E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Polycythemia Vera |
Policitemia vera |
|
E.1.1.1 | Medical condition in easily understood language |
Polycythemia Vera, that is a disease characterized by an uncontrolled proliferation of blood, that increase (red cells, white cells and platelets). |
Policitemia vera, una malattia caratterizzata dalla proliferazione incontrollata delle cellule del sangue, che aumentano (globuli rossi, globuli bianchi e piastrine). |
|
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 | LLT |
E.1.2 | Classification code | 10036061 |
E.1.2 | Term | Polycythemia vera |
E.1.2 | System Organ Class | 100000004864 |
|
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 assess whether the addition of Pegylated Proline-interferon alpha-2b to the best therapeutic current strategy available based on phlebotomies and low dose acetylsalicilic acid (ASA) could improve the efficacy of treatment of patients with PV at low risk in term of control of recommended level of hematocrit < 45%, over a period of 12 months. |
Valutare se l’aggiunta della Prolina-interferone alfa-2b peghilato alla strategia terapeutica basata sui salassi può migliorare l’efficacia del trattamento dei pazienti con PV a basso rischio, in termini di controllo dell’ematocrito (HCT) ai livelli raccomandati < 45%, valutato lungo il periodo di 12 mesi. |
|
E.2.2 | Secondary objectives of the trial |
Comparative evaluation of: • Reduction of the need of phlebotomies • Hematological response • Thrombotic and hemorrhagic events • Proportion of patients with not palpable spleen • Bone marrow histological remission • Molecular response • Quality of life of patients • Rate of assigned treatment withdrawal due to any protocol drug-related toxicity • Adverse events rate
|
Valutazione comparata tra i due bracci di: • Riduzione del bisogno dei salassi • Risposta ematologica • Risposta molecolare • Eventi trombotici ed emorragici • Proporzione dei pazienti con milza non palpabile Remissione istologica del midollo osseo • Qualità di vita dei pazienti • Tasso di interruzioni della terapia assegnata, dovute a qualsiasi tossicità relativa al trattamento in corso da protocollo • Tasso di eventi avversi
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Molecular study within the Low-PV trial (Version 2.1, 15/02/2016): the explorative objective is to determine the efficacy of treatment on the JAK2V617F allele burden.
|
Studio molecolare del trial Low-PV (Versione 2.1, 15/02/2016): l'obiettivo esplorativo è quello di determinare l'efficacia della terapia sull'espressione allelica di JAK2V617F. |
|
E.3 | Principal inclusion criteria |
1. Age 18-60 years 2. Diagnosis of Polycythemia Vera according to WHO 2008 criteria 3. Diagnosis of Polycythemia Vera performed within 3 years prior inclusion in the study and never treated with cytoreductive drugs 4. HCT<45% 5. Ability and willingness to comply with all study requirements 6. Signed written informed consent |
1. Età di 18-60 anni 2. Diagnosi di Policitemia Vera in accordo con i criteri WHO 2008 3. Diagnosi di Policitemia Vera entro i 3 anni che precedono l’inclusione in studio e che non abbiano mai ricevuto farmaci citoriduttivi in precedenza 4. HCT<45% 5. Abilità e buona volontà di accettare tutte le richieste necessarie per la conduzione dello studio 6. Firma del consenso informato scritto |
|
E.4 | Principal exclusion criteria |
1. Any previous well documented cardiovascular PV-related events (see Appendix 1 for description) 2. Previous cytoreductive drugs 3. Known hypersensitivity or contraindications to the IMP (Pegylated Proline-Interferon alpha-2b) 4. Previous exposure to a non-pegylated or pegylated interferon α 5. Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis 6. Systemic infections, e.g. hepatitis B, hepatitis C, or HIV at screening 7. Significant liver (AST or ALT > 2.5 times ULN) or renal disease (creatinine > 2 mg/ml) 8. Presence of any life-threatening condition or of any disease (e.g. cancer) that is likely to significantly shorten life expectancy 9. History of active substance or alcohol abuse within the last year 10. Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety or be associated with poor adherence to the protocol 11. Pregnant or lactating women and women*/men of childbearing potential who are not using or are not willing to use any effective means of contraception |
1. Qualsiasi evento cardiovascolare documentato correlato alla PV (vedi Appendice 1 per descrizione) 2. Somministrazione precedente di farmaci citoriduttivi. 3. Ipersensibilità o controindicazioni note al farmaco in sperimentazione (IMP) Prolina-interferone alfa-2b peghilato 4. Esposizione precedente all’ interferone peghilato o non peghilato 5. Infiltrati polmonari di rilevanza clinica e polmonite 6. Infezioni sistemiche, e.g. epatite B, epatite C, o HIV allo screening 7. Disturbi epatici (AST or ALT > 2.5 volte ULN) o renali (creatinina > 2 mg/ml) significativi 8. Presenza di condizioni potenzialmente mortali o di altri disturbi (e.g. cancro) che facciano prevedere una breve sopravvivenza. 9. Storie di abuso di alcol o di droghe nell’ultimo anno 10. Ogni condizione che nell’opinione dello sperimentatore metterebbe in pericolo la valutazione di efficacia e sicurezza o potrebbe essere associata a una insufficiente aderenza al protocollo 11. Donne in gravidanza o in allattamento oppure donne*/uomini che non adottino o non vogliono adottare metodi efficaci di contraccezione |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion (%) of responders to assigned treatment strategy defined as patients who maintain the median HCT values <45% during 12 months after treatment in each arm, without progression of disease and no need of any extra-protocol cytoreductive drugs. |
Proporzione (%) dei pazienti che rispondono alla strategia di trattamento assegnato, definiti come quelli che mantengono la mediana dei valori di HCT <45% durante i 12 mesi dopo la randomizzazione, in ciascun braccio di trattamento, senza progressione di malattia e bisogno di ulteriori farmaci citoriduttivi. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Quality of Life (QoL): • Functional Assessment of Cancer Therapy-Anemia (FACT-An) • Myeloproliferative Neoplasm Symptoms Assessment Form total symptom score (MPN-SAF TSS/MPN10) |
Qualità della vita (QoL): • Valutazione funzionale dell’anemia legata al trattamento del cancro (FACT-An) • Questionario per la valutazione dei sintomi nelle malattie mieloproliferative croniche- 10 (MPN-10) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline (before starting the protocol therapy), every 3 months until the end of the study and at the completion of the study. |
Al basale (prima di iniziare la terapia da protocollo), ogni 3 mesi fino alla fine dello studio e al suo completamento. |
|
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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Lo studio prevede 2 fasi: 1) studio core; 2) fase di estensione. |
The study includes 2 phase: 1)core study; 2) extension phase. |
|
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 |
Regime standard raccomandato basato sui salassi e acido acetilsalicilico a basso dosaggio (100mg). |
Standard recommended therapy based on phlebotomies and low dose of acetylsalicylic acid (100mg). |
|
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 | 22 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | 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
|
|
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 |