Phase III, multicentre study assessing the long term safety and efficacy of repeated treatments with Dysport in the treatment of arm spasticity in adult patients with hemiparesis.

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2010-019162-83-BE
• Date of registration: 07/04/2011
• Prospective Registration: Yes
• Primary sponsor: Ipsen Innovation
• Public title: Phase III, multicentre study assessing the long term safety and efficacy of repeated treatments with Dysport in the treatment of arm spasticity in adult patients with hemiparesis.
• Scientific title: 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
• Date of first enrolment: 07/06/2011
• Target sample size: 228
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019162-83
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1

Countries of recruitment

Belgium, Czech Republic, Hungary, Italy, Poland, Russian Federation, Slovakia, United States

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects who have completed the double blind study (Study 145) up to the Week 12, Week 16, Week 20 or Week 24 follow up visit will be eligible for this open label extension study.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 103

Exclusion criteria:
• Major limitation in the passive ROM at the affected wrist, fingers and elbow, as defined by:
o Maximum passive elbow extension <150º (0º corresponding to the minimal stretch of the elbow flexors, which corresponds to a fully flexed elbow position).
o Maximum passive wrist extension <70º (0º corresponding to the minimal stretch of the wrist flexors, which corresponds to a fully flexed wrist position).
o Maximum passive finger extension <70º (0º corresponding to the minimal stretch of the extrinsic finger flexors, which corresponds to a formed fist with the second phalanx parallel to the metacarpal).
• Previous surgery to treat spasticity on the affected muscles and ligaments, tendons, nerve trunks or bones of the treated upper limb.
• Previous treatment with phenol and/or alcohol in the treated upper limb anytime before the study.
• Any medical condition (including severe dysphagia or airway disease) that may increase, in the opinion of the Investigator, the likelihood of AEs related to botulinum toxin (BTX) treatment.
• Major neurological impairment other than spastic paresis (including major proprioceptive ataxia or apraxia on the paretic side) that could negatively impact on the functional performance of the subject.
• Known disease of the neuromuscular junction (such as Lambert Eaton myasthenic syndrome or myasthenia gravis).
• Inability to understand protocol procedures and requirements which, in the opinion of the Investigator, could negatively impact on protocol compliance.
• Known sensitivity to BTX or any excipients of Dysport.
• Infection at the injection site(s).
• Unwillingness or inability to comply with the protocol.
• 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.
• Pregnant women, or premenopausal women not willing to use contraceptive measures throughout the duration of the study.
• Treatment with a new investigational drug in the 4 weeks prior to enrolment into the study or scheduled to receive such a drug during the study period.
• Any underlying disease (not associated with the stroke or brain trauma) likely to affect upper limb function and/or muscle tone and/or spasticity.
• Any medical condition (or laboratory finding), which in the opinion of the Investigator may compromise compliance with the objectives and/or procedures of this protocol or preclude the administration of BTX.
• Subjects treated or likely to be treated with intrathecal baclofen
during the course of the study


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Arm spasticity
MedDRA version: 14.1 Level: LLT Classification code 10048970 Term: Arm spasticity System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: DYSPORT™ for Injection
Pharmaceutical Form: Powder for solution for injection
CAS Number: 93384-43-1
Other descriptive name: BOTULINUM TOXIN TYPE A
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Primary end point(s): Safety Endpoints:
•Adverse events (AEs)
•Vital signs (systolic and diastolic BP and HR)
•Clinical laboratory parameters (haematology and clinical chemistry)
•Presence of BTX A Abs
•A 12 lead ECG

Timepoint(s) of evaluation of this end point: • Adverse events (AEs) at each study visit.
• Vital signs (systolic and diastolic BP and HR) at Day 1 of Treatment Cycle 1 and at each study visit.
• Clinical laboratory parameters (haematology and clinical chemistry) 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 ECG at Day 1 of Treatment Cycle 1, Week 4 of each treatment cycle and at the end of study or early withdrawal.

Secondary Objective: The secondary study objective is to assess the long term efficacy of repeated treatment with Dysport

Main Objective: The primary study objective is to assess the long term safety of Dysport in hemiparetic subjects with upper limb spasticity due to stroke or traumatic brain injury over repeated treatment cycles.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The study visits considered for the analysis of the efficacy endpoints (with the exception of QoL) will be Week 4, Week 12 and potentially Week 16, Week 20 and Week 24 of each treatment cycle. The study visit considered for the analyses of the QoL will be the end of the study or early withdrawal.

Secondary end point(s): In all of the following endpoints, the baseline is defined as the baseline in the double blind study.
• Mean change from baseline in the MAS in the primary targeted muscle group.
• Mean change from baseline in the MAS in the following muscle groups: shoulder extensors, elbow flexors and pronators, wrist flexors and extrinsic finger flexors in subjects injected in these muscle groups and having a baseline MAS score =2.
• Proportion of subjects with at least one grade decrease from baseline on the MAS in the primary targeted muscle group.
• Mean PGA score.
• Mean change from baseline in the Principal Target of Treatment (PTT) of the DAS.
• Mean change from baseline in the MFS overall score (i.e. mean score over the 10 tasks).
• 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.
• Mean change from baseline in the TS in the primary targeted muscle group (spasticity grade, angle of catch and spasticity angle).
• Mean change from baseline in the TS in the shoulder extensors, elbow flexors and pronators, wrist flexors and extrinsic finger flexors in subjects injected in these muscle groups and with a baseline spasticity angle >10º (spasticity grade, angle of catch and spasticity angle).
• Mean change from baseline in the active ROM 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 and European QoL 5 Dimensions scales.

Secondary ID(s)

Y5252120148

Source(s) of Monetary Support

Ipsen Innovation