E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lower limb spasticity due to cerebral palsy |
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E.1.1.1 | Medical condition in easily understood language |
Lower limb spasticity due to cerebral palsy |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058977 |
E.1.2 | Term | Spastic paresis |
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 purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the leg(s) are effective in treating children/adolescents (age 2-17 years) with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Female or male subject of 2 to 17 years of age (inclusive).
2. Uni- or bilateral cerebral palsy with clinical need for uni- or bilateral LL injections with BoNT for the treatment of spasticity.
3. Ashworth Scale [AS] score ≥2 in plantar flexors (at least unilaterally).
4. Clinical need for a total dose of 16 U/kg BW NT 201 (maximum of 400 U) for the treatment of LL spasticity according to the clinical judgment of the investigator.
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E.4 | Principal exclusion criteria |
1. Fixed contracture defined as severe restriction of the range of joint movement on passive stretch or predominant forms of muscle hypertonia other than spasticity (e.g., dystonia) in the target limb(s).
2. Surgery on pes equinus on side(s) intended to be treated with BoNT injections in this study within 12 months prior to Screening Visit (V1), in the screening period or planned for the time of participation in this study.
3. Hip flexion requiring BoNT injection.
4. Limitation of hip abduction to less than 40° or pre-diagnosed migrational percentage greater than 30.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline (Day 1) in the AS score of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 29 (Week 4) of the 1st injection cycle.
Co-primary efficacy variable (to fulfil the PMC, for US regulatory authorities only):
• Investigator’s Global Impression of Change of Plantar Flexor Spasticity Scale [GICS-PF] (for subjects with bilateral treatment on same body side as chosen for the primary efficacy variable) at Day 29 (Week 4) of the 1st injection cycle.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
week 4 of 1st injection cycle
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E.5.2 | Secondary end point(s) |
- For subjects with bilateral treatment: Change from baseline in the AS score of plantar flexors of the other treated body side at Day 29 (Week 4) of the 1st and 2nd injection cycle.
- Change from baseline in the AS score of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 29 (Week 4) of the 2nd injection cycle.
- Changes from baseline in AS score of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 57 (Week 8) and Day 85 (Week 12) of the 1st and of the 2nd injection cycle.
- For subjects with unilateral treatment: Changes from baseline in AS score of knee flexors or thigh adductors at Day 29 (Week 4) of the 1st and of the 2nd injection cycle.
- Changes from baseline in modified Tardieu Scale [MTS] of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the 1st and of the 2nd injection cycle.
- Investigator’s, Child’s/Adolescent’s, and Parent’s/Caregiver’s Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the 1st and 2nd injection cycle.
- Investigator’s Global Impression of Change of Plantar Flexor Spasticity [GICS-PF] (for subjects with bilateral treatment on same body side as chosen for the primary efficacy variable) at Day 29 (Week 4) of the 1st and 2nd injection cycle.
- Changes from baseline in Gross Motor Function Measure [GMFM]-66 score at the End of 1st Cycle Visit V6 and at the End of Study Visit V11.
- Change in scores of pain intensity (from subjects) and pain frequency (from parent/caregiver) assessed with ‘Questionnaire on Pain caused by Spasticity [QPS]’ to all post baseline visits of the 1st and of the 2nd injection cycle.
- Time to reinjection for each of the three dose groups for the 1st and 2nd injection cycle.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
between week 4 and week 72 (for details see definition of endpoints) |
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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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 |
same IMP, 3 different doses arms |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
Austria |
Czech Republic |
Estonia |
Germany |
Israel |
Korea, Republic of |
Poland |
Romania |
Russian Federation |
Slovakia |
South Africa |
Spain |
Turkey |
Ukraine |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |