E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Upper limb spasticity in children |
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E.1.1.1 | Medical condition in easily understood language |
Upper limb spasticity (altered skeletal muscle performance) in children |
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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 | 20.0 |
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 two doses of Dysport (8 U/kg and 16 U/kg) compared to Dysport 2 U/kg used in the treatment of upper limb spasticity in children with CP following a single treatment. |
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E.2.2 | Secondary objectives of the trial |
The secondary study objective is to assess the long term safety of multiple treatments of Dysport used in this study population.
The tertiary study objectives will evaluate the long term efficacy of Dysport, its effect on pain in the study limb and quality of life (QoL) following multiple treatments.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
((1) Signed informed consent obtained from the child’s parent(s)/guardian(s) and, if applicable, a signed assent from the child. (2) Be from 2 to 17 years of age, inclusive. (3) Body weight of 10 kg or more at the baseline visit. (4) Have a diagnosis of CP, as defined by Rosenbaum. (5) Have increased muscle tone/spasticity in at least one upper limb. (6) Have a MAS score ≥2 in the upper limb primary targeted muscle group (elbow flexors or wrist flexors) of the study limb (the limb to be injected in the first treatment) at the baseline visit. (7) Be classified as Gross Motor Function Classification System Level 1 to 4. (8) If undergoing therapy, such as physiotherapy, occupational therapy, or use of splints and/or orthoses, therapy must have been initiated at least 30 days prior to the baseline visit and agreed to continue the therapy throughout the study and at the minimum, up to Week 16 following the first treatment administration.
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E.4 | Principal exclusion criteria |
(1) Fixed myocontracture in the primary targeted muscle group (elbow flexors or wrist flexors) of the study limb defined as having an available range of motion angle of <40°, regardless of the starting and finishing angles, measured at the Tardieu Scale (TS) slow (XV1) speed at the baseline visit. (Available range for wrist flexors should be measured without holding the fingers and allowing free finger flexion). (2) Subjects likely to be treated with BTX in the lower limb(s) and/or the nonstudy upper limb before Treatment 2 of the study. (3) Inadequate washout from previous BTX injection of any serotype for any condition: • Within 6 months prior to the baseline visit in the study limb, or • Within 3 months prior to the baseline visit in any other part of the body. (4) Subjects who require BTX treatment in a single muscle group in the study limb in Treatment 1. (5) Severe athetoid or dystonic movements in the study limb. (6) Previous or planned surgery for spasticity in the primary targeted muscle group(s) of the study limb. (7) Previous injection of alcohol and/or phenol within 1 year prior to the baseline visit affecting the study limb wrist flexors and/or elbow flexors selected for injection in Treatment 1. (8) Treatment with any drug that interferes either directly or indirectly with neuromuscular function (e.g. aminoglycoside antibiotics) or neuroblocking agents used during surgery (e.g. curare) within the last 30 days prior to study treatment. (9) Are pregnant and/or lactating. (10) Female subjects not willing to use contraceptive measures throughout the course of the study if postpubertal and sexually active. (11) Inability or unwillingness to comply with the protocol. (12) Subjects with any clinical (or sub-clinical) evidence of marked defective neuromuscular transmission (e.g. Lambert-Eaton syndrome or myasthenia gravis) or persistent clinically significant neuromuscular disorders. (13) Known sensitivity to BTX or to any of the components in the formulation or allergy to cow’s milk protein. (14) An infection at the injection site(s). (15) Previous rhizotomy less than 6 months prior to the baseline visit or rhizotomy planned/anticipated during the course of the study. (16) Subjects treated or likely to be treated with intrathecal baclofen within 30 days prior to the baseline visit or during the course of the study. (17) Treatment with a new investigational drug within 30 days prior to the baseline visit or scheduled to receive such a drug during the course of the study. (18) Subjects with a history of aspiration or conditions which put them at risk of aspiration, such as severe dysphagia. (19) Concurrent or history of frequent lower respiratory tract infections, aspiration pneumonia, or, as judged by the Investigator, has compromised respiratory function. (20) Any known medical condition, laboratory or diagnostic procedure finding, which might compromise compliance with the objectives and procedures of this protocol or preclude administration of botulinum toxin type A (BTX-A), as judged by the Investigator. (21) Any uncontrolled clinically significant medical condition other than CP. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: Mean change from Baseline to Treatment 1, Week 6 in MAS score in the Treatment 1 primary targeted muscle group (elbow flexors or wrist flexors). |
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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 at Treatment 1, Week 6. Mean GAS score at Treatment 1, Week 6. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
two doses of Dysport (8 units (U)/kg and 16 U/kg) compared to Dysport 2 U/kg |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Australia |
Brazil |
Bulgaria |
Chile |
Colombia |
Czech Republic |
France |
Georgia |
Israel |
Lithuania |
Mexico |
Poland |
Portugal |
Russian Federation |
South Africa |
Spain |
Turkey |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |