Clinical trial NCT01348490
Conditions: MPN (Myeloproliferative Neoplasms)
Keywords: PMF PPV-MF PET-MF
Sponsor: Incyte Corporation
Start date: 2011-06-15; Completion date: 2018-12-19
Enrollment: 66 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
To evaluate the effects of treatment with ruxolitinib (INCB018424) on spleen volume, symptoms and potential side effects in participants with PMF, PPV-MF and PET-MF who have platelet counts of 50 x 10\^9/L to 100 x 10\^9/L. It is anticipated that individualized dose optimization from the starting ruxolitinib level of 5 mg bid will be associated with reductions in splenomegaly, MF-associated symptoms and inflammatory cytokine levels.

Detailed description:

Arms: arm 1: Participants began administration with 5 mg ruxolitinib twice daily (BID) orally. Beginning at the Week 4 visit, doses of ruxolitinib could be increased in 5 mg once a day (QD) increments every 4 weeks every 4 weeks not to exceed a dose of 25 mg BID.
Interventions: intervention 1: Ruxolitinib
Intervention descriptions: intervention 1: Ruxolitinib (INCB018424), 5 mg bid

Protocol documents:
Prot_000.pdf: 
Incyte Corporation 
Page 1 of 92 
Protocol INCB 18424-258 Amendment 2 
09 AUG 2013 
CONFIDENTIAL 
Clinical Study Protocol 
INCB 18424-258 / NCT01348490
An Open Label Assessment of Safety and Efficacy of Ruxolitinib 
(INCB018424) in Subjects With Primary Myelofibrosis, Post Essential 
Thrombocythemia-Myelofibrosis and Post Polycythemia Vera-
Myelofibrosis Who Have Platelet Counts of 50 × 109/L to 100 × 109/L 
Product: 
Ruxolitinib 
IND Number: 
77,456 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
Route 141 & Henry Clay Road 
Building E336 
Wilmington, DE 19880 US 
Date of Protocol: 
29 MAR 2011 
Date of Protocol Amendment 1: 
17 AUG 2011 
Date of Protocol Amendment 2: 
09 AUG 2013 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study protocol, Good Clinical Practices as defined in Title 21 of the US 
Code of Federal Regulations Parts 50, 54 56, 312, and Part 11 as well as ICH GCP consolidated guidelines (E6) and 
applicable regulatory requirements. 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without the prior 
written consent of Incyte Corporation. 


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Protocol INCB 18424-258 Amendment 2 
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CONFIDENTIAL 
INVESTIGATOR'S AGREEMENT 
I have received and read the Investigator’s Brochure for ruxolitinib.   I have read the 
INCB 18424-258 Protocol Amendment 2 and agree to conduct the study as outlined.  I agree 
to maintain the confidentiality of all information received or developed in connection with this 
protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 
 
 
 


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CONFIDENTIAL 
1. 
SYNOPSIS 
Name of Investigational Product:  ruxolitinib   
Throughout this protocol, ruxolitinib will be used to designate the drug substance (ruxolitinib 
phosphate) and drug product (ruxolitinib phosphate tablets) 
Title of Study:  An open label assessment of safety and efficacy of ruxolitinib (INCB018424) in 
subjects with primary myelofibrosis, post essential thrombocythemia-myelofibrosis and post 
polycythemia vera-myelofibrosis who have platelet counts of 50 x 109/L to 100 x 109/L 
Protocol Number: INCB 18424-258 
Study Phase:   2 
Primary Objectives: 
• 
To determine the effects of ruxolitinib on spleen volume and symptomatic burden in patients 
with primary myelofibrosis (PMF), post polycythemia vera-myelofibrosis (PPV-MF) and post 
essential thrombocythemia-myelofibrosis (PET-MF) who have baseline platelet count of 
50 x 109/L to 100 x 109/L.  
• 
To determine the safety and tolerability of ruxolitinib in patients with PMF, PPV-MF, and 
PET-MF who have a baseline platelet count of 50 x 109/L to 100 x 109/L. 
Secondary Objective: 
• 
To determine appropriate dosing for patients with low platelets. 
• 
To determine the long-term safety and efficacy effects of ruxolitinib in patients with PMF, 
PPV-MF and PET-MF who have baseline platelet count of 50 x 109/L to 100 x 109/L. 
Overall Study Design:  
This is an open label study of ruxolitinib in patients with PMF, PPV-MF, and PET-MF.  The study is 
comprised of 4 phases: 
Screening: 
Up to 21 days 
Baseline: 
Exactly 7 days 
Core Treatment Phase: 
24 weeks   
Extended Treatment Phase: 
132 weeks; subjects receiving benefit will continue ruxolitinib 
treatment until Week 156 
Follow-up Phase: 
All subjects will be followed for safety (eg, reporting of AEs and 
serious AEs) for 30 to 37 days after the last dose of study drug is 
administered 
Study Drug, Dosage and Mode of Administration and dose adjustments:  
All subjects will begin dosing at 5 mg bid ruxolitinib.  Doses should be taken morning and evening, 
approximately 12 hours apart, and without regards to food. 
During the core treatment phase, doses of ruxolitinib may be increased in 5 mg qd increments up to a 
dose of 10 mg bid starting at the Week 4 visit and at subsequent study visits (no more than every 
4 weeks) if platelet count was always ≥ 40 x 109/L since the last scheduled study visit, platelet count, if 
decreased since the last visit, is decreased by ≤ 20%, no dose decreases or holds for safety have 
occurred during the preceding 4 week interval, no ≥ Grade 2 hemorrhage events have occurred since 
initiating treatment and ANC is > 1000/µL.  Doses may not exceed 10 mg bid except in subjects who 
continue to meet the above dose escalation criteria, and who have, in addition, a PGIC score of 
minimally worse, much worse or very much worse while receiving 10 mg bid.  Such subjects may 
continue dose escalation to a maximum dose of 15 mg bid. 


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CONFIDENTIAL 
During the extended treatment phase, doses of ruxolitinib may be increased in 5 mg qd increments up 
to a dose of 25 mg bid if the subject meets the above dose escalation criteria, or per the investigator’s 
discretion.   
Doses may never exceed 25 mg bid. 
Subjects will be required to decrease the dose for platelet count < 35 x 109/L, and to hold dosing for 
platelet count < 25 x 109/L.  Subjects will have the option to restart or re-escalate the dose with 
improving platelet count. 
Subjects will be required to interrupt dosing for any Grade 2 or higher hemorrhage events.  Subjects 
will be able to restart ruxolitinib dosing with resolution of Grade 2 events; restart after a second event 
requires review and discussion of pertinent data with the sponsor.  Restarts of ruxolitinib will only be 
permitted in some cases of Grade 3 and 4 events, after review and discussion of pertinent data with the 
sponsor. 
Sites will provide information on incidents of Grade 4 thrombocytopenia and Grade 3/ Grade 4 
hemorrhage events via FAX to the sponsor or its designee within 24 hours of learning of the event.  
The overall incidence of these events will be continuously monitored by the sponsor, and with ongoing 
data review, could result in a temporary hold for further enrollment, a reduction in the maximum 
allowable dose for subjects in the study, or a protocol amendment to modify dose titration rules. 
Duration of Participation:  
Up to 4 weeks for screening + baseline phases 
Up to 24 weeks for the core treatment phase   
Up to 132 weeks for the extended treatment phase (to Week 156) 
Up to 37 days for follow-up 
Total:  165 weeks, 2 days  
Study Population:    
Male or female individuals, aged 18 years or older who have been diagnosed with myelofibrosis (either 
PMF, PPV-MF or PET-MF), with a platelet count between 50 and 100 × 109/L and for whom treatment 
of MF is indicated may enroll.  Subjects must score at least 1 point according to the DIPSS prognostic 
criteria (Passamonti et al 2010).  Enrolled subjects must have a life expectancy of > 6 months. 
Key Inclusion Criteria: 
Must be diagnosed with PMF, PPV-MF or PET-MF as confirmed by bone marrow biopsy.  Must have 
platelet count between 50 and 100 × 109/L at the screening and/or baseline visit.  Must score at least 1 
point on the DIPSS scale for prognostic risk factors, have active symptoms of MF and have peripheral 
blast count < 5% at both screening and baseline laboratory assessments.  Subjects must discontinue all 
drugs used to treat underlying MF disease no later than Day -14.  Subjects must not have INR > 1.5, or 
PTT value > 1.5 × ULN.  Subjects must have hemoglobin levels at least 6.5 g/dL at screening, and be 
willing to accept transfusions to treat low hemoglobin levels.   
Key Exclusion Criteria: 
Females who are pregnant or breastfeeding, and males and females who cannot comply with 
requirements to avoid fathering a child or becoming pregnant.  Subjects with confirmed platelet count 
< 50 × 109/L or ANC < 1 × 109/L at the screening visit.  Inadequate liver or renal function, clinically 
significant concurrent infections requiring therapy, using potent or moderate CYP 3A4 inhibitors at 
screening, unstable cardiac function, gastric or esophageal varices, (subjects with a history of an 
incidental finding of small varices (< 5 mm) may be permitted in the study with sponsor approval), 
hemorrhagic strokes, intracranial bleeds or invasive malignancy over the previous 2 years except 
treated early stage carcinomas of the skin completely resected intraepithelial carcinoma of the cervix 
and completely resected papillary thyroid and follicular thyroid cancers.  


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Planned Number of Subjects:  Approximately 150 
Study Schedule/Procedures: 
There will be study visits and laboratory-only visits in the study.   
Core Treatment Phase: 
Subjects will have a regularly scheduled study visit at screening, baseline, Day 1, Week 4, Week 8, 
Week 12, Week 16, Week 20 and Week 24, where blood samples, assessments, spleen measurements, 
etc. will be obtained.  Optional dose increases may occur at these monthly study visits.  All hematology 
labs and coagulation parameters will be analyzed by local laboratories.  Serum chemistries, serology, 
and lipid panel will be analyzed by a central laboratory. 
Subjects will have laboratory-only visits to collect hematology lab samples at Week 1, Week 2, 
Week 3, Week 5, Week 6, Week 7, Week 10, Week 14, and Week 18.  The laboratory visits at 
Week 14 and Week 18 may be skipped for subjects who do not increase their dose at Week 12 or 
Week 16, and who have maintained platelet counts > 75 x 109/L since the last hematology assessment.  
Additional blood draws for hematology assessment will be required if platelet count falls below 
35 x 109/L.   
Subjects will have an MRI of the upper and lower abdomen and pelvis to determine the spleen volume 
at baseline and Week 24.  CT scan will be substituted for subjects who are not candidates for MRI, or 
when MRI is not readily available. Patients Global Impression of Change (PGIC) questionnaire will be 
completed monthly.  Measurement of spleen length below the left costal margin will be measured by 
palpation at each study visit.  
Subjects will complete an electronic symptom diary (the Modified Myelofibrosis Symptom Assessment 
Form (MFSAF) v2.0) from baseline thru the Week 24 visits (total of 25 weeks).   
Extended Treatment Phase: 
Subjects will have a study visit every 12 weeks (eg, Weeks 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 
and 156) through Week 156 where blood samples, clinical assessments, and palpable spleen 
measurements will be obtained.  Subjects will have laboratory-only visits to collect hematology 
samples 6 weeks after the Week 24 visit (eg, Week 30), then after each extended treatment phase visit 
(eg, Weeks 42, 54, 66, 78, 90, 102, 114, 126, 138, and 150).  Additional hematology assessments will 
be required if the subject has a dose modification or as clinically indicated. 
Co-Primary Endpoints: 
• 
Correlation of % change in spleen volume at Week 24 compared to baseline versus final 
titrated dose. 
• 
Correlation of % change in Total Symptom Score as measured by the modified MFSAF v2.0 
diary at Week 24 compared to baseline versus final titrated dose. 
Safety Endpoint: 
• 
Safety and tolerability will be assessed by monitoring the frequency, duration and severity of 
adverse events, performing physical examinations, collecting vital signs, collecting laboratory 
data for hematology, serum chemistry, and coagulation parameters through Week 156.  In 
addition, analyses will include: 
− 
Proportion of subjects with new onset Grade 4 thrombocytopenia events as assessed by 
CTCAE v4.03. 
− 
Proportion of subjects with new onset Grade 2 or higher hemorrhage as assessed by 
CTCAE v4.03 


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Secondary Endpoints: 
• 
Percent change in spleen volume at Week 24 compared to Baseline 
• 
Percent change in Total Symptom Score as measured by the modified MFSAF v2.0 diary at 
Week 24 compared to baseline. 
• 
Proportion of subjects with ≥ 35% reduction in spleen volume at Week 24 compared to 
baseline. 
• 
Proportion of subjects with ≥ 10% reduction in spleen volume at Week 24 compare to baseline. 
• 
Proportion of subjects with ≥ 50% improvement in total symptom score as measured by the 
modified MFSAF v2.0 diary at Week 24 compared to baseline. 
• 
Long-term efficacy of ruxolitinib will be assessed by monitoring change and percent change in 
spleen length, as measured by palpation, and change in PGIC score from baseline to each visit 
where the variables are measured through Week 156. 
Planned Number of Study Sites:  approximately 60 sites that have previous experience with MF 
patients 
Estimated Study Duration:  
Estimated date first subject enrolled:  May 2011 
Estimated date last subject completed:  September 2020 
Statistical Methods:  
The correlation between final titrated dose and % change of spleen volume measured by MRI, and % 
change in Total Symptom Score from baseline to Week 24 will each be calculated, and the null 
hypothesis of no correlation will be tested with the t test for correlation. In addition, the overall effect 
size (drug effect over all patients) will be estimated with 95% confidence intervals. 
Safety data will be tabulated from baseline through Week 156 including AE, labs, and vital signs. 
Proportion of subjects with new onset of Grade 4 thrombocytopenia events, and proportion of subjects 
with new onset of Grade 2 or higher hemorrhage, as measured by CTCAE will be tabulated with 
summary statistics.  The hazard functions of time to onset of the above two safety measures will be 
estimated using life table method. 
The percent change in spleen volume at Week 24 compared to Baseline, the percent change in total 
symptom score as measured by the modified MFSAF v2.0 diary at Week 24 compared to Baseline, the 
proportion of subjects with ≥ 35% reduction in spleen volume at Week 24 compared to Baseline, 
proportion of subjects with ≥ 10% reduction in spleen volume at Week 24 compared to Baseline and 
the proportion of subjects with ≥ 50% improvement in total symptom score as measured by the 


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CONFIDENTIAL 
modified MFSAF v2.0 diary at Week 24 compared to Baseline will be tabulated with summary 
statistics.  Change and percentage change in spleen length from baseline as measured by palpation at 
each visit where the parameter is assessed through Week 156 will be tabulated with summary statistics. 
The data will be summarized as one group and by the final titrated dose. 
Data Monitoring Committee: 
An independent data monitoring committee will be formed, consisting of qualified individuals who are 
not involved in the conduct of the study.  The roles, responsibilities and composition of the committee 
will be established in a charter. 


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2. 
TABLE OF CONTENTS 
1. 
SYNOPSIS ...................................................................................................................3 
2. 
TABLE OF CONTENTS .............................................................................................8 
3. 
LIST OF ABBREVIATIONS.....................................................................................14 
4. 
INTRODUCTION ......................................................................................................16 
4.1. 
Background Information on Ruxolitinib Tablets ........................................................18 
4.1.1. 
Pharmacology Summary .............................................................................................18 
4.1.2. 
Drug Disposition Summary ........................................................................................18 
4.1.3. 
Nonclinical Toxicology Summary ..............................................................................19 
4.1.4. 
Clinical Summary .......................................................................................................20 
4.1.5. 
Interim Analysis Data from Study INCB 18424-258 .................................................22 
4.2. 
Trial Rationale ............................................................................................................24 
4.3. 
Potential Risks and Benefits of the Treatment Regimen ............................................24 
4.3.1. 
Potential Risks ............................................................................................................24 
4.3.2. 
Potential Benefits ........................................................................................................25 
5. 
STUDY OBJECTIVES AND PURPOSE ..................................................................25 
5.1. 
Primary Objective .......................................................................................................25 
5.2. 
Secondary Objectives .................................................................................................25 
6. 
SUBJECT ELIGIBILITY ...........................................................................................26 
6.1. 
Study Population .........................................................................................................26 
6.2. 
Subject Inclusion Criteria ...........................................................................................26 
6.3. 
Subject Exclusion Criteria ..........................................................................................27 
6.4. 
Subjects Who Fail to Meet Screening Criteria ...........................................................29 
7. 
INVESTIGATIONAL PLAN .....................................................................................30 
7.1. 
Overall Study Design ..................................................................................................30 
7.2. 
Study Endpoints ..........................................................................................................31 
7.2.1. 
Co-Primary Endpoints ................................................................................................31 
7.2.2. 
Safety Endpoints: ........................................................................................................31 
7.2.3. 
Secondary Endpoints ..................................................................................................31 
 
32 
7.3. 
Measures Taken to Avoid Bias ...................................................................................32 


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7.4. 
Number of Subjects ....................................................................................................32 
7.5. 
Criteria for Study Termination ...................................................................................32 
8. 
TREATMENT OF SUBJECTS ..................................................................................33 
8.1. 
Treatment Arms and Study Drug Administration ......................................................33 
8.2. 
Treatment Compliance ................................................................................................33 
8.3. 
Randomization and Blinding ......................................................................................33 
8.4. 
Duration of Treatment and Subject Participation .......................................................33 
8.5. 
Considerations for Dose Modifications ......................................................................33 
8.6. 
Dose Adjustments .......................................................................................................33 
8.6.1. 
Dose Increases ............................................................................................................33 
8.6.2. 
Mandatory Dose Interruptions, Dose Discontinuations and Dose Reductions ...........34 
8.6.3. 
Restarting or Increasing Ruxolitinib after Recovery of Platelet or ANC 
Levels or Resolution of Hemorrhage ..........................................................................35 
8.6.3.1. 
Restarting or Re-Escalating with Improving Platelet Counts .....................................35 
8.6.3.2. 
Use of Platelet Transfusions .......................................................................................36 
8.6.3.3. 
Restarting or Re-Escalating with Improving ANC .....................................................36 
8.6.3.4. 
Restarting with Resolution of Hemorrhage Event ......................................................37 
8.6.4. 
Possible Changes in Study Conduct Because of Frequent Hemorrhage or 
Thrombocytopenia Events ..........................................................................................37 
8.6.5. 
Management of Anemia .............................................................................................38 
8.6.6. 
Optional Dose Tapering Strategy ...............................................................................38 
8.6.7. 
Procedures for Interruption of Study Medication .......................................................38 
8.6.8. 
Procedures for Permanent Discontinuation of Study Drug ........................................38 
8.7. 
Withdrawal of Subjects from the Study......................................................................39 
8.7.1. 
Withdrawal Criteria ....................................................................................................39 
8.8. 
Concomitant Medications and Measures ....................................................................40 
8.9. 
Restricted and Prohibited Medications and Measures ................................................40 
8.9.1. 
Restricted Medications and Measures ........................................................................40 
8.9.2. 
Prohibited Medications and Measures ........................................................................41 
9. 
STUDY ASSESSMENTS ..........................................................................................41 
9.1. 
Screening + Baseline Phase ........................................................................................45 
9.1.1. 
Screening Assessments ...............................................................................................45 
9.1.2. 
Baseline Assessments .................................................................................................46 


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9.2. 
Core Treatment Phase .................................................................................................48 
9.3. 
Extended Treatment Phase .........................................................................................53 
9.4. 
End of Treatment (± 5 days) .......................................................................................55 
9.5. 
Follow-Up Phase ........................................................................................................55 
9.6. 
Unscheduled Visits .....................................................................................................56 
10. 
STUDY ASSESSMENT PROCEDURES .................................................................56 
10.1. 
Demographics and Medical History ...........................................................................56 
10.2. 
Order of Assessments .................................................................................................56 
10.3. 
Safety Assessments .....................................................................................................56 
10.3.1. 
Adverse Events ...........................................................................................................56 
10.3.2. 
Physical Examination .................................................................................................57 
10.3.2.1. 
Targeted Physical ........................................................................................................57 
10.3.3. 
Vital Signs ..................................................................................................................57 
10.3.4. 
Concomitant Medications ...........................................................................................57 
10.3.5. 
Twelve-Lead Electrocardiograms ...............................................................................57 
10.3.6. 
Laboratory Assessments .............................................................................................58 
10.3.6.1. 
Hematology .................................................................................................................58 
10.3.6.2. 
Chemistry ....................................................................................................................58 
10.3.6.3. 
Pregnancy and Fertility Testing ..................................................................................58 
10.3.6.4. 
Serology ......................................................................................................................58 
10.4. 
Efficacy Assessments .................................................................................................58 
10.5. 
Symptom and Quality of Life Assessments................................................................59 
 
60 
 
60 
 
60 
 
60 
 
61 
 
61 
 
61 
 
61 
10.9. 
Other Study Procedures ..............................................................................................62 
10.9.1. 
Administration of Informed Consent Form ................................................................62 
10.9.2. 
IVRS/IWRS Procedures .............................................................................................62 


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10.9.3. 
Study Drug Administration.........................................................................................62 
10.9.4. 
Study Drug Dispensation ............................................................................................62 
10.9.5. 
Assessment of Study Drug Compliance .....................................................................62 
10.9.6. 
Distribution of Subject Reminder Cards and Diaries .................................................62 
11. 
SAFETY MONITORING AND REPORTING .........................................................63 
11.1. 
Adverse Events ...........................................................................................................63 
11.1.1. 
Definitions and Reporting ...........................................................................................63 
11.2. 
Laboratory Test Abnormalities ...................................................................................64 
11.2.1. 
Definitions and Reporting ...........................................................................................64 
11.3. 
Serious Adverse Events ..............................................................................................64 
11.3.1. 
Definitions ..................................................................................................................64 
11.3.2. 
Reporting ....................................................................................................................65 
11.4. 
Emergency Unblinding of Treatment Assignment .....................................................66 
11.5. 
Pregnancy ...................................................................................................................66 
11.6. 
Warnings and Precautions ..........................................................................................67 
11.7. 
Data Safety Monitoring ..............................................................................................67 
11.7.1. 
Data Monitoring Committee .......................................................................................67 
11.7.2. 
Reporting of Grade 4 Thrombocytopenia Events and > Grade 2 Hemorrhage 
Events During the Study .............................................................................................67 
11.7.3. 
Safety Reviews ...........................................................................................................68 
11.7.3.1. 
Review After Enrollment of 20th Subject ...................................................................68 
11.7.3.2. 
Review After Enrollment of 40th Subject ...................................................................69 
11.7.4. 
Continuous Safety Monitoring ...................................................................................69 
11.8. 
Product Complaints ....................................................................................................69 
12. 
STATISTICS ..............................................................................................................70 
12.1. 
Study Population .........................................................................................................70 
12.2. 
Statistical Analyses .....................................................................................................70 
12.2.1. 
Primary Analyses ........................................................................................................70 
12.2.2. 
Secondary Analyses ....................................................................................................72 
12.2.3. 
Other Analyses ............................................................................................................72 
12.3. 
Interim Analysis ..........................................................................................................73 
12.4. 
Selection of Sample Size ............................................................................................73 
12.5. 
Level of Significance ..................................................................................................73 


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13. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................74 
13.1. 
Investigational Product Description ...........................................................................74 
13.1.1. 
Study Drug Packaging, Labeling and Preparation ......................................................74 
13.1.2. 
Study Drug Storage and Stability ...............................................................................74 
13.2. 
Study Drug Accountability, Handling, and Disposal .................................................74 
14. 
STUDY ADMINISTRATION ...................................................................................75 
14.1. 
Data Management .......................................................................................................75 
14.1.1. 
Data Collection ...........................................................................................................75 
14.1.2. 
Data Management .......................................................................................................75 
14.2. 
Study Monitoring ........................................................................................................75 
14.3. 
Protocol Adherence ....................................................................................................76 
14.4. 
Financial Disclosure ...................................................................................................76 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................77 
15.1. 
Sponsor Audits............................................................................................................77 
15.2. 
Inspection by Regulatory Authorities .........................................................................77 
16. 
ETHICS ......................................................................................................................77 
16.1. 
Ethical Conduct of the Study ......................................................................................77 
16.2. 
Written Informed Consent ..........................................................................................77 
16.3. 
Ethics Review .............................................................................................................78 
16.4. 
Data Privacy ................................................................................................................79 
17. 
DATA HANDLING AND RECORDKEEPING .......................................................79 
17.1. 
Inspection of Records .................................................................................................79 
17.2. 
Retention of Records ..................................................................................................79 
17.3. 
Confidentiality ............................................................................................................80 
18. 
PUBLICATION POLICY ..........................................................................................80 
19. 
LIST OF REFERENCES ............................................................................................81 
APPENDIX 1. 2008 WORLD HEALTH ORGANIZATION CRITERIA FOR 
DIAGNOSIS OF PRIMARY MYELOFIBROSIS .....................................................83 
APPENDIX 2. PROPOSED DIAGNOSTIC CRITERIA FOR PPV-MF AND PET-MF 
BY THE INTERNATIONAL WORKING GROUP FOR 
MYELOFIBROSIS RESEARCH AND TREATMENT ............................................84 
APPENDIX 3. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS ...............................................................................85 
APPENDIX 4. CLINICAL LABORATORY TESTS ................................................................86 


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APPENDIX 5. PATIENT GLOBAL IMPRESSION OF CHANGE (PGIC) .............................87 
APPENDIX 6. BONE MARROW BIOPSY EVALUATION....................................................88 
APPENDIX 7. SCREENING SYMPTOM FORM.....................................................................89 
APPENDIX 8. INHIBITORS AND INDUCERS OF CYTOCHROME – P450 3A4................91 
APPENDIX 9. DRUGS THAT INTERFERE WITH COAGULATION OR INHIBIT 
PLATELET FUNCTION ...........................................................................................92 
 
LIST OF TABLES 
Table 1: 
Abbreviations and Special Terms ...............................................................................14 
Table 2: 
Mandatory Dose Reductions and Dose Holds for Safety ...........................................35 
Table 3: 
Table of Assessments .................................................................................................42 
Table 4: 
Table of Laboratory Assessments ...............................................................................44 
 
60 
 


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3. 
LIST OF ABBREVIATIONS  
The following abbreviations and special terms are used in this study protocol. 
Table 1: 
Abbreviations and Special Terms 
Term 
Explanation 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
bid 
twice daily 
CBC 
complete blood count 
Cmax 
maximum observed plasma concentration 
CRF 
case report form 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DIPSS 
Dynamic International Prognostic Scoring System 
dL 
deciliter  
DLT 
dose limiting toxicity 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram  
eCRF 
electronic case report forms 
ECOG 
Eastern Cooperative Oncology Group 
ET 
essential thrombocythemia 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IVRS 
Interactive Voice Response System 
IWG-MRT 
International Working Group for Myelofibrosis Research and Therapy 
JAK 
Janus kinase 


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Table 1: 
Abbreviations and Special Terms (Continued) 
Term 
Explanation 
MF 
myelofibrosis 
MFSAF v2.0 
Modified Myelofibrosis Symptom Assessment Form v2.0 (electronic 
symptom diary) 
mg 
milligram 
MPN 
myeloproliferative neoplasm 
MRI 
magnetic resonance imaging 
PD 
pharmacodynamic 
PET-MF 
post essential thrombocythemia myelofibrosis 
PGIC 
Patient Global Impression of Change 
PI 
Principal Investigator 
PK 
pharmacokinetics 
PMF 
primary myelofibrosis 
PV 
polycythemia vera 
PPV-MF 
post polycythemia vera myelofibrosis 
PR 
partial remission 
PTT 
partial thromboplastin time 
qd 
once daily 
Ruxolitinib 
Ruxolitinib phosphate or ruxolitinib phosphate tablets, based on context 
SAE 
serious adverse event 
STAT 
signal transduction and activator of transduction 
ULN 
upper limit of normal 
WBC 
white blood cells 


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4. 
INTRODUCTION 
The four classic myeloproliferative neoplasms (MPNs) include chronic myelogenous leukemia 
(CML), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis 
(PMF). Myelofibrosis (MF) can present as a de novo disorder (PMF) or evolve secondarily from 
previous PV or ET (post-PV-MF or post ET-MF).  Regardless of whether MF is a primary or 
secondary disorder, it is characterized by a clonal stem cell proliferation associated with 
production of elevated serum levels of multiple inflammatory and proangiogenic cytokines, a 
characteristic bone marrow stromal pattern that includes varying degrees of collagen fibrosis, 
osteosclerosis and angiogenesis and a peripheral blood smear showing a leukoerythroblastic 
pattern with varying degrees of circulating progenitor cells.  Clinically, MF is characterized by 
progressive anemia, leukopenia or leukocytosis, thrombocytopenia or thrombocythemia and 
multi-organ extramedullary hematopoiesis most prominently involving the liver and spleen.  
Patients may experience severe constitutional symptoms, sequelae of massive splenomegaly 
(pain, limitations of movement, early satiety and shortness of breath, hepatic obstruction, and 
splenic infarction), a hypermetabolic state with cachexia, progressive hematopoietic failure, 
progression to leukemia, and premature death. 
The median age at diagnosis is approximately 60 to 65 years.  The incidence of PMF has been 
estimated at 1.5 cases per 100,000 people.  Survival in MF varies with the presence or absence of 
specific risk factors.  A prognostic scoring system based on a time-dependent risk evaluation has 
been developed: the Dynamic International Prognostic Scoring System (DIPSS) for PMF 
(Passamonti et al 2010), age of greater than 65 years, presence of constitutional symptoms, 
anemia (Hemoglobin less than 100 g/L), leukocytosis (white blood cell count (WBC) greater 
than 25 x109/L), and a circulating blast percentage of 1% or higher were assessed for their 
impact on survival when analyzed as time-dependent covariates in a multivariate Cox 
proportional hazard model.  The approach showed that acquisition of anemia over time affects 
survival with a hazard ratio roughly double that of other parameters; anemia was therefore 
assigned a score of 2, while the other 4 factors were assigned scores of 1.  Four risk categories 
with non-overlapping survival curves have been described: 
Total Risk Score 
Risk Category 
Median Survival (months) 
0 
Low 
not reached 
1 or 2 
Intermediate-1 
170 
3 or 4 
Intermediate-2 
48 
5 or 6 
High 
18 
For a subset of patients who are younger (generally less than 65 years), otherwise healthy and 
have a histocompatible donor, allogeneic stem cell transplantation may provide a curative option, 
although with substantial (10-20%) risks of mortality, (Deeg et al 2003).  Drug therapies used, 
including hydroxyurea, busulfan, 6-mercaptopurine, anagrelide, thalidomide, lenalidomide, 
interferon, corticosteroids, and erythropoiesis stimulating agents or growth factors, have not been 
shown to improve survival.  Some can increase the risk of leukemic transformation, and/or are 
poorly tolerated, and all have limited effectiveness in improving splenomegaly and constitutional 
symptoms.  Splenectomy, performed in approximately 10% of the patient cohort reported by 
(Cervantes et al 2009), is associated with significant morbidity and mortality.  Splenic irradiation 


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is also employed to reduce symptoms secondary to splenomegaly, but symptomatic improvement 
is variable and short-lived; moreover, transient and life-threatening pancytopenia and an 
approximate 20% treatment-related mortality have been noted. 
Thrombocytopenia, although not found to be an independent variable in the multivariate analyses 
of prognostic factors proposed by the International Working Group for Myelofibrosis Research 
and Treatment (Cervantes et al 2009, Passamonti et al 2010), is considered to be an adverse risk 
factor by the Mayo Clinic group, (Elliott et al 2007).  More recently, low platelet count 
(< 100 x 109/L), was shown to be a Dynamic International Prognostic Scoring System (DIPSS)-
independent factor for survival and leukemia-free survival (Gangat et al 2011).  Apart from 
being an indicator of diminished bone marrow reserve, thrombocytopenia may also be a limiting 
factor with regards to therapy intensity with multiple agents including ruxolitinib, whose DLT is 
thrombocytopenia.  Therefore, thrombocytopenic patients are often excluded from 
investigational studies despite having MF requiring therapy. 
Within the past 5 years it was discovered that approximately 95% of patients with PV and about 
50% of patients with PMF and ET have a somatic gain-of function mutation in the Janus Kinase 
2 (JAK2) gene resulting in substitution of phenylalanine for valine at position 617 (JAK2 
V617F) within the pseudokinase domain of the encoded protein. JAK 2 is one of four Janus 
kinases along with JAK1, JAK 3 and TYK 2.  Together the Janus kinases are responsible for 
transduction of cell signaling from Type I and II cytokine receptors families because these 
receptors do not possess catalytic kinases to activate downstream signal transduction.  Under 
physiologic conditions, the JAKs associate with the intracellular domain of the cytokine 
receptors in response to cytokine binding.  They then undergo autophosphorylation resulting in 
conformational changes which enable them to transduce intracellular signaling by 
phosphorylating and activating transcription factors called Signal Transduction and Activator of 
Transduction (STAT) proteins.  The activated STATs translocate to the nucleus where they 
regulate transcription of a number of genes involved in cellular activation, proliferation and 
survival. JAKs associate with the intracellular domain of the Type I and II receptors in pairs, 
which may be homodimers (eg, two JAK2s) or heterodimers (eg, a JAK 1 and a JAK2).  
Erythropoeitin (EPO), which is responsible for stimulating erythropoiesis, thrombopoietin (TPO) 
which is responsible for stimulating thrombopoiesis and GM-CSF have been shown to signal 
only through receptors which utilize JAK2 homodimers.  A large number of other inflammatory 
mediators are known to signal primarily through receptors that utilize JAK heterodimers.  It is 
also apparent that MF, as well as ET and even PV occur in the absence of the JAK2 V617F 
mutation.  In a minority of patients other mutations in the JAK -STAT pathway have been 
identified but in many patients the mutations have not been identified yet or don’t exist.  
However it appears that majority of patients with MF have over-activation of the JAK STAT 
pathway, regardless of JAK2 V617F status.  In MF, excessive cytokine signaling through both 
JAK 1 and JAK2 have been observed both in patients harboring the JAK2V617F mutation and in 
patients without known mutations.  Therefore, JAK inhibitors have the potential to treat some or 
all of the manifestations of MF, despite the potential for mechanism-based myelosuppression, 
given the role of JAK kinases in normal bone marrow function. 


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4.1. 
Background Information on Ruxolitinib Tablets 
4.1.1. 
Pharmacology Summary 
Ruxolitinib represents a novel, potent, and selective inhibitor of JAK1 (IC50 = 3.3 ± 1.2 nM) and 
JAK2 (IC50 = 2.8 ± 1.2 nM) with modest to marked selectivity against TYK2 (IC50 = 19 ± 
3.2 nM) and JAK3 (IC50 = 428 ± 243 nM), respectively.  Ruxolitinib is inactive (ie, < 30% 
inhibition) against 28 additional kinases when tested at 200 nM.  
In cell-based assays relevant to the pathogenesis of MPNs, such as JAK/STAT signaling and 
growth of the cytokine-dependent tumor cell lines, ruxolitinib demonstrates IC50 values of 
80-185 nM.  This effect is not due to general cytotoxicity, because ruxolitinib (up to 25 μM) had 
no significant effect on the growth of cells driven by the BCR-ABL oncoprotein.  
Pharmacological data obtained with in vitro and in vivo model systems supports the potential 
utility of orally administered ruxolitinib in the treatment of inflammatory diseases such as RA as 
well as malignancies, including MPNs.  See Quintas-Cardama et al 2010 and the Investigator’s 
Brochure (IB) for additional information. 
4.1.2. 
Drug Disposition Summary 
Ruxolitinib has high solubility and permeability. It is designated as a Class I molecule in the 
Biopharmaceutical Classification System and exhibits moderate-to-high clearance, volume of 
distribution and oral bioavailability in preclinical species.  The apparent elimination half-life is 
short (< 5 hr) in all species.  The primary clearance pathway is oxidative metabolism and the 
metabolism by human liver microsomes is catalyzed predominantly by CYP3A4.  In a study 
using 14C-ruxolitinib in healthy volunteers, unchanged ruxolitinib was the predominant 
circulating drug-related entity with 2 major circulating metabolites observed, both of which are 
mono-oxidation products.  The metabolites of ruxolitinib retain varying degrees of JAK-related 
pharmacological activity.  Excretion was fairly rapid by both urinary and fecal routes with parent 
drug accounting for < 1% of the administered dose.  Tissue distribution studies in rats indicate 
rapid and complete elimination of radioactivity in most tissues.  Ruxolitinib exhibits high plasma 
protein binding in humans with an unbound fraction of 3.3%.  
PK information is available from single and repeat dose studies in healthy volunteers, an ongoing 
study in subjects with myelofibrosis (MF), and a study in patients with RA.  Ruxolitinib was 
absorbed rapidly, attaining mean peak plasma concentrations within 1-2 hours after 
administration.  The mean ruxolitinib Cmax and AUC0-∞ increased approximately proportional to 
dose over the entire dose range of 5 mg to 200 mg.  The mean terminal phase elimination 
half-life was approximately 3 hours.  There was no appreciable accumulation with repeat dosing.  
Administration of the 25 mg ruxolitinib with a high-fat, high-calorie meal slowed the absorption 
of ruxolitinib, prolonging the mean Tmax from 1.3 to 2.7 h, and lowered the mean Cmax by 24% 
but did not significantly affect the AUC compared to fasted administration.  The overall 
magnitude of the food effect on ruxolitinib exposure is not expected to be clinically important.  
Therefore, ruxolitinib can be dosed without regards to meals.  PK parameters in patients with RA 
and MF were similar to those seen in healthy volunteers.   
Ruxolitinib was well tolerated in single dose drug-drug interaction studies with inhibitors and an 
inducer of the CYP P450 family of metabolizing enzymes, when co-administered with 
methotrexate, in subjects with renal insufficiency, and in subjects with hepatic dysfunction.  


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Co-administration of methotrexate does not alter the pharmacokinetic parameters of ruxolitinib 
while administration of erythromycin slightly increases AUC by 26%.  Therefore no dose 
adjustments are required when ruxolitinib is administered together with moderate CYP3A4 
inhibitors such as erythromycin, including grapefruit juice, or with methotrexate.  Ketoconazole 
significantly increases the exposure to ruxolitinib when co-administered with ruxolitinib; it is 
recommended that dosage of ruxolitinib be decreased by 50% when co-administered with 
systemic ketoconazole, or other potent inhibitors of the CYP3A4 family of metabolizing 
enzymes.  Co-administration with rifampin significantly decreased the exposure to ruxolitinib; 
however, increases in the relative amount of active metabolites in the presence of this potent 
inducer of CYP3A4 resulted in nearly identical levels of overall JAK inhibitory activity as 
assessed by measurement of inhibition of IL-6-induced STAT phosphorylation.  Therefore, there 
is no required dose adjustment when ruxolitinib is co-administered with rifampin or other 
CYP3A4 inducers, but these agents should be used with caution in combination with ruxolitinib 
and alternative therapy used if available.  
Ruxolitinib pharmacokinetics and pharmacodynamics (as measured by IL-6 induced STAT3 
phosphorylation (pSTAT3)) were similar in subjects with normal renal function and with mild, 
moderate or severe renal impairment.  In subjects with end stage renal disease on dialysis 
ruxolitinib PK parameters were similar to healthy subjects, whether ruxolitinib was dosed prior 
to or following a dialysis session, but ruxolitinib pharmacodynamics were prolonged in subjects 
dosed following a dialysis session.  Therefore, ruxolitinib may be dosed to subjects with varying 
degrees of renal impairment without dose adjustment with the exception of subjects with end 
stage renal disease receiving hemodialysis.  In a hepatic impairment study, there was an 88% 
increase in AUC in mild, 29% increase in moderate, and a 66% increase in severe hepatic disease 
(based on the Childs-Pugh classification) and the terminal elimination half-life ranged from 
4.6 hours in mild, 4.1 hours in moderate, and 5.1 hours in severe hepatic impairment subjects 
compared to 2.8 hours in healthy subjects.  No significant differences in pharmacodynamics 
were observed among subjects with mild or moderate hepatic dysfunction compared to healthy 
subjects.  In subjects categorized as having severe hepatic impairment, the inhibition of IL-6 
induced pSTAT3 levels appeared to be prolonged following a single dose of ruxolitinib.  In 
subjects with hepatic impairment, it is suggested to reduce the initial starting dose (total daily 
dose) of ruxolitinib by 25% to 50% compared to the recommended therapeutic starting dose.  
Subjects should be carefully monitored and the dose titrated accordingly. 
See the IB for additional information regarding the disposition of ruxolitinib. 
4.1.3. 
Nonclinical Toxicology Summary 
Effects noted in multiple dose toxicity studies in mice (up to 4 weeks), rats (up to 6 months), and 
dogs (up to 12 months) were primarily those associated with the mechanism of action of 
ruxolitinib, a potent and reversible inhibitor of JAK-STAT signaling.  Decreases in red blood 
cells, reticulocytes, eosinophils and lymphocytes have been observed along with lymphoid 
depletion in bone marrow and lymphoid organs.  In addition, in dogs, demodectic mange, 
bacterial pneumonia and viral-induced papillomas, expected consequences of the pharmacology 
of JAK inhibition, were noted. 
In a respiratory safety pharmacology study, an adverse decrease in minute volume was noted in 
female but not in male rats at the highest dose, 150 mg/kg.  In a cardiovascular evaluation of 


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ruxolitinib in dogs, electrocardiogram (ECG) parameters were unaffected at all doses.  
Administration of ruxolitinib at the highest dose evaluated (30 mg/kg) resulted in an adverse 
lowering of blood pressure along with an increase in heart rate compared to vehicle control.  The 
IC50 for inhibition of the hERG channel was determined to be 131.6 µM. 
Ruxolitinib was not mutagenic or clastogenic nor did it demonstrate potential for carcinogenicity 
in a 6 month study in Tg.rasH2 mice. 
In embryo-fetal assessments in rat and rabbit, maternal toxicity and minimal embryo-fetal 
toxicity were noted at the highest doses evaluated.  Ruxolitinib was not teratogenic in either rat 
or rabbit.  In an evaluation of fertility and early embryonic development, no effects were noted 
on reproductive performance or fertility in male or female rats.  Increases in post-implantation 
loss were noted at the higher doses.  In a pre- and post-natal development and maternal function 
study in rats, no adverse effects were noted.  Ruxolitinib passed into the milk of lactating rats 
with an exposure that was 13-fold higher than maternal plasma exposure.  See the IB for 
additional information. 
4.1.4. 
Clinical Summary 
Ruxolitinib has been administered to over 180 healthy volunteers as single, repeat single, or 
multiple doses of up to 10 days duration.  Ruxolitinib has been administered to approximately 
450 subjects with MF for periods of up to > 24 months, and over 100 subjects with prostate 
cancer, multiple myeloma, polycythemia vera or essential thrombocythemia for periods of up to 
> 24 months.   
In healthy volunteer studies, a transient, reversible decrease in neutrophil count has frequently 
been seen following dosing, which reverses after 12 to 24 hours off drug, suggestive that the 
neutropenia may reflect an effect of ruxolitinib blocking IL-6 signaling and causing neutrophil 
margination on blood vessel walls.  In a repeat dose healthy volunteer study, neutropenia of any 
severity grade was seen in 22% of placebo subjects, 11% of subjects receiving 50 mg qd, 67% of 
subjects receiving 100 mg qd, 13% of subjects receiving 15 mg bid, 33% of subjects receiving 
25 mg bid and 67% of subjects receiving 50 mg bid.  Importantly, these neutropenia events were 
of Grade 1 or Grade 2 severity with a single instance of severe Grade 4 neutropenia that led to 
discontinuation of study drug in 1 subject receiving ruxolitinib at 50 mg bid (highest dose).  The 
maximum tolerated dose in healthy volunteers was determined to be 25 mg bid and no dose 
limiting toxicities (DLT) were seen at 100 mg qd. 
A definitive QT study was carried out in 50 healthy volunteers, evaluating the effects of single 
doses of 25 mg or 200 mg ruxolitinib compared with placebo and 400 mg moxifloxacin (positive 
control).  The overall conclusion was that there appeared to be no adverse impact on ventricular 
repolarization (no increase in QTcF) and little change in heart rate, QRS duration, and a slight, 
non-clinically significant, increase in PR interval with the administration of ruxolitinib. 
In an ongoing study in subjects with myelofibrosis (MF) where median time on drug is 
~ 15 months (N=154), ruxolitinib was well tolerated by this elderly population (median age 65) 
with advanced disease.  The DLT was thrombocytopenia.  Initial dose ranging established an 
MTD of 25 mg bid and 100 mg qd in the MF population.  Most adverse events were mild to 
moderate in severity and considered unrelated to administration of study drug.  Related adverse 
events occurring in at least 5% (8 subjects) of the 154 subjects included in the safety database 


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through December 31, 2009 were restricted to anemia (45 subjects), thrombocytopenia 
(66 subjects), weight increased (11 subjects), diarrhea (10 subjects) and fatigue (8 subjects).  
Both anemia and thrombocytopenia represent JAK-inhibitor induced myelosuppression.  
Forty (40) subjects (26% of study population) had a Grade 3 or Grade 4 decline in platelet count 
during the study (31 Grade 3 events, 9 Grade 4 events).  Subjects with Grade 3 or 4 
thrombocytopenia entered the study, in general, with platelet counts less than 200 x 109/L, 
although there are exceptions to this trend.  Twenty percent of Grade 3 + 4 thrombocytopenia 
events occurred in the first 4 weeks of dosing, just under half (48%) of Grade 3 + 4 events 
occurred in the first 16 weeks of treatment.  The incidence of thrombocytopenia was dose 
dependent, as anticipated.  For most subjects, thrombocytopenia was rapidly reversible and 
manageable with ruxolitinib dose interruption and/or dose reduction.   
The risk of spontaneous hemorrhage in patients as a result of thrombocytopenia generally does 
not become manifest until platelet counts fall below 10 to 20 x109/L (Slichter 2004).  In Study 
INCB 18424-251, the lowest platelet counts observed (grade 4 thrombocytopenia events) ranged 
from 6-22 x 109/L.  There was one patient with associated petechiae and no events of 
hemorrhage in the 9 patients with grade 4 platelet declines. 
There were 2 deaths in study INCB 18424-251 where the primary cause of death was related to 
hemorrhage (upper gastric and cerebral hemorrhage).  In the case of upper gastric hemorrhage, 
the patient had emergency surgical repair of a bleeding duodenal ulcer and died of post-operative 
complications.  The PLT count was 447 x 109/L and there was a history of antecedent aspirin use 
and epistaxis.  The event was considered unrelated to ruxolitinib.  In the case of cerebral 
hemorrhage, the patient had normal PLT count (201 x 109/L), normal coagulation tests, and a 
history of hypertension.  The event was assessed as possibly related to ruxolitinib. 
Other SAEs in study INCB 18424-251 that involved hemorrhage of any kind have been 
examined.  One patient was admitted to the hospital with a PLT count of 
 x 109/L and 
ultimately required splenectomy, following which a post-operative hemorrhage was noted in the 
surgical drains.  The patient was discharged from the hospital but chose to discontinue study 
drug.  Another patient had  episodes of lower gastrointestinal hemorrhage that were assessed as 
unrelated to ruxolitinib.  No information about PLT counts during the course of the event was 
provided.  A patient suffered from gastrointestinal hemorrhage of unknown source with a PLT 
count of 
x 109/L.  One patient had hematuria due to 
 surgery; the PLT count was 
 x 10 /L.  Another patient suffering from splenomegaly developed an intra-abdominal 
hematoma adjacent to the spleen, with a PLT count of 
 x 109/L.  One patient was hospitalized 
for melena with a PLT count of 
 x109/L.  Thus overall hemorrhage events in subjects on 
ruxolitinib in Study INCB 18424-251 were not associated with drug-induced thrombocytopenia. 
Ruxolitinib has demonstrated marked reduction in spleen size in the ongoing study in patients 
with MF, and without regard to presence of the JAK2 V617F mutation (Verstovsek et al 2010).  
In addition to spleen size reduction, Eastern Cooperative Oncology Group (ECOG) scores and 
symptoms thought to be related to splenomegaly, as well as symptoms related to elevated 
cytokine levels, all show improvement with ruxolitinib treatment.  As a surrogate marker for 
functional benefit, exercise capacity was assessed with a standardized six minute walk test 
(6MWT).  Ruxolitinib therapy resulted in improved 6MWT performance after 1, 3 or 6 months 
of therapy.  After an initial small weight loss likely due to resolution of ascites and/or reduction 


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in splenomegaly, there is an increase in total body weight; importantly, there is weight gain in 
subjects with low body mass index at entry, ie, cachectic subjects. 
Two Phase 3 registrations studies are ongoing.  Study INCB 18424-351 is a double blind, 
placebo controlled study of ruxolitinib in subjects with MF, and Study INCB 18424-352 is an 
open label comparative study of ruxolitinib versus best available therapy in subjects with MF.  In 
both Phase 3 studies, subjects began dosing at 20 mg bid if Baseline platelet count was 
> 200 x 109/L and at 15 mg bid for platelet count of 100 x109/L to 200 x 109/L, inclusive.  The 
data was analyzed when the last subject had completed the Week 24 visit, and at least 50% of 
subjects remaining in the study had completed the Week 36 visit, and the data base was frozen.  
The primary endpoint was the response rate defined as the percentage of patients achieving a 
35% or greater reduction in spleen volume at 24 weeks as measured by magnetic resonance 
imaging, or computerized tomography, comparing the rates in patients receiving ruxolitinib or 
placebo.  The primary analysis was recently conducted, and the primary and key secondary 
endpoints were met.  The response rate for spleen volume reduction was 42% in patients 
randomized to ruxolitinib versus < 1% in patients randomized to placebo (p 0.0001).  A 
significantly larger proportion of subjects in the ruxolitinib group achieved a ≥ 50% 
improvement from baseline in the modified MFSAF v2.0 diary total symptom score at Week 24 
compared with the placebo group (45.9% versus 5.3%, respectively, P < 0.0001).  At Week 24, 
the median total symptom scores were 6.6 and 17.6 in the ruxolitinib and placebo groups, 
respectively.  This represents a median improvement (score decrease) of 6.9 in the ruxolitinib 
group and a worsening (score increase) of 2.0 in the placebo group compared to baseline (Incyte 
confidential data on file).  The safety profile of ruxolitinib was consistent with previous studies, 
which included reversible thrombocytopenia and anemia.  Platelet counts declined over the first 
4 weeks of therapy in the ruxolitinib group, however the median count remained in the normal 
range.  Overall, 20 (12.9%) subjects in the INCB018424 group and 2 (1.3%) subjects in the 
placebo group had a new or worsening Grade 3 or 4 thrombocytopenia, usually as a single 
occurrence.  As in earlier studies, thrombocytopenia was managed with dose reductions and/or 
interruptions; only 1 subject receiving ruxolitinib discontinued from the study because of 
thrombocytopenia (Incyte confidential data on file). 
See the IB (Incyte Corporation) for additional details on clinical development of ruxolitinib. 
4.1.5. 
Interim Analysis Data from Study INCB 18424-258 
In Study INCB 18424-258, subjects with platelet counts of 50 to 100 x 109/L were enrolled to 
begin administration of ruxolitinib at 5 mg BID, which is a dose that represents a conservatively 
low starting dose, that data from earlier studies suggested should have a limited impact on 
platelet count.  Subjects could then titrate their dose to an appropriate dose that offers benefit (eg, 
symptomatic and/or spleen size improvements) with cautious monitoring to avoid levels of 
thrombocytopenia associated with higher risk of spontaneous hemorrhage.  Ruxolitinib 
administration was interrupted for a platelet count below 25 x 109/L or for Grade 2 or higher 
hemorrhage events. 
The study is currently in the enrollment phase; however, an interim analysis was conducted 
based on a data cutoff when it was expected that at least 20 subjects would have completed 
24 weeks of treatment.  At the time of the interim analysis, a total of 50 subjects had enrolled in 
the study.  Of the 50 subjects enrolled, 33 (66.0%) subjects completed the Week 24 visit, 


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8 (16.0%) discontinued prior to Week 24, and 9 (18.0%) subjects remained on study and had not 
yet completed their Week 24 visit. 
Most subjects were titrated to a ruxolitinib dose of 10 mg BID or higher by Week 24 and 20.0% 
of subjects had a ≥ 35% reduction in spleen volume at Week 24.  This is consistent with the 
proportion of subjects in Study INCB 18424-351 who had a ≥ 35% reduction in spleen volume at 
Week 24 who initiated treatment at a dose of 15 mg BID (21.8%), and substantially higher than 
that observed for placebo-treated subjects in Study INCB 18424-351 (1.7%).  In addition, 
Mesa et al (2011) has shown that a spleen volume reduction of ≥ 10% is associated with 
meaningful improvements in symptoms and other measures of patient-perceived benefit (Patient 
Global Impression of Change [PGIC] and Myelofibrosis Symptom Assessment Form 
[MFSAF v2.0]). 
In Study INCB 18424-258, the proportion of ruxolitinib-treated subjects achieving a ≥ 50% 
improvement in TSS at Week 24 was 34%.  This is consistent with the proportion of subjects in 
Study INCB 18424-351 who had a ≥ 50% improvement in TSS at Week 24 who initiated 
treatment at a dose of 15 mg BID (31.4%).  Although this was an unblinded study, the gradual 
time course of improvement is consistent with the gradual dose escalation in the study.  The 
proportion of subjects who achieved a ≥ 50% improvement in TSS gradually increased over time 
through approximately Week 13, which is consistent with the time that the majority of subjects 
reached 10 mg BID at Week 13.  This is in contrast with the rapid improvement seen in Study 
INCB 18424-351, suggesting that the observed effect is related to ruxolitinib titration. 
Subjects also showed improvement based on the PGIC, which is an assessment of overall 
impression of treatment benefit.  In Study INCB 18424-258 as early as Week 4, 36.6% of 
subjects rated themselves as much improved or very much improved, and at Week 24, 53.7% of 
subjects rated themselves as much improved or very much improved. 
There were no unexpected safety signals during this study.  The most common nonhematologic 
adverse events (AEs) were diarrhea (28.0%), peripheral edema (26.0%), nausea (24.0%), 
abdominal pain (24.0%), and fatigue (22.0%).  Most nonhematologic AEs were Grade 1 or 2.  
The majority of subjects were able to escalate to a dose of 10 mg BID and maintain platelet 
counts above 35 x 109/L.  Subjects who had dose decreases or interruptions per protocol showed 
recovery of platelet counts.  Based on laboratory values, 8 subjects (16%) had a Grade 4 
decreased platelet count (< 25 x 109/L).  One subject withdrew from the study because of 
thrombocytopenia. 
The gradual increase in dose from 5 mg BID in Study INCB 18424-258 seemed to avoid the 
initial drop in hemoglobin seen in Study INCB 18424-351, in which subjects began therapy with 
15 mg or 20 mg BID.  In addition, in Study INCB 18424-258, a maximum dose of 10 mg BID 
was not associated with significant changes in hemoglobin through Week 24 in subjects who did 
not receive transfusions through the study.   
These preliminary findings suggest that a dosing strategy starting with lower doses of ruxolitinib 
with subsequent dose optimization is efficacious and well tolerated in subjects who have platelet 
counts of 50 to 100 x 109/L at treatment initiation.  In most subjects, ruxolitinib could be titrated 
to 10 mg BID, which provided clinically meaningful reductions in spleen volume and TSS.  
Thrombocytopenia was manageable with dose reduction or dose interruption and mean 
hemoglobin levels remained stable throughout the study.  Although this study is ongoing, data 


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from this interim analysis will help support individualized ruxolitinib dosing strategies in 
subjects with MF and lower platelet counts. 
4.2. 
Trial Rationale 
As noted in the Introduction, the ongoing phase 1/2 study INCB 18424-251 in MF patients 
examined twice daily dose regimens ranging from 10 mg bid to 50 mg bid, and once daily dosing 
regimens ranging from 25 mg qd to 200 mg qd; doses of 50 mg bid and 200 mg qd were not well 
tolerated; 25 mg bid and 100 mg qd were designated maximum tolerated doses.  To date, all 
patients enrolling in this study, or in the ongoing Phase 3 studies, have been required to have a 
pre-study platelet count of at least 100 x109/L.  However, there is a significant population of MF 
patients who have chronic mild or moderate thrombocytopenia, with platelet counts in the range 
of 50 x109/L to 100 x109/L.  Based on epidemiology data (Mesa et al 2007), 16.5% of all MF 
patients are reported to have PLT counts < 100 x109/L at diagnosis.  According to chart reviews 
of nearly 800 subjects with PMF at the Mayo Clinic, the proportion of subjects with platelets 
below 100 x109 in various risk categories based on the Dynamic International Prognostic Scoring 
system (DIPSS) ranged from 7% for low risk to 32% in intermediate-2 risk groups (Gangat et al 
2011).  While JAK inhibition is clearly, and not unexpectedly, associated with decreasing 
platelet counts, emergent thrombocytopenia is easily detected, and can be managed with dose 
decreases or brief drug interruptions.  A Phase 1 /2 study with another JAK inhibitor, CYT387, is 
being conducted in subjects with platelet counts as low as 50 x109/L (http://clinicaltrials.gov, 
identifier: NCT00935987, Pardanani et al 2011). 
An exploratory analysis of subjects who enrolled in the Phase 1/2 study with platelet counts 
< 150 x109/L who had extended (many weeks) periods of Grade 1 or 2 platelet decline, was 
carried out in order to identify the dose(s) associated with stable platelet counts in the range of 
50 x109/L to 100 x109/L.  Fourteen subjects were identified that fit these criteria; 9 of the 
subjects maintained platelet counts between 50,000/µL and 100,000/µL while receiving 5 mg 
bid, 2 subjects maintained platelets in this range taking 10 mg bid, one subject was receiving 
10 mg PM/5 mg AM, one was receiving 5 mg qd and one was receiving 10 mg qd.  Importantly, 
splenomegaly and/or symptom improvements were maintained in 11 of the 14 subjects at a level 
similar to that observed with their initial, higher dose regimen.  These data suggest that a dose of 
5 mg bid, with dose escalation and reductions in response to platelet count response may be 
associated with symptom and spleen size improvements, while allowing platelet counts to be 
maintained near or above the 50 x109/L level.  In the present study, patients with Grade 1 and 2 
thrombocytopenia, having platelet counts of 50 x109/L to 100 x109/L will be enrolled to begin 
dosing at 5 mg bid, and titrated to an appropriate dose that offers benefit (symptomatic and/or 
spleen size improvements) balanced with risk (worsening thrombocytopenia).   
4.3. 
Potential Risks and Benefits of the Treatment Regimen 
4.3.1. 
Potential Risks 
No specific findings in nonclinical repeat dose toxicity studies identify clinical risks other than 
noting that consequences of immunosuppression may occur.  Hypotension and increases in heart 
rate were noted at a high dose in a cardiovascular preclinical study.  However, these findings 
have not been recapitulated in a clinical setting.   


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The primary clinical risks with ruxolitinib treatment are the potential sequelae of decreased 
hematopoietic proliferation secondary to the inhibition of growth factor pathways by JAK2 
inhibition.  Dose-dependent, reversible thrombocytopenia has been observed in subjects with MF 
and represents the DLT.  The risk of spontaneous hemorrhage in patients as a result of 
thrombocytopenia generally does not become manifest until platelet counts fall below 10 x 109/L 
(Slichter 2004); platelet counts below 25 x 109/L (Grade 4) were not observed in any subjects 
initiating ruxolitinib at starting doses of 10 mg bid or 15 mg bid in the ongoing phase 1 /2 study.  
In the current study, dosing must be interrupted for platelet count below 25 x 109/L, or for 
Grade 2 or higher hemorrhage events that are assessed as at least possibly related to ruxolitinib 
therapy. 
Anemia and, less frequently, neutropenia have also been observed in patients with MF treated 
with ruxolitinib.  Increased rates of infection and anemia are potential risks of myelosuppression, 
and there are multiple sequelae of anemia including the burden and risks of transfusion.  A few 
subjects have had an apparent worsening of their pre-morbid disease symptoms following rapid 
cessation of ruxolitinib therapy and a gradual tapering and use of steroids in fragile subjects may 
be considered when stopping ruxolitinib therapy.   
4.3.2. 
Potential Benefits 
The clinical efficacy results of ruxolitinib that have emerged from the ongoing Phase 1/2 and 
Phase 3 studies are notable, including marked reduction in splenomegaly, improvement in 
symptoms, performance status and activity level, and reduction in plasma levels of 
inflammatory, prothrombotic and angiogenic cytokines.  In those subjects with prolonged 
exposure to ruxolitinib (median of 15 months therapy), these positive effects have been 
maintained.  In the present study, it is anticipated that individualized dose optimization from the 
starting level of 5 bid will be associated with reductions in splenomegaly, MF-associated 
symptoms and inflammatory cytokine levels. 
5. 
STUDY OBJECTIVES AND PURPOSE 
5.1. 
Primary Objective 
• To determine the effects of ruxolitinib on spleen volume and symptom burden in 
patients with primary myelofibrosis (PMF), post polycythemia vera-myelofibrosis 
(PPV-MF) and post essential thrombocythemia-myelofibrosis (PET-MF) who have 
Baseline platelet count of 50 x 109/L to 100 x 109/L. 
• To determine the safety and tolerability of ruxolitinib in patients with PMF, PPV-MF 
and PET-MF who have Baseline platelet count of 50 x 109/L to 100 x 109/L. 
5.2. 
Secondary Objectives 
• To determine an appropriate dosing strategy for patients with low platelets. 
• To determine the long-term safety and efficacy effects of ruxolitinib in patients with 
PMF, PPV-MF, and PET MF who have a baseline platelet count of 50 x 109/L to 
100 x 109/L. 


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6. 
SUBJECT ELIGIBILITY 
6.1. 
Study Population 
Male or female individuals, aged 18 years or older who have been diagnosed with myelofibrosis 
(either PMF, PPV-MF or PET-MF), who have platelet counts between 50 and 100 x109/L and for 
whom treatment of MF is indicated may enroll.  Subjects must score at least 1 point according to 
the DIPSS prognostic criteria (Passamonti et al 2010).  Enrolled subjects must have a life 
expectancy of > 6 months. 
6.2. 
Subject Inclusion Criteria 
All subjects must meet the following inclusion criteria: 
1. Subjects who are able to understand and sign an informed consent document. 
2. Subjects 18 years of age or older. 
3. Subjects must be diagnosed with PMF, PPV-MF or PET-MF, according to the 
investigator’s expert judgment, guided by the criteria outlined in the 2008 World Health 
Organization criteria (see Appendix 1) for PMF, and the proposed criteria for PPV-MF 
and PET-MF outlined by the International Working Group for Myeloproliferative 
Neoplasms Research and Treatment (IWG-MRT) (see Appendix 2) irrespective of JAK2 
mutation status.  A bone marrow biopsy will provide the relevant information; subjects 
without a prior biopsy report obtained in the 2 months prior to screening for review must 
have a biopsy at screening or baseline or will not be able to enroll in the study. 
4. Subjects with MF requiring therapy must have at least 1 point using the DIPSS 
prognostic criteria developed by the IWG-MRT (Passamonti et al 2010), using the 
information from laboratory assessments and ongoing medical history recorded at the 
screening visit.  The prognostic variables and assigned point values are:  
Prognostic Variable 
Value 
0 Points 
1 Point 
2 Points 
Hemoglobin
a 
≥ 10 g/dL 
 
< 10 g/dL 
Age, Years 
< 65 
≥ 65 
 
White Blood Cell Count 
≤ 25 x 109/L 
> 25 x 109/L 
 
Peripheral Blood Blasts 
< 1% 
≥ 1% 
 
Constitutional Symptomsb 
No 
Yes 
 
a A hemoglobin value < 10 g/dL must be demonstrated during the screening visit for subjects who are not 
transfusion dependent.  Subjects receiving at least 2 units of packed red blood cells in the 12 weeks prior 
to Screening will be considered to have hemoglobin < 10 g/dL for the purpose of evaluation of risk 
factors. 
b Constitutional symptoms are defined as any of the following:  10% or more weight loss in the 6 months 
prior to screening, night sweats, unexplained fever (> 37.5°C). 


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5. Subjects in whom treatment of MF is indicated based on the Investigator’s expert 
judgment.  
6. Subjects with active symptoms of MF at the screening Visit as demonstrated by presence 
of one symptom score of at least 5 or two symptom scores of at least 3 using the 
Screening Symptom Assessment Form (Appendix 7). 
7. Subjects who have platelet counts between 50 and 100 x 109/L at the screening and/or 
baseline visits.  Platelet counts must be without the assistance of growth factors, 
thrombopoietic factors, or platelet transfusions.   
8. Subjects with hemoglobin value at the screening visit ≥ 6.5 g/dL and who are willing to 
receive red blood cell transfusions to treat low hemoglobin levels. 
9. Subjects must have discontinued all drugs used to treat underlying MF disease no later 
than Day -14. 
10. Subjects must not currently have the option of stem cell transplantation, either because 
they are not a candidate, or because a suitable donor is not available. 
11. Subjects with an ECOG performance status of 0, 1, 2 or 3 (Appendix 5) at the screening 
visit. 
12. Subjects with peripheral blood blast count of < 5% at both screening and baseline visits. 
6.3. 
Subject Exclusion Criteria 
Any of the following are causes for exclusion from the study, and must be demonstrated not to 
be present at the screening visit (historical data for measurements or labs may not be used): 
1. Subjects with a life expectancy of less than 6 months. 
2. Subjects in whom MF disease is well controlled with current therapy. 
3. Females who are pregnant or are currently breastfeeding. 
4. Subjects of childbearing potential who are unwilling to take appropriate precautions 
(from screening through follow-up) to avoid becoming pregnant or fathering a child.   
• Females of non-childbearing potential are defined as women who (a) are ≥ 55 years 
of age with history of amenorrhea for 1 year, OR (b) are surgically sterile for at least 
3 months. 
• For females of childbearing potential, or for males, appropriate precautions are those 
that are at least 99% effective in preventing the occurrence of pregnancy.  These 
methods should be communicated to the subjects and their understanding confirmed 
(Appendix 3).  
5. Subjects with inadequate bone marrow reserve as demonstrated by: 
• Absolute neutrophil count (ANC) that is < 1 x 109/L at the screening or baseline visits 
or had ANC levels < 500/µL in the month (30 days) prior to screening.  Subjects 
must not have received growth factors for at least 1 month (30 days) prior to 
receiving the first dose of study drug.  


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• Confirmed platelet count that is < 50 x 109/L or subjects with a known history of 
platelet counts < 25,000/µL, in the absence of cytoreductive therapy. 
6. Subjects with platelet count > 100 x 109/L at BOTH screening and baseline visits. 
7. Subjects with recent (within 12 months of screening) major bleed requiring transfusion(s) 
or resulting in a decrease in hemoglobin by 3 g/dL or more.  
8. Subjects with inadequate coagulation parameters as follows:  INR > 1.5 or PTT > 1.5 x 
upper limit of laboratory normal (ULN). 
9. Subjects with known history of esophageal or gastric varices, or any intracranial 
bleeding.  Subjects with a history of an incidental finding of small varices (< 5 mm) may 
be permitted in the study with Sponsor approval. 
10. Subjects with inadequate liver or renal function at screening and baseline visits as 
demonstrated by:  
• Direct bilirubin ≥ 2 x ULN (NOTE: direct bilirubin will only be determined if total 
bilirubin is ≥ 2.0 x ULN). 
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 2.5 x ULN. 
• Serum creatinine > 2.0 mg/dL or creatinine clearance < 30 mL/min measured or 
calculated by Cockroft-Gault Equation.  
11. Subjects with clinically meaningful, active bacterial, fungal, parasitic or viral infection 
which require therapy, or who are HIV positive 
12. Subjects with acute bacterial infections requiring antibiotic use should delay 
screening/enrollment until the course of antibiotic therapy has been completed and the 
event is considered resolved. 
13. Subjects who are currently receiving therapy with a moderate or potent CYP3A4 
inhibitor (Appendix 8).  Subjects may enter the screening phase when therapy with the 
moderate or potent CYP3A4 inhibitor is completed, and use of moderate inhibitors 
during the study will be permitted. 
14. Subjects with an invasive malignancy over the previous 2 years except treated early stage 
carcinomas of the skin completely resected intraepithelial carcinoma of the cervix and 
completely resected papillary thyroid and follicular thyroid cancers. 
15. Subjects with recent severe or unstable cardiac disease. 
16. Subjects who have had splenic irradiation within 6 months prior to Day 1. 
17. Subjects who have previously received treatment with a JAK inhibitor.  
18. Subjects being treated concurrently with any prohibited medications (see Section 8.9.2 
for specific prohibited medications and the associated timeframe over which they are 
prohibited). 
19. Subjects with active alcohol or drug addiction that would interfere with their ability to 
comply with the study requirements. 


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20. Subjects with any concurrent condition that, in the investigator’s opinion, would 
jeopardize the safety of the subject or compliance with the protocol. 
21. Subjects who are unable to complete the daily symptom diary, which is available in 
English and Spanish versions. 
6.4. 
Subjects Who Fail to Meet Screening Criteria 
A subject who has a laboratory test result(s), vital signs, or ECG finding(s) that does not satisfy 
the entrance criteria may have the test(s) repeated once.  These tests may be repeated as soon as 
the investigator believes that the retest result is likely to be within the acceptable range to satisfy 
the entrance criteria, but must be completed within the 3 week screening phase (Days -28 to -8).  
In this case, the subject will not be required to sign another ICF, and the original subject 
identification number will be used.  In the event that the laboratory test(s) cannot be performed 
within the screening period, or the re-test(s) do not meet the entrance criteria or the subject’s 
medical condition has changed significantly during the screening phase so that 
inclusion/exclusion criteria are no longer met, the subject is considered a screen failure, and must 
be withdrawn from the study.  Therefore, sites should consider the testing schedule carefully so 
that any potential retests are accomplished in the 3 week time frame.  If the subject and 
investigator agree to re-screening, the subject must sign a new ICF, a new subject identification 
number will be assigned, and all required screening activities must be performed when the 
subject is re-screened for participation in the study (except bone marrow biopsy if already 
performed at screening).  An individual subject may only re-screen once for the study. 
If all screening activities cannot be completed in the screening phase because of an event 
unrelated to a laboratory finding, ECG finding, or medical history finding, including scheduling 
difficulties at the clinic site, the subject may retain the original subject number and complete the 
remaining screening activities as soon as possible, within a maximum of 42 days (6 weeks) from 
the original screening visit date.  A blood draw for hematology and serum chemistry must be 
taken at the time the subject returns for completion of screening activities, and will be used to 
determine eligibility. 


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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This is an open label study of ruxolitinib in patients with PMF, PPV-MF, and PET-MF.  The 
study is comprised of 4 phases: 
Screening: 
Up to 21 days 
Baseline: 
Exactly 7 days 
Core Treatment Phase: 
24 weeks   
Extended Treatment Phase: 
132 weeks; subjects receiving benefit will continue 
ruxolitinib treatment until Week 156  
Follow-up Phase: 
All subjects will be followed for safety (eg, reporting of 
AEs and SAEs) for 30 to 37 days after the last dose of 
study drug is administered  
Core Treatment Phase: 
During the core treatment phase, there will be study visits and laboratory-only visits.  Subjects 
will have a regularly scheduled study visit at screening, baseline, Day 1, Week 4, Week 8, 
Week 12, Week 16, Week 20 and Week 24, where blood samples, assessments, spleen 
measurements, etc. will be obtained.  All hematology labs and coagulation parameters will be 
analyzed by local laboratories.  Serum chemistries, serology, and lipid panel will be analyzed by 
a central laboratory. 
Subjects will have laboratory-only visits to collect hematology lab samples at Week 1, Week 2, 
Week 3, Week 5, Week 6, Week 7, Week 10, Week 14, and Week 18.  The laboratory visits at 
Week 14 and Week 18 may be skipped for subjects who do not increase their dose at Week 12 or 
Week 16, and who have maintained platelet counts > 75 x 109/L since the last hematology 
assessment.  Additional, at least weekly laboratory-only visits to collect hematology lab samples 
will be required if platelet count falls below 35 x 109/L; more frequent monitoring is 
recommended if counts fall below 25 x 109/L.  These laboratory visits can occur at the study site 
laboratory, or any local laboratory that can provide the data and appropriate certificates and 
normal laboratory ranges to the study site for review for subject management in a timely fashion.   
Subjects will have an MRI of the upper and lower abdomen and pelvis to determine the spleen 
volume at baseline and Week 24.  A CT scan will be substituted for subjects who are not 
candidates for MRI, or when MRI is not readily available.  Patients Global Impression of Change 
(PGIC) questionnaire will be completed monthly.  Measurement of spleen length below the left 
costal margin will be measured by palpation at each study visit.  
Subjects will complete an electronic symptom diary from baseline through the Week 24 visits 
(total of 25 weeks).  Subjects will be trained on the use and care of the diary, and symptom diary 
data will be transmitted automatically each night wirelessly or using the diary docking station 
provided to subjects. 


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Extended Treatment Phase: 
Subjects will have a study visit every 12 weeks (eg, Weeks 36, 48, 60, 72, 84, 96, 108, 120, 132, 
144, and 156), through Week 156 where blood samples, clinical assessments, and palpable 
spleen measurements, etc. will be obtained.  Subjects will have laboratory-only visits to collect 
hematology samples 6 weeks after the Week 24 visit (eg, Week 30), then after each extended 
treatment phase visit (eg, Weeks 42, 54, 66, 78, 90, 102, 114, 126, 138, and 150).  Additional 
hematology assessments will be required if the subject has a dose modification or as clinically 
indicated. 
Follow-Up Phase: 
All subjects will be followed for safety (eg, reporting of AEs and serious AEs) for 30 to 37 days 
after the last dose of study drug is administered.  
7.2. 
Study Endpoints 
7.2.1. 
Co-Primary Endpoints 
• Correlation of % change in spleen volume at Week 24 compared to baseline versus 
final titrated dose. 
• Correlation of % change in Total Symptom Score as measured by the modified 
MFSAF v2.0 diary at Week 24 compared to baseline versus final titrated dose. 
7.2.2. 
Safety Endpoints: 
• Safety and tolerability will be assessed by monitoring the frequency, duration and 
severity of adverse events, performing physical examinations, collecting vital signs, 
collecting laboratory data for hematology, serum chemistry, and coagulation 
parameters through Week 156.  In addition, analyses will include: 
− Proportion of subjects with new onset Grade 4 thrombocytopenia events as 
assessed by CTCAE v4.03. 
− Proportion of subjects with new onset Grade 2 or higher hemorrhage as assessed 
by CTCAE v4.03. 
7.2.3. 
Secondary Endpoints 
• Percent change in spleen volume at Week 24 compared to Baseline. 
• Percent change in Total Symptom Score as measured by the modified MFSAF v2.0 
diary at Week 24 compared to baseline. 
• Proportion of subjects with ≥ 35% reduction in spleen volume at Week 24 compared 
to baseline. 
• Proportion of subjects with ≥ 10% reduction in spleen volume at Week 24 compared 
to baseline. 
• Proportion of subjects with ≥ 50% improvement in total symptom score as measured 
by the modified MFSAF v2.0 diary at Week 24 compared to baseline. 


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• Long-term efficacy of ruxolitinib will be assessed by monitoring change and percent 
change in spleen length, as measured by palpation, and change in PGIC score from 
baseline to each visit where the variables are measured through Week 156. 
7.3. 
Measures Taken to Avoid Bias 
This is an open label study.  Measurement of spleen volume by MRI (or CT scan in applicable 
subjects) and determination of thrombocytopenia grade (by CTCAE criteria) are objective 
responses. 
7.4. 
Number of Subjects 
Approximately 150 subjects may be enrolled. 
7.5. 
Criteria for Study Termination 
Both the Sponsor and the Investigator reserve the right to terminate the study, according to the 
terms specified in the study contract.  The Investigator is to notify the IRB/IEC in writing of the 
study’s completion or early termination, and send a copy of the notification to the Sponsor or 
Sponsor’s designee and retain one copy for the site study regulatory file. 


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8. 
TREATMENT OF SUBJECTS 
8.1. 
Treatment Arms and Study Drug Administration 
All subjects will begin dosing at 5 mg bid ruxolitinib.  Doses should be taken morning and 
evening, approximately 12 hours apart, and without regards to food. 
Dose increases will be allowed for subjects with adequate platelet counts, and mandatory dose 
reductions and interruptions will be required for declining platelet counts, declining ANC levels 
or Grade 2 and higher hemorrhage events.  See Section 8.6, Dose Adjustments. 
8.2. 
Treatment Compliance 
Subjects will bring all bottles of unopened, empty, and opened/partially used study drug with 
them to each study visit.  Investigative site staff will perform a count of returned pills to assess 
compliance, and this information will be entered on the eCRF.  Study drug, including all bottles 
of unopened, partially opened or empty bottles cannot be returned to the depot until a monitor 
reviews and verifies all pill counts for compliance. 
8.3. 
Randomization and Blinding 
Not applicable, study is open label and single arm. 
8.4. 
Duration of Treatment and Subject Participation 
Participation will be for approximately 165 weeks and 2 days, including the screening and 
baseline phases (see Section 9.1), core treatment phase (see Section 9.2), extended treatment 
phase (see Section 9.3), and follow-up phase (see Section 9.5). 
8.5. 
Considerations for Dose Modifications 
Inhibition of JAKs by a JAK 1/2 inhibitor such as ruxolitinib is associated with 
thrombocytopenia and anemia in subjects with MF.  See the Investigator’s Brochure for 
additional details on hematologic consequences of JAK inhibition.  Platelet count, ANC and 
hemoglobin levels will be assessed on a regular basis.  Complete blood count (CBC) will be 
monitored more frequently in the first few weeks of the study, and more frequent monitoring 
may be done at the Investigator’s discretion at any time.   
8.6. 
Dose Adjustments  
The goal of dose modifications in the study is to permit individual dose optimization for subjects 
to obtain maximum benefit, while maintaining a stable platelet count > 25 x 109/L, and an 
ANC > 0.5 x 109/L. 
8.6.1. 
Dose Increases 
Dose increases are optional. 


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During the core treatment phase, doses of ruxolitinib may be increased in 5 mg qd increments 
up to a dose of 10 mg bid starting at the Week 4 visit and at subsequent study visits.  Dose 
increases can occur no more frequently than every 4 weeks, and only if: 
• Platelet count was always ≥ 40 x 109/L since the last scheduled study visit 
• Platelet count, if decreased since the last scheduled study visit, is decreased by no 
more than 20% of the platelet count at the last scheduled visit 
• No dose decreases or holds for safety have occurred during the preceding 4-week 
interval 
• ANC > 1.0 x 109/L since the last scheduled study visit. 
• For subjects with prior ≥ Grade 2 hemorrhage events, please see below under 
Section 8.6.3.4, Restarting with Resolution of Hemorrhage Events 
Doses may not exceed 10 mg bid except in subjects who continue to meet the above dose 
escalation criteria, and who have, in addition, a PGIC score of 3 (minimally improved) to 7 (very 
much worse) while receiving 10 mg bid.  Such subjects may continue dose escalation to a 
maximum dose of 15 mg bid.  Note that when a 5 mg qd increment is added, creating a regimen 
such as 5 mg/10 mg, the higher dose should be taken in the evening and the lower dose in the 
morning.  
During the extended treatment phase, doses of ruxolitinib may be increased in 5 mg qd 
increments up to a dose of 25 mg bid if the subject meets the above dose escalation criteria, or 
per the investigator’s discretion. 
Doses may never exceed 25 mg bid. 
8.6.2. 
Mandatory Dose Interruptions, Dose Discontinuations and Dose Reductions 
Dosing must be held if any of the following occur: 
• Platelet counts decline below 25 x 109/L (dosing must be interrupted immediately.  A 
repeat assessment should be performed as soon as feasible, but follow-up platelet 
values to trigger the restart guidelines from Section 8.6.3 may only follow beginning 
at least 3 days later).  
• ANC declines to < 0.5 x 109/L.   
• Ongoing Grade 2 or higher hemorrhage event, regardless of causality. 
The dose must be reduced for a confirmed platelet count < 35 x 109/L as follows:  
• An observation of platelets between 25 x 109/L and 35 x 109/L should trigger a repeat 
laboratory measurement of platelet counts.  Dosing need not be adjusted until the 
results of the confirmatory test are known. 
• The reduction will be based on the current dose, and on the rapidity with which 
counts declined to the < 35 x 109/L level and are ≥ 25 x 109/L (see Table 2).  
• Subjects who have implemented a dose reduction because of platelets falling below 
35 x 109/L DO NOT need to further decrease their dose provided the platelet count 
remains ≥ 25 x 109/L even if they remain below 35 x 109/L.   
• Mandatory dose reductions are summarized in Table 2. 
 


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Table 2: 
Mandatory Dose Reductions and Dose Holds for Safety 
Thrombocytopenia 
Platelet Count at Time of Decline 
Action with Respect to Dose 
≥ 35 x 109/L throughout study 
Continue on dose established according to Section 8.6.1  
< 35 x 109/L and ≥ 25 x 109/L (confirmed by 
repeat lab), and platelet count decline is >20% 
from prior visit 
Decrease current dose level by 5 mg bid or to a dose of 
5 mg qd if currently receiving 5 mg bid.  If current dose 
is 5 mg qd, can continue at that dose. 
< 35 x 109/L and ≥  25 x 109/L (confirmed by 
repeat lab), and platelet count decline is 
≤ 20% from prior visit 
Decrease current dose level by 5 mg qd or to a dose of 
5 mg qd if currently receiving 5 mg bid.  If current dose 
is 5 mg qd, can continue at that dose. 
< 25 x 109/L 
Must hold dosing 
Active Hemorrhage 
Worst CTCAE Grade  
Action with Respect to Dose 
Grade 1 
May continue dosing (frequent platelet counts 
recommended) 
Grade ≥ 2  
Must hold dosing 
Neutropenia 
ANC at Time of Decline 
Action with Respect to Dose 
< 0.5 x 109/L 
Must hold dosing 
NOTE:  Investigators may also decrease the dose for any reason based on their clinical judgment, 
including taking a more conservative approach to hematological abnormalities or because of 
nonhematologic safety findings.  Dose re-escalation will follow the guidelines provided in 
Section 8.6.1 (Dose Increases).   
8.6.3. 
Restarting or Increasing Ruxolitinib after Recovery of Platelet or ANC Levels or 
Resolution of Hemorrhage 
Note that the restarting and re-escalation doses in this section are the maximum allowed under 
this protocol.  Individual investigators may elect to adopt a more cautious approach to restarting 
or escalating doses at their discretion, but they may not restart sooner or re-escalate more rapidly 
than outlined in this section. 
8.6.3.1. 
Restarting or Re-Escalating with Improving Platelet Counts 
For subjects who had never previously increased their dose above 5 mg bid, and have a platelet 
count decline necessitating drug hold, ruxolitinib may be restarted as follows: 
• Ruxolitinib may be restarted at 5 mg qd when the platelet count has risen above 
35 x 109/L. 
• After no less than 2 weeks, and provided there are at least 2 consecutive platelet count 
results, at least 3 days apart, of ≥ 40 x 109/L, the dose may be increased to 5 mg bid.  
No further increase in dose is allowed. 
• A second platelet decline below 25 x 109/L will necessitate a second drug hold.  
Ruxolitinib may be restarted at 5 mg qd when the platelet count has risen above 
35 x 109/L.  No further increase in dose is allowed. 
− The subject may remain on 5 mg qd provided platelet counts remain ≥ 25 x 109/L. 


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For subjects who had previously increased their dose to a level above 5 mg bid, and have a 
platelet count decline necessitating drug hold, ruxolitinib may be restarted as follows: 
• Ruxolitinib may be restarted at 5 mg qd when the platelet count has risen above 
35 x 109/L. 
• After no less than 2 weeks, and provided there are at least 2 consecutive platelet count 
results, at least 3 days apart, of ≥ 40 x 109/L, the dose may be increased to a dose up 
to the highest dose that previously qualified for further dose increases according to 
Section 8.6.1 (Dose Increases).  For example, if a subject tolerated 10 mg bid 
ruxolitinib and qualified for a dose increase, but the platelet counts fell sharply at the 
increased dose of 10 mg AM/15 mg PM, and drug was halted; the highest dose this 
subject may now use is the previously tolerated dose of 10 mg bid.   
• A second platelet decline below 25 x 109/L will necessitate a second drug hold.  
Ruxolitinib may be restarted at 5 mg qd when the platelet count has risen above 
35 x 109/L, and may be increased to 5 mg bid after ≥ 2 weeks with at least 2 
consecutive measures above 40 x 109/L at least 3 days apart.  No further increase in 
dose is allowed. 
For subjects who previously decreased dose, but never held dose, dose increases using the dose 
increase guidelines in Section 8.6.1 may be implemented once platelet counts are ≥ 40 x 109/L on 
at least 2 consecutive measurements at least 3 days apart, however, the maximum dose may not 
exceed the higher of a dose of 5 mg bid or a dose that is 5 mg qd less than the dose at the time 
the decline to below 35 x 109 first began.   
8.6.3.2. 
Use of Platelet Transfusions 
Platelet transfusions may be used at Investigator’s discretion to treat thrombocytopenia.  Dosing 
restart or increase decisions may not be based on platelet count values observed within 7 days of 
a platelet transfusion. 
8.6.3.3. 
Restarting or Re-Escalating with Improving ANC 
For subjects who had never previously increased their dose above 5 mg bid, and have an ANC 
decline necessitating drug hold, ruxolitinib may be restarted as follows:   
• The dose may be restarted at 5 mg qd when ANC levels are > 0.75 x 109/L.   
• After no less than 2 weeks, and provided there are at least 2 consecutive ANC levels 
≥ 1.0 x 109/L at least 3 days apart, the dose may be increased to 5 mg bid.  No further 
increase in dose is allowed. 
• A second ANC decline below 0.5 x 109/L will necessitate a second drug hold.  
Ruxolitinib may be restarted at 5 mg qd when the ANC is > 0.75 x 109/L.  No further 
increase in dose is allowed 


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For subjects who had previously increased their dose to a level above 5 mg bid, and have an 
ANC decline necessitating drug hold, ruxolitinib may be restarted as follows:   
− The dose may be restarted at 5 mg qd when ANC levels are > 0.75 x 109/L.   
− After no less than 2 weeks, and provided there are at least 2 consecutive ANC 
levels  ≥ 1.0 x 109/L at least 3 days apart, the dose may be increased to a dose up 
to the highest dose that previously qualified for further dose increases according 
to Section 8.6.1 (Dose Increases). 
− A second ANC decline below 0.5 x 109/L will necessitate a second drug hold.  
Ruxolitinib may be restarted at 5 mg qd when the ANC is > 0.75 x 109/L, and 
may be increased to 5 mg bid with at least 2 consecutive measures, at least 3 days 
apart of ≥ 1.0 x 109/L.  No further increase in dose is allowed. 
In order to provide sufficient data to make the dose restart decisions, it is recommended that 
hematology parameters be obtained at least 2 times weekly for platelet count < 25 x 109/L, or for 
ANC levels < 0.5 x 109/L.  
8.6.3.4. 
Restarting with Resolution of Hemorrhage Event 
• For Grade 2 hemorrhage events of any causality, dosing may be restarted at the prior 
level once the event is resolved to Grade 0, and its underlying cause has been 
alleviated or resolved, as long as platelet count and ANC do not preclude a restart at 
that dose level.  Restart of dosing after a second Grade 2 hemorrhage event may only 
occur following discussion with the sponsor taking into account causality, resolution 
of the bleeding and underlying etiology and likelihood of recurrence, in order to reach 
agreement that the potential benefits of a restart at an appropriate dose outweigh risks 
of recurrent hemorrhage. 
• For Grade 3 or 4 hemorrhage events of any causality, dosing may only be restarted 
provided: platelet count and ANC do not preclude a restart, the event has resolved to 
Grade 0, and the underlying cause has been alleviated or resolved, and following 
discussion with the sponsor taking into account causality, resolution of the bleeding 
and underlying etiology and likelihood of recurrence, in order to reach agreement that 
the potential benefits of a restart at an appropriate dose outweigh risks of recurrent 
hemorrhage.  Further dose escalations in these subjects will also require discussion 
with the sponsor. 
Note that if more than one finding (thrombocytopenia, neutropenia or hemorrhage) was the 
cause for the dose reduction or interruption, improvements in all parameters must be considered 
in restarting ruxolitinib and the lowest calculated dose must be used.    
8.6.4. 
Possible Changes in Study Conduct Because of Frequent Hemorrhage or 
Thrombocytopenia Events 
Events of Grade 4 thrombocytopenia and > Grade 2 hemorrhage will be reported by Investigators 
to sponsor on a continuous basis, and this data will be reviewed by sponsor on an ongoing basis.  
A Data Monitoring Committee (DMC) will also review this data.  The protocol may be modified 
on the basis of this ongoing safety monitoring.  See Section 11.7, Data Safety Monitoring for a 


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complete description of study safety monitoring for Grade 4 thrombocytopenia, and > Grade 2 
hemorrhage events, and possible changes in study conduct. 
8.6.5. 
Management of Anemia 
Subjects with a hemoglobin level < 6.5 g/dL must receive red cell transfusion(s) to maintain a 
level of ≥ 6.5 g/dL. Erythropoietin (EPO) use is discouraged, but is permitted at the 
Investigator’s discretion, although use is not permitted in lieu of transfusions for hemoglobin 
below 6.5 g/dL. 
8.6.6. 
Optional Dose Tapering Strategy 
In ongoing clinical studies with ruxolitinib, exacerbation of underlying cardiopulmonary disease 
and return of MF symptoms has been occasionally observed in subjects after drug 
discontinuation.  When a decision is made to permanently discontinue ruxolitinib therapy for 
reasons other than low platelet counts or ANC levels, tapering of ruxolitinib dosage may be 
considered, based on evaluation of the condition of the subject, current dose regimen and the 
clinical judgment of the investigator.  Doses of ruxolitinib may be very slowly lowered until the 
subject is completely off drug.  If medically indicated, doses of ruxolitinib may be temporarily 
restarted after they have been discontinued.  If considered to be medically necessary, the 
investigator may use any treatment to manage withdrawal from ruxolitinib including, but not 
limited to, the management of events which may be secondary to discontinuation, and 
interruption or reduction of dose administered of ruxolitinib.  Short-term courses of high-dose 
corticosteroids, equivalent to doses of > 10 mg/day of prednisolone have been used to moderate 
the withdrawal of ruxolitinib and may be considered as part of a tapering strategy.  
Corticosteroids may be started prior to, or concurrent with, ruxolitinib tapering in anticipation of 
the possibility of occurrence of withdrawal symptoms.  When a decision has been made to 
discontinue the subject with utilization of a tapering strategy, regardless of the use of 
concomitant medications, safety data will continue to be assessed in accordance with the 
protocol.  An end of study and subsequent follow-up visit must be scheduled.  
8.6.7. 
Procedures for Interruption of Study Medication 
In some circumstances, it may be necessary to temporarily interrupt treatment as a result of 
adverse experiences that may have an unclear relationship to study drug.  Except in cases of 
emergency, it is recommended that the Investigator consult with the Sponsor Medical Monitor 
(or other representative of the Sponsor) before temporarily interrupting therapy for reasons other 
than protocol mandated medication holds for platelet or ANC counts.  Additionally, the 
Investigator must notify the sponsor’s medical monitor and study project manager via email 
before restarting study drug that was temporarily discontinued for an adverse experience. 
8.6.8. 
Procedures for Permanent Discontinuation of Study Drug 
In the event that any subject discontinues the study drug and subsequently withdraws from the 
study prior to completion, regardless of reason, reasonable efforts should be made to have the 
subject return for an early termination visit and have the end-of-treatment procedures completed 
as described in Section 9.4. 


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The date the subject discontinued the study drug and the specific reason for discontinuation will 
be recorded in the eCRF.  This will include reasons such as discontinuation due to treatment 
failure or withdrawn due to adverse event.  This information will be used to summarize the 
reasons for study discontinuation and treatment failure. 
8.7. 
Withdrawal of Subjects from the Study 
8.7.1. 
Withdrawal Criteria 
Subjects may choose to withdraw from the study at any time without penalty of jeopardizing 
their health care or loss of benefits to which the subject is otherwise entitled.  Every reasonable 
effort should be made to determine the reason a subject withdraws prematurely, and this 
information should be recorded in the eCRF.   
A subject may be withdrawn from the study, if, in the investigator’s expert medical judgment, 
the subject is non-compliant with the study requirements.  Subjects may be withdrawn at the 
discretion of the Food and Drug Administration (FDA) or the investigator.   
Subjects must be discontinued from study drug and withdrawn from the study for the following 
reasons: 
• In the Investigator’s medical judgment, further participation would be injurious to the 
subject’s health or well-being 
• Positive urine pregnancy test, confirmed by positive serum pregnancy (serum human 
chorionic gonadotropin) test results 
• Consent is withdrawn 
• Termination of the study by the sponsor, local health authority, or IRB/IEC. 
• The subject requires splenic irradiation. 
• The subjects exhibits leukemic transformation (as evidenced by bone marrow blast 
counts of at least 20%, or peripheral blast counts of at least 20% lasting at least 
8 consecutive weeks). 
• The subject cannot maintain platelet counts of at least 25 x 109/L over a given 4 week 
interval at the lowest possible dose of 5 mg qd. 
• The subject experiences 3 or more Grade 2 hemorrhage events. Note withdrawal after 
a second Grade 2 hemorrhage event may occur following the sponsor and investigator 
review of pertinent data. 
• The subject experiences 2 hemorrhage events of ≥ Grade 2, at least one of which is 
Grade 3 or Grade 4, and believed to be from the same source or etiology.   
If a subject is withdrawn from the study:   
• The study monitor or sponsor must be notified.   
• The reason(s) for withdrawal must be documented in the subject’s medical record and 
eCRF.   
• The end-of-treatment/early termination visit should be performed. 


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• All subjects must be followed for safety until the time of the follow-up evaluation or 
until study drug related toxicities resolve, return to baseline or are deemed 
irreversible, whichever is longer.  
8.8. 
Concomitant Medications and Measures 
All concomitant medications and treatments must be recorded in the CRF.  Any prior medication 
received up to 30 days prior to the baseline visit will be recorded in the CRF.  Concomitant 
treatments that are required to manage a subject’s medical condition during the study will also be 
recorded in the CRF.   
8.9. 
Restricted and Prohibited Medications and Measures 
8.9.1. 
Restricted Medications and Measures 
The following medications have restrictions on use or doses that may be used during this study: 
• Aspirin in doses exceeding 81 mg per day is not permitted.  Low dose aspirin 
(81 mg/day or less) is permitted. Acetaminophen and non-steroidal anti-inflammatory 
agents (eg, ibuprofen, NSAIDs) may be used at over-the-counter doses.  Subjects 
receiving over-the-counter NSAIDs should not exceed the recommended dose and 
should be encouraged to use gastroprotective agents (antacids, H2 antagonists, or 
proton pump inhibitors).   
• Inducers of CYP3A4 (Appendix 8) may be used with caution, and investigators 
should seek other options if available. 
• Moderate CYP3A4 inhibitors (Appendix 8) may be used with caution.  Differences in 
individual sensitivity and variation in potency of inhibition of various CYP enzymes 
may result in the need for a reduced dose of ruxolitinib during a period of 
concomitant medication use.  If required for safety, the study drug dose may be 
reduced from bid to qd in these circumstances.  The sponsor’s medical monitor may 
be consulted for advice when using these agents. 
• Use of potent inhibitors of CYP3A4 (ketoconazole, clarithromycin, itraconazole, 
nefazodone or telithromycin, voriconazole or posaconazole, see Appendix 8) and use 
of fluconazole should be avoided, and if used, a 50% ruxolitinib dose reduction is 
recommended along with frequent platelet monitoring during the period of co-
administration.  Based on the low overall bioavailability of topical ketoconazole, 
there are no restrictions on topical ketoconazole in the study. 
• Hematopoietic growth factor receptor agonists (eg, erythropoietin) may be used at 
investigator’s discretion in certain circumstances as described in Section 8.6.5, 
Management of Anemia.   
• If concomitant administration of an anticoagulant/antiplatelet medication is indicated, 
caution and enhanced monitoring is required.  History of thrombocytopenia, and any 
concurrent ruxolitinib-related thrombocytopenia should be a factor in the choice of 
anticoagulant and dose.  Medications that interfere with coagulation or inhibit platelet 
function are listed in Appendix 9. 


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8.9.2. 
Prohibited Medications and Measures 
• Any prior or concomitant use of another JAK inhibitor. 
• Any investigational medication other than the study drugs.  Use of such medications 
within 14 days or 6 half-lives, whichever is longer, prior to the first dose of study 
drug and during the study through the follow-up visit is prohibited.   
• Systemic corticosteroid doses greater than the equivalent of 10 mg prednisolone per 
day are not permitted, unless use is part of a ruxolitinib dose tapering strategy (see 
Section 8.6.6 Optional Dose Tapering Strategy). 
• Romiplostim or eltrombopag are not permitted beginning with the baseline visit 
(Day -7) through the final dose of ruxolitinib.  
• St John’s Wort and rifampin are not permitted at any time during participation in the 
study. 
• Use of hydroxyurea, interferon, thalidomide, busulfan, lenalidomide, anagrelide, or 
any investigational medication used to treat MF is not permitted at any time 
beginning on Day -14 up until the time that ruxolitinib therapy is permanently 
discontinued.  Use of androgens to treat anemia is permitted. 
9. 
STUDY ASSESSMENTS 
All study assessments will be performed as shown in the Table of Assessments (Table 3) and 
Table of Laboratory Assessments (Table 4).  The order of assessments is suggested by the order 
of mention in the Table of Assessments.  For instructions on each assessment, please refer to 
Section 10.  


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Table 3: 
Table of Assessments 
Study Phase 
Screening & Baseline 
Core Treatment Phase 
Extended Treatment Phase 
End of Treatment & Follow-Up 
 
Screening 
Baseline 
Day 1 
Study Visits 
Weeks 4, 8, 
12, 16, 20 
Week 24 
Study Visits  
Weeks 36, 48, 60, 72, 
84, 96, 108, 120, 132, 
144 (q12 weeks) 
Week 156 
End of Treatment 
or Early 
Termination Visit 
(EOT) 
Follow-Up 
30-37 days after 
last dose of 
study drug 
Evaluation/window 
Day  
-28 to -8a 
Day  
-7 to -1 
Day 1 
± 5 days 
± 5 days 
± 5 days 
± 5 days 
± 5 days 
 
Assign Subject # 
X 
 
 
 
 
 
 
 
 
Informed consent / 
eligibility criteria 
X 
X 
 
 
 
 
 
 
 
Prior medical & medication 
history  
X 
X 
 
 
 
 
 
 
 
Concomitant medication 
review 
 
X 
X 
X 
X 
X 
X 
X 
X 
Transfusion history/status 
Xb 
Xb 
 
X 
X 
X 
X 
X 
 
Discontinue prior MF 
therapies 
Xc 
 
 
 
 
 
 
 
 
Screening Symptom Form 
X 
 
 
 
 
 
 
 
 
Record AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Comprehensive physical 
examination 
Xd 
X 
 
 
X 
X 
X 
X 
 
Targeted physical 
examinatione  
 
 
X 
X 
 
 
 
 
X 
Spleen palpation 
X 
X 
 
X 
X 
X 
X 
X 
 
Vital signs 
X 
X 
 
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
BM biopsy  
Xf 
Xf 
 
 
 
 
 
 
 
MRI of upper and lower 
abdomen and pelvis 
 
Xg, h 
 
 
X 
 
 
Xi 
 
Modified MFSAF v2.0 
(see Section 9.1.2)  
 
Diary is completed each evening from Day -7 to 
the Week 24 visit 
 
 
 
 
Dispense and/or bring 
MFSAF v2.0 diary to visit 
 
X 
X 
X 
X 
 
 
 
 
PGIC (see Appendix 5) 
 
 
 
X 
X 
X 
X 
X 
 
ECOG status 
X 
X 
 
X 
X 
X 
X 
X 
 
Dispense reminder cardk 
 
X 
X 
X 
X 
X 
 
 
 
Contact IVRS 
X 
 
X 
X 
X 
X 
X 
X 
 


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Table 3: 
Table of Assessments (Continued) 
Study Phase 
Screening & Baseline 
Core Treatment Phase 
Extended Treatment Phase 
End of Treatment & Follow-Up 
 
Screening 
Baseline 
Day 1 
Study Visits 
Weeks 4, 8, 
12, 16, 20 
Week 24 
Study Visits  
Weeks 36, 48, 60, 72, 
84, 96, 108, 120, 132, 
144 (q12 weeks) 
Week 156 
End of Treatment 
or Early 
Termination Visit 
(EOT) 
Follow-Up 
30-37 days after 
last dose of 
study drug 
Evaluation/window 
Day  
-28 to -8 
Day  
-7 to -1 
Day 1 
± 5 days 
± 5 days 
± 5 days 
± 5 days 
± 5 days 
 
Dispense study drug  
 
 
Xl 
Xm 
 
 
 
Drug accountability 
assessment 
 
 
 
X 
X 
X 
X 
X 
 
a If all screening activities cannot be completed in the screening phase because of an event unrelated to a laboratory finding, ECG finding, or medical history finding, including 
scheduling difficulties at the clinic site, the subject may retain the original subject number and complete the remaining screening activities as soon as possible, within a 
maximum of 42 days (6 weeks) from the original screening visit date. 
b Complete transfusion history should be recorded where possible, but must include at least the 12 weeks prior to screening. 
c Confirm that all drugs, used to treat the underlying MF disease are discontinued by Day -14, so that at least 1 week will have elapsed between the last dose of medication(s) used 
to treat MF and the baseline MRI (or CT scan in applicable subjects) and diary dispensing. 
d Height will be measured at the screening visit only. 
e The targeted physical examination should include the subject's weight. 
f A bone marrow biopsy is required at screening or baseline if a biopsy was not previously obtained within the prior 2 months or if all data from the samples are not available.   
g MRI of the upper and lower abdomen and pelvis will be performed, to assess spleen volumes.  CT scan may be performed if subject is not a candidate for MRI, or if MRI is not 
readily available.  The MRI (or CT scan in applicable subjects) should be performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site 
radiologist should send the scan to the central imaging laboratory that same day. 
h The first MRI may be delayed for up to 2 weeks because of scheduling or other issues at the clinic site, but must be completed within 56 days, maximum from the start of the 
original Screening Visit date, and this must occur prior to the subject receiving the first dose of study drug. 
i An MRI should be conducted at the end of treatment visit only if treatment was is discontinued prior to Week 24. 
 
 
k Reminder cards will be sent home with subjects to state upcoming visit scheduling, and to record the time subjects took their last dose of study drug prior to each visit. 
l On Day 1, the first dose of ruxolitinib will be administered to the subject in a fasted state at the site and the exact time of administration will be recorded on the eCRF. 
m Subject should be instructed NOT to take the morning dose of study drug on the day of the Week 4 study visit, as study drug will be administered to the subject in a fasted state 
at  the clinic. 


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Table 4: 
Table of Laboratory Assessments 
Study Phase  
Screening & Baseline 
Core Treatment Phase  
Extended 
Treatment 
Phase 
End of Treatment &  
Follow-Up 
 
Screening 
Baselinea 
Day 
1a 
Lab Only 
Visits 
Weeks 1,2, 
3,5,6,7,10, 
14, 18 
Week 
4a 
Week 
8 
Week 
12 
Weeks 
16 and 
20  
Week 
24a 
Lab 
Only 
Visitsb 
Study 
Visitsb 
End of 
Treatment or 
Early 
Termination 
Visit (EOT) 
Follow-Up 
30-37 days 
After Last 
Dose of 
Study Drug 
Evaluation/window 
Day  
-28 to -8 
Day  
-7 to -1 
Day 
1 
± 3 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 days 
± 5 days 
Serum Chemistry 
X 
Xc 
 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
Hematology 
X 
Xc 
 
Xd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panel 
X 
X 
 
 
 
 
X 
 
X 
 
X 
X 
 
Lipid Panel 
 
X 
 
 
X 
 
X 
 
X 
 
X 
X 
 
Serum Pregnancy Test 
(childbearing females 
only)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
Serology for HIV, 
HBV, HCV 
X 
 
 
 
 
 
 
 
 
 
 
 
 
a For blood samples drawn at baseline, Day 1, Week 4, and Week 24, subjects should arrive in a fasted state after an overnight fast of at least 8 hours or since midnight.  Lack of 
fasting will be noted on the eCRF page regarding blood sampling, but this will not constitute a protocol violation or deviation. 
b Extended treatment phase visits will occur at Weeks 36, 48, 60, 72, 84, 96, 108, 120, 132, 144 (eg, every 12 weeks).  Subjects will have laboratory-only visits to collect 
hematology samples 6 weeks after the Week 24 visit (eg, Week 30), then after each extended treatment phase visit (eg, Weeks 42, 54, 66, 78, 90, 102, 114, 126, 138, and 150).  
Additional hematology assessments will be required if the subject has a dose modification or as clinically indicated. 
c Blood samples for hematology and serum chemistry should be taken as close as possible to Day 1.  If, on the baseline assessment of serum chemistry and hematology 
parameters, an exclusionary value is observed, the test may be repeated once, no more than 3 days following the first observation. 
d The laboratory visits at Week 14 and Week 18 may be skipped for subjects who do not increase their dose at Week 12 or Week 16, and who have maintained platelet counts > 75 
x 109/L since the last hematology assessment.  Additional, twice-weekly laboratory-only visits to collect hematology lab samples will be required if platelet count falls below 35 
x 109/L. 
 
 
 


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9.1. 
Screening + Baseline Phase 
The screening + baseline phase may not exceed 28 days (4 weeks), with the exception of delays 
caused by scheduling issues, see Section 6.4).  The length of the screening visit for a given 
individual subject will be determined by the requirement to discontinue all drugs used to treat 
MF at least 7 days prior to the first baseline evaluation (ie, must discontinue prior MF therapy by 
Day -14).  Subjects who are not currently taking any drugs to treat their MF may complete all 
screening activities in a few days, and proceed to the baseline phase. 
9.1.1. 
Screening Assessments  
Prospective participants will be scheduled for a screening visit by site staff.  A subject number 
will be assigned by an Interactive Voice Response System (IVRS).  All procedures for screening 
and baseline must be completed within the 21-day screening + 7-day baseline phase, except as 
noted in Section 6.4.  The following procedures will be performed: 
Obtain informed consent before any study specific procedures are conducted. 
• A subject number will be assigned by IVRS. 
• Review of eligibility criteria including discussion of methods known to be at least 
99% effective in preventing pregnancy (Appendix 3). 
• Review of medical history, prior medication history and prior history of medications 
used to treat MF (see Section 8.8, Prior and Concomitant Medications).  Record 
medication histories on the eCRF. 
• Review of transfusion history.  Complete transfusion history should be recorded 
where possible, but must include at least the 12 weeks prior to Screening.  The history 
should be recorded on the eCRF. 
• Confirm that all drugs, used to treat underlying MF disease will be discontinued by 
Day -14, so that at least 1 week will have elapsed between the last dose of 
medication(s) used to treat MF and the baseline MRI (or CT scan in applicable 
subjects) and diary dispensing.  Prior MF medication(s) may be discontinued in one 
of the 3 following ways: 
1. Prior to and independent of considering enrollment in this study (prior to signing 
the ICF).  These subjects can proceed to the baseline visit as soon as screening 
activities are completed, 7 days have elapsed since the prior MF medications were 
discontinued and eligibility is verified. 
2. At the time of signing the ICF.  These subjects can proceed to the baseline visit 
7 days after signing the ICF, if screening activities are completed and eligibility is 
verified. 
3. After confirming eligibility via the screening symptom form, laboratory 
assessments, and medical history.  These subjects must obtain necessary screening 
visit results within the first 14 days in order to have 7 days for drug 
discontinuation prior to baseline (total screening time elapsed = 21 days). 


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• NOTE:  The timing for the screening hematology blood samples should take 
the possible discontinuation of a prior MF therapy into account, in order to 
allow time for possible recovery of low platelet count values caused by the 
prior MF regimen.  It is suggested that the hematology blood sample be taken 
around Day -8, eg, at the end of the possible wash-out period for prior 
therapy. 
• Complete Screening Symptom Form. 
• Record adverse events. 
• Comprehensive physical examination including body weight and height. 
• Measurement of spleen length below the costal margin by palpation.  
• Vital signs  
• ECOG status assessment. 
• 12-lead electrocardiogram (ECG).  
• Bone marrow biopsy for confirmation of MF diagnosis.  NOTE:  a bone marrow 
biopsy at screening or baseline is required if a biopsy was not previously obtained 
within the prior 2 months or if all data from the samples are not available for review 
by the Study Investigator of Study INCB 18424-258.  The prior data will need to be 
entered into the eCRF for this study, with explanation as to the origin of the data (date 
of biopsy).   
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests  
− Hematology  
− Coagulation tests  
− Serum pregnancy test (females of childbearing potential only)  
− Serology tests for HIV and hepatitis  
9.1.2. 
Baseline Assessments 
The results from the screening visit evaluations will be reviewed to determine if the subject 
continues to meet the eligibility requirements as specified in the protocol.  Subjects who have 
signed the ICF and meet all the entry criteria (see Section 6) may be enrolled in the study, and 
will be contacted by clinical site staff to schedule the baseline visit. Subjects will be reminded by 
site staff that they must arrive for the baseline visit where blood draws for lipid profile will be 
taken after an overnight fast of at least 8 hours or since midnight.  
Subjects will begin completing the evening diary the evening of the first baseline assessment 
(Day -7).  The MRI (or CT scan in applicable subjects) should be conducted on the first or 
second day to allow ample time for the central imaging laboratory to verify scan quality.  Blood 
samples for hematology and serum chemistry should be taken as close as possible to Day 1, but 
in ample time for the results to be returned from the central laboratory (or in the case of 


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hematology and coagulation labs, the local laboratory).  If, on the baseline assessment of serum 
chemistry and hematology parameters, an exclusionary value is observed, the test may be 
repeated once, no more than 3 days following the first observation.   
The following procedures will be performed during the 7-day baseline period and prior to 
enrollment for all subjects:  
• Confirm that the subject continues to meet all eligibility criteria. 
• Update medication history and concurrent medications; confirm that all drugs used to 
treat underlying MF disease have been discontinued for at least 7 days.   
• Update transfusion history status. 
• Record adverse events. 
• Conduct a comprehensive physical examination. 
• Measurement of spleen length below the costal margin by palpation.  
• Vital signs.  
• ECOG status assessment. 
 
 
• Bone marrow biopsy (only if not performed at screening and no prior biopsy data are 
available to the Investigator for review). 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests  
− Hematology  
− Coagulation tests  
− Lipid panel 
 
 
 
 
 
 
• MRI of the upper and lower abdomen and pelvis will be performed, to assess spleen 
volumes.  CT scan may be performed if subject is not a candidate for MRI, or if MRI is 
not readily available.  The MRI (or CT scan in applicable subjects) should be performed 
on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site 
radiologist should send the scan to the central imaging laboratory that same day.  Scans 
can be sent by file transfer protocol (ftp) or by mailing it on a CD-ROM by pre-paid 
mailer provided for the study.  The MRI central reader will assess the quality of the scan 
and will send a notice of acceptance via FAX and/or email to the site within 48 hours of 
receipt of the scan at their offices.  A notice of acceptance MUST be received by the site 
before the subject can begin dosing.  If a notice of “non-acceptance” is received by the 
investigator, the subject must have a repeat MRI (or CT in applicable subjects) prior to 


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receiving the first dose of study drug.  This MRI should be performed within 2 weeks of 
the first MRI.  In rare cases, the central imaging laboratory may suggest that CT scan be 
performed instead of MRI because of subject’s abdominal anatomy.   
− NOTE: the first MRI may be delayed for up to 2 weeks because of scheduling or 
other issues at the clinic site, but must be completed within 56 days, maximum 
from the start of the original screening visit date, and this must occur prior to the 
subject receiving the first dose of study drug.  
− In the case where the MRI is delayed for scheduling or other issues, or a repeat 
MRI is required because of scan quality issues, a repeat hematology assessment 
should be completed 2 to 7 days prior to the planned Day 1. 
• Distribution of modified MFSAF v2.0 diary.  Subjects will be issued a hand-held device, 
and will complete the diary questions each night beginning on Day -7 up to the Week 24 
Visit.  Subjects will be instructed to place the device on the docking station (also 
provided), for automatic data transmittal each night after completing the questions.  
Subjects will be instructed to leave the device in the docking station when not answering 
the questions so that the unit remains fully charged.  Subjects will receive training on the 
device by study site staff prior to leaving the site.  Subjects will bring the device with 
them to Study Visits on Day 1, Week 4, Week 8, Week 12, Week 16 and Week 20 so that 
the device charging can be verified, and to download accumulated data.  The device will 
then be returned to the subject at these same visits for continued use each night.  Subjects 
will return the device and the docking station for the final time at the Week 24 Visit, so 
that all data can be archived.  All subjects will complete the diary through Week 24. 
• Subjects will be given a reminder card with the date and time of the Day 1 visit.  Subjects 
will be reminded to arrive for the study visit after an overnight fast of at least 8 hours or 
since midnight. 
9.2. 
Core Treatment Phase 
Refer to Table 3, Study Visit Assessments and Table 4, Scheduled Laboratory Assessments for 
procedures to be performed at on-study visits and laboratory-only visits.  Subjects do not need to 
come in for study visits in the fasted state except for baseline, Day 1, Week 4, and Week 24, 
when they should arrive for the visit after an overnight fast of at least 8 hours or since midnight. 
The site must ensure that the subject is instructed NOT to take the dose of study drug on the day 
of the Week 4 study visit, as study drug will be administered in the clinic at that visit 
 
  Reminder cards will be used to send home with subjects to state 
upcoming visit scheduling, and to record the time subjects took their last dose prior to each visit.  
Use of the reminder cards by site staff is mandatory, and they will be retained in the subject’s 
records.  
The procedures are summarized as follows: 
Day 1 
• Record adverse events 
• Update concomitant medications 


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• Complete a targeted physical examination 
• Administration of first dose of ruxolitinib, exact time recorded on eCRF.   
 
  
 
 
 
 
 
 
 
 
• Study drug will be dispensed via IVRS. 
• MFSAF v2.0 diary collection, data downloading and return to subject. 
• Dispense reminder card to record time of dose on the day prior to Week 4 visit, and to 
remind subject NOT to take their morning dose the day of the Week 4 visit, to arrive 
for the visit after an overnight fast of at least 8 hours or since midnight, and to 
provide visit scheduling details.   
Weeks 1, 2, 3, 5, 6, 7, 10, 14, and 18 (± 3 days) 
• Subjects will go to the study site laboratory, or a local laboratory for blood draws for 
hematology assessments. 
• The laboratory visits at Week 14 and Week 18 may be skipped for subjects who do 
not increase their dose at Week 12 or Week 16, and who have  maintained platelet 
counts > 75 x 109/L since the last hematology assessment.  Additional, twice-weekly 
laboratory-only visits to collect hematology lab samples will be required if platelet 
count falls below 35 x 109/L. 
Week 4 (± 5 days) 
• Review concomitant medications. 
• Review transfusion status. 
• Record adverse events. 
• Complete a targeted physical examination. 
• Measurement of spleen length below the costal margin by palpation.  
• Vital signs. 
• Complete PGIC question (Appendix 5). 
• ECOG status assessment. 
 
. 
• Reminder card will be distributed to record the time of the dose taken the day of the 
Week 8 visit, to record the time of the meal prior to the visit, and to provide visit 
scheduling details. 


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• Dispense study drug via IVRS. 
• Perform study drug accountability assessment. 
• MFSAF v2.0 diary collection, data downloading and return to subject. 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests 
− Hematology  
− Lipid panel 
 
 
 
 
 
 
• Administration of ruxolitinib, exact time recorded on eCRF.   
 
 
 
 
 
 
 
 
Week 8 (± 5 days) 
• Review concomitant medications. 
• Review transfusion status. 
• Record adverse events. 
• Complete a targeted physical examination 
• Measurement of spleen length below the costal margin by palpation.  
• Vital signs. 
• Complete PGIC question (Appendix 5). 
• ECOG status assessment. 
• Dispense reminder card with Week 12 visit scheduling details. 
• Dispense study drug via IVRS. 
• Perform study drug accountability assessment. 
• MFSAF v2.0 diary collection, data downloading and return to subject. 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests 
− Hematology  
− Sample for plasma level of ruxolitinib (prior meal/dose times will be recorded) 


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Week 12 (± 5 days)  
• Review concomitant medications. 
• Review transfusion status. 
• Record adverse events. 
• Complete a targeted physical examination. 
• Measurement of spleen length below the costal margin by palpation.  
• Vital signs. 
• Complete PGIC question (Appendix 5). 
• ECOG status assessment. 
 
. 
• Reminder card will be distributed with Week 16 visit scheduling details. 
• MFSAF v2.0 diary collection, data downloading and return to subject. 
• Dispense study drug via IVRS. 
• Perform study drug accountability assessment. 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests 
− Hematology 
− Lipid panel 
 
 
− Coagulation panel  
Week 16 (± 5 days) 
• Review concomitant medications. 
• Review transfusion status. 
• Record adverse events. 
• Complete targeted physical examination. 
• Measurement of spleen length below the costal margin by palpation.  
• Vital signs. 
• Complete PGIC question (Appendix 5). 
• ECOG status assessment. 
• Reminder card will be distributed with Week 20 visit scheduling details. 
• MFSAF v2.0 diary collection, data downloading and return to subject. 


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• Dispense study drug via IVRS. 
• Perform study drug accountability assessment. 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests 
− Hematology  
Week 20 (± 5 days) 
• Review concomitant medications. 
• Review transfusion status. 
• Record adverse events. 
• Complete targeted physical examination. 
• Measurement of spleen length below the costal margin by palpation.  
• Vital signs. 
• Complete PGIC question (Appendix 5). 
• ECOG status assessment. 
• Reminder card will be distributed to remind subjects to arrive for the Week 24 visit 
after an overnight fast of at least 8 hours or since midnight, and with Week 24 visit 
scheduling details.   
• MFSAF v2.0 diary collection, data downloading and return to subject. 
• Dispense study drug via IVRS. 
• Perform study drug accountability assessment. 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests 
− Hematology  
Week 24 (± 5 days)  
• Review concomitant medications. 
• Review transfusion status. 
• Record adverse events. 
• Perform comprehensive physical examination. 
• Measurement of spleen length below the costal margin by palpation.  
• Vital signs. 
• MRI (or CT scan in applicable subjects). 
• Complete PGIC question (Appendix 5). 


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• ECOG status assessment. 
 
. 
• Collect MFSAF v2.0 diary and all cords and charging stations. 
• Dispense reminder card for subsequent visit scheduling, if subject will continue to 
receive study drug. 
• Dispense study drug via IVRS if subject will continue to receive study drug. 
• Perform study drug accountability assessment. 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests 
− Hematology  
− Coagulation tests 
− Lipid panel 
 
 
 
 
 
 
9.3. 
Extended Treatment Phase 
Visits will occur every 12 weeks (eg, Weeks 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156) 
beginning with Week 36 (± 5 days).  Subjects will have laboratory-only visits to collect 
hematology samples 6 weeks after the Week 24 visit (eg, Week 30), then after each extended 
treatment phase visit (eg, Weeks 42, 54, 66, 78, 90, 102, 114, 126, 138, and 150).  Additional 
hematology assessments will be required if the subject has a dose modification or as clinically 
indicated.   
The following procedures will be performed every 12 weeks: 
• Review concomitant medications. 
• Review transfusion status. 
• Record adverse events. 
• Measurement of spleen length below the costal margin by palpation.  
• Perform comprehensive physical examination. 
• Vital signs. 
• Complete PGIC question (Appendix 5). 
• ECOG status assessment. 
 
. 
• Reminder card will be distributed with subsequent visit scheduling details. 


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• Dispense study drug via IVRS. 
• Perform study drug accountability assessment. 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests 
− Hematology 
− Lipid panel 
 
 
− Coagulation panel  
Week 156 (± 5 days) 
• Review concomitant medications. 
• Review transfusion status. 
• Record adverse events. 
• Perform comprehensive physical examination. 
• Measurement of spleen length below the costal margin by palpation.  
• Vital signs. 
• Complete PGIC question (Appendix 5). 
• ECOG status assessment. 
 
. 
• Update subject status in IVRS. 
• Perform study drug accountability assessment. 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests 
− Hematology  
− Coagulation tests 
− Lipid panel 
 
 


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9.4. 
End of Treatment (± 5 days) 
If a decision is made that the subject will withdraw from study participation, the end-of-
treatment visit (EOT) should be conducted.  If the EOT Visit coincides with a regular study visit, 
the end-of-treatment evaluations will supersede those of that scheduled visit, the data should be 
entered in the end of treatment visit in the CRF.  The subject should be encouraged to return for 
the follow-up visit.  The following will be performed: 
• Review concomitant medications. 
• Review transfusion status. 
• Record adverse events. 
• Perform complete physical examination. 
• Measurement of spleen length below the costal margin by palpation.  
• Vital signs. 
• MRI (or CT scan in applicable subjects) should only be performed at the EOT visit if 
the subject discontinues treatment prior to Week 24. 
• Complete PGIC question (Appendix 5). 
• ECOG status assessment. 
• Perform study drug accountability assessment. 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests 
− Hematology  
− Coagulation tests 
− Lipid panel 
 
 
• Contact IVRS to register subject discontinuation. 
9.5. 
Follow-Up Phase 
The follow-up phase is the interval between the EOT visit and the scheduled follow-up visit, 
which should occur 30 to 37 days following the EOT visit (or following the last dose of study 
drug if the EOT visit was not performed).  If no follow-up visit is performed the follow-up phase 
is considered to be 30 days past the last dose of study drug.  Reasonable efforts should be made 
to have the subject return for the follow-up visit, and report any AEs that may occur during this 
phase.  The following procedures will be performed: 
• Review concomitant medications. 
• Record adverse events. 
• Perform a targeted physical examination. 


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• Vital signs. 
• Blood sampling for the following laboratory tests (see Appendix 4): 
− Serum chemistry tests 
− Hematology  
9.6. 
Unscheduled Visits 
Unscheduled visits for laboratory assessments may be conducted anytime at the Investigator’s 
discretion.  
 
 
10. 
STUDY ASSESSMENT PROCEDURES 
10.1. 
Demographics and Medical History 
Demographic data and a complete medical and medication history will be collected at screening, 
after informed consent has been signed.  Height and body weight measurements will be 
performed; body mass index will be calculated automatically in the eCRF.  Complete transfusion 
history should be collected at the screening visit where possible, but must include at least 
12 weeks prior to screening.  All medical, medication and transfusion history will be recorded in 
the eCRF.   
10.2. 
Order of Assessments 
Multiple assessments are scheduled during the study visits.  In order to standardize the visits, a 
suggested order of assessments is implied by the ordering of events in the description of study 
visits.  Where feasible, vital signs and ECG measurements should be collected prior to blood 
draws. 
 
 
  Site staff should discuss the importance of 
the Subject Reminder Cards with the subject at the Day 1 visit so that the subject will be 
compliant with its return each visit.  If the subject does not bring the reminder card, or it is blank, 
the site staff will discuss the prior dose timing with the subject, and will record the information 
in the subjects chart (site may use a blank reminder card for the specified visit). 
10.3. 
Safety Assessments 
10.3.1. 
Adverse Events 
Adverse events will be monitored from the time the subject signs informed consent.  Subjects 
will be instructed to report all AEs during the study and subjects will be assessed for the 
occurrence of AEs throughout the study.  In order to avoid bias in eliciting AEs, subjects will be 
asked general, nonleading questions such as "How are you feeling?"  All AEs (serious and 
nonserious) must be recorded on the source documents and case report forms regardless of the 


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assumption of a causal relationship with the study drug.  The definition, reporting, and recording 
requirements for AEs are described in Section 11. 
10.3.2. 
Physical Examination 
A comprehensive physical examination will be performed at the times indicated on the Table of 
Assessments (Section 9).  The comprehensive physical examination will include the following 
organ or body system assessments: skin; head, eyes, ears, nose, and throat; thyroid; lungs; 
cardiovascular; abdomen (liver, spleen); extremities, lymph nodes, assessment for edema and/or 
ascites, measurement of weight and a brief neurological exam.  Height will be measured at the 
Screening visit only.  Physical exams must be performed by a medically qualified individual 
such as a licensed physician, Physician’s Assistant or advanced Registered Nurse Practitioners as 
local law permits.  Clinically significant findings will be recorded in the eCRF.   
10.3.2.1. Targeted Physical 
A targeted physical examination will be a symptom-directed evaluation.  The targeted physical 
examination will include assessment(s) of the body systems or organs, as indicated by subject 
symptoms, AE, or other findings as determined by the Investigator or designee.  The targeted 
physical examination should also include an assessment of the subject’s weight.  
10.3.3. 
Vital Signs 
Vital sign measurements (blood pressure, heart rate, body temperature) will be collected on the 
days and times noted in the Table of Assessments (Section 9).  Vital signs will be taken with the 
subject in the sitting position after 5 minutes of rest.  Vital signs will be recorded in the eCRF. 
10.3.4. 
Concomitant Medications 
Concomitant medications will be collected on the days and times noted in the Table of 
Assessments (Section 9) and recorded in the eCRF. 
10.3.5. 
Twelve-Lead Electrocardiograms 
All 12-lead ECGs will be performed with the subject in a recumbent position after 5 minutes of 
rest. 
The screening ECG will be interpreted by the Investigator or another appropriately trained 
individual at the site.  If ECG abnormalities that are clinically meaningful are present, they will 
be recorded on the eCRF.  Normal ECG findings or non-clinically meaningful abnormal ECG 
findings will not be recorded on the eCRF, other than data indicating the ECG was performed.  
Twelve-lead ECGs may be conducted during the study at the Investigator’s discretion.  ECGs 
that are identified as abnormal and clinically meaningful compared to the Screening assessment 
should be reported as AEs.  For such AEs, the findings of the abnormal ECGs and the 
corresponding baseline ECG findings must be reported in the eCRF, and copies of the abnormal 
tracings and corresponding baseline tracings will also be sent to the Sponsor and CRO for their 
records.  For Sponsor: 
 MD 
 (FAX) 


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10.3.6. 
Laboratory Assessments 
A central laboratory or as instructed in the lab manual will perform the clinical laboratory tests 
except for hematology and coagulation panel which will be performed by the local laboratory.  
Samples for serum chemistry, lipid panel, serology, 
 and serum pregnancy test 
will be prepared using standard procedures.  All subjects will have samples of blood collected on 
the days and times noted in the Table of Laboratory Assessments (Table 4) for analysis of serum 
chemistry and hematology.  Appendix 4 provides a complete list of laboratory tests that will be 
performed.  Please refer to the laboratory manual for further details and specifications for sample 
handling, processing and shipping. 
10.3.6.1. Hematology 
Hematology assessments, including complete blood count (CBC) with manual differential will 
be performed by the local laboratory during study visits, and may be performed at this same 
laboratory, or at a local laboratory identified by the subject and investigator for laboratory-only 
visits as outlined in Table 4, and any other time additional hematology monitoring is deemed 
necessary.  The investigator is responsible for obtaining the data from such local laboratories, as 
well as the normal lab ranges used by that laboratory.  A standardized local laboratory range will 
be used in analysis of hematology lab data. 
10.3.6.2. Chemistry 
Chemistry labs will be analyzed by a central laboratory. 
10.3.6.3. Pregnancy and Fertility Testing 
Blood will be collected during screening for females of childbearing potential to conduct a 
pregnancy test.  Females of non-childbearing potential are defined as women who are: 
• At least 55 years of age with history of amenorrhea for 1 year   OR 
• Are surgically sterile for at least 3 months 
Subsequently, pregnancy tests will be conducted only as medically indicated.  A positive urine 
pregnancy test will be confirmed by a serum pregnancy test.  Pregnancy status will be 
documented at each visit on the eCRF. 
10.3.6.4. Serology 
Serology labs will be analyzed by a central laboratory. 
10.4. 
Efficacy Assessments 
• Imaging.  The primary measure of spleen size will be by MRI (or CT scan in 
applicable subjects).  MRI of the upper and lower abdomen and pelvis will be 
performed at baseline and Week 24.  MRI will be performed with a body coil because 
the objective is to measure organ volume, not to find very small lesions.  MRIs will 
be read initially by local radiologists who will assess the scan for quality, and send all 
scans (MRI or CT) to the central imaging laboratory the same day, if at all possible.  
The scans from an individual subject will be read by a central reader.  Spleen and 
liver volume will be obtained by outlining the circumference of the organ and 


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determining the volume using the validated technique of least squares.  The MRI will 
not determine spleen length below the costal margin, as there are no validated 
approaches for determining this measurement.  Procedure specific training for 
scanning and image capture will be provided by the Vendor.   
MRI is the preferred method for obtaining spleen volume data.  However, CT scans 
may be performed at the visits where MRI is designated if the subject is not a 
candidate for MRI (because of the presence of metal clips in the body, or because of 
claustrophobia, for example), or if MRI is not readily available.  CT scans will be 
similarly processed by the same central laboratory as used for MRIs.  Procedure 
specific training for scanning and image capture will be provided by the Vendor. 
NOTE:  The same method (MRI versus CT) must be used for both visits for a given 
subject unless a new contraindication to the use of MRI (eg, pacemaker insertion) 
occurs.   
• Spleen length.  Spleen length will be assessed by manual palpation as outlined in 
Table 3.  Investigators will be provided with a soft centimeter ruler so that palpable 
spleen length is measured in centimeters and not in finger breadths.  The edge of the 
spleen shall be determined by palpation, and measured in centimeters, using a soft 
ruler, from the costal margin to the point of greatest splenic protrusion.  Spleen length 
must be recorded on the eCRF. 
10.5. 
Symptom and Quality of Life Assessments 
• Symptom Diary.  Symptoms of MF will be assessed using a symptom diary 
(modified MFSAF v2.0 diary).  Subjects will be issued a hand-held device on which 
to record answers to queries regarding MF symptoms.  Symptoms assessed will 
include filling up quickly/early satiety, abdominal discomfort, abdominal pain, 
inactivity, night sweats, itching, and bone/muscle pain.  The modified MFSAF v2.0 
diary will be completed by subjects each night beginning at Day -7 (first day of 
Baseline), and continuing to the Week 24 visit (25 weeks total).  Subjects will bring 
the device to the study site at Study visits on Day 1, Week 4, Week 8, Week 12 and 
Week 16, so that the device charging can be verified, and to download accumulated 
data.  NOTE:  subjects who will have overnight stays associated with their Study 
Visit must also bring their docking station so that their device can be fully charged at 
all times, and so they can complete the evening diary entries.  The device will then be 
returned to the subject at these same visits for continued use each night.  The subject 
will return the device and the docking station for the final time at the Week 24 visit so 
that the data can be archived.  Detailed directions for the administration of the 
modified MFSAF v2.0 diary will be provided in a Reference Manual.  Spanish 
translations of the modified MFSAF v2.0 diary will be available.   
• Patient Global Impression of Change will be administered at each visit beginning 
with Week 4, and consists of a single question to which the subject responds with 
answer on a scale of 1 to 7.  See Appendix 5. 
 
 
 


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10.9. 
Other Study Procedures 
10.9.1. 
Administration of Informed Consent Form 
Valid informed consent must be obtained from the study subject prior to conducting any study-
specific procedures.  The granting of informed consent for participation in the study must be 
documented in writing, using an ICF that contains all the elements required by ICH E6 and 
describes the nature, scope, and possible consequences of the study in a form understandable to 
the study subject.  Local and institutional guidelines for ICF content and administration must be 
followed, and a copy of the signed ICF must be provided to the study subject.   
Subjects of childbearing potential must agree to take appropriate measures to avoid pregnancy or 
fathering a child in order to participate in the study (Appendix 3). 
10.9.2. 
IVRS/IWRS Procedures 
An IVRS system will be used to assign subject numbers and to dispense study drug.  Procedures 
to be followed will be provided in an IVRS manual. 
10.9.3. 
Study Drug Administration 
Subjects will take their dose of ruxolitinib morning and evening, approximately 12 hours apart, 
and without regards to food. 
10.9.4. 
Study Drug Dispensation 
Site staff will contact an IVRS to obtain the subject study drug assignment.  The investigator or 
designee will select the assigned bottles from their stock that correspond to the number provided 
by IVRS and dispense the medication.  The investigator will enter the bottle numbers in the 
eCRF.  At subsequent medication dispensing visits, the investigator or designee will follow the 
same procedures as described above.  Full details will be provided in the IVRS manual. 
10.9.5. 
Assessment of Study Drug Compliance  
Compliance will be calculated by the Sponsor based on the drug accountability documented by 
the site staff and monitored by the Sponsor/designee (tablet counts).  The objective is 100% 
compliance and investigators and their staff should evaluate compliance at each visit, and take 
appropriate steps to optimize compliance.  For the purpose of subgroup analyses, subjects with at 
least 80% compliance over the total duration of dosing from the first day of dosing to the 
analysis of the study will be considered to be compliant. 
10.9.6. 
Distribution of Subject Reminder Cards and Diaries 
Subjects will be provided with subject reminder cards at each visit.  The subject reminder cards 
will indicate the date/time of the next visit, and will also remind the subject when they should not 
take their morning dose of study drug, and when they should arrive for the visit after an 
overnight fast of at least 8 hours or since midnight.  The reminder cards will have an area on 
which the date and time of the last dose taken prior to each study visit will be recorded by the 
subject, and to record time of last meal (certain visits only). 


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11. 
SAFETY MONITORING AND REPORTING 
11.1. 
Adverse Events 
11.1.1. 
Definitions and Reporting 
An Adverse Event (AE) for the purposes of this protocol is defined as the appearance of (or 
worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that 
occur after a subject’s signed informed consent has been obtained.  Abnormal laboratory values 
or test results occurring after informed consent constitute AEs only if they induce clinical signs 
or symptoms, are considered clinically meaningful, require therapy (eg, hematologic abnormality 
that requires transfusion), or require changes in study drug(s). 
Adverse Events that begin or worsen after informed consent should be recorded in the Adverse 
Events section of the CRF. Conditions that were already present at the time of informed consent 
should be recorded in the medical history section of the CRF.  Adverse Event monitoring should 
be continued through the follow-up visit or for at least 30 days following the last dose of study 
treatment, whichever comes later.  Adverse Events (including lab abnormalities that constitute 
AEs) should be described using a diagnosis whenever possible, rather than individual underlying 
signs and symptoms.  When a clear diagnosis cannot be identified, each sign or symptom should 
be reported as a separate AE. 
Adverse Events will be assessed according to the Common Terminology Criteria for Adverse 
Events (CTCAE) v4.03.  If CTCAE grading is not used for a study, the severity of mild, 
moderate, severe, and life-threatening, or Grades 1 - 4, will be used. CTCAE Grade 5 (death) 
will not be used in this study; rather, information about deaths will be collected as an outcome of 
the event.  The occurrence of AEs should be sought by non-directive questioning of the subject 
during the screening process after signing informed consent and at each visit during the study.  
Adverse Events may also be detected when they are volunteered by the subject during the 
screening process or between visits, or through physical examination, laboratory test, or other 
assessments.  As far as possible, each AE should be evaluated to determine:  
• The severity grade (CTCAE Grade 1-4) 
• Reasonable possibility that AE is related to the study treatment: (no, yes) 
• Reasonable possibility that AE is related to a study procedure: (no, yes) 
• Start and end dates, unless unresolved at final exam 
• Action taken with respect to study medication (none, dose adjusted, temporarily 
interrupted, permanently discontinued, unknown, not applicable) 
• Outcome (not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown) 
• Whether it is serious, as per Serious Adverse Event (SAE) definition provided in 
Section 11.3.1. 
Unlike routine safety assessments, SAEs are monitored continuously and have special reporting 
requirements, see Section 11.3.2. 


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All AEs should be treated appropriately.  If a concomitant medication or non-drug therapy is 
given, this action should be recorded on the AE CRF as well as the Prior/Concomitant 
medications CRF. 
Once an AE is detected, it should be followed until its resolution or until it is judged to be 
permanent; assessment should be made at each visit (or more frequently if necessary) of any 
changes in severity, the suspected relationship to the study medication, the interventions required 
to treat it, and the outcome. 
Disease progression should not be regarded or reported as an AE itself, unless it is associated 
with a separate AE. 
11.2. 
Laboratory Test Abnormalities 
11.2.1. 
Definitions and Reporting 
Laboratory abnormalities that constitute an AE in their own right (are considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy or require changes 
in study treatment), should be recorded on the AE CRF.  Whenever possible, a diagnosis, rather 
than a symptom should be provided (eg, anemia instead of low hemoglobin).  Laboratory 
abnormalities that meet the criteria for AEs should be followed until they have returned to 
normal or an adequate explanation of the abnormality is found.  When an abnormal laboratory or 
test result corresponds to a sign or symptom of a previously reported AE, it is not necessary to 
separately record the lab/test result as an additional event. 
Laboratory abnormalities that do not meet the definition of an AE should not be reported as AEs.  
A Grade 3 or 4 (severe) event, as per CTCAE, does not automatically indicate a SAE unless it 
meets the definition of serious, as defined below, and/or as per investigator’s discretion.  A dose 
hold or medication for the lab abnormality may be required by the protocol in Section 8.6 and 
should not contribute to the designation of a laboratory test abnormality as a SAE. 
11.3. 
Serious Adverse Events 
11.3.1. 
Definitions 
Serious Adverse Event (SAE) is defined as one of the following:  
• Is fatal or life-threatening (ie, immediate risk of dying) 
• Results in persistent or significant disability/incapacity 
• Constitutes a congenital anomaly or birth defect 
• Is clinically meaningful, (ie, defined as an event that jeopardizes the subject or 
requires potential medical or surgical intervention to prevent 1 of the outcomes listed 
above).  Considered meaningful by the Investigator as an important medical event 
that may not result in death, be life-threatening, or require hospitalization, but may be 
considered a SAE when, based upon appropriate medical judgment, it may jeopardize 
the subject or may require medical or surgical intervention to prevent 1 of the 
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• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is due to:  
− Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition.  
− Elective or pre-planned treatment for a pre-existing condition that is unrelated to 
the indication under study and has not worsened since signing the informed 
consent. 
− Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission. 
− Social reasons and respite care, in the absence of any deterioration in the subject’s 
general condition. 
− Any SAEs that are expected due to the condition being treated, including if the 
SAE is a primary outcome measure, and whether there has been a clear agreement 
with regulators not to consider these as SAEs, provided the information is 
collected elsewhere. 
11.3.2. 
Reporting 
To ensure subject safety, every SAE, regardless of suspected causality, occurring after the 
subject has signed the informed consent form (ICF) and until (at least) the Follow-up Visit or 
30 days after the subject has stopped study treatment (whichever comes later) must be reported 
to the Sponsor or designee within 24 hours of learning of its occurrence.  Any SAEs experienced 
after this period of at least 30 days should only be reported to the Sponsor, or designee, if the 
Investigator suspects a causal relationship to the study mediation.  Recurrent episodes, 
complications, or progression of the initial SAE must be reported as the follow-up to the original 
episode within 24 hours of the Investigator receiving the follow-up information.  An SAE 
occurring at a different time interval or otherwise considered completely unrelated to a 
previously reported one should be reported separately as a new event.  Serious AE collection 
begins after the subject has signed the ICF.  If a subject experiences an SAE after signing the 
ICF, but prior to receiving study medication, the event will not be collected unless the 
Investigator feels the event may have been caused by a protocol procedure.  Previously planned 
(prior to signing the ICF) surgeries should not be reported as SAEs unless the underlying 
medical condition worsens over the course of the study. 
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form.  The Investigator must assess and record the relationship of each SAE to each specific 
study medication (if there is more than 1), complete the SAE Report Form in English, and send 
the completed, signed form by fax within 24 hours to the Sponsor (or designee).  The 
investigator must assess if there is a Reasonable possibility that the SAE is related to the study 
treatment: no (unrelated), yes (related). 
SAEs related to unblinded comparator drugs or concomitant medications/drug delivery systems 
are reported directly to the manufacturers of those drugs/devices in accordance with the package 
insert. 


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The telephone and facsimile number of the Sponsor’s contact persons, specific to the study, are 
listed in the investigator folder provided to each site.  The original copy of the SAE Report Form 
and the fax confirmation sheet must be kept with the case report form documentation at the study 
site. 
Follow-up information is sent to the same person to whom the original SAE Report Form was 
sent, using a new SAE Report Form stating that this is a follow-up to the previously reported 
SAE and giving the date of the original report.  Each re-occurrence, complication, or progression 
of the original event should be reported as a follow-up to that event regardless of when it occurs.  
The follow-up information should describe whether the event has resolved or continues, if and 
how it was treated, and whether the subject continued or withdrew from study participation or if 
study medication was interrupted or discontinued. 
If the SAE is not previously documented in the Investigator’s Brochure for the study medication 
(new occurrence) and is thought to be related to the Sponsor’s study drug, a Sponsor’s associate 
may urgently require further information from the Investigator for reporting to Health 
Authorities.   
The Sponsor may need to issue an Investigator Notification (IN) to inform all Investigators 
involved in any study with the same drug that this SAE has been reported.  Suspected 
Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to the 
competent authorities and relevant ethics committees in accordance with Directive 2001/20/EC 
or as per national regulatory requirements in participating countries.  If the study is open-label, 
no special unblinding procedures are needed for exceptional circumstances or medical 
emergencies. 
11.4. 
Emergency Unblinding of Treatment Assignment 
Not applicable, study is open label. 
11.5. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE, unless there is suspicion that study 
medication may have interfered with the effectiveness of a contraceptive medication or method.  
The procedures that will be followed based on whether a pregnancy is confirmed by a positive 
serum or urine test result are listed below: 
• Investigator and subject must notify each other immediately 
• Investigator must notify the Sponsor immediately  
• Study medication must be discontinued immediately 
• Subject must be withdrawn from the study 
• Perform the required End-of-treatment Visit evaluations 
• Investigator must complete and submit the Pregnancy Initial and Follow-up report 
forms to the Sponsor 


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• A serum pregnancy test must be performed to confirm the urine test result.  (The 
serum test should be performed at the investigative site to ensure the test will be 
performed promptly and the result available immediately for review.) 
If a negative serum test does not confirm the urine test result, then: 
• The Investigator will use his/her expert judgment, based on an assessment of the 
potential benefit/risk to the subject, to determine if it is in the subject’s best interest to 
resume study drug and continue participation in the study. 
To ensure subject safety, each pregnancy in a subject during maternal or paternal 
exposures to study medication must be reported within 24 hours of learning of its 
occurrence.  Data on fetal outcome and breast-feeding are collected for regulatory reporting and 
drug safety evaluation.  The pregnancy should be followed-up to determine outcome, including 
spontaneous or voluntary termination, details of the birth, and the presence or absence of any 
birth defects, congenital abnormalities, or maternal and/or newborn complications by following 
until the first well-baby visit.  Pregnancy should be recorded on a Clinical Study Pregnancy 
Form and reported by the Investigator to the Sponsor.  Pregnancy follow-up should be recorded 
on the same form and should include an assessment of the possible relationship to the Sponsor’s 
study medication of any pregnancy outcome and follow-up to the first well-baby visit.  Any SAE 
experienced during pregnancy must be reported on the SAE Report Form and needs to be 
reported to Incyte Corporation. 
11.6. 
Warnings and Precautions 
No evidence available at the time of the approval of this study protocol indicated that special 
warnings or precautions were appropriate, other than those noted in the provided Investigator 
Brochure.  Additional safety information collected between IB updates will be communicated in 
the form of Investigator Notifications (INs).  This information will be included in the subject 
informed consent and should be discussed with the subject during the study as needed. 
11.7. 
Data Safety Monitoring 
11.7.1. 
Data Monitoring Committee 
An independent Data Monitoring Committee (DMC) will be formed.  It will consist of qualified 
individuals who are not involved with the conduct of the study.  The establishment, composition, 
roles, duties and responsibilities of the DMC will be addressed in an approved DMC charter.  
The timing of data review by the DMC will be specified in the charter, but at a minimum, will 
include review of safety data with an emphasis on events of thrombocytopenia and hemorrhage 
at least 28 days after 20 subjects have been enrolled into the study and 28 days after 40 subjects 
have been enrolled into the study. 
11.7.2. 
Reporting of Grade 4 Thrombocytopenia Events and > Grade 2 Hemorrhage 
Events During the Study 
The study is designed to assess the efficacy and safety of ruxolitinib in a myelofibrosis patient 
population with platelet counts of 50 to100 x 109/L.  As these patients are potentially at higher 
risk for greater degrees of thrombocytopenia and bleeding, events of Grade 4 thrombocytopenia 


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and > Grade 2 hemorrhage will be monitored on an ongoing basis.  Investigators will be required 
to notify the sponsor via FAX of any Grade 4 thrombocytopenia event and any Grade 3 or 
Grade 4 event of hemorrhage, regardless of suspected causality.  The notification must occur 
within 24 hours of the time the site first becomes aware of the event.  All such events occurring 
after a subject has signed informed consent and received at least one dose of study drug up to the 
follow-up visit (or at least 30 days after the last dose of study drug is taken) must be reported.  
The notification form (supplied by sponsor) will require the site to provide information regarding 
dosing history, platelet count, event description and any other information pertinent to the event.   
11.7.3. 
Safety Reviews 
As ruxolitinib has been studied extensively in the myelofibrosis population in Phase II and III 
trials, its safety profile is generally well characterized in patients with platelet counts above 
100 x 109/L.  Because this trial is designed to assess the efficacy and safety of ruxolitinib in a 
myelofibrosis patient population with platelet counts of 50 to100 x 109/L, there will be a review 
of safety with an emphasis on events of thrombocytopenia and hemorrhage at regularly 
scheduled intervals corresponding to when: 
1. 20 patients have been enrolled  
2. 40 patients have been enrolled  
Additional safety reviews as deemed necessary by the DMC or the sponsor may be conducted at 
any time 
11.7.3.1. Review After Enrollment of 20th Subject 
When the 20th patient is enrolled, additional screening of subjects will be paused for at least 
28 days and up to approximately 42 days.  Subjects in screening at that time will be allowed to 
enroll if they are found to be eligible.  During this period, enrolled subjects will be allowed to 
continue on study per protocol.  At least twenty eight days from the enrollment of the 20th 
subject, safety data will be assessed by the DMC and the sponsor.  Subjects will be analyzed if 
they have completed at least 28 days on the study or have discontinued the study due to Grade 4 
thrombocytopenia or > Grade 2 hemorrhage.  If fewer than 33% of the subjects had an event of 
Grade 4 thrombocytopenia and fewer than 10% of these subjects had an event of > Grade 2 
hemorrhage, the study may resume enrollment without amendment.  If these criteria are not met, 
or other safety concerns are reveled, a recommendation will be made for one of the following 
actions: 
1. Stop the trial 
2. Recommend amendments and suspend enrollment until the amendments can be 
implemented 
3. Continue enrollment with a new dosing cap (with subsequent amendment of the protocol) 
4. Continue the trial without amendment (must be agreed upon by both the Sponsor and the 
DSMC) 


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11.7.3.2. Review After Enrollment of 40th Subject 
At least 28 days from the enrollment of the 40th subject, safety data will be assessed by the DMC 
and the sponsor.  Since the first dose escalation opportunity in the study is at Day 28 and the 
starting dose for all subjects of 5 mg bid will have been adequately assessed for safety at the first 
safety review after the enrollment of 20 patients, screening will not be suspended following 
enrollment of the 40th subject.  If safety of the 5 mg bid dose is not clear from this first data 
review, the DMC and sponsor may mandate a hold on screening at the review that occurs with 
enrollment of the 40th subject.  Subjects will be analyzed if they have completed at least 28 days 
on the study or discontinued due to grade 4 thrombocytopenia or > Grade 2 hemorrhage.  If 33% 
or fewer of the subjects had an event of Grade 4 thrombocytopenia and 10% or fewer of these 
subjects had an event of > Grade 2 hemorrhage, the study may resume enrollment without 
amendment.  If these criteria are not met, or other safety concerns are reveled, a recommendation 
will be made for one of the following actions: 
1. Stop the trial 
2. Recommend amendments and suspend enrollment until the amendments can be 
implemented 
3. Continue enrollment with a new dosing cap (with subsequent amendment of the protocol) 
4. Continue the trial without amendment (must be agreed upon by both the Sponsor and the 
DSMC) 
The DMC and the sponsor will also specifically evaluate the event rates for Grade 4 
thrombocytopenia and > Grade 2 hemorrhage in subjects from the initial cohort of 20 subjects 
who have had longer follow-up and opportunities for dose escalation. 
11.7.4. 
Continuous Safety Monitoring 
Events of Grade 4 thrombocytopenia and > Grade 2 hemorrhage will be monitored continuously.  
Subjects will be analyzed if they have completed at least 28 days on the study or discontinued 
due to Grade 4 thrombocytopenia or > Grade 2 hemorrhage.  If at any time > 33% of these 
subjects have an event of Grade 4 thrombocytopenia, or > than 10% of the subjects have an event 
of  > Grade 2 hemorrhage, the sponsor will temporarily hold further screening and seek 
consultation with the DMC.  A recommendation will be made for one of the following actions: 
1. Stop the trial 
2. Recommend amendments and suspend enrollment until the amendments can be 
implemented 
3. Continue enrollment with a new dosing cap (with subsequent amendment of the protocol) 
4. Continue the trial without amendment (must be agreed upon by both the Sponsor and the 
DMC). 
11.8. 
Product Complaints 
Incyte collects product complaints on study medications and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, to monitor quality, and to 
facilitate process and product improvements. 


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All product complaints associated with material packaged, labeled, and released by Incyte or its 
designee will be reported. 
The Investigator or his/her designee is responsible for handling the following aspects of the 
product complaint process in accordance with the instructions provided for this study: 
• Recording a complete description of the product complaint reported and any 
associated AEs using the study-specific complaint forms provided for this purpose 
• Faxing the completed product complaint form within 24 hours to Incyte or its 
designee. 
If the Investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint form with the product. 
12. 
STATISTICS 
12.1. 
Study Population 
Intent-to-treat (ITT):  includes all subjects enrolled in the study. 
Per-protocol (PP):  includes subjects who are considered to be sufficiently compliant with the 
protocol. 
Safety Evaluable: includes subjects who received at least 1 dose of study drug. 
 
 
 
 
12.2. 
Statistical Analyses 
12.2.1. 
Primary Analyses 
Co-Primary Endpoints: 
• Correlation of % change in spleen volume at Week 24 compared to baseline versus 
final titrated dose. 
• Correlation of % change in Total Symptom Score as measured by the modified 
MFSAF v2.0 diary at Week 24 compared to baseline versus final titrated dose. 
The null hypothesis is that the correlation between percent change in spleen volume or total 
symptom score and final titrated dose is zero.  The test will be based on the t test for a product-
moment correlation coefficient: 
t = rxy √(n – 2) / √(1 – rxy
2) 
(Cohen 1988, Formula 3.1.1) 


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A two-sided alpha of 5% will be used.  With a sample size of 150, the critical correlation that is 
needed to reject H0 is 0.16. if the absolute value of the observed correlation is 0.16 or higher, H0 
will be rejected.  In order to keep the overall alpha at 5%, a sequential testing procedure will be 
used: First we will test the correlation with % change in spleen volume, and only if the null 
hypothesis of no correlation can be rejected will we continue to test the correlation with % 
change in Total Symptom Score. 
Safety Endpoints: 
Safety and tolerability will be assessed by monitoring the frequency, duration and severity of 
adverse events, performing physical examinations, collecting vital signs, collecting laboratory 
data for hematology, serum chemistry, coagulation parameters, and lipid panel through 
Week 156. 
Change in platelet count from baseline to each visit where the variables are measured will be 
tabulated with summary statistics.  
Proportion of subjects with new onset of Grade 4 thrombocytopenia events, and proportion of 
subjects with new onset of Grade 2 or higher hemorrhage, as measured by CTCAE will be 
tabulated with summary statistics.  The hazard functions of time to onset of the above two safety 
measures will be estimated using life table method. 
Adverse events will be tabulated by the Medical Dictionary for Regulatory Activities 
(MedDRA®) preferred term and by system organ class.  Severity of AEs will be based on the 
CTCAE scale as indicated in Section 11.1.1. 
The subset of AEs that are considered by the Investigator to be related to study drug will be 
considered to be treatment-related AEs.  If the Investigator does not specify the relationship of 
the AE to study drug, the AE will be considered to be treatment-related.  The incidence of AEs 
and treatment-related AEs will be tabulated.  
Clinical Laboratory Tests 
The clinical laboratory data will be analyzed using summary statistics (eg, means and 
frequencies), and no formal statistical comparisons among the treatments are planned. 
Vital Signs 
Descriptive statistics and mean change from baseline will be determined for vital signs (body 
temperature, respiratory rate, blood pressure and heart rate) at each assessment time.  Vital sign 
results will be reviewed for clinically notable abnormalities according to the criteria shown 
below; subjects exhibiting clinically notable vital sign abnormalities will be listed. 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 160 mm Hg 
< 85 mm Hg 
Diastolic blood pressure 
> 100 mm Hg 
< 50 mm Hg 
Respiratory Rate 
> 24 per minute 
< 8 per minute 
Heart rate 
> 100 bpm 
< 45 bpm 
Note:  mm Hg = millimeters of mercury; bpm = beats per minute. 


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12.2.2. 
Secondary Analyses 
Secondary Endpoints 
• Percent change in spleen volume at Week 24 compared to Baseline 
• Percent change in Total Symptom Score as measured by the modified MFSAF v2.0 
diary at Week 24 compared to baseline 
• Proportion of subjects with ≥ 35% reduction in spleen volume at Week 24 compared 
to baseline 
• Proportion of subjects with ≥ 10% reduction in spleen volume at Week 24 compare to 
baseline 
• Proportion of subjects with ≥ 50% improvement in total symptom score as measured 
by the modified MFSAF v2.0 diary at Week 24 compared to baseline 
Long-term efficacy of ruxolitinib will be assessed by monitoring change and percent change in 
spleen length, as measured by palpation, and change in PGIC score from baseline to each visit 
where the variables are measured through Week 156.  The percent change in spleen volume at 
Week 24 compared to baseline, the percent change in Total Symptom Score as measured by the 
modified MFSAF v2.0 diary at Week 24 compared to baseline, the proportion of subjects with 
≥ 35% reduction in spleen volume at Week 24 compared to baseline, proportion of subjects with 
≥ 10% reduction in spleen volume at Week 24 compared to baseline, and the proportion of 
subjects with ≥ 50% improvement in total symptom score as measured by the modified MFSAF 
v2.0 diary at Week 24 compared to baseline will be tabulated with summary statistics.  Change 
and percentage change in spleen length from baseline as measured by palpation at each visit 
where the parameter is assessed through Week 156 will be tabulated with summary statistics.  
The data will be summarized as one group and by the final titrated dose.  The final titrated dose 
will be based on dosing data up to Week 24. 
 
 


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12.3. 
Interim Analysis 
Interim data review focused on thrombocytopenia and hemorrhage events will occur as described 
in Section 11.7 Data Safety Monitoring. 
12.4. 
Selection of Sample Size 
Approximately 150 subjects will be enrolled.  Using an alpha of 5% (two-sided), this sample size 
gives a power of 96% to reject the null hypothesis of no dose-effect correlation if the true 
correlation is 0.30.  The power is 87% if the true correlation is 0.25, and the power is 69% if the 
true correlation is 0.20.  These calculations are based on (Cohen 1988, Formula 12.3.4). 
In addition, the mean percent change of spleen volume measured by MRI, and mean percent 
change in Total Symptom Score from baseline to Week 24 will each be estimated with a 95% 
confidence interval.  With 150 subjects, the half-length of the 95% confidence interval of the 
spleen volume change from baseline to Week 24 is about 3%.  This is based on the Phase III 
study (INCB 18424-351), where the standard deviation of the percent change of spleen volume 
from baseline to Week 24 was 19%.  
12.5. 
Level of Significance 
All confidence intervals will be 95% and tests will be performed at two sided 0.05% level.  Since 
this is an exploratory study, no multiplicity adjustment will be performed. 


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13. 
STUDY DRUG MATERIALS AND MANAGEMENT 
13.1. 
Investigational Product Description 
Ruxolitinib Phosphate tablets will be provided as 5 mg tablets packaged as 60 count in 
high-density polyethylene bottles. 
13.1.1. 
Study Drug Packaging, Labeling and Preparation 
All bottles of Incyte investigational product contain the following language: “Caution: New 
Drug—Limited by Federal law to investigational use.” 
13.1.2. 
Study Drug Storage and Stability 
Ruxolitinib Phosphate 5 mg tablets are packaged as 60-count in high-density polyethylene 
(HDPE) bottles.  The bottles of tablets should be stored at room temperature, 15°C to 30°C (59°F 
to 86°F).  Stability studies will be conducted on clinical batches to support the clinical trial.   
13.2. 
Study Drug Accountability, Handling, and Disposal 
Responsibility for drug accountability at the study site rests with the Investigator; however, the 
Investigator may assign some of the drug accountability duties to an appropriate pharmacist or 
designee.  Inventory and accountability records must be maintained and readily available for 
inspection by the study monitor and are open to inspection at any time by any applicable 
regulatory authorities. 
The Investigator or designee will be expected to collect and retain all used, unused, and partially 
used containers of study medication until the end of the study.  The Investigator or designee must 
maintain records that document: 
• investigational product delivery to the study site 
• the inventory at the site 
• use by each subject including pill/unit counts from each supply dispensed 
• return to the Investigator or designee.   
These records should include dates, quantities, batch/serial numbers (if available), and the unique 
code numbers (if available) assigned to the investigational product and study subjects.   
The investigational product must be used only in accordance with the protocol.  The Investigator 
will also maintain records adequately documenting that the subjects were provided the correct 
study medication specified. 
Completed accountability records will be archived by the site.  At the completion of the study, 
the Investigator or designee will oversee shipment of any remaining study drug back to the 
Sponsor or Sponsor’s designee for destruction according to institutional standard operating 
procedures.  If local procedures mandate site destruction of investigational supply, prior written 
approval must be obtained from Incyte. 


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14. 
STUDY ADMINISTRATION 
14.1. 
Data Management 
14.1.1. 
Data Collection 
The Investigator will be provided with an eCRF for each subject.  Entries made in the eCRF 
must be verifiable against source documents, or, in certain circumstances, as directed by the 
Sponsor, have been directly entered into the eCRF, in which case the entry in the eCRF will be 
considered as the source data.  Data reported in the eCRF that are derived from source 
documents should be consistent with the source documents or the discrepancies should be 
explained.  The Investigator will be responsible for reviewing all data and eCRF entries and will 
sign and date the designated pages in each subject’s eCRF, verifying that the information is true 
and correct.  Queries generated by Data Management will be sent to the study site for resolution.  
The Investigator is responsible for the review and approval of all responses. 
14.1.2. 
Data Management 
Data management will be performed from electronic case report forms (eCRFs).  All eCRF data 
will be entered into a validated database.  Laboratory data will be imported to the database 
electronically.  All data entry, verification and validation will be performed in accordance with 
the current standard operating procedures of the Data Management Department at Incyte or its 
designee.  The database will be authorized for lock once no data queries are outstanding, all 
study data are considered clean, and all defined procedures completed. 
14.2. 
Study Monitoring 
Qualified representatives of the Sponsor or Sponsor designees, “study monitors,” will monitor 
the study according to a predetermined monitoring plan.  Monitoring visits provide the Sponsor 
with the opportunity to: 
• Evaluate the progress of the study. 
• Verify the accuracy and completeness of CRFs. 
• Assure that all protocol requirements, applicable laws and/or regulations, and 
Investigator’s obligations are being fulfilled. 
• Resolve any inconsistencies in the study records.   
The Investigator must allow the study monitors to periodically review, at mutually convenient 
times, during the study and after the study has been completed, all CRFs and office, hospital, and 
laboratory records supporting the participation of each subject in the study.  The CRFs and other 
documentation supporting the study must be kept up-to-date by the Investigator and the research 
staff at the investigative site.  These study materials must be available for review by the study 
monitor, and/or other qualified representatives of the Sponsor, at each monitoring visit. 
The study monitor will review the various records of the study (CRFs, subject medical and 
laboratory records, and other pertinent data).  The study monitor will verify the CRF data against 
original source documentation for accuracy and completeness.  The study monitor will identify 


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data discrepancies and collaborate with the Investigator and research staff to resolve the 
discrepancies in a timely manner.  Protocol deviations will also be identified and recorded on a 
“Protocol Deviation Log.”  The study monitor will follow an “Issue Escalation” plan in order to 
ensure that each issue identified during a monitoring visit is appropriately documented, reported, 
and resolved in a timely manner in accordance with the plan’s requirements. 
14.3. 
Protocol Adherence 
The Principal Investigator must obtain IRB approval for the investigation.  Initial IRB approval, 
and all materials approved by the IRB for this study including the subject informed consent form 
and recruitment materials must be maintained by the Investigator and made available for 
inspection. 
Each Investigator must adhere to the protocol as described in this document and agree that 
changes to the protocol, with the exception of medical emergencies, must be discussed and 
approved, firstly, by the Sponsor and, secondly, by the IRB/EC.  Each Investigator is responsible 
for enrolling subjects who have met the protocol inclusion and exclusion criteria.  The IRB/EC 
that granted original approval, or the IRB/EC currently responsible for overseeing the conduct of 
the study must be notified of all changes in and deviations from the protocol that may increase 
risk to the subject, and/or that may adversely affect the rights of the subject or validity of the 
investigation.  The Investigator must send a copy of the approval letter from the IRB/EC to the 
Sponsor or CRO and retain the original in the site study regulatory file. 
Major eligibility deviations must be reported to the IRB/EC in accordance with the IRB/EC 
requirements.  During the course of the study, the monitor must notify the Sponsor of subjects 
found not to have met eligibility criteria.  The medical monitor, in collaboration with the 
Investigator, will determine if the subject should be withdrawn from the study. 
14.4. 
Financial Disclosure 
All clinical investigators participating in clinical studies subject to FDA Regulation Title 21 
Code of Federal Regulations (CFR) Part 54 – Financial Disclosure by Clinical Investigators, are 
required prior to study initiation to submit a completed Clinical Investigator Financial Disclosure 
Request Form that sufficiently details any financial interests and arrangements that apply.  For 
the purpose of this regulation, clinical investigator is defined as any investigator or 
subinvestigator who is directly involved in the treatment or evaluation of research subjects, 
including the spouse and each dependent child of the clinical investigator.  These requirements 
apply to both US and foreign clinical investigators conducting covered clinical studies. 
Any new investigators or sub-investigators added to the covered clinical study during its conduct 
must also submit a completed Clinical Investigator Financial Disclosure Request Form.  During a 
covered clinical study, any changes to the financial information previously reported by a clinical 
investigator must be reported to the Sponsor/designee.  At the conclusion of the covered clinical 
study, the clinical investigators will be reminded of their obligation to report to the 
Sponsor/designee any changes to the financial information previously reported.  The clinical 
investigators will also be reminded that they must report any changes in their financial 
information for a period of 1 year after completion of the covered clinical study.   


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15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
15.1. 
Sponsor Audits 
At some point during the study, individuals from the Sponsor’s Quality Assurance department 
and/or their authorized representative may visit the Investigator’s site to conduct an audit of the 
study.  The purpose of this visit will be to determine the Investigator’s adherence to the protocol, 
applicable regulations, and the Sponsor’s procedures, in addition to assessing the accuracy of the 
study data.  Prior to initiating this audit, the Investigator will be contacted by the Sponsor to 
arrange a convenient time for this visit.  The Investigator and staff are expected to cooperate with 
the auditors and allow access to all subject records supporting the CRFs and other study-related 
documents. 
15.2. 
Inspection by Regulatory Authorities 
At some point during the investigational product’s development program, a regulatory authority 
may visit the Investigator to conduct an inspection of the study and the site.  The Investigator and 
staff are expected to cooperate with the inspectors and allow access to all source documents 
supporting the CRFs and other study related documents.  The Investigator must immediately 
notify the Sponsor when contacted by any regulatory authority for purposes of conducting an 
inspection. 
16. 
ETHICS 
16.1. 
Ethical Conduct of the Study 
This study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and conducted in adherence to the study protocol, Good Clinical 
Practices as defined in Title 21 of the US Code of Federal Regulations Parts 50, 54 56, 312 and 
Part 11 as well as ICH GCP consolidated guidelines (E6) and applicable regulatory requirements.  
16.2. 
Written Informed Consent 
An informed consent form (ICF) that includes both information about the study and the consent 
form will be prepared and given to the subject.  This document will contain all the elements 
required by the ICH E6 Guideline for Good Clinical Practice and any additional elements 
required by local regulations.  The document must be in a language understandable to the subject 
and must specify who informed the subject.  Where required by local law, the person who 
informs the subject must be a physician. 
The Principal Investigator(s) at each center will ensure that the subject is given full and adequate 
verbal and written information about the nature, purpose, and the possible risk and benefit of the 
study.  Subjects must also be notified that they are free to discontinue study medication and 
withdraw from the study at any time.  The subject should be given the opportunity to ask 
questions and allowed time to consider the information provided. 


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The subject’s signed and dated ICF must be obtained before conducting any study procedures.  
The Principal Investigator(s) must maintain the original, signed ICF.  A copy of the signed ICF 
must be given to the subject. 
Preparation of the consent form is the responsibility of the Investigator and must include all 
elements required by the ICH GCP, and applicable regulatory requirements, and must adhere to 
the ethical principles that have their origin in the Declaration of Helsinki.   
A template will be provided by Incyte.  Incyte or its designee must review and approve all 
changes to site-specific ICFs.  
The consent form must include a statement that the Sponsor or designee and regulatory 
authorities have direct access to subject records.  Prior to the beginning of the study, the IRBs 
and/or IECs must provide the Investigator with written approval/favorable opinion of the written 
ICF and any other information to be provided to the subjects. 
The Investigator will not undertake any measures specifically required for the clinical study until 
valid consent has been obtained. 
The Investigator should inform the subject’s primary physician about the subject’s participation 
in the study if the subject has a primary physician and if the subject agrees to the primary 
physician being informed. 
16.3. 
Ethics Review 
It is the responsibility of the Investigator to assure that all aspects of the ethics review are 
conducted in accordance with the Declaration of Helsinki as described in the International 
Conference on Harmonization (ICH) E6: Guideline for Good Clinical Practice (GCP), and/or 
local laws, whichever provides the greatest level of protection for the study participants.  The 
protocol and any information supplied to the subject to obtain informed consent including 
written ICFs, subject recruitment procedures (eg, advertisements), and written information to be 
provided to subjects (information leaflets) must be reviewed and approved by a qualified 
IRB/EC prior to enrollment of participants in the study.  Prior to initiation of the study, the 
Sponsor must receive documentation of the IRB/EC approval, which specifically identifies the 
study/protocol, and a list of the committee members. 
The Principal Investigator is responsible for informing the IRB or EC of any amendment to the 
protocol in accordance with local requirements.  Protocol Amendments and revisions to the 
informed consent must be submitted to and approved by the IRB/EC. 
Investigators must submit progress reports to the IRB/EC in accordance with the IRB/EC 
requirements and local regulations.  Annual re-approval of the study must be obtained.  Copies 
of progress reports and annual re-approvals must be sent to the Sponsor. 
The Principal Investigator is also responsible for providing the IRB/EC with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product.  Incyte will provide this information to the Principal Investigator. 
When the Sponsor provides the Investigator with a safety report, the Investigator must promptly 
forward a copy to the IRB/EC. 


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After completion or termination of the study, the Investigator must submit a final report to the 
IRB/EC and to the Sponsor.   
The Investigator, as part of the records retention requirements for the study, must maintain 
documentation of all submissions, correspondence, and approvals to and from the IRB/IEC. 
Each clinical Investigator is responsible to conduct the study in accordance with the protocol, all 
applicable laws, regulations, and GCP according to ICH guidelines. 
16.4. 
Data Privacy 
The Investigator and Sponsor must adhere to applicable data privacy laws and regulations.  The 
Investigator and Sponsor are responsible for ensuring that sensitive information is handled in 
accordance with local requirements (eg, HIPAA).  Appropriate consent and authorizations for 
use and disclosure and/or transfer (if applicable) of protected information must be obtained. 
17. 
DATA HANDLING AND RECORDKEEPING 
17.1. 
Inspection of Records 
The Sponsor will be allowed to conduct site visits to the investigation facilities for the purpose of 
monitoring any aspect of the study.  The Investigator agrees to allow the monitor to inspect the 
drug storage area, study drug stocks, drug accountability records, subject charts and study source 
documents, and other records relative to study conduct. 
The Investigator must ensure that all records pertaining to the conduct of the clinical study (as 
listed above) are adequately maintained for a period of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region, or at least 2 years have elapsed since the formal termination of 
clinical development of the investigational product. 
17.2. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 
2 years after the last marketing application approval, or if not approved, 2 years following the 
termination of the test article for investigation.  If it becomes necessary for the Sponsor or the 
Regulatory Authority to review any documentation relating to the study, the Investigator must 
permit access to such records. 
The Investigator must not destroy any records associated with the study without receiving 
approval from Incyte.  The Investigator must notify the Sponsor in the event of accidental loss or 
destruction of any study records.  If the Investigator leaves the institution where the study was 
conducted, Incyte must be contacted to arrange alternative record storage options. 
Whenever possible, an original recording of an observation must be retained as the source 
document.  However, a photocopy of a record is acceptable, provided it is legible and is a 
verified copy of the original document. 
All CRF data entered by the site (including audit trail), as well as computer hardware and 
software (for accessing the data), will be maintained or made available at the site in compliance 


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with applicable record retention regulations.  The Sponsor will retain the original CRF data and 
audit trail.   
17.3. 
Confidentiality 
Subject names will not be supplied to the Sponsor.  Only the subject number and subject initials 
will be recorded in the CRF, and if the subject name appears on any other document (eg, 
laboratory report), it must be obliterated on the copy of the document to be supplied to the 
Sponsor.  Study findings stored on a computer will be stored in accordance with local data 
protection laws.  The subjects will be informed that representatives of the Sponsor, IRB/IEC, or 
regulatory authorities may inspect their medical records to verify the information collected, and 
that all personal information made available for inspection will be handled in strictest confidence 
and in accordance with local data protection laws. 
18. 
PUBLICATION POLICY 
By signing the study protocol, the Investigator and his or her institution agree that the results of 
the study may be used by the Sponsor, Incyte Corporation (Incyte), for the purposes of national 
and international registration, publication, and information for medical and pharmaceutical 
professionals.  If necessary, the authorities will be notified of the Investigator’s name, address, 
qualifications, and extent of involvement. 
The terms regarding the publication of study results are contained in the agreement signed with 
Incyte or its contract research organization.  The signed agreement is retained by Incyte or its 
contract research organization. 


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19. 
LIST OF REFERENCES 
Barosi G, Mesa RA, Thiele J, et al.  Proposed criteria for the diagnosis of post-polycythemia vera 
and post-essential thrombocythemia myelofibrosis: a consensus statement from the International 
Working Group for Myelofibrosis Research and Treatment. Leukemia. 2008;22(2):437-438.  
Cervantes F, Dupriez B, Pereira A, et al.  A new prognostic scoring system for primary 
myelofibrosis based on a study of the International Working Group for Myelofibrosis Research 
and Treatment [published online ahead of print]. Blood. 2009;113:2895-2901.  
Cohen J: Statistical Power Analysis for the Behavioral Sciences. Second Edition. Hillsdale, NJ, 
1988. 
Deeg HJ, Gooley TA, Flowers ME, et al. Allogeneic hematopoietic stem cell transplantation for 
myelofibrosis. Blood. 2003;102:3912-3918. 
Elliott M, Verstovsek S, Dingli D, et al. Monocytosis is an adverse prognostic factor for survival 
in younger patients with primary myelofibrosis. Leuk Res. 2007;31(11):1503-1509. 
Gangat N, Caramazza D, Vaidya R, et al. DIPSS Plus: a refined dynamic international prognostic 
scoring system for primary myelofibrosis that incorporates prognostic information from 
karyotype, platelet count and transfusion status. J Clinical Oncology. 2011;29:392-397. 
Incyte Corporation. Investigator’s Brochure INCB018424 Phosphate Capsules/Tablets, 
Version 9, October 2010. 
Mesa RA, Niblack J, Wadleigh M, et al. The Burden of Fatigue and Quality of Life in 
Myeloproliferative Disorders (MPDs). Cancer. 2007;109:68-76. 
Mesa RA, Gotlib J, Gupta V, et al. Associations between improvements in myelofibrosis (MF) 
symptoms and quality of life measures with splenomegaly reduction in COMFORT-I: a 
randomized, double-blind, phase III trial of the JAK1 and JAK2 inhibitor ruxolitinib versus 
placebo in patients with MF. Blood (ASH Annual Meeting Abstracts) 2011;118:Abstract 3842. 
Pardanani A, George G, Lasho T, et al. A Phase I/II study of CYT387, an oral Jak-1/2 inhibitor 
in meylofibrosis: significant response rates in anemia splenomegaly and constitutional 
symptoms.  Blood. 2010;116(21):460. 
Passamonti F, Cervantes F, Vannucchi AM, et al.  A dynamic prognostic model to predict 
survival in primary meylofibrosis: a study by the IWG-MRT (International Working Group for 
Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115(9):1703-1708. 
Quintas-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective 
JAK1/JAK2 inhibitor INCB018424: implications for the treatment of myeloproliferative 
neoplasms. Blood. 2010;115(15):3109-3117. 
Slichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients. 
Transfusion Medicine Reviews. 2004;18:153-167. 
Tefferi A, Barosi G, Mesa RA, et al. International Working Group (IWG) consensus criteria for 
treatment response in myelofibrosis with myeloid metaplasia, for the IWG for myelofibrosis 
research and treatment (IWG-MRT). Blood. 2006;108:1497-1503. 


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Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: The 
2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 
2008;22:14-22. 
Trussell J. Contraceptive failure in the United States. Contraception. 2004;70:89–96. 
Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and 
JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010;16;363(12):1117-1127. 
World Medical Association Declaration of Helsinki Ethical Principles for Medical Research 
Involving Human Subjects. Adopted by the 18th WMA General Assembly, Helsinki, Finland, 
June 1964, and amended by the 29th WMA General Assembly, Tokyo, Japan, October 1975, 
35th WMA General Assembly, Venice, Italy, October 1983, 41st WMA General Assembly, 
Hong Kong, September 1989, 48th WMA General Assembly, Somerset West, Republic of South 
Africa, October 1996, and the 52nd WMA General Assembly, Edinburgh, Scotland, October 
2000. Note of Clarification on Paragraph 29 added by the WMA General Assembly, Washington 
2002. Note of Clarification on Paragraph 30 added by the WMA General Assembly, Tokyo 
2004. Available at <http://www.wma.net/e/policy/b3.htm>. 


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APPENDIX 1. 2008 WORLD HEALTH ORGANIZATION CRITERIA 
FOR DIAGNOSIS OF PRIMARY MYELOFIBROSIS 
 
Reference:  Tefferi and Vardiman 2008. 


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APPENDIX 2. PROPOSED DIAGNOSTIC CRITERIA FOR PPV-MF AND 
PET-MF BY THE INTERNATIONAL WORKING GROUP 
FOR MYELOFIBROSIS RESEARCH AND TREATMENT 
 
Reference:  Barosi et al 2008. 


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APPENDIX 3. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For Males Subjects Participating in the Study: 
The following methods have been determined to be more than 99% effective (failure rate less 
than 1% per year, when used consistently and correctly) (Trussell 2004), by the male subject and 
his partner and are permitted under this protocol: 
 
• Complete abstinence from sexual intercourse  
• Double barrier methods  
− condom with spermicide in conjunction with use of an intrauterine device (IUD)  
− condom with spermicide in conjunction with use of a diaphragm  
• Oral, injectable, or implanted contraceptives  
• Tubal ligation or vasectomy (surgical sterilization)  
For Female Subjects Participating in the Study: 
The following methods have been determined to be more than 99% effective (failure rate less 
than 1% per year, when used consistently and correctly) (Trussell 2004), by the female subject 
and her partner and are permitted under this protocol: 
• Complete abstinence from sexual intercourse  
• Double barrier methods  
− condom with spermicide in conjunction with use of an IUD  
− condom with spermicide in conjunction with use of a diaphragm  
• Tubal ligation or vasectomy (surgical sterilization)  
• Oral, injectable, or implanted contraceptives 


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APPENDIX 4. CLINICAL LABORATORY TESTS 
Serum Chemistry  
Hematology 
Other  
Albumin * 
Alkaline phosphatase* 
ALT* 
AST* 
Bicarbonate 
BUN* 
Calcium 
Chloride  
Creatinine* 
Gamma glutamyl 
transferase* 
Glucose 
Iron* 
Lactate dehydrogenase* 
Phosphorus 
Potassium 
Serum lipase* 
Sodium 
Total Bilirubin* 
Total Protein 
Uric acid 
Transferrin 
Ferritin 
Complete Blood Count (CBC) 
Manual Differential*, 
   including reporting of % blasts 
Platelets*  
Reticulocyte count* 
Hemoglobin* 
Hematocrit* 
Serology*: 
Hepatitis A virus antibody (IgM) 
Hepatitis B surface antigen 
Hepatitis B surface antigen antibody 
Hepatitis B core antibody 
Hepatitis C virus antibody 
HIV Antibody 
 
Pregnancy Test*: 
Female subjects of childbearing 
potential only; serum test at 
screening.  
Lipid Panel 
Coagulation 
Immunology 
Total cholesterol* 
Triglycerides 
LDL 
HDL 
HS-CRP  
PT (INR) 
PTT 
 
 
Values denoted with * will be reported to the sponsor.  All laboratory data 
will be retained in source documents.   
ALT = alanine aminotransferase, AST = aspartate aminotransferase, BUN = blood urea nitrogen, 
PT = prothrombin time, PTT = partial thromboplastin time, HS-CRP = high sensitivity C-reactive 
protein 


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APPENDIX 5. PATIENT GLOBAL IMPRESSION OF CHANGE (PGIC) 
Instructions:  Circle the answer that is most appropriate. 
Since the start of the treatment you’ve received in this study, your myelofibrosis symptoms 
are: 
1. Very much improved 
2. Much improved 
3. Minimally improved 
4. No change 
5. Minimally worse 
6. Much worse 
7. Very much worse 


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APPENDIX 6. BONE MARROW BIOPSY EVALUATION 
• Grading of bone marrow biopsy fibrosis density 
Fibrosis Grade 
Description 
0 
Scattered linear reticulin with no intersections corresponding to normal 
bone marrow 
1 
Loose network of reticulin with many intersections, especially in 
perivascular areas 
2 
Diffuse and dense increase in reticulin with extensive intersections, 
occasionally with only focal bundles of collagen and/or focal 
osteosclerosis 
3 
Diffuse and dense increase in reticulin with extensive intersections with 
coarse bundles of collagen, often associated with significant osteosclerosis 
Note:  Fibrosis density should be assessed in hematopoietic areas. 
Source:  Tefferi et al 2006. 
 
Bone Marrow Biopsy Pathology Reporting Guidelines 
The following should be assessed: 
• Assessment of cellularity. 
• 500-cell differential of aspirate, (if collected) correlated, if possible, with data from 
appropriate marrow biopsy section. Percentage of pronormoblasts, blasts, 
normoblasts, myelocytes, metamyelocytes 
• Blast percentage, indicating what cellular types are being considered as blast 
equivalents, and the degree of maturation and dysplastic abnormalities within the 
neoplastic population should be described. 
• Characterization of erythrocyte and megakaryocyte morphology. 
• Characterization and gradation of fibrosis within hematopoietic cellular areas. 
• Diagnostic interpretation with specific mention of (expected) absence of an 
infiltrative or granulomatous process 
• Pathologist’s diagnosis (PMF, PPV-MF, etc.) 


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APPENDIX 7. SCREENING SYMPTOM FORM 
Instructions to Subjects:  Please answer all questions to the best of your ability, based on your memory over the past 7 days 
(1 week).  There is no right or wrong answer. 
1. During the past 7 days, how severe were your worst night 
sweats (or feeling hot or flushed) due to MF? 
0 (Absent)  1    2    3    4    5    6    7    8    9    10 (Worst Imaginable) 
2. During the past 7 days, how severe was your worst itchiness 
due to MF? 
0 (Absent)  1    2    3    4    5    6    7    8    9    10 (Worst Imaginable) 
3. During the past 7 days, how severe was your worst abdominal 
discomfort (feel uncomfortable, pressure or bloating) due to 
MF? 
0 (Absent)  1    2    3    4    5    6    7    8    9    10 (Worst Imaginable) 
4. During the past 7 days, how severe was your worst pain under 
the ribs on the left side due to MF? 
0 (Absent)  1    2    3    4    5    6    7    8    9   10 (Worst Imaginable) 
5. During the past 7 days, what was the worst feeling of fullness 
(early satiety) you had after beginning to eat, due to MF? 
0 (Absent)  1    2    3    4    5    6    7    8    9   10 (Worst Imaginable) 
6. During the past 7 days, how severe was your worst bone or 
muscle pain due to MF (diffuse, not joint or arthritis pain)? 
0 (Absent)  1    2    3    4    5    6    7    8    9   10 (Worst Imaginable) 
7. During the past 7 days, what was the worst degree of inactivity 
(including work and social activities) you had due to MF? 
0 (Absent)  1    2     3    4    5    6    7    8    9   10 (Worst Imaginable) 


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Investigators/Site Staff: 
Please complete the table below to confirm the criterion used to confirm the subject’s eligibility 
in the trial based on an assessment of his/her active symptoms of myelofibrosis. 
ELIGIBILITY CRITERION 
CONFIRMATION 
A symptom score of at least 5 on at least one of the symptoms 
□ Yes □ No 
A symptom score of 3 or greater on at least 2 of the symptoms 
□ Yes □ No 
 


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APPENDIX 8. INHIBITORS AND INDUCERS OF CYTOCHROME – 
P450 3A4 
CYP3A4 Inhibitors 
CYP 3A4 Inducers:* 
 A Strong inhibitor. 
 A Moderate inhibitor. 
 A Weak inhibitor. 
 All other inhibitors.  
HIV Antivirals: 
efavirenz1 
nevirapine1 
barbiturates 
carbamazepine 
glucocorticoids 
modafinil 
nevirapine 
oxcarbazepine 
phenobarbital 
phenytoin 
pioglitazone 
rifabutin 
rifampin3 
St. John's wort3 
 
Other Prohibited Medications3: 
systemic steroids exceeding 10 mg 
prednisolone equivalents per day except as part 
of a taper strategy or to prevent reactions to 
blood component transfusions 
aspirin > 81 mg daily 
other investigational medication 
hydroxyurea 
interferon 
thalidomide 
busulfan 
lenalidomide 
anagrelide 
 
thrombopoietin receptor agonists (romiplostim, 
eltrombopag) 
HIV Antivirals: 
 indinavir1 
 nelfinavir1 
 ritonavir1 
 saquinavir1 
 
 clarithromycin2 
 itraconazole2 
 ketoconazole2 
 nefazodone2 
 posaconazole2 
 voriconazole2 
 telithromycin2 
 aprepitant 
 erythromycin 
 fluconazole2 
 grapefruit juice 
 verapamil 
 diltiazem 
 cimetidine 
 amiodarone 
 chloramphenicol 
 delaviridine 
 diethyl-dithiocarbamate 
 fluvoxamine 
 gestodene 
 imatinib 
 mibefradil 
 mifepristone 
 norfloxacin 
 norfluoxetine 
 starfruit 
*Use of all CYP3A4 inhibitors or inducers is discouraged as they may have effects on ruxolitinib levels, and 
alternative therapies should be sought if available. 
1 Subjects receiving these medications should not be allowed in the study as HIV+ patients are excluded 
2 Use of these medications should be avoided and if used, a 50% ruxolitinib dose reduction is recommended along 
with frequent platelet monitoring during the period of co-administration. 
3 These medications are prohibited during this study.   


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APPENDIX 9. DRUGS THAT INTERFERE WITH COAGULATION OR INHIBIT PLATELET 
FUNCTION 
Antiplatelet 
Agentsa 
 
 
Anticoagulant 
Agentsa 
 
 
Procoagulant 
Agents 
 
 
Synthetic 
inhibitors of 
factor Xa 
 
Thrombolytic 
Agents 
 
 
Direct 
thrombin 
inhibitors 
 
NSAIDs and 
Acetaminophen 
 
PERMITTED AT 
RECOMMENDED 
DOSESb 
Food supplements 
 
 
PROHIBITED 
Aspirin 
(> 81 mg) 
PROHIBITED 
Heparin 
Aminocaproic 
Acid 
Fondaparinux 
Urokinase 
Argatroban 
Ibuprofen, Naproxen, 
Fenoprofen, Ketoprofen, 
Flurbiprofen, Oxaprozin, 
Indomethacin, Sulindac, 
Etodolac, Ketorolac, 
Diclofenac, 
Nabumetone, Piroxicam, 
Meloxicam, Tenoxicam, 
Droxicam, Lornoxicam, 
Isoxicam, Mefenamic 
acid, Meclofenamic acid, 
Flufenamic acid, 
Tolfenamic acid 
Nattokinase 
(extracted and from 
a Japanese food 
called natto) 
Ticlopidine 
Warfarin 
Desmopressin 
Idraparinux 
Streptokinase 
Lepirudin 
Clopidogrel 
Dicumarol 
 
 
Anistreplase 
Bivalirudin 
Lumbrokinase 
(present in the 
earthworm 
Lumbricus bimastus) 
Prasugrel 
Phenprocoumon 
 
 
Tissue 
Plasminogen 
Activator (tPA) 
Dabigatran 
Cilostazol 
Acenocoumarol 
 
 
 
 
Abciximab 
Anisindione 
 
 
 
 
Eptifibatide 
Dalteparin 
 
 
 
 
Tirofiban 
Danaparoid 
 
 
Alteplase 
 
 
 
Dipyridamole 
Enoxaparin 
 
 
Reteplase 
 
 
 
Epoprostenol 
Tinzaparin 
 
 
Tenecteplase 
 
Acetaminophen 
 
 
Phenindione 
 
 
 
 
 
 
a If concomitant administration of an anticoagulant/antiplatelet medication is indicated, caution and enhanced monitoring is required.  History of 
thrombocytopenia, and any concurrent ruxolitinib-related thrombocytopenia should be a factor in the choice of anticoagulant and dose.  
b Over-the-counter acetaminophen and NSAIDS (ibuprofen and naproxen) are permitted in this study.  All prescription strength NSAIDs are prohibited. 
 


Signature Manifest
Document Number: IC-DEV-PROT-AMEND-0039
Revision: 0
Title: INCB 18424-258 Protocol Amendment 2
All dates and times are in Eastern Standard Time.
APPROVAL: 18424-258 Protocol Amend2
Approval and Release
Name/Signature
Title
Date
Meaning/Reason
 
09 Aug 2013, 03:35:34 PM
Approved
09 Aug 2013, 05:16:50 PM
Approved
 
12 Aug 2013, 09:26:17 AM
Approved
 
13 Aug 2013, 02:19:14 PM
Approved
Page 1 of 1
Signature Manifest
8/13/2013
file://de-mcweb01/efp$/mastercontrol/mastercontrol/publish/manifests/97949D140...

SAP_001.pdf: 
Statistical Analysis Plan - Final  
Incyte Corporation 
INCB 18424-258 / 
NCT01348490
17 JAN 2012 
1 
STATISTICAL ANALYSIS PLAN 
PHASE 2 
DATE OF PLAN: 
17 JAN 2012 
BASED ON: 
Protocol Amendment 1 on 17 August 2011 
CRF Study Design Version 2.1 on 24 October 2011 (by Central Designer™)  
STUDY DRUG: 
RUXOLITINIB PHOSPHATE TABLETS / INC 18424 
PROTOCOL NUMBER: 
258 
STUDY TITLE: 
AN OPEN LABEL ASSESSMENT OF SAFETY AND EFFICACY OF RUXOLITINIB 
(INCB018424) IN SUBJECTS WITH PRIMARY MYELOFIBROSIS, POST ESSENTIAL 
THROMBOCYTHEMIA-MYELOFIBROSIS AND POST POLYCYTHEMIA VERA-
MYELOFIBROSIS WHO HAVE PLATELET COUNTS OF 50 x 109/L TO 100 x 109/L 
SPONSOR: 
Incyte Corporation 
Route 141 & Henry Clay Road 
Building E336 
Wilmington, DE  19880 United States 
This study is being conducted in compliance with good clinical practice, 
including the archiving of essential documents. 


Incyte Corporation 
INCB 18424-258
Statistical Analysis Plan - Final 
                            17 JAN 2012
2


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
3 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS.......................................................................................6 
2. 
INTRODUCTION........................................................................................................9 
3. 
STUDY OBJECTIVES AND ENDPOINTS..............................................................10 
3.1. 
Study Objectives and Endpoints.................................................................................10 
3.1.1. 
Study Objectives.........................................................................................................10 
3.1.2. 
Study Endpoints..........................................................................................................10 
3.1.2.1. 
Co-Primary Endpoints ................................................................................................10 
3.1.2.2. 
Safety Endpoint(s) ......................................................................................................10 
3.1.2.3. 
Secondary Endpoints ..................................................................................................11 
11 
3.2. 
Statistical Hypotheses.................................................................................................11 
4. 
STUDY DESIGN .......................................................................................................12 
4.1. 
Overall Description.....................................................................................................12 
4.2. 
Scheduled Visits .........................................................................................................13 
4.3. 
Sample Size Considerations .......................................................................................16 
5. 
DATA HANDLING DEFINITIONS AND CONVENTIONS..................................18 
5.1. 
Scheduled Analyses....................................................................................................18 
5.1.1. 
First DMC Data Review Meeting...............................................................................18 
5.1.2. 
Second DMC Data Review Meeting ..........................................................................18 
5.2. 
Treatment Groups.......................................................................................................19 
5.3. 
Analysis Populations ..................................................................................................19 
5.3.1. 
Safety Population........................................................................................................19 
5.3.2. 
Intent-to-Treat Population ..........................................................................................19 
5.3.3. 
Per-Protocol Population..............................................................................................19 
 
19 
5.4. 
Statistical Methodology..............................................................................................19 
5.4.1. 
General Methodology.................................................................................................19 
5.4.2. 
Control of Type I Error...............................................................................................20 
5.5. 
Baseline Values ..........................................................................................................20 
5.6. 
Day 1, Study Day, and Study Time Points.................................................................20 
5.7. 
Concomitant Medications and Partial Dates...............................................................21 


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5.8. 
Adverse Events and Missing Data..............................................................................22 
5.9. 
Variable Definitions and/or Derivation Rules ............................................................23 
5.9.1. 
Spleen Volume Value at Week 24..............................................................................23 
5.9.2. 
Total Symptom Score .................................................................................................23 
5.9.2.1. 
Daily Total Symptom Score .......................................................................................23 
5.9.2.2. 
Baseline Total Symptom Score ..................................................................................23 
5.9.2.3. 
Total Symptom Score at Weeks 4, 8, 12, 16, 20, and 24............................................24 
5.9.3. 
Dosing Level and Compliance....................................................................................24 
5.9.3.1. 
Final Titrated Dose Level...........................................................................................24 
5.9.3.2. 
Last Average Daily Dose Level During the Treatment Period...................................24 
5.9.3.3. 
Study Drug Compliance .............................................................................................25 
5.9.3.4. 
Last Dose Level Prior to an Adverse Event................................................................25 
5.9.4. 
Blood Transfusion Independence at Baseline.............................................................25 
5.9.5. 
Blood Transfusion Independence at Post-Baseline ....................................................26 
5.9.6. 
Derivation of Per-protocol Population........................................................................26 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................27 
6.1. 
Baseline and Demographics .......................................................................................27 
6.2. 
Disposition and Enrollment........................................................................................27 
6.3. 
Protocol Deviations ....................................................................................................27 
6.4. 
Exposure .....................................................................................................................27 
6.5. 
Study Medication Compliance ...................................................................................27 
6.6. 
Medical History ..........................................................................................................27 
6.7. 
Concomitant Medication ............................................................................................28 
6.8. 
Blood Transfusion Dependency .................................................................................28 
7. 
EFFICACY ANALYSES...........................................................................................29 
7.1. 
Primary Efficacy Endpoints........................................................................................29 
7.2. 
Secondary Endpoint(s) and Analyses.........................................................................29 
30 
8. 
SAFETY ANALYSES ...............................................................................................31 
8.1. 
Adverse Events...........................................................................................................31 
8.2. 
Laboratory Values ......................................................................................................32 
8.3. 
Vital Signs ..................................................................................................................33 


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8.4. 
Electrocardiograms.....................................................................................................33 
9. 
CLINICAL PHARMACOLOGY/
34 
34 
9.2. 
Subject Demographic, Clinical Laboratory, and Disease-Related Variables.............34 
9.3. 
Concomitant Medication ............................................................................................34 
34 
 
35 
 
35 
10. 
LIST OF PLANNED TABLES, LISTINGS, AND FIGURES..................................35 
10.1. 
Tables..........................................................................................................................35 
10.2. 
Figures ........................................................................................................................38 
10.3. 
Listings .......................................................................................................................39 
11. 
REFERENCES ...........................................................................................................41 
12. 
APPENDICES............................................................................................................42 
APPENDIX A. MEDDRA PREFERRED TERMS INCLUDED IN THE SMQ TO 
IDENTIFY HEMORRHAGE ADVERSE EVENTS.................................................43 
APPENDIX B. SHELLS FOR POST-TEXT TABLES .............................................................51 
 
LIST OF TABLES 
Table 1: 
List of Abbreviations....................................................................................................6 
Table 2: 
List of Assessments ....................................................................................................14 
Table 3: 
Table of Laboratory Assessments...............................................................................15 
Table 4: 
Windows for Total Symptom Score at Given Study Time Points..............................24 
Table 5: 
Example Shift Summary for Applicable Laboratory Assessments ............................33 
Table 6: 
High and Low Threshold Values for Alert Vital Sign Observations..........................33 
 
LIST OF FIGURES 
Figure 1: 
Power and Sample Size Curves for 3 Alternative Hypotheses on the Level of 
Dose-Effect Correlation..............................................................................................16 
 


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1. 
LIST OF ABBREVIATIONS 
Table 1: 
List of Abbreviations 
Abbreviation 
Term 
AE 
Adverse event 
ALB 
Albumin (G/L) 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase  
AUC 
Area under the concentration-time curve 
AUC(0-) 
AUC from time zero (pre-dose) extrapolated to infinite time 
AUC(0-) 
AUC from time zero (pre-dose) to time of last observed quantifiable concentration 
within a subject across all treatments 
BLQ 
Below limit of quantification 
BMI 
Body mass index 
bid. 
Twice daily 
BP 
Blood pressure 
bpm 
Beats per minute 
BUN 
Blood urea nitrogen 
C 
Degrees Celsius 
Ca 
Calcium 
Cl 
Chloride 
CLr 
Renal clearance 
Cmax 
Maximum observed concentration 
CRF 
Case report form 
CSR 
Clinical study report 
Ct 
Last observed quantifiable concentration 
DBP 
Diastolic blood pressure 
DL 
Deciliter 
DOB 
Date of birth 
ECG 
Electrocardiogram 
oF 
Degrees fahrenheit 
GCP 
Good Clinical Practices 


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Table 1: 
List of Abbreviations (Continued) 
Abbreviation 
Term 
GGT 
Gamma-glutamyl transferase 
HGB 
Hemoglobin 
In 
Inches 
IP 
Investigational product 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat population 
IU 
International units 
K 
Potassium 
λz 
Terminal phase rate constant 
LDH 
Lactate dehydrogenase 
LFTs 
Liver function tests 
LLN 
Lower limit of normal 
MedDRA 
Medical Dictionary for Regulatory Activities Terminology 
mg 
Milligrams 
mL 
Milliliter 
mmHg 
Millimeters of mercury 
msec 
Milliseconds 
Na 
Sodium 
ng 
Nanograms 
 
PET-MF 
Post Essential Thrombocythemia-Myelofibrosis 
 
PMF 
Primary Myelofibrosis 
PP 
Per-protocol population 
PPV-MF 
Post Polycythemia Vera-Myelofibrosis 
RBC 
Red blood cell count 
SAE 
Serious adverse event 
SAS 
Statistical Analysis System  
SBP 
Systolic blood pressure 
SGOT 
Serum glutamic oxaloacetic transaminase 
SGPT 
Serum glutamic pyruvic transaminase 


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Table 1: 
List of Abbreviations (Continued) 
Abbreviation 
Term 
t1/2 
Terminal phase half-life 
tmax 
Time of occurrence of Cmax 
TIBC 
Total iron binding capacity 
UIBC 
Unsaturated iron-binding capacity 
ULN 
Upper limit of normal 
WBC 
White blood cell count 
WHO 
World Health Organization  


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2. 
INTRODUCTION 
The purpose of this document is to provide a detailed statistical analysis plan (SAP) for the data 
collected during the conduct of the study protocol (entitled “An open label assessment of safety 
and efficacy of ruxolitinib (INCB018424) in subjects with primary myelofibrosis (PMF), post 
essential thrombocythemia-myelofibrosis (PET-MF) and post polycythemia vera-myelofibrosis 
(PPV-MF) who have platelet counts of 50 x 109/L to 100 x 109/L”, Amendment 1 dated 
17 August 2011) which will be analyzed, summarized, and presented in the clinical study report 
(CSR).  The case report form (CRF) version covered by this SAP is Study Design Version 1.6 
(dated 28 July 2011, generated by Central Designer™). 
Section 4 of the protocol provides a detailed description of the investigational product, target 
patient population, the rationale for doses to be examined, and the potential risks and benefits of 
ruxolitinib (INCB018424). 


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives and Endpoints 
3.1.1. 
Study Objectives 
Primary Objectives: 
 To determine the effects of ruxolitinib on spleen volume and symptom burden in 
patients with PMF, PPV-MF, and PET-MF who have a baseline platelet count of 
50 x 109/L to 100 x 109/L.  
 To determine the safety and tolerability of ruxolitinib in subjects with PMF, PPV-MF, 
and PET-MF who have a baseline platelet count of 50 x 109/L to 100 x 109/L. 
Secondary Objective: 
 To determine an appropriate dosing strategy for subjects with low platelets. 
3.1.2. 
Study Endpoints 
3.1.2.1. 
Co-Primary Endpoints 
 Correlation of percent change from baseline in spleen volume at Week 24 versus final 
titrated dose. 
 Correlation of percent change from baseline in total symptom score as measured by 
the modified MFSAF v2.0 diary at Week 24 versus final titrated dose. 
3.1.2.2. 
Safety Endpoint(s) 
 Safety and tolerability will be assessed by monitoring the frequency, duration, and 
severity of adverse events (AEs), performing physical examinations, collecting vital 
signs, collecting laboratory data for hematology, serum chemistry, coagulation 
parameters, and urinalysis.  In addition, analyses will include: 
 Proportion of subjects with new onset Grade 4 thrombocytopenia events as 
assessed by CTCAE v4.03; 
 Proportion of subjects with new onset Grade 2 or higher hemorrhage as assessed 
by CTCAE v4.03. 


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3.1.2.3. 
Secondary Endpoints 
 Percent change from baseline in spleen volume at Week 24. 
 Percent change from baseline in total symptom score as measured by the modified 
MFSAF v2.0 diary at Week 24. 
 Proportion of subjects with ≥ 35% reduction from baseline in spleen volume at 
Week 24. 
 Proportion of subjects with ≥ 10% reduction from baseline in spleen volume at 
Week 24. 
 Proportion of subjects with ≥ 50% improvement from baseline in total symptom score 
as measured by the modified MFSAF v2.0 diary at Week 24. 
 Change and percentage change from baseline in spleen length as measured by 
palpation at each visit where the parameter is assessed. 
3.2. 
Statistical Hypotheses 
The null hypothesis is that the correlation between percent change in spleen volume or total 
symptom score and final titrated dose is zero.  The alternative hypothesis is that the correlation is 
not zero. 


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4. 
STUDY DESIGN 
4.1. 
Overall Description 
This is an open label study of 24 weeks duration of ruxolitinib in subjects with PMF, PPV-MF, 
and PET-MF.  The study is comprised of 4 phases (see protocol Section 7.1, Overall Study 
Design): 
Screening:  up to 21 days. 
Baseline:  exactly 7 days. 
Treatment Phase:  24 weeks.  For subjects receiving benefit from treatment, further 
participation may continue up to the time of commercial availability of ruxolitinib. 
Follow-up Phase:  30 to 37 days after the last dose of ruxolitinib is taken. 
All subjects will begin dosing at 5 mg bid ruxolitinib.  Doses should be taken morning and 
evening, approximately 12 hours apart, and without regard to food. 
Doses of ruxolitinib may be increased in 5 mg qd increments up to 10 mg bid starting at the 
Week 4 visit and at subsequent study visits (no more than every 4 weeks) if subjects meet 
prespecified criteria (refer to protocol Section 8.6, Dose Adjustments). 
Doses may not exceed 10 mg bid except in subjects who continue to meet the dose escalation 
criteria (see Protocol, Section 8.6, Dose Adjustments), and who have, in addition, a PGIC score 
of minimally worse, much worse, or very much worse while receiving 10 mg bid.  Such subjects 
may continue dose escalation to a maximum dose of 15 mg bid. 
Doses may never exceed 15 mg bid, and no dose increases may occur after Week 16. 
Subjects will be required to decrease the dose for platelet count < 35 x 109/L, and to hold 
administration for platelet count < 25 x 109/L.  Subjects will have the option to restart or 
re-escalate the dose with improving platelet count. 
Subjects will be required to interrupt administration for any Grade 2 or higher hemorrhage 
events.  Subjects will be able to restart ruxolitinib administration with resolution of Grade 2 
events; restart after a second event requires review and discussion of pertinent data with the 
sponsor.  Restarts of ruxolitinib will only be permitted in some cases of Grade 3 and 4 events, 
after review and discussion of pertinent data with the sponsor. 
Sites will provide information on incidents of Grade 4 thrombocytopenia and Grade 3 and 
Grade 4 hemorrhage events via FAX to the sponsor within 24 hours of learning of the event.  
The overall incidence of these events will be continuously monitored by the sponsor, and with 
ongoing data review, could result in a temporary hold for further enrollment, a reduction in the 
maximum allowable dose for subjects in the study, or a protocol amendment to modify dose 
titration rules (see protocol Section 11.7, Study Safety Monitoring). 


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4.2. 
Scheduled Visits 
Table 2 (source: protocol Table 3) and Table 3 (source: protocol Table 4) on the next pages 
provide detailed study visits and measurements of safety and efficacy variables defined for this 
study. 


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Table 2: 
List of Assessments 
 
Screening  
 
Baseline 
 
Day 
1 
Weeks 1,2, 
3,5,6,7,10, 14, 
18, 28 and q4 
weeks 
thereafter 
Week 
4 
Week 
8 
Week 
12 
Week 
16 
Week 
20 
Week 
24 
Extension 
Phase Visits 
(q12 weeks 
after Week 24) 
End of 
Treatment or 
Early 
Termination 
Visit (EOT) 
Follow-Up 30-
37 days after 
last dose of 
ruxolitinib or 
EOT visit 
Evaluation/window 
Day -28 to 
-8 
Day -7 to 
-1 
Day 
1 
± 3  
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 days 
± 5 days 
 
Assign Subject Number 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent / 
Eligibility Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Prior Medical & 
medication history  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medication 
review 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Transfusion history/status 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Discontinue prior MF 
therapies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Screening Symptom Form 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Record AEs 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination  
X 
X 
 
 
 
 
X 
 
 
X 
X 
X 
X 
Spleen Palpation 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
BM biopsy  
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
MRI of upper and lower 
abdomen and pelvis 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
Modified MFSAF v2.0  
 
Diary is completed each evening from Day -7 to the Week 24 visit 
 
 
 
Dispense and/or Bring 
MFSAF v2.0 diary to visit 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
 
 
PGICb 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
ECOG status 
X 
X 
 
 
X 
X 
X 
 
 
X 
X 
X 
 
Dispense reminder card 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Contact IVRS 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Administer study drug 
during visit 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
Dispense study drug 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Drug accountability 
assessment 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
a If not completed at Screening visit, and biopsy in prior 2 months is not available. 
b PGIC = Patient Global Impression of Change (protocol Appendix V). 


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Table 3: 
Table of Laboratory Assessments 
 
Screening  
 
Baseline 
 
Day 
1 
Weeks 1,2, 
3,5,6,7,10, 
14, 18, 28 
and q 4 
weeks 
thereafter 
Week 
4 
Week 
8 
Week 
12 
Week 
16 
Week 
20 
Week 
24 
Extension 
Phase Visits 
(q12 weeks 
after Week 24) 
End of 
Treatment  or 
Early 
Termination 
Visit (EOT) 
Follow-Up 
30 to 37 days 
after last dose 
of ruxolitinib 
or EOT visit 
Laboratory Assessment 
Day -28 to 
-8 
Day -7 to 
-1 
Day 
1 
± 3  
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 5 days 
± 5 days 
± 5 days 
 
Serum Chemistry 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panel 
X 
X 
 
 
 
 
X 
 
 
X 
X 
X 
X 
Lipid Panel 
 
X 
 
 
X 
 
X 
 
 
X 
X 
X 
X 
Serum Pregnancy Testa 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Urine Pregnancy Testa 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Serology for HIV, 
HBV, HCV 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysis 
 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
a Women of childbearing potential only. 


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4.3. 
Sample Size Considerations 
Approximately 150 subjects will be enrolled in order to assess (on the efficacy side) the dose-
effect correlation (between percent changes from baseline in spleen volume/total symptom score 
at Week 24 and final titrated dose level).  Using an alpha of 5% (2-sided), this sample size gives 
a power of 96% to reject the null hypothesis of no dose-effect correlation if the true correlation is 
0.30.  The power is 87% if the true correlation is 0.25, and the power is 69% if the true 
correlation is 0.20.  These calculations are based on Cohen 1988, Formula 12.3.4.  SAS 
procedure POWER is used and the power curves are displayed in Figure 1. 
Figure 1: 
Power and Sample Size Curves for 3 Alternative Hypotheses on the Level of 
Dose-Effect Correlation 
 
It is noted that the above sample size calculation is based on the rationale that the first primary 
endpoint (correlation between percent change from baseline in spleen volume at Week 24 by the 
final titrated dose ) is powered following the procedure of the sequential test used for this study 
(see Section 5.4.2).  At the given sample size, power can also be assessed for the second 
co-primary endpoint (correlation between percent change from baseline in total symptom score 
at Week 24 by the final titrated dose. 
In addition, the mean percent change from baseline in spleen volume measured by MRI, and 
mean percent change from baseline in total symptom score at Week 24 will each be estimated 
with a 95% confidence interval.  With 150 subjects, the half-length of the 95% confidence 


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interval of the change from baseline in spleen volume at Week 24 is approximately 3%.  This is 
based on the Phase 3 study (INCB 18424-351), where the standard deviation of the percent 
change from baseline in spleen volume at Week 24 was 19%.  


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5. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
5.1. 
Scheduled Analyses 
In addition to the planned final CSR analysis, interim data reviews by the DMC focused on 
events of thrombocytopenia and hemorrhage on predefined schedules are planned. 
 28 days after 20 subjects have enrolled. 
 28 days after 40 subjects have enrolled. 
 Other reviews can be scheduled only if the DMC deems it necessary that additional 
data would need to be reviewed to assess safety parameters as specified by the 
protocol. 
Since all interim data reviews are focused on safety only, there is no alpha-spend of the final 
CSR efficacy analysis. 
5.1.1. 
First DMC Data Review Meeting 
When the 20th patient is enrolled, additional screening of subjects will be paused for at least 
28 days and up to approximately 42 days.  Subjects in screening at that time will be allowed to 
enroll if they are found to be eligible.  During this period, enrolled subjects will be allowed to 
continue on study per the protocol.  At least 28 days from the enrollment of the 20th subject, 
safety data will be assessed by the DMC and the sponsor.  Subjects will be analyzed if they have 
completed at least 28 days on the study or have discontinued the study because of Grade 4 
thrombocytopenia or > Grade 2 hemorrhage.  Demographics, baseline characteristics, and dose 
exposure will be summarized for those subjects.  Also AE and laboratory parameters will be 
analyzed. 
5.1.2. 
Second DMC Data Review Meeting 
At least 28 days from the enrollment of the 40th subject, safety data will be assessed by the 
DMC and the sponsor.  Since the first dose escalation opportunity in the study is at Day 28 and 
the starting dose for all subjects of 5 mg bid will have been adequately assessed for safety at the 
first safety review after the enrollment of 20 patients, screening will not be suspended following 
enrollment of the 40th subject.  If safety of the 5 mg bid dose is not clear from this first data 
review, the DMC and the sponsor may mandate a hold on screening at the review that occurs 
with enrollment of the 40th subject.  Subjects will be analyzed when they have completed at least 
28 days on the study or discontinued due to Grade 4 thrombocytopenia or > Grade 2 hemorrhage.  
Demographics, baseline characteristics, and exposure will be summarized for those subjects.  
Also AE and laboratory parameters will be analyzed. 
More details were described in the protocol Section 11.7, Data Safety Monitoring and the 
corresponding DMC charter. 


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5.2. 
Treatment Groups 
Subjects will be summarized as 1 group regardless of dose titration.  For certain summaries of 
AEs by dose received (details can be found in the appendix of table shells), subjects will be 
grouped into the following categories:  ≤ 5 mg, > 5 to 10 mg, > 10 to 15 mg, > 15 to 20 mg, 
> 20 to 25 mg, and > 25 mg based on the final titrated total daily dose (see Section 5.9.3.1). 
In addition, for the summary of exposure, final titrated dose groups as defined above may be 
used as treatment groups and additional efficacy analysis may utilize these dose categories. 
5.3. 
Analysis Populations 
5.3.1. 
Safety Population 
All subjects who are enrolled and have taken at least 1 dose of study drug comprise the safety 
population.  The safety population will be used to conduct all safety analyses, including baseline 
and demographics. 
5.3.2. 
Intent-to-Treat Population 
All subjects who are enrolled and have taken at least 1 dose of study drug constitute the intent-
to-treat (ITT) population.  All efficacy analyses will be conducted using the ITT population.  It is 
noted that the ITT population is effectively identical to the safety population for this study. 
5.3.3. 
Per-Protocol Population 
The per-protocol (PP) population includes those subjects in the ITT population who are 
considered to be sufficiently compliant with the protocol.  The PP population will be used for 
certain supportive sensitivity analysis of efficacy and safety.  Derivation rules for PP population 
can be found in Section 5.9.6. 
5.4. 
Statistical Methodology 
5.4.1. 
General Methodology 
Unless otherwise denoted, SAS procedures (Version 9 or above) will be employed for the 
generation of all tables, graphs, and statistical analyses. 
 
 
  Descriptive summaries for continuous 
variables will include, but not be limited to, the number of observations, mean, standard 


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deviation, median, minimum, and maximum.  Descriptive summaries for categorical variables 
will include the number and percentage of subjects in each category. 
The Safety Population will be used for all safety analyses, and the ITT population will be used 
for all efficacy analyses.  The primary efficacy analysis will also be repeated by using the 
PP population. 
 
 
5.4.2. 
Control of Type I Error 
All confidence intervals will be 95% and tests will be performed at 2-sided 0.05% level.  
Because of the exploratory nature of the study analyses, except for tests regarding the coprimary 
endpoints, no multiplicity adjustment will be performed.  To control overall Type I error in 
testing hypotheses regarding the coprimary endpoints, a sequential testing procedure will 
be used. 
 Step 1 will test the correlation between percent change from baseline in spleen 
volume at Week 24 and the last titrated dose level, and only if the null hypothesis of 
no correlation can be rejected, Step 2 will be carried out. 
 Step 2 will test the correlation between percent change from baseline in total 
symptom score at Week 24 and the last titrated dose level.  In case Step 1 fails to 
reject the null hypothesis, the inferential comparison (p-values) of Step 2 will still be 
generated for descriptive purposes only. 
5.5. 
Baseline Values 
A baseline value (for analysis purposes) is the last, non-missing measurement obtained during 
the screening visit and baseline visit unless otherwise stated, with the exception of laboratory 
values and the total symptom score.  For laboratory assessments, values obtained on Day 1 
(see Section 5.6) will be included in deriving baseline as the laboratory values are scheduled to 
be obtained before on-site administration of study drug.  For total symptom scores, different 
derivation rules will be used (see Section 5.9.2.2). 
5.6. 
Day 1, Study Day, and Study Time Points 
Day 1 is the date of first dose of study medication.   
The study day at a visit/reporting date will be calculated by the visit/reporting Date – Day 1 + 1.  
This study day will be subtracted by 1 if it is less than or equal to zero, so that a study day of 
zero will never occur.  A study day of -1 indicates 1 day prior to Day 1. 
Other study time points will use nominal weeks, such as Weeks 4, 8, 12, etc, according to the 
Schedules of Assessments (see Table 2 and Table 3), as recorded on the CRF, regardless of the 
actual time windows these visits fall into, unless otherwise stated.  This is especially true for 
analyses such as laboratory values and vital sign values where by-study-week summaries are to 
be generated, as well as for spleen palpation length over time summaries.  


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Exceptions to the statements about study time points described above include (but are not limited 
to) spleen volume at Week 24 (see Section 5.9.1), total symptom score at several major study 
time points (see Section 5.6), and final titrated dose level (see Section 5.9.3.1).  
Another exception is related to spleen palpation length analysis.  Per study CRF design, if a 
subject’s EOT Visit coincides with a scheduled visit, then in database, only EOT Visit data will 
be available.  So when a subject has spleen palpation length data collected on an “EOT Visit” (or 
End of Extension Phase Visit, as appropriate and if applicable), an effort will be made to see if 
the data actually falls into a scheduled visit, such as Weeks 4, 8, 12, 16, 20, 24 (treatment phase), 
36, 48, 60, etc (extension phase) by using the window of Week of scheduled visit*7 ± 5 days. 
Following the situation described above, if EOT data contain spleen volume measurements and 
the situation is not resolved by the time of database lock, then similar effort will be made by 
treating spleen volume data labeled from “EOT Visit” as data collected from unscheduled visit.  
See Section 5.9.1 for how spleen volume data from unscheduled visits will be used in the 
analysis. 
The situation described above is not an issue of importance to other variables such as laboratory 
values, since in analyses by time point, “EOT” will be one of the time points to be displayed. 
5.7. 
Concomitant Medications and Partial Dates 
Prior medication is defined as any non-study medication started prior to the date of first study 
drug administration. 
Concomitant medication is defined as any non-study medication that is:  
 Started before the date of first study drug administration and is ongoing throughout 
the study or ends on/after the date of first study drug administration; 
 Started on/after the date of first study drug administration and is ongoing or ends 
during the course of study medication. 
A prior medication could also be classified as “both prior and concomitant medication” if the end 
date is on or after first dose of study medication.  In the listing, it will be indicated whether or not 
a medication is prior-only, concomitant-only, or both prior and concomitant medication. 


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The start/stop dates recorded by the Investigator and his/her research staff in the eCRF will be 
used to identify when a concomitant medication was taken during the study.  Any missing start 
date must be queried for resolution.  Unresolved missing start dates will be handled according to 
the following order of steps. 
 If the date is completely missing, the medication will be considered both prior and 
concomitant. 
 If only the day is missing, and the last day of the month is prior the first dose date on 
Day 1, then the concomitant medication will be considered as starting prior to Day 1, 
and the incomplete date will be handled as if it is the last day of the month.  
 If only the day is missing, and the first day of the month is after the first dose date on 
Day 1, then the concomitant medication will be considered as starting after Day 1, 
and the incomplete date will be handled as if it is the first day of the month. 
 If only the day is missing, and the month is equal to the month of the first dose date 
on Day 1, then the missing day will be handled as if it is the first day of the month. 
 If both the month and day are missing, and the last day of the year is prior to the first 
dosing date on Day 1, then the concomitant medication will be considered as starting 
before Day 1, and the incomplete date will be handled as if it is the last day of the 
year.  Otherwise, the missing date will be handled as if it is the first day of the year. 
5.8. 
Adverse Events and Missing Data 
A treatment-emergent adverse event (TEAE) is any AE either reported for the first time or 
worsening of a pre-existing event after first dose of study medication.  Analysis of AEs will be 
limited to TEAEs, but data listings will include all AEs. 
Severity of AEs will be described and graded using the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE).  CTCAE v4.03 is used for this protocol.  If 
the toxicity is not included in the CTCAE v4.03 criteria it will be rated on a 1 to 4 scale as 
follows: mild = 1; moderate = 2; severe =3; and life-threatening = 4. 
An AE will also be assessed by its relationship to study medication as well as by seriousness.  
These assessments will be directly from data collected on eCRFs and are described in details in 
the protocol.  
Any missing onset date, causality, or severity must be queried for resolution.  Unsolved missing 
values will be handled according to the following rules: 
 An unsolved missing causality will be considered treatment related 
 An unsolved missing severity will be identified as an unknown severity  


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 For purposes of analysis, all AEs will be considered TEAEs unless the AE can 
unequivocally be defined as not treatment emergent.  Therefore, an unsolved missing 
onset date will be considered treatment emergent, with the following examples 
illustrating exceptions: 
 If the stop/resolution date is before the first dose date on Day 1, then the AE will 
be considered as not being treatment emergent. 
 If both the month and day are missing, and the last day of the year is before the 
first dose date on Day 1, then the AE will not be considered treatment emergent.  
 If only the day is missing, and the last day of the month is before the first dose 
date on Day 1, then the AE will not be considered treatment emergent. 
 If only the day is missing, and the first day of the month is after the first dosing 
date on Day 1, then the AE will be considered treatment emergent. 
5.9. 
Variable Definitions and/or Derivation Rules 
5.9.1. 
Spleen Volume Value at Week 24 
If Week 24 spleen volume value is obtained in the manner of by-schedule visit, it will be used as 
the analytic value for study analysis regardless of the actual time window it falls into.  However, 
if the only values available are from unscheduled visits, then the last available value within the 
window of Day 141 to Day 175 (=168 + 7 days) will be used as Week 24 spleen volume analytic 
value.  When spleen volume data are available for both by-schedule and unscheduled visits 
(within the window), the value from the scheduled visit will be used. 
5.9.2. 
Total Symptom Score 
5.9.2.1. 
Daily Total Symptom Score 
Daily total symptom score is derived as the sum of 6 individual symptom scores (the total score 
excludes scores for degree of inactivity); this score will be missing if there are any missing 
individual scores.  Observations with an un-resolved missing date will be excluded from 
analysis. 
5.9.2.2. 
Baseline Total Symptom Score 
Baseline value of total symptom score is derived as the average of the prorated daily total 
symptom score for the 7 days before the first dose on Day 1 (ie, from Day -7 to Day -1).  If ≥ 4 
daily total symptom score values are missing during this period of time, the baseline total 
symptom score value is set as missing. 


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5.9.2.3. 
Total Symptom Score at Weeks 4, 8, 12, 16, 20, and 24 
Week X (where X = 4, 8, 12, 16, 20, and 24) total symptom score is derived as the average of the 
daily total symptom scores collected from the last 28 consecutive days covering the interval 
between up to Day (X+n)*7, where n is 1 for Week 24 and 0 otherwise, and Day (X-4)*7 + 1 as 
presented in Table 4. 
Table 4: 
Windows for Total Symptom Score at Given Study Time Points 
Study Time Point 
Window 
Note 
Week 4 
Day 1 to Day 28 
 
Week 8 
Day 29 to Day 56 
 
Week 12 
Day 57 to Day 84 
 
Week 16 
Day 85 to Day 112 
 
Week 20 
Day 113 to Day 140 
 
Week 24 
Last 28 days of the window from 
Day 141 to the last day when daily 
total symptom score value is 
available and it is ≤ Day 175.  
If the last evaluation day is 
before Day 168-7 = 161 then 
total symptom score will be 
set as missing for Week 24. 
 
Total symptom score for given study time points displayed above will be missing if there are 
more than 8 values missing in the 28-day window.  It should be noted that a score of 0 is not a 
missing value. 
5.9.3. 
Dosing Level and Compliance 
5.9.3.1. 
Final Titrated Dose Level 
The analytic value of the last titrated dose level will be derived as the average of the total daily 
dose (excluding periods of dose interruption) during the time interval of Day 141 and Day 168, 
or the last 28 days of available dosing data (for subjects who discontinued treatment early).  All 
available data points in the time interval will be used for this calculation. 
5.9.3.2. 
Last Average Daily Dose Level During the Treatment Period 
For subjects who have the analytic value of the last titrated dose level derived, the last average 
daily dose level during the treatment period will be the same.  For subjects who discontinued and 
do not have last titrated dose level derived, it will be the average of the last 28 days (excluding 
periods of dose interruption) of treatment.  For subjects who discontinued study before Day 28, it 
is the same as the average daily dose level during the study. 


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5.9.3.3. 
Study Drug Compliance 
Study drug compliance (%) is calculated as 
100  [total dose taken]/[total dose prescribed] 
where total dose taken is calculated as before, and total dose prescribed will be based on the 
dosing prescription as collected through the CRF pages of EX domain.  If prescribed dose 
collected from EX domain is 0, it also indicates a prescribed dose interruption; in addition, dose 
reduction or increase as recorded in EX domain are all regarded as investigator-mandated 
prescriptions on study drug for the subjects to follow. 
Study drug compliance will be calculated only for the pre-extension phase of 24 weeks.  Based 
on need of exploratory analysis, compliance for other periods may be derived as well. 
Because of the eCRF design, other than calculating study drug compliance, data collected on the 
EX domain of the eCRF will be used as actual study drug administration information in order to 
carry out other dose-response type analyses, such as AEs by the dose level before the AE 
(Section 5.9.3.4).  In the case of a serious discrepancy between the prescribed dose and the dose 
received, additional actions may be taken to modify data entries.  
5.9.3.4. 
Last Dose Level Prior to an Adverse Event 
The last dose level prior to an AE is derived as the last non-zero dose (from EX domain) prior to 
the day an AE occurred.  The reason to use “prior to the day” which excludes the day on which 
an AE occurred is that daily dose is divided into morning and evening doses and no dose 
administration time is collected on eCRF, making the last dose prior to an AE difficult to verify 
if “on the same day” dose levels are also included in the derivation. 
It is noted that the data collected through the EX domain is treated as actual doses (rather than 
the prescribed dose schedule, as is the case of deriving compliance, defined earlier).  This 
approach is used throughout when dose-response analyses (for both safety and efficacy) are 
carried out. 
5.9.4. 
Blood Transfusion Independence at Baseline 
Transfusion independence at baseline is defined in 2 ways. 
1. It is defined as receiving no transfusions (of red blood cell products) in the 8 weeks 
before Day 1. 
2. It is defined as receiving no transfusions (of red blood cell products) in the 12 weeks 
before Day 1. 


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5.9.5. 
Blood Transfusion Independence at Post-Baseline 
Transfusion independence during post-baseline period is defined in 2 ways. 
1. It is defined as receiving no transfusions (of red blood cell products) during the final 
8 weeks of a subject’s participation before the data cutoff date. 
2. It is defined as receiving no transfusions (of red blood cell products) during the final 
12 weeks of a subject’s participation before the data cutoff date. 
5.9.6. 
Derivation of Per-protocol Population 
The following process will be followed in deriving the PP population.  
 Analysis programming team will generate a study drug compliance listing (by 
Week 24) and pass it to the clinical team.  
 Based on study drug compliance and protocol deviation information from the clinical 
monitoring database, the clinical team will generate a PP population file indicating 
the membership of subjects to this population, and pass this file to the analysis 
programming team. 
 Analysis programming team will use the PP population file to set the population 
indicator in analysis datasets for analysis. 
In addition, the clinical team will also generate a source document containing all protocol 
deviations collected through the clinical monitoring process and pass it to the analysis 
programming team for generation of the protocol deviation listing. 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
6.1. 
Baseline and Demographics 
Descriptive summaries for demographic and baseline characteristics will include, but not limited 
to, age, age group (≤ 65 vs > 65), sex, race, ethnicity, weight, height, ECOG performance status, 
transfusion history status, 
 history of usage of any and all other 
drugs used to treat MF, and spleen palpation length.  A data listing will be provided. 
6.2. 
Disposition and Enrollment 
The number and percentage of subjects enrolled, completed, and withdrawn from the study with 
a primary reason of withdrawal will be summarized for the safety population.  Per study design, 
disposition is applicable to the following 3 contexts:  End of Treatment Phase or Early 
Termination, End of Extension Phase or Early Termination, and End of Study.  Summaries will 
be provided for each of these 3 contexts and support listing will also be provided. 
In addition, a listing for screen failures will be provided and will include information regarding 
demographics and eligibility status.  
6.3. 
Protocol Deviations 
Protocol deviations captured will be listed in subject data listings. 
6.4. 
Exposure  
For subjects in the safety population, descriptive statistics will be provided for duration of 
treatment (defined as days or weeks between first dose and last dose inclusive disregard dose 
interruptions in between); total patient years of exposure; total dose (mg); average daily dose 
(mg), which is defined as the total dose divided by duration of treatment; last titrated dose level 
(mg/day); and last average daily dose.  Average daily dose (mg) will also be summarized by the 
major study time points (ie, during Weeks 1, 4, 8, 12, 16, 20, and 24).  A data listing will be 
provided. 
6.5. 
Study Medication Compliance 
Overall compliance (%) will be summarized and a data listing will be provided. 
6.6. 
Medical History 
Medical history will be summarized.  Summaries will include the number and percentage 
of subjects with significant medical history for each body system/organ class listed on the 
CRF page. 


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6.7. 
Concomitant Medication 
Concomitant medications will be summarized by WHO drug class and WHO drug term.  In the 
data listing, each record will be flagged as whether or not the medication is of prior, 
concomitant, or both prior and concomitant usage. 
Prior medication information will also be reviewed by the clinical monitor to identify anti-cancer 
medication received by subjects prior to enrollment into the study.  Prior anti-cancer medication 
data will be summarized as well as listed. 
6.8. 
Blood Transfusion Dependency 
The proportion of subjects who were blood-transfusion dependent at baseline and at 
post-baseline will be summarized by baseline platelet count group (50-75 GI/L vs > 75 GI/L).  A 
shift summary including the number and percentage of subjects who changed transfusion status 
was also produced by baseline platelet count group.  In addition, the total units and average 
monthly units of transfusions will also be summarized by baseline platelet count group. 


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7. 
EFFICACY ANALYSES 
7.1. 
Primary Efficacy Endpoints 
For the co-primary endpoints (correlation of percent change from baseline in spleen volume at 
Week 24 versus final titrated dose, and correlation of percent change from baseline in total 
symptom score at Week 24 versus final titrated dose), the following t-test will be used generate 
the p-values: 
0
2
2
|
~
1
2
H
t
r
n
r
T
n




 
where r is the product-moment (Pearson) correlation coefficient, n is the sample size of paired 
observations, and 
0
2 |
~
H
tn
 means the test statistic will follow a t-distribution with n-2 degrees 
of freedom under the null hypothesis.  
In addition, correlation estimate and the corresponding approximate 95% confidence intervals 
will be calculated by using the Fisher’s r-to-z transformation.  The following SAS codes will be 
used to generate the all these statistics: 
ODS OUTPUT  FisherPearsonCorr=correst PearsonCorr=pval; 
PROC CORR FISHER PEARSON; 
     VAR X Y; 
RUN; ***CORREST has point estimate and CI from Fisher z-transformation, and 
PVAL has p-value and the raw Pearson correlation coefficient ***; 
The analysis will be generated for the ITT population.  The same analysis will be repeated by 
using The PP population as a sensitivity analysis (Sensitivity Analysis 1). 
An additional sensitivity analysis may be generated in dealing with missing data by using 
multiple imputation procedures (Sensitivity Analysis 2).  
7.2. 
Secondary Endpoint(s) and Analyses 
For the following secondary endpoints, descriptive summaries will be provided for overall as 
well as for the final titrated dose group: 
 Percent change from baseline in spleen volume at Week 24. 
 Percent change from baseline in total symptom score at Week 24. 
 Proportion of subjects with ≥ 35% reduction from baseline in spleen volume at 
Week 24. 
 Proportion of subjects with ≥ 10% reduction from baseline in spleen volume at 
Week 24. 


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 Proportion of subjects with ≥ 50% improvement from baseline in total symptom score 
at Week 24. 
 Change and percentage change from baseline in spleen length as measured by 
palpation at each visit where the parameter is assessed. 
Supporting data listings will also be provided. 


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8. 
SAFETY ANALYSES 
8.1. 
Adverse Events 
The following summaries will be produced for AEs for the overall subject group: 
High Level Summary 
 Number (%) of subjects reporting any TEAEs 
 Number (%) of subjects reporting any DLT 
 Number (%) of subjects reporting any treatment-related AEs 
 Number (%) of subjects reporting any SAEs 
 Number (%) of subjects reporting any Grade 3 or 4 AEs 
 Number (%) of subjects who discontinued study drug because of AEs 
 Number (%) of subjects with study drug dose reductions because of AEs 
 Number (%) of subjects who died 
By MedDRA Term: 
 Number (%) of subjects reporting TEAEs by organ class and preferred term 
 Number (%) of subjects reporting Grade 3 or 4 TEAEs by organ class and preferred 
term 
 Number (%) of subjects reporting treatment-related AEs by organ class and preferred 
term 
 Number (%) of subjects reporting treatment-emergent SAEs by organ class and 
preferred term 
 Number (%) of subjects reporting treatment-emergent non-serious AEs by organ class 
and preferred term 
In addition, a listing of DLTs will be provided.  
These TEAEs occurring in 2 or more subjects in the safety population will be summarized by the 
Medical Dictionary for Regulatory Activities (MedDRA) preferred term for all causalities as 
well as for treatment-related causalities.  


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Proportion of subjects with new onset of Grade 4 thrombocytopenia events based on laboratory 
data and as measured by CTCAE grades will be summarized.  The hazard function of time to 
onset of Grade 4 thrombocytopenia will be estimated using life table method. 
Proportion of subjects with new onset of Grade 2 or higher hemorrhage based on preferred terms 
included in the Standardized MedDRA Query (SMQ) for “Haemorrhage terms (excluding 
laboratory terms) (SMQ)” and as measured by CTCAE grades will be summarized.  The hazard 
functions of time to onset will be estimated using life table method. 
Proportion of subjects with new onset of Grade 4 anemia based on laboratory data and as 
measured by CTCAE grades will be summarized.  The hazard functions of time to onset will be 
estimated using life table method. 
For the above 3 types of AEs, additional analyses using summary tables as well as data listings 
may be provided taking into account the blood transfusion status at baseline and post-baseline 
blood transfusion history.  
Selected maximal severity AE summary tables will also be generated by the dose level the 
subject received. 
8.2. 
Laboratory Values 
Clinical laboratory tests including hematology, serum chemistry, coagulation, and urinalysis will 
be performed for each subject during the study in accordance with the Schedule of Observations 
(see Table 3).  If specific safety issues arise, additional, unscheduled laboratory tests/analyses 
may be performed at the discretion of the investigator. 
All test results and associated normal ranges from central laboratories will be reported in 
Standard International units (SI unit).  All tests with numeric values will have a unique unit per 
test.  Any laboratory results and associated normal ranges from local laboratories will be 
converted to SI units.  When there are multiple laboratory values for a subject’s particular test at 
a given visit, the last non-missing value will be used in the by-visit tabulations and summaries 
described below. 
Numeric laboratory values will be summarized descriptively, and non-numeric test values will be 
tabulated by study visit using data collected from scheduled visits. 
For those tests with available normal ranges, the number and percentage of subjects with the 
laboratory values being low, normal, or high will be calculated for each test.  A shift summary 
will be produced, which presents the change from baseline as shown in Table 5. 


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Table 5: 
Example Shift Summary for Applicable Laboratory Assessments 
At a Post-baseline Visit 
 
At Baseline 
Missing 
Low-Only 
Normal 
High-Only 
Both Low and High 
Missing 
N (%) 
N (%) 
N (%) 
N (%) 
N (%) 
Low 
N (%) 
N (%) 
N (%) 
N (%) 
N (%) 
Normal 
N (%) 
N (%) 
N (%) 
N (%) 
N (%) 
High 
N (%) 
N (%) 
N (%) 
N (%) 
N (%) 
Total 
N (%) 
N (%) 
N (%) 
N (%) 
N (100%) 
Laboratory test values outside the normal range will be assessed for severity based on severity 
CTCAE grade or CTCAE grade criteria (where clinical intervention is required for CTCAE 
grading).  Shift tables relative to baseline will be generated using all available data from 
scheduled and unscheduled visits. 
8.3. 
Vital Signs 
Descriptive statistics for measurements, as well as change from baseline values, will be provided 
for vital signs (blood pressure, heart rate, respiratory rate, and body temperature) at each 
assessment time.  Subjects exhibiting clinically notable vital sign abnormalities will be listed. 
A value will be considered an “alert” value if it is outside the established range and shows a 
change from baseline greater than 25%, according to the high and/or low threshold values listed 
in Table 6. 
Table 6: 
High and Low Threshold Values for Alert Vital Sign Observations 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 160 mm Hg 
< 85 mm Hg 
Diastolic blood pressure 
> 100 mm Hg 
< 50 mm Hg 
Respiratory Rate 
> 24 per minute 
< 8 per minute 
Heart rate 
> 100 bpm 
< 45 bpm 
mm Hg = millimeters of mercury; bpm = beats per minute. 
Alert vital sign data will also be listed. 
8.4. 
Electrocardiograms 
Electrocardiogram data collected at the screening visit will be listed.  If additional data are 
collected, they will be listed and may be summarized as appropriate. 


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9. 
CLINICAL PHARMACOLOGY/ 
 
 
9.2. 
Subject Demographic, Clinical Laboratory, and Disease-Related 
Variables 
Subject demographic assessments (age, weight, body mass index, sex, and race), disease-related 
evaluations (baseline platelet count, tumor type), and clinical laboratory measurements 
(creatinine clearance, ALB, total bilirubin, alkaline phosphatase, alanine aminotransferase, AST) 
may be explored as time independent predictors of 
 variability.   
9.3. 
Concomitant Medication 
CYP3A4 inhibitors and inducers may be may be tested as time dependent variables of 
 
variability if more than 15% of patients will take them as concomitant medications. 


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9.5. 
Pharmacokinetic-Pharmacodynamic Data Analysis 
The relationship between PK model predicted concentrations/parameters and pharmacologic, 
safety, and efficacy read-outs are planned.  A longitudinal analysis of platelets (absolute values 
or change from pre-dose) using predicted PK and baseline platelet values as covariates will be 
performed to assess platelet change over time.  The population PK model will be used to derive 
estimates of individual steady-state exposure measures for PK-PD analysis. 
9.6. 
Output 
A population PK report will be prepared in accordance with guidance of both US and EU 
regulatory authorities. 
10. 
LIST OF PLANNED TABLES, LISTINGS, AND FIGURES 
10.1. 
Tables 
Table Number 
Title 
Population 
 
Baseline and Demographic Characteristics 
14.1.1 
Summary of Subject Enrollment and Exit Status 
Safety 
14.1.2 
Summary of Demographics  
Safety 
14.1.3 
Summary of Baseline Characteristics 
Safety 
14.1.4 
Summary of Medical History by MedDRA System Organ Class and 
Preferred Term 
Safety 
14.1.5.1 
Summary of Prior Medications 
Safety 
14.1.5.2 
Summary of Concomitant Medications 
Safety 
14.1.5.3 
Summary of Prior Anti-Cancer Treatment 
Safety 
14.1.6.1 
Summary of Change in Status of Blood Component Transfusion 
Dependency by Baseline Platelet Count Group 
Safety 
14.1.6.2 
Summary of Blood Component Transfusions by Baseline Platelet Count 
Group 
Safety 
 
Efficacy 
14.2.1.1 
Summary of Correlations of Final Titrated Dose vs. Percent Change 
from Baseline in Spleen Volume at Week 24 and vs. Percent Change 
in Total Symptom Score at Week 24 
ITT 


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Table Number 
Title 
Population 
14.2.1.2 
Summary of Correlations of Final Titrated Dose vs. Percent Change 
from Baseline in Spleen Volume at Week 24 and vs. Percent Change 
in Total Symptom Score at Week 24: Sensitivity Analysis 1 
Per-Protocol 
14.2.1.3 
Summary of Correlations of Final Titrated Dose vs. Percent Change 
from Baseline in Spleen Volume at Week 24 and vs. Percent Change 
in Total Symptom Score at Week 24: Sensitivity Analysis 2 
ITT 
14.2.2.1 
Summary of Spleen Volume Data by Study Week and Final Titrated 
Dose Group 
ITT 
14.2.2.2 
Summary of Proportion of Subjects with >= 35% Reduction from 
Baseline in Spleen Volume at Week 24 by Final Titrated Dose 
Group 
ITT 
14.2.2.3 
Summary of Proportion of Subjects with >= 10% Reduction from 
Baseline in Spleen Volume at Week 24 by Final Titrated Dose 
Group 
ITT 
 
 
 
14.2.3.1 
Summary of Total Symptom Score Data by Study Week and Final 
Titrated Dose Group 
ITT 
14.2.3.2 
Summary of Proportion of Subjects with >= 50% Reduction from 
Baseline in Total Symptom Score by Study Week and Final Titrated 
Dose Group 
ITT 
14.2.4.1 
Summary of Spleen Palpation Length Data by Study Week and Final 
Titrated Dose Group 
ITT 
14.2.4.2 
Summary of Proportion of Subjects with >= 50% Reduction from 
Baseline in Spleen Palpation Length by Study Week and Final 
Titrated Dose Group 
ITT 
14.2.4.3 
Summary of Proportion of Subjects with >= 20% Reduction from 
Baseline in Spleen Palpation Length by Study Week and Final 
Titrated Dose Group 
ITT 
 
Safety: Exposure 
14.3.1.1    
Summary of Exposure and Duration of Exposure to Study 
Medication Through Week 24 
Safety 
14.3.1.2 
Summary of Exposure to Ruxolitinib Through Week 4 
Safety 
14.3.1.3 
Summary of Average Daily Dose of Ruxolitinib by Study Week 
Safety 
 
Safety: Adverse Events 
14.3.2.1 
Overall Summary of Treatment-Emergent Adverse Events by Dose 
Level Ever Received 
Safety 
 
 
 
14.3.2.2.1 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) by MedDRA System Organ Class, Preferred 
Term, and Maximum Severity 
Safety 


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Table Number 
Title 
Population 
14.3.2.2.2 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) by MedDRA System Organ Class, Preferred 
Term, and Dose Level Ever Received 
Safety 
 
 
 
14.3.2.3.1 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) by MedDRA Preferred Term (Sorted by 
Decreasing Frequency) and Maximal Severity 
Safety 
14.3.2.3.2 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) by MedDRA Preferred Term (Sorted by 
Decreasing Frequency) and Dose Level Ever Received 
Safety 
14.3.2.3.3 
Summary of Subjects Reporting Treatment-Emergent Hemorrhage 
Adverse Events (All Causalities) by MedDRA Preferred Term and 
Dose Level Ever Received 
Safety 
14.3.2.3.4 
Summary of Subjects Reporting Treatment-Emergent Hemorrhage 
Adverse Events (All Causalities) of Grade 3 or Higher by MedDRA 
Preferred Term and Dose Level Ever Received 
Safety 
 
 
 
14.3.2.4.1 
Summary of Subjects Reporting Treatment-Emergent Treatment-
Related Adverse Events (All Causalities) by MedDRA System 
Organ Class, Preferred Term, and Maximum Severity 
Safety 
14.3.2.4.2 
Summary of Subjects Reporting Treatment-Emergent Treatment-
Related Adverse Events (All Causalities) by MedDRA System 
Organ Class, Preferred Term, and Dose Level Ever Received 
Safety 
 
 
 
14.3.2.5.1 
Summary of Subjects Reporting Treatment-Emergent Serious 
Adverse Events (All Causalities) by MedDRA System Organ Class, 
Preferred Term, and Dose Level Ever Received 
Safety 
14.3.2.6 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) Leading to Study Medication Decrease or 
Interruption by MedDRA System Organ Class, Preferred Term, and 
Dose Level Ever Received 
Safety 
14.3.2.7 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) Leading to Study Discontinuation by 
MedDRA System Organ Class, Preferred Term, and Dose Level 
Ever Received 
Safety 
14.3.2.8 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) Leading to On-Study Death by MedDRA 
System Organ Class, Preferred Term, and Dose Level Ever 
Received 
Safety 
 
Safety: Laboratory Data 
14.3.3.1.1 
Summary of Laboratory Values – Hematology 
Safety 
14.3.3.1.2 
Shift Summary of Laboratory Values in Normal Ranges - 
Hematology 
Safety 
14.3.3.2.1 
Summary of Laboratory Values – Serum Chemistry 
Safety 
14.3.3.2.2 
Shift Summary of Laboratory Values in Normal Ranges – Serum 
Chemistry 
Safety 
14.3.3.3.1 
Summary of Laboratory Values – Coagulation 
Safety 
14.3.3.3.2 
Shift Summary of Laboratory Values in Normal Ranges – 
Coagulation 
Safety 
14.3.3.4.1 
Summary of Laboratory Values – Urinalysis 
Safety 
14.3.3.4.2 
Shift Summary of Laboratory Values in Normal Ranges – Urinalysis 
Safety 
14.3.3.5.1 
Shift Summary of Laboratory Values in CTC Grade - To the Worst 
Abnormal Value (Tests with One Directional CTC Grade) 
Safety 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
38 
Table Number 
Title 
Population 
14.3.3.5.2 
Shift Summary of Laboratory Values in CTC Grade - To the Worst 
Abnormal Value (Tests with Two Directional CTC Grade) 
Safety 
14.3.3.6.1 
Summary of Subjects with Treatment Emergent Thrombocytopenia 
of Grade 4 as Derived From Laboratory Data by Dose Level Ever 
Received 
Safety 
14.3.3.6.2 
Summary of Subjects with Treatment Emergent Anemia of Grade 4 
as Derived From Laboratory Data by Dose Level Ever Received 
Safety 
 
Safety: Vital Signs 
14.3.4.1 
Summary of Systolic Blood Pressure 
Safety 
14.3.4.2 
Summary of Diastolic Blood Pressure  
Safety 
14.3.4.3 
Summary of Heart Rate  
Safety 
14.3.4.4 
Summary of Respiratory Rate  
Safety 
14.3.4.5 
Summary of Body Temperature 
Safety 
10.2. 
Figures 
Figure 
Number 
Title 
Population  
14.2.1.1.1 
Scatter Plot of Percent Change from Baseline in Spleen Volume at 
Week 24 vs. Final Titrated Dose Level 
ITT 
14.2.1.1.2 
Scatter Plot of Percent Change from Baseline in Spleen Volume vs. 
Percent Change in Total Symptom Score at Week 24 
ITT 
14.2.1.2.1 
Mean (95%) Percent Change from Baseline in Spleen Volume at 
Week 24 
ITT 
14.2.1.2.2 
Median Percent Change from Baseline in Spleen Volume at Week 
24 by Final Titrated Dose Group 
ITT 
14.2.1.3.1 
Bar Plot of Percent of Subjects with >= 35% Reduction from 
Baseline in Spleen Volume at Week 24 by Final Titrated Dose 
Group 
ITT 
14.2.1.3.2 
Bar Plot of Percent of Subjects with >= 10% Reduction from 
Baseline in Spleen Volume at Week 24 by Final Titrated Dose 
Group 
ITT 
 
 
 
14.2.2.1.1 
Scatter Plot of Percent Change from Baseline in Total Symptom 
Score at Week 24 vs. Final Titrated Dose Level 
ITT 
14.2.2.2.1 
Mean (95%) Percent Change from Baseline in Total Symptom Score 
at Week 24 by Final Titrated Dose Group 
ITT 
14.2.2.2.2 
Median Percent Change from Baseline in Total Symptom Score at 
Week 24 by Final Titrated Dose Group 
ITT 
14.2.2.3.1 
Bar Plot of Percent of Subjects with >= 50% Reduction from 
Baseline in Total Symptom Score at Week 24 by Final Titrated Dose 
Group 
ITT 
14.2.3.1.1 
Scatter Plot of Percent Change from Baseline in Spleen Palpation 
Length at Week 24 vs. Final Titrated Dose Level 
ITT 
14.2.3.2.1 
Mean (95%) Percent Change from Baseline in Spleen Palpation 
Length at Week 24 by Final Titrated Dose Group 
ITT 
14.2.3.2.2 
Median Percent Change from Baseline in Spleen Palpation Length at 
Week 24 by Final Titrated Dose Group 
ITT 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
39 
Figure 
Number 
Title 
Population  
14.2.3.3.1 
Bar Plot of Percent of Subjects with >= 50% Reduction from 
Baseline in Spleen Palpation Length at Week 24 by Final Titrated 
Dose Group 
ITT 
14.2.3.3.2 
Bar Plot of Percent of Subjects with >= 20% Reduction from 
Baseline in Spleen Palpation Length at Week 24 by Final Titrated 
Dose Group 
ITT 
14.2.3.3.3 
Bar Plot of Percent of Subjects with >= 50% Reduction from 
Baseline in Spleen Palpation Length by Study Week 
ITT 
14.2.3.3.4 
Bar Plot of Percent of Subjects with >= 20% Reduction from 
Baseline in Spleen Palpation Length at Week 24 by Study Week 
ITT 
 
 
 
14.3.1.1.1 
Subject Laboratory Value over Time: Hemoglobin (G/L) 
Safety 
14.3.1.1.2 
Mean (95% CI) Laboratory Value Over Time: Hemoglobin (G/L) 
Safety 
14.3.1.2.1 
Subject Laboratory Value over Time: Platelet (GI/L) 
Safety 
14.3.1.2.2 
Mean (95% CI) Laboratory Value Over Time: Platelet (GI/L) 
Safety 
14.3.1.3.1 
Subject Laboratory Value over Time: WBC (GI/L) 
Safety 
14.3.1.3.2 
Mean (95% CI) Laboratory Value Over Time: WBC (GI/L) 
Safety 
14.3.1.4.1 
Subject Laboratory Value over Time: Neutrophil (GI/L) 
Safety 
14.3.1.4.2 
Mean (95% CI) Laboratory Value Over Time: Neutrophil (GI/L) 
Safety 
10.3. 
Listings 
Listing 
Number 
Title 
Population  
16.2.1.1 
Subject Enrollment and Exit Status 
Safety 
16.2.1.2 
Screening Failure Subjects 
Safety 
16.2.2 
Protocol Deviations/Violations 
Safety 
16.2.3 
Data Excluded from 
 Efficacy, and/or Safety Analyses 
Safety 
16.2.4.1 
Demographic and Baseline Characteristics 
Safety 
16.2.4.2.1 
Medical History 
Safety 
16.2.4.2.2 
Baseline Disease Stage 
Safety 
16.2.4.3 
Prior and Concomitant Drug Treatments 
Safety 
16.2.4.4 
Prior Myelofibrosis Therapy 
Safety 
16.2.4.5 
Prior Anti-Cancer Treatment 
Safety 
16.2.6.1     
Derived Efficacy Variables – Part I 
 ITT 
16.2.6.2     
Derived Efficacy Variables – Part II 
 ITT 
16.2.7.1.1 
Study Drug Activities and Dosing Compliance 
Safety 
16.2.7.2.1 
Adverse Events 
Safety 
16.2.7.2.2 
Serious Adverse Events 
Safety 
16.2.7.2.3 
Adverse Event Leading to Study Drug Decrease, Interruption, and 
Discontinuation 
Safety 
16.2.7.2.4 
Adverse Events of Hemorrhage as Identified by SMQ 
Safety 
16.2.7.2.5 
Adverse Events Leading to Discontinuation from the Study 
Safety 
16.2.7.2.6 
Adverse Events Leading to On-Study Death 
Safety 
16.2.8.1.1 
Clinical Laboratory Values 
Safety 
16.2.8.1.2 
Abnormal Clinical Laboratory Values 
Safety 
16.2.8.1.3 
Selected Hematology Laboratory Data 
Safety 
16.2.8.1.4 
Selected Hematology Laboratory Data for Subjects with Grade 4 
Thrombocytopenia or Grade 4 Anemia 
Safety 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
40 
Listing 
Number 
Title 
Population  
16.2.8.2.1 
Vital Signs 
Safety 
16.2.8.2.2 
Abnormal Vital Sign Values 
Safety 
16.2.8.2.3 
Alert Vital Sign Values 
 
16.2.8.3.1 
12-Lead ECG Values 
Safety 
16.2.8.3.2 
Abnormal 12-Lead ECG Values 
Safety 
16.2.8.4 
Physical Examinations 
Safety 
16.2.8.5 
Blood Component Transfusions 
Safety 
16.2.8.6 
Serum Pregnancy Test 
Safety 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
41 
11. 
REFERENCES 
INCB18424-2581 Protocol Amendment 1. 
US Department of Health and Human Services, “Common Terminology Criteria for Adverse 
Events (CTCAE) Version 4.03” 2010. 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf 
CTEP, National Cancer Institute Drug Branch, “CTEP Guidance: CTCAE v4.0 Grading Scales 
with Numeric Component” 2010.  
http://evs.nci.nih.gov/ftp1/CTCAE/Documentation/CTEP_Guidance_Quant-Grade_2010-05-
17.doc  
US FDA, “Guidance for Industry: Clinical Trial Endpoints for the Approval of Cancer Drugs and 
Biologics” 2007. 
SAS/STAT User Guides, Version 9. 
Cohen J: Statistical Power Analysis for the Behavioral Sciences. Second Edition. Hillsdale, NJ, 
1988. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
42 
12. 
APPENDICES 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
43 
APPENDIX A. MEDDRA PREFERRED TERMS INCLUDED IN THE 
SMQ TO IDENTIFY HEMORRHAGE ADVERSE EVENTS 
Name 
Code 
Level 
Scope 
Cate-
gory 
Weight 
Status 
Add. 
Ver. 
Last 
Mod. 
Ver. 
Abdominal wall haematoma 
10067383 
PT 
Narrow 
A 
0 
Active 
10.1 
12 
Abdominal wall haemorrhage 
10067788 
PT 
Narrow 
A 
0 
Active 
11 
12 
Abnormal withdrawal bleeding 
10069195 
PT 
Narrow 
A 
0 
Active 
12 
12 
Acute haemorrhagic 
leukoencephalitis 
10058994 
PT 
Narrow 
A 
0 
Active 
9 
12 
Adrenal haematoma 
10059194 
PT 
Narrow 
A 
0 
Active 
9 
12 
Adrenal haemorrhage 
10001361 
PT 
Narrow 
A 
0 
Active 
9 
12 
Anal haemorrhage 
10049555 
PT 
Narrow 
A 
0 
Active 
9 
12 
Anal ulcer haemorrhage 
10063896 
PT 
Narrow 
A 
0 
Active 
9 
12 
Anastomotic haemorrhage 
10056346 
PT 
Narrow 
A 
0 
Active 
9 
12 
Anastomotic ulcer haemorrhage 
10002244 
PT 
Narrow 
A 
0 
Active 
9 
12 
Aneurysm ruptured 
10048380 
PT 
Narrow 
A 
0 
Active 
9 
12 
Anorectal varices haemorrhage 
10068925 
PT 
Narrow 
A 
0 
Active 
12 
12 
Antepartum haemorrhage 
10002667 
PT 
Narrow 
A 
0 
Active 
9 
12 
Aortic aneurysm rupture 
10002886 
PT 
Narrow 
A 
0 
Active 
9 
12 
Aortic dissection rupture 
10068119 
PT 
Narrow 
A 
0 
Active 
11 
12 
Aortic intramural haematoma 
10067975 
PT 
Narrow 
A 
0 
Active 
11 
12 
Aortic rupture 
10060874 
PT 
Narrow 
A 
0 
Active 
9 
12 
Application site bleeding 
10048938 
PT 
Narrow 
A 
0 
Active 
9 
12 
Application site haematoma 
10068317 
PT 
Narrow 
A 
0 
Active 
11.1 
12 
Arterial haemorrhage 
10060964 
PT 
Narrow 
A 
0 
Active 
9 
12 
Arteriovenous fistula site haematoma 
10055150 
PT 
Narrow 
A 
0 
Active 
9 
12 
Arteriovenous fistula site 
haemorrhage 
10055123 
PT 
Narrow 
A 
0 
Active 
9 
12 
Arteriovenous graft site haematoma 
10055152 
PT 
Narrow 
A 
0 
Active 
9 
12 
Arteriovenous graft site haemorrhage 
10055126 
PT 
Narrow 
A 
0 
Active 
9 
12 
Astringent therapy 
10067372 
PT 
Narrow 
A 
0 
Active 
10.1 
12 
Atrial rupture 
10048761 
PT 
Narrow 
A 
0 
Active 
13 
13 
Auricular haematoma 
10003797 
PT 
Narrow 
A 
0 
Active 
9 
12 
Basal ganglia haemorrhage 
10067057 
PT 
Narrow 
A 
0 
Active 
10 
12 
Bladder tamponade 
10062656 
PT 
Narrow 
A 
0 
Active 
9 
12 
Bleeding peripartum 
10048607 
PT 
Narrow 
A 
0 
Active 
9 
12 
Bleeding varicose vein 
10005144 
PT 
Narrow 
A 
0 
Active 
9 
12 
Blood blister 
10005372 
PT 
Narrow 
A 
0 
Active 
9 
12 
Blood urine 
10005863 
PT 
Narrow 
A 
0 
Active 
9 
12 
Blood urine present 
10018870 
PT 
Narrow 
A 
0 
Active 
9 
12 
Bloody discharge 
10057687 
PT 
Narrow 
A 
0 
Active 
9 
12 
Bloody peritoneal effluent 
10067442 
PT 
Narrow 
A 
0 
Active 
10.1 
12 
Brain stem haemorrhage 
10006145 
PT 
Narrow 
A 
0 
Active 
9 
12 
Breast haematoma 
10064753 
PT 
Narrow 
A 
0 
Active 
9 
12 
Breast haemorrhage 
10006254 
PT 
Narrow 
A 
0 
Active 
9 
12 
Broad ligament haematoma 
10006375 
PT 
Narrow 
A 
0 
Active 
9 
12 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
44 
Name 
Code 
Level 
Scope 
Cate-
gory 
Weight 
Status 
Add. 
Ver. 
Last 
Mod. 
Ver. 
Bronchial haemorrhage 
10065739 
PT 
Narrow 
A 
0 
Active 
9 
12 
Carotid aneurysm rupture 
10051328 
PT 
Narrow 
A 
0 
Active 
9 
12 
Catheter site haematoma 
10055662 
PT 
Narrow 
A 
0 
Active 
9 
12 
Catheter site haemorrhage 
10051099 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cephalhaematoma 
10008014 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cerebellar haematoma 
10061038 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cerebellar haemorrhage 
10008030 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cerebral aneurysm ruptured 
syphilitic 
10008076 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cerebral arteriovenous malformation 
haemorrhagic 
10008086 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cerebral haematoma 
10053942 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cerebral haemorrhage 
10008111 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cerebral haemorrhage foetal 
10050157 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cerebral haemorrhage neonatal 
10008112 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cerebral haemorrhage traumatic 
10008113 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cerebral microhaemorrhage 
10067277 
PT 
Narrow 
A 
0 
Active 
10 
12.1 
Cervix haematoma uterine 
10050020 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cervix haemorrhage uterine 
10050022 
PT 
Narrow 
A 
0 
Active 
9 
12 
Choroidal haematoma 
10068642 
PT 
Narrow 
A 
0 
Active 
11.1 
12 
Choroidal haemorrhage 
10008786 
PT 
Narrow 
A 
0 
Active 
9 
12 
Chronic gastrointestinal bleeding 
10050399 
PT 
Narrow 
A 
0 
Active 
9 
12 
Ciliary body haemorrhage 
10057417 
PT 
Narrow 
A 
0 
Active 
9 
12 
Coital bleeding 
10065019 
PT 
Narrow 
A 
0 
Active 
9 
12 
Colonic haematoma 
10009996 
PT 
Narrow 
A 
0 
Active 
9 
12 
Conjunctival haemorrhage 
10010719 
PT 
Narrow 
A 
0 
Active 
9 
12 
Contusion 
10050584 
PT 
Narrow 
A 
0 
Active 
13 
13 
Corneal bleeding 
10051558 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cullen's sign 
10059029 
PT 
Narrow 
A 
0 
Active 
9 
12 
Cystitis haemorrhagic 
10011793 
PT 
Narrow 
A 
0 
Active 
9 
12 
Diarrhoea haemorrhagic 
10012741 
PT 
Narrow 
A 
0 
Active 
9 
12 
Disseminated intravascular 
coagulation 
10013442 
PT 
Narrow 
A 
0 
Active 
9 
12 
Diverticulitis intestinal haemorrhagic 
10013541 
PT 
Narrow 
A 
0 
Active 
9 
12 
Diverticulum intestinal haemorrhagic 
10013560 
PT 
Narrow 
A 
0 
Active 
9 
12 
Duodenal ulcer haemorrhage 
10013839 
PT 
Narrow 
A 
0 
Active 
9 
12 
Duodenitis haemorrhagic 
10013865 
PT 
Narrow 
A 
0 
Active 
9 
12 
Dysfunctional uterine bleeding 
10013908 
PT 
Narrow 
A 
0 
Active 
9 
12 
Ear haemorrhage 
10014009 
PT 
Narrow 
A 
0 
Active 
9 
12 
Ecchymosis 
10014080 
PT 
Narrow 
A 
0 
Active 
9 
12 
Encephalitis haemorrhagic 
10014589 
PT 
Narrow 
A 
0 
Active 
9 
12 
Enterocolitis haemorrhagic 
10014896 
PT 
Narrow 
A 
0 
Active 
9 
12 
Epistaxis 
10015090 
PT 
Narrow 
A 
0 
Active 
9 
12 
Exsanguination 
10015719 
PT 
Narrow 
A 
0 
Active 
9 
12 
Extradural haematoma 
10015769 
PT 
Narrow 
A 
0 
Active 
9 
12 
Extravasation blood 
10015867 
PT 
Narrow 
A 
0 
Active 
9 
12 
Eye haemorrhage 
10015926 
PT 
Narrow 
A 
0 
Active 
9 
12 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
45 
Name 
Code 
Level 
Scope 
Cate-
gory 
Weight 
Status 
Add. 
Ver. 
Last 
Mod. 
Ver. 
Eyelid bleeding 
10053196 
PT 
Narrow 
A 
0 
Active 
9 
12 
Foetal-maternal haemorrhage 
10016871 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastric haemorrhage 
10017788 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastric ulcer haemorrhage 
10017826 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastric ulcer haemorrhage, 
obstructive 
10017829 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastric ulcer perforation 
10017835 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastric varices haemorrhage 
10057572 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastritis alcoholic haemorrhagic 
10017857 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastritis haemorrhagic 
10017866 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastroduodenal haemorrhage 
10053768 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastroduodenitis haemorrhagic 
10048712 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastrointestinal angiodysplasia 
haemorrhagic 
10017929 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastrointestinal haemorrhage 
10017955 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gastrointestinal ulcer haemorrhage 
10056743 
PT 
Narrow 
A 
0 
Active 
9 
12 
Genital haemorrhage 
10061178 
PT 
Narrow 
A 
0 
Active 
9 
12 
Gingival bleeding 
10018276 
PT 
Narrow 
A 
0 
Active 
9 
12 
Graft haemorrhage 
10063577 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemarthrosis 
10018829 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haematemesis 
10018830 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haematochezia 
10018836 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haematoma 
10018852 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haematoma evacuation 
10060733 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haematoma infection 
10051564 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haematomyelia 
10066960 
PT 
Narrow 
A 
0 
Active 
10 
12 
Haematosalpinx 
10050468 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haematospermia 
10018866 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haematotympanum 
10063013 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haematuria 
10018867 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haematuria traumatic 
10018871 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemobilia 
10058947 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemophilic arthropathy 
10065057 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemoptysis 
10018964 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhage 
10055798 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhage coronary artery 
10055803 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhage foetal 
10061191 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhage intracranial 
10018985 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhage neonatal 
10061993 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhage subcutaneous 
10018999 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhage subepidermal 
10019001 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhage urinary tract 
10055847 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic anaemia 
10052293 
PT 
Narrow 
A 
0 
Active 
9.1 
12 
Haemorrhagic arteriovenous 
malformation 
10064595 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic ascites 
10059766 
PT 
Narrow 
A 
0 
Active 
9 
12 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
46 
Name 
Code 
Level 
Scope 
Cate-
gory 
Weight 
Status 
Add. 
Ver. 
Last 
Mod. 
Ver. 
Haemorrhagic cerebral infarction 
10019005 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic diathesis 
10062713 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic disease of newborn 
10019008 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic disorder 
10019009 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic erosive gastritis 
10067786 
PT 
Narrow 
A 
0 
Active 
11 
12 
Haemorrhagic hepatic cyst 
10067796 
PT 
Narrow 
A 
0 
Active 
11 
12 
Haemorrhagic infarction 
10019013 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic ovarian cyst 
10060781 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic stroke 
10019016 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic transformation stroke 
10055677 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic tumour necrosis 
10054096 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhagic urticaria 
10059499 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemorrhoidal haemorrhage 
10054787 
PT 
Narrow 
A 
0 
Active 
9 
12 
Haemostasis 
10067439 
PT 
Narrow 
A 
0 
Active 
10.1 
12 
Haemothorax 
10019027 
PT 
Narrow 
A 
0 
Active 
9 
12 
Henoch-Schonlein purpura 
10019617 
PT 
Narrow 
A 
0 
Active 
9 
12 
Hepatic haemangioma rupture 
10054885 
PT 
Narrow 
A 
0 
Active 
9 
12 
Hepatic haematoma 
10019676 
PT 
Narrow 
A 
0 
Active 
9 
12 
Hepatic haemorrhage 
10019677 
PT 
Narrow 
A 
0 
Active 
9 
12 
Hereditary haemorrhagic 
telangiectasia 
10019883 
PT 
Narrow 
A 
0 
Active 
9 
12 
Hyphaema 
10020923 
PT 
Narrow 
A 
0 
Active 
9 
12 
Implant site haematoma 
10063780 
PT 
Narrow 
A 
0 
Active 
9 
12 
Implant site haemorrhage 
10053995 
PT 
Narrow 
A 
0 
Active 
9 
12 
Incision site haematoma 
10059241 
PT 
Narrow 
A 
0 
Active 
9 
12 
Incision site haemorrhage 
10051100 
PT 
Narrow 
A 
0 
Active 
9 
12 
Increased tendency to bruise 
10021688 
PT 
Narrow 
A 
0 
Active 
9 
12 
Induced abortion haemorrhage 
10052844 
PT 
Narrow 
A 
0 
Active 
9 
12 
Infusion site haematoma 
10065463 
PT 
Narrow 
A 
0 
Active 
9 
12 
Infusion site haemorrhage 
10065464 
PT 
Narrow 
A 
0 
Active 
9 
12 
Injection site haematoma 
10022066 
PT 
Narrow 
A 
0 
Active 
9 
12 
Injection site haemorrhage 
10022067 
PT 
Narrow 
A 
0 
Active 
9 
12 
Intestinal haemorrhage 
10059175 
PT 
Narrow 
A 
0 
Active 
9 
12 
Intra-abdominal haematoma 
10056457 
PT 
Narrow 
A 
0 
Active 
9 
12 
Intra-abdominal haemorrhage 
10061249 
PT 
Narrow 
A 
0 
Active 
9 
12 
Intracerebral haematoma evacuation 
10062025 
PT 
Narrow 
A 
0 
Active 
9 
12 
Intracranial haematoma 
10059491 
PT 
Narrow 
A 
0 
Active 
9 
12 
Intracranial tumour haemorrhage 
10022775 
PT 
Narrow 
A 
0 
Active 
9 
12 
Intrapartum haemorrhage 
10067703 
PT 
Narrow 
A 
0 
Active 
10.1 
12 
Intraventricular haemorrhage 
10022840 
PT 
Narrow 
A 
0 
Active 
9 
12 
Intraventricular haemorrhage 
neonatal 
10022841 
PT 
Narrow 
A 
0 
Active 
9 
12 
Iris haemorrhage 
10057418 
PT 
Narrow 
A 
0 
Active 
9 
12 
Lacrimal haemorrhage 
10069930 
PT 
Narrow 
A 
0 
Active 
13 
13 
Large intestinal haemorrhage 
10052534 
PT 
Narrow 
A 
0 
Active 
9 
12 
Large intestinal ulcer haemorrhage 
10061262 
PT 
Narrow 
A 
0 
Active 
9 
12 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
47 
Name 
Code 
Level 
Scope 
Cate-
gory 
Weight 
Status 
Add. 
Ver. 
Last 
Mod. 
Ver. 
Laryngeal haemorrhage 
10065740 
PT 
Narrow 
A 
0 
Active 
9 
12 
Lip haematoma 
10066304 
PT 
Narrow 
A 
0 
Active 
9.1 
12 
Lip haemorrhage 
10049297 
PT 
Narrow 
A 
0 
Active 
9 
12 
Lower gastrointestinal haemorrhage 
10050953 
PT 
Narrow 
A 
0 
Active 
9 
12 
Majocchi's purpura 
10052316 
PT 
Narrow 
A 
0 
Active 
9 
12 
Mallory-Weiss syndrome 
10026712 
PT 
Narrow 
A 
0 
Active 
9 
12 
Mediastinal haematoma 
10049941 
PT 
Narrow 
A 
0 
Active 
9 
12 
Mediastinal haemorrhage 
10056343 
PT 
Narrow 
A 
0 
Active 
9 
12 
Melaena 
10027141 
PT 
Narrow 
A 
0 
Active 
9 
12 
Melaena neonatal 
10049777 
PT 
Narrow 
A 
0 
Active 
9 
12 
Meningorrhagia 
10052593 
PT 
Narrow 
A 
0 
Active 
9 
12 
Menometrorrhagia 
10027295 
PT 
Narrow 
A 
0 
Active 
9 
12 
Menorrhagia 
10027313 
PT 
Narrow 
A 
0 
Active 
9 
12 
Metrorrhagia 
10027514 
PT 
Narrow 
A 
0 
Active 
9 
12 
Mouth haemorrhage 
10028024 
PT 
Narrow 
A 
0 
Active 
9 
12 
Mucosal haemorrhage 
10061298 
PT 
Narrow 
A 
0 
Active 
9 
12 
Muscle haemorrhage 
10028309 
PT 
Narrow 
A 
0 
Active 
9 
12 
Myocardial haemorrhage 
10048849 
PT 
Narrow 
A 
0 
Active 
9 
12 
Myocardial rupture 
10028604 
PT 
Narrow 
A 
0 
Active 
13 
13 
Naevus haemorrhage 
10062955 
PT 
Narrow 
A 
0 
Active 
9 
12 
Nail bed bleeding 
10048891 
PT 
Narrow 
A 
0 
Active 
9 
12 
Nephritis haemorrhagic 
10029132 
PT 
Narrow 
A 
0 
Active 
9 
12 
Nipple exudate bloody 
10029418 
PT 
Narrow 
A 
0 
Active 
9 
12 
Ocular retrobulbar haemorrhage 
10057571 
PT 
Narrow 
A 
0 
Active 
9 
12 
Oesophageal haemorrhage 
10030172 
PT 
Narrow 
A 
0 
Active 
9 
12 
Oesophageal ulcer haemorrhage 
10030202 
PT 
Narrow 
A 
0 
Active 
9 
12 
Oesophageal varices haemorrhage 
10030210 
PT 
Narrow 
A 
0 
Active 
9 
12 
Oesophagitis haemorrhagic 
10030219 
PT 
Narrow 
A 
0 
Active 
9 
12 
Operative haemorrhage 
10030860 
PT 
Narrow 
A 
0 
Active 
9 
12 
Optic disc haemorrhage 
10030919 
PT 
Narrow 
A 
0 
Active 
9 
12 
Optic nerve sheath haemorrhage 
10030941 
PT 
Narrow 
A 
0 
Active 
9 
12 
Osteorrhagia 
10051937 
PT 
Narrow 
A 
0 
Active 
9 
12 
Ovarian haematoma 
10033263 
PT 
Narrow 
A 
0 
Active 
9 
12 
Ovarian haemorrhage 
10065741 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pancreatic haemorrhage 
10033625 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pancreatitis haemorrhagic 
10033650 
PT 
Narrow 
A 
0 
Active 
9 
12 
Papillary muscle haemorrhage 
10059164 
PT 
Narrow 
A 
0 
Active 
9 
12 
Paranasal sinus haematoma 
10069702 
PT 
Narrow 
A 
0 
Active 
13 
13 
Parathyroid haemorrhage 
10059051 
PT 
Narrow 
A 
0 
Active 
9 
12 
Parotid gland haemorrhage 
10051166 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pelvic haematoma 
10054974 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pelvic haematoma obstetric 
10034248 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pelvic haemorrhage 
10063678 
PT 
Narrow 
A 
0 
Active 
9 
12 
Penile haemorrhage 
10034305 
PT 
Narrow 
A 
0 
Active 
9 
12 
Peptic ulcer haemorrhage 
10034344 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pericardial haemorrhage 
10034476 
PT 
Narrow 
A 
0 
Active 
9 
12 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
48 
Name 
Code 
Level 
Scope 
Cate-
gory 
Weight 
Status 
Add. 
Ver. 
Last 
Mod. 
Ver. 
Perineal haematoma 
10034520 
PT 
Narrow 
A 
0 
Active 
9 
12 
Periorbital haematoma 
10034544 
PT 
Narrow 
A 
0 
Active 
9 
12 
Perirenal haematoma 
10049450 
PT 
Narrow 
A 
0 
Active 
9 
12 
Peritoneal haematoma 
10058095 
PT 
Narrow 
A 
0 
Active 
9 
12 
Peritoneal haemorrhage 
10034666 
PT 
Narrow 
A 
0 
Active 
9 
12 
Petechiae 
10034754 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pharyngeal haematoma 
10068121 
PT 
Narrow 
A 
0 
Active 
11 
12 
Pharyngeal haemorrhage 
10034827 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pituitary haemorrhage 
10049760 
PT 
Narrow 
A 
0 
Active 
9 
12 
Placenta praevia haemorrhage 
10035121 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pleural haemorrhage 
10035601 
PT 
Narrow 
A 
0 
Active 
9 
12 
Polymenorrhagia 
10064050 
PT 
Narrow 
A 
0 
Active 
9 
12 
Post abortion haemorrhage 
10036246 
PT 
Narrow 
A 
0 
Active 
9 
12 
Post procedural haematoma 
10063188 
PT 
Narrow 
A 
0 
Active 
9 
12 
Post procedural haematuria 
10066225 
PT 
Narrow 
A 
0 
Active 
9.1 
12 
Post procedural haemorrhage 
10051077 
PT 
Narrow 
A 
0 
Active 
9 
12 
Postmenopausal haemorrhage 
10055870 
PT 
Narrow 
A 
0 
Active 
9 
12 
Postpartum haemorrhage 
10036417 
PT 
Narrow 
A 
0 
Active 
9 
12 
Premature separation of placenta 
10036608 
PT 
Narrow 
A 
0 
Active 
9 
12 
Proctitis haemorrhagic 
10036778 
PT 
Narrow 
A 
0 
Active 
9 
12 
Prostatic haemorrhage 
10036960 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pulmonary alveolar haemorrhage 
10037313 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pulmonary haematoma 
10054991 
PT 
Narrow 
A 
0 
Active 
9 
12 
Pulmonary haemorrhage 
10037394 
PT 
Narrow 
A 
0 
Active 
9 
12 
Puncture site haemorrhage 
10051101 
PT 
Narrow 
A 
0 
Active 
9 
12 
Purpura 
10037549 
PT 
Narrow 
A 
0 
Active 
9 
12 
Purpura neonatal 
10037557 
PT 
Narrow 
A 
0 
Active 
9 
12 
Purpura senile 
10037560 
PT 
Narrow 
A 
0 
Active 
9 
12 
Putamen haemorrhage 
10058940 
PT 
Narrow 
A 
0 
Active 
9 
12 
Rectal haemorrhage 
10038063 
PT 
Narrow 
A 
0 
Active 
9 
12 
Rectal ulcer haemorrhage 
10038081 
PT 
Narrow 
A 
0 
Active 
9 
12 
Renal cyst haemorrhage 
10059846 
PT 
Narrow 
A 
0 
Active 
9 
13 
Renal haematoma 
10038459 
PT 
Narrow 
A 
0 
Active 
9 
12 
Renal haemorrhage 
10038460 
PT 
Narrow 
A 
0 
Active 
9 
12 
Respiratory tract haemorrhage 
10038727 
PT 
Narrow 
A 
0 
Active 
9 
12 
Respiratory tract haemorrhage 
neonatal 
10038728 
PT 
Narrow 
A 
0 
Active 
9 
12 
Retinal haemorrhage 
10038867 
PT 
Narrow 
A 
0 
Active 
9 
12 
Retinopathy haemorrhagic 
10051447 
PT 
Narrow 
A 
0 
Active 
9 
12 
Retroperitoneal haematoma 
10058360 
PT 
Narrow 
A 
0 
Active 
9 
12 
Retroperitoneal haemorrhage 
10038980 
PT 
Narrow 
A 
0 
Active 
9 
12 
Retroplacental haematoma 
10054798 
PT 
Narrow 
A 
0 
Active 
9 
12 
Ruptured cerebral aneurysm 
10039330 
PT 
Narrow 
A 
0 
Active 
9 
12 
Scleral haemorrhage 
10050508 
PT 
Narrow 
A 
0 
Active 
9 
12 
Scrotal haematocoele 
10061517 
PT 
Narrow 
A 
0 
Active 
9 
12 
Scrotal haematoma 
10039749 
PT 
Narrow 
A 
0 
Active 
9 
12 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
49 
Name 
Code 
Level 
Scope 
Cate-
gory 
Weight 
Status 
Add. 
Ver. 
Last 
Mod. 
Ver. 
Shock haemorrhagic 
10049771 
PT 
Narrow 
A 
0 
Active 
9 
12 
Skin haemorrhage 
10064265 
PT 
Narrow 
A 
0 
Active 
9 
12 
Skin ulcer haemorrhage 
10050377 
PT 
Narrow 
A 
0 
Active 
9 
12 
Small intestinal haemorrhage 
10052535 
PT 
Narrow 
A 
0 
Active 
9 
12 
Small intestinal ulcer haemorrhage 
10061550 
PT 
Narrow 
A 
0 
Active 
9 
12 
Soft tissue haemorrhage 
10051297 
PT 
Narrow 
A 
0 
Active 
9 
12 
Spermatic cord haemorrhage 
10065742 
PT 
Narrow 
A 
0 
Active 
9 
12 
Spinal cord haemorrhage 
10048992 
PT 
Narrow 
A 
0 
Active 
9 
12 
Spinal epidural haemorrhage 
10049236 
PT 
Narrow 
A 
0 
Active 
9 
12 
Spinal haematoma 
10048464 
PT 
Narrow 
A 
0 
Active 
9 
12 
Splenic haematoma 
10041646 
PT 
Narrow 
A 
0 
Active 
9 
12 
Splenic haemorrhage 
10041647 
PT 
Narrow 
A 
0 
Active 
9 
12 
Splenic varices haemorrhage 
10068662 
PT 
Narrow 
A 
0 
Active 
11.1 
12 
Splinter haemorrhages 
10041663 
PT 
Narrow 
A 
0 
Active 
9 
12 
Spontaneous haematoma 
10065304 
PT 
Narrow 
A 
0 
Active 
9 
12 
Stomatitis haemorrhagic 
10042132 
PT 
Narrow 
A 
0 
Active 
9 
12 
Subarachnoid haemorrhage 
10042316 
PT 
Narrow 
A 
0 
Active 
9 
12 
Subarachnoid haemorrhage neonatal 
10042317 
PT 
Narrow 
A 
0 
Active 
9 
12 
Subcutaneous haematoma 
10042345 
PT 
Narrow 
A 
0 
Active 
9 
12 
Subdural haematoma 
10042361 
PT 
Narrow 
A 
0 
Active 
9 
12 
Subdural haematoma evacuation 
10042363 
PT 
Narrow 
A 
0 
Active 
9 
12 
Subdural haemorrhage 
10042364 
PT 
Narrow 
A 
0 
Active 
9 
12 
Subdural haemorrhage neonatal 
10042365 
PT 
Narrow 
A 
0 
Active 
9 
12 
Subgaleal haematoma 
10069510 
PT 
Narrow 
A 
0 
Active 
12.1 
12.1 
Testicular haemorrhage 
10051877 
PT 
Narrow 
A 
0 
Active 
9 
12 
Thalamus haemorrhage 
10058939 
PT 
Narrow 
A 
0 
Active 
9 
12 
Third stage postpartum haemorrhage 
10043449 
PT 
Narrow 
A 
0 
Active 
9 
12 
Thoracic haemorrhage 
10062744 
PT 
Narrow 
A 
0 
Active 
9 
12 
Thrombocytopenic purpura 
10043561 
PT 
Narrow 
A 
0 
Active 
9 
12 
Thrombotic thrombocytopenic 
purpura 
10043648 
PT 
Narrow 
A 
0 
Active 
9 
12 
Thyroid haemorrhage 
10064224 
PT 
Narrow 
A 
0 
Active 
9 
12 
Tongue haematoma 
10043959 
PT 
Narrow 
A 
0 
Active 
9 
12 
Tongue haemorrhage 
10049870 
PT 
Narrow 
A 
0 
Active 
9 
12 
Tonsillar haemorrhage 
10057450 
PT 
Narrow 
A 
0 
Active 
9 
12 
Tooth socket haemorrhage 
10064946 
PT 
Narrow 
A 
0 
Active 
9 
12 
Tracheal haemorrhage 
10062543 
PT 
Narrow 
A 
0 
Active 
9 
12 
Traumatic haematoma 
10044522 
PT 
Narrow 
A 
0 
Active 
9 
12 
Traumatic haemorrhage 
10053476 
PT 
Narrow 
A 
0 
Active 
9 
12 
Traumatic intracranial haemorrhage 
10061387 
PT 
Narrow 
A 
0 
Active 
9 
12 
Tumour haemorrhage 
10049750 
PT 
Narrow 
A 
0 
Active 
9 
12 
Ulcer haemorrhage 
10061577 
PT 
Narrow 
A 
0 
Active 
9 
12 
Umbilical cord haemorrhage 
10064534 
PT 
Narrow 
A 
0 
Active 
9 
12 
Umbilical haematoma 
10068712 
PT 
Narrow 
A 
0 
Active 
11.1 
12 
Umbilical haemorrhage 
10045455 
PT 
Narrow 
A 
0 
Active 
9 
12 
Upper gastrointestinal haemorrhage 
10046274 
PT 
Narrow 
A 
0 
Active 
9 
12 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
50 
Name 
Code 
Level 
Scope 
Cate-
gory 
Weight 
Status 
Add. 
Ver. 
Last 
Mod. 
Ver. 
Ureteric haemorrhage 
10065743 
PT 
Narrow 
A 
0 
Active 
9 
12 
Urethral haemorrhage 
10049710 
PT 
Narrow 
A 
0 
Active 
9 
12 
Urinary bladder haemorrhage 
10046528 
PT 
Narrow 
A 
0 
Active 
9 
12 
Urogenital haemorrhage 
10050058 
PT 
Narrow 
A 
0 
Active 
9 
12 
Uterine haematoma 
10063875 
PT 
Narrow 
A 
0 
Active 
9 
12 
Uterine haemorrhage 
10046788 
PT 
Narrow 
A 
0 
Active 
9 
12 
Vaccination site haematoma 
10069472 
PT 
Narrow 
A 
0 
Active 
12.1 
12.1 
Vaccination site haemorrhage 
10069475 
PT 
Narrow 
A 
0 
Active 
12.1 
12.1 
Vaginal haematoma 
10046909 
PT 
Narrow 
A 
0 
Active 
9 
12 
Vaginal haemorrhage 
10046910 
PT 
Narrow 
A 
0 
Active 
9 
12 
Varicose vein ruptured 
10046999 
PT 
Narrow 
A 
0 
Active 
9 
12 
Vascular pseudoaneurysm ruptured 
10053949 
PT 
Narrow 
A 
0 
Active 
9 
12 
Vascular purpura 
10047097 
PT 
Narrow 
A 
0 
Active 
9 
12 
Vascular rupture 
10053649 
PT 
Narrow 
A 
0 
Active 
9 
12 
Venous haemorrhage 
10065441 
PT 
Narrow 
A 
0 
Active 
9 
12 
Ventricle rupture 
10047279 
PT 
Narrow 
A 
0 
Active 
13 
13 
Vessel puncture site haematoma 
10065902 
PT 
Narrow 
A 
0 
Active 
9 
12 
Vessel puncture site haemorrhage 
10054092 
PT 
Narrow 
A 
0 
Active 
9 
12 
Vitreous haemorrhage 
10047655 
PT 
Narrow 
A 
0 
Active 
9 
12 
Vulval haematoma 
10047756 
PT 
Narrow 
A 
0 
Active 
9 
12 
Vulval haematoma evacuation 
10047757 
PT 
Narrow 
A 
0 
Active 
9 
12 
Vulval haemorrhage 
10063816 
PT 
Narrow 
A 
0 
Active 
9 
12 
Wound haemorrhage 
10051373 
PT 
Narrow 
A 
0 
Active 
9 
12 
 
 
 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
51 
APPENDIX B. SHELLS FOR POST-TEXT TABLES 
Shells for post-text tables are presented starting from next page. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
52 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 3) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.1 
 
Summary of Subject Enrollment and Exit Status 
(Population: Safety Evaluable Subjects) 
______________________________________________________________________________________________________________________ 
                                                                              Ruxolitinib   
                Variable                                                        (N=xxx)     
______________________________________________________________________________________________________________________ 
                Number (%) of Subjects Completed Treatment Phase              xxx ( xx.x)   
                Number (%) of Subjects Entered Extension Phase                xxx ( xx.x)   
                Number (%) of Subjects Still on Study                         xxx ( xx.x)   
              
 
                Number (%) of Subjects Discontinued During Treatment Phase    xxx ( xx.x)   
 
                  Primary Reason of Discontinuation: Treatment Phase 
                    Death                                                     xxx ( xx.x)   
                    Adverse Event                                             xxx ( xx.x)   
                    Consent Withdrawn                                         xxx ( xx.x)   
                    Protocol Deviation                                        xxx ( xx.x)   
                    Disease Progression                                       xxx ( xx.x)   
                    Lost to Follow-up                                         xxx ( xx.x)   
                    Non-Compliance with Study Medication                      xxx ( xx.x)   
                    Non-Compliance with Study Procedures                      xxx ( xx.x)   
                    Termination of the Clinical Trial by the Sponsor          xxx ( xx.x)   
                    Other                                                     xxx ( xx.x)   
  
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_DISP.SAS\T_TERM1.LST                                                     DATE(TIME): DDMMMYY(HH:MM) 
 
Reference: Listing 16.2.1.1 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
53 
PROTOCOL: INCB 18424-258                                                                                (Page 2 of 3) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.1 
 
Summary of Subject Enrollment and Exit Status 
(Population: Safety Evaluable Subjects) 
______________________________________________________________________________________________________________________ 
                                                                              Ruxolitinib   
                Variable                                                        (N=xxx)     
______________________________________________________________________________________________________________________ 
                Number (%) of Subjects Discontinued During Extension Phase    xxx ( xx.x)   
 
                  Primary Reason of Discontinuation: Extension Phase 
                    Death                                                     xxx ( xx.x)   
                    Adverse Event                                             xxx ( xx.x)   
                    Consent Withdrawn                                         xxx ( xx.x)   
                    Protocol Deviation                                        xxx ( xx.x)   
                    Disease Progression                                       xxx ( xx.x)   
                    Lost to Follow-up                                         xxx ( xx.x)   
                    Non-Compliance with Study Medication                      xxx ( xx.x)   
                    Non-Compliance with Study Procedures                      xxx ( xx.x)   
                    Termination of the Clinical Trial by the Sponsor          xxx ( xx.x)   
                    Other                                                     xxx ( xx.x)   
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_DISP.SAS\T_TERM1.LST                                                     DATE(TIME): DDMMMYY(HH:MM) 
 
Reference: Listing 16.2.1.1 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
54 
PROTOCOL: INCB 18424-258                                                                                (Page 3 of 3) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.1 
 
Summary of Subject Enrollment and Exit Status 
(Population: Safety Evaluable Subjects) 
______________________________________________________________________________________________________________________ 
                                                                              Ruxolitinib   
                Variable                                                        (N=xxx)     
______________________________________________________________________________________________________________________ 
                Number (%) of Subjects Discontinued During the Study          xxx ( xx.x)   
 
                  Primary Reason of Discontinuation: Extension Phase 
                    Death                                                     xxx ( xx.x)   
                    Adverse Event                                             xxx ( xx.x)   
                    Consent Withdrawn                                         xxx ( xx.x)   
                    Protocol Deviation                                        xxx ( xx.x)   
                    Disease Progression                                       xxx ( xx.x)   
                    Lost to Follow-up                                         xxx ( xx.x)   
                    Non-Compliance with Study Medication                      xxx ( xx.x)   
                    Non-Compliance with Study Procedures                      xxx ( xx.x)   
                    Termination of the Clinical Trial by the Sponsor          xxx ( xx.x)   
                    Other                                                     xxx ( xx.x)   
  
______________________________________________________________________________________________________________________ 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_DISP.SAS\T_TERM1.LST                                                     DATE(TIME): DDMMMYY(HH:MM) 
 
Reference: Listing 16.2.1.1 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
55 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 4) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.2 
 
Summary of Demographics 
(Population: Safety Evaluable Subjects) 
  
______________________________________________________________________________________________________________________ 
                                                         Ruxolitinib 
  Variable                                                (N=xxx) 
______________________________________________________________________________________________________________________ 
  Age (yrs) 
    n                                                       xxx 
    Mean                                                     xx.x 
    STD                                                       x.xx 
    Min                                                      xx.x 
    Median                                                   xx.x 
    Max                                                      xx.x 
  
    <=65 years                                            xxx ( xx.x) 
    >65 years                                             xxx ( xx.x) 
  
  Gender - n (%) 
    Male                                                  xxx ( xx.x) 
    Female                                                xxx ( xx.x) 
  
  Ethnicity - n (%) 
    Hispanic or Latino                                    xxx ( xx.x) 
    Not Hispanic or Latino                                xxx ( xx.x) 
  
  Race - n (%) 
    Black or African American                             xxx ( xx.x) 
    White                                                 xxx ( xx.x) 
    Asian                                                 xxx ( xx.x) 
    Native Hawaiian or Pacific Islander                   xxx ( xx.x) 
    American-Indian or Alaska Native                      xxx ( xx.x) 
    Other                                                 xxx ( xx.x) 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_DEMOG.SAS\T_DEMOG1.LST                                                   DATE(TIME): DDMMMYY(HH:MM) 
  
Reference: Listings 16.2.4.1 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
56 
PROTOCOL: INCB 18424-258                                                                                (Page 2 of 4) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.2 
 
Summary of Demographics 
(Population: Safety Evaluable Subjects) 
  
______________________________________________________________________________________________________________________ 
                                                         Treatment Group 
                                                          
                                                         Ruxolitinib 
  Variable                                                (N=xxx) 
______________________________________________________________________________________________________________________ 
  Height at Screening (cm) 
    n                                                       xxx 
    Mean                                                     xx.x 
    STD                                                       x.xx 
    Min                                                      xx.x 
    Median                                                   xx.x 
    Max                                                      xx.x 
  
  Height of Males at Screening (cm) 
    n                                                       xxx 
    Mean                                                     xx.x 
    STD                                                       x.xx 
    Min                                                      xx.x 
    Median                                                   xx.x 
    Max                                                      xx.x 
  
  Height of Females at Screening (cm) 
    n                                                       xxx 
    Mean                                                     xx.x 
    STD                                                       x.xx 
    Min                                                      xx.x 
    Median                                                   xx.x 
    Max                                                      xx.x 
  
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_DEMOG.SAS\T_DEMOG1.LST                                                   DATE(TIME): DDMMMYY(HH:MM) 
  
Reference: Listings 16.2.4.1 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
57 
PROTOCOL: INCB 18424-258                                                                                (Page 3 of 4) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.2 
 
Summary of Demographics 
(Population: Safety Evaluable Subjects) 
  
______________________________________________________________________________________________________________________ 
                                                         Treatment Group 
                                                          
                                                         Ruxolitinib 
  Variable                                                (N=xxx) 
______________________________________________________________________________________________________________________ 
  Weight at Screening (kg) 
    n                                                       xxx 
    Mean                                                     xx.x 
    STD                                                       x.xx 
    Min                                                      xx.x 
    Median                                                   xx.x 
    Max                                                      xx.x 
  
  Weight of Males at Screening (kg) 
    n                                                       xxx 
    Mean                                                     xx.x 
    STD                                                       x.xx 
    Min                                                      xx.x 
    Median                                                   xx.x 
    Max                                                      xx.x 
  
  Weight of Females at Screening (kg) 
    n                                                       xxx 
    Mean                                                     xx.x 
    STD                                                       x.xx 
    Min                                                      xx.x 
    Median                                                   xx.x 
    Max                                                      xx.x 
  
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_DEMOG.SAS\T_DEMOG1.LST                                                   DATE(TIME): DDMMMYY(HH:MM) 
  
Reference: Listings 16.2.4.1 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
58 
PROTOCOL: INCB 18424-258                                                                                (Page 4 of 4) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.2 
 
Summary of Demographics 
(Population: Safety Evaluable Subjects) 
  
______________________________________________________________________________________________________________________ 
                                                         Treatment Group 
                                                          
                                                         Ruxolitinib 
  Variable                                                (N=xxx) 
______________________________________________________________________________________________________________________ 
  BMI (kg/m^2) 
    n                                                       xxx 
    Mean                                                     xx.x 
    STD                                                       x.xx 
    Min                                                      xx.x 
    Median                                                   xx.x 
    Max                                                      xx.x 
  
  Resting Systolic Blood Pressure at Screening (mmHg) 
    n                                                       xxx 
    Mean                                                     xx.x 
    STD                                                       x.xx 
    Min                                                      xx.x 
    Median                                                   xx.x 
    Max                                                      xx.x 
  
  Resting Diastolic Blood Pressure at Screening (mmHg) 
    n                                                       xxx 
    Mean                                                     xx.x 
    STD                                                       x.xx 
    Min                                                      xx.x 
    Median                                                   xx.x 
    Max                                                      xx.x 
  
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_DEMOG.SAS\T_DEMOG1.LST                                                   DATE(TIME): DDMMMYY(HH:MM) 
  
Reference: Listings 16.2.4.1 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
59 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 9) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.3 
 
Summary of Baseline Characteristics 
(Population: Safety Evaluable Subjects) 
 
______________________________________________________________________________________________________________________ 
  
 Footnote Page 
 
  
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_DEMOG.SAS\T_DISEASE1.LST                                                 DATE(TIME): DDMMMYY(HH:MM) 
  
Note: Baseline = the last measurement prior to 1st dose of study medication. 
[1] Year since initial diagnosis = (first dose date - diagnosis date + 1)/365.25. 
    In case of partial date, first month of the year and/or first day of the month were used where applicable. 
[2] ECOG Status: 0=Fully active, able to carry on all pre-disease performance without restriction 
                 1=Restricted in physically strenuous activity but ambulatory and able to carry out 
                   work of a light or sedentary nature 
                 2=Ambulatory and capable of all selfcare but unable to carry out any work activities 
                   Up and about more than 50% of waking hours 
                 3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 
                 4=Completely disabled. Cannot carry on any  selfcare. Totally confined to bed or chair 
                 5=Dead 
Reference: Listings 16.2.4.1 and 16.2.4.2.2


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
60 
PROTOCOL: INCB 18424-258                                                                                (Page 2 of 9) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.3 
 
Summary of Baseline Characteristics 
(Population: Safety Evaluable Subjects) 
   
______________________________________________________________________________________________________________________ 
                                                                          Ruxolitinib              
  Variable                                                                (N=xxx)                 
 ______________________________________________________________________________________________________________________ 
  Tumor Type - n (%) 
    Primary Myelofibrosis                                                 xxx ( xx.x)                  
    Post Polycythemia Vera Myelofibrosis                                  xxx ( xx.x)       
    Post Essential Thrombocythemia Myelofibrosis                          xxx ( xx.x              
  
  Time (year) Since Initial Diagnosis [1] 
    n                                                                       xxx                    
    Mean                                                                      x.x                    
    STD                                                                       x.xx                 
    Min                                                                       x.x              
    Median                                                                    x.x                 
    Max                                                                      xx.x             
  
  With History Blood Component Transfusion - n (%) 
    Yes                                                                   xxx ( xx.x)                  
  
  Previous Hydroxyurea Use (HU) - n (%) 
    Yes                                                                   xxx ( xx.x)                  
  
______________________________________________________________________________________________________________________ 


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Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
61 
PROTOCOL: INCB 18424-258                                                                                (Page 3 of 9) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.3 
 
Summary of Baseline Characteristics 
(Population: Safety Evaluable Subjects) 
   
______________________________________________________________________________________________________________________ 
                                                                          Ruxolitinib              
  Variable                                                                (N=xxx)                 
 ______________________________________________________________________________________________________________________ 
 
  Fibrosis Grade at Baseline - n (%) [2] 
           0                                                              xxx ( xx.x)                  
           1                                                              xxx ( xx.x)                  
           2                                                              xxx ( xx.x)                  
           3                                                              xxx ( xx.x)                  
  
  Platelets at Baseline (GI/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  Hemoglobin at Baseline (G/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
______________________________________________________________________________________________________________________ 


Incyte Corporation 
Statistical Analysis Plan - Final  
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17 JAN 2012 
 
62 
 
PROTOCOL: INCB 18424-258                                                                                (Page 4 of 9) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.3 
 
Summary of Baseline Characteristics 
(Population: Safety Evaluable Subjects) 
   
______________________________________________________________________________________________________________________ 
                                                                          Ruxolitinib              
  Variable                                                                (N=xxx)                 
 ______________________________________________________________________________________________________________________ 
  Neutrophils at Baseline (GI/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  Leukocytes at Baseline (GI/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  Total Cholesterol at Baseline (MMOL/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
______________________________________________________________________________________________________________________ 


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Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
63 
PROTOCOL: INCB 18424-258                                                                                (Page 5 of 9) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.3 
 
Summary of Baseline Characteristics 
(Population: Safety Evaluable Subjects) 
   
______________________________________________________________________________________________________________________ 
                                                                          Ruxolitinib              
  Variable                                                                (N=xxx)                 
 ______________________________________________________________________________________________________________________ 
 
  Creatinine at Baseline (UMOL/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  Aspartate Aminotransferase at Baseline (U/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  Alanine Aminotransferase at Baseline (U/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
______________________________________________________________________________________________________________________ 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
64 
PROTOCOL: INCB 18424-258                                                                                (Page 6 of 9) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.3 
 
Summary of Baseline Characteristics 
(Population: Safety Evaluable Subjects) 
   
______________________________________________________________________________________________________________________ 
                                                                          Ruxolitinib              
  Variable                                                                (N=xxx)                 
 ______________________________________________________________________________________________________________________ 
 
  Bilirubin at Baseline (UMOL/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  Calcium at Baseline (MMOL/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  Glucose at Baseline (MMOL/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
______________________________________________________________________________________________________________________ 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
65 
 
PROTOCOL: INCB 18424-258                                                                                (Page 7 of 9) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.3 
 
Summary of Baseline Characteristics 
(Population: Safety Evaluable Subjects) 
   
______________________________________________________________________________________________________________________ 
                                                                          Ruxolitinib              
  Variable                                                                (N=xxx)                 
 ______________________________________________________________________________________________________________________ 
  Potassium at Baseline (MMOL/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  Sodium at Baseline (MMOL/L) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  DIPSS Score 
    HIGH RISK (5-6)                                                       xxx ( xx.x)                  
    INTERMEDIATE-2 (3-4)                                                  xxx ( xx.x)                  
  
______________________________________________________________________________________________________________________ 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
66 
PROTOCOL: INCB 18424-258                                                                                (Page 8 of 9) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.3 
 
Summary of Baseline Characteristics 
(Population: Safety Evaluable Subjects) 
   
______________________________________________________________________________________________________________________ 
                                                                          Ruxolitinib              
  Variable                                                                (N=xxx)                 
 ______________________________________________________________________________________________________________________ 
 
  Spleen Volume at Baseline (cm^3) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  Spleen Palpation Length at Baseline (cm) 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
  Total Symptom Score at Baseline 
    n                                                                       xxx                    
    Mean                                                                    xxx.x                    
    STD                                                                     xxx.xx                 
    Min                                                                      xx.x              
    Median                                                                  xxx.x                 
    Max                                                                     xxx.x             
  
______________________________________________________________________________________________________________________ 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
67 
PROTOCOL: INCB 18424-258                                                                                (Page 9 of 9) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.3 
 
Summary of Baseline Characteristics 
(Population: Safety Evaluable Subjects) 
   
______________________________________________________________________________________________________________________ 
                                                                          Ruxolitinib              
  Variable                                                                (N=xxx)                 
 ______________________________________________________________________________________________________________________ 
 
  ECOG at Baseline [3] 
           0                                                              xxx ( xx.x)                  
           1                                                              xxx ( xx.x)                  
           2                                                              xxx ( xx.x)                  
           3                                                              xxx ( xx.x)                  
           4                                                              xxx ( xx.x)                  
 
  Percent 
 at Baseline 
    Yes                                                                   xxx ( xx.x)                  
    No                                                                    xxx ( xx.x)                  
    Missing                                                               xxx ( xx.x)                  
  
______________________________________________________________________________________________________________________ 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
68 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.4 
 
Summary of Medical History by MedDRA System Organ Class and Preferred Term 
(Population: Safety Evaluable Subjects) 
 
_______________________________________________________________________________________________________________________               
MedDRA System Organ Class                                                 Ruxolitinib   
   Preferred Term                                                           (N=xxx)      
_______________________________________________________________________________________________________________________ 
Subjects With Any Medical History                                          xxx (xxx.x)    
 
SOC 1                                                                      xxx (xxx.x)    
  Preferred Term 1                                                         xxx (xxx.x)    
  . . . .  
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxxx.SAS\T_xxxxxx.LST                                                   DATE(TIME): DDMMMYY(HH:MM) 
  
Reference: Listings 16.2.4.2.1


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
69 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.5.1 
 
Summary of Prior Medications 
(Population: Safety Evaluable Subjects) 
  
_______________________________________________________________________________________________________________________               
                                                                                               Ruxolitinib   
                                 ATC Class/WHO Preferred Term                                    (N=xxx)      
_______________________________________________________________________________________________________________________ 
                                 Subjects With Any Prior Medications                     xxx (xxx.x)    
  
                                 WHO Drug Class 1                                              xxx (xxx.x)    
                                   WHO Preferred Term 1                                        xxx (xxx.x)    
                                   WHO Preferred Term 2                                        xxx (xxx.x)    
                                   WHO Preferred Term 3                                        xxx (xxx.x)    
                                   WHO Preferred Term 4                                        xxx (xxx.x)    
  
                                 WHO Drug Class 2                                              xxx (xxx.x)    
                                   WHO Preferred Term 1                                        xxx (xxx.x)    
                                   WHO Preferred Term 2                                        xxx (xxx.x)    
                                   WHO Preferred Term 3                                        xxx (xxx.x)    
                                   WHO Preferred Term 4                                        xxx (xxx.x)    
 
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_DEMOG.SAS\T_DEMOG1.LST                                                   DATE(TIME): DDMMMYY(HH:MM) 
  
Reference: Listings 16.2.4.3 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
70 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.5.2 
 
Summary of Concomitant Medications 
(Population: Safety Evaluable Subjects) 
 
 
NOTE TO THE PROGRAMMER: THIS TABLE WILL BE SIMILARLY PROGRAMMED AS Table 14.1.5.1 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
71 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.1.5.3 
 
Summary of Prior Anti-Cancer Treatment 
(Population: Safety Evaluable Subjects) 
 
 
NOTE TO THE PROGRAMMER: THIS TABLE WILL BE SIMILARLY PROGRAMMED AS Table 14.1.5.1 
 
Reference: Listing 16.2.4.5 
 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
72 
 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
  
Table 14.1.6.1 
 
Summary of Change in Status of Blood Component Transfusion Dependency by Baseline Platelet Count Group 
(Population: Safety Evaluable Subjects) 
  
______________________________________________________________________________________________________________________ 
Pattern of                                                      Baseline Platelet Count Group 
Change in                                                   ___________________________________       
Dependency         Time                                     50-75 GI/L           >75 GI/L           Total 
Status             Interval                                  N   n (%)          N    n (%)        N   n (%) 
_____________________________________________________________________________________________________________________ 
Depend. to Indep.  8 Weeks before Day 1 to Final 8 Weeks     xx  xx(xx.x)       xx xx (xx.x)      xx xx (xx.x) 
                   12 Weeks before Day 1 to Final 12 Weeks   xx  xx(xx.x)       xx xx (xx.x)      xx xx (xx.x) 
 
Indep. to Depend.  8 Weeks before Day 1 to Final 8 Weeks     xx  xx(xx.x)       xx xx (xx.x)      xx xx (xx.x) 
                   12 Weeks before Day 1 to Final 12 Weeks   xx  xx(xx.x)       xx xx (xx.x)      xx xx (xx.x) 
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxxx.SAS\T_xxxx.LST                                                    DATE(TIME): ddmmmyyyy(hh:mm) 
  
Note 1: N = # subjects at the beginning of the first interval, and n (%) = # (%) subjects at the end of the second 
        interval. The first interval covered within 8 (or 12) weeks prior to Day 1, and the second interval covered  
        last 8 (or 12) weeks after Day 1. Percents are calculated as n/N*100 for each row of each group. 
Note 2: Transfusion dependence is defined as subjects received at least 1 unit of red blood cell product(s) during 
        the given period. Independence is defined as subjects received 0 unit of red blood cell product(s) during  
        the given period. 
Reference: xxxx 
 
 
 
 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
73 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
  
Table 14.1.6.2 
 
Summary of Blood Component Transfusions by Baseline Platelet Count Group 
(Population: Safety Evaluable Subjects) 
  
______________________________________________________________________________________________________________________ 
                                                                     Baseline Platelet Count Group 
                                                               ___________________________________________ 
                                                                   50-75 GI/L         > 75 GI/L              Total 
Variable                                                            (N = xx)           (N = xx)              (N =xx) 
______________________________________________________________________________________________________________________ 
Monthly Units of RBC Transfusion: Baseline 
  n 
  Mean (Std) 
  Median 
  Min, Max 
 
Total Units of RBC Transfusion: Post-Baseline 
  n 
  Mean (Std) 
  Median 
  Min, Max 
 
Monthly Units of RBC Transfusion: Post-Baseline 
  n 
  Mean (Std) 
  Median 
  Min, Max 
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxxx.SAS\T_xxxx.LST                                                    DATE(TIME): ddmmmyyyy(hh:mm) 
  
Note 1: Total units = all units during the treatment phase from Day 1 to the last scheduled visit. 
Note 2: Monthly units = total units divided by the treatment duration (in months where 1 month = 30.4375 days). 
Reference: Listing xxxxx. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
74 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.1.1 
 
Summary of Correlation of Final Titrated Dose vs. Percent Change from Baseline in Spleen Volume at Week 24 
and vs. Percent Change in Total Symptom Score at Week 24 
(Population: ITT Subjects) 
 
_______________________________________________________________________________________________________________________               
                                                                  Ruxolitinib                                                        
Variable                                                            (N=xxx)    
_______________________________________________________________________________________________________________________ 
 
Dose vs. % Chg in Spleen Volume 
  Sample size, n                                                       xxx        
  Pearson correlation coefficient – raw value                         x.xxx        
  p-value from t-test                                                 0.xxx      
  Estimated corr coeff – Fisher transformation (95% CI)         x.xxx (x.xxx, x.xxx) 
 
Dose vs. % Chg in Total Symptom Score 
  Sample size, n                                                       xxx        
  Pearson correlation coefficient – raw value                         x.xxx        
  p-value from t-test                                                 0.xxx      
  Estimated corr coeff – Fisher transformation (95% CI)         x.xxx (x.xxx, x.xxx) 
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxxx.SAS\T_xxxxxx.LST                                                   DATE(TIME): DDMMMYY(HH:MM) 
 
Note: t-test was based on the raw Pearson correlation coefficient; and 95% confidence interval is based on the 
      Approximation from Fisher’s r-to-z transformation. 
Reference: Listings 16.2.6. 
 
 
NOTE TO THE TEAM: if protocol is further amended, we should consistently specify p-value and 95% CI calculation, that 
they all come from Fisher r-to-z transformation. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
75 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.1.2 
 
Summary of Correlation of Final Titrated Dose vs. Percent Change from Baseline in Spleen Volume at Week 24 
and vs. Percent Change in Total Symptom Score at Week 24: Sensitivity Analysis 1 
(Population: Per-Protocol Subjects) 
 
 
NOTE TO THE PROGRAMMER: this table will be similarly programmed as 14.2.1.1. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
76 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.1.3 
 
Summary of Correlation of Final Titrated Dose vs. Percent Change from Baseline in Spleen Volume at Week 24 
and vs. Percent Change in Total Symptom Score at Week 24: Sensitivity Analysis 2 
(Population: ITT Subjects) 
 
 
NOTE TO THE PROGRAMMER: this table will be similarly programmed as 14.2.1.1. 
 
Footnote need to add MI model and procedure for this sensitivity analysis. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
77 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 2) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.2.1 
 
Summary of Spleen Volume (cm^3) by Study Week and Final Titrated Dose Group 
(Population: ITT Subjects) 
 
_______________________________________________________________________________________________________________________               
                                                             Ruxolitinib Final Titrated Dose (mg) Group 
                                               ---------------------------------------------------------------------- 
Study Week                       Total                < 5            >5 to 15           >15 to 25                >25 
  Variable                      (N=xxx)              (N=xx)           (N=xx)             (N=xx)                 (N=xx) 
_______________________________________________________________________________________________________________________ 
 
Baseline 
  n                            xxx                xx                 xx                xx                     xx 
  Mean                        xxxx.x            xxxx.x             xxxx.x            xxxx.x                xxxx.x        
  Std                         xxxx.xx           xxxx.xx            xxxx.xx           xxxx.xx               xxxx.xx  
  Median                      xxxx.x            xxxxx.x            xxxx.x             xxxx.x                xxxx.x              
  Min, Max               (xxxx.x, xxxx.x)   (xxxx.x, xxxx.x)   (xxxx.x, xxxx.x)   (xxxx.x, xxxx.x)     (xxxx.x, xxxx.x) 
 
Week 24: raw 
  n                                xxx               xx                xx               xx                 xx 
  Mean                            xxxx.x           xxxx.x            xxxx.x           xxxx.x             xxxx.x        
  Std                             xxxx.xx          xxxx.xx           xxxx.xx          xxxx.xx            xxxx.xx  
  Median                          xxxx.x           xxxxx.x           xxxx.x            xxxx.x            xxxx.x              
  Min, Max                   (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x) 
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxxx.SAS\T_xxxxxx.LST                                                   DATE(TIME): DDMMMYY(HH:MM) 
 
Reference: Listing 16.2.6.


Incyte Corporation 
Statistical Analysis Plan - Final  
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17 JAN 2012 
 
78 
PROTOCOL: INCB 18424-258                                                                                (Page 2 of 2) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.2.1 
 
Summary of Spleen Volume (cm^3) by Study Week and Final Titrated Dose Group 
(Population: ITT Subjects) 
 
_______________________________________________________________________________________________________________________               
                                                             Ruxolitinib Final Titrated Dose (mg) Group 
                                               ---------------------------------------------------------------------- 
Study Week                       Total                < 5            >5 to 15           >15 to 25                >25 
  Variable                      (N=xxx)              (N=xx)           (N=xx)             (N=xx)                 (N=xx) 
_______________________________________________________________________________________________________________________ 
 
Week 24: Chg from Baseline 
  n                                xxx               xx                xx               xx                 xx 
  Mean                            xxxx.x           xxxx.x            xxxx.x           xxxx.x             xxxx.x        
  Std                             xxxx.xx          xxxx.xx           xxxx.xx          xxxx.xx            xxxx.xx  
  Median                          xxxx.x           xxxxx.x           xxxx.x            xxxx.x            xxxx.x              
  Min, Max                   (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x) 
  p-value from t-test             0.xxxx            0.xxxx            0.xxxx            0.xxxx            0.xxxx 
  p-value from WRS-test           0.xxxx            0.xxxx            0.xxxx            0.xxxx            0.xxxx 
 
Week 24: %Chg from Baseline 
  n                                xxx               xx                xx               xx                 xx 
  Mean                            xxxx.x           xxxx.x            xxxx.x           xxxx.x             xxxx.x        
  Std                             xxxx.xx          xxxx.xx           xxxx.xx          xxxx.xx            xxxx.xx  
  Median                          xxxx.x           xxxxx.x           xxxx.x            xxxx.x            xxxx.x              
  Min, Max                   (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x)  (xxxx.x, xxxx.x) 
  p-value from t-test             0.xxxx            0.xxxx            0.xxxx            0.xxxx            0.xxxx 
  p-value from WRS-test           0.xxxx            0.xxxx            0.xxxx            0.xxxx            0.xxxx 
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxxx.SAS\T_xxxxxx.LST                                                   DATE(TIME): DDMMMYY(HH:MM) 
 
Reference: Listing 16.2.6. 


Incyte Corporation 
Statistical Analysis Plan - Final  
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17 JAN 2012 
 
79 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.2.2 
 
Summary of Proportion of Subjects with >= 35% Reduction from Baseline in Spleen Volume at Week 24  
by Final Titrated Dose Group 
(Population: ITT Subjects) 
 
_______________________________________________________________________________________________________________________               
                                                        Ruxolitinib Final Titrated Dose (mg) Group 
                                              ---------------------------------------------------------------------- 
Study Week                         Total          < 5            >5 to 15           >15 to 25                >25 
  Variable                        (N=xxx)       (N=xx)           (N=xx)             (N=xx)                 (N=xx) 
_______________________________________________________________________________________________________________________ 
 
Week 24: Reduction of >= 35% 
from Baseline – n (%) 
  No                              xxx (xx.x)    xxx (xx.x)      xxx (xx.x)          xxx (xx.x)          xxx (xx.x) 
  Yes                             xxx (xx.x)    xxx (xx.x)      xxx (xx.x)          xxx (xx.x)          xxx (xx.x) 
  95% CI for response rate [1]   (xx.x, xx.x)  (xx.x, xx.x)    (xx.x, xx.x)        (xx.x, xx.x)        (xx.x, xx.x) 
 
Reasons for not Achieving 
the reduction of >= 35% - n (%) 
  Discontinued prior to Week 24   xxx (xx.x)   xxx (xx.x)       xxx (xx.x)          xxx (xx.x)          xxx (xx.x) 
  Data missing/out of window      xxx (xx.x)   xxx (xx.x)       xxx (xx.x)          xxx (xx.x)          xxx (xx.x) 
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxxx.SAS\T_xxxxxx.LST                                                   DATE(TIME): DDMMMYY(HH:MM) 
 
[1]: 95% CI is from exact binomial distribution. 
Reference: Listing 16.2.6. 


Incyte Corporation 
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17 JAN 2012 
 
80 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.2.3 
 
Summary of Proportion of Subjects with >= 10% Reduction from Baseline in Spleen Volume at Week 24  
by Final Titrated Dose Group 
(Population: ITT Subjects) 
 
 
NOTE TO THE PROGRAMMER: this table will be programmed similarly to Table 14.2.2.2. 
 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
81 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 2) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.3.1 
 
Summary of Total Symptom Score by Study Week and Final Titrated Dose Group 
(Population: ITT Subjects) 
 
 
NOTE TO THE PROGRAMMER: this table will be programmed similarly to Table 14.2.2.1 but Study Weeks will be 0, 4, 8, 12, 
16, 20, 24.  


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
82 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.3.2 
 
Summary of Proportion of Subjects with >= 50% Reduction from Baseline in Total Symptom Score  
by Study Week and Final Titrated Dose Group 
(Population: ITT Subjects) 
 
NOTE TO THE PROGRAMMER: this table will be similarly program as Table 14.2.2.2 but will not derive/display reason of 
not achieving a response. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
83 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
 
 
  
 
 
NOTE TO THE PROGRAMMER: this table will be similarly program as Table 14.2.2.2 but will not derive/display reason of 
not achieving a response. 
 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
84 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 2) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.4.1 
 
Summary of Spleen Palpation Length Data by Study Week and Final Titrated Dose Group 
(Population: ITT Subjects) 
 
 
NOTE TO THE PROGRAMMER: this table will be programmed similarly to Table 14.2.2.1 but Study Weeks will be the nominal 
weeks where spleen length data are scheduled to be collected.  


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
85 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.4.2 
 
Summary of Proportion of Subjects with >= 50% Reduction from Baseline in Spleen Palpation Length 
by Study Week and Final Titrated Dose Group 
(Population: ITT Subjects) 
 
NOTE TO THE PROGRAMMER: this table will be similarly program as Table 14.2.2.2 but will not derive/display reason of 
not achieving a response. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
86 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.4.3 
 
Summary of Proportion of Subjects with >= 20% Reduction from Baseline in Spleen Palpation Length  
by Study Week and Final Titrated Dose Group 
(Population: ITT Subjects) 
 
NOTE TO THE PROGRAMMER: this table will be similarly program as Table 14.2.2.2 but will not derive/display reason of 
not achieving a response. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
87 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
Table 14.2.5.1 
 
Summary of Patient Global Impression of Change Score by Study Week and Final Titrated Dose Group 
(Population: ITT Subjects) 
 
NOTE TO THE PROGRAMMER: this table will be similarly program as Table 14.2.2.1 but no change and percent change will be 
derived. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
88 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
 
 
 
 
NOTE TO THE PROGRAMMER: this table will be similarly program as Table 14.2.2.1. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
89 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
 
 
 
 
 
NOTE TO THE PROGRAMMER: this table will be similarly program as Table 14.2.2.1. 
 
 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
90 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 3) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
  
Table 14.3.1.1 
 
Summary of Exposure and Duration of Exposure to Study Medication Through Week 24 by Final Titrate Dose Level 
(Population: Safety Evaluable Subjects) 
 
______________________________________________________________________________________________________________________ 
                                                             Ruxolitinib Final Titrated Dose (mg) 
                                               ---------------------------------------------------------------------- 
                                        Total        < 5          >5 to 15     >15 to 25         >25 
Variable                               (N=xxx)      (N=xx)        (N=xx)        (N=xx)          (N=xx) 
______________________________________________________________________________________________________________________ 
Duration of Treatment (weeks) [1] 
  n                                      xxx           xx           xx             xx             xx 
  Mean                                  xxxx.x        xxxx.x       xxxx.x         xxxx.x         xxxx.x        
  Std                                   xxxx.xx       xxxx.xx      xxxx.xx        xxxx.xx        xxxx.xx  
  Median                                 xxxx.x       xxxxx.x       xxxx.x         xxxx.x         xxxx.x              
  Min, Max                            (xx.x, xx.x)  (xx.x, xx.x)  (xx.x, xx.x)   (xx.x, xx.x)   (xx.x, xx.x) 
 
  <=30 Days                             xx (xx.x)     xx (xx.x)     xx (xx.x)      xx (xx.x)      xx (xx.x) 
  31-90 Days                            xx (xx.x)     xx (xx.x)     xx (xx.x)      xx (xx.x)      xx (xx.x) 
  91-120 Days                           xx (xx.x)     xx (xx.x)     xx (xx.x)      xx (xx.x)      xx (xx.x) 
  121-150 Days                          xx (xx.x)     xx (xx.x)     xx (xx.x)      xx (xx.x)      xx (xx.x) 
  >150 Days                             xx (xx.x)     xx (xx.x)     xx (xx.x)      xx (xx.x)      xx (xx.x) 
 
Patient Year [2]                          x.xx          x.xx         x.xx            x.xx            x.xx 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxx.SAS\T_xxxx.LST                                                    DATE(TIME): ddmmmyy(hh:mm) 
[1] Duration of treatment is calculated as (last dose date during the treatment period – first dose date +1)/7 
    disregard interruptions in between. 
[2] Patient year is calculated based on duration of treatment. 
[3] Average daily dose is calculated as total dose (mg) divided by duration of treatment expressed in days. 
[4] Overall compliance is calculated as (total # of tablets consumed)/(total # of tablets expected to be consumed)*100, 
    where total # of tablets expected to be consumed is based on prescribed doses (including interruption) from CRF 
    domain of EX. 
Reference: Listing 16.2.7.1.1. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
91 
PROTOCOL: INCB 18424-258                                                                                (Page 2 of 3) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
  
Table 14.3.1.1 
 
Summary of Exposure and Duration of Exposure to Study Medication Through Week 24 by Final Titrate Dose Level 
(Population: Safety Evaluable Subjects) 
 
______________________________________________________________________________________________________________________ 
                                                             Ruxolitinib Final Titrated Dose (mg) 
                                               ---------------------------------------------------------------------- 
                                        Total        < 5          >5 to 15     >15 to 25         >25 
Variable                               (N=xxx)      (N=xx)        (N=xx)        (N=xx)          (N=xx) 
______________________________________________________________________________________________________________________ 
Average Daily Dose (mg) [3] 
  n                                      xxx           xx           xx             xx             xx 
  Mean                                  xxxx.x        xxxx.x       xxxx.x         xxxx.x         xxxx.x        
  Std                                   xxxx.xx       xxxx.xx      xxxx.xx        xxxx.xx        xxxx.xx  
  Median                                 xxxx.x       xxxxx.x       xxxx.x         xxxx.x         xxxx.x              
  Min, Max                            (xx.x, xx.x)  (xx.x, xx.x)  (xx.x, xx.x)   (xx.x, xx.x)   (xx.x, xx.x) 
 
Last 7 Days Average Daily Dose (mg) 
  n                                      xxx           xx           xx             xx             xx 
  Mean                                  xxxx.x        xxxx.x       xxxx.x         xxxx.x         xxxx.x        
  Std                                   xxxx.xx       xxxx.xx      xxxx.xx        xxxx.xx        xxxx.xx  
  Median                                 xxxx.x       xxxxx.x       xxxx.x         xxxx.x         xxxx.x              
  Min, Max                            (xx.x, xx.x)  (xx.x, xx.x)  (xx.x, xx.x)   (xx.x, xx.x)   (xx.x, xx.x) 
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxx.SAS\T_xxxx.LST                                                    DATE(TIME): ddmmmyy(hh:mm) 
[1] Duration of treatment is calculated as (last dose date during the treatment period – first dose date +1)/7 
    disregard interruptions in between. 
[2] Patient year is calculated based on duration of treatment. 
[3] Average daily dose is calculated as total dose (mg) divided by duration of treatment expressed in days. 
[4] Overall compliance is calculated as (total # of tablets consumed)/(total # of tablets expected to be consumed)*100, 
    where total # of tablets expected to be consumed is based on prescribed doses (including interruption) from CRF 
    domain of EX. 
Reference: Listing 16.2.7.1.1. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
92 
PROTOCOL: INCB 18424-258                                                                                (Page 3 of 3) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
  
Table 14.3.1.1 
 
Summary of Exposure and Duration of Exposure to Study Medication Through Week 24 by Final Titrate Dose Level 
(Population: Safety Evaluable Subjects) 
 
______________________________________________________________________________________________________________________ 
                                                             Ruxolitinib Final Titrated Dose (mg) 
                                               ---------------------------------------------------------------------- 
                                        Total        < 5          >5 to 15     >15 to 25         >25 
Variable                               (N=xxx)      (N=xx)        (N=xx)        (N=xx)          (N=xx) 
______________________________________________________________________________________________________________________ 
 
Overall Compliance (%) [4] 
       <=50                              xx (xx.x)     xx (xx.x)     xx (xx.x)      xx (xx.x)      xx (xx.x) 
       >51-80                            xx (xx.x)     xx (xx.x)     xx (xx.x)      xx (xx.x)      xx (xx.x) 
       >80                               xx (xx.x)     xx (xx.x)     xx (xx.x)      xx (xx.x)      xx (xx.x) 
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxx.SAS\T_xxxx.LST                                                    DATE(TIME): ddmmmyy(hh:mm) 
[1] Duration of treatment is calculated as (last dose date during the treatment period – first dose date +1)/7 
    disregard interruptions in between. 
[2] Patient year is calculated based on duration of treatment. 
[3] Average daily dose is calculated as total dose (mg) divided by duration of treatment expressed in days. 
[4] Overall compliance is calculated as (total # of tablets consumed)/(total # of tablets expected to be consumed)*100, 
    where total # of tablets expected to be consumed is based on prescribed doses (including interruption) from CRF 
    domain of EX. 
Reference: Listing 16.2.7.1.1. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
93 
PROTOCOL: INCB 18424-258                                                                                (Page 3 of 3) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
  
Table 14.3.1.2 
 
Summary of Exposure and Duration of Exposure to Study Medication Through Week 4 by Final Titrate Dose Level 
(Population: Safety Evaluable Subjects) 
 
 
NOTE TO THE PROGRAMMER: this table will programmed similarly to Table 14.3.1.1 but present only average daily dose. 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
94 
PROTOCOL: INCB 18424-258                                                                                (Page 3 of 3) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
  
Table 14.3.1.3 
 
Summary of Average Daily Dose of Ruxolitinib by Study Week and Final Titrate Dose Level 
(Population: Safety Evaluable Subjects) 
 
______________________________________________________________________________________________________________________ 
                                                             Ruxolitinib Final Titrated Dose (mg) 
                                               ---------------------------------------------------------------------- 
                                        Total        < 5          >5 to 15     >15 to 25         >25 
Variable                               (N=xxx)      (N=xx)        (N=xx)        (N=xx)          (N=xx) 
______________________________________________________________________________________________________________________ 
Average Daily Dose (mg) for Week 1 
  n                                      xxx           xx           xx             xx             xx 
  Mean                                  xxxx.x        xxxx.x       xxxx.x         xxxx.x         xxxx.x        
  Std                                   xxxx.xx       xxxx.xx      xxxx.xx        xxxx.xx        xxxx.xx  
  Median                                 xxxx.x       xxxxx.x       xxxx.x         xxxx.x         xxxx.x              
  Min, Max                            (xx.x, xx.x)  (xx.x, xx.x)  (xx.x, xx.x)   (xx.x, xx.x)   (xx.x, xx.x) 
 
Average Daily Dose (mg) for Week 2 
  . . . .  
 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxx.SAS\T_xxxx.LST                                                    DATE(TIME): ddmmmyy(hh:mm) 
 
Reference: Listing 16.2.7.1.1. 
 
 
NOTE TO THE PROGRAMMER: Table is continued to Week 48 as long as data is available.


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
95 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
  
Table 14.3.2.1 
 
Overall Summary of Treatment-Emergent Adverse Events by Dose Ever Received 
(Population: Safety Evaluable Subjects) 
  
 ______________________________________________________________________________________________________________________ 
                                                                         Dose Level (mg) Subjects Ever Received 
                                                        All      ______________________________________________________ 
                                                      Subjects      <=5       >5 10      >10 15     >15 20     >20 25 
 Variable                                              (N=23)      (N=2)      (N=23)     (N=14)     (N=7)      (N=1) 
 ______________________________________________________________________________________________________________________ 
 Treatment-Emergent Adverse Events (TEAE) Reported       33          1          8          21         3      0 (  0.0) 
  
 Subjects with a TEAE                                10 ( 43.5)  1 ( 50.0)  3 ( 13.0)  5 ( 35.7)  1 ( 14.3)  0 (  0.0) 
 Subjects with a Treatment-Related TEAE              2 (  8.7)   0 (  0.0)  1 (  4.3)  1 (  7.1)  0 (  0.0)  0 (  0.0) 
 Subjects with a Serious TEAE                        2 (  8.7)   1 ( 50.0)  0 (  0.0)  1 (  7.1)  0 (  0.0)  0 (  0.0) 
 Subjects with TEAE of Grade 3 or Higher             4 ( 17.4)   1 ( 50.0)  1 (  4.3)  2 ( 14.3)  0 (  0.0)  0 (  0.0) 
 Subjects with a Dose Increase Due to TEAE           0 (  0.0)   0 (  0.0)  0 (  0.0)  0 (  0.0)  0 (  0.0)  0 (  0.0) 
 Subjects with a Dose Reduction Due to TEAE          1 (  4.3)   0 (  0.0)  0 (  0.0)  1 (  7.1)  0 (  0.0)  0 (  0.0) 
 Subjects with Procedures Performed Due to TEAE      2 (  8.7)   0 (  0.0)  0 (  0.0)  2 ( 14.3)  0 (  0.0)  0 (  0.0) 
 Subjects with a TEAE requiring Concomitant          5 ( 21.7)   0 (  0.0)  1 (  4.3)  4 ( 28.6)  0 (  0.0)  0 (  0.0) 
 Medication 
 Subjects with Study Drug Withdrawn Due to TEAE      0 (  0.0)   0 (  0.0)  0 (  0.0)  0 (  0.0)  0 (  0.0)  0 (  0.0) 
 Subjects with an TEAE Leading to Discontinuation    0 (  0.0)   0 (  0.0)  0 (  0.0)  0 (  0.0)  0 (  0.0)  0 (  0.0) 
 from the Study 
 Subjects with a TEAE Leading to Death               0 (  0.0)   0 (  0.0)  0 (  0.0)  0 (  0.0)  0 (  0.0)  0 (  0.0) 
  
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_AESUM1.SAS\T_AE1.LST                                                     DATE(TIME): 12DEC11(11:30) 
  
Note 1:TEAEs: AEs that began or worsened from baseline following the first administration of the study drug. 
Note 2:Treatment-Related AEs:TEAEs with a possible, probable, definite, or missing casuality. 
Note 3:Severity vs CTCAE Grade: Mild=Grade 1, Moderate=Grade 2, Severe=Grade 3, Life-Threatening=Grade 4. 
Note 4:For an AE that occurred for more than once to a subject, it is counted in the lowest dose when 
       the highest severity grade is recorded. 
Reference: Listings 16.2.7.2.1 
 
NOTE to the reviewer: numbers in the shell is from draft DMC output and is intended to show shell only. 
 


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
96 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                   VERSION: First DMC-Draft 
  
                                                    Table 14.3.2.2.1 
  
                 Summary of Subjects Reporting Treatment-Emergent Adverse Events (All Causalities) by 
                               MedDRA System Organ Class, Preferred Term, and Maximum Severity 
                                       (Population: Safety Evaluable Subjects) 
 
 
NOTE TO THE PROGRAMMER: shell will following the standard output. 
 
Reference: 16.2.7.2.1 
  


Incyte Corporation 
Statistical Analysis Plan - Final  
INCB 18424-258 
17 JAN 2012 
 
97 
PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                   VERSION: First DMC-Draft 
  
                                                    Table 14.3.2.2.2 
  
                 Summary of Subjects Reporting Treatment-Emergent Adverse Events (All Causalities) by 
                               MedDRA System Organ Class, Preferred Term, and Dose Level Ever Received 
                                       (Population: Safety Evaluable Subjects) 
 
______________________________________________________________________________________________________________________ 
                                                                             CTCAE Grade 
                                                     All     ______________________________________________________ 
                                                   Subjects     0       >5 10      >10 15     >15 20     >20 25 
    Variable                                        (N=23)     (N=2)      (N=23)     (N=14)     (N=7)      (N=1) 
______________________________________________________________________________________________________________________ 
    Number (%) of Subjects With Any TEAEs         10 ( 43.5) 1 ( 50.0)  3 ( 13.0)  5 ( 35.7)  1 ( 14.3)   0 ( 0.0) 
  
    Blood and lymphatic system disorders           1 ( 4.3)   0 ( 0.0)   0 ( 0.0)   1 ( 7.1)   0 ( 0.0)   0 ( 0.0) 
      Anaemia                                      1 ( 4.3)   0 ( 0.0)   0 ( 0.0)   1 ( 7.1)   0 ( 0.0)   0 ( 0.0) 
  
    Gastrointestinal disorders                    6 ( 26.1)   0 ( 0.0)   0 ( 0.0)  4 ( 28.6)  2 ( 28.6)   0 ( 0.0) 
      Abdominal pain                               2 ( 8.7)   0 ( 0.0)   1 ( 4.3)   1 ( 7.1)   0 ( 0.0)   0 ( 0.0) 
      Anorectal discomfort                         1 ( 4.3)   0 ( 0.0)   0 ( 0.0)   1 ( 7.1)   0 ( 0.0)   0 ( 0.0) 
      Diarrhoea                                   3 ( 13.0)   0 ( 0.0)   0 ( 0.0)  2 ( 14.3)  1 ( 14.3)   0 ( 0.0) 
      Dry mouth                                    1 ( 4.3)   0 ( 0.0)   0 ( 0.0)   0 ( 0.0)  1 ( 14.3)   0 ( 0.0) 
      Haemorrhoidal haemorrhage                    1 ( 4.3)   0 ( 0.0)   0 ( 0.0)   1 ( 7.1)   0 ( 0.0)   0 ( 0.0) 
      Nausea                                       1 ( 4.3)   0 ( 0.0)   0 ( 0.0)   1 ( 7.1)   0 ( 0.0)   0 ( 0.0) 
. . . . . 
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_AESUM1.SAS\T_AE2.LST                                                     DATE(TIME): 12DEC11(11:30) 
  
Note 1:TEAEs: AEs that began or worsened from baseline following the first administration of the study drug. 
Note 2:N=the number of subjects who ever took a dose within the dose group, based on which the percent is calculated. 
Note 3:For an AE that occurred for more than once to a subject, it is counted in the lowest dose when 
       the highest severity grade is recorded. 
Reference: Listings 16.2.7.2.1 
 
 
NOTE to the reviewer: numbers in the shell is from draft DMC output and is intended to show shell only. 


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PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
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                                                    Table 14.3.2.3.1 
  
                 Summary of Subjects Reporting Treatment-Emergent Adverse Events (All Causalities) by 
                               MedDRA Preferred Term (Sorted by Decreasing Frequency) and Maximal Severity 
                                       (Population: Safety Evaluable Subjects) 
 
 
 
 
NOTE TO THE PROGRAMMER: shell will following the standard output. 
 
Reference: 16.2.7.2.1 
 


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PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                   VERSION: First DMC-Draft 
  
                                                    Table 14.3.2.3.2 
  
                 Summary of Subjects Reporting Treatment-Emergent Adverse Events (All Causalities) by 
                               MedDRA Preferred Term (Sorted by Decreasing Frequency) and Dose Ever Received 
                                       (Population: Safety Evaluable Subjects) 
 
 
 
 
NOTE TO THE PROGRAMMER: shell will following the standard output and table will be similarly programmed as 14.3.2.2.2. 
 
Reference: 16.2.7.2.1 


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NOTE: Shells for the following tables are not provided here but they will be programmed similarly to those presented 
above. 
 
14.3.2.3.2 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) by MedDRA Preferred Term (Sorted by 
Decreasing Frequency) and Dose Level Ever Received 
Safety 
14.3.2.3.3 
Summary of Subjects Reporting Treatment-Emergent Hemorrhage 
Adverse Events (All Causalities) by MedDRA Preferred Term and 
Dose Level Ever Received 
Safety 
14.3.2.3.4 
Summary of Subjects Reporting Treatment-Emergent Hemorrhage 
Adverse Events (All Causalities) of Grade 3 or Higher by MedDRA 
Preferred Term and Dose Level Ever Received 
Safety 
 
 
 
14.3.2.4.1 
Summary of Subjects Reporting Treatment-Emergent Treatment-
Related Adverse Events (All Causalities) by MedDRA System 
Organ Class, Preferred Term, and Maximum Severity 
Safety 
14.3.2.4.2 
Summary of Subjects Reporting Treatment-Emergent Treatment-
Related Adverse Events (All Causalities) by MedDRA System 
Organ Class, Preferred Term, and Dose Level Ever Received 
Safety 
 
 
 
14.3.2.5.1 
Summary of Subjects Reporting Treatment-Emergent Serious 
Adverse Events (All Causalities) by MedDRA System Organ Class, 
Preferred Term, and Dose Level Ever Received 
Safety 
14.3.2.6 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) Leading to Study Medication Decrease or 
Interruption by MedDRA System Organ Class, Preferred Term, and 
Dose Level Ever Received 
Safety 
14.3.2.7 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) Leading to Study Discontinuation by 
MedDRA System Organ Class, Preferred Term, and Dose Level 
Ever Received 
Safety 
14.3.2.8 
Summary of Subjects Reporting Treatment-Emergent Adverse 
Events (All Causalities) Leading to On-Study Death by MedDRA 
System Organ Class, Preferred Term, and Dose Level Ever 
Received 
Safety 
 


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NOTE: the following lab tables will be programmed according to standard output. 
 
14.3.3.1.1 
Summary of Laboratory Values – Hematology 
Safety 
14.3.3.1.2 
Shift Summary of Laboratory Values in Normal Ranges - 
Hematology 
Safety 
14.3.3.2.1 
Summary of Laboratory Values – Serum Chemistry 
Safety 
14.3.3.2.2 
Shift Summary of Laboratory Values in Normal Ranges – Serum 
Chemistry 
Safety 
14.3.3.3.1 
Summary of Laboratory Values – Coagulation 
Safety 
14.3.3.3.2 
Shift Summary of Laboratory Values in Normal Ranges – 
Coagulation 
Safety 
14.3.3.4.1 
Summary of Laboratory Values – Urinalysis 
Safety 
14.3.3.4.2 
Shift Summary of Laboratory Values in Normal Ranges – Urinalysis 
Safety 
14.3.3.5.1 
Shift Summary of Laboratory Values in CTC Grade - To the Worst 
Abnormal Value (Tests with One Directional CTC Grade) 
Safety 
14.3.3.5.2 
Shift Summary of Laboratory Values in CTC Grade - To the Worst 
Abnormal Value (Tests with Two Directional CTC Grade) 
Safety 


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PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
  
                                                      Table 14.3.3.6.1 
  
Summary of Subjects with Treatment Emergent Thrombocytopenia of Grade 4 as Derived from Laboratory Data  
by Last Dose Before Onset 
                                       (Population: Safety Evaluable Subjects) 
  
______________________________________________________________________________________________________________________ 
                                                                       Dose Level (mg) Subjects Ever Received 
                                                              ________________________________________________________ 
                                                     All         <=5     >5 10   >10 15   >15 20   >20 25     >25  
                                                   Subjects   ________ ________ ________ ________ ________   ________  
MedDRA Preferred Term                               (N=xx)        N=xx     N=xx     N=xx     N=xx     N=xx      N=xx 
______________________________________________________________________________________________________________________ 
Number (%) of Subjects With Grade 4               xx ( xx.x)    xx xx%   xx xx%   xx xx%   xx xx%   xx xx%    xx xx%     
    Thrombocytopenia [1]                
______________________________________________________________________________________________________________________ 
PROGRAM\OUTPUT: T_xxxx.SAS\T_xxxxx.LST                                                     DATE(TIME): DDMMMYY(HH:MM) 
  
Treatment-Emergent AEs: AEs that began or worsened from baseline following the first administration of study drug. 
Note: Subjects are counted only once under in the lowest dose group. 
Note: N=the number of subjects who ever took a dose within the dose group, based on which the percent is calculated. 
Note: AEs that occurred following the date of treatment crossover were not included. 
[1] Grade 4 Thrombocytopenia is defined as any occurrence of a treatment emergent hematology lab below 25 GI/L 
Reference: Listing 16.2.8.1.4 
 


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PROTOCOL: INCB 18424-258                                                                                (Page 1 of 1) 
DRUG/INDICATION: Ruxolitinib/Myelofibrosis                                                             VERSION: Final 
  
                                                      Table 14.3.3.6.2 
  
Summary of Subjects with Treatment Emergent Anemia of Grade 4 as Derived from Laboratory Data  
by Last Dose Before Onset 
                                       (Population: Safety Evaluable Subjects) 
  
 
NOTE TO THE PROGRAMMER: similarly program this as Table 14.3.3.6.1, just need to update footnote about G4 anemia. 
 


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NOTE: the following vital sign tables will be programmed according to standard output. 
 
 
14.3.4.1 
Summary of Systolic Blood Pressure 
Safety 
14.3.4.2 
Summary of Diastolic Blood Pressure  
Safety 
14.3.4.3 
Summary of Heart Rate  
Safety 
14.3.4.4 
Summary of Respiratory Rate  
Safety 
14.3.4.5 
Summary of Body Temperature 
Safety 
 


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NOTE: the following laboratory tables will be programmed according to standard output. 
 
14.2.1.1 
Scatter Plot of Percent Change from Baseline in Spleen Volume at 
Week 24 vs. Final Titrated Dose Level 
ITT 
14.2.1.2 
Scatter Plot of Percent Change from Baseline in Total Symptom 
Score at Week 24 vs. Final Titrated Dose Level 
ITT 
14.2.1.3 
Scatter Plot of Percent Change from Baseline in Spleen Volume vs. 
Percent Change in Total Symptom Score at Week 24 
ITT 
14.2.2.1 
Bar Plot of Percent of Subjects with >= 35% Reduction from 
Baseline in Spleen Volume at Week 24 by Final Titrated Dose 
Group 
ITT 
14.2.2.2 
Bar Plot of Percent of Subjects with >= 10% Reduction from 
Baseline in Spleen Volume at Week 24 by Final Titrated Dose 
Group 
ITT 
14.2.2.3.1 
Mean (95%) Percent Change from Baseline in Spleen Volume at 
Week 24 
ITT 
14.2.2.3.2 
Mean (95%) Percent Change from Baseline in Spleen Volume at 
Week 24 by Final Titrated Dose Group 
ITT 
 
 
 
14.3.1.1.1 
Subject Laboratory Value over Time: Hemoglobin (G/L) 
Safety 
14.3.1.1.2 
Mean (95% CI) Laboratory Value Over Time: Hemoglobin (G/L) 
Safety 
14.3.1.2.1 
Subject Laboratory Value over Time: Platelet (GI/L) 
Safety 
14.3.1.2.2 
Mean (95% CI) Laboratory Value Over Time: Platelet (GI/L) 
Safety 
14.3.1.3.1 
Subject Laboratory Value over Time: WBC (GI/L) 
Safety 
14.3.1.3.2 
Mean (95% CI) Laboratory Value Over Time: WBC (GI/L) 
Safety 
14.3.1.4.1 
Subject Laboratory Value over Time: Neutrophils (GI/L) 
Safety 
14.3.1.4.2 
Mean (95% CI) Laboratory Value Over Time: Neutrophils (GI/L) 
Safety