E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spasticity due to cerebral palsy (CP) or traumatic central nervous system injury. |
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E.1.1.1 | Medical condition in easily understood language |
Cerebral Palsy or head injury leading to tightness of the muscles (spasticity) |
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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 | PT |
E.1.2 | Classification code | 10028335 |
E.1.2 | Term | Muscle spasticity |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 assess the efficacy of Sativex on spasticity in a population of children and adolescents aged from 8 to 18 years with CP or traumatic central nervous system injury. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of Sativex compared to placebo in a population of children and adolescents aged from 8 to 18 years with CP or traumatic central nervous system injury.
To assess the efficacy of Sativex compared to placebo on change in spasticity, sleep quality, pain, quality of life (of the caregiver), comfort and the caregiver’s global impression of change.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males and females aged between 8 and 18 years suffering from Cerebral Palsy or traumatic central nervous system injury.
• Participant and/or authorised representative is willing and able to give informed consent for participation in the study.
• Participant is able (in the investigators opinion) and willing to comply with all study requirements.
• Participant has received inadequate efficacy and/or experienced unacceptable side effects from previous or current treatment with at least one of the following medications for spasticity:
Baclofen, Diazepam (or another benzodiazepine) Dantrolene, Tizanidine, Gabapentin, Trihexyphenidyl.
• Gross Motor Function Classification Scale (GMFCS) Level III – V.
• MAS of two or higher in at least one muscle group. |
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E.4 | Principal exclusion criteria |
• Any known or suspected history of:
o Schizophrenia or other psychotic illness, or diagnosis of schizophrenia in a first-degree relative.
o Alcohol or substance abuse.
• Participants who have received an IMP within the 12 weeks prior to the screening visit.
• Any other significant disease or disorder, which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, may influence the result of the study, or the participant’s ability to participate in the study.
• Following a physical examination, the participant has any abnormalities that, in the opinion of the investigator would prevent the participant from safe participation in the study.
• Unwilling to abstain from donation of blood during the study.
• Hypersensitivity to cannabinoids or any of the excipients of the IMP.
• Significant cardiac, renal or hepatic disease.
• Weight less than 15 kg.
• Has been treated with botulinum toxin in the previous 12 weeks.
• Concomitant use of botulinum toxin.
• Planned surgical procedure during the randomised phase of the study.
• Travel outside the country of residence planned during the study.
• Participants previously randomised into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Spasticity NRS (0 - 10). This will be entered into the participant’s diary which is to be completed daily throughout the randomised study period, and weekly throughout the open-label phase. The endpoint for analysis will be the comparison between Sativex and placebo in the change in NRS from baseline to the end of the acute phase (Week 12 or last 7 days prior to withdrawal). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluated daily in a diary for the first 12 weeks and weekly in a diary for the following 24 weeks. |
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E.5.2 | Secondary end point(s) |
- Modified Tardieu Scale (MTS) score of the most affected limb
- Modified Ashworth Scale (MAS) score of the main muscle groups
- Sleep quality*
- Paediatric Pain profile (PPP)
- Change in comfort*
- Caregiver QOL questionnaire
- Caregiver Global Impression of Change (CGIC)
Safety endpoints (AEs, laboratory parameters and vital signs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluated at each assessment visit (Day -7; 0; 28; 56; 84; 140; 196 and 252) or assessed on a daily or weekly basis in the diary (*). |
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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 | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Israel |
United Kingdom |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |