RESPONSE-2: Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02038036
• Collaborator: (none)
• Enrollment: 149
• Locations: 48
• Arms: 2
• Actual Duration (Months): 72.4
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study compared the efficacy and safety of ruxolitinib to Best Available Therapy (BAT) in patients with polycythemia vera (PV) who were hydroxyurea (HU) resistant or intolerant and did not have a palpable spleen.

Condition or Disease	Intervention/Treatment	Phase
Polycythemia Vera	Drug: Best Available Therapy; Drug: Ruxolitinib	Phase 3

Detailed Description

This was a prospective, multi-center, open-label, randomized, Phase IIIb study evaluating efficacy and safety of ruxolitinib versus BAT as selected by the Investigator in patients with PV who are resistant to, or intolerant of HU.

The study comprised of the following periods:

Screening Period (up to 5 weeks: Day -35 to Day -1): Screening evaluations were performed at one or more clinic visits, and reviewed to determine eligibility before the patient was randomized in the study.

Core Treatment Period (Day 1 to Week 80):

Patients were randomized in 1:1 ratio to either treatment group (ruxolitinib or BAT) and were to be treated with their randomized treatment.

Crossover Treatment Period (Week 28 or after) for BAT patients only:

Patients randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib. Patients crossing over on or after Week 28 had to complete all assessments for the End of Treatment (EoT) visit of the Core Treatment Period followed by the assessments in Cross-over visit evaluation schedule.

Extended Treatment Period (Week 80 to Week 260):

Patients receiving ruxolitinib at Week 80 (including patients who have crossed over from BAT) were eligible to continue up to Week 260 in the Extended Treatment Period. Patients continued the ruxolitinib dose that they received at Week 80. Patients who received BAT at Week 80 were not eligible to enter the Extended Treatment Period and had to have the EoT visit at Week 80 and an End of study (EoS) visit 30 days after the EoT visit.

Follow-up Period:

Patients were followed for safety during 30 days after the last dose of study drug and EoS visit assessments were performed post 30 days after the last dose of study drug. Patients who completed EoT (Week 80 for patients who received BAT, Week 260 for patients who received ruxolitinib or from the time of premature discontinuation) were to be followed-up for every 3 months for survival till the end of the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 149 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Open Label, Multicenter Phase IIIb Study Evaluating the Efficacy and Safety of Ruxolitinib Versus Best Available Therapy in Patients With Polycythemia Vera Who Are Hydroxyurea Resistant or Intolerant (Response 2)
• Actual Study Start Date: Mar 25, 2014
• Actual Primary Completion Date: Sep 29, 2015
• Actual Study Completion Date: Apr 7, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ruxolitinib Ruxolitinib was administered at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid.	Drug: Ruxolitinib; Ruxolitinib was administered at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid.; Other Names: INC424
Active Comparator: Best Available Therapy (BAT) Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib.	Drug: Best Available Therapy; Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib.; Other Names: BAT

Outcome Measures

Primary Outcome Measures

1. Number of Participants Achieving Hematocrit (Hct) Control at Week 28 [Week 28]

   Proportion of patients achieving Hct control at Week 28 was 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 was 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 occurred 2 to 14 days subsequent to the initial observation.

Secondary Outcome Measures

1. Number of Participants Achieving a Complete Hematological Remission at Week 28 [Week 28]

   Proportion of patients achieving a complete hematological remission at Week 28 was 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

2. Number of Participants Achieving a Hematocrit (Hct) Control at Week 52 and Week 80 [Week 52 and 80]

   Proportion of patients achieving a Hct control at Week 52 was defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52, and no more than one phlebotomy eligibility occurring post randomization and prior to Week 8 - Endpoint for Week 80 was defined, similarly.

3. Number of Participants Achieving a Complete Hematological Remission at Week 52 and Week 80 [Week 52 and 80]

   Proportion of patients achieving a complete hematological remission at Week 52, was 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 White Blood Count (WBC) < 10 x10^9/L at Week 52, and Platelets ≤ 400 x 10^9/L at Week 52 Endpoint for Week 80 was defined, similarly.

4. Number of Participants With Phlebotomies Over Time [Baseline to Week 260]

   Phlebotomy eligibility was 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 occurred 2 to 14 days subsequent to the initial observation.

5. Change From Baseline in Hematocrit (Hct) at Each Visit [Baseline, Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 66, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234, 247 and 260]

   Hematocrit is the volume percentage of red blood cells (RBC) in the blood.

6. Change From Baseline in Hematocrit (Hct) at Each Scheduled Visit After Crossover in Participants Randomized to BAT Who Cross Over to Ruxolitinib [Baseline (last assessment before cross over), Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 64, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206, 219 and 232 after cross-over]

   Hematocrit is the percentage of red blood cells (RBC) in the blood.

7. Spleen Length by Visit [Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 66, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234, 247 and 260]

   Spleen length was assessed by manual palpation at every study visit.

8. Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to Week 28 [Baseline and Week 28]

   The ECOG scale of performance status described the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. The ECOG performance was recorded as per ECOG performance status grades ranging from 0 (fully active, able to carry on all pre-disease performance without restriction) to 5 (dead).

9. Number of Participants Achieving a Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 28 [Week 28]

   Proportion of patients achieving a partial remission at Week 28, based on the ELN and IWG-MRT criteria, as defined by: Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (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 x10^9/L at Week 28, and Platelets ≤ 400 x 10^9/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).

10. Number of Participants Who Achieved Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 52 and Week 80 [Week 52 and 80]

    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). Endpoint for Week 80 was defined, similarly.

11. Number of Participants Achieving a Hematocrit (Hct) Control at Week 104, Week 156, Week 208 and Week 260. [From Week 8 to Week 104, 156, 208 and 260]

    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 were defined, similarly.

12. Number of Participants Achieving a Complete Hematological Remission at Week 104, Week 156, Week 208 and Week 260 [From Week 8 to Week 104, 156, 208 and 260]

    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 x10^9/L at Week 104, and Platelets ≤ 400 x 10^9/L at Week 104 Endpoint for Week 156, Week 208 and Week 260 were defined, similarly.

13. Number of Participants Who Achieved Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 104, Week 156, Week 208 and Week 260. [From Week 8 to Week 104, 156, 208 and 260]

    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 x10^9/L at Week 104, and Platelets ≤ 400 x 10^9/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) Endpoint for Week 156, Week 208 and Week 260 are defined, similarly.

14. Number of Participants With Transformation Free Survival Events [Week 260 (ruxolitinib arm) and Week 80 (BAT arm)]

    Transformation-free survival is defined as one of the following: Myelofibrosis (MF) as evidenced by bone marrow biopsy, or Acute leukemia as evidenced by bone marrow blast counts of at least 20%, or peripheral blast counts of at least 20% lasting at least 2 weeks. Death due to any cause during treatment period

15. Number of Participants With Overall Survival (OS) Events [up to Week 260]

    Overall survival (OS) event is defined as death due to any cause. OS events were counted in the BAT arm, irrespective of whether participants crossed over to receive ruxolitinib when the event occurred.

16. Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) [Baseline, Week 4, 8, 16, 28, 40, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247]

    The MPN-SAF TSS is a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms. Each item is scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable).The MPN-SAF TSS is computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus has a possible score range of 0 to 100 where a decrease indicates improvement.

17. Change From Baseline in Total Scores of MPN-SAF by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover [Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, 52, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247 after cross-over]

    The MPN-SAF TSS is a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms. Each item is scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable).The MPN-SAF TSS is computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus has a possible score range of 0 to 100 where a decrease indicates improvement.

18. Change From Baseline in Score as Per European Quality of Life 5-Dimension 5-level (EQ-5D-5L) Questionnaire [Baseline, Week 4, 8, 16, 28, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247]

    EQ-5D-5L is a standardized instrument for measuring health outcomes in a wide range of health conditions and treatments. It consists of visual analogue scale (EQ VAS) which records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'Best imaginable health state' and 'worst imaginable health state'. The EQ VAS scores were anchored on 100 = the best health you can imagine and 0 = worst health you can imagine.

19. Change From Baseline in EQ-5D-5L VAS, by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover [Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 52, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247 after cross-over]

    EQ-5D-5L is a standardized instrument for measuring health outcomes in a wide range of health conditions and treatments. It consists of visual analogue scale (EQ VAS) which records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'Best imaginable health state' and 'worst imaginable health state'. The EQ VAS scores were anchored on 100 = the best health you can imagine and 0 = worst health you can imagine.

20. Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire [Baseline, Week 4, 8, 16, 28, 52 and 80]

    The Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a six item questionnaire which intended to measure work and activity impairment associated with polycythemia vera. WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the polycythemia vera; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the polycythemia vera on productivity while working; Q6=Impact of the polycythemia vera on productivity while doing regular daily activities other than work). Higher WPAI scores indicated greater activity impairment. Scores were multiplied by 100 to express in percentages. Percent work time missed due to problem (past 7 days) =Q2/(Q2+Q4) Percent impairment while working due to problem (past 7 days): Q5/10 Percent overall work impairment due to problem (past 7 says): Q2/(Q2+Q4)+[(1 Q2/(Q2+Q4))x(Q5/10)] Percent activity impairment due to problem (past 7 says): Q6/10

21. Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI), by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover [Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28 and 52 after cross-over]

    The Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a six item questionnaire which intended to measure work and activity impairment associated with polycythemia vera. WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the polycythemia vera; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the polycythemia vera on productivity while working; Q6=Impact of the polycythemia vera on productivity while doing regular daily activities other than work). Higher WPAI scores indicated greater activity impairment. Scores were multiplied by 100 to express in percentages. Percent work time missed due to problem (past 7 days) =Q2/(Q2+Q4) Percent impairment while working due to problem (past 7 days): Q5/10 Percent overall work impairment due to problem (past 7 says): Q2/(Q2+Q4)+[(1 Q2/(Q2+Q4))x(Q5/10)] Percent activity impairment due to problem (past 7 says): Q6/10

22. Patient Global Impression of Change (PGIC) [Week 4, 8, 16, 28, 40, 52 and 80]

    The Patient Global Impression of Change (PGIC) is comprised of a single question intended to measure a patient's perspective of improvement or deterioration over time relative to treatment. The PGIC uses a seven-point scale where one (1) equals very much improved and seven (7) equals very much worse.

23. Summary of Patient Global Impression of Change (PGIC), by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover [Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, and 52 after cross-over]

    The Patient Global Impression of Change (PGIC) is comprised of a single question intended to measure a patient's perspective of improvement or deterioration over time relative to treatment. The PGIC uses a seven-point scale where one (1) equals very much improved and seven (7) equals very much worse.

24. Number of Participants Developing Thrombosis [From randomization to Week 80 for BAT and Week 260 for Ruxolitinib]

    Proportion of participants developing any arterial or venous thromboembolic event

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

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 inclusion/exclusion criteria apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Herston	Queensland	Australia	4029
2	Novartis Investigative Site	Antwerpen		Belgium	2060
3	Novartis Investigative Site	Leuven		Belgium	3000
4	Novartis Investigative Site	Toronto	Ontario	Canada	M4N 3M5
5	Novartis Investigative Site	Bayonne	Bayonne Cedex	France	64109
6	Novartis Investigative Site	Bordeaux		France	33076
7	Novartis Investigative Site	Brest		France	29200
8	Novartis Investigative Site	Lille cedex		France	59020
9	Novartis Investigative Site	Nice Cedex		France	06202
10	Novartis Investigative Site	Paris		France	75010
11	Novartis Investigative Site	Toulouse		France	31059
12	Novartis Investigative Site	Mannheim	Baden-Wuerttemberg	Germany	68305
13	Novartis Investigative Site	Augsburg		Germany	86150
14	Novartis Investigative Site	Dresden		Germany	01307
15	Novartis Investigative Site	Jena		Germany	07740
16	Novartis Investigative Site	Leipzig		Germany	04103
17	Novartis Investigative Site	Magdeburg		Germany	39120
18	Novartis Investigative Site	Mainz		Germany	55131
19	Novartis Investigative Site	Minden		Germany	32429
20	Novartis Investigative Site	Ulm		Germany	89081
21	Novartis Investigative Site	Budapest		Hungary	1085
22	Novartis Investigative Site	Debrecen		Hungary	4032
23	Novartis Investigative Site	Kaposvar		Hungary	7400
24	Novartis Investigative Site	Mumbai	Maharashtra	India	400012
25	Novartis Investigative Site	Vellore	Tamil Nadu	India	632 004
26	Novartis Investigative Site	Nahariya		Israel	22100
27	Novartis Investigative Site	Netanya		Israel	42150
28	Novartis Investigative Site	Tel Aviv		Israel	6423906
29	Novartis Investigative Site	Bologna	BO	Italy	40138
30	Novartis Investigative Site	Firenze	FI	Italy	50134
31	Novartis Investigative Site	Roma	Lazio	Italy	00168
32	Novartis Investigative Site	Milano	MI	Italy	20122
33	Novartis Investigative Site	Pavia	PV	Italy	27100
34	Novartis Investigative Site	Torino	TO	Italy	10126
35	Novartis Investigative Site	Varese	VA	Italy	21100
36	Novartis Investigative Site	Seoul		Korea, Republic of	03080
37	Novartis Investigative Site	Seoul		Korea, Republic of	03722
38	Novartis Investigative Site	Malaga	Andalucia	Spain	29010
39	Novartis Investigative Site	Salamanca	Castilla Y Leon	Spain	37007
40	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
41	Novartis Investigative Site	Alicante	Comunidad Valenciana	Spain	03010
42	Novartis Investigative Site	La Coruna	Galicia	Spain	15006
43	Novartis Investigative Site	Las Palmas de Gran Canaria	Las Palmas De G.C	Spain	35010
44	Novartis Investigative Site	Pamplona	Navarra	Spain	31008
45	Novartis Investigative Site	Madrid		Spain	28034
46	Novartis Investigative Site	Madrid		Spain	28046
47	Novartis Investigative Site	Izmir		Turkey	35040
48	Novartis Investigative Site	Talas / Kayseri		Turkey	38039

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02038036
• Other Study ID Numbers: CINC424B2401
• First Posted: Jan 16, 2014
• Last Update Posted: Jul 20, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Polycythemia Vera; Hematologic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Hydroxyurea; INC424; Ruxolitinib
• Additional relevant MeSH terms: Polycythemia Vera; Polycythemia

Study Results

Participant Flow

Recruitment Details	Participants were randomized in 48 centers across 12 countries: Australia (1), Belgium (2), Canada (1), France (7), Germany (9), Hungary (3), India (2), Israel (3), Italy (7), South Korea (2), Spain (9) and Turkey (2)
Pre-assignment Detail	Participants were randomized in a 1:1 ratio either to Ruxolitinib or Best available Therapy (BAT). Randomization was stratified by patients who were resistant to or intolerant of Hydroxyurea (HU).

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Period Title: Core Study
STARTED	74	75
Full Analysis Set	74	75
Crossover Set	0	58
COMPLETED	59	61
NOT COMPLETED	15	14
Period Title: Core Study
STARTED	0	58
COMPLETED	0	38
NOT COMPLETED	0	20

Baseline Characteristics

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)	Total
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib	Total of all reporting groups
Overall Participants	74	75	149
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.8 (11.31)	66.0 (11.12)	64.4 (11.29)
Sex: Female, Male (Count of Participants)
Female	35 47.3%	28 37.3%	63 42.3%
Male	39 52.7%	47 62.7%	86 57.7%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	67 90.5%	66 88%	133 89.3%
Asian	4 5.4%	5 6.7%	9 6%
Other	3 4.1%	4 5.3%	7 4.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Achieving Hematocrit (Hct) Control at Week 28
Description	Proportion of patients achieving Hct control at Week 28 was 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 was 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 occurred 2 to 14 days subsequent to the initial observation.
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Count of Participants [Participants]	46 62.2%	14 18.7%

2. Secondary Outcome

Title	Number of Participants Achieving a Complete Hematological Remission at Week 28
Description	Proportion of patients achieving a complete hematological remission at Week 28 was 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
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Count of Participants [Participants]	17 23%	4 5.3%

3. Secondary Outcome

Title	Number of Participants Achieving a Hematocrit (Hct) Control at Week 52 and Week 80
Description	Proportion of patients achieving a Hct control at Week 52 was defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 52, and no more than one phlebotomy eligibility occurring post randomization and prior to Week 8 - Endpoint for Week 80 was defined, similarly.
Time Frame	Week 52 and 80

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Week 52	44 59.5%	5 6.7%
Week 80	35 47.3%	2 2.7%

4. Secondary Outcome

Title	Number of Participants Achieving a Complete Hematological Remission at Week 52 and Week 80
Description	Proportion of patients achieving a complete hematological remission at Week 52, was 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 White Blood Count (WBC) < 10 x10^9/L at Week 52, and Platelets ≤ 400 x 10^9/L at Week 52 Endpoint for Week 80 was defined, similarly.
Time Frame	Week 52 and 80

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Week 52	17 23%	3 4%
Week 80	18 24.3%	2 2.7%

5. Secondary Outcome

Title	Number of Participants With Phlebotomies Over Time
Description	Phlebotomy eligibility was 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 occurred 2 to 14 days subsequent to the initial observation.
Time Frame	Baseline to Week 260

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Phlebotomy frequency: >0 - <=2	12 16.2%	29 38.7%
Phlebotomy frequency: >2 - <=4	7 9.5%	17 22.7%
Phlebotomy frequency: >4 - <=6	4 5.4%	2 2.7%
Phlebotomy frequency: >6 - <=8	0 0%	1 1.3%

6. Secondary Outcome

Title	Change From Baseline in Hematocrit (Hct) at Each Visit
Description	Hematocrit is the volume percentage of red blood cells (RBC) in the blood.
Time Frame	Baseline, Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 66, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234, 247 and 260

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Week 4	-0.65 (2.943)	1.25 (2.994)
Week 8	-1.22 (3.634)	1.63 (3.344)
Week 12	-2.33 (4.581)	1.70 (3.485)
Week 16	-3.25 (4.179)	1.83 (3.439)
Week 20	-3.05 (4.307)	1.45 (3.984)
Week 24	-2.85 (4.094)	1.52 (2.934)
Week 28	-2.60 (4.101)	2.09 (3.852)
Week 40	-2.77 (4.538)	2.05 (4.587)
Week 52	-2.49 (4.445)	1.68 (4.854)
Week 66	-3.06 (4.573)	2.73 (2.922)
Week 80	-3.20 (3.886)	0.62 (4.436)
Week 92	-2.91 (4.203)
Week 104	-3.19 (4.314)
Week 117	-2.86 (4.540)
Week 130	-3.13 (4.263)
Week 143	-3.50 (3.463)
Week 156	-3.54 (4.005)
Week 169	-3.57 (4.477)
Week 182	-2.94 (4.428)
Week 195	-3.36 (4.515)
Week 208	-3.23 (4.150)
Week 221	-3.55 (4.413)
Week 234	-3.31 (4.621)
Week 247	-3.45 (4.053)
Week 260	-2.93 (3.799)

7. Secondary Outcome

Title	Change From Baseline in Hematocrit (Hct) at Each Scheduled Visit After Crossover in Participants Randomized to BAT Who Cross Over to Ruxolitinib
Description	Hematocrit is the percentage of red blood cells (RBC) in the blood.
Time Frame	Baseline (last assessment before cross over), Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 64, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206, 219 and 232 after cross-over

Outcome Measure Data

Analysis Population Description

Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

Arm/Group Title	All Crossover Patients
Arm/Group Description	Participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib
Measure Participants	58
Week +4	-2.44 (3.394)
Week +8	-4.24 (5.322)
Week +12	-5.73 (6.597)
Week +16	-6.27 (7.101)
Week +20	-5.76 (6.563)
Week +24	-5.29 (6.518)
Week +28	-6.04 (5.825)
Week +40	-6.06 (6.301)
Week +52	-5.91 (6.399)
Week +64	-7.06 (6.051)
Week +76	-6.16 (6.247)
Week +89	-6.79 (6.046)
Week +102	-6.21 (6.599)
Week +115	-7.04 (6.103)
Week +128	-7.41 (6.812)
Week +141	-7.00 (6.310)
Week +154	-7.06 (7.000)
Week +167	-7.44 (7.426)
Week +180	-7.51 (7.298)
Week +193	-7.16 (5.331)
Week +206	-7.09 (5.742)
Week +219	-6.95 (5.936)
Week +232	-7.51 (5.880)

8. Secondary Outcome

Title	Spleen Length by Visit
Description	Spleen length was assessed by manual palpation at every study visit.
Time Frame	Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 66, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234, 247 and 260

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT were not collected.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Week 4	0.00 (0.000)	0.04 (0.351)
Week 8	0.00 (0.000)	0.01 (0.119)
Week 12	0.00 (0.000)	0.01 (0.120)
Week 16	0.00 (0.000)	0.23 (1.010)
Week 20	0.00 (0.000)	0.13 (0.716)
Week 24	0.00 (0.000)	0.09 (0.555)
Week 28	0.00 (0.000)	0.20 (0.909)
Week 40	0.01 (0.120)	0.52 (1.473)
Week 52	0.06 (0.482)	0.07 (0.258)
Week 66	0.00 (0.000)	0.00 (0.000)
Week 80	0.03 (0.246)	0.00 (0.000)
Week 92	0.00 (0.000)
Week 104	0.05 (0.378)
Week 117	0.12 (0.985)
Week 130	0.18 (1.162)
Week 143	0.08 (0.458)
Week 156	0.05 (0.372)
Week 169	0.05 (0.378)
Week 182	0.05 (0.381)
Week 195	0.00 (0.000)
Week 208	0.00 (0.000)
Week 221	0.02 (0.129)
Week 234	0.00 (0.000)
Week 247	0.02 (0.136)
Week 260	0.10 (0.617)

9. Secondary Outcome

Title	Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to Week 28
Description	The ECOG scale of performance status described the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. The ECOG performance was recorded as per ECOG performance status grades ranging from 0 (fully active, able to carry on all pre-disease performance without restriction) to 5 (dead).
Time Frame	Baseline and Week 28

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
0: Fully active, able to carry on all pre-disease performance without restriction	49 66.2%	17 22.7%
1: Restricted in physically strenuous activity and able to carry out light or sedentary work	2 2.7%	1 1.3%
2: Ambulatory and capable of all self-care but unable to carry out any work activities	0 0%	0 0%
3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours	0 0%	0 0%
4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair	0 0%	0 0%
Missing	2 2.7%	38 50.7%
0: Fully active, able to carry on all pre-disease performance without restriction	9 12.2%	1 1.3%
1: Restricted in physically strenuous activity and able to carry out light or sedentary work	10 13.5%	5 6.7%
2: Ambulatory and capable of all self-care but unable to carry out any work activities	1 1.4%	0 0%
3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours	0 0%	0 0%
4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair	0 0%	0 0%
Missing	1 1.4%	13 17.3%

10. Secondary Outcome

Title	Number of Participants Achieving a Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 28
Description	Proportion of patients achieving a partial remission at Week 28, based on the ELN and IWG-MRT criteria, as defined by: Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (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 x10^9/L at Week 28, and Platelets ≤ 400 x 10^9/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).
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Count of Participants [Participants]	7 9.5%	0 0%

11. Secondary Outcome

Title	Number of Participants Who Achieved Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 52 and Week 80
Description	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). Endpoint for Week 80 was defined, similarly.
Time Frame	Week 52 and 80

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Week 52	5 6.8%	0 0%
Week 80	4 5.4%	0 0%

12. Secondary Outcome

Title	Number of Participants Achieving a Hematocrit (Hct) Control at Week 104, Week 156, Week 208 and Week 260.
Description	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 were defined, similarly.
Time Frame	From Week 8 to Week 104, 156, 208 and 260

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT were not collected.

Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid
Measure Participants	74
HU Resistant	9 12.2%
HU Intolerant	25 33.8%
HU Resistant	9 12.2%
HU Intolerant	21 28.4%
HU Resistant	7 9.5%
HU Intolerant	18 24.3%
HU Resistant	4 5.4%
HU Intolerant	12 16.2%

13. Secondary Outcome

Title	Number of Participants Achieving a Complete Hematological Remission at Week 104, Week 156, Week 208 and Week 260
Description	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 x10^9/L at Week 104, and Platelets ≤ 400 x 10^9/L at Week 104 Endpoint for Week 156, Week 208 and Week 260 were defined, similarly.
Time Frame	From Week 8 to Week 104, 156, 208 and 260

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT were not collected.

Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid
Measure Participants	74
Week 104	15 20.3%
Week 156	19 25.7%
Week 208	11 14.9%
Week 260	9 12.2%

14. Secondary Outcome

Title	Number of Participants Who Achieved Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 104, Week 156, Week 208 and Week 260.
Description	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 x10^9/L at Week 104, and Platelets ≤ 400 x 10^9/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) Endpoint for Week 156, Week 208 and Week 260 are defined, similarly.
Time Frame	From Week 8 to Week 104, 156, 208 and 260

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT were not collected.

Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid
Measure Participants	74
Week 104	4 5.4%
Week 156	9 12.2%
Week 208	4 5.4%
Week 260	0 0%

15. Secondary Outcome

Title	Number of Participants With Transformation Free Survival Events
Description	Transformation-free survival is defined as one of the following: Myelofibrosis (MF) as evidenced by bone marrow biopsy, or Acute leukemia as evidenced by bone marrow blast counts of at least 20%, or peripheral blast counts of at least 20% lasting at least 2 weeks. Death due to any cause during treatment period
Time Frame	Week 260 (ruxolitinib arm) and Week 80 (BAT arm)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Count of Participants [Participants]	4 5.4%	3 4%

16. Secondary Outcome

Title	Number of Participants With Overall Survival (OS) Events
Description	Overall survival (OS) event is defined as death due to any cause. OS events were counted in the BAT arm, irrespective of whether participants crossed over to receive ruxolitinib when the event occurred.
Time Frame	up to Week 260

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Count of Participants [Participants]	3 4.1%	6 8%

17. Secondary Outcome

Title	Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
Description	The MPN-SAF TSS is a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms. Each item is scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable).The MPN-SAF TSS is computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus has a possible score range of 0 to 100 where a decrease indicates improvement.
Time Frame	Baseline, Week 4, 8, 16, 28, 40, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Week 4	-8.43 (12.341)	0.40 (12.586)
Week 8	-9.86 (12.210)	1.37 (12.046)
Week 16	-9.14 (13.980)	1.41 (10.760)
Week 28	-10.29 (14.204)	2.34 (13.047)
Week 40	-9.35 (14.027)	0.10 (9.586)
Week 52	-8.63 (13.403)	0.63 (9.334)
Week 80	-9.04 (13.520)
Week 92	-7.69 (11.971)
Week 104	-6.82 (13.297)
Week 117	-6.76 (13.702)
Week 130	-8.26 (16.234)
Week 143	-8.56 (15.653)
Week 156	-8.48 (15.081)
Week 169	-7.65 (14.392)
Week 182	-9.34 (14.675)
Week 195	-7.57 (14.922)
Week 208	-9.26 (16.347)
Week 221	-7.20 (16.054)
Week 234	-7.50 (15.922)
Week 247	-7.82 (16.905)

18. Secondary Outcome

Title	Change From Baseline in Total Scores of MPN-SAF by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Description	The MPN-SAF TSS is a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms. Each item is scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable).The MPN-SAF TSS is computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus has a possible score range of 0 to 100 where a decrease indicates improvement.
Time Frame	Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, 52, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247 after cross-over

Outcome Measure Data

Analysis Population Description

Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

Arm/Group Title	Best Available Therapy (BAT)
Arm/Group Description	Participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib
Measure Participants	58
Week +4	-8.00 (10.532)
Week +8	-9.76 (11.543)
Week +16	-9.40 (12.040)
Week +24	-9.15 (12.738)
Week +28	-8.46 (12.212)
Week +40	-8.58 (13.302)
Week +52	-7.15 (14.392)
Week 92	-10.49 (13.902)
Week 104	-8.08 (16.288)
Week 117	-9.01 (14.708)
Week 130	-10.18 (15.740)
Week 143	-8.36 (17.030)
Week 156	-9.54 (14.573)
Week 169	-11.15 (14.305)
Week 182	-10.13 (16.113)
Week 195	-10.88 (14.357)
Week 208	-9.43 (15.360)
Week 221	-10.02 (15.986)
Week 234	-8.01 (14.404)
Week 247	-9.84 (14.979)

19. Secondary Outcome

Title	Change From Baseline in Score as Per European Quality of Life 5-Dimension 5-level (EQ-5D-5L) Questionnaire
Description	EQ-5D-5L is a standardized instrument for measuring health outcomes in a wide range of health conditions and treatments. It consists of visual analogue scale (EQ VAS) which records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'Best imaginable health state' and 'worst imaginable health state'. The EQ VAS scores were anchored on 100 = the best health you can imagine and 0 = worst health you can imagine.
Time Frame	Baseline, Week 4, 8, 16, 28, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Week 4	4.24 (11.661)	0.04 (18.323)
Week 8	7.62 (14.846)	-2.73 (16.097)
Week 16	6.35 (17.946)	-3.12 (14.435)
Week 28	7.56 (14.309)	0.16 (15.201)
Week 52	7.36 (13.996)	2.50 (10.697)
Week 80	4.50 (18.273)
Week 92	6.77 (18.948)
Week 104	6.25 (18.143)
Week 117	6.42 (15.130)
Week 130	7.70 (16.488)
Week 143	5.68 (17.332)
Week 156	4.74 (19.032)
Week 169	6.08 (18.717)
Week 182	7.68 (17.992)
Week 195	6.41 (18.239)
Week 208	7.94 (18.614)
Week 221	3.64 (19.866)
Week 234	5.48 (18.625)
Week 247	6.28 (17.854)

20. Secondary Outcome

Title	Change From Baseline in EQ-5D-5L VAS, by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Description	EQ-5D-5L is a standardized instrument for measuring health outcomes in a wide range of health conditions and treatments. It consists of visual analogue scale (EQ VAS) which records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labeled 'Best imaginable health state' and 'worst imaginable health state'. The EQ VAS scores were anchored on 100 = the best health you can imagine and 0 = worst health you can imagine.
Time Frame	Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 52, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247 after cross-over

Outcome Measure Data

Analysis Population Description

Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

Arm/Group Title	Best Available Therapy (BAT)
Arm/Group Description	Participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib
Measure Participants	58
Week +4	4.54 (14.756)
Week +8	4.62 (15.807)
Week +16	6.58 (14.667)
Week +24	6.38 (17.564)
Week +28	5.26 (15.923)
Week +52	4.71 (21.006)
Week 92	8.09 (16.119)
Week 104	6.48 (18.085)
Week 117	4.92 (16.983)
Week 130	4.87 (20.047)
Week 143	3.19 (17.798)
Week 156	2.65 (20.221)
Week 169	4.59 (13.731)
Week 182	2.71 (19.673)
Week 195	5.65 (18.286)
Week 208	5.35 (18.099)
Week 221	7.71 (16.701)
Week 234	5.30 (18.342)
Week 247	4.14 (16.427)

21. Secondary Outcome

Title	Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire
Description	The Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a six item questionnaire which intended to measure work and activity impairment associated with polycythemia vera. WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the polycythemia vera; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the polycythemia vera on productivity while working; Q6=Impact of the polycythemia vera on productivity while doing regular daily activities other than work). Higher WPAI scores indicated greater activity impairment. Scores were multiplied by 100 to express in percentages. Percent work time missed due to problem (past 7 days) =Q2/(Q2+Q4) Percent impairment while working due to problem (past 7 days): Q5/10 Percent overall work impairment due to problem (past 7 says): Q2/(Q2+Q4)+[(1 Q2/(Q2+Q4))x(Q5/10)] Percent activity impairment due to problem (past 7 says): Q6/10
Time Frame	Baseline, Week 4, 8, 16, 28, 52 and 80

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Percent work time missed due to problem (past 7 days) Week 4	-5.50 (18.425)	-0.40 (13.928)
Percent work time missed due to problem (past 7 days) Week 8	-4.88 (13.381)	-4.35 (20.820)
Percent work time missed due to problem (past 7 days) Week 16	4.50 (35.948)	4.79 (25.917)
Percent work time missed due to problem (past 7 days) Week 28	-5.85 (17.119)	-2.19 (9.852)
Percent work time missed due to problem (past 7 days) Week 52	-2.82 (30.770)	-8.33 (11.785)
Percent work time missed due to problem (past 7 days) Week 80	1.87 (34.151)
Percent impairment while working due to problem (past 7 days) Week 4	-6.67 (23.310)	0.00 (14.951)
Percent impairment while working due to problem (past 7 days) Week 8	-13.16 (19.164)	-0.59 (13.449)
Percent impairment while working due to problem (past 7 days) Week 16	-14.00 (21.374)	4.12 (16.977)
Percent impairment while working due to problem (past 7 days) Week 28	-14.29 (23.994)	-10.00 (14.142)
Percent impairment while working due to problem (past 7 days) Week 52	-10.00 (23.170)	-20.00 (42.426)
Percent impairment while working due to problem (past 7 days) Week 80	-14.76 (26.385)
Percent overall work impairment due to problem (past 7 days) Week 4	-9.63 (22.495)	-2.34 (14.807)
Percent overall work impairment due to problem (past 7 days) Week 8	-11.32 (18.505)	-4.38 (17.568)
Percent overall work impairment due to problem (past 7 days) Week 16	-10.26 (33.296)	5.34 (22.063)
Percent overall work impairment due to problem (past 7 days) Week 28	-15.98 (23.077)	-8.85 (11.722)
Percent overall work impairment due to problem (past 7 days) Week 52	-12.61 (27.576)	-22.50 (45.962)
Percent overall work impairment due to problem (past 7 days) Week 80	-14.36 (30.691)
Percent activity impairment due to problem (past 7 days) Week 4	-11.97 (22.122)	2.42 (24.310)
Percent activity impairment due to problem (past 7 days) Week 8	-11.58 (24.985)	1.97 (16.413)
Percent activity impairment due to problem (past 7 days) Week 16	-14.36 (25.222)	0.65 (18.980)
Percent activity impairment due to problem (past 7 days) Week 28	-11.67 (25.826)	2.73 (23.941)
Percent activity impairment due to problem (past 7 days) Week 52	-11.23 (25.360)	0.00 (15.374)
Percent activity impairment due to problem (past 7 days) Week 80	-11.09 (24.166)

22. Secondary Outcome

Title	Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI), by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Description	The Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) is a six item questionnaire which intended to measure work and activity impairment associated with polycythemia vera. WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the polycythemia vera; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the polycythemia vera on productivity while working; Q6=Impact of the polycythemia vera on productivity while doing regular daily activities other than work). Higher WPAI scores indicated greater activity impairment. Scores were multiplied by 100 to express in percentages. Percent work time missed due to problem (past 7 days) =Q2/(Q2+Q4) Percent impairment while working due to problem (past 7 days): Q5/10 Percent overall work impairment due to problem (past 7 says): Q2/(Q2+Q4)+[(1 Q2/(Q2+Q4))x(Q5/10)] Percent activity impairment due to problem (past 7 says): Q6/10
Time Frame	Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28 and 52 after cross-over

Outcome Measure Data

Analysis Population Description

Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

Arm/Group Title	Best Available Therapy (BAT)
Arm/Group Description	Participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib
Measure Participants	58
Percent work time missed due to problem (past 7 days) Week +4	-7.45 (28.102)
Percent work time missed due to problem (past 7 days) Week +8	-3.90 (33.237)
Percent work time missed due to problem (past 7 days) Week +16	-2.66 (40.422)
Percent work time missed due to problem (past 7 days) Week +24	-1.67 (5.000)
Percent work time missed due to problem (past 7 days) Week +28	7.06 (21.757)
Percent work time missed due to problem (past 7 days) Week +52	1.12 (3.175)
Percent impairment while working due to problem (past 7 days) Week +4	-5.33 (9.904)
Percent impairment while working due to problem (past 7 days) Week +8	-4.29 (11.579)
Percent impairment while working due to problem (past 7 days) Week +16	-10.83 (20.207)
Percent impairment while working due to problem (past 7 days) Week +24	-6.92 (13.156)
Percent impairment while working due to problem (past 7 days) Week +28	-3.33 (23.868)
Percent impairment while working due to problem (past 7 days) Week +52	-6.00 (13.499)
Percent overall work impairment due to problem (past 7 days) Week +4	-10.98 (20.249)
Percent overall work impairment due to problem (past 7 days) Week +8	-6.91 (24.416)
Percent overall work impairment due to problem (past 7 days) Week +16	-4.73 (30.167)
Percent overall work impairment due to problem (past 7 days) Week +24	-6.06 (14.099)
Percent overall work impairment due to problem (past 7 days) Week +28	-1.81 (20.220)
Percent overall work impairment due to problem (past 7 days) Week +52	-4.03 (12.712)
Percent activity impairment due to problem (past 7 days) Week +4	-10.43 (19.886)
Percent activity impairment due to problem (past 7 days) Week +8	-8.63 (20.978)
Percent activity impairment due to problem (past 7 days) Week +16	-8.82 (21.877)
Percent activity impairment due to problem (past 7 days) Week +24	-6.47 (25.363)
Percent activity impairment due to problem (past 7 days) Week +28	-6.94 (26.395)
Percent activity impairment due to problem (past 7 days) Week +52	-7.00 (22.781)

23. Secondary Outcome

Title	Patient Global Impression of Change (PGIC)
Description	The Patient Global Impression of Change (PGIC) is comprised of a single question intended to measure a patient's perspective of improvement or deterioration over time relative to treatment. The PGIC uses a seven-point scale where one (1) equals very much improved and seven (7) equals very much worse.
Time Frame	Week 4, 8, 16, 28, 40, 52 and 80

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all participants to whom study treatment was assigned by randomization and had valid measurements for the outcome measure. Data after crossover for participants randomized to BAT are reported as separate outcome measure.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Very much improved	10 13.5%	0 0%
Much improved	22 29.7%	8 10.7%
Minimally improved	21 28.4%	7 9.3%
No change	14 18.9%	50 66.7%
Minimally worse	1 1.4%	6 8%
Much worse	0 0%	0 0%
Very much worse	0 0%	1 1.3%
Very much improved	11 14.9%	1 1.3%
Much improved	27 36.5%	14 18.7%
Minimally improved	15 20.3%	9 12%
No change	15 20.3%	35 46.7%
Minimally worse	0 0%	10 13.3%
Much worse	1 1.4%	0 0%
Very much worse	0 0%	1 1.3%
Very much improved	18 24.3%	2 2.7%
Much improved	25 33.8%	13 17.3%
Minimally improved	13 17.6%	12 16%
No change	8 10.8%	33 44%
Minimally worse	2 2.7%	4 5.3%
Much worse	0 0%	5 6.7%
Very much worse	0 0%	0 0%
Very much improved	19 25.7%	0 0%
Much improved	25 33.8%	4 5.3%
Minimally improved	12 16.2%	5 6.7%
No change	9 12.2%	15 20%
Minimally worse	1 1.4%	3 4%
Much worse	0 0%	0 0%
Very much worse	0 0%	0 0%
Very much improved	23 31.1%	0 0%
Much improved	30 40.5%	7 9.3%
Minimally improved	5 6.8%	2 2.7%
No change	6 8.1%	10 13.3%
Minimally worse	2 2.7%	0 0%
Much worse	0 0%	0 0%
Very much worse	0 0%	0 0%
Very much improved	27 36.5%	2 2.7%
Much improved	28 37.8%	5 6.7%
Minimally improved	8 10.8%	1 1.3%
No change	5 6.8%	5 6.7%
Minimally worse	2 2.7%	1 1.3%
Much worse	0 0%	0 0%
Very much worse	0 0%	0 0%
Very much improved	23 31.1%	1 1.3%
Much improved	31 41.9%	1 1.3%
Minimally improved	6 8.1%	3 4%
No change	6 8.1%	0 0%
Minimally worse	1 1.4%	0 0%
Much worse	0 0%	0 0%
Very much worse	0 0%	0 0%
Very much improved	22 29.7%	0 0%
Much improved	24 32.4%	0 0%
Minimally improved	9 12.2%	0 0%
No change	10 13.5%	0 0%
Minimally worse	2 2.7%	0 0%
Much worse	0 0%	0 0%
Very much worse	1 1.4%	0 0%

24. Secondary Outcome

Title	Summary of Patient Global Impression of Change (PGIC), by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover
Description	The Patient Global Impression of Change (PGIC) is comprised of a single question intended to measure a patient's perspective of improvement or deterioration over time relative to treatment. The PGIC uses a seven-point scale where one (1) equals very much improved and seven (7) equals very much worse.
Time Frame	Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, and 52 after cross-over

Outcome Measure Data

Analysis Population Description

Cross-over set consisted of all participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib.

Arm/Group Title	Best Available Therapy (BAT)
Arm/Group Description	Participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib
Measure Participants	58
Very much improved	10 13.5%
Much improved	13 17.6%
Minimally improved	13 17.6%
No change	16 21.6%
Minimally worse	0 0%
Much worse	0 0%
Very much improved	11 14.9%
Much improved	25 33.8%
Minimally improved	9 12.2%
No change	7 9.5%
Minimally worse	1 1.4%
Much worse	0 0%
Very much improved	12 16.2%
Much improved	28 37.8%
Minimally improved	6 8.1%
No change	6 8.1%
Minimally worse	0 0%
Much worse	0 0%
Very much improved	19 25.7%
Much improved	17 23%
Minimally improved	5 6.8%
No change	8 10.8%
Minimally worse	1 1.4%
Much worse	0 0%
Very much improved	18 24.3%
Much improved	19 25.7%
Minimally improved	6 8.1%
No change	6 8.1%
Minimally worse	1 1.4%
Much worse	0 0%
Very much improved	18 24.3%
Much improved	15 20.3%
Minimally improved	5 6.8%
No change	6 8.1%
Minimally worse	0 0%
Much worse	0 0%
Very much improved	17 23%
Much improved	16 21.6%
Minimally improved	6 8.1%
No change	3 4.1%
Minimally worse	0 0%
Much worse	0 0%

25. Secondary Outcome

Title	Number of Participants Developing Thrombosis
Description	Proportion of participants developing any arterial or venous thromboembolic event
Time Frame	From randomization to Week 80 for BAT and Week 260 for Ruxolitinib

Outcome Measure Data

Analysis Population Description

Safety Set comprised of all randomized participants who received at least one dose of ruxolitinib or BAT.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Count of Participants [Participants]	0 0%	0 0%

26. Post-Hoc Outcome

Title	Total Number of Deaths
Description	On-treatment deaths were reported from the day of first dose of study medication to the End of study (End of Treatment +30 days) visit which was Week 260 or prior (+30 days for Rux + crossover) and Week 80 or prior (+30 days for BAT only). Post-treatment deaths were reported following completion study treatment (Week 80 for patients receiving BAT, or Week 260 for patients receiving ruxolitinib) or from the time of premature discontinuation. Patients were followed for survival every three months up to end of study.
Time Frame	Up to Week 260

Outcome Measure Data

Analysis Population Description

Safety Set comprised of all randomized participants who received at least one dose of ruxolitinib or BAT.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid	Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib
Measure Participants	74	75
Death occurring up to 30 days after end of randomised treatment.	1 1.4%	1 1.3%
Death occurring among patients who died after cross over to ruxolitinib (BAT arm only).	0 0%	3 4%
Death occurring more than 30 days after end of treatment.	2 2.7%	2 2.7%

Adverse Events

Time Frame	Adverse events were collected from the day of first dose of study medication to the End of study (End of Treatment +30 days) visit which was Week 260 or prior (+30 days for Rux + crossover) and Week 80 or prior (+30 days for BAT only).
Adverse Event Reporting Description	Any signs or symptoms that occured from the day of first dose of study medication to the End of study (End of Treatment +30 days) visit which was Week 260 or prior (+30 days for Rux + crossover) and Week 80 or prior (+30 days for BAT only).
Arm/Group Title	Ruxolitinib		Best Available Therapy		All Crossover Patients
Arm/Group Description	Ruxolitinib at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid		Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib		Participants randomized to the BAT arm, who crossed over and received at least one dose of ruxolitinib
All Cause Mortality
	Ruxolitinib		Best Available Therapy		All Crossover Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/74 (1.4%)		1/75 (1.3%)		3/58 (5.2%)
Serious Adverse Events
	Ruxolitinib		Best Available Therapy		All Crossover Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/74 (45.9%)		9/75 (12%)		23/58 (39.7%)
Blood and lymphatic system disorders
Anaemia	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Hyperleukocytosis	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Neutropenia	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Thrombocytopenia	0/74 (0%)		2/75 (2.7%)		0/58 (0%)
Thrombocytosis	0/74 (0%)		1/75 (1.3%)		1/58 (1.7%)
Cardiac disorders
Acute myocardial infarction	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Angina pectoris	2/74 (2.7%)		0/75 (0%)		0/58 (0%)
Aortic valve incompetence	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Atrial fibrillation	2/74 (2.7%)		1/75 (1.3%)		1/58 (1.7%)
Cardiac disorder	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Cardiac failure	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Coronary artery disease	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Mitral valve incompetence	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Myocardial infarction	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Pericardial effusion	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Ear and labyrinth disorders
Vertigo positional	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Eye disorders
Glaucoma	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Retinal artery occlusion	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Vision blurred	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Visual acuity reduced	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Gastrointestinal disorders
Abdominal discomfort	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Abdominal pain	1/74 (1.4%)		0/75 (0%)		1/58 (1.7%)
Constipation	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Gastrointestinal haemorrhage	1/74 (1.4%)		1/75 (1.3%)		1/58 (1.7%)
Gastrointestinal inflammation	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Gastrooesophageal reflux disease	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Inguinal hernia	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Nausea	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Oesophageal varices haemorrhage	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Rectal haemorrhage	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Small intestinal obstruction	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
General disorders
Asthenia	0/74 (0%)		0/75 (0%)		2/58 (3.4%)
Fatigue	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
General physical health deterioration	1/74 (1.4%)		0/75 (0%)		1/58 (1.7%)
Non-cardiac chest pain	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Pyrexia	1/74 (1.4%)		0/75 (0%)		1/58 (1.7%)
Hepatobiliary disorders
Cholelithiasis	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Infections and infestations
Bronchitis	3/74 (4.1%)		0/75 (0%)		0/58 (0%)
Cellulitis	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Cystitis	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Influenza	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Localised infection	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Lower respiratory tract infection	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Meningitis	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Ophthalmic herpes zoster	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Pneumonia	0/74 (0%)		1/75 (1.3%)		2/58 (3.4%)
Pyelonephritis	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Pyonephrosis	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Respiratory tract infection	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Sepsis	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Septic shock	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Sinusitis	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Urinary tract infection	2/74 (2.7%)		0/75 (0%)		0/58 (0%)
Urosepsis	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Injury, poisoning and procedural complications
Hip fracture	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Lumbar vertebral fracture	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Muscle rupture	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Post procedural haemorrhage	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Radius fracture	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Spinal fracture	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Tendon rupture	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Ulna fracture	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Investigations
Blood creatinine increased	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Blood lactate dehydrogenase increased	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Blood uric acid increased	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Weight decreased	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Metabolism and nutrition disorders
Decreased appetite	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Dehydration	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Diabetes mellitus	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Hyperuricaemia	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Hyponatraemia	0/74 (0%)		1/75 (1.3%)		1/58 (1.7%)
Musculoskeletal and connective tissue disorders
Foot deformity	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Haemarthrosis	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Intervertebral disc protrusion	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Musculoskeletal pain	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Osteoarthritis	2/74 (2.7%)		0/75 (0%)		3/58 (5.2%)
Pain in extremity	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Basal cell carcinoma	5/74 (6.8%)		0/75 (0%)		1/58 (1.7%)
Basosquamous carcinoma of skin	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Bladder transitional cell carcinoma	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Blast cell crisis	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Bone marrow tumour cell infiltration	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Bowen's disease	2/74 (2.7%)		0/75 (0%)		0/58 (0%)
Breast cancer	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Carcinoma in situ	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Juvenile melanoma benign	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Lung adenocarcinoma	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Metastases to spine	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Metastatic malignant melanoma	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Myelofibrosis	0/74 (0%)		1/75 (1.3%)		1/58 (1.7%)
Non-small cell lung cancer metastatic	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Parathyroid tumour benign	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Prostate cancer	2/74 (2.7%)		0/75 (0%)		0/58 (0%)
Prostatic adenoma	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Renal cancer	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Skin cancer	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Squamous cell carcinoma of skin	3/74 (4.1%)		0/75 (0%)		1/58 (1.7%)
Uterine neoplasm	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Vaginal cancer	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Nervous system disorders
Cerebrovascular accident	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Cognitive disorder	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Dizziness	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Epilepsy	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Facial neuralgia	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Headache	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Ischaemic stroke	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Syncope	0/74 (0%)		1/75 (1.3%)		1/58 (1.7%)
Renal and urinary disorders
Haematuria	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Nephrolithiasis	1/74 (1.4%)		0/75 (0%)		1/58 (1.7%)
Renal failure	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Ureterolithiasis	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Urethral stenosis	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Dyspnoea exertional	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Hypoxia	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Pulmonary embolism	1/74 (1.4%)		0/75 (0%)		2/58 (3.4%)
Respiratory failure	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Skin and subcutaneous tissue disorders
Actinic keratosis	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Vascular disorders
Blue toe syndrome	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Extremity necrosis	0/74 (0%)		1/75 (1.3%)		0/58 (0%)
Peripheral arterial occlusive disease	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Peripheral artery occlusion	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Peripheral artery thrombosis	0/74 (0%)		0/75 (0%)		1/58 (1.7%)
Venous haemorrhage	1/74 (1.4%)		0/75 (0%)		0/58 (0%)
Other (Not Including Serious) Adverse Events
	Ruxolitinib		Best Available Therapy		All Crossover Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/74 (98.6%)		56/75 (74.7%)		56/58 (96.6%)
Blood and lymphatic system disorders
Anaemia	27/74 (36.5%)		1/75 (1.3%)		19/58 (32.8%)
Leukocytosis	5/74 (6.8%)		4/75 (5.3%)		3/58 (5.2%)
Thrombocytopenia	5/74 (6.8%)		6/75 (8%)		3/58 (5.2%)
Thrombocytosis	8/74 (10.8%)		3/75 (4%)		5/58 (8.6%)
Ear and labyrinth disorders
Tinnitus	3/74 (4.1%)		2/75 (2.7%)		3/58 (5.2%)
Vertigo	4/74 (5.4%)		1/75 (1.3%)		1/58 (1.7%)
Gastrointestinal disorders
Abdominal discomfort	1/74 (1.4%)		2/75 (2.7%)		4/58 (6.9%)
Abdominal distension	5/74 (6.8%)		1/75 (1.3%)		0/58 (0%)
Abdominal pain	10/74 (13.5%)		1/75 (1.3%)		8/58 (13.8%)
Abdominal pain upper	5/74 (6.8%)		3/75 (4%)		2/58 (3.4%)
Constipation	13/74 (17.6%)		4/75 (5.3%)		8/58 (13.8%)
Diarrhoea	7/74 (9.5%)		7/75 (9.3%)		4/58 (6.9%)
Dyspepsia	5/74 (6.8%)		2/75 (2.7%)		4/58 (6.9%)
Flatulence	1/74 (1.4%)		1/75 (1.3%)		3/58 (5.2%)
Nausea	4/74 (5.4%)		5/75 (6.7%)		3/58 (5.2%)
Vomiting	2/74 (2.7%)		1/75 (1.3%)		4/58 (6.9%)
General disorders
Asthenia	8/74 (10.8%)		6/75 (8%)		6/58 (10.3%)
Fatigue	13/74 (17.6%)		6/75 (8%)		6/58 (10.3%)
Oedema peripheral	10/74 (13.5%)		2/75 (2.7%)		6/58 (10.3%)
Pyrexia	13/74 (17.6%)		1/75 (1.3%)		7/58 (12.1%)
Infections and infestations
Bronchitis	12/74 (16.2%)		2/75 (2.7%)		2/58 (3.4%)
Cystitis	10/74 (13.5%)		0/75 (0%)		2/58 (3.4%)
Herpes zoster	11/74 (14.9%)		0/75 (0%)		8/58 (13.8%)
Influenza	10/74 (13.5%)		4/75 (5.3%)		2/58 (3.4%)
Nasopharyngitis	8/74 (10.8%)		2/75 (2.7%)		10/58 (17.2%)
Sinusitis	1/74 (1.4%)		0/75 (0%)		3/58 (5.2%)
Upper respiratory tract infection	5/74 (6.8%)		7/75 (9.3%)		5/58 (8.6%)
Urinary tract infection	6/74 (8.1%)		0/75 (0%)		2/58 (3.4%)
Investigations
Blood creatine phosphokinase increased	9/74 (12.2%)		0/75 (0%)		2/58 (3.4%)
Blood lactate dehydrogenase increased	2/74 (2.7%)		1/75 (1.3%)		4/58 (6.9%)
Gamma-glutamyltransferase increased	5/74 (6.8%)		1/75 (1.3%)		1/58 (1.7%)
Haematocrit increased	0/74 (0%)		5/75 (6.7%)		1/58 (1.7%)
Weight decreased	1/74 (1.4%)		4/75 (5.3%)		0/58 (0%)
Weight increased	19/74 (25.7%)		1/75 (1.3%)		9/58 (15.5%)
Metabolism and nutrition disorders
Decreased appetite	5/74 (6.8%)		4/75 (5.3%)		0/58 (0%)
Dyslipidaemia	0/74 (0%)		0/75 (0%)		4/58 (6.9%)
Hypercholesterolaemia	5/74 (6.8%)		0/75 (0%)		5/58 (8.6%)
Hypertriglyceridaemia	4/74 (5.4%)		0/75 (0%)		0/58 (0%)
Hyperuricaemia	3/74 (4.1%)		1/75 (1.3%)		3/58 (5.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	20/74 (27%)		3/75 (4%)		6/58 (10.3%)
Back pain	12/74 (16.2%)		0/75 (0%)		7/58 (12.1%)
Bone pain	4/74 (5.4%)		0/75 (0%)		0/58 (0%)
Intervertebral disc protrusion	4/74 (5.4%)		0/75 (0%)		1/58 (1.7%)
Muscle spasms	5/74 (6.8%)		1/75 (1.3%)		0/58 (0%)
Musculoskeletal pain	4/74 (5.4%)		1/75 (1.3%)		1/58 (1.7%)
Myalgia	5/74 (6.8%)		2/75 (2.7%)		2/58 (3.4%)
Osteoarthritis	5/74 (6.8%)		1/75 (1.3%)		2/58 (3.4%)
Osteoporosis	4/74 (5.4%)		0/75 (0%)		0/58 (0%)
Pain in extremity	11/74 (14.9%)		2/75 (2.7%)		4/58 (6.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	2/74 (2.7%)		0/75 (0%)		3/58 (5.2%)
Nervous system disorders
Dizziness	8/74 (10.8%)		5/75 (6.7%)		7/58 (12.1%)
Headache	13/74 (17.6%)		9/75 (12%)		8/58 (13.8%)
Memory impairment	0/74 (0%)		0/75 (0%)		4/58 (6.9%)
Neuropathy peripheral	0/74 (0%)		0/75 (0%)		3/58 (5.2%)
Paraesthesia	7/74 (9.5%)		0/75 (0%)		2/58 (3.4%)
Psychiatric disorders
Depression	5/74 (6.8%)		1/75 (1.3%)		2/58 (3.4%)
Respiratory, thoracic and mediastinal disorders
Cough	7/74 (9.5%)		2/75 (2.7%)		6/58 (10.3%)
Dyspnoea	11/74 (14.9%)		2/75 (2.7%)		4/58 (6.9%)
Epistaxis	4/74 (5.4%)		2/75 (2.7%)		7/58 (12.1%)
Skin and subcutaneous tissue disorders
Erythema	2/74 (2.7%)		4/75 (5.3%)		0/58 (0%)
Night sweats	6/74 (8.1%)		5/75 (6.7%)		1/58 (1.7%)
Pruritus	12/74 (16.2%)		17/75 (22.7%)		7/58 (12.1%)
Skin ulcer	4/74 (5.4%)		0/75 (0%)		2/58 (3.4%)
Vascular disorders
Haematoma	10/74 (13.5%)		1/75 (1.3%)		4/58 (6.9%)
Hypertension	15/74 (20.3%)		3/75 (4%)		11/58 (19%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.