E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058978 |
E.1.2 | Term | Spastic hemiparesis |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess the responder rate as defined by the improvement of composite active range of motion (AROM) in the primary targeted limb, either upper limb (UL) or lower limb (LL), depending on which one has been selected as a primary treatment target (TT), following two consecutive AbobotulinumtoxinA injections combined with a Guided Self rehabilitation Contract (GSC) in subjects with spastic hemiparesis following acquired brain injury (ABI). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are as follows:
- to assess the effectiveness of AbobotulinumtoxinA combined with a GSC on:
- to assess subject satisfaction with regard to the use of a GSC
- to measure the changes in subject and physiotherapist beliefs that a GSC will help to improve function
- to assess subject compliance with the GSC
- to assess global benefits by both the investigator and the subject (or caregiver)
- in subjects not reinjected at Week 12, to assess satisfaction with longer than 12 weeks interval between 2 injections
- to assess health-related quality of life
- to assess safety parameters |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Subjects aged at least the national legal adult age.
2) Subjects with hemiparesis due to ABI (i.e. stroke or traumatic brain injury (TBI)) presenting with muscle overactivity impeding motor function based on investigator’s judgement including, but not limited to, at least one of the following requiring botulinum neurotoxin (BoNT) treatment: typical clenched fist; flexed wrist; flexed elbow; or plantar flexed foot pattern.
3) At least 12 months since the ABI.
4) Naïve or non-naïve to BoNT treatment; if non-naïve, at least 4 months after the last BoNT injection, of any serotype.
5) Upper limb active function with an overall score between 2 and 7, as assessed by MFS locally rated score, if the primary TT limb is the UL.
6) A 10-metre maximal WS barefoot between 0.2 and 1.4 m/s, if the primary TT limb is the LL. Maximal WS barefoot will be performed without walking aids. However, a cane may be permitted if absolutely necessary (although this may prevent detection of treatment-induced improvements). In this case, the same aid will have to be used for all WS assessments during the study.
7) Subjects must provide written informed consent to participate in the study prior to any study-related procedures.
8) 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 until the last visit of the subjects and for at least 12 weeks post injection. Acceptable methods of contraception include total abstinence, male partner has had a vasectomy, double barrier method (e.g. male condom plus spermicide, or female diaphragm plus spermicide), intrauterine device, or hormonal contraceptive (oral, transdermal, implanted and injected)..
9) 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 |
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E.4 | Principal exclusion criteria |
1) Inability to understand protocol procedures and requirements, which, in the opinion of the investigator, could negatively impact on protocol compliance, in particularly inability to exercise according to the GSC.
2) Previous surgery on the affected muscles and ligaments, tendons, nerve trunks, or bones of the treated upper or lower limb.
3) Previous treatment with phenol and/or alcohol in any of the treated limbs any time before the study.
4) Any medical condition (including severe dysphagia or breathing
difficulties) that may increase, in the opinion of the investigator, the likelihood of adverse events (AEs) related to BoNT A treatment.
5) Subjects treated, or likely to be treated, with intrathecal baclofen during the course of the study or during the 4 weeks before study entry.
6) Current, planned or received within the last 4 weeks prior to study treatment, treatment with any drug that interferes either directly or indirectly with neuromuscular function (for example, aminoglycosides).
7) 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.
8) Known disease of the neuromuscular junction (such as Lambert-Eaton myasthenic syndrome or myasthenia gravis).
9) Known sensitivity to BoNT-A or any excipient of Dysport.
10) Infection at the injection site(s).
11) Current pregnancy or lactation. 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).
12) Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
13) Abnormal baseline findings or any other medical condition(s) that, in the opinion of the investigator, might jeopardise the subject’s safety.
14) Subjects who have participated in any therapeutic clinical study/received any investigational agent within 30 days of enrolment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percentage of responder subjects at Week 6 after the second injection, according to composite AROM in the primary TT limb. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy endpoint is the percentage of responder subjects at Week 6 after the second injection, according to composite AROM in the primary TT limb. |
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E.5.2 | Secondary end point(s) |
The first secondary efficacy endpoints is the percentage of responder subjects at Week 6 after the first injection, according to composite AROM in the primary TT limb.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The first secondary efficacy endpoints is the percentage of responder subjects at Week 6 after the first injection, according to composite AROM in the primary TT limb. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Czech Republic |
France |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |