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 |
A type of blood cancer |
Tumore del sangue |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036057 |
E.1.2 | Term | Polycythaemia vera |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036061 |
E.1.2 | Term | Polycythemia vera |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 safety and efficacy of rusfertide in subjects with polycythemia vera in maintaining hematocrit control. |
Valutare la sicurezza e l'efficacia di Rusfertide in soggetti affetti da policitemia vera con ematocrito di controllo |
|
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 |
-Male and female subjects aged 18 (or the minimum country specific age of consent if >18) years or older. -Meet revised 2016 World Health Organization (WHO) criteria for the diagnosis of polycythemia vera and have either JAK2 V617F mutation or JAK2 exon 12 mutation -Phlebotomy requiring defined as: At least 3 phlebotomies due to inadequate hematocrit control in 6 months before randomization or at least 5 phlebotomies due to inadequate hematocrit control in 1 year before randomization, and -CBC values immediately prior to randomization: a. Hematocrit <45%, b. WBC 4000/µL to 20,000/µL (inclusive), and c. Platelets 100,000/µL to 1,000,000/µL (inclusive). -Subjects receiving cytoreductive therapy at randomization must be on a stable PV therapy regimen -Subjects treated with phlebotomy alone at randomization must havestopped cytoreductive therapy 2 to 6 months before screening. |
-Soggetti maschi e femmine di età pari o superiore a 18 anni (o il minimo specifico per paese età del consenso se >18) anni o più. -Soddisfare i criteri dell'Organizzazione Mondiale della Sanità (OMS) rivisti del 2016 per la diagnosi di policitemia vera: mutazione JAK2 V617F o Mutazione dell'esone 12 di JAK2 -Requisito di flebotomia definito come: Almeno 3 flebotomie dovute a un inadeguato controllo dell'ematocrito 6 mesi prima della randomizzazione o almeno 5 flebotomie dovute a un ineguato controllo dell'ematocrito 1 anno prima della randomizzazione -Valori CBC immediatamente prima della randomizzazione: a.ematocrito <45%, b.WBC da 4000/µL a 20.000/µL (incluso) c.Piastrine da 100.000/µL a 1.000.000/µL (incluse). -I soggetti che ricevono la terapia citoriduttiva alla randomizzazione devono essere in un regime di terapia PV stabile -I soggetti trattati con la sola flebotomia alla randomizzazione devono avere interrotto la terapia citoriduttiva da 2 a 6 mesi prima dello screening. |
|
E.4 | Principal exclusion criteria |
-Clinically meaningful laboratory abnormalities at Screening -Subjects who require phlebotomy at hematocrit levels lower than 45%. -Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 2 months prior to randomization. -Active or chronic bleeding within 2 months prior to randomization. -History of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer. -Subjects with non-invasive non-melanomatous (e.g., squamous cell or basal cell carcinoma) skin cancer during screening unless adequately treated before randomization. -Received busulfan, pipobroman or 32Phosphorus within 7 months prior to screening. |
-Anomalie di laboratorio clinicamente significative allo screening -Soggetti che necessitano di flebotomia a livelli di ematocrito inferiori a 45%. -Trombosi clinicamente significativa (ad es. trombosi venosa profonda o splenica trombosi venosa) entro 2 mesi prima della randomizzazione. -Sanguinamento attivo o cronico entro 2 mesi prima della randomizzazione. -neoplasie maligne invasive negli ultimi 5 anni, eccetto carcinoma prostatico curato localizzato e carcinoma cervicale. -Soggetti con non melanomatosi non invasivi (es. cellule squamose o carcinoma basocellulare) cancro della pelle durante lo screening se non adeguatamente trattati prima della randomizzazione. -Ricevuto busulfano, pipobroman o 32fosforo entro 7 mesi prima dello screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects achieving a response starting at Week 20 through Week 32 (inclusive) who receive rusfertide compared to placebo. A response is defined as absence of phlebotomy eligibility. Phlebotomy eligibility is defined as either: • a confirmed hematocrit =45% and that is at least 3% higher than the baseline hematocrit (value immediately prior to randomization at Week 0); or • a hematocrit =48%. |
Percentuale di soggetti che ottengono una risposta dalla settimana 20 alla settimana 32 (inclusa) che ricevono rusfertide rispetto al placebo. Una risposta è definita come assenza di ammissibilità alla flebotomia. L'idoneità alla flebotomia è definita come: • un ematocrito confermato =45% e che sia almeno il 3% superiore all' ematocrito basale (valore immediatamente prima della randomizzazione alla settimana0); o • un ematocrito =48%. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 20 through Week 32 (inclusive) |
Dalla settimana 20 alla settimana 32 (incluse) |
|
E.5.2 | Secondary end point(s) |
1. Mean number of phlebotomies between Week 0 through Week 32 (inclusive). 2. Proportion of subjects with all hematocrit values <45% between Week 0 through Week 32 (inclusive). 3. Mean change from baseline in total fatigue score based on PROMIS® Short Form 8a at Week 32. 4. Mean change from baseline in total score based on MFSAF v4.0 at Week 32. |
1. Numero medio di flebotomie tra la settimana 0 e la settimana 32 (compreso). 2. Proporzione di soggetti con tutti i valori di ematocrito <45% tra la settimana 0 e la settimana 32 (inclusa). 3. Variazione media rispetto al basale del punteggio di fatica totale basato su PROMIS® Modulo abbreviato 8a alla settimana 32. 4. Cambiamento medio dal basale nel punteggio totale basato su MFSAF v4.0 alla Settimana 32. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 0 through Week 32 (inclusive) |
Dalla settimana 0 alla settimana 32 (incluse) |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Yes |
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 |
Studio in 3 parti. Parte 1a: come sopra. Parti 1b e 2: in aperto; i soggetti riceveranno il trattam |
3-part study. Part 1a: as above. Parts 1b and 2: open-label; subjects receive active treatment. |
|
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
Hong Kong |
Israel |
United States |
Austria |
France |
Poland |
Netherlands |
Spain |
Czechia |
Germany |
Italy |
Belgium |
Hungary |
Turkey |
United Kingdom |
|
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
|
|
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |