E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Polycythemia vera resistant or intolerant to hydroxyurea |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036061 |
E.1.2 | Term | Polycythemia vera |
E.1.2 | System Organ Class | 100000004864 |
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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 |
efficacy of ruxolitinib to BAT as assessed by Hct control at Week 28 |
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E.2.2 | Secondary objectives of the trial |
Key secondary:
1. efficacy of ruxolitinib to BAT as assessed by peripheral blood count remission at Week 28
Other secondary:
2. efficacy of ruxolitinib to BAT as assessed by durable Hct control at Week 52
3. efficacy of ruxolitinib to BAT as assessed by durable peripheral blood count remission at Week 52
4. change in ECOG status
5. change in spleen length
6. efficacy of ruxolitinib to BAT as assessed by partial remission based on the ELN and IWG-MRT criteria at Week 28
7. efficacy of ruxolitinib to BAT as assessed by durable partial remission based on the ELN and IWG-MRT criteria at Week 52
8. efficacy of BAT patients after they cross over to ruxolitinib
9. changes in MPN-SAF TSS
10. resolution of disease related symptoms in MPN-SAF TSS at Week 28
11. changes in patient reported outcomes
12. safety of ruxolitinib and Best Available Therapy
13. safety of BAT patients after they cross over |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Confirmed diagnosis of PV according to the 2008 World Health Organization criteria
- Non-palpable spleen
- Phlebotomy dependent, Resistant to or intolerant of hydroxyurea
- ECOG performance status of 0, 1 or 2.
Other inclusion criteria as defined by protocol may apply |
|
E.4 | Principal exclusion criteria |
- Inadequate liver or renal function
- Significant bacterial, fungal, parasitic, or viral infection requiring treatment
- Active malignancy within the past 5 years, excluding specific skin cancers
- Previously received treatment with a JAK inhibitor
- Being treated with any investigational agent
- Women who are pregnant or nursing.
Other exclusion criteria as defined by protocol may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving Hct control at Week 28 as defined by:
• Hct < 45% at Week 16 and maintained until Week 28, and
• No phlebotomy from Week 4 to Week 28, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit. |
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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) |
Key secondary:
1. Proportion of patients achieving a peripheral blood count remission at Week 28 as defined by:
• Hct < 45% at Week 16 and maintained until Week 28, and
• WBC < 10 x109/L at Week 16 and maintained until Week 28, and
• Platelets ≤ 400 x 109/L at Week 16 and maintained until Week 28, and
• No phlebotomy from Week 4 to Week 28, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit.
Other secondary:
2. Proportion of patients achieving a Hct control at Week 52 as defined by:
• Hct < 45% at Week 16 and maintained until Week 52, and
• No phlebotomy from Week 4 to Week 28, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit, and
• In the BAT arm, no change in the treatment regimen or crossover to the ruxolitinib arm
3. Proportion of patients achieving a peripheral blood count remission at Week 52 as defined by:
• Hct < 45% at Week 16 and maintained until Week 52, and
• WBC < 10 x109/L at Week 16 and maintained until Week 52, and
• Platelets ≤ 400 x 109/L at Week 16 and maintained until Week 52, and
• No phlebotomy from Week 4 to Week 52, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit, and
• In the BAT arm, no change in the treatment regimen or crossover to the ruxolitinib arm.
4. Change in ECOG status from baseline to Week 28.
5. Change from Baseline in spleen length at each scheduled visit
6. Proportion of patients achieving a partial remission at Week 28, based
on the ELN and IWG-MRT criteria, as defined by:
• MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 16 and maintained until Week 28 (for patients with a baseline score of 20 or more), and
• Hct < 45% at Week 16 and maintained until Week 28, and
• No phlebotomy from Week 4 to Week 28, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit, and
• WBC < 10 x109/L at Week 16 and maintained until Week 28, and
• Platelets ≤ 400 x 109/L at Week 16 and maintained until Week 28, and
• No palpable spleen at Week 16 and maintained until Week 28, and
• No hemorrhagic or thrombotic events, and
• No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia.
7. Proportion of patients who achieved partial remission at Week 52, based on the ELN and IWG-MRT criteria, as defined by:
• MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 16 and maintained until Week 52 (for patients with a baseline score of 20 or more), and
• Hct < 45% at Week 16 and maintained until Week 52, and
• No phlebotomy from Week 4 to Week 52, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit, and
• WBC < 10 x109/L at Week 16 and maintained until Week 52, and
• Platelets ≤ 400 x 109/L at Week 16 and maintained until Week 52, and
• No palpable spleen at Week 16 and maintained until Week 52, and
• No hemorrhagic or thrombotic events, and
• No transformation into post-PV myelofibrosis, myelodysplastic syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria), and
• In the BAT arm, no change in the treatment regimen or crossover to the ruxolitinib arm.
8. Among patients randomized to BAT who cross over to ruxolitinib, proportion of patients achieving Hct < 45% at each visit after cross over
9. Proportion of patients achieving at least a 50% reduction from baseline in MPN-SAF TSS score at each visit where it is measured.
10. Proportion of patients achieving a resolution of disease related symptoms in MPN-SAF TSS at Week 28 defined as:
• MPN-SAF TSS score reduction of greater than or equal to 10 points from baseline to Week 16 and maintained until Week 28 (for patients with a baseline score of 20 or more).
11. Change in MPN-SAF TSS from baseline to each visit where measured
• PSIS at each visit where measured.
• Change in EQ-5D-5L score from baseline to each visit where
measured.
• Change in WPAI from baseline to each visit where measured.
• PGIC at each visit where measured.
12. Safety will be assessed by monitoring the frequency, duration and severity of Adverse Events, and evaluating changes in vital signs, electrocardiograms (ECGs), serum chemistry, hematology and urinalysis results.
13. Safety will be assessed by monitoring the frequency, duration and severity of Adverse Events, and evaluating changes in vital signs, electrocardiograms (ECGs), serum chemistry, hematology and urinalysis results. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For key secondary,
1. week 28
For other secondary:
2. week 52
3. week 52
4. week 28
5. week 4, 8, 12, 16, 20, 24, 28, 40, 52/End of Treatment
6. week 28
7. week 52
8. +4, +8, +12, +16, +20, +24 weeks after crossover
9. week 4, 8, 16, 28, 40, 52/End of Treatment
10. week 28
11. week 4, 8, 16, 28, 40, 52/End of Treatment
12. week 28, 52/End of Treatment
13. +52/End of Treatment |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
document medical resource utilization (MRU) |
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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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Best available therapy (BAT) |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Canada |
France |
Italy |
Australia |
Germany |
Hungary |
India |
Korea, Republic of |
Spain |
Israel |
Switzerland |
Turkey |
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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
|
Last Patient Last Visit defined as after all patients have either discontinued or completed the Week 52 visit or the applicable cross-over visit plus the 30 day follow up visit |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |