E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Thrombocytopenia associated with ITP |
Trombocitopenia associata a ITP |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021245 |
E.1.2 | Term | Idiopathic 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 |
To evaluate the incidence of collagen fibrosis as evidenced by trichrome staining at Year 1, Year 2, or Year 3 after initial exposure to romiplostim. |
Valutare l`incidenza di fibrosi collagenica, evidenziata mediante colorazione tricromica all`anno 1, all`anno 2 o all`anno 3 dopo l`esposizione iniziale a romiplostim. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the presence of collagen fibrosis as evidenced by trichrome staining 12 weeks after romiplostim discontinuation in subjects who developed collagen fibrosis at Year 1, Year 2, or Year 3 after exposure of romiplostim. To evaluate the incidence of increased reticulin fibrosis as evidenced by silver staining at Year 1, Year 2, or Year 3 after exposure of romiplostim. To evaluate electrocardiogram (ECG) changes after exposure to romiplostim. To evaluate the incidence of cytopenias (anemia or neutropenia) after exposure to romiplostim. To evaluate the overall safety as evidenced by adverse events and the development of neutralizing antibodies to romiplostim or cross-reacting antibodies to endogenous thrombopoietin. |
Valutare la presenza di fibrosi collagenica,evidenziata mediante colorazione tricromica,12 settimane dopo l`interruzione di romiplostim in soggetti che hanno sviluppato fibrosi collagenica all`anno 1,all`anno 2 o all`anno 3 dopo l`esposizione iniziale a romiplostim.Valutare l`incidenza dell`aumento di fibrosi reticolinica,evidenziata mediante colorazione argentica,all`anno 1,all`anno 2 o all`anno 3 dopo l`esposizione a romiplostim.Valutare le variazioni dell`elettrocardiogramma (ECG) dopo esposizione a romiplostim.Valutare l`incidenza di citopenie (anemia o neutropenia) dopo esposizione a romiplostim.Valutare la sicurezza complessiva,indicata dagli effetti indesiderati e dallo sviluppo di anticorpi neutralizzanti romiplostim o di anticorpi cross reagenti con la trombopoietina endogena. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
`Diagnosis of ITP according to the American Society of Hematology (ASH) guidelines `Subject must have had a bone marrow biopsy within one year prior to planned first dose of romiplostim (with available bone marrow tissue block or unstained histological slides to send to a central laboratory for interpretation) or must consent to a pre-treatment bone marrow biopsy within 3 weeks prior to planned first dose of romiplostim. Central laboratory interpretation is required prior to first dose of romiplostim `Baseline bone marrow reticulin grade of 0, 1, 2 or 3 according to the modified Bauermeister grading scheme as assessed by central laboratory interpretation `Subject must agree to a scheduled bone marrow biopsy at Year 1, Year 2, or Year 3 following romiplostim treatment and any unscheduled biopsies if clinically indicated `Subject platelet count is < 50x 109/L `Subject > 18 years of age `Must have received at least 1 prior ITP therapy (examples of ITP therapy include corticosteroids, IVIG, splenectomy) `Subject (or legally-acceptable representative) is willing and able to provide written informed consent |
`Diagnosi di ITP secondo le linee guida della American Society of Hematology (ASH) `Il soggetto deve essere stato sottoposto a biopsia del midollare osseo nell`anno precedente la prima dose programmata di romiplostim (con la disponilbilita` di un blocco di tessuto midollare o sezioni istologiche non colorate da inviare a un laboratorio centralizzato per la loro interpretazione) oppure deve acconsentire a sottoporsi a una biopsia midollare pretrattamento nelle 3 settimane precedenti la prima dose programmata di romiplostim. E` necessaria l`interpretazione da parte del laboratorio centralizzato prima della prima dose programmata di romiplostim. `Reticolina nel midollo osseo al basale di grado 0, 1, 2 o 3 secondo la scala di classificazione di Bauermeister modificata, valutata dall`interpretazione del laboratorio centralizzato. `I soggetti devono acconsentire a sottoporsi ad una biopsia del midollo osseo programmata all`anno 1, all`anno 2, o all`anno 3 dopo la terapia con romiplostim e ad eventuali biopsie non programmate, se indicato dal punto di vista clinico `Conta piastrinica < 50x 109/L `Pazienti di eta`> 18 anni `Deve aver ricevuto almeno 1 precedente terapia per ITP (tra gli esempi di terapia per ITP rientrano corticosteroidi, IVIG, splenectomia) `Il soggetto intende rilasciare il proprio consenso informato scritto, ed e` in grado di farlo |
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E.4 | Principal exclusion criteria |
`Baseline bone marrow biopsy positive for collagen fibrosis `Any known history of or currently active bone marrow stem cell disorder, hematological malignancy, myeloproliferative disorder, or myelodysplastic syndrome `Any current active malignancy `Any prior exposure to cytostatic chemotherapy or radiotherapy for malignancy `Subject has undergone pacemaker placement, cardiac ablation of arrhythmia, and/or any current treatment with Vaughan Williams Class IA - IC and Class III agents `Subject has participated in any study evaluating PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), or thrombopoietin receptor agonists (ie romiplostim or eltrombopag) `Subject has a known hypersensitivity to any recombinant E coli-derived product `Subject is currently enrolled in or has not yet completed (at least 4 weeks since ending) other investigational device or drug trial(s) or subject is receiving other investigational agent(s) `Other investigational procedures are excluded `Subject of child-bearing potential is evidently pregnant (eg, positive pregnancy test) or is breast feeding `Subject is not using adequate contraceptive precautions `Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and does not have a legally acceptable representative and/or is unable to comply with study procedures |
`Biopsia del midollo osseo al basale positiva per fibrosi collagenica `Disordini delle cellule staminali del midollo osseo, tumori ematologici maligni, disordini mieloproliferativi, o sindrome mielodisplastica pregressi o in corso `Tumori maligni di qualsiasi tipo in corso `Qualsiasi esposizione precedente a chemioterapia citostatica o a radioterapia per tumori maligni `Al soggetto e` stato impiantato un pacemaker, e` stato sottoposto ad ablazione di un aritmia cardiaca, e/o e` al momento sottoposto a trattamento con agenti di classe IA - IC e classe secondo classificazione di II Vaughan Williams `Il soggetto ha partecipato a studi di valutazione di PEG-rHuMGDF, trombopoietina ricombinante umana (rHuTPO), o agonisti del recettore della trombopoietina (romiplostim o eltrombopag) `Il soggetto presenta nota ipersensibilita` ai prodotti derivati da E coli ricombinante `Il soggetto e` al momento arruolato o non ha ancora completato (almeno 4 settimane dalla fine) uno o piu` trials su altri dispositivi o farmaci sperimentali, oppure il soggetto sta ricevendo uno o piu` agenti sperimentali `Sono escluse altre procedure sperimentali `Il soggetto potenzialmente in grado di avere figli e` in accertato stato di gravidanza (test di gravidanza positivo) o sta allattando al seno `Il soggetto non sta utilizzando delle misure contraccettive adeguate `Il soggetto presenta disturbi di qualsiasi tipo che compromettano la sua capacita` di rilasciare il proprio consenso informato scritto, e/o non e` in grado di seguire le procedure dello studio |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of collagen fibrosis as evidenced by trichrome staining at Years 1, 2, or 3 after initial romiplostim exposure using the modified Bauermeister grading scale. |
l`endpoint primario e` l`incidenza di fibrosi collagenica, evidenziata mediante colorazione tricromica, agli anni 1, 2, o 3 dopo esposizione iniziale a romiplostim usando la scala di classificazione Bauermeister modificata. |
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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 | No |
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 | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | 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
|
I soggetti saranno sottoposti aad una visita di Fine Studio 4 settimane dopo l'interruzione del trattamento con romiplostim. |
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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 | 5 |
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 | 5 |
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 |