E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Polycythemia vera resistant or intolerant to hydroxyurea |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036061 |
E.1.2 | Term | Polycythemia vera |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
|
E.2.2 | Secondary objectives of the trial |
Key
1. efficacy of RUX to BAT assessed by complete hematological remission at W28
Other
2. efficacy of RUX to BAT assessed by durable Hct control at W52 and
W80
3. efficacy of RUX to BAT assessed by durable complete hematological remission at W52 &
W80
4. assess phlebotomies over time
5. change in Hct
6. assess spleen length
7. ECOG status change
8. efficacy of RUX to BAT assessed by partial remission based on
ELN+IWG-MRT criteria at W28
9. efficacy of RUX to BAT assessed by durable partial remission based on
ELN+IWG-MRT criteria at W52 & W80
10. efficacy of BAT pts after crossover
11. efficacy of RUX pts measured by durable Hct control at W104, 156,
208, 260
12. efficacy of RUX pts measured by durable complete hematological remission at W104,
156, 208, 260
13. efficacy of RUX pts by partial remission based on ELN+IWG-MRT
criteria at W104, 156, 208, 260
14. transformation-free survival
15. OS
16. changes in PRO |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Confirmed diagnosis of PV according to the 2008 World Health
Organization criteria
2. Non-palpable spleen at Screening and Baseline
3. Phlebotomy dependent, Resistant to or intolerant of hydroxyurea
4. 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving Hct control at Week 28 as defined by
the absence of phlebotomy eligibility starting at Week 8 and continuing
through Week 28, with no more than one phlebotomy eligibility
occurring post randomization and prior to Week 8.
Phlebotomy eligibility will be defined by:
• Confirmed Hct > 45% that is at least 3 percentage points higher than
the Hct obtained at Baseline
Or
• Confirmed Hct > 48%.
The confirmation will occur 2 to 14 days subsequent to the initial
observation. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Key secondary:
Proportion of patients achieving a complete hematological remission at Week 28 as defined by:
• Hct control at Week 28 defined by the absence of phlebotomy eligibility
starting at Week 8 and continuing through Week 28, with no more than
one phlebotomy eligibility occurring post randomization and prior to
Week 8, and
• WBC < 10 x109/L at Week 28, and
• Platelets ≤ 400 x 109/L at Week 28
Other secondary:
1. Proportion of patients achieving a Hct control at Week 52 as defined
by:
• the absence of phlebotomy eligibility starting at Week 8 and continuing
through Week 52, with no more than one phlebotomy eligibility
occurring post randomization and prior to Week 8
In the BAT arm, no change in the treatment regimen or crossover to the
ruxolitinib arm. Endpoint for Week 80 is defined, similarly.
2. Proportion of patients achieving a complete hematological remission at Week 52 as defined by:
• Hct control at Week 52 as defined by the absence of phlebotomy
eligibility starting at Week 8 and continuing through Week 52, with no
more than one phlebotomy eligibility occurring post randomization and
prior to week 8, and
• WBC < 10 x109/L at Week 52, and
• Platelets ≤ 400 x 109/L at Week 52, and
In the BAT arm, no change in the treatment regimen or crossover to the
ruxolitinib arm. Endpoint for Week 80 is defined, similarly.
3. Number of phlebotomies from Baseline up to Week 28
4. Change from Baseline in Hct at each scheduled visit
5. Summary of spleen length by visit
6. Change in ECOG status from baseline to Week 28.
7. 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 28 and
• Hct control defined by the absence of phlebotomy eligibility starting at
Week 8 and continuing through Week 28, with no more than one
phlebotomy eligibility occurring post randomization and prior to Week 8,
and
• WBC < 10 x109/L at Week 28, and
• Platelets ≤ 400 x 109/L at Week 28, and
• No palpable spleen at Week 28, and
• No hemorrhagic or thrombotic events, and
No transformation into post-PV myelofibrosis, myelodysplastic syndrome
(IWG-MRT criteria) or acute leukemia (WHO criteria).
8. 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 52, and
• Hct control defined by the absence of phlebotomy eligibility starting at
Week 8 and continuing through Week 52, with no more than one
phlebotomy eligibility occurring post randomization and prior to Week 8,
and
• WBC < 10 x109/L at Week 52, and
• Platelets ≤ 400 x 109/L at Week 52, and
• No palpable spleen at 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. Endpoint for Week 80 is defined, similarly.
9. Change from Baseline (last assessment before crossover) in Hct at each scheduled visit after crossover in patients randomized to BAT who
cross over to RUX
10.Proportion of patients achieving a Hct control at Week 104 as
defined by:
• The absence of phlebotomy eligibility starting at Week 8 and
continuing through Week 104 and
• with no more than one phlebotomy eligibility occurring post
randomization and prior to Week 8
Endpoint for Week 156, Week 208 and Week 260 are defined, similarly.
11. Proportion of patients achieving a complete hematological remission
at Week 104 as defined by:
• Hct control defined by the absence of phlebotomy eligibility starting at
Week 8 and continuing through Week 104, with no more than one
phlebotomy eligibility occurring post randomization and prior to Week 8,
and
• WBC < 10 x109/L at Week 104, and
• Platelets ≤ 400 x 109/L at Week 104
Endpoint for Week 156, Week 208 and Week 260 are defined, similarly
12. Proportion of patients who achieved partial remission at Week 104,
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 104, and
• Hct control defined by the absence of phlebotomy eligibility starting at
Week 8 and continuing through Week 104, with no more than one
phlebotomy eligibility occurring post randomization and prior to Week 8,
and
• WBC < 10 x109/L at Week 104, and
• Platelets ≤ 400 x 109/L at Week 104, and
• No palpable spleen at Week 104, and
• No hemorrhagic or thrombotic events, and
• No transformation into post-PV myelofibrosis, myelodysplastic
syndrome (IWG-MRT criteria) or acute leukemia (WHO criteria), and
Endpoint for Week 156, Week 208 and Week 260 are defined, similarly. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
For key secondary,
1. week 28
For other secondary:
1. week 52
2. week 52
3. week 4, 8, 12, 16, 20, 24, 28, 40, 52/End of Treatment
4. week 4, 8, 12, 16, 20, 24, 28, 40, 52/End of Treatment
5. week 4, 8, 12, 16, 20, 24, 28, 40, 52/End of Treatment
6. week 28
7. week 28
8. week 52
9. +4, +8, +12, +16, +20, +24 weeks after crossover
10. week 104
11. week 104
12. week 104 |
|
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) |
|
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) |
|
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.8.5 | 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 |
Australia |
Belgium |
Canada |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Korea, Republic of |
Spain |
Switzerland |
Turkey |
|
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
|
The end of study will occur 5 years and 30 days from the date when the last patient was randomized. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 3 |