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 |
Polycythemia Vera |
Policitemia Vera |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 compare the efficacy of ruxolitinib and HU for reducing the cluster of symptoms defined by tiredness, itching, muscle aches, night sweats, and sweats while awake in subjects with PV. |
Comparar la eficacia de ruxolitinib e hidroxiurea (HU) en la reducción del conjunto de síntomas definido por cansancio, prurito, dolor muscular, sudoración nocturna y sudoración durante la vigilia en pacientes con policitemia vera (PV) |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of ruxolitinib and HU for reducing the following individual symptoms: ? Tiredness ? Itching ? Muscle aches ? Night sweats ? Sweats while awake ? To evaluate the durability of symptomatic improvement in subjects experiencing relief from the cluster of symptoms that includes tiredness, itching, muscle aches, night sweats, and sweats while awake, and for each of these symptoms individually. ? To evaluate the safety of ruxolitinib and HU. |
? Comparar la eficacia de ruxolitinib e hidroxiurea en la reducción de los síntomas individuales que se indican a continuación: -Cansancio -Prurito -Dolor muscular -Sudoración nocturna -Sudoración durante la vigilia
? Evaluar la durabilidad de la mejora de los síntomas en pacientes que obtienen alivio del conjunto de síntomas definido por cansancio, prurito, dolor muscular, sudoración nocturna y sudoración durante la vigilia, y de cada uno de esos síntomas por separado. ?Evaluar la seguridad de ruxolitinib e hidroxiurea |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Men or women aged ? 18 years with a confirmed diagnosis of PV according to the revised World Health Organization criteria. ? Subjects must currently be reporting symptoms on a stable dose of HU monotherapy and be eligible to continue HU on study after randomization. Before screening, the subject must have been receiving HU for at least 12 weeks and on the same dose for the last 4 weeks. ? Subjects must have completed the modified MPN-SAF screening symptom form and have a screening total symptom score (TSS) of ? 8 for the cytokine-related symptoms, or symptom cluster C (TSS-C): tiredness, itching, muscle aches, night sweats, and sweats while awake. ? Subjects should meet at least one of the following criteria with respect to phlebotomy and splenomegaly: ? No more than 1 phlebotomy within the 6 months before screening OR ? No palpable splenomegaly ? Subjects must have a hematocrit that can be controlled within 35% to 48% (inclusive) before randomization. (A phlebotomy may be performed during the screening phase to achieve this target range.) ? Subjects must have recovered from all side effects associated with phlebotomy, and at least 1 week must have elapsed between the phlebotomy and the beginning of the baseline phase. ? Subjects with Eastern Cooperative Oncology Group performance status of 0, 1, or 2 at screening. |
?Hombres o mujeres con edad igual o superior a los 18 años con diagnóstico de policitemia vera confirmado conforme a los criterios revisados de la Organización Mundial de la Salud ?Los pacientes deben notificar síntomas en ese momento aun utilizando monoterapia estable con hidroxiurea y ser adecuados para continuar usándola durante el estudio después de la aleatorización. Antes de la selección, el paciente debe haber estado recibiendo hidroxiurea durante al menos 12 semanas y, durante las últimas 4 semanas, a la misma dosis. ?Los pacientes deben haber rellenado el formulario de síntomas de selección MPN-SAF modificado y tener una puntuación total de síntomas (TSS, por sus siglas en inglés) igual o superior a 8 para los síntomas relacionados con las citocinas o el conjunto de síntomas C (TSS-C): cansancio, prurito, dolor muscular, sudoración nocturna y sudoración durante la vigilia. ?Los pacientes deberían cumplir al menos uno de los criterios que se indican a continuación en relación con la flebotomía y esplenomegalia: -No más de 1 flebotomía en los 6 meses antes de la selección o -Ninguna esplenomegalia palpable ?Los pacientes deben obtener un hematocrito que pueda controlarse comprendido entre el 35 % y el 48 % (inclusive) antes de la aleatorización. (Puede realizarse una flebotomía durante la fase de selección para alcanzar este rango objetivo.) ?Los pacientes deben haberse recuperado de todos los efectos secundarios asociados con la flebotomía y debe haber transcurrido al menos 1 semana entre la flebotomía y el comienzo de la fase inicial. ?Pacientes con estado general de 0, 1 o 2 conforme al Eastern Cooperative Oncology Group (ECOG) en el momento de la selección. |
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E.4 | Principal exclusion criteria |
? Subjects with inadequate liver or renal function at screening as demonstrated by: ? Encephalopathy ? Grade 2 as per Child-Pugh System ? Hepatocellular disease ? Total bilirubin > 2 × upper limit of normal (ULN), unless direct bilirubin is < 2 × ULN ? Alanine aminotransferase > 2.5 × ULN ? Modification of Diet in Renal Disease estimated glomerular filtration rate < 30 mL/min/1.73 m2 or on dialysis ? Subjects with platelet count < 100 × 10^9/L or an absolute neutrophil count of < 1 × 10^9/L ? Subjects with peripheral blood blast count of > 0% at screening. |
?Pacientes con función hepática o renal inadecuada en el momento inicial según se demuestre por: -Encefalopatía de grado igual o superior a 2 conforme al sistema de Child-Pugh -Enfermedad hepatocelular -Bilirrubina total superior al doble del límite superior de la normalidad (LSN), a menos que la bilirrubina directa sea inferior al doble de dicho LSN -Alaninoaminotransferasa superior a 2,5 veces el LSN -Modificación de la alimentación en caso de nefropatía con una tasa de filtración glomerular calculada inferior a 30 ml/min/1,73 m2 o en diálisis ?Pacientes con una cantidad de trombocitos inferior a 100 × 10^ 9/l o una cantidad absoluta de neutrófilos inferior a 1 × 10^9/l ?Pacientes con una cantidad de blastos en la sangre periférica superior al 0 % en el momento inicial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with ? 50% reduction in the TSS-C (tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16 compared to baseline, as measured by the modified MPN-SAF diary. |
Proporción de pacientes con una reducción igual o superior al 50 % en la puntuación TSS-C (cansancio, prurito, dolor muscular, sudoración nocturna y sudoración durante la vigilia) en la semana 16 en comparación con el momento inicial, según se haya medido mediante el diario MPN-SAF modificado |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
? Proportion of subjects with ? 50% reduction in individual symptoms at Week 16 compared to baseline, as measured by the modified MPN-SAF diary for the following items: ? Tiredness ? Itching ? Muscle aches ? Night sweats ? Sweats while awake Noncomparative Secondary Endpoints ? Proportion of subjects in Arm A who achieve a durable response, defined as a ? 50% reduction in TSS-C at Week 16 that is maintained at Week 48. ? Proportions of subjects in Arm A who achieve a durable response, defined as a ? 50% reduction in the individual symptoms in TSS-C (tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16 that is maintained at Week 48. ? Safety of ruxolitinib and HU. |
Proporción de pacientes con una reducción igual o superior al 50 % en las puntuaciones de los síntomas individuales en la semana 16 en comparación con el inicio, según lo medido utilizando el diario MPN-SAF modificado para los siguientes síntomas: -Cansancio -Prurito -Dolor muscular -Sudoración nocturna -Sudoración durante la vigilia
Criterios de valoración secundarios no comparativos ?Proporción de pacientes aleatorizados al grupo de tratamiento A que obtiene una respuesta duradera, definida como una reducción igual o superior al 50 % en la puntuación TSS-C en la semana 16 que se mantiene en la semana 48. ?Proporción de pacientes aleatorizados al grupo de tratamiento A que alcanza una respuesta duradera, definida como una reducción igual o superior al 50 % en los síntomas individuales en la escala TSS-C (cansancio, prurito, dolor muscular, sudoración nocturna y sudoración durante la vigilia) en la semana 16 que se mantiene en la semana 48. ?Seguridad de ruxolitinib e hidroxiurea. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 16 and week 48 |
Semana 16 y semana 48 |
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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 | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Belgium |
Italy |
Spain |
United Kingdom |
United States |
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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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Subjects who remain on study at the end of the formal data collection period (when all enrolled subjects have reached Week 48 on study or have been withdrawn) will be withdrawn from the study. |
Los pacientes que permanezcan en el estudio al final del período formal de recogida de datos (definido como el momento en el que todos los pacientes incluidos han llegado a la semana 48 del estudio o han sido retirados), dejarán el estudio. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |