E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with hereditary spastic paraparesis (HSP) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019903 |
E.1.2 | Term | Hereditary spastic paraplegia |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to investigate whether optimal dosages of BTX-A, injected bilaterally in the spastic lower leg muscles of patients with HSP (750 U Dysport® in each dorsal muscle group), can improve their dynamic balance capacity while preserving or improving their capacity to ambulate. Dynamic balance is selected as the primary outcome, because clinical experience indicates that, above all, balance problems determine the incapacity to perform basic skills such as standing, turning and making transfers as well as various gait skills. |
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E.2.2 | Secondary objectives of the trial |
A secondary objective is to better understand through what mechanisms functional balance and gait (at the ICF level of (dis)abilities) are optimized and how such functional improvements are associated with changes in spasticity and voluntary force at the level of the muscles (ICF level of impairments). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- diagnosis based on molecular diagnosis (e.g. SPG-4 mutations) - age between 18 and 70 years - disabling bilateral calf muscle spasticity (including clonus) without excessive passive stiffness or contracture (i.e. Modified Ashworth Scale 1-3 / 5) - comfortable walking speed greater than 1 km/hr (using a 10m walking test) - being able to stand and walk for 10m without aids
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E.4 | Principal exclusion criteria |
- impaired tactile and joint motion perception, or cerebellar signs, suggesting ‘complicated’ HSP - other disorders of the neuro-musculo-skeletal system - prior treatment with botulinum toxin or neurolysis of the lower limbs within 6 months - unwillingness or impossibility to keep any oral spasmolytic drugs constant - severe (> 15 degrees) contracture at the knees or hip joints - being unable to load the heels while standing with extended knees (due to ankle contracture) - pregnancy - addiction to drugs or alcohol - any inability to cooperate with the assessments and to give written informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
Dynamic balance is selected as the primary outcome, because clinical experience indicates that, above all, balance problems determine the incapacity to perform basic skills such as standing, turning and making transfers as well as various gait skills. Therefore, the primary outcome is expressed as the success rate after external perturbations, i.e. the percentage of successful trials during which upright standing can be maintained without making a step or grabbing for support. |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |