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] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048970 |
E.1.2 | Term | Arm spasticity |
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 study objective is to assess the efficacy of Dysport compared to placebo in reducing upper limb muscle tone in hemiparetic subjects with upper limb spasticity due to stroke or traumatic brain injury. The primary study objective will be assessed by comparing between treatment groups at Week 4 the change from baseline in muscle tone (using the Modified Ashworth Scale (MAS)) in the primary targeted muscle group. |
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E.2.2 | Secondary objectives of the trial |
The secondary study objectives include assessments of the efficacy of Dysport compared to placebo on:
• The Physician’s Global Assessment (PGA) of treatment response.
• The upper limb passive function using the Principal Target of Treatment (PTT) of the Disability Assessment Scale (DAS).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Provision of written informed consent prior to any study related procedures.
• Subjects with hemiparesis and aged between 18 and 80 years of age, inclusive.
• Subjects who had 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).
• At least 6 months post-stroke or post traumatic brain injury.
• Modified Ashworth Scale (MAS) score ≥2 in the primary targeted muscle group for toxin naïve subjects or MAS score ≥3 in the primary targeted muscle group for toxin non naïve subjects at least 4 months after the last BTX injection, of any serotype.
• Disability Assessment Scale (DAS) score ≥2 on the PTT.
• Spasticity angle (measured on the TS) ≥10° in the primary targeted muscle group.
• Modified Frenchay Scale (MFS) overall score (average of all task scores) between 1 and 8 (including limit values).
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E.4 | Principal exclusion criteria |
• Major limitation in the passive ROM at the affected elbow, wrist and fingers, as defined by:
o Maximum passive elbow extension <150° (0° corresponding to the minimal stretch of the elbow flexors, which corresponds to a fully flexed elbow position),
o Maximum passive wrist extension <70° (0° corresponding to the minimal stretch of the wrist flexors, which corresponds to a fully flexed wrist position),
o 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).
• Physiotherapy initiated less than 4 weeks before entry or expected to be initiated during the study.
• Previous treatment with BTX of any type within 4 months prior to study entry for any condition.
• Subjects likely to be treated with BTX of any type in the lower limb during the course of this double blind study.
• Previous primary or secondary non response to any BTXs for the targeted condition.
• Previous surgery to treat spasticity of the affected 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 adverse events (AEs) related to 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 excipient 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 (i.e. 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 traumatic brain injury) 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 or during the 4 weeks before study entry
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E.5 End points |
E.5.1 | Primary end point(s) |
• Modified Ashworth Scale (MAS) for rating muscle tone in the primary targeted muscle group. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Mean PGA Score
• Mean change from baseline in the PTT of the DAS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Mean PGA Score at Week 4.
• Mean change from baseline in the PTT of the DAS at Week 4.
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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 | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 | Information not present in EudraCT |
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 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 21 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 21 |