E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV MF) or Post essential thrombocythemia myelofibrosis (PET-MF) |
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E.1.1.1 | Medical condition in easily understood language |
|
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 evaluate the efficacy of daily oral doses of 15mg BID or 20mg BID of INC424 in patients with PMF, PPV-MF, or PET-MF, based on the proportion of patients experiencing treatment success at the 48 week timepoint. |
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E.2.2 | Secondary objectives of the trial |
To document the best overall response rate to INC424 in patients with PMF, PPV-MF, or PET-MF as evaluated by the investigator
To collect quality of life (QoL) information
To document medical resource utilization |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must give written informed consent according to local guideliens prior to any screening procedures
2. Patients must not be eligible for another ongoing INC424 clinical trial
3. Male or female patients aged ≥ 18 years of age
4. Patients must be diagnosed with PMF, PPV MF or PET MF according to the WHO criteria 2008
5. Patients with PMF requiring therapy must be classified as high risk or intermediate risk level 2 or intermediate risk level 1 with enlarged spleen
6. Patients with Intermediate-1 and splenomegaly must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion
See protocol for further criteria |
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E.4 | Principal exclusion criteria |
1. Patients eligible for hematopoietic stem cell transplantation
2. Patients with a history of malignancy in the past 3 years, except for treated early stage squamous or basal cell carcinoma in situ
3. Patients undergoing treatment with haematopoietic growth factor receptor agonists at any time within 2 weeks prior to screening or 4 weeks prior to baseline
4. Patients currently participating in COMFORT-I and COMFORT -II trials
5. Patients receiving any medications listed in the "prohibited medications" listing
6. Impairment of GI function or GI disease that may significantly alter the absorption of oral INC424
7. Patients with cardiac disease which may jeopardize the safety of the patient or compliance with the protocol
8. Patients with currently uncontrolled or unstable angina, rapid or paroxysmal fibrillation or recent myocardial infarction or acute coronary syndrome
9. Patients with clinically significant infections (for further details see protocol)
10. Patients with known active hepatitis A, B, C or who are HIV -positive
11. Patients with coagulation parameters ≥1.5
12. Pregnant or nursing women
See protocol for further criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
Treatment success measured by change in spleen size by palpation and/or change in myelofibrosis symptoms assessment form (MF-SAF). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monthly for the first 3 months, then every 3 months and at study discontinuation |
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E.5.2 | Secondary end point(s) |
To assess the best overall response rate of INC424 in patients with PMF, PPV-MF or PET-MF, as evaluated by the investigator
To collect Quality of Life (QoL) information
To document Medical Resource Utilization (MRU)
To collect safety data |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Monthly for the first 3 months, then every 3 months and at study discontinuation |
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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 | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
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 | 11 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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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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 | |