A phase III, prospective, multicenter, open label, extension study, to assess the long term safety and efficacy of repeated treatment of Dysport intramuscular injection in the treatment of lower limb spasticity in adult subjects with spastic hemiparesis due to stroke or traumatic brain injury.
Subjects requiring treatment at the end of the double blind (DB) study will receive a maximum of four treatment cycles occurring at intervals of 12 to 24 weeks, depending on the efficacy and safety response of each subject. The first open label treatment cycle should start on the same day as the last follow up visit (Week 12, Week 16, Week 20 or Week 24) of the DB study. The last treatment cycle will end once the total follow-up duration (including the treatment cycle in the DB study) reaches 12 months, but not before the Week 12 visit of the last treatment cycle in this open label study. Subjects who do not require treatment at the end of the DB study, will enter an observational phase of this open label 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, calculated from the start of the DB study. When the retreatment criteria are met, the subject(s) will receive Treatment Cycle 1 in this open label study.
at Treatment Cycle 1 of this open label study, all subjects will receive 1500 u of Dysport. Subjects who would have experienced an ae in the double-blind study that, in the opinion of the investigator, would pose an unacceptable risk, were the subject to continue receiving Dysport 1500u, will receive Dysport 1000u or be withdrawn from the study.
at Treatment Cycles 2, 3 and 4, subjects will receive Dysport injections as described in the study treatment section. Following each treatment cycle in this open label study, all subjects will attend follow up visits at Week 4, and Week 12 and potentially at Week 16, Week 20 and Week 24.
at the Week 24 follow up visit of Treatment Cycle 1 or 2 subjects will have follow up visits every 4 weeks until a new treatment cycle is required or he/she reaches 12 months follow up calculated from the start of the DB study but not less than 12 weeks following the last treatment. if subjects were unable to receive four injections in the open label study, within the 12 month study period (including the DB study), but have received at least three injections they will be eligible to receive the fourth injection no later than Week 16 of Treatment Cycle 3.
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 after the Week 4 visit of any treatment cycle.
adverse events (aes)
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 (hematology and clinical chemistry)
Presence of Botulinum Toxin Type a antibodies 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 eCG performed at Day 1 of Treatment Cycle 1, Week 4 of each treatment cycle and at the end of study or early withdrawal
Mean change from baseline in the muscle tone measured in the Gastroc-soleus complex GSC) and soleus muscle
Proportion of subjects with at least one grade reduction in the muscle tone (MaS) measured in the GSC and the soleus muscle
Mean Physician's Global assessment score
Mean change from baseline in the 10 meter comfortable and maximal walking speed test (WST) with shoes and barefoot and without walking aids: walking speed, step length and cadence
Mean change from baseline in spasticity (Tardieu Scale - TS) measured in the GSC and soleus muscle
Mean change from baseline in the range of active ankle dorsiflexion, both with the knee flexed (90[Degrees]) and with the knee extended
Mean change from baseline in lower limb pain
Change from baseline in the use of walking aids/orthoses
Mean change from baseline in Quality of life scales
Mean change from baseline in muscle tone (MaS) measured in each of the injected upper limb muscle groups
* Completion of the double blind study (Study 140) up to the Week 12, Week 16, Week 20 or Week 24 follow up visit, without major protocol deviation in the double blind study (Study 140) and/or any ongoing AEs (either of which, in the opinion of the Investigator, would pose an unacceptable risk to the subjects were he/she to continue receiving treatment) in this open label study.
* Provision of written informed consent for this open label study prior to administration of study treatment.