A phase III, placebo controlled clinical trial to assess efficacy and safety of one dose of Dysport solution in the treatment of upper limb spasticity in adults after stroke

• Register: EUCTR
• Last refreshed on: 21 August 2023
• Main ID: EUCTR2015-000554-38-CZ
• Date of registration: 21/05/2015
• Prospective Registration: Yes
• Primary sponsor: Ipsen Innovation
• Public title: A phase III, placebo controlled clinical trial to assess efficacy and safety of one dose of Dysport solution in the treatment of upper limb spasticity in adults after stroke
• Scientific title: A Phase III, Multicenter, Double Blind, Randomised, Placebo Controlled Study to Assess the Efficacy and the Safety of a Single Cycle of Dysport Solution in the Treatment of Upper Limb Spasticity in Adult Subjects with Spastic Hemiparesis due to Stroke
• Date of first enrolment: 20/08/2015
• Target sample size: 93
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000554-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, Italy, Slovakia

Contacts

• Name: Global Drug Development
• Affiliation: Ipsen Innovation

• Name: Global Drug Development
• Affiliation: Ipsen Innovation

Key inclusion & exclusion criteria

Inclusion criteria:
1.Provision of written informed consent prior to any study related procedures.
2.Male or female subjects between 18 and 80 years of age, inclusive.
3.Subjects with spastic hemiparesis, who had only one clinically defined stroke episode.
4.Subjects who are at least 6 months post-stroke.
5.Subjects who have a MAS score =2 in the primary targeted muscle group (PTMG) for toxin-naive subjects (never received any Botulinum toxin [BTX] in the affected upper limb) or =3 in the PTMG for toxin non-naive subjects.
6.Spasticity angle (X of the Tardieu scale) =10° in the PTMG
7.Female subjects of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 90 days after participation in the study. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device, or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
8.Subjects must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow-up evaluation as specified in the protocol.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 43
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1.Major limitation in the passive ROM (XV1 of the Tardieu scale) at the affected elbow, wrist, and fingers, as defined by:
•Maximum passive elbow extension <150° (0° corresponding to the minimal stretch of the elbow flexors, which corresponds to a fully flexed elbow position)
•Maximum passive wrist extension <70° (0° corresponding to the minimal stretch of the wrist flexors, which corresponds to a fully flexed wrist position)
•Maximum passive finger extension <70° (0° corresponding to the minimal stretch of the extrinsic finger flexors, which corresponds to a formed fist with the second phalanx parallel to the metacarpal)
2.Subjects treated with BTX of any type within four months prior to study entry for any condition.
3.Subjects who have experienced remote spread of effect of previous treatment with BTX (including generalized muscle weakness).
4.Subjects likely to be treated with BTX of any type during the course of this study.
5.Previous primary or secondary non-response to any BTXs for the targeted condition.
6.Previous surgery to treat spasticity of the affected upper limb.
7.Previous treatment with phenol and/or alcohol in the affected upper limb at any time before the study.
8.Subjects treated or likely to be treated with intrathecal baclofen during the course of the study or during the 4 weeks before study entry.
9.Physiotherapy initiated less than 4 weeks before entry or expected to be initiated during the study in the affected upper limb.
10.Any medical condition (including severe dysphagia or airway disease) that may increase, in the opinion of the Investigator, the likelihood of Adverse Events related to BTX treatment.
11.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.
12.Known disease of the neuromuscular junction (such as Lambert Eaton myasthenic syndrome or myasthenia gravis).
13.Known sensitivity to BTX or any component of Dysport Solution.
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.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.
17.Any underlying disease (not associated with the stroke) likely to affect upper limb function and/or muscle tone and/or spasticity.
18.Is pregnant or lactating. A pregnancy test will be performed at the start of the study for all female subjects of childbearing potential (i.e. not surgically sterile or 2 years postmenopausal).
19.Has a history of, or known current, problems with substance or alcohol abuse.
20.Has any mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
21.Has any other medical condition(s) that, in the opinion of the investigator, might jeopardise the subject’s safety.



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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

upper limb spastic hemiparesis due to stroke
MedDRA version: 18.0 Level: LLT Classification code 10058978 Term: Spastic hemiparesis System Organ Class: 100000004852

Intervention(s)

Product Name: Dysport Solution
Product Code: BTX-A-HAC NG
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CLOSTRIDIUM BOTULINUM TOXIN TYPE A
CAS Number: 93384-43-1
Current Sponsor code: BTX-A-HAC
Other descriptive name: BOTULINUM TOXIN A - HAEMAGGLUTININ COMPLEX
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Secondary Objective: The secondary study objective is the assessment of efficacy after one treatment cycle of Dysport Solution 1000 U compared to placebo on:
•The Physician’s Global Assessment (PGA) of treatment response.
•The spasticity using the Tardieu Scale (TS)
•The active range of motion (ROM) against the upper limb muscles
•The passive/perceived function using the Disability Assessment Scale (DAS)
•A subject assessment of treatment response using a Visual Analog Scale (VAS)
•The active upper limb function using the Box and Block test (BBT)
The safety of Dysport Solution will also be assessed.

Primary end point(s): •Modified Ashworth Scale (MAS) raw score in the PTMG which can be elbow flexors, wrist flexors or extrinsic finger flexors

Main Objective: To assess the efficacy of Dysport Solution 1000 U compared to placebo in reducing the upper limb muscle tone (using the Modified Ashworth Scale (MAS)) in adult subjects with upper limb spastic hemiparesis due to stroke after one treatment cycle.

Timepoint(s) of evaluation of this end point: Week 4

Secondary Outcome(s)

Secondary end point(s): •Change from baseline in the MAS score in the PTMG
•Number of subjects with a reduction of at least 1 grade on MAS score in PTMG.
•Number of subjects with a reduction of at least 2 grades on MAS score in PTMG.
•Change from baseline in the MAS score in shoulder extensors, elbow flexors, wrist flexors, and extrinsic finger flexors.
•PGA score of treatment response.
•Number of subjects reaching at least the grade +1 on the PGA.
•Change from baseline in the TS parameters in the shoulder extensors, elbow flexors, wrist flexors, and extrinsic finger flexors.
•Change from baseline in the active ROM in the shoulder extensors, elbow flexors, wrist flexors, and extrinsic finger flexors.
•Number of subjects with a decrease from baseline of at least one grade in each of the 4 domains of the DAS scale.
•Subject assessment of treatment response (VAS).
•Change from baseline in performance of the BBT.
Safety:
•Adverse events throughout the study after signature of the Informed Consent form.
•Vital signs (sitting systolic and diastolic blood pressure and heart rate)

The safety endpoints are:
•Adverse events throughout the study, after the signature of the Informed Consent form.
•Vital signs (sitting systolic and diastolic blood pressure (BP) and heart rate (HR))

Timepoint(s) of evaluation of this end point: The study visits considered for the analyses of efficacy endpoints will be baseline, Week 4, Week 12 (end of study) or early withdrawal.
Vital signs at each study visit.

Secondary ID(s)

2015-000554-38-BE

D-FR-52120-221

Source(s) of Monetary Support

Ipsen Innovation

Ethics review

Status: Approved
Approval date: 20/08/2015
Contact:

Results

• Results available: Yes
• Date Posted: 24/07/2020
• Date Completed: 16/06/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000554-38/results