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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021740 |
E.1.2 | Term | Infantile cerebral palsy |
E.1.2 | System Organ Class | 100000004850 |
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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 |
to evaluate whether injections of BoNT-A in the calf muscles (mm. gastrocnemius and soleus) make walking easier in children with cerebral palsy within a time span of 6 months. |
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E.2.2 | Secondary objectives of the trial |
to evaluate whether an improvement in energy cost during walking is associated with less pain, increased daily activity and perceived improved performance and satisfaction. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Eligible to participate in the study are children and adolescents with spastic cerebral palsy referred to the out-patient clinics at the participating sites and regional partners, for injection of BoNT-A in the calf muscles.
All of the following conditions must apply to the prospective patient at screening prior to receiving study agent (e.g.):
• Diagnosed with unilateral or bilateral CP in their medical record
• GMFCS level I and II
• Must be at least 4 years of age.
• Spasticity in the calf muscles, clinically judged as grade 2 or 3 (the presence of a spastic catch) according to the Tardieu Scale.
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations. |
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria:
• BoNT-A injections in the lower limbs in the last 6 months before intervention
• History of adverse reactions to BoNT-A
• Known hypersensitivity to BoNT-A or to any of the excipients
• Orthopedic surgery in the lower limbs in the last 2 years
• Major cognitive impairments (must be able to take verbal instructions and conduct the test procedure)
• Presence of infection at the proposed injection site(s)
• Subclinical or clinical evidence of defective neuromuscular transmission e.g. myasthenia gravis or Lambert-Eaton Syndrome in patients with peripheral motor neuropathic diseases (e.g. amyotrophic lateral sclerosis or motor neuropathy) or other underlying neurological disorders that may be affected by BoNT-A injections
• Pregnant or breast-feeding
• Childbearing potential not using contraception
• Any reason why, in the opinion of the investigator, the patient should not participate
• Children in need for deep sedation under treatment. Children receiving concurrent injections in the upper limbs where deep sedation is standard procedure, are not excluded |
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E.5 End points |
E.5.1 | Primary end point(s) |
energy cost during walking, measured during a 5-minutes submaximal Walk Test (5MWT) at a self-chosen velocity with simultaneous gas-exchange measurements |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at baseline, 4, 12, 24 weeks |
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E.5.2 | Secondary end point(s) |
1. Habitual activity, measured by a body worn accelerometer over a period of 7 consecutive days during three time periods.
2. Mobility, measured by the Functional Mobility Scale (FMS). Through an interview, the FMS measures mobility over three distinct distances in order to represent mobility at home (5 meters), at school (50 meters) and in the wider community (500 meters) (30). The FMS captures walking performance or what the child usually does in his/her usual environment.
3. Perceived change in performance and satisfaction, measured by the Canadian Occupational Performance Measure (COPM). The COPM is used to detect changes in self-perceived activity performance in the areas of self-care, productivity (i.e., school), and leisure. The instrument is administered as semi-structured interviews that focuses on activities that the participants want, need, or are expected to perform.
4 Recurrent musculoskeletal pain, measured by the two questions on pain from Child Health Questionnaire (Norwegian version) and elements from Brief Pain Inventory
5 Fatiguability measured by the OMNI rating of perceived exertion scale (OMNI-RPE) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at baseline, 4, 12, 24 weeks |
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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 | 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 | 2 |
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 | 4 |
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 | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |