E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028537 |
E.1.2 | Term | Myelofibrosis |
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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 |
o To compare the efficacy, safety and tolerability of INCB018424 given twice daily to the best-available therapy, in subjects with primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV-MF) or post essential thrombocythemia myelofibrosis (PET-MF). |
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E.2.2 | Secondary objectives of the trial |
o To evaluate the population pharmacokinetics of INCB018424 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female subjects, aged 18 years or older, with diagnosis of PMF, PPV-MF or PET-MF. Subjects with a palpable spleen length of 5 cm or greater below the costal margin Subjects must have either 2 (Intermediate risk) or 3 or more (High risk) prognostic factors (Cervantes et al, 2008). These prognostic factors are: a) Age > 65 yrs b) Presence of constitutional symptoms (weight loss, fever, night sweats) c) Marked anemia (Hgb < 10g/dL) d) Leukocytosis (history of WBC > 25 x 109/L) e) Circulating blasts &#8805; 1% Subjects with peripheral blood blasts of < 10% Subjects must have been on a stable therapeutic regimen for at least 2 weeks before Screening and at least 4 weeks prior to Baseline. |
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E.4 | Principal exclusion criteria |
Subjects with a life expectancy of < 6 months. Subjects with inadequate bone marrow reserve as follows: a) Absolute neutrophil count (ANC) that is &#8804; 1000/�L. b) Platelet count that is < 100,000/�L without the assistance of growth factors, thrombopoietic factors or platelet transfusions. Subjects with any history of platelet counts < 50,000/�L or ANC < 500/�L except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason. Subjects having clinically significant infections or current malignancies. |
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E.5 End points |
E.5.1 | Primary end point(s) |
o Proportion of subjects achieving at least 35% reduction in spleen volume from Baseline to Week 48 as measured by MRI (or by CT for applicable subjects). |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
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 |
migliore terapia disponibile scelta sperimentatore |
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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 | 86 |
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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
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 | 1 |