A phase III, multicentre, double blind, prospective, randomised, placebo controlled study, assessing the efficacy and safety of Dysport used for the treatment of lower limb spasticity in adult subjects with hemiparesis due to stroke or traumatic brain injury.
This is a phase III, multicentre, randomized, placebo controlled, single treatment cycle, double blind study.
Given the study design, three arms will be considered: Dysport 1000 U, Dysport 1500 U and placebo. The Sponsor[Right Quote]s Randomization Manager who is a statistician independent from the study will prepare:
- The List A: a list of randomization numbers produced on a balanced ratio [one placebo, one Dysport 1000 U, and one Dysport 1500 U] and stratified between Botulinum toxin naive or non naive subjects at baseline.
- The list B: a list of [Double Quote]treatment number / treatment[Double Quote] which will be dispatched to the sites, and also produced on a balanced ratio basis [one placebo, one Dysport 1000 U, and one Dysport 1500 U].
The treatment arm allocation as well as the treatment numbers to be supplied at Cycle 1 will be managed by an Interactive Voice Response System (IVRS) service. Any subject meeting the randomization criteria will be assigned to a randomization number in his(her) stratum and allocated to the associated treatment arm. A treatment number associated to this treatment arm will be then allocated to the subject and the treatment corresponding will be administered to the subject.
All subjects are planned to have a single treatment cycle. All subjects receiving treatment (Day 1) are expected to be followed for a minimum of 12 weeks and a maximum of 24 weeks. All subjects who have had at least a 12 week follow up will be considered to have completed the study. Subjects will be randomized into one of the treatment groups (Dysport 1000 U, 1500 U or placebo) in a ratio of 1:1:1.
Primary efficacy endpoint:
* Mean change from baseline in the muscle tone measured in the Gastroc Soleus Complex (GSC) on the Modified Ashworth Scale (MAS) at Week 4
Secondary efficacy endpoints:
The following secondary efficacy endpoints will be assessed:
* Mean Physicians Global Assessment (PGA) score at Week 4
* Mean change from baseline in comfortable barefoot walking speed without walking aids at Week 4
Tertiary efficacy endpoints
The following tertiary efficacy endpoints will also be assessed at Week 1 (except QoL and the PGA of treatment response), Week 4 (for endpoints not assessed as primary or secondary ones), Week 12 and potentially Week 16, Week 20 and Week 24:
* Mean change from baseline in the muscle tone (MAS) measured in the GSC
* Mean change from baseline in the muscle tone (MAS) measured in the soleus muscle
* Mean PGA Score
* Proportion of subjects with at least one grade reduction in the muscle tone (MAS) measured in the GSC and the soleus muscle
* Mean change from baseline in the comfortable barefoot walking speed (WS)
* Mean change from baseline in the comfortable WS with shoes
* Mean change from baseline in the maximal WS with shoes
* Mean change from baseline in the maximal barefoot WS
* Mean change from baseline in spasticity Tardieu Scale (TS) measured in the soleus and gastrocnemius muscles with the knee extended (angle of catch, spasticity angle and spasticity grade)
* Mean change from baseline in spasticity (TS) measured in the soleus muscle with the knee flexed (angle of catch, spasticity angle and spasticity grade)
* Mean change from baseline in step length and cadence under the following conditions:
− Comfortable speed with shoes
− Comfortable speed barefoot
− Maximal speed with shoes
− Maximal speed barefoot
* Mean change from baseline in th
• Provision of written informed consent prior to any study related procedures.
• Subjects with hemiplegia and who are between 18 and 80 years of age
• Subjects who had only one clinically defined stroke episode, as defined by the World Health Organization (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).
• Toxin naïve subjects who have a Modified Ashworth Scale (MAS) score ≥ 2 in the affected Gastroc-Soleus Complex (GSC) (knee extended) or toxin non naïve subjects who have a MAS score ≥ 3 in the affected GSC (knee extended) at least four months after the last injection of Botulinum toxin (BTX) in the lower limb affected. Please note that for the purpose of this protocol, a naïve subject is defined as a subject who has never received any BTX in the affected lower limb.
• Ambulatory subjects with spastic hemiparesis that causes a gait deficiency with a comfortable barefoot walking speed between 0.1m/s and 0.8m/s at baseline as measured on a 10-metre comfortable Walk Speed Test (WST) without walking aids.
• Subjects who are at least 6 months post-stroke or post-brain trauma.
• Spasticity angle ≥ 5° for the GSC of the affected leg as measured by the Tardieu Scale (TS) (knee extended).