muscle group.
* Mean change from baseline in the ease of applying splints.
* Mean change from baseline in QoL measured on the Short Form (36) Health Survey (SF-36) and european QoL-5 Dimensions (eQ-5D) scales.

Participant Eligibility


* Completion of the double blind study (Study 145) up to the Week 12, Week 16, Week 20 or Week 24 follow up visit, without any major protocol deviation and/or any ongoing AEs, either of which, in the opinion of the Investigator would pose an unacceptable risk to the subjects were they to continue receiving treatment in this open label extension study.

* Provision of written informed consent form for this open label extension study prior to entry into this extension study.

De novo subjects must satisfy all of the following inclusion criteria to be eligible for the study:
(1) Provision of written informed consent prior to any study related procedures.
(2) Subjects with hemiparesis and aged between 18 and 80 years, inclusive.
(3) Subjects who had one clinically defined stroke episode, as defined by the World Health Organisation (WHO) criteria or who have had one brain trauma, 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).
(4) At least 6 months post-stroke or traumatic brain injury.
(5) 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. Please note that 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.
(6) Disability Assessment Scale (DAS) score >=2 on the PTT.
(7) Spasticity angle >=10[Degrees] in the primary targeted muscle group.
(8) Modified Frenchay Scale (MFS) overall score (average of all task scores) between 1 and 8 (including limit values).
(9) Subjects able to receive 1000 U in their upper limb at Treatment Cycle 1.