E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Polycythemia Vera |
Policitemia Vera |
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E.1.1.1 | Medical condition in easily understood language |
A type of blood cancer |
Tipo de cancer en la sangre |
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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) |
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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) |
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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 safety and efficacy of rusfertide in subjects with polycythemia vera in maintaining hematocrit control. |
Evaluar la seguridad y la eficacia de rusfertida en sujetos con policitemia vera para mantener el control del hematocrito |
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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 |
1. Male and female subjects aged 18 (or the minimum country specific age of consent if >18) years or older. 3. 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 4. Phlebotomy requiring defined as: a. 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 5. 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). 11. Subjects receiving cytoreductive therapy at randomization must be on a stable PV therapy regimen 12. Subjects treated with phlebotomy alone at randomization must have stopped cytoreductive therapy 2 to 6 months before screening. |
1. Varones y mujeres de 18 (o la edad mínima de consentimiento específica del país si es > 18) años o más. 3. Cumplir los criterios revisados de 2016 de la Organización Mundial de la Salud (OMS) para el diagnóstico de policitemia vera y presentar la mutación V617F JAK2 o mutación en el exón 12 de JAK. 4. Precisa flebotomías, lo que se define como: a. Al menos 3 flebotomías debido a un control insuficiente del hematocrito en los 6 meses previos a la aleatorización o al menos 5 flebotomías debido a un control insuficiente del hematocrito en 1 año antes de la aleatorización. 5. Valores del hemograma completo inmediatamente antes de la aleatorización: a. Hematocrito <45 %, b. Leucocitos de 4000/µl a 20.000/µl (incluidos) y c. Plaquetas de 100.000/µl a 1.000.000/µl (incluidos). 11. Los sujetos que estén recibiendo tratamiento citorreductor en la aleatorización deberán estar recibiendo una pauta estable de tratamiento para la PV 12. Los sujetos tratados con flebotomía sola en la aleatorización deberán haber interrumpido terapia citoreductiva de 2 a 6 meses antes del screening |
|
E.4 | Principal exclusion criteria |
1. Clinically meaningful laboratory abnormalities at Screening 2. Subjects who require phlebotomy at hematocrit levels lower than 45%. 4. Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 2 months prior to randomization. 5. Active or chronic bleeding within 2 months prior to randomization. 10. History of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer. 11. Subjects with non-invasive non-melanomatous (e.g., squamous cell or basal cell carcinoma) skin cancer during screening unless adequately treated before randomization. 15. Received busulfan, pipobroman or 32Phosphorus within 7 months prior to screening. |
1. Anomalías analíticas clínicamente significativas en la selección 2. Pacientes que precisen flebotomía con un hematocrito inferior al 45 %. 4. Trombosis clínicamente significativa (por ejemplo, trombosis venosa profunda o trombosis de la vena esplénica) en los 2 meses previos a la aleatorización. 5. Hemorragia activa o crónica en los 2 meses previos a la aleatorización. 10. Antecedentes de neoplasias malignas invasivas en los últimos 5 años, excepto cáncer de próstata y cáncer de cuello uterino localizados curados. 11. Pacientes con cáncer de piel no melanomatoso invasivo (p. ej., carcinoma basocelular o espinocelular) durante la selección a menos que reciban un tratamiento adecuado antes de la aleatorización. 15. Haber recibido busulfán, pipobromán o fósforo-32 en los 7 meses previos a la selección. |
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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%. |
Proporción de sujetos que logren una respuesta desde la semana 20 hasta la semana 32 (inclusive) con rusfertida en comparación con placebo. La respuesta se define como la ausencia de elegibilidad para flebotomía. La elegibilidad para la flebotomía se define como cualquiera de los siguientes: • un hematocrito confirmado ≥ 45 % y que sea al menos un 3 % mayor que el hematocrito basal (valor inmediatamente anterior a la aleatorización en la semana 0); confirmación obligatoria en el plazo de 1 a 7 días; o • un hematocrito ≥ 48 %. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 20 through Week 32 (inclusive) |
Entre la semana 20 y la semana 32 (inclusive) |
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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. Número medio de flebotomías entre las semanas 0 y 32 (inclusive). 2. Proporción de sujetos con todos los valores de hematocrito < 45 % entre las semanas 0 y 32 (inclusive). 3. Variación media de la puntuación total del cansancio basada en el cuestionario abreviado PROMIS® 8a entre el momento basal y la semana 32. 4. Variación media de la puntuación total basada en MFSAF v4.0 entre el momento basal y la semana 32. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 0 through Week 32 (inclusive) |
Entre la semana 0 y la semana 32 (inclusive) |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 |
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 | 5 |
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 | No |
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 |
Belarus |
Hong Kong |
Israel |
Korea, Republic of |
Malaysia |
Russian Federation |
Turkey |
United States |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
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
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LVLS |
Última visita del último paciente |
|
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 | 5 |
E.8.9.1 | In the Member State concerned days | |
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 |