Dysport LowerLimb-Double Blind (140)

Overview

Status: Recruiting
Keywords: Spasticity , Stroke , TBI
IRB Number: 00048709
Specialty: Physical Medicine and Rehabilitation, Physical Medicine and Rehabilitation, Physical Medicine and Rehabilitation
Sub Specialties: Spasticity Management, Stroke , Traumatic Brain Injury

Brief Summary

Dysport has been investigated in a number of studies of upper and lower limb spasticity of various etiologies in adults and in children. In these studies improvements in spasticity and muscle tone were observed in targeted muscles. Dysport is licensed in over 75 countries for various indications including the treatment of adult lower limb spasticity. The maximum dose for this indication is 1500 U.
 
A prospective, single treatment cycle, multinational, multicentre, placebo controlled, dose-ranging study was conducted in adult subjects with spastic equinovarus deformity of the foot using three doses of Dysport (500 U, 1000 U, 1500 U) and injecting the gastrocnemius-soleus complex (GSC). The greatest benefits on muscle tone (MAS) were observed in subjects receiving the 1500 U Dysport dose. Improvement in pain and dependence on walking aids was also reported in the 1500 U Dysport treatment groups as compared to placebo. All three doses of Dysport were well tolerated, with a similar number of subjects reporting adverse events in all groups including placebo.
 
The present Phase III, double blind, single treatment cycle, multicentre, prospective, randomized, placebo controlled study has been designed to assess the efficacy of Dysport for the treatment of lower limb spasticity in adult subjects with hemiparesis due to stroke or traumatic brain injury. Effects on the GSC muscle tone will be assessed as primary criterion, the Physician Global Assessment of treatment response and the comfortable barefoot walking speed will be considered as secondary endpoints. Both the efficacy and safety profile of Dysport administered at 1000 U and 1500 U will be compared to placebo. Long-term safety and efficacy will be assessed in an open label extension study for all eligible subjects (IRB#50826).
 

 

Principal Investigator: Steven Edgley
Department: Physical Medicine & Rehab
Co Investigator:

Contact Information

Name:Jacob Smith
Phone: 801-581-5328
Email: Jacob.Smith@hsc.utah.edu

Inclusion Criteria

All subjects must fulfil the following:

(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 only 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) Toxin naïve subjects who have a MAS score 2 in the affected 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 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.

(5) Ambulatory subjects with spastic hemiparesis that causes a gait deficiency with a comfortable barefoot walking speed between 0.1 m/s and 0.8 m/s at baseline as measured on a 10-metre comfortable WST without walking aids.

(6) Subjects who are at least 6 months post-stroke or post-brain trauma.

(7) Spasticity angle ≥5° for the GSC of the affected leg as measured by the TS (knee extended).

Exclusion Criteria

Subjects will not be included in the study if any of the following are present/apply:

(1) Major limitation in the passive range of motion at the affected hip, knee or ankle, as defined by:

- maximum passive hip flexion (knee flexed) <30°,

- maximum passive knee flexion (hip flexed) <70°,

- maximum passive ankle dorsi flexion (knee flexed) <-10°,

- maximum passive knee extension <160°.

(2) Physiotherapy initiated less than 4 weeks before entry or expected to be initiated during the trial.

(3) Previous treatment with BTX of any type within four months prior to study entry for any condition.

(4) Subjects likely to be treated with BTX of any type in the upper limb during the course of this double blind study.

(5) Previous primary or secondary non responder to any BTX treatment for the targeted condition.

(6) Previous surgery to treat spasticity of the affected lower limb.

(7) Previous treatment with phenol and/or alcohol in lower limb at any time before the study.

(8) Cognitive impairment altering the capacity to comply with the trial according to Investigator’s judgement.

(9) Severe neurological impairment (not associated with the stroke or brain trauma) due to an underlying neuromuscular disease or any other underlying disease or condition affecting gait (e.g. Multiple Sclerosis).

(10) Known disease of the neuromuscular junction (such as Lambert-Eaton disease or myasthenia gravis).

(11) Unwillingness or inability to comply with the protocol.

(12) Major hypoaesthesia or ataxia on the paretic side.

(13) Known sensitivity to BTX or any Dysport excipients.

(14) Infection at the injection site(s).

(15) Current or planned treatment with any drug that interferes either directly or indirectly with neuromuscular function (e.g. aminoglycosides) within the last 4 weeks prior to study treatment.

(16) Pregnant women, or pre-menopausal women that are not willing to use contraceptive measures throughout the duration of the study.

(17) Treatment with a new investigational drug within 4 weeks prior to enrolment into the study or scheduled treatment with such a drug during the study period.

(18) Any medical condition (or laboratory finding), that in the opinion of the Investigator may compromise compliance with the objectives and/or procedures of this protocol or preclude the administration of BTX.

(19) Subjects treated or likely to be treated with intrathecal baclofen during the course of the study or during the 4 weeks before study entry.