E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acquired Thrombotic thrombocytopenic purpura |
Porpora Trombotica Trombocitopenica acquisita |
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E.1.1.1 | Medical condition in easily understood language |
TTP is a rare condition in which the blood becomes "sticky" and forms clots within the blood vessels in different parts of the body. |
La PTT ¿ una condizione rara in cui il sangue diviene "appiccicoso" e forma coaguli all'interno dei vasi sanguigni in vari distretti del corpo |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
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 | 10043648 |
E.1.2 | Term | Thrombotic thrombocytopenic purpura |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
For adults: To evaluate efficacy of caplacizumab in more rapidly restoring normal platelet counts as measure of prevention of further microvascular thrombosis. For pediatric subjects:To report the efficacy, safety, PK and PD properties and immunogenicity of caplacizumab in pediatric subjects experiencing an acute episode of acquired TTP. |
Per gli adulti: Valutare l'efficacia del caplacizumab nel riportare pi¿ rapidamente a conta di piastrine normali come misura preventiva di ulteriori trombosi microvascolari. Per soggetti pediatrici: Registrare l'efficacia, la sicurezza, le propriet¿ di PK e PD e l'immunogenicit¿ di caplacizumab in soggetti pediatrici che manifestano episodi acuti di PTT acquisita. |
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E.2.2 | Secondary objectives of the trial |
-to evaluate the effect of study drug on a composite endpoint consisting of TTP-related mortality, recurrence of TTP and major thromboembolic events during study drug treatment -to evaluate the effect of study drug on prevention of recurrence of TTP over the entire study period -to evaluate the effect of study drug on refractoriness to treatment -to evaluate the effect of study drug on biomarkers of organ damage: lactate dehydrogenase (LDH), cardiac troponin I (cTnI), and serum creatinine -to evaluate the effect of study drug on PE parameters (days of PE and volume), days in intensive care unit (ICU), days in hospital
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-Valutare l¿effetto del farmaco in studio su un endpoint composito, costituito da mortalit¿ correlata a TTP, ricomparsa di TTP ed eventi tromboembolici rilevanti durante il trattamento con il farmaco in studio -valutare l¿effetto del farmaco in studio sulla prevenzione della ricomparsa di TTP nell¿arco dell¿intero periodo dello studio -valutare l¿effetto del farmaco in studio sulla refrattariet¿ al trattamento -valutare l'effetto del farmaco in studio sui biomarcatori di danno d'organo: lattato deidrogenasi (LDH), troponina I cardiaca (cTnI) e creatinina nel siero -valutare l¿effetto del farmaco in studio sui parametri relativi a PE (giorni di PE e volume), giorni in unit¿ di terapia intensiva (UTI), giorni in ospedale
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Adult male or female = 18 years of age at the time of signing the informed consent form (ICF) or, Male or female child (aged = 2 to < 12 years) or adolescent (aged = 12 to <18 years) at the time of obtaining informed consent/assent (as applicable). 2.Clinical diagnosis of acquired TTP (initial or recurrent), which includes thrombocytopenia and microscopic evidence of red blood cell fragmentation (e.g. schistocytes) 3.Requires initiation of daily PE treatment and has received PE treatment prior to randomization for adult subjects, and prior to start of first dose of study drug for pediatric subjects. |
- Adulti di sesso maschile o femminile = a 18 anni al momento della firma del consenso informato. (ICF) o Bambini (età da = 2 a < 12 anni) o adolescenti (età da = 12 a <18 anni) di sesso maschile o femminile al momento dell'ottenimento del consenso/assenso informato (come applicabile). - Diagnosi clinica di PTT acquisita (iniziale o ricorrente)che includa trombocitopenia e evidenza microscopica di frammentazione dei globulirossi (e.g. shistociti). -Richiede l'inizio di trattamento di Plasmaferesi giornaliera ed ah ricevuto almento un trattamento di PE prima della randomizzazione per i soggetti adulti e prima dell'inizio della somministrazione della prima dose di farmaco in studio per i soggetti pediatrici. |
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E.4 | Principal exclusion criteria |
1.Platelet count =100×10E9/L 2.Serum creatinine level >200 µmol/L in case platelet count is >30×109/L 3.Known other causes of thrombocytopenia |
-conta piastrinica =100×10E9/L -livello di creatinina sierica >200 µmol/L se conta piastrinica >30×109/L -altre cause note di trombocitopenia |
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E.5 End points |
E.5.1 | Primary end point(s) |
Applicable for adults only:Time to platelet count response defined as initial platelet count = 150×109/L with subsequent stop of daily PE within 5 days. Pediatric subjects Data of pediatric subjects will be analyzed separately from data of adult subjects. No endpoints are defined for the pediatric subjects. Data will be analyzed descriptively.
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Applicabili solo per gli adulti; Tempo alla risposta della conta piastrinica definito come conta piastrinica iniziale = 150×109/L con successiva interruzione della PE giornaliera entro 5 giorni. I dati dei soggetti pediatrici saranno analizzati separatamente dai dati dei soggetti adulti. Non sono definiti endpoint per i soggetti pediatrici. I dati saranno analizzati in modo descrittivo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Daily PE period, for maximum 6 months |
Tempo di PE giornaliera, per massimo 6 mesi |
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E.5.2 | Secondary end point(s) |
1. Proportion of subjects with TTP-related death, a recurrence of TTP, or at least one treatment-emergent major thromboembolic event during the study drug treatment period (including extensions). 2. Proportion of subjects with a recurrence of TTP in the overall study period (including 4-week FU period). 3. Proportion of subjects with refractory TTP, defined as absence of platelet count doubling after 4 days of standard treatment, and LDH >ULN 4. Time to normalization of all 3 of the following organ damage marker levels: - Time to LDH = 1 x upper limit of normal (ULN), and - Time to cTnI = 1 x ULN, and - Time to serum creatinine = 1 x ULN |
1. Proporzione di soggetti con decesso correlato a PTT, ricomparsa di PTT, o almeno un evento tromboembolico rilevante emergente dal trattamento (per esempio infarto miocardico, evento cerebrovascolare, embolia polmonare o trombosi venosa profonda [DVT]; Si veda anche la Sezione 3.4.3.6) durante il trattamento con il farmaco in studio (incluse estensioni). 2. Proporzione di soggetti con una ricomparsa di PTT nel periodo complessivo dello studio (incluso il periodo fi FU di 4 settimane) 3. Proporzione di soggetti con PTT refrattaria definita come mancato raddoppio della conta piastrinica dopo 4 giorni di trattamento standard e LDH > ULN 4. Tempo alla normalizzazione di tutti e 3 i seguenti livelli di marcatori del danno d'organo: - Tempo al livello di LDH = 1 x il limite superiore della norma (ULN) e - livello di cTnI = 1 x ULN e - livello di creatinina nel siero = 1 x ULN
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. During the treatment period (ie daily PE period + post-daily PE treatment period) 2. During the overall study period (including the FU period) 3. Will be evaluated during the daily PE period 4. During the overall study period (including the FU period) |
1. Durante il periodo di trattamento (ie periodo di PE giornaliera + periodo di trattamento post PE-giornaliera 2.Durante tutta la durata dello studio (incluso il periodo di FU) 3.Verr¿ valutato durante il periodo di PE-giornaliera 4. Durante tutta la durata dello studio (incluso il periodo di FU) |
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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) | 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 |
Per bambini & adolescenti trattamento open-label con Caplacizumab |
For children & Adolescents open-label treatment with Caplacizumab |
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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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 | Information not present in EudraCT |
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 |
Canada |
Israel |
New Zealand |
Turkey |
United States |
Austria |
Belgium |
Czechia |
France |
Germany |
Hungary |
Italy |
Netherlands |
Spain |
Switzerland |
United Kingdom |
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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 | 2 |
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 | 2 |
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 |