A phase III, prospective, multicentre, 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.

• Register: EUCTR
• Last refreshed on: 16 November 2015
• Main ID: EUCTR2009-017723-26-IT
• Date of registration: 29/03/2012
• Prospective Registration: No
• Primary sponsor: IPSEN PHARMA SAS
• Public title: A phase III, prospective, multicentre, 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.
• Scientific title: A phase III, prospective, multicentre, 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.
• Date of first enrolment: 29/04/2011
• Target sample size: 348
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017723-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1

Countries of recruitment

Belgium, Czech Republic, Hungary, Italy, Portugal, Russian Federation, United States

Contacts

• Name: Medical Development
• Affiliation: Ipsen Innovation

• Name: Medical Development
• Affiliation: Ipsen Innovation

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects who have completed the double blind study (Study 140), up to the Week 12, Week 16, Week 20 or Week 24 follow up visit, and who do not have 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) will be eligible for the study. Additionally, an informed consent for this open label extension study will be signed
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 191
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 157

Exclusion criteria:
Major limitation in the passive range of motion at the affected hip, knee or ankle, as defined by: ° maximum passive hip flexion (knee flexed) < 30º, ° maximum passive knee flexion (hip flexed) < 70º, ° maximum passive ankle dorsiflexion (knee flexed) < 10º, ° maximum passive knee extension < 160º. • Previous surgery on the affected muscles and ligaments, tendons or nerve trunks of the treated lower limb. • Previous treatment with phenol and/or alcohol in the treated lower limb at any time before the study. • Cognitive impairment altering the capacity to comply with the trial according to Investigator’s judgement. • 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 (for example, Multiple Sclerosis). • Known disease of the neuromuscular junction (such as Lambert Eaton myasthenic syndrome or myasthenia gravis). • Unwillingness or inability to comply with the protocol. • Major hypoaesthesia or ataxia on the paretic side. • Known sensitivity to Botulinum toxin (BTX) or any Dysport excipients. • Infection at the injection site(s). • Current or planned treatment with any drug that interferes either directly or indirectly with neuromuscular function (for example, 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 within 4 weeks prior to enrolment into the study or scheduled treatment with such a drug during the study period. • 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.


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

Health Condition(s) or Problem(s) studied

Leg Spasticity
MedDRA version: 14.1 Level: SOC Classification code 10029205 Term: Nervous system disorders 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
INN or Proposed INN: BOTULINUM TOXIN TYPE A
CAS Number: 93384-43-1
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Adverse events: throughout the study • Vital signs (systolic and diastolic BP and HR) 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 (haematology and clinical chemistry). • 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 performed 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 the assessment of the long term efficacy including: • Muscle tone in the gastrocnemius-soleus complex (GSC) (knee extended), • Muscle tone in the soleus muscle (knee flexed), • Physician’s Global Assessment (PGA) of treatment response, • Maximal and comfortable barefoot walking speeds, • Maximal and comfortable walking speeds with shoes, • Spasticity in the GSC (knee extended), • Spasticity in the soleus muscle (knee flexed), • Step length and cadence under different conditions, • Range of active ankle dorsiflexion, • Lower limb pain, • Quality of life (QoL), • Use of walking aids

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

Primary end point(s): Safety endpoints: • Adverse events. • Vital signs (systolic and diastolic BP and HR) • Clinical laboratory parameters (haematology and clinical chemistry). • Presence of BTX A Abs . The antibodies will be measured in serum samples, initially by screening radioimmunoprecipitation assay (RIPA). If RIPA is positive, the result will be confirmed by a competitive RIPA confirmatory assay. Samples positive for the presence of binding antibodies in both the screening and confirmatory RIPAs, will be analysed for the presence of neutralising antibodies using the mouse protection assay (MPA). • A 12 lead ECG performed - Efficacy endpoints: In all of the following endpoints, the baseline is defined as the baseline in the double blind study. • Mean change from baseline in the muscle tone (MAS) measured in the GSC (knee extended). • Mean change from baseline in the muscle tone (MAS) measured in the soleus muscle (knee flexed). • Proportion of subjects with at least one grade reduction in the muscle tone (MAS) measured in the GSC (knee extended). • Proportion of subjects with at least one grade reduction in the muscle tone (MAS) measured in the soleus muscle (knee flexed). • Mean PGA score. • Mean change from baseline in the 10 metre comfortable WST with shoes and without walking aids: walking speed, step length and cadence. • Mean change from baseline in the 10 metre maximal WST with shoes and without walking aids: walking speed, step length and cadence. • Mean change from baseline in the 10 metre comfortable WST barefoot and without walking aids: walking speed, step length and cadence. • Mean change from baseline in the 10 metre maximal WST barefoot and without walking aids: walking speed, step length and cadence. • Mean change from baseline in spasticity (TS) measured in the GSC with the knee extended (angle of catch (Xv3), spasticity angle (X) and spasticity grade (Y)). • Mean change from baseline in spasticity (TS) measured in the soleus muscle with the knee flexed (angle of catch (Xv3), spasticity angle (X) and spasticity grade (Y)). • Mean change from baseline in the range of active ankle dorsiflexion, both with the knee flexed (90°) 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 QoL scales. • Mean change from baseline in muscle tone (MAS) measured in each of the injected upper limb muscle groups.

Secondary Outcome(s)

Secondary end point(s): not applicable

Timepoint(s) of evaluation of this end point: not applicable

Secondary ID(s)

Y-55-52120-142

2009-017723-26-BE

Source(s) of Monetary Support

IPSEN PHARMA SAS