E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multifocal spasticity of the upper and lower limb due to cerebral palsy |
Spasticità multifocale dell'arto superiore e inferiore dovuta a paralisi cerebrale |
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E.1.1.1 | Medical condition in easily understood language |
Spasticity of the upper and lower limb due to cerebral palsy |
Spasticità dell'arto superiore e inferiore dovuta a paralisi cerebrale |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033560 |
E.1.2 | Term | Palsy cerebral |
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 investigate the efficacy of IncobotulinumtoxinA in the treatment of both BoNT-A naïve and pretreated children for upper and lower limb spasticity using a dose titration approach over three injection cycles, with a flexible observation period after injection of 12 to 20 weeks and a total duration of exposure up to 60 weeks |
Studiare l'efficacia di IncobotulinumtoxinA nel trattamento sia di bambini naïve che pretrattati con tossina botulinica per spasticità agli arti superiori e inferiori utilizzando un approccio di dose titration con tre cicli di iniezione, periodo di osservazione da 12 a 20 settimane dopo iniezione e una durata massima di esposizione di 60 settimane |
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E.2.2 | Secondary objectives of the trial |
To investigate the safety of IncobotulinumtoxinA in the treatment of both BoNT-A naïve and pretreated children for upper and lower limb spasticity using a dose titration approach over three injection cycles, with a flexible observation period after injection of 12 to 20 weeks and a total duration of exposure up to 60 weeks. |
Studiare la sicurezza di IncobotulinumtoxinA nel trattamento sia di bambini naïve che pretrattati con tossina botulinica per spasticità agli arti superiori e inferiori utilizzando un approccio di dose titration con tre cicli di iniezione, periodo di osservazione da 12 a 20 settimane dopo iniezione e una durata massima di esposizione di 60 settimane |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Children (female or male) aged 2 to 17 years • Patients with upper and lower limb spasticity due to cerebral palsy • Gross Motor Function Classification System (GMFCS) from Level II to Level V • Selected target clinical pattern diagnosed by a qualified health care professional (i.e. physiatrist) • Focal spasticity scored at least 2 points on the Ashworth scale (AS) in the joints associate with the selected target clinical pattern [12] • Patients deemed by the investigator to require a total body dose up to 22U/kg (maximum 550U) during the study period • In the case of children pretreated with BoNT-A, time from last injection at least 5 months • Informed consent signed by parents |
• Bambini (femmine o maschi) dai 2 ai 17 anni • Pazienti con spasticità degli arti superiori e inferiori a causa di paralisi cerebrale • Gross Motor Function Classification System (GMFCS) dal livello II al livello V • Diagnosi da parte di un professionista sanitario qualificato (es. Fisiatra) • Spasticità focale di almeno 2 punti sulla scala di Ashworth (AS) negli arti colpiti • Pazienti che secondo parere dello sperimentatore richiedono una dose corporea totale fino a 22 U/kg (massimo 550U) durante il periodo di studio • nel caso di bambini pretrattati con BoNT-A, tempo dall'ultima iniezione almeno 5 mesi • Consenso informato firmato dai genitori |
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E.4 | Principal exclusion criteria |
• Participation in other trials • BoNT-A treatment contraindicated • Presence of fixed contractures, or bony deformities of the affected limbs • Previous treatment of spastic muscles with nerve phenolization • Other neurological or orthopedic conditions involving the affected limbs • institutionalized patients • girls with childbearing potential (defined as females post menarche) |
• Partecipazione ad altri trial • Trattamento con BoNT-A controindicato • Presenza di contratture fisse o deformità ossee degli arti colpiti • Trattamento precedente dei muscoli spastici con fenolizzazione dei nervi • Altre condizioni neurologiche o ortopediche che coinvolgono gli arti colpiti • pazienti istituzionalizzati • ragazze in età fertile (definite come femmine post menarca) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in Ashworth scale values between the injection cycle baseline visits and the control ones of respective injection cycle (single interventional effect). |
Variazione degli score della Scala di Ashworth valutati nella visita baseline di ciascun ciclo in cui avviene l’iniezione rispetto alla visita di controllo dello stesso ciclo di iniezione. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
V2 vs V3, V5 vs V6, V8 vs V9 V2 vs V10 |
V2 vs V3, V5 vs V6, V8 vs V9 V2 vs V10 |
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E.5.2 | Secondary end point(s) |
Efficacy endpoint: Ashworth scale; Efficacy endpoints - REsistance to PAssive movement Scale (REPAS) - The GMFCS - The visual analog scale (VAS); Efficacy endpoints - The Goal Attainment scale (GAS) - The Global Assessment of Efficacy; Safety endpoints: Valori di pressione, frequenza cardiaca e frequenza respiratoria; Peso; eventi avversi |
Efficacy endpoint: Scala di Ashworth; Efficacy endpoints - REsistance to PAssive movement Scale (REPAS) - The GMFCS - The visual analog scale (VAS); Efficacy endpoints - The Goal Attainment scale (GAS) - The Global Assessment of Efficacy; Safety endpoints: Values of blood pressure, heart rate, and respiratory rate; Values of Body Weight; adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
V2 vs V6 V2 vs V9 V2 vs V5 V2 vs V8; V2 vs V3, V5 vs V6, V8 vs V9 V2 vs V6 V2 vs V9 V2 vs V5 V2 vs V8 V2 vs V10; V5, V8, V10; V1, V2, V3, V4, V5, V6, V7, V8, V9, V10 V2 vs V4 V2 vs V7 V2 vs V10; V1, V2, V5, V8; from V2 and during the study |
V2 vs V6 V2 vs V9 V2 vs V5 V2 vs V8; V2 vs V3, V5 vs V6, V8 vs V9 V2 vs V6 V2 vs V9 V2 vs V5 V2 vs V8 V2 vs V10; V5, V8, V10; V1, V2, V3, V4, V5, V6, V7, V8, V9, V10 V2 vs V4 V2 vs V7 V2 vs V10; V1, V2, V5, V8; da V2 e per tutta la durata dello studio |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Dose titration |
Dose titration |
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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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |