Clinical trial NCT01728805
Conditions: Cutaneous T-Cell Lymphoma
Keywords: Cutaneous T-Cell Lymphoma (CTCL) myocis fungoides (MF) Sezary Syndrome (SS)
Sponsor: Kyowa Kirin, Inc.
Start date: 2012-11-01; Completion date: 2021-02-17
Enrollment: 372 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare the progression free survival of KW-0761 versus vorinostat for subjects with relapsed or refractory CTCL.

Detailed description:
Phase 3 randomized study to compare the progression free survival of subjects with relapsed/refractory CTCL who receive KW-0761 versus those who receive vorinostat. Subjects who progress on vorinostat will be allowed to cross over to KW-0761 upon progression.

Arms: arm 1: anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) arm 2: vorinostat 400 mg once daily
Interventions: intervention 1: KW-0761 intervention 2: Vorinostat
Intervention descriptions: intervention 1: 1.0 mg/kg weekly x 4 in cycle 1 then every other week until progression intervention 2: None

Protocol documents:
Prot_002.pdf: 
 
CONFIDENTIAL 
1 
PROTOCOL 0761-010 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell 
Lymphoma 
REVISED TO INCORPORATE AMENDMENT 10 
Protocol Number: 
0761-010 
Replaces 
Amendment 9: 
 
20 Apr 2018 
Amendment 10: 
31 May 2018 
Phase: 
3 
IND Number: 
101,843 
EudraCT Number: 
2012-004766-17 
Sponsor: 
Kyowa Kirin Pharmaceutical Development, Inc. 
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
+1 609 919-1100 
 
Study Monitors: 
 
 
  
 
 
 
 
  
Medical Monitors: 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
The information contained in this document is the property of or under the control of Kyowa Kirin Pharmaceutical 
Development, Inc. and its affiliated companies. This information is provided to you in confidence as an investigator, 
potential investigator or consultant, for review by you, your staff and applicable Institutional Review Board/Ethics 
Committee. You shall not disclose this information to others without prior written authorization from Kyowa Kirin 
Pharmaceutical Development, Inc., except to the extent necessary to obtain informed consent from those persons to whom 
the drug may be administered, and except as may be required by federal, state, or local laws or regulations. 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
2 
 
Principal Investigator Signature Page 
Protocol Title:  Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal 
Antibody KW-0761 (mogamulizumab) Versus Vorinostat in Subjects with Previously 
Treated Cutaneous T-Cell Lymphoma 
 
Protocol Number:  0761-010, Amendment 10 
 
CONFIDENTIALITY STATEMENT 
This protocol contains information that is proprietary to Kyowa Kirin Pharmaceutical 
Development, Inc. (KKD). This information is being provided to you for the purpose of 
conducting a clinical trial on behalf of KKD. You may disclose the contents of this protocol 
to the study personnel under your supervision and to your Institutional Review Board (IRB) 
or Ethics Committee (EC). As a Clinical Investigator participating in this study you agree to 
not disclose the contents of this protocol to any other parties (unless such disclosure is 
required by government regulations or laws) without the prior written permission of KKD. 
Any supplemental information (e.g., protocol amendment, Investigator’s Brochure) that may 
accompany this document is also proprietary to KKD and should be handled consistent with 
the terms stated above. 
By my signature below, the Principal Investigator attests that they have read, understood, and 
agree to abide by all conditions, instructions, and restrictions contained in this protocol 
(including appendices). The Principal Investigator will not initiate this study without approval 
from the appropriate IRB or Ethics Committee and understands that any changes in the 
protocol must be approved in writing by the Sponsor and the IRB or Ethics Committee before 
they can be implemented, except where necessary to eliminate immediate hazards to the 
subject. 
 
Principal Investigator: 
 
______________________________________________    ________________________ 
Printed Name/Signature 
 
 
 
 
Date 
________________________________________________________________________ 
Institution 
________________________________________________________________________ 
Address 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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3 
 
Protocol Signature Page  
Protocol Title:  Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal 
Antibody KW-0761 (mogamulizumab) Versus Vorinostat in Subjects with Previously 
Treated Cutaneous T-Cell Lymphoma 
 
Protocol Number:  0761-010, Amendment 10 
 
 
 
 
Signature 
 
 
  
 
 
Date 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
4 
 
Summary of Changes in Amendment 10 
A new section (Section 7.8) was added to the protocol to specify procedures to be followed 
for subjects who are ongoing in the study at the time of initial marketing authorization.  
These procedures should be implemented upon notification by the Sponsor. 
1) For subjects who are continuing to receive KW-0761, the Sponsor will continue to 
supply study drug until KW-0761 becomes commercially available (reimbursable) in 
the country/region of the study site or until KW-0761 is not approved for marketing 
for the indication and regimen under study in the country/region of the study site. 
2) For all ongoing subjects, i.e., subjects who are continuing to receive KW-0761 or who 
are in safety or survival follow-up at the time of initial marketing authorization, 
changes in study procedures and data collection are described. 
References to Section 7.8 were added as relevant in other protocol sections. 
Other minor updates were made for consistency. 
The Sponsor does not consider that these changes impact the overall risk/benefit of this study. 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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Serious Adverse Event Contact Information 
US, Europe, Australia 
Japan 
Drug Safety Surveillance 
Phone: +1-609-919-1100 
Available 9:00 am-5:00 pm (Eastern time) 
2:00 pm-10:00 pm (GMT) 
US SAE Fax: +1-800-209-2251 
UK SAE Fax:  +44 808 171 9999 
e-mail address:  saesource@kyowakirin.com 
Available 24 hours daily 
 
Drug Safety Surveillance 
SAE Fax: +81-3-6683-7721 
 
 
After hours Contacts: 
All US, EU, Australian Study Sites: 
Dmitri O. Grebennik, MD 
Medical Monitor-KKD 
Phone: +1-609-902-4703 
dmitri.grebennik@kyowakirin.com 
 
Japanese Study Sites: 
Yoshihiro Hara, MD, PhD 
CMIC Co., Ltd. 
Tel：+81-80-3341-3861 
Fax：+81-3-6683-7721 
yoshihiro-hara.kh@cmic.co.jp 
 
 
 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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Table of Contents 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE ...................................................... 2 
PROTOCOL SIGNATURE PAGE ..................................................................................... 3 
SUMMARY OF CHANGES IN AMENDMENT 10 .......................................................... 4 
SERIOUS ADVERSE EVENT CONTACT INFORMATION .......................................... 5 
TABLE OF CONTENTS ..................................................................................................... 6 
LIST OF IN-TEXT TABLES ............................................................................................ 11 
LIST OF APPENDICES.................................................................................................... 11 
PROTOCOL SYNOPSIS .................................................................................................. 12 
LIST OF ABBREVIATIONS ............................................................................................ 27 
1 
BACKGROUND AND RATIONALE .................................................................... 30 
1.1 
Cutaneous T-Cell Lymphomas ............................................................................... 30 
1.2 
Treatment of Cutaneous T-cell Lymphomas ........................................................... 31 
1.3 
Chemokine Receptor 4 and T-Cell Malignancies .................................................... 31 
1.4 
KW-0761 (mogamulizumab) .................................................................................. 33 
1.5 
Safety and Efficacy of KW-0761 ............................................................................ 33 
1.6 
Vorinostat (ZOLINZA®) ........................................................................................ 34 
1.7 
Rationale ................................................................................................................ 36 
2 
OBJECTIVES .......................................................................................................... 37 
2.1 
Primary Objectives ................................................................................................. 37 
2.2 
Secondary Objectives ............................................................................................. 37 
2.3 
Exploratory Objectives ........................................................................................... 38 
3 
STUDY POPULATION .......................................................................................... 38 
3.1 
Subject Selection .................................................................................................... 38 
3.2 
Inclusion Criteria .................................................................................................... 38 
3.3 
Exclusion Criteria ................................................................................................... 40 
3.4 
Eligibility for Cross-over to KW-0761 .................................................................... 41 
4 
INVESTIGATIONAL PLAN .................................................................................. 42 
4.1 
Overview of Study Design ...................................................................................... 42 
4.2 
Number of Subjects ................................................................................................ 42 
4.3 
Investigational Centers ........................................................................................... 42 


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5 
TREATMENT PLAN .............................................................................................. 42 
5.1 
Assignment to Study............................................................................................... 42 
5.2 
Study Treatments.................................................................................................... 42 
5.2.1 
Study Drug: KW-0761 (mogamulizumab) ........................................................... 43 
5.2.1.1 
Premedication Prior to KW-0761 Infusion ....................................................... 43 
5.2.1.2 
Definition of Treatment Cycle ......................................................................... 43 
5.2.1.3 
Delays in Dosing ............................................................................................. 43 
5.2.1.4 
Duration of Treatment ..................................................................................... 43 
5.2.1.5 
Replacement of Subjects .................................................................................. 44 
5.2.1.6 
Dose Modifications .......................................................................................... 44 
5.2.1.7 
Treatment of Hypersensitivity-Like Reactions ................................................. 44 
5.2.1.8 
Treatment Emergent Skin Rash ........................................................................ 46 
5.2.2 
Study Drug: Vorinostat (ZOLINZA®) ................................................................. 48 
5.2.2.1 
Definition of Treatment Cycle ......................................................................... 49 
5.2.2.2 
Delays in Dosing ............................................................................................. 49 
5.2.2.3 
Duration of Treatment ..................................................................................... 49 
5.2.2.4 
Replacement of Subjects .................................................................................. 50 
5.2.2.5 
Dose Modifications .......................................................................................... 50 
5.3 
Cross-over to Study Drug KW-0761 ....................................................................... 50 
5.4 
Concomitant Therapy ............................................................................................. 51 
5.4.1 
Permitted Treatment ............................................................................................ 51 
5.4.2 
Prohibited Treatment........................................................................................... 52 
5.5 
Criteria for Removal from Study ............................................................................ 53 
6 
STUDY PROCEDURES.......................................................................................... 54 
7 
STUDY MEASUREMENTS ................................................................................... 54 
7.1 
Safety Evaluations .................................................................................................. 55 
7.1.1 
Clinical Laboratory Evaluations .......................................................................... 55 
7.1.2 
Vital Signs and Body Weight .............................................................................. 57 
7.1.3 
Physical Examination .......................................................................................... 58 
7.1.4 
Electrocardiograms ............................................................................................. 58 
7.1.5 
Blood Sample for Determination of Natural Ligands ........................................... 58 


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7.1.6 
Genomic Sampling (For subjects receiving KW-0761 as first assigned 
therapy only) ....................................................................................................... 59 
7.1.7 
Immunogenicity (For subjects receiving KW-0761) ............................................ 59 
7.2 
Efficacy Evaluations ............................................................................................... 59 
7.2.1 
Evaluation of Skin Disease.................................................................................. 60 
7.2.1.1 
Skin Biopsy ..................................................................................................... 60 
7.2.1.2 
Skin Photographs ............................................................................................. 61 
7.2.1.3 
Modified Severity Weighted Assessment Tool (mSWAT) ............................... 62 
7.2.1.4 
Response Criteria for Skin ............................................................................... 63 
7.2.1.5 
Pruritus Evaluation .......................................................................................... 64 
7.2.2 
Evaluation of Blood Disease ............................................................................... 64 
7.2.2.1 
Flow Cytometric Analysis ............................................................................... 64 
7.2.2.2 
Response Criteria in Blood .............................................................................. 65 
7.2.3 
Evaluation of Disease in Lymph Nodes and Viscera............................................ 65 
7.2.3.1 
Baseline Tumor Assessments ........................................................................... 65 
7.2.3.2 
Method of Tumor Response Assessment .......................................................... 65 
7.2.3.3 
Determination of Response in Lymph Nodes and Viscera ................................ 66 
7.2.4 
Global Composite Response Score ...................................................................... 68 
7.2.4.1 
Independent Review of Progression ................................................................. 69 
7.3 
Pharmacokinetics (for subjects receiving KW-0761) .............................................. 70 
7.4 
Quality of Life Assessments ................................................................................... 70 
7.5 
Follow-Up .............................................................................................................. 70 
7.6 
Follow-Up for Subjects Achieving a Complete Response ....................................... 71 
7.7 
Study Procedures for Subjects Continuing Study Treatment at the Time 
of Primary Efficacy Analysis .................................................................................. 72 
7.8 
Study Procedures for Subjects Ongoing at the Time of Regional Drug 
Approval ................................................................................................................ 73 
8 
STUDY AGENTS .................................................................................................... 74 
8.1 
KW-0761 (mogamulizumab) .................................................................................. 74 
8.1.1 
Description ......................................................................................................... 74 
8.1.2 
Preparation of Dose............................................................................................. 74 
8.1.3 
Study Drug Administration ................................................................................. 74 


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8.1.4 
KW-0761 Formulation and Storage ..................................................................... 75 
8.1.5 
Packaging and Labeling of KW-0761 .................................................................. 75 
8.1.5.1 
Labeling .......................................................................................................... 76 
8.1.6 
Drug Accountability ............................................................................................ 76 
8.1.7 
Return and Destruction ....................................................................................... 76 
8.2 
Vorinostat (ZOLINZA®) Capsules.......................................................................... 76 
8.2.1 
Description ......................................................................................................... 76 
8.2.2 
Administration .................................................................................................... 77 
8.2.3 
Vorinostat Adverse Events .................................................................................. 77 
8.2.4 
Return and Destruction ....................................................................................... 77 
9 
ADVERSE EVENT REPORTING IN CLINICAL TRIALS ................................ 77 
9.1 
Definitions ............................................................................................................. 78 
9.1.1 
Adverse Events ................................................................................................... 78 
9.1.2 
Adverse Event Severity ....................................................................................... 79 
9.1.3 
Adverse Event Relationship to Study Drug ......................................................... 79 
9.2 
Serious Adverse Events .......................................................................................... 80 
9.3 
Other Safety Considerations ................................................................................... 82 
9.4 
Adverse Event Contacts .......................................................................................... 82 
9.5 
Data Safety Monitoring Board ................................................................................ 82 
10 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS........................... 82 
10.1 
Populations to be Analyzed .................................................................................... 83 
10.2 
Analyses of Safety Data.......................................................................................... 83 
10.3 
Analyses of Efficacy Data ...................................................................................... 84 
10.4 
Exposure-Response Analysis .................................................................................. 88 
11 
ETHICAL ASPECTS .............................................................................................. 88 
11.1 
Ethics and Good Clinical Practice ........................................................................... 88 
11.2 
Ethics Committee/Institutional Review Board ........................................................ 89 
11.3 
Informed Consent ................................................................................................... 89 
12 
INVESTIGATOR OBLIGATIONS AND STUDY MANAGEMENT .................. 91 
12.1 
Administrative ........................................................................................................ 91 
12.2 
Changes in Protocol ................................................................................................ 91 


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12.3 
Protocol Deviations ................................................................................................ 91 
12.4 
Monitoring and Quality Assurance ......................................................................... 91 
12.5 
Electronic Case Report Forms (eCRFs) and Source Documentation ....................... 92 
12.6 
Record Retention .................................................................................................... 93 
12.7 
Confidentiality ....................................................................................................... 93 
12.8 
Disclosure .............................................................................................................. 94 
12.9 
Termination of Study .............................................................................................. 94 
12.10 
Final Report/Publications ....................................................................................... 94 
13 
REFERENCES ........................................................................................................ 96 
14 
APPENDICES ....................................................................................................... 101 
 
 
 


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List of In-text Tables 
Table 1 
Study Procedures:  First Treatment Cycle ....................................20 
Table 2 
Study Procedures:  Subsequent Cycles in Year 1 .........................22 
Table 3 
Study Procedures:  Subsequent Cycles in Year 2 and Beyonda ....24 
Table 5.2.1-1 
Guidelines for Treatment of Skin Rash ........................................48 
Table 7.1.1-1 
Clinical Laboratory Assessments .................................................57 
Table 7.2.1-1 
Modified Severity Weighted Assessment Tool ............................62 
Table 7.2.1-2 
Modified Severity Weighted Assessment Tool Score ..................63 
Table 7.2.1-3 
Response Criteria for Skin, as assessed by mSWAT scoresa ........64 
Table 7.2.2-1 
Blood Response Criteriaa .............................................................65 
Table 7.2.3-1 
Response in Lymph Nodesa .........................................................67 
Table 7.2.3-2 
Response in Viscera ....................................................................68 
Table 7.2.4-1 
Global Composite Scoring System ..............................................69 
Table 10.3-1 
Required PFS Events and Power for Comparison of PFS Kaplan-
Maier Curves Between the Vorinostat and KW-0761 Arms at the 
0.025 Level .................................................................................88 
 
List of Appendices 
Appendix 1 
Modified ISCL/EORTC Revisions to the TNMB Classification 
of MF/SS .................................................................................. 102 
Appendix 2 
Eastern Cooperative Oncology Group (ECOG) Scale ................ 103 
Appendix 3 
NYHA Classification ................................................................ 104 
Appendix 4 
Autoimmune Screening Questionnaire ...................................... 105 
Appendix 5 
Itchy Quality of Life Questionnaire ........................................... 106 
Appendix 6 
Skindex-29 ................................................................................ 107 
Appendix 7 
FACT-G .................................................................................... 108 
Appendix 8 
EQ-5D-3L ................................................................................. 109 
Appendix 9 
Likert Scale for Pruritus Evaluation ........................................... 110 


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 PROTOCOL SYNOPSIS 
Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
Study Location: 
United States, Europe, Japan, and Australia 
Clinical Phase:  
3 
Study Period: 
Planned enrollment period: 24 months  
Planned study period: 36 months  
Study Drug: 
KW-0761 
Comparator Drug: 
Vorinostat (ZOLINZA®) 
Population Size: 
It is anticipated that approximately 317 subjects may be required to enroll in this study in order to achieve the 
necessary 255 progression-free survival (PFS) events for analysis. 
Study Design: 
This is an open-label, multi-center randomized, Phase 3 study with 1:1 randomization of study drug, KW-0761 
versus the comparator, vorinostat. 
Study Population: 
This study will enroll subjects with Stage IB, II-A, II-B, III and IV mycosis fungoides (MF) or Sézary syndrome 
(SS) who have failed at least one prior course of systemic therapy.  
Study Objectives: 
Primary Objective 
• 
To compare the progression free survival of KW-0761 versus vorinostat for subjects with relapsed or 
refractory Cutaneous T-Cell Lymphoma (CTCL). 
Secondary Objectives 
• 
To compare the overall response rate of KW-0761 versus vorinostat in subjects with relapsed or refractory 
CTCL; 
• 
To evaluate and compare improvements in Quality of Life (QoL) measurements, Skindex-29, FACT-G, and 
EQ-5D-3L for subjects receiving KW-0761 versus vorinostat; 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
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Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
• 
To evaluate and compare improvements in the Pruritus Evaluation (Likert scale & Itchy QoL) for subjects 
receiving KW-0761 versus vorinostat;  
• 
To estimate the duration of response for both the KW-0761 and vorinostat arms for those subjects with 
relapsed or refractory CTCL responding to treatment; 
• 
To determine if subjects who relapse on vorinostat can achieve response upon cross over to treatment with 
KW-0761;  
• 
To further assess the safety of KW-0761; 
• 
To describe the immunogenicity of KW-0761; 
Exploratory Objectives 
• 
To compare the overall survival of KW-0761 versus vorinostat for subjects with relapsed or refractory 
CTCL.  
• 
To conduct exploratory evaluation of KW-0761 exposure-response relationships. 
Inclusion Criteria: 
1) Voluntarily signed and dated Institutional Review Board / Ethics Committee approved informed 
consent form in accordance with regulatory and institutional guidelines. Written informed consent must 
be obtained prior to performing any study-related procedure; 
Age and Sex 
2) Males and female subjects ≥ 18 years of age at the Pre-treatment Visit, i.e., at the time that written 
informed consent is obtained, except in Japan where subjects must be ≥  20 years of age; 
Target Population 
3) Histologically confirmed diagnosis of MF or SS; 
a. 
For SS (defined as meeting T4 plus B2 criteria), where the biopsy of erythrodermic skin may only 
reveal suggestive but not diagnostic histopathologic features, the diagnosis may be based on either 
a node biopsy or fulfillment of B2 criteria including a clone in the blood that matches that of the 
skin. 
4) Stage IB, II-A, II-B, III and IV; 
5) Subjects who have failed at least one prior course of systemic therapy (e.g., interferon, denileukin 
diftitox, bexarotene, photopheresis, anti-neoplastic chemotherapy, etc.). Psoralen plus ultraviolet light 
therapy (PUVA) is not considered to be a systemic therapy; 
6) Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1; 
7) The subject has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤ 1 
by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 


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Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
(NCI-CTCAE, v.4.0) excluding the specifications required in 8, 9 and 10 below. 
8) Adequate hematological function:  
a. 
absolute neutrophil count (ANC) ≥ 1,500 cells/μL (≥ 1,500/mm3); 
b. platelets ≥ 100,000 cells/μL; (≥ 100,000/mm3); 
c. 
in subjects with known bone marrow involvement, ANC must be ≥ 1,000 cells/μL (≥ 1,000/mm3) 
and platelets ≥ 75,000 cells/μL. (≥ 75,000/mm3). 
9) Adequate hepatic function:  
a. 
bilirubin ≤ 1.5 times the specific institutional upper limit of normal (ULN), except for subjects 
with Gilbert’s syndrome;  
b. aspartate transaminase (AST) and alanine transaminase (ALT) each ≤ 2.5 x ULN or ≤ 5.0 x ULN 
in the presence of known hepatic involvement by CTCL.  
10) Adequate renal function:  
a. 
serum creatinine ≤ 1.5 x ULN; 
                                            or  
b. calculated creatinine clearance > 50 mL/min using the Cockcroft-Gault formula. 
11) Subjects previously treated with anti-CD4 antibody or alemtuzumab are eligible provided their CD4+ 
cell counts are ≥ 200/mm3. 
12) Subjects with MF and a known history of non-complicated staphylococcus infection/colonization are 
eligible provided they continue to receive stable doses of prophylactic antibiotics. 
13) Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days of 
receiving study medication. 
14) WOCBP must agree to use effective contraception, defined as oral contraceptives, double barrier 
method (condom plus spermicide or diaphragm plus spermicide) or practice true abstinence from 
sexual intercourse (periodic abstinence, e.g., calendar, ovulation, symptothermal, post-ovulation 
methods and withdrawal are not acceptable methods of contraception) during the study and for 
3 months after the last dose. WOCBP includes any female who has experienced menarche and who has 
not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea 
≥ 12 consecutive months without an alternative medical cause); 
15) Male subjects and their female partners of child bearing potential must be willing to use an appropriate 
method of contraception defined as oral contraceptives, double barrier method (condom plus 
spermicide or diaphragm plus spermicide) or practice true abstinence from sexual intercourse (periodic 
abstinence, e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not 
acceptable methods of contraception) during the study and for 3 months after the last dose. 


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Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
NOTE:  For subjects continuing to receive study treatment as of protocol Amendment 8, the period of 
contraceptive use should be extended to 6 months after the last dose of KW-0761. 
Exclusion Criteria: 
Medical History and Concurrent Diseases 
1) Current evidence of large cell transformation (LCT). Subjects with clinical features suggestive of LCT 
must have a biopsy performed within 4 months prior to Cycle 1 Day 1 to rule out transformed disease. 
Subjects with a history of LCT but without current aggressive disease and no current evidence of LCT 
on pathology in skin or lymph nodes would be eligible; 
2) Diagnosed with a malignancy in the past 2 years. However, subjects with non-melanoma skin cancers, 
melanoma in situ, localized cancer of the prostate with current prostate-specific antigen of 
< 0.1 ng/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of 
the breast with in the past 2 years may enroll as long as there is no current evidence of disease.  
3) Clinical evidence of central nervous system (CNS) metastasis. 
4) Psychiatric illness, disability or social situation that would compromise the subject’s safety or ability to 
provide consent, or limit compliance with study requirements. 
5) Significant uncontrolled intercurrent illness including, but not limited to:  
a. 
uncontrolled infection requiring antibiotics;  
b. clinically significant cardiac disease (class III or IV of the New York Heart Association 
classification);  
c. 
unstable angina pectoris;  
d. angioplasty, stenting, or myocardial infarction within 6 months;  
e. 
uncontrolled hypertension (systolic blood pressure (BP) > 160 mm Hg or diastolic BP 
> 100 mm Hg, found on 2 consecutive measurements separated by a 1-week period) despite 2 anti-
hypertensive medications;  
f. 
clinically significant cardiac arrhythmia; or  
g. uncontrolled diabetes.  
6) Known or tests positive for human immunodeficiency virus, human T-cell leukemia virus, hepatitis B 
or hepatitis C disease. 
7) Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes who started taking 
medication at least 30 days prior to the Pre-treatment Visit, and have no active signs of active infection, 
and whose last active infection was more than 6 months ago, may enter the study, and should continue 
to take the prescribed medication for the duration of the study. 
8) Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins. 
9) Known active autoimmune disease will be excluded. (For example, Graves’ disease; systemic lupus 


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16 
 
Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
erythematosus; rheumatoid arthritis; Crohn’s disease; psoriasis). 
10) Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating. 
Prohibited Therapies and/or Medications 
11) Prior treatment with KW-0761. 
12) Prior treatment with vorinostat. Patients who were exposed  to vorinostat for a short time, did not 
progress while on treatment, and did not have intolerable toxicity but were discontinued for another 
reason (e.g., comorbidity) may be permitted to enter the study after discussion with the Medical 
Monitor. 
13) Have had any therapy directed against the subject’s underlying cancer or any investigational 
medications within four weeks of randomization (skin directed treatments, including topicals and 
radiation within 2 weeks of randomization). However, subjects with rapidly progressive malignant 
disease may be enrolled prior to this period after discussion with the Medical Monitor.  
14) Subjects on a stable dose of a low dose systemic corticosteroid (≤ 20 mg prednisone equivalent) for at 
least 4 weeks prior to the Pre-treatment Visit may continue use although the investigator should attempt 
to taper the use to the lowest dosage tolerable while on study. Initiation of treatment with systemic 
corticosteroids or increase in dose while on study is not permitted except to treat an infusion reaction 
(see Section 5.2.1.7). Subjects may receive intra-articular corticosteroid injections, intraocular 
corticosteroid drops, inhalation or nasal corticosteroids and replacement doses of systemic 
corticosteroids as needed.  
15) Subjects on a stable dose of medium or low potency topical corticosteroids for at least 4 weeks prior to 
the Pre-treatment Visit may continue use at the same dose, although the investigator should attempt to 
taper the use to the lowest dosage tolerable while on study. Initiation of treatment with topical 
corticosteroids while on study is not permitted except to treat an acute rash. 
16) History of allogeneic transplant. 
17) Autologous hematopoietic stem cell transplant within 90 days of the Pre-treatment Visit. 
18) Subjects on any immunomodulatory drug for concomitant or intercurrent conditions other than T-cell 
lymphoma or who have received any of these agents within 4 weeks of treatment, including but not 
limited to the following, will be excluded:  low dose or oral methotrexate; azathioprine; intravenous 
(iv) immunoglobulin; low dose or oral cyclophosphamide; cyclosporine; mycophenolate; infliximab; 
etanercept; leflunomide; adalimumab; lenalidomide; abatacept; rituximab; anakinra; interferon-β; IL-2 
and natalizumab. 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
17 
 
Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
Methods: 
Subjects will be randomized 1:1 to receive either KW-0761 or vorinostat. Treatment will be administered on an 
outpatient basis. The dose of KW-0761 will be 1.0 mg/kg. The dose of vorinostat will be the recommended dose 
of 400 mg (once daily with food).  
Each treatment cycle is 28 days. Subjects will receive KW-0761 as an iv infusion over at least 1 hour on Days 1, 
8, 15 and 22 of the first cycle and on Days 1 and 15 of subsequent cycles. Vorinostat will be administered orally 
daily beginning on Day 1. 
Duration of Treatment 
Subjects may remain in the treatment phase up until progressive disease (PD), drug intolerance, or unacceptable 
toxicity, or until any of the other criteria for study removal are met. If the subject experiences an overall CR, the 
subject may continue treatment for up to 12 months or until progression, whichever comes first. 
Cross-over to Study Drug KW-0761 
Subjects who have received at least 2 full treatment cycles and demonstrate progression of disease on treatment 
with vorinostat at the 8 week (Cycle 2, Day 26-28) assessment, or anytime thereafter, may cross over to 
treatment with KW-0761 after discussion with Medical Monitor or designee and receipt of approval for cross 
over from KKD. Investigators should strive to maintain subjects on treatment for at least the 8 week period, 
adjusting the dose of vorinostat as needed for toxicities in order to allow sufficient time to see effect. In cases 
where a subject’s disease progresses rapidly (i.e., prior to 8 weeks), the Medical Monitor or designee should be 
contacted and may consider the possibility of early crossover, if appropriate for that subject. All subjects must 
undergo the full extent of disease evaluations (including computed tomography scanning) to document PD prior 
to crossover.  
Study Procedures for Subjects Continuing Study Treatment at the Time of Primary Efficacy Analysis 
and for Ongoing Subjects at the Time of Initial Marketing Authorization 
For subjects who are continuing to receive study treatment at the time of the primary efficacy analysis, 
procedures and assessments are described in Section 7.7.  Procedures to be followed for subjects who are 
ongoing in the study (i.e., subjects who are continuing to receive KW-0761 or who are in safety or survival 
follow-up) at the time of initial marketing authorization are described in Section 7.8. 
Replacement of Subjects 
Subjects will not be replaced. 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
18 
 
Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
Criteria for Evaluation: 
Safety:  The safety of KW-0761 and vorinostat will be determined by reported AEs, changes in physical 
examinations, vital sign measurements, ECGs and laboratory analyses. Safety evaluations will be performed 
throughout the study.  
Efficacy:  Efficacy evaluations will be based on response to treatment (partial response [PR] or better), time to 
PD, duration of overall response, and quality of life. 
Statistical Analysis: 
The following analysis sets will be used in the study: 
• 
Intent-to-Treat (ITT) Set:  Includes all subjects randomized to a therapy and assigned a study number. 
• 
Safety Analysis Set:  Includes all subjects who received at least one dose of the assigned study agent (even 
a partial dose).  
• 
Efficacy Evaluable Set: Includes all subjects who receive the first cycle of treatment and who have baseline 
and the Day 26-28 on-study assessment for response.  
• 
Pharmacokinetic (PK) Analysis Set:  All subjects who provide at least one post-dose KW-0761 
concentration measurement will be included in the PK analysis dataset.  
Evaluation of the data for this study will consist primarily of data listings and summary displays. Demographic 
and other baseline characteristic information will be summarized for the ITT Set. All summaries for the Safety 
Analysis Set will be prepared for each treatment arm. Adverse events will be tabulated by body system, severity, 
and relation to treatment. Similar presentations will be provided for serious adverse events, AEs leading to 
withdrawal from study, and AEs leading to death. The tabulation of laboratory parameters will indicate the 
normal range for each parameter. Each value will be classified as falling above, below, or within the normal 
range.  
Subjects will be evaluated for response in each compartment. Progression-free-survival, overall response, 
duration of response, and QoL will be analyzed. For any time-to-event endpoints, the date of disease progression 
will be determined by both the on-site investigator’s assessment and by independent review (IR). All efficacy 
analyses will be conducted on both the ITT and Efficacy Evaluable sets.  
The primary comparison of PFS between both arms will be performed on the ITT set based upon the results of 
the on-site investigator’s assessment using a stratified Log-rank test at the one-sided 2.5% significance level. 
Stratification is done by disease type, either SS or MF, and disease stage, either IB/II or III/ IV. A similar 
secondary analysis will be performed on the results based on the IR. An IR will review each subject to make a 
determination regarding progression and the date of progression in each compartment. 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
19 
 
Name and Address of 
Sponsor/Company: 
Kyowa Kirin Pharmaceutical 
Development, Inc.  
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Individual Study Table Referring 
to Part of the Dossier. 
Volume:  
 
Page:  
(For National Authority Use 
only) 
Name of Finished Product: 
 
Name of Active Ingredient: 
KW-0761 (mogamulizumab) 
Study Title: 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell Lymphoma  
Protocol No. 
0761-010 
Each analysis will also be conducted for the Efficacy Evaluable Set. PFS, which will be analyzed using Kaplan-
Meier survival analysis methods, is defined as the time from the first day of randomization to a treatment arm 
until documented progression or death.  
For PFS events, all deaths will be attributed to progression and, hence, the time to progression will equal the 
time to death and will be uncensored. Subjects who die without a reported prior progression will still be 
considered to have progressed on the day of their death. In the event that a randomized subject withdraws from 
the study for any reason before documented progression, the time from the day of randomization to the last 
tumor assessment (from any compartment) will be used as a censored time point. For all subjects randomized to 
a treatment arm but withdrawing prior to first tumor assessment for any reason other than disease progression, 
the PFS time will be censored at last documented visit.  
ORR will be calculated as the proportion of subjects who are responders (complete response, and PR) and the 
95% exact confidence interval for response will be calculated. 
Since the primary endpoint is PFS, the reference median PFS for vorinostat is assumed to be 169 days. The 
median PFS for KW-0761 therapy is targeted for 254 days, a 50% improvement over this reference median. The 
ITT set is used for this primary analysis. The same analysis conducted using the Efficacy Evaluable set is 
considered secondary. 
Under these assumptions, for the ITT population, a total of 255 PFS events will give 90% power. In the event 
that the study is stopped prior to 255 PFS events are observed, the primary test will be performed at less than 
90% power under the current assumptions. 
A total sample size of 288 may be necessary for 255 PFS events to occur within the projected 36 months of the 
trial. A 10% inflation factor is applied to this total (about 29 subjects) to take into account those subjects that 
may be lost to follow-up prior to documented progression, for a total of 317 enrolled subjects to observe 
255 PFS events. If the 255 PFS events are not observed within 36 months from the start of enrollment the study 
will be stopped at approximately 24 months after the last randomized subject’s first dose. 
 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
20 
 
Table 1 
Study Procedures:  First Treatment Cycle 
 
Pre-
treatment 
Visit 
First Treatment Cycle 
Procedures 
D 1 
D 8 
D 15 
D 22 
D 26-28a 
Visit Window 
Up to 
Day -30 
 
±2 days 
±2 days 
±2 days 
+ 2 days 
Informed consent 
X 
 
 
 
 
 
Review of subject eligibility 
X 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
Physical examinationb 
X 
X 
 
X 
 
X 
ECOG performance status (PS) 
X 
X 
 
X 
 
X 
Vital signs, Weight 
X 
Xc 
Xc 
Xc 
Xc 
X 
ECG 
X 
 
 
 
 
 
Pregnancy test (within 7 days)  
X 
 
 
 
 
 
Urinalysis 
X 
 
 
 
 
X 
Hematology profile 
X 
Xd 
Xd 
Xd 
Xd 
X 
Chemistry profile 
X 
Xd 
Xd 
Xd 
Xd 
X 
Coagulation profile 
X 
Xd 
 
 
 
 
Thyroid function tests (Free T4, TSH) 
X 
 
 
 
 
X 
Hepatitis B & C, HIV, HTLV-1 
X 
 
 
 
 
 
Flow Cytometric Analysis 
X 
 
 
 
 
X 
Blood sample for determination of 
natural ligands 
X 
 
 
 
 
X 
Serum sample for KW-0761 
concentration assessmente 
 
X 
X 
X 
X 
X 
Saliva sample for genetic analysis 
 
Xf 
 
 
 
 
KW-0761 Administrationg 
 
X 
Xh 
Xh 
Xh 
 
Vorinostat Administration 
 
Xi 
Adverse event assessmentj 
X 
X 
X 
X 
X 
X 
Concomitant medication assessmentk 
X 
X 
X 
X 
X 
X 
CT (diagnostic quality) 
X 
 
 
 
 
X 
Bone marrow aspiration & biopsyl 
X 
 
 
 
 
X 
Skin biopsy for assessment of disease 
Xm 
 
 
 
 
Xn 
Skin biopsy or archival tissue for CCR4 
expressiono 
X 
 
 
 
 
 
Skin photographs 
 
X 
 
 
 
X 
Modified Severity Weighted 
Assessment Tool (mSWAT) 
 
X 
 
 
 
X 
Pruritus Evaluation (Likert Scale & 
Itchy QoL) 
 
X 
 
 
 
X 
Skindex-29 , FACT-G & EQ-5D-3L 
 
X 
 
 
 
X 
Immunogenicityp 
 
X 
 
 
 
X 
Disease Progressionq 
 
Survival statusr 
 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
21 
 
Footnotes to Table 1 
a: If progression is noted at Day 26-28, visit should take place before initiation of new therapy. In cases where the definition 
of PD or relapse is met but the clinical impression is questionable, subjects may remain on study until the next evaluation 
(4 weeks later if questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after Year 1 if 
questionable finding in lymph nodes or viscera, with at least stable disease in other compartments) to avoid a subject 
being removed prematurely from the study. For subjects receiving a subsequent treatment course, procedures performed 
at this time can also be used to satisfy the Day 1 requirements for the subsequent course, provided they are performed 
within ± 2 days of next KW-0761 administration. For subjects who will not receive subsequent treatment, this visit will be 
considered the final treatment visit and subjects should undergo testing/procedures specified for End-of-treatment visit 
(See Table 3).  
b: Complete physical examination including height at Pre-treatment Visit; brief physical examination of pertinent systems at 
other times. Responses to questions for surveillance of autoimmune type symptoms (See Appendix 4) should be 
documented at time of physical exam. 
c: For subjects receiving KW-0761, vital signs will be checked and recorded prior to the start of each infusion, at the end of 
each infusion and 1 hour after the completion of the infusion. For subjects taking vorinostat, vital signs can be taken 
irrespective of dosing. Weight will be checked with vitals. 
d: Blood can be drawn 1 day prior to visit, if needed, to ensure results are available. In subjects receiving KW-0761, results 
must be reviewed prior to infusion. The platelet count must be ≥ 100,000 / mm3 and the ANC must be ≥ 1,500/mm3 
before a subject can receive study drug.  
e: Serum samples will be collected for subjects treated with KW-0761 pre-dose on days indicated (sample collection will 
still be needed even if dosing is not performed at a visit), as applicable. On Day 1, an additional sample should be 
obtained from the arm contralateral to that of study drug administration at the end of infusion (10-15 minutes after 
completion of the infusion) as well. At selected sites, 4 additional samples will be drawn between 6 and 8 hours, and at 
24, 48, and 72 - 96 hours after the first infusion on Day 1. 
f: Samples to be obtained for subjects assigned to KW-0761 as first assigned therapy only. 
g: KW-0761 is to be administered over at least one hour. 
h: If the study visit does not occur within ± 2 days of the scheduled visits, KW-0761 should not be administered at the visit 
and the next dose should be administered at the next timepoint.  
i: Vorinostat is administered orally daily beginning on Day 1 with food. 
j: If a subject who is receiving KW-0761 develops a skin rash, notify KKD and refer to Section 5.2.1.8 to treat and 
document the rash. 
k: Medication taken within 30 days prior to the first dose of study drug, and at any time after the start of treatment until 
30 days after the final study drug administration will be recorded.  
l: To be performed in subjects with cytopenia or other clinical suspicions of bone marrow involvement, at the discretion of 
the investigator. 
m: Subjects with clinical features suggestive of LCT must have a biopsy performed within 4 months prior to Cycle 1/Day 1 
to rule out transformed disease.  
n: Biopsy at the end of the cycle is optional and can be performed at the discretion of the investigator. Analysis of the biopsy 
will be done by a pathologist at the study site. 
o: To be performed for CCR4 expression as determined by IHC. IHC analysis will be performed by central laboratory 
designated by the Sponsor. The paraffin block or a fresh sample, if the study site is unable to process the tissue on the day 
obtained, may be submitted. Submission of unstained slides, while not recommended due to stability concerns with the 
sample, will be accepted. In the event, it is not possible to obtain a skin biopsy, use of an archived sample (taken within 
6 months prior to treatment) may be allowed with prior authorization from the Sponsor. For subjects receiving vorinostat 
who cross over to treatment with KW-0761, investigators are strongly encouraged to perform another biopsy for 
determination of CCR4 expression prior to treatment with KW-0761.  
p: KW-0761 subjects only for determination of anti-KW-0761 antibodies. 
q: Subjects who terminate for reasons other than disease progression or their referring physicians will be contacted every 
3 months (± 14 days) until documented disease progression or death or initiation of alternative therapy.  
r: All subjects or their referring physician will be contacted every 3 months (± 14 days) to ascertain survival status 
following discontinuation of treatment. 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
22 
 
Table 2 
Study Procedures:  Subsequent Cycles in Year 1 
 
Subsequent Cycles 2 through 13a 
Procedures 
D 1 
D 15 
D 26-28 
(Cycles 2, 4, 6, 
8, 10, 12)b 
D 26-28
(Cycles 3, 5, 7, 
9, 11, 13)b 
Visit Window 
 
± 2 days 
+ 2 days 
+ 2 days 
Physical examinationc 
X 
X 
X 
X 
ECOG PS 
X 
X 
X 
X 
Vital signs, Weight 
Xd 
Xd 
X 
X 
ECG 
 
 
 
 
Urinalysis 
X 
 
 
 
Hematology profile 
Xe 
Xe 
X 
X 
Chemistry profile 
Xe 
Xe 
X 
X 
Coagulation profile 
Xe 
 
 
 
Thyroid function tests (Free T4, TSH) 
 
 
 
X 
Flow Cytometric Analysisf 
 
 
X 
X 
Blood sample for determination of 
natural ligands 
 
 
 
X 
Serum sample for KW-0761 
concentration assessment 
Xg 
Xg 
 
 
KW-0761 Administration 
Xh 
Xh 
 
 
Vorinostat Administration 
Xi 
Adverse event assessmentj 
X 
X 
X 
X 
Concomitant medication assessmentk 
X 
X 
X 
X 
CT (diagnostic quality)f 
 
 
 
X 
Bone marrow aspiration & biopsyl 
 
 
 
X 
Skin biopsy 
 
 
 
Xm 
Skin photographsf 
 
 
X 
X 
Modified Severity Weighted 
Assessment Tool (mSWAT)f 
 
 
X 
X 
Pruritus Evaluation (Likert scale & 
Itchy QoL) 
 
 
X 
X 
Skindex-29, FACT-G & EQ-5D-3L 
 
 
 
X 
Immunogenicityn 
 
 
 
X 
Disease Progressiono 
 
Survival Statusp 
 
a: Subject may remain in treatment phase up until progressive disease, drug intolerance, or unacceptable toxicity, or until 
any of the other criteria for removal (See Section 5.5) are met. At each cycle, the Investigator must minimally have 
reviewed the mSWAT to determine if progression of skin disease has occurred prior to subsequent dosing (see Section 
5.2.1.4). For subjects who are continuing to receive study treatment at the time of the primary efficacy analysis, 
procedures and assessments are described in Section 7.7.  Procedures to be followed for subjects who are ongoing in the 
study at the time of initial marketing authorization are described in Section 7.8. 
 
 
 
 
 
 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
23 
 
Footnotes to Table 2 (continued). 
b: For subjects receiving a subsequent treatment course, procedures performed at this time can also be used to satisfy the 
Day 1 requirements for the subsequent course, provided they are performed within ± 2 days of next KW-0761 
administration. For subjects who will not receive subsequent treatment, this visit will be considered the final treatment 
visit and subjects should undergo testing/procedures specified for End-of-treatment visit (See Table 3). If progression is 
noted at Day 26-28, visit should take place before initiation of new therapy. In cases where the definition of PD or relapse 
is met but the clinical impression is questionable, subjects may remain on study until the next evaluation (4 weeks later if 
questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after Year 1 if questionable finding in  
lymph nodes or viscera, with at least stable disease in other compartments) to avoid a subject being removed prematurely 
from the study.  
c: Brief physical examination of pertinent systems to be performed during subsequent treatment cycles. Complete physical 
exam to be performed at End of Treatment visit. Responses to questions for surveillance of autoimmune type symptoms 
(See Appendix 4) should be documented at time of physical exam. 
d: For subjects receiving KW-0761, vital signs will be checked and recorded prior to the start of each infusion, at the end of 
each infusion and 1 hour after the completion of the infusion. For subjects taking vorinostat, vital signs can be taken 
irrespective of dosing. Weight will be checked with vitals. 
e: Blood can be drawn 1 day prior to visit, if needed, to ensure results are available. In subjects receiving KW-0761, results 
must be reviewed prior to infusion. The platelet count must be ≥ 100,000 / mm3 and the ANC must be ≥ 1,500/mm3 
before a subject can receive study drug. 
f: If clinical progression is noted at any time prior to the scheduled assessments for efficacy, CT, mSWAT, skin 
photographs and flow cytometry assessments should be done at that time to fully document disease progression, i.e., 
Global Composite Response Score. CT must be performed even if previously negative at baseline. 
g: Serum samples for PK assessment should be collected for subjects treated with KW-0761 prior to infusion of KW-0761 in 
Cycles 2 and 3 (sample collection will still be needed even if dosing is not performed at a visit). 
h: KW-0761 is to be administered over at least one hour. 
i: Vorinostat is administered orally daily beginning on Day 1 with food. 
j: If a subject who is receiving KW-0761 develops a skin rash, notify KKD and refer to Section 5.2.1.8 to treat and 
document the rash. 
k: Medication taken at any time after the start of treatment until 30 days after the final study drug administration will be 
recorded.  
l: To be performed in subjects with cytopenia or other clinical suspicions of bone marrow involvement, at the discretion of 
the investigator. If a bone marrow biopsy was performed at baseline and determined to unequivocally be indicative of 
lymphomatous involvement, then to confirm a global CR where blood assessment now meets criteria for B0, a repeat 
bone marrow biopsy must show no residual disease or the response should be considered a PR only (See Table 7.2.2-1). 
m: Biopsies at the end of the cycle and to confirm a CR (See Table 7.2.1-3) are optional and can be performed at the 
discretion of the investigator. Analysis of these biopsies will be done by a pathologist at the study site. 
n: KW-0761 subjects only for determination of anti-KW-0761 antibodies and concentration of KW-0761. 
o: Subjects who terminate for reasons other than disease progression or their referring physicians will be contacted every 
3 months (± 14 days) until documented disease progression or death or initiation of alternative therapy.  
p: All subjects or their referring physician will be contacted every 3 months (± 14 days) to ascertain survival status 
following discontinuation of treatment. 
 
 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
24 
 
Table 3 
Study Procedures:  Subsequent Cycles in Year 2 and Beyonda 
Procedures 
D 1 
D 15 
D 26-28 
(Cycles 
14, 16, 
18, 20, 
etc)b 
D 26-28  
(Cycles 15, 
17, 19, 21, 
etc)b 
D 26-28  
Q 16 
wks 
(Cycles 
17, 21, 
etc) 
End-of-
treatment  
visit 
Follow-
upc 
Visit Window 
 
± 2 days 
+ 2 days 
+ 2 days 
+ 5 days 
Within 30 
days of last 
dose 
 
Physical examinationd 
X 
X 
X 
X 
 
X 
 
ECOG PS 
X 
X 
X 
X 
 
X 
 
Vital signs, Weight 
Xe 
Xe 
X 
X 
 
X 
 
ECG 
 
 
 
 
 
X 
 
Urinalysis 
X 
 
 
 
 
X 
 
Hematology profile 
Xf 
Xf 
X 
X 
 
X 
 
Chemistry profile 
Xf 
Xf 
X 
X 
 
X 
 
Coagulation profile 
Xf 
 
 
 
 
 
 
Thyroid function tests 
(Free T4, TSH) 
 
 
 
X 
 
X 
 
Flow Cytometric 
Analysisg 
 
 
X 
X 
 
 
 
Blood sample for 
determination of 
natural ligands 
 
 
 
X 
 
 
 
Serum sample for 
KW-0761 
concentration 
assessment 
 
 
 
 
 
X 
 
KW-0761 
Administration 
Xh 
Xh 
 
 
 
 
 
Vorinostat 
Administration 
Xi 
 
 
 
Adverse event 
assessmentj 
X 
X 
X 
X 
 
X 
Xk 
Concomitant 
medication assessmentl 
X 
X 
X 
X 
 
X 
X 
CT (diagnostic quality)g 
 
 
 
 
X 
 
 
Bone marrow 
aspiration & biopsym 
 
 
 
X 
 
 
 
Skin biopsy 
 
 
 
Xn 
 
 
 
Skin photographsg 
 
 
X 
X 
 
 
 
Modified Severity 
Weighted Assessment 
Tool (mSWAT)g 
 
 
X 
X 
 
 
 
Pruritus Evaluation 
(Likert scale & Itchy 
QoL) 
 
 
X 
X 
 
 
 


Protocol 0761-010, Amendment 10 
 
 
 
 
 
 
CONFIDENTIAL 
25 
 
Table 3 
Study Procedures:  Subsequent Cycles in Year 2 and Beyonda 
Procedures 
D 1 
D 15 
D 26-28 
(Cycles 
14, 16, 
18, 20, 
etc)b 
D 26-28  
(Cycles 15, 
17, 19, 21, 
etc)b 
D 26-28  
Q 16 
wks 
(Cycles 
17, 21, 
etc) 
End-of-
treatment  
visit 
Follow-
upc 
Visit Window 
 
± 2 days 
+ 2 days 
+ 2 days 
+ 5 days 
Within 30 
days of last 
dose 
 
Skindex-29, FACT-G 
& EQ-5D-3L 
 
 
 
X 
 
X 
 
Immunogenicityo 
 
 
 
 
 
X 
 
CD4, CD8 (for 
KW-0761 subjects) 
 
 
 
 
 
Xp 
Xp 
Disease Progressionq 
 
Survival Statusr 
 
a: Subject may remain in treatment phase up until progressive disease, drug intolerance or unacceptable toxicity, or until any 
of the other criteria for removal (See Section 5.5) are met. At each cycle, the investigator must minimally have reviewed 
the mSWAT to determine if progression of skin disease has occurred prior to subsequent dosing (see Section 5.2.1.4). For 
subjects who are continuing to receive study treatment at the time of the primary efficacy analysis, pending notification 
by the Sponsor, subjects may be followed according to institutional standard of care for subsequent assessments of 
treatment efficacy as described in Section 7.7.  Procedures to be followed for subjects who are ongoing in the study at the 
time of initial marketing authorization are described in Section 7.8. 
b: For subjects receiving a subsequent treatment course, procedures performed at this time can also be used to satisfy the 
Day 1 requirements for the subsequent course, provided they are performed within ± 2 days of next KW-0761 
administration. For subjects who will not receive subsequent treatment, this visit will be considered the final treatment 
visit and subjects should undergo testing/procedures specified for End-of-treatment visit. If progression is noted at Day 
26-28, visit should take place before initiation of new therapy. In cases where the definition of PD or relapse is met but 
the clinical impression is questionable, subjects may remain on study until the next evaluation (4 weeks later if 
questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after Year 1 if questionable finding in 
lymph nodes or viscera, with at least stable disease in other compartments) to avoid a subject being removed prematurely 
from the study.  
c: For subjects going off treatment after achieving a CR, refer to Section 7.6 for study procedures and timing. 
d: Brief physical examination of pertinent systems to be performed during subsequent treatment cycles. Complete physical 
exam to be performed at End of Treatment visit. Responses to questions for surveillance of autoimmune type symptoms 
(See Appendix 4) should be documented at time of physical exam. 
e: For subjects receiving KW-0761, vital signs will be checked and recorded prior to the start of each infusion, at the end of 
each infusion and 1 hour after the completion of the infusion. For subjects taking vorinostat, vital signs can be taken 
irrespective of dosing. Weight will be checked with vitals. 
f: Blood can be drawn 1 day prior to visit, if needed, to ensure results are available. In subjects receiving KW-0761, results 
must be reviewed prior to infusion. The platelet count must be ≥ 100,000 / mm3 and the ANC must be ≥ 1,500/mm3 
before a subject can receive study drug. 
 
 
 
 


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Table 3 
Study Procedures:  Subsequent Cycles in Year 2 and Beyonda 
Procedures 
D 1 
D 15 
D 26-28 
(Cycles 
14, 16, 
18, 20, 
etc)b 
D 26-28  
(Cycles 15, 
17, 19, 21, 
etc)b 
D 26-28  
Q 16 
wks 
(Cycles 
17, 21, 
etc) 
End-of-
treatment  
visit 
Follow-
upc 
Visit Window 
 
± 2 days 
+ 2 days 
+ 2 days 
+ 5 days 
Within 30 
days of last 
dose 
 
Footnotes to Table 3 continued. 
g: If clinical progression is noted at any time prior to the scheduled assessments for efficacy, CT, mSWAT, skin 
photographs and flow cytometry assessments should be done at that time to fully document disease progression, i.e., 
Global Composite Response Score. CT must be performed even if previously negative at baseline.  
h: KW-0761 is to be administered over at least one hour. 
i: Vorinostat is administered orally daily beginning on Day 1 with food. 
j: If a subject who is receiving KW-0761 develops a skin rash, notify KKD and refer to Section 5.2.1.8 to treat and 
document the rash. 
k: Adverse events will be collected every 30 days (± 7 days) for up to 90 days after the last dose of study drug or initiation 
of alternative therapy. In all subjects who cross over from vorinostat to KW-0761, the causality should be assessed for 
both drugs for 30 days after vorinostat was stopped (or later if the event is considered to be related to vorinostat).   
l:  Medication taken at any time after the start of treatment until 30 days after the final study drug administration will be 
recorded. A medication taken during follow-up will also be recorded if it is used to treat an AE or is temporally associated 
with an AE and may have a causal relationship. 
m: To be performed in subjects with cytopenia or other clinical suspicions of bone marrow involvement, at the discretion of 
the investigator. If a bone marrow biopsy was performed at baseline and determined to unequivocally be indicative of 
lymphomatous involvement, then to confirm a global CR where blood assessment now meets criteria for B0, a repeat 
bone marrow biopsy must show no residual disease or the response should be considered a PR only (See Table 7.2.2-1) 
n: Biopsies at the end of the cycle and to confirm a CR (See Table 7.2.1-3) are optional and can be performed at the 
discretion of the investigator. Analysis of these biopsies will be done by pathologist at the study site. 
o: KW-0761 subjects only for determination of anti-KW-0761 antibodies. 
p: If CD4 and CD8 counts are less than 200/mm3 at the End-of-treatment visit, they will be followed every 3 months 
(±14 days) until they return to at least 200/mm3, initiation of alternative therapy or 1 year, whichever comes first. 
Assessments will be performed at the study site. 
q: Subjects who terminate for reasons other than disease progression or their referring physicians will be contacted every 
3 months (± 14 days) until documented disease progression or death or initiation of alternative therapy.  
r: All subjects or their referring physician will be contacted every 3 months (± 14 days) to ascertain survival status following 
discontinuation of treatment. 
 
 


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List of Abbreviations 
Abbreviations 
Ab 
antibody 
ADCC 
antibody dependent cellular cytotoxicity 
AE 
adverse event 
Ag 
antigen 
ALT 
Alanine transaminase 
ANC 
absolute neutrophil count 
ASCO 
American Society of Clinical Oncology  
ASH 
American Society of Hematology 
AST 
aspartate transaminase 
ATL 
adult T-cell leukemia-lymphoma 
β-HCG 
beta-human chorionic gonadotrophin 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CCR4 
CC chemokine receptor 4, chemokine (C-C motif) receptor 4 
CNS 
central nervous system 
CR 
complete response 
CS 
clinically significant 
CT 
computed tomography 
CTA 
Clinical Trial Authorization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTCL 
cutaneous T-cell lymphoma 
CTIVRS 
ClinTrak Interactive Voice/Web Response System 
DOR 
duration of response 
DSMB 
Data Safety Monitoring Board  
EC 
Ethics Committee 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EMA 
European Medicines Agency 
EORTC 
European Organization for Research and Treatment of Cancer  
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
HDAC 
histone deacetylase  
HEENT 
head, eyes, ears, nose and throat 
HIV 
human immunodeficiency virus 
HSCT 
hematopoetic stem cell transplantation 
HTLV-1 
human T-cell lymphotropic virus type-1 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonization 
IHC 
immunohistochemistry 
IND 
Investigational New Drug Application 


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Abbreviations 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IR 
Independent Review/Reviewer  
ISCL 
International Society of Cutaneous Lymphomas  
ITT 
Intent-to-Treat 
iv 
intravenous 
KKD 
Kyowa Kirin Pharmaceutical Development, Inc. 
KW-0761 
humanized monoclonal antibody against CCR4 
LDH 
lactate dehydrogenase 
Mab 
monoclonal antibody 
MDC 
macrophage derived chemokine 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF 
mycosis fungoides 
mSWAT 
modified Severity Weighted Assessment Tool 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NCS 
not clinically significant 
NHL 
non-Hodgkin’s Lymphoma 
NYHA 
New York Heart Association  
ORR 
objective response rate 
OS 
overall survival  
PD 
progressive disease 
PDF 
Portable Document Format 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PR 
partial response 
PS 
performance status 
PT 
prothrombin time 
PTCL 
peripheral T-cell lymphoma 
PTT 
partial thromboplastin time 
QoL 
Quality of Life 
SAE 
serious adverse event 
SD 
stable disease 
SEER 
Surveillance Epidemiology and End Results 
SGOT  
serum glutamic oxaloacetic-transaminase  
SGPT  
serum glutamic pyruvic-transaminase  
SJS 
Stevens-Johnson syndrome 
SPD 
sum of the product of the diameters 
SS 
Sézary Syndrome 
TARC 
thymus- and activation-regulated chemokine 
TBSA 
total body surface area 
TEAE 
treatment-emergent adverse event 
TEN 
toxic epidermal necrolysis 
TTP 
time to progression 
ULN 
upper limit of normal 
US 
United States  


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Abbreviations 
USCLC 
United States Cutaneous Lymphoma Consortium  
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
 
Definition of Terms 
pH 
hydrogen ion concentration; negative logarithm of hydrogen ion activity 
p.r.n. 
as needed 
QT interval  
in electrocardiography, the time from the beginning of the QRS complex to the end of the T 
wave. 
QTc interval 
QT interval corrected for heart rate  
 


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1 
BACKGROUND AND RATIONALE  
1.1 
Cutaneous T-Cell Lymphomas 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
  
 
 
 
 
 
  
 
 
 
 
  


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1.2 
Treatment of Cutaneous T-cell Lymphomas 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
.  
1.3 
Chemokine Receptor 4 and T-Cell Malignancies 
 
 
 
 
 
 


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1.4 
KW-0761 (mogamulizumab) 
 
 
 
 
 
 
 
1.5 
Safety and Efficacy of KW-0761 
 
 
 
 
 
 
 
 
 
 


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1.6 
Vorinostat (ZOLINZA®) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.7 
Rationale  
 
 
 
 
 
 
 
 
 
 
 
  
 
 


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2 
OBJECTIVES 
2.1 
Primary Objectives 
The primary objective of this study will be: 
• 
To compare the progression free survival of KW-0761 versus vorinostat for subjects with 
relapsed or refractory CTCL.  
2.2 
Secondary Objectives 
The secondary objectives will be: 
• 
To compare the overall response rate of KW-0761 versus vorinostat in subjects with 
relapsed or refractory CTCL; 
• 
To evaluate and compare improvements in QoL measurements, Skindex-29, FACT-G and 
EQ-5D-3L for subjects receiving KW-0761 versus vorinostat; 
• 
To evaluate and compare improvements in the Pruritus Evaluation (Likert scale & Itchy 
QoL) for subjects receiving KW-0761 versus vorinostat;  
• 
To estimate the duration of response for both the KW-0761 and vorinostat arms for those 
subjects with relapsed or refractory CTCL responding to treatment; 
• 
To determine if subjects who relapse on vorinostat can achieve response upon cross over 
to treatment with KW-0761;  
• 
To further assess the safety of KW-0761; 
• 
To describe the immunogenicity of KW-0761. 


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2.3 
Exploratory Objectives 
• 
To compare the overall survival of KW-0761 versus vorinostat for subjects with relapsed 
or refractory CTCL;  
• 
To conduct exploratory evaluation of KW-0761 exposure-response relationships. 
3 
STUDY POPULATION 
3.1 
Subject Selection 
This study will enroll subjects with CTCL who have failed at least one prior course of 
systemic therapy. This should be adequately documented in the subject’s medical record. 
3.2 
Inclusion Criteria 
Subject must meet the following criteria for inclusion in this study: 
Signed Written Informed Consent 
1) Voluntarily signed and dated Institutional Review Board (IRB)/ Ethics Committee 
approved informed consent form in accordance with regulatory and institutional 
guidelines. Written informed consent must be obtained prior to performing any 
study-related procedure; 
Age and Sex 
2) Males and female subjects ≥ 18 years of age at the Pre-treatment Visit, i.e., at the 
time that written informed consent is obtained, except in Japan where subjects must 
be ≥ 20 years of age; 
Target Population 
3) Histologically confirmed diagnosis of MF or SS; 
a. For SS (defined as meeting T4 plus B2 criteria), where the biopsy of 
erythrodermic skin may only reveal suggestive but not diagnostic 
histopathologic features, the diagnosis may be based on either a node biopsy or 
fulfillment of B2 criteria including a clone in the blood that matches that of the 
skin (Olsen, 2011).  
4) Stage IB, II-A, II-B, III and IV (Olsen, 2011) (see Appendix 1); 
5) Subjects who have failed at least one prior course of systemic therapy (e.g., 
interferon, denileukin diftitox, bexarotene, photopheresis, anti-neoplastic 
chemotherapy, etc.). Psoralen plus ultraviolet light therapy (PUVA) is not 
considered to be a systemic therapy; 
6) Eastern Cooperative Oncology Group (ECOG) performance status score (Oken, 
1982) of ≤ 1 (see Appendix 2). 
7) The subject has resolution of all clinically significant toxic effects of prior cancer 
therapy to Grade ≤ 1 by the National Cancer Institute Common Terminology 


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Criteria for Adverse Events, version 4.0 (NCI-CTCAE, v.4.0) excluding the 
specifications required in 8, 9 and 10 below. 
8) Adequate hematological function:  
a. absolute neutrophil count (ANC) ≥ 1,500 cells/μL (≥ 1,500/mm3); 
b. platelets ≥ 100,000 cells/μL (≥ 100,000/mm3); 
c. in subjects with known bone marrow involvement, ANC must be 
≥ 1,000 cells/μL (≥ 1,000/mm3) and platelets ≥ 75,000 cells/μL (≥ 75,000/mm3).  
9) Adequate hepatic function:  
a. bilirubin ≤ 1.5 times the specific institutional upper limit of normal (ULN), 
except for subjects with Gilbert’s syndrome;  
b. aspartate transaminase (AST) and alanine transaminase (ALT) each 
≤ 2.5 x ULN or ≤ 5.0 x ULN in the presence of known hepatic involvement by 
CTCL.  
10) Adequate renal function:  
a. serum creatinine ≤ 1.5 x ULN  
                                            or  
b. calculated creatinine clearance > 50 mL/min using the Cockcroft-Gault formula. 
11) Subjects previously treated with anti-CD4 antibody or alemtuzumab are eligible 
provided their CD4+ cell counts are ≥ 200/mm3. 
12) Subjects with MF and a known history of non-complicated staphylococcus 
colonization/infection are eligible provided they continue to receive stable doses of 
prophylactic antibiotics. 
13) Women of childbearing potential (WOCBP) must have a negative pregnancy test 
within 7 days of receiving study medication. 
14) WOCBP must agree to use effective contraception, defined as oral contraceptives, 
double barrier method (condom plus spermicide or diaphragm plus spermicide) or 
practice true abstinence from sexual intercourse (periodic abstinence, e.g., calendar, 
ovulation, symptothermal, post-ovulation methods and withdrawal are not 
acceptable methods of contraception) during the study and for 3 months after the 
last dose. WOCBP includes any female who has experienced menarche and who has 
not undergone successful surgical sterilization or is not postmenopausal (defined as 
amenorrhea ≥ 12 consecutive months without an alternative medical cause). 
15) Male subjects and their female partners of child bearing potential must be willing to 
use an appropriate method of contraception defined as oral contraceptives, double 
barrier method (condom plus spermicide or diaphragm plus spermicide) or practice 
true abstinence from sexual intercourse (periodic abstinence, e.g., calendar, 
ovulation, symptothermal, post-ovulation methods and withdrawal are not 
acceptable methods of contraception) during the study and for 3 months after the 
last dose. 
NOTE:  For subjects continuing to receive study treatment as of protocol Amendment 8, the 
period of contraceptive use should be extended to 6 months after the last dose of KW-0761. 


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3.3 
Exclusion Criteria 
Subjects with any of the following will be excluded from the study:  
Medical History and Concurrent Diseases 
1) Current evidence of large cell transformation (LCT). Subjects with clinical features 
suggestive of LCT must have a biopsy performed within 4 months prior to Cycle 1 
Day 1 to rule out transformed disease. Subjects with a history of LCT but without 
current aggressive disease and no current evidence of LCT on pathology in skin or 
lymph nodes would be eligible. 
2) Diagnosed with a malignancy in the past 2 years. However, subjects with non-
melanoma skin cancers, melanoma in situ, localized cancer of the prostate with 
current prostate-specific antigen of < 0.1 ng/mL, treated thyroid cancer or cervical 
carcinoma in situ or ductal/lobular carcinoma in situ of the breast with in the past 
2 years may enroll as long as there is no current evidence of disease.  
3) Clinical evidence of central nervous system (CNS) metastasis. 
4) Psychiatric illness, disability or social situation that would compromise the subject’s 
safety or ability to provide consent, or limit compliance with study requirements. 
5) Significant uncontrolled intercurrent illness including, but not limited to:  
a. uncontrolled infection requiring antibiotics;  
b. clinically significant cardiac disease (class III or IV of the New York Heart 
Association [NYHA] classification, see Appendix 3);  
c. unstable angina pectoris;  
d. angioplasty, stenting, or myocardial infarction within 6 months;  
e. uncontrolled hypertension (systolic blood pressure (BP) > 160 mm Hg or diastolic 
BP > 100 mm Hg, found on 2 consecutive measurements separated by a 1-week 
period) despite 2 anti-hypertensive medications;  
f. clinically significant cardiac arrhythmia or  
g. uncontrolled diabetes.  
6) Known or tests positive for human immunodeficiency virus (HIV), human T-cell 
lymphotropic virus (HTLV-1), hepatitis B or hepatitis C disease.  
7) Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes who 
started taking medication at least 30 days prior to the Pre-treatment Visit, and have no 
active signs of active infection, and whose last active infection was more than 
6 months ago, may enter the study, and should continue to take the prescribed 
medication for the duration of the study. 
8) Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins. 
9) Known active autoimmune disease will be excluded. (For example, Graves’ disease; 
systemic lupus erythematosus; rheumatoid arthritis; Crohn’s disease; psoriasis). 
10) Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or 
lactating. 


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Prohibited Therapies and/or Medications 
11) Prior treatment with KW-0761. 
12) Prior treatment with vorinostat. Patients who were exposed to vorinostat for a short 
time, did not progress while on treatment, and did not have intolerable toxicity but 
were discontinued for another reason (e.g., comorbidity) may be permitted to enter the 
study after discussion with the Medical Monitor. 
13) Have had any therapy directed against the subject’s underlying cancer or any 
investigational medications within four weeks of randomization (skin directed 
treatments, including topicals and radiation within 2 weeks of randomization). 
However, subjects with rapidly progressive malignant disease may be enrolled prior 
to this period after discussion with the Medical Monitor. 
14) Subjects on a stable dose of a low dose systemic corticosteroid (≤ 20 mg prednisone 
equivalent) for at least 4 weeks prior to the Pre-treatment Visit may continue use 
although the investigator should attempt to taper the use to the lowest dosage tolerable 
while on study. Initiation of treatment with systemic corticosteroids or increase in 
dose while on study is not permitted except to treat an infusion reaction (see Section 
5.2.1.7). Subjects may receive intra-articular corticosteroid injections, intraocular 
corticosteroid drops, inhalation or nasal corticosteroids and replacement doses of 
systemic corticosteroids as needed.  
15) Subjects on a stable dose of medium or low potency topical corticosteroids for at least 
4 weeks prior to the Pre-treatment Visit may continue use at the same dose, although 
the investigator should attempt to taper the use to the lowest dosage tolerable while on 
study. Initiation of treatment with topical corticosteroids while on study is not 
permitted except to treat an acute rash. 
16) History of allogeneic transplant. 
17) Autologous hematopoietic stem cell transplant within 90 days of the Pre-treatment 
Visit. 
18) Subjects on any immunomodulatory drug for concomitant or intercurrent conditions 
other than T-cell lymphoma or who have received any of these agents within 4 weeks 
of treatment, including but not limited to the following, will be excluded:  low dose or 
oral methotrexate; azathioprine; iv immunoglobulin; low dose or oral 
cyclophosphamide; cyclosporine; mycophenolate; infliximab; etanercept; 
leflunomide; adalimumab; lenalidomide; abatacept; rituximab; anakinra; interferon-β; 
IL-2 and natalizumab.  
3.4 
Eligibility for Cross-over to KW-0761 
Subjects who are randomized to the vorinostat arm may cross over to KW-0761 upon 
progression or in the event of intolerable toxicity (see Section 5.3). Crossover may take place 
following discussion with the Medical Monitor or designee and receipt of approval for cross 
over from Kyowa Kirin Pharmaceutical Development, Inc. (KKD). However, they must 


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continue to fulfill inclusion criteria 6 through 15, and will be excluded if they fulfill the 
exclusion criteria, except for exclusion criteria 1, 12 and 13 (refer to Section 3.3).  
4 
INVESTIGATIONAL PLAN 
4.1 
Overview of Study Design 
This is an open-label, multi-center randomized, Phase 3 study with 1:1 randomization of 
study drug, KW-0761 versus the comparator, vorinostat. 
4.2 
Number of Subjects 
Approximately 317 subjects may enroll in this study over a period of 24 months. The primary 
analysis will be conducted when 255 total progression-free survival (PFS) events have been 
observed or 24 months after the last randomized subject’s first dose, whichever comes first. 
4.3 
Investigational Centers 
It is anticipated that approximately 75 investigational centers in the US, Europe, Japan and 
Australia will participate in this study.  
5 
TREATMENT PLAN 
5.1 
Assignment to Study  
After a subject signs consent, screening numbers should be assigned by the investigator (or 
designee) using ClinTrak Interactive Voice/Web Response System (CTIVRS). Once 
assigned, numbers for any screen failures or non-treated, non-evaluable, or discontinued 
subjects will not be re-used. 
A subject who meets all entry criteria will be randomized in a 1:1 ratio to receive KW-0761 
or vorinostat. The randomization to treatment groups will be stratified by disease type (MF or 
SS) and disease stage (IB/II or III/IV). When a subject is determined to be eligible for 
randomization the investigator (or designee) will contact CTIVRS to obtain the 
randomization assignment for the subject. If a subject is randomized in error, or a dosing 
error occurs, KKD (or designee) should be notified as soon as the error is discovered. 
5.2 
Study Treatments 
In this protocol, study treatments are KW-0761 and vorinostat. Subjects will be randomized 
to the study drug, KW-0761 or comparator, vorinostat, in a 1:1 ratio. 


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5.2.1 
Study Drug: KW-0761 (mogamulizumab) 
Treatment can be administered on an outpatient basis. Subjects will receive 1.0 mg/kg of 
KW-0761 as an iv infusion over at least 1 hour on Days 1, 8, 15, and 22 of the first cycle and 
on Days 1 and 15 of subsequent cycles. No other investigational or commercial agents or 
therapies other than the study treatment and those described in Section 5.4.1 may be 
administered with the intent to treat the subject’s malignancy. 
5.2.1.1 
Premedication Prior to KW-0761 Infusion 
It is recommended that subjects be premedicated with acetaminophen or paracetamol orally 
and diphenhydramine 50 mg iv (or equivalent anti-histamine) before the first KW-0761 
infusion. For subjects who experience an infusion related reaction, premedication is 
recommended prior to every subsequent infusion. 
5.2.1.2 
Definition of Treatment Cycle 
Each treatment cycle is 28 days.  
5.2.1.3 
Delays in Dosing 
During the first treatment cycle, KW-0761 should be administered beginning on Day 1 and 
within ± 2 days of the other scheduled visits (i.e., Days 8, 15 and 22 during Cycle 1; Day 15 
during subsequent cycles). If the study visit does not occur within this visit window, 
KW-0761 should not be administered at the visit and the next dose should be administered at 
the next timepoint. 
A subject’s next cycle should begin within 2 weeks of the completion of the prior cycle. The 
start of a new cycle may be delayed to allow resolution of treatment-related toxicities or for 
non-medical reasons (holidays, vacations, etc.). Delay of the start of a new cycle greater than 
2 weeks must be discussed with the Medical Monitor or designee. 
5.2.1.4 
Duration of Treatment 
Subjects may remain in the treatment phase up until PD, drug intolerance or unacceptable 
toxicity, or until any of the other criteria for study removal are met, as defined in Section 5.5. 
Except in cases of unacceptable toxicity or drug intolerance, every effort should be made to 
ensure the subject remains in the study until disease progression (See Section 7.2.4, regarding 
definition of disease progression). 
At each cycle, the investigator must minimally have reviewed the modified Severity 
Weighted Assessment Tool (mSWAT) to determine if progression of skin disease has 


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occurred prior to subsequent dosing. Ideally, results of flow cytometry and CT assessment, as 
applicable, should be reviewed at this visit as well. However, it is understood that these 
results may not be reported for several days and may not be available. Once those results are 
obtained evidence of progression in all compartments should be determined. 
In cases where the definition of PD or relapse is met but the clinical impression is 
questionable, subjects may remain on study until the next evaluation (4 weeks later if 
questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after 
Year 1 if questionable finding in lymph nodes or viscera, with at least stable disease in other 
compartments) to avoid a subject being removed prematurely from the study. If PD is 
confirmed at this subsequent evaluation, subject should be discontinued from treatment. If PD 
is not confirmed at this subsequent evaluation, the subject may remain on study. 
This course of action only applies to cases where the clinical impression is questionable; 
subjects in frank or obvious PD in any compartment should be discontinued from protocol 
therapy. 
If clinical progression is noted at any time prior to the scheduled assessments for efficacy, the 
assessments (computed tomography [CT], mSWAT, skin photographs and flow cytometry) 
should be done at that time to fully document disease progression. CT must be performed 
even if previously negative at baseline.  
If the subject experiences an overall CR, the subject may continue treatment for up to 
12 months or until progression, whichever comes first.  
For subjects who are continuing to receive study treatment at the time of the primary efficacy 
analysis, procedures and assessments are described in Section 7.7. Procedures to be followed 
for subjects who are continuing to receive KW-0761 at the time of initial marketing 
authorization are described in Section 7.8. 
5.2.1.5 
Replacement of Subjects 
Subjects will not be replaced.  
5.2.1.6 
Dose Modifications 
No dose modifications of the KW-0761 will be permitted in this study.  
5.2.1.7 
Treatment of Hypersensitivity-Like Reactions 
It may be difficult to differentiate an infusion reaction from a true hypersensitivity (i.e., 
allergic) reaction. If a reaction occurs during infusion of KW-0761, investigators may use the 
following guidelines to best treat the subject’s symptoms: 


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Grade 1/2: 
• 
Stop the infusion for 15–30 minutes; 
• 
Acetaminophen or paracetamol orally and diphenhydramine 50 mg iv or equivalent 
anti-histamine may be administered;  
• 
If symptoms abate, re-start the infusion at one-half the previous rate; 
• 
If symptoms do not abate after 30 minutes, discontinue that day’s treatment. Additional 
medical measures, such as administration of corticosteroids (see below) may be 
considered for reactions that do not abate after 30 minutes. 
Grade 3 
• 
Stop the infusion for 15–30 minutes; 
• 
Consider administering the following: 
– Acetaminophen or paracetamol orally;  
– Diphenhydramine 50 mg iv or an equivalent anti-histamine; 
– Dexamethasone 20 mg iv or an equivalent corticosteroid; 
– Albuterol or salbutamol inhaler 2 puffs p.r.n. for bronchospasm or an equivalent 
bronchodilator; 
– O2 by nasal cannula.  
• 
Additional agents may be administered per institutional guidelines for the treatment of 
infusion reactions; 
• 
If symptoms abate, re-start the infusion at one-half the previous rate; 
• 
If symptoms do not abate after 30 minutes, discontinue the subject from the study.  
Grade 4 
• 
Administration of the agents specified for a Grade 3 infusion reaction above should be 
considered. 
• 
Any subject who experiences a Grade 4 infusion reaction is to be discontinued from the 
study. 
If a reaction with severity of Grade 2 or higher occurs upon re-challenge with KW-0761, or if 
in the opinion of the investigator the reaction represents a true hypersensitivity (i.e., allergic) 
reaction of Grade 2 or higher, KW-0761 should be stopped and not restarted and the subject 
should be discontinued from the study. 
If an infusion reaction occurs, a serum sample should be obtained and sent to the designated 
central laboratory for analysis of anti-KW-0761 antibodies.  (As of Amendment 10, central 
laboratory analysis of samples will no longer be performed [see Section 7.8].) 


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If an infusion reaction occurs, the duration of administration of KW-0761 should be increased 
to 2 hours for the next 2 infusions. Subsequent infusion duration may be 1 to 2 hours, as 
tolerated. 
For infusion reactions occurring after completion of the infusion, administration of the agents 
specified for a Grade 3 infusion reaction above should be considered, along with any other 
medical intervention stipulated in institutional guidelines for the treatment of infusion 
reactions. 
Any subject who experiences an infusion reaction requiring the administration of systemic 
vasopressors or that results in hospitalization (directly due to infusion reaction symptoms) of 
the subject is to be removed from the study. 
5.2.1.8 
Treatment Emergent Skin Rash 
In the event a subject develops a treatment emergent skin rash, the following measures must 
be taken to appropriately document the event. 
Patients should be closely monitored for symptoms or signs that suggest SJS or TEN. 
If they occur, mogamulizumab should be interrupted and treatment should not restart 
unless SJS or TEN is ruled out and cutaneous reaction has resolved to Grade 1 or less. 
Initial Work-up of All Skin Rashes (new and re-challenge) 
1) Notify KKD of the skin rash. 
2) Photograph the rash. (As of Amendment 8, collection of photographs is no longer 
required.) 
3) If the rash is ≥ Grade 2 or if the affected area cannot be differentiated from a new area 
of lymphoma, a biopsy must be performed. Biopsy the rash as well as an area of skin 
unaffected by the rash in order to compare possible drug eruption to background 
lymphoma involved skin. If the rash is Grade 1 and topical steroids are to be applied, 
the rash must be biopsied prior to steroid treatment. 
4) Confer with Medical Monitor or designee after completion of one week of treatment 
with topical corticosteroids to assess response to treatment.  
5) Forward all results to Medical Monitor and discuss with Medical Monitor or designee 
a treatment plan and medical follow up. 
6) Biopsy should be read by the dermatopathologist at the study center. Additional 
sample should be sent to the laboratory designated by the Sponsor for central review 
as well. Specific instructions for sample preparation and handling for central 
laboratory will be provided in the Laboratory Manual. (As of Amendment 10, central 
laboratory analysis of samples will no longer be performed [see Section 7.8].) 
7) If biopsy indicates that rash is a drug eruption record appropriately as AE/SAE. If 
biopsy indicates that rash is lymphoma, do not record as an AE. 


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Rash Treatment Guidelines (after initial work-up): 
Grade 1 Rash (drug related or non-drug related) 
1) Treatment with KW-0761 may continue. 
2) Treat rash with topical corticosteroids as needed. 
Grade 2 or above Rash (drug related) 
1) Treatment with KW-0761 must be stopped. 
2) Treat rash with 2-week course of topical corticosteroids.  
3) After 2-week course, re-assess rash per the steps outlined in initial assessment; if 
resolved completely or to Grade 1, KW-0761 treatment may be resumed. If not 
resolved, contact the Medical Monitor for further discussion. 
Grade 2 or above rash on Re-challenge 
1) If rash recurs and becomes a Grade 3, the subject must be discontinued from the trial 
and the rash work up above must be completed. 
2) If the rash recurs at a Grade 2, follow the steps above for Grade 2 Rash. 
3) If the rash recurs at Grade 2 or higher for a third time, the rash work up must be 
performed and the subject must be discontinued from the trial.  


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Table 5.2.1-1 
Guidelines for Treatment of Skin Rash 
Rash 
Grade 
Photographs 
Biopsy 
Medical 
Monitor 
or 
designee 
Consult 
Treatment 
Regimen 
KW-0761 
Study 
Participation 
Initial Drug Rash 
1 
Yes 
Required if 
topical 
steroids will 
be used 
Yes 
Topical 
corticosteroids 
as needed 
Continue 
Continue 
2 
Yes 
Yes 
Yes 
2-week 
topical steroid 
Temporarily 
Stop; re-start 
if ≤ Grade1 
within 2 
weeks 
If rash does not 
resolve to ≤ Grade 
1 within 2 weeks 
consult with 
medical monitor 
3a 
Yes 
Yes 
Yes 
2-week 
topical steroid 
Temporarily 
Stop: re-start 
if ≤ Grade 1 
within 2 
weeks  
If rash does not 
resolve to 
≤ Grade 1 within 
2 weeks consult 
with medical 
monitor 
Subsequent Drug Rash/Rechallenge 
1 
Yes 
Yes 
Yes 
Topical 
corticosteroids 
as needed 
Continue 
Continue 
2 
Yes 
Yes 
Yes 
2-week 
topical steroid 
Temporarily 
Stop: re-start 
if ≤ Grade 1 
within 2 
weeks 
D/C if rash does 
not resolve to 
≤ Grade 1 within 
2 weeks 
3 
Yes 
Yes 
Yes 
2-week 
topical steroid 
Discontinue 
Discontinue 
a Patients should be closely monitored for symptoms or signs that suggest SJS or TEN. If they occur, mogamulizumab 
should be interrupted and treatment should not restart unless SJS or TEN is ruled out and cutaneous reaction has resolved 
to Grade 1 or less. 
Subjects who require systemic steroid therapy to treat a severe skin rash including SJS/TEN 
should be discontinued from the study. 
5.2.2 
Study Drug: Vorinostat (ZOLINZA®) 
Treatment can be administered on an outpatient basis. Subjects will take 400 mg orally once 
daily with food.  


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Vorinostat is approved for marketing in the US, Japan and Australia and is indicated for the 
treatment of progressive, persistent or recurrent CTCL. Investigators will administer 
according to the currently approved US prescribing information (e.g. dosage and 
administration, warnings, precautions, adverse reactions, dose modifications and omissions 
and storage information). No other investigational or commercial agents or therapies other 
than the study treatments and those described in Section 5.4.1 may be administered with the 
intent to treat the subject’s malignancy. 
5.2.2.1 
Definition of Treatment Cycle 
Each treatment cycle is 28 days.  
5.2.2.2 
Delays in Dosing 
Refer to Section 5.2.2.5. 
5.2.2.3 
Duration of Treatment 
Subjects may remain in the treatment phase up until PD, drug intolerance or unacceptable 
toxicity, or until any of the other criteria for study removal are met, as defined in Section 5.5. 
Except in cases of unacceptable toxicity or drug intolerance, every effort should be made to 
ensure the subject remains in the study until disease progression (See Section 7.2.4, regarding 
definition of disease progression). 
At each cycle, the investigator must minimally have reviewed the mSWAT to determine if 
progression of skin disease has occurred prior to subsequent dosing. Ideally, results of flow 
cytometry and CT assessment, as applicable, should be reviewed at this visit as well. 
However, it is understood that these results may not be reported for several days and may not 
be available. Once those results are obtained evidence of progression in all compartments 
should be determined. 
In cases where the definition of PD or relapse is met but the clinical impression is 
questionable, subjects may remain on study until the next evaluation (4 weeks later if 
questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after 
Year 1 if questionable finding in lymph nodes or viscera, with at least stable disease in other 
compartments) to avoid a subject being removed prematurely from the study. If PD is 
confirmed at this subsequent evaluation, subject should be discontinued from treatment. If PD 
is not confirmed at this subsequent evaluation, the subject may remain on study. 


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This course of action only applies to cases where the clinical impression is questionable; 
subjects in frank or obvious PD in any compartment should be discontinued from protocol 
therapy. 
If clinical progression is noted at any time prior to the scheduled assessments for efficacy, the 
assessments (CT, mSWAT, skin photographs and flow cytometry) should be done at that 
time to fully document disease progression. CT must be performed even if previously 
negative at baseline.  
If the subject experiences an overall CR, the subject may continue treatment for up to 
12 months or until progression, whichever comes first.  
For subjects who are continuing to receive study treatment at the time of the primary efficacy 
analysis, procedures and assessments are described in Section 7.7.   
5.2.2.4 
Replacement of Subjects 
Subjects will not be replaced.  
5.2.2.5 
Dose Modifications 
Management of severe or intolerable adverse reactions may require dose omission, reduction 
or interruption of vorinostat therapy. Refer to US prescribing information for complete 
recommendations regarding dose modifications. 
5.3 
Cross-over to Study Drug KW-0761 
Subjects who have received 2 full treatment cycles and demonstrate progression of disease on 
treatment with vorinostat at the 8 week (Cycle 2, Day 26-28) assessment, or anytime 
thereafter, may cross over to treatment with KW-0761 after discussion with Medical Monitor 
or designee and receipt of approval for cross over from KKD. Investigators should strive to 
maintain subjects on treatment for at least the 8 week period, adjusting the dose of vorinostat 
as needed for toxicities in order to allow sufficient time to see effect. In cases where a 
subject’s disease progresses rapidly (i.e., prior to 8 weeks), the Medical Monitor or designee 
should be contacted and may consider the possibility of early crossover, if appropriate for 
that subject. All subjects must undergo the full extent of disease evaluations (including CT 
scanning) to document PD prior to crossover.  
There must be at least 2 weeks between the last dose of vorinostat and first dose of KW-0761. 
Subject must continue to meet eligibility criteria outlined in Section 3.4 and all toxicity must 
have resolved to Grade ≤ 1 or to baseline in order to receive KW-0761. Treatment with 
KW-0761 should commence with procedures outlined for Day 1 in Table 1 of Study 


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Procedures for the first treatment cycle. In cases where a subject’s disease progresses rapidly, 
the Medical Monitor or designee should be contacted and may consider initiation of treatment 
with KW-0761 prior to the 2-week washout period. 
For subjects who are unable to tolerate the toxicities associated with vorinostat treatment, 
dose reduction should be initiated in an attempt to have the subject complete 2 full cycles of 
treatment. If the subject is unable to tolerate treatment with vorinostat despite attempts at 
dose reduction and has not had documented disease progression, the subject may receive 
KW-0761 after consultation with the Medical Monitor or designee and subsequent approval 
documentation from the Sponsor.  
Drug intolerance is defined as: 
• 
A serious AE attributed to the drug; 
• 
≥ Grade 3 AEs excluding inadequately treated nausea, vomiting and diarrhea and 
alopecia. 
5.4 
Concomitant Therapy 
Subjects should receive appropriate medical care for all intercurrent medical conditions 
consistent with community standards of medical care. Subjects are to receive vigorous 
supportive care for study medication-related toxicities and appropriate palliation for tumor 
symptoms, such as pain and anorexia.  
All concomitant treatments whether for treatment of concurrent medical conditions, toxicity, 
management of pain, infections or other complications of the malignancy, must be recorded 
on the relevant electronic case report form (eCRF) page along with the reason for use. 
Medication taken within 30 days prior to the first dose of study drug, and at any time after the 
start of treatment until 30 days after the final study drug administration will be recorded. A 
medication taken during follow-up will also be recorded if it is used to treat an AE or is 
temporally associated with an AE and may have a causal relationship. 
While on study treatment, subjects are not permitted to receive any experimental therapy or 
anticancer therapy other than the study medication. Any subject requiring other anticancer 
therapy is to be removed from study treatment.  
5.4.1 
Permitted Treatment 
• 
Hematopoietic growth factors and erythropoiesis-stimulating agents (based on threshold 
and target hemoglobin levels in the American Society of Hematology (ASH)/American 
Society of Clinical Oncology (ASCO) guidelines) (Rizzo, 2010) are allowed, if consistent 
with regional approved prescribing information, after completing Cycle 1. 


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• 
Subjects on a stable dose of a low dose systemic corticosteroid (≤ 20 mg prednisone 
equivalent) for at least 4 weeks prior to the Pre-treatment Visit may continue use. 
Subjects may receive intra-articular corticosteroid injections, intraocular corticosteroids 
drops, inhalation or nasal corticosteroids and replacement doses of systemic 
corticosteroids as needed. 
• 
Subjects on a stable dose of medium or low potency topical corticosteroids for at least 
4 weeks prior to the Pre-treatment Visit may continue use at the same dose, although the 
investigator should attempt to taper the use to the lowest dosage tolerable while on study. 
• 
Prophylactic treatment for the infectious complications of T-cell lymphoma is permitted 
at the discretion of the investigator. 
• 
For subjects receiving vorinostat, prolongation of prothrombin time (PT) and 
International Normalized Ratio (INR) have been observed in subject receiving 
concomitant therapy with coumarin-derivative anticoagulants, carefully monitor PT and 
INR in these subjects. 
• 
Influenza vaccination consisting of killed virus or viral particles may be administered to 
subjects on study. Subjects should not receive an influenza vaccine containing live 
attenuated virus. It should also be understood that because KW-0761, as well as CTCL, 
can affect the immune system, immunity to influenza may not be achieved despite 
vaccination. 
5.4.2 
Prohibited Treatment 
• 
Initiation of treatment with systemic steroids or increase in dose while on study is not 
permitted except to treat an infusion reaction (see Section 5.2.1.7). Subjects who require 
systemic steroid therapy to treat a severe skin rash should be discontinued from the study 
(see Section 5.2.1.8). 
• 
Initiation of treatment with topical corticosteroids while on study is not permitted except 
to treat an acute rash. 
• 
Any experimental therapy or anticancer therapy including radiation and phototherapy 
other than the study medications. 
• 
Any live or live attenuated vaccine. 
• 
Alternative medicines, particularly use of St. John’s Wort. 
• 
Immunomodulatory agents such as methotrexate; azathioprine; iv immunoglobulin; 
cyclophosphamide; cyclosporine; mycophenolate; infliximab; etanercept; leflunomide; 
adalimumab; lenalidomide; abatacept; rituximab; anakinra; interferon-α; interferon-β; 
IL-2 and natalizumab.  
• 
Other concurrent HDAC inhibitors including valproic acid. 
• 
Whenever possible, concomitant use of drugs which may cause a prolongation of the QTc 
interval should be avoided. If such a drug is necessary (e.g., anti-emetics), monitor the 
QTc interval closely. 


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5.5 
Criteria for Removal from Study 
In the absence of a medical contraindication or significant protocol violation, every effort will 
be made by the Principal Investigator to keep the subject in the study. However, should the 
subject decide to discontinue treatment, all efforts will be made to complete and report the 
observations as thoroughly as possible, including a complete final evaluation at the time of 
the subject’s withdrawal with an explanation of why the subject is withdrawing from the 
study. 
Study treatment will be stopped if any of the following events occur:  
• 
Disease progression (as defined in Section 7.2.4); 
• 
An infusion-related reaction (see Section 5.2.1.7);  
– with a severity of ≥ Grade 2 upon re-challenge with KW-0761, 
– with a severity of Grade 3 with symptoms that do not abate after 30 minutes, 
– with a severity of Grade 4, 
– requiring the administration of systemic vasopressors, 
– that results in hospitalization (directly due to infusion reaction symptoms), 
• 
Initiation of treatment with systemic corticosteroids, except when initiated to treat an 
infusion reaction (see Section 5.2.1.7); 
• 
A true hypersensitivity (i.e., allergic) reaction to KW-0761 with a severity of ≥ Grade 2; 
• 
A rash which recurs and becomes Grade 3 on re-challenge (see Section 5.2.1.8); 
• 
A rash which recurs at Grade 2 or higher for a third time on re-challenge (see Section 
5.2.1.8); 
• 
A rash which requires systemic steroid therapy (see Section 5.2.1.8); 
• 
Confirmed SJS/TEN (see Section 5.2.1.8); 
• 
The subject has any clinical AE, laboratory abnormality, intercurrent illness, or other 
medical condition that indicates to the Investigator that continued participation is not in 
the best interest of the subject. The Investigator should make a distinction between AEs 
that may require only interruption of study medication and those that require 
discontinuation; 
• 
The subject wishes to withdraw consent from the study in the absence of a medical need 
to withdraw as determined by the Investigator; 
• 
The Investigator concludes that it is in the best interest of the subject to discontinue study 
treatment including subjects who have not benefited from treatment; 
• 
Subject is willingly or inadvertently noncompliant in the opinion of the Investigator; 
• 
Administrative reasons determined by the Sponsor; or 
• 
If pregnancy is suspected while the subject is receiving study treatment, the study 
medication must immediately be withheld until the result of pregnancy testing is known. 


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If pregnancy is confirmed, the study medication will be permanently discontinued and the 
subject withdrawn from treatment. 
In the case of pregnancy that occurs while the subject is receiving study medication through 
6 months after the last dose of study medication, the Investigator must immediately notify the 
Sponsor of this event and record the pregnancy on the Pregnancy Surveillance Form. The 
Sponsor must also be notified if a partner of a study subject becomes pregnant while the 
subject was receiving study medication through 6 months after the last dose of study 
medication. Reasonable attempts will be made to follow the pregnancy to conclusion in order 
to obtain information regarding the outcome. 
The Investigator must complete all applicable End-of-treatment visit procedures (i.e., safety 
laboratory parameters, electrocardiogram (ECG), physical examination, vital signs) and 
eCRF pages for subjects who discontinue treatment, and include the reason for 
discontinuation of treatment.  
6 
STUDY PROCEDURES 
The key study procedures and the frequency of their occurrences are outlined in the Study 
Procedures Tables (Table 1, Table 2, and Table 3). Labs, ECG, and physical exams on day of 
treatment should be obtained prior to study treatment.  
For subjects who are continuing to receive study treatment at the time of the primary efficacy 
analysis, procedures and assessments are described in Section 7.7. Procedures to be followed 
for subjects who are ongoing in the study (i.e., subjects who are continuing to receive 
KW-0761 or who are in safety or survival follow-up) at the time of initial marketing 
authorization are described in Section 7.8.  
7 
STUDY MEASUREMENTS 
Screening evaluations used to determine the subject’s study eligibility must be completed 
within 30 days prior to starting treatment unless otherwise specified. 
Written informed consent must be obtained prior to any study-specific procedures. 
Results of all screening evaluations must be reviewed by the Investigator or his/her designee 
to ensure that all eligibility criteria have been satisfied prior to registering the subject with the 
Sponsor. All pathology reports relevant to confirmation of the diagnosis of CTCL (mycosis 
fungoides or Sezary syndrome) for all enrolled subjects should be de-identified and provided 
to the Sponsor. For subjects with SS, this would include results confirming fulfillment of B2 
criteria including a clone in the blood that matches that of the skin per Section 3.2.  


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An End-of-treatment visit must be conducted for all subjects who discontinue from study 
treatment. This visit must occur within 30 days after the last dose of study medication. All 
End-of-treatment assessments must be conducted prior to the initiation of new therapy. 
7.1 
Safety Evaluations 
The safety of KW-0761 and vorinostat will be determined by reported AEs, changes in 
physical examinations, vital sign measurements, ECGs and laboratory analyses. Safety 
evaluations will be performed throughout the study. All subjects who received at least one 
dose, including a partial dose, of study drug will be evaluated for safety. The NCI-CTCAE 
v4.0 system will be used to grade AEs, both clinical and laboratory. AEs will be grouped and 
tabulated by Medical Dictionary for Regulatory Activities (MedDRA) preferred terms by 
system organ class. All subjects will be assessed regularly for potential occurrence of AEs 
from the time of signing the informed consent until 90 days after the last dose or initiation of 
alternative therapy whichever comes first. In all subjects who cross over from vorinostat to 
KW-0761, the causality of any reported AEs should be assessed for both drugs for 30 days 
after vorinostat was stopped (or later if the event is considered to be related to vorinostat).   
7.1.1 
Clinical Laboratory Evaluations 
Clinical laboratory assessments will be performed at the visits specified in the Study 
Procedures. A pregnancy test (serum or urine) is to be performed for all women of 
childbearing potential prior to administration of study medication.  
Any clinically important abnormal laboratory values noted at the screening visit will be 
recorded as medical history. In addition, in order for KKD to collect additional information 
about clinically important laboratory abnormalities, at minimum, the following laboratory 
abnormalities should be captured on the non-serious or serious AE pages of the eCRF as 
appropriate: 
• 
Any laboratory test result that meets the criteria for a SAE; 
• 
Any laboratory abnormality that requires the subject to have study medication 
discontinued or interrupted; 
• 
Any laboratory abnormality that requires the subject to receive specific corrective 
therapy. 
All clinically important abnormal laboratory tests occurring during the study will be repeated 
at appropriate intervals until (1) the value returns to baseline, (2) the value is judged to be 
clinically acceptable by the Investigator and the Sponsor, or (3) a diagnosis that explains the 


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abnormal laboratory value is made. When possible, the Investigator should report the clinical 
rather than the laboratory term (e.g., anemia versus low hemoglobin). 
Clinical laboratory assessments will include the following: 


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Table 7.1.1-1 
Clinical Laboratory Assessments 
Serum Chemistry 
Sodium 
Albumin 
Calcium 
Potassium 
SGPT (ALT) 
Phosphorus  
Glucose 
SGOT (AST) 
Chloride 
Blood urea nitrogen 
(BUN) 
Alkaline phosphatase 
Bicarbonate (serum or blood) 
Creatinine 
Total bilirubin 
Uric acid 
Total protein 
Lactate dehydrogenase 
(LDH) 
Magnesium 
Thyroid function 
T4 (free) 
TSH 
Coagulation Panel 
International normalized ratio (INR) 
Partial thromboplastin time 
(PTT) or 
Activated Partial 
thromboplastin time (aPTT) 
Hematology  
Complete blood count 
(CBC) and 
differential 
Platelet count 
Absolute neutrophil 
count 
 
T-cell counts 
Absolute CD4 count 
Absolute CD8 count 
CD4 and CD8 counts will be reported based on the flow cytometric sample sent to 
Quest while the subject is on study. On site counts need only be obtained at End-of-
treatment visit with appropriate follow up if less than 200/mm3. 
Urinalysis 
routine urinalysis or dipstick measurements and, if clinically indicated, microscopic 
analysis. Parameters should include: 
Color 
WBC 
 
Specific Gravity 
RBC or hemoglobin 
 
pH 
Protein 
 
Glucose 
Ketones 
Pregnancy Test 
A serum or urine pregnancy test will be performed for all women of childbearing 
potential at screening.  
Virus Testing 
hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis 
C antibodies (HC Ab) 
HIV  
HTLV-1 
7.1.2 
Vital Signs and Body Weight 
Vital signs (pulse, respiration rate, temperature, and blood pressure) will be measured, with 
the subject in the seated position, at the visits specified in the Study Procedures (Table 1, 
Table 2, and Table 3). Additional vital signs will be obtained if clinically significant signs or 
symptoms occur. 


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Weight will be included in vital sign assessments. The subject’s height will be measured at 
the Pre-Treatment visit.  
7.1.3 
Physical Examination 
The Investigator will perform a full physical examination at the Pre-treatment (including 
height at only this visit) and End-of-treatment visits and brief physical examinations at other 
visits specified in the Study Procedures (Table 1, Table 2, and Table 3). The full physical 
examination requires assessment of the following categories:  head, eyes, ears, nose, and 
throat (HEENT), heart, lungs, abdomen, skin, musculoskeletal, extremities, neurological, 
lymph nodes and ‘other.’ Brief physical examination consists of examination of pertinent 
systems, i.e., those in which abnormalities were noted previously as well as those likely to be 
affected during the course of therapy and those suggested by reported adverse experiences.  
Attention should be paid to those body systems referable to possible autoimmune disorders, 
such as the joints, the eyes, the GI tract as well as signs and symptoms of hypothyroidism. To 
assist in this surveillance, a list of directed questions and suggested actions is provided in 
Appendix 4. 
ECOG Performance Status (PS) will be assessed at each exam according to the ECOG PS 
criteria (Appendix 2). 
7.1.4 
Electrocardiograms 
A baseline 12-lead ECG is to be obtained at the Pre-treatment Visit. Follow up ECGs should 
be performed during the study if clinically indicated and then at the End of Treatment visit. 
The Investigator will have the responsibility for evaluating the ECG interpretation in 
relationship to clinical signs and symptoms and for reaching a medical decision regarding the 
subject’s medical status. If not within normal limits, the ECG findings should be marked 
“clinically significant” or “not clinically significant” (i.e., “CS” or “NCS”) and the ECG 
should be initialed and dated by the Investigator.  
7.1.5 
Blood Sample for Determination of Natural Ligands 
Blood samples will be drawn to measure the concentration of natural ligands such as 
CCL17/TARC and CCL22/MDC at the visits specified in the Study Procedures. Analysis of 
samples will be performed by a central laboratory designated by the Sponsor. Instructions for 
preparation and shipment of samples will be provided in the Laboratory Manual. (As of 


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Amendment 10, central laboratory analysis of samples will no longer be performed [see 
Section 7.8].) 
7.1.6 
Genomic Sampling (For subjects receiving KW-0761 as first assigned 
therapy only) 
A saliva sample will be collected to obtain baseline germline DNA sample to assess 
Fc-gamma receptor polymorphisms. Exploratory analysis of the effect of this genetic 
determinant on safety parameters may be performed. 
Analysis will be performed by a central laboratory designated by the Sponsor. Instructions for 
preparation and shipment of samples will be provided in the Laboratory Manual. 
7.1.7 
Immunogenicity (For subjects receiving KW-0761) 
Serum samples will be drawn for the determination of anti-KW-0761 antibodies and 
concentration of KW-0761 at the visits specified in the Study Procedures. Analysis of 
samples will be performed by a central laboratory designated by the Sponsor. Instructions for 
preparation and shipment of samples will be provided in the Laboratory Manual. (As of 
Amendment 10, central laboratory analysis of samples will no longer be performed [see 
Section 7.8].) 
7.2 
Efficacy Evaluations 
Response in skin and blood will be evaluated every 4 weeks during treatment. In the first year 
of treatment, response in lymph nodes and viscera will be documented at 4 weeks after the 
start of study treatment (end of Cycle 1) and every 8 weeks thereafter. After the first year, 
response in the lymph nodes and viscera will be documented every 16 weeks. In the first year 
of treatment, the global composite response (including skin, blood, lymph nodes and viscera) 
will be assessed at 4 weeks (end of Cycle 1) and every 8 weeks thereafter (Cycle 3, 5, etc.); 
after the first year, global composite response will be assessed every 16 weeks (Cycle 17, 21, 
etc.).   
For those subjects who cross over from the vorinostat arm to KW-0761 treatment, response 
within the second arm of the study will be measured from the first day of dosing with 
KW-0761. Baseline measurements for this arm are considered to be those taken at the last 
assessment which documented progression on vorinostat or if repeated, assessment 
completed closest to and before the first KW-0761 infusion (i.e., mSWAT done on Cycle 1, 
Day 1 is the new baseline). 


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Prior to starting study treatment, visual inspection of the skin with photographs and 
measurements (mSWAT), assessment of CT images and hematological examinations will be 
done to document extent of disease. Skin disease will be evaluated using a modification of 
the SWAT (Olsen, 2007; Stevens, 2002). Response for skin will be based on mSWAT scores. 
In addition, pruritus will be evaluated using a Likert scale and Itchy QoL. Lymph nodes and 
visceral disease will be evaluated by CT. The response in blood will be assessed by flow 
cytometry. 
The response in all compartments (skin, blood, lymph nodes and viscera, as applicable) and 
overall response will be assessed, except as otherwise noted, in accordance with the response 
criteria determined by consensus of the International Society of Cutaneous Lymphomas 
(ISCL), the United States Cutaneous Lymphoma Consortium (USCLC) and the Cutaneous 
Lymphoma Task Force of the European Organization for Research and Treatment of Cancer 
(EORTC) (Olsen, 2011).  
If clinical progression is noted at any time prior to the scheduled assessments for efficacy, the 
assessments (CT, mSWAT, skin photographs and flow cytometry) should be done at that 
time to fully document disease progression. CT must be performed even if previously 
negative at baseline. 
7.2.1 
Evaluation of Skin Disease 
7.2.1.1 
Skin Biopsy 
7.2.1.1.1 CCR4 Expression 
A skin biopsy will be taken at baseline for determination of CCR4 expression by IHC. In the 
event it is not possible to obtain a skin biopsy, use of an archived sample (taken within 
6 months prior to treatment) may be allowed with prior authorization from the Sponsor. To 
determine if vorinostat alters CCR4 expression, investigators are strongly encouraged to 
obtain an additional skin biopsy for the determination of CCR4 expression, prior to treatment 
with KW-0761, in subjects who cross over from treatment with vorinostat.  
Tissue is typically expected to have been prepared for standard histopathological examination 
following formalin or other fixation and embedding in paraffin. The paraffin block is to be 
submitted to a Central Laboratory designated by the Sponsor. If the study site is unable to 
process the tissue, a fresh sample may be sent to the Central Laboratory on the day obtained. 
Submission of unstained slides, while not recommended due to stability concerns with the 
sample, will be accepted. Specific instructions for sample preparation and handling will be 
provided in the Laboratory Manual. 


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With the consent of the subject, the remainder of the skin or lymph node biopsy specimens, 
i.e., the tissue that is left over after the study-specific tests are conducted, will be archived 
and the remainders of the specimens will be used in the development of an 
immunohistochemical assay for the semi-quantitative detection of CCR4. All specimens 
submitted for the purpose of the development of this assay should be managed by the 
investigator and his/her staff with adequate precautions to ensure subject confidentiality, in 
accordance with applicable national and/or local laws and regulations on personal data 
protection. 
7.2.1.1.2 Disease Status/Other Biopsy Recommendations 
Subjects with clinical features suggestive of LCT must have a biopsy performed within 
4 months prior to Cycle 1 Day 1 to rule out transformed disease. 
Skin biopsies at the end of the cycle and to confirm a CR are optional and can be performed 
at the discretion of the investigator. Analysis of these biopsies will be done by the pathologist 
at the study site. 
Additional translational assessments may be performed to further characterize the response in 
skin on any biopsy samples obtained. 
7.2.1.2 
Skin Photographs 
Cameras will be supplied to the study site by Canfield Scientific, Inc. for use in this study. 
All involved areas that are representative of the subject’s extent of disease, will be selected at 
baseline and measured and photographed using the digital camera provided by Canfield. In 
addition, half-body global photos (waist to feet, waist to top of head and sides) will also be 
obtained. Photos should be taken against a blue backdrop.  
Skin photographs should be obtained prior to administration of study drug on Day 1 of the 
first treatment cycle and then as specified in the Study Procedures tables.  
Special care should be taken to shield the subject’s identity in accordance with local 
guidelines on data privacy.  
Photos must be labeled with only the subject identification number and initials. Digital photos 
will then be submitted on an ongoing basis to Canfield Scientific, Inc. for quality review. 
Canfield Scientific, Inc. will review photographs on an ongoing basis for assessment of 
image quality and provide feedback to sites to ensure the photographs are appropriately 
representative of extent of skin disease. (As of Amendment 8, submission of photographs to 
Canfield Scientific, Inc. is no longer required.) 


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More detailed instructions regarding photographing of skin lesions will be provided in the 
Photography User Manual. 
7.2.1.3 
Modified Severity Weighted Assessment Tool (mSWAT) 
Skin lesions and erythema will be evaluated using the mSWAT.  
The mSWAT is an objective, quantitative, severity-weighted method to assess the extent of 
skin lesions. An mSWAT score is derived by measuring each lesion as a percentage of total 
body surface area (%TBSA) and multiplying it by a severity-weighting factor (1 = patch, 
2 = plaque, 4 = tumor). All individual numbers are then added to produce a total score.  
Areas of skin involvement identified as patch, plaque, or tumor and erythema are defined in 
Table 7.2.1-1 and Table 7.2.1-2: 
Table 7.2.1-1 
Modified Severity Weighted Assessment Tool 
Skin Lesion Definitions 
Lesion Type 
Abnormal Skin 
Erythema 
Patch 
Abnormal skin not elevated from 
normal skin 
Flat erythema or erythema with mild 
infiltration 
Plaque 
Abnormal skin elevated from normal 
skin by < 5 mm 
Elevated erythema or erythema with moderate 
infiltration 
Tumor 
Abnormal skin elevated from normal 
skin by ≥ 5 mm 
Erythema with fissuring, ulceration, or tumor 
mSWAT Score Calculation 
Sum of %TBSA from all body regions affected by patches x severity-weighting factor of 1  
+ Sum of %TBSA from all body regions affected by plaques x severity-weighting factor of 2  
+ Sum of %TBSA from all body regions affected by tumors x severity-weighting factor of 4 
= Total mSWAT (maximum score = 400). 
 
 


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Table 7.2.1-2 
Modified Severity Weighted Assessment Tool Score 
Body region (%BSA) 
Patch* 
Plaque* 
Tumor* 
      Head (7 %) 
 
 
 
      Neck (2%) 
 
 
 
      Anterior trunk (13%) 
 
 
 
      Arms (8%) 
 
 
 
      Forearms (6%) 
 
 
 
      Hands (5%) 
 
 
 
      Posterior trunk (13%) 
 
 
 
      Buttocks (5%) 
 
 
 
      Thighs (19%) 
 
 
 
      Legs (14%) 
 
 
 
      Feet (7%) 
 
 
 
      Groin (1%) 
 
 
 
Subtotal of lesion BSA 
 
 
 
Weighting factor 
x1 
x2 
x4 
Subtotal lesion BSA x weighting factor 
 
 
 
mSWAT score = summation of each column line above =  
patch = any size lesion without induration or significant elevation above the surrounding uninvolved skin: poikiloderma may 
be present.  
plaque = any size lesion that is elevated or indurated; crusting, ulceration or poikiloderma may be present.  
tumor = any solid or nodular lesion ≥ 1 cm in diameter with evidence of deep infiltration in the skin and/or vertical growth.  
 
7.2.1.4 
Response Criteria for Skin 
Response in skin will be determined by changes in mSWAT score as specified in Table 
7.2.1-3. Responses (CR and PR) must be confirmed for a minimum of 4 weeks. 


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Table 7.2.1-3 
Response Criteria for Skin, as assessed by mSWAT scoresa 
Response 
Definition 
CR 
100% clearance of skin lesionsb  
PR 
50 to 99% clearance of skin disease from baseline without new tumors (T3) in subjects with T1, 
T2 or T4 only skin disease 
SD 
< 25% increase to <50% clearance in skin disease from baseline without new tumors (T3) in 
subjects with T1, T2 or T4 only skin disease 
PDc 
(1) ≥ 25% increase in skin disease from baseline or 
(2) New tumors (T3) in subjects with T1, T2 or T4 only skin disease or 
(3) Loss of response:  in those with CR or PR, increase of skin score of greater than the sum of 
nadir plus 50% baseline score 
Relapsed 
Any disease recurrence in those with CR  
a: Based on mSWAT score. 
b: A biopsy of normal appearing skin is unnecessary to assign a CR. However, a skin biopsy should be performed of a 
representative area of the skin if there is any question of residual disease where otherwise a CR would exist. If histologic 
features are suspicious or suggestive of MF/SS (see histologic criteria for early MF7), the response should be considered 
a PR only. 
c: Whichever criterion occurs first. 
d: For purposes of the study, relapse should be defined as loss of response (as defined for PD) in those with CR, ie, increase 
of skin score of greater than the sum of nadir plus 50% baseline score. Subjects may remain on treatment until subsequent 
measurement to confirm progression. 
 
7.2.1.5 
Pruritus Evaluation 
The extent of pruritus can have a significant impact on the subject’s QoL. A Likert scale 
(Appendix 9) will be completed by each subject to assess their degree of pruritus at the visits 
specified in the Study Procedures. The Itchy Quality of Life questionnaire (Desai, 2008) (see 
Appendix 5) will also be completed at these visits to further evaluate the impact of pruritus 
on their QoL. Medications taken to treat pruritus will be documented. 
7.2.2 
Evaluation of Blood Disease 
7.2.2.1 
Flow Cytometric Analysis 
A peripheral blood sample will be used to evaluate circulating malignant T-cells and further 
assess immune cells in the blood.  
Samples will be sent to a central laboratory designated by the Sponsor. Specific directions for 
sample preparation and packaging will be provided in the Laboratory Manual. (As of 
Amendment 10, central laboratory analysis of samples will no longer be performed [see 
Section 7.8].) 


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7.2.2.2 
Response Criteria in Blood 
In subjects with blood involvement, all blood  responses (CR and PR) must be confirmed for 
a minimum of 4 weeks.  
Response criteria are specified in Table 7.2.2-1. 
Table 7.2.2-1 
Blood Response Criteriaa 
CRb 
B0 
PRc 
> 50% decrease in quantitative measurements of blood tumor burden from baseline in those with 
high tumor burden at baseline (B2)  
SD 
Fails to attain criteria for CR, PR or PD 
PDd 
(1) B0 to B2 or  
(2) > 50% increase from baseline and at least 5,000 neoplastic cells/μL or 
(3) Loss of response: in those with PR who were originally B2 at baseline, > 50% increase from 
nadir and at least 5,000 neoplastic cells/μL 
Relapse 
Increase of neoplastic blood lymphocytes to ≥ B1 in those with CR 
a: As determined by absolute numbers of neoplastic cells/uL. 
b: If a bone marrow biopsy was performed at baseline and determined to unequivocally be indicative of lymphomatous 
involvement, then to confirm a global CR where blood assessment now meets criteria for B0, a repeat bone marrow 
biopsy must show no residual disease or the response should be considered a PR only.  
c: There is no PR in those with B1 disease at baseline as the difference within the range of neoplastic cells that define B1 is 
not considered significant and should not affect determination of global objective response. 
d: Whichever occurs first. 
 
7.2.3 
Evaluation of Disease in Lymph Nodes and Viscera 
7.2.3.1 
Baseline Tumor Assessments 
The baseline tumor burden will be assessed by CT of the neck, chest, abdomen and pelvis 
within 30 days prior to the first dose of study drug. The Investigator will identify, 
prospectively, the lesions to be followed to evaluate the subject’s response to therapy. Lymph 
nodes must be > 15 mm in the long axis (greatest transverse diameter, GTD) or > 10 mm in 
the short axis if the GTD is > 10 to ≤ 15 mm. 
Lymph node biopsies may be performed, at the discretion of the Investigator, to rule out 
inflammation or to confirm disease. Analysis of these biopsies will be done by the pathologist 
at the study site. 
7.2.3.2 
Method of Tumor Response Assessment 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at Screening and at reassessment during treatment. 
Imaging-based evaluation is preferred to evaluation by clinical examination when both 


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methods have been used to assess the anti-tumor effect of a treatment. Lesions evaluated 
clinically will only be considered measurable when they are superficial (e.g., skin nodules, 
palpable lymph nodes). In the case of skin lesions, documentation by color photography, 
including a ruler to estimate the size of the lesion, is recommended. Contrast enhanced CT 
will be considered the best currently available and reproducible method to measure target 
lesions selected for response assessment. For subjects who are allergic to contrast agents, 
non-contrast CT can be performed. The allergy must be documented on the Medical History 
eCRF. Ultrasound is not an acceptable method to measure disease. Central review of 
radiology may be performed to confirm the date of disease progression. Images should be 
transmitted to the central radiology group as described in the Imaging Manual. 
7.2.3.3 
Determination of Response in Lymph Nodes and Viscera 
The Investigator will make a determination of response based on criteria as specified in Table 
7.2.3-1 and Table 7.2.3-2. In subjects with lymph node and/or visceral involvement, 
responses (CR and PR) must be confirmed for a minimum of 4 weeks. 


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Table 7.2.3-1 
Response in Lymph Nodesa 
CR 
All lymph nodes are now ≤ 15 mm in GTD by the method used to assess lymph nodes at baseline. 
In addition, lymph nodes that were ≤ 15 mm in GTD and > 10 mm in the short axis at baseline 
must now be ≤ 10 mm in the short axis. 
PR 
Cumulative reduction ≥ 50% of the SPD as compared to baseline and no new lymph node 
(> 15 mm in the GTD or > 10 mm in the short axis if the GTD is > 10 mm to ≤ 15 mm).  
SD 
Fails to attain the criteria for CR, PR, or PD 
PD 
Must meet any of the following: 
(1) ≥ 50% increase in SPD from baseline of lymph nodes, or 
(2) Loss of response, which is > 50% increase from nadir SPD of lymph nodes in subjects 
previously assessed as PR, or 
(3) > 50% increase compared to nadir, but which does not meet the criteria for PR (i.e., up to a 
50% reduction compared to baseline), or 
(4) Any new nodal lesion > 15 mm in the GTD or >10 mm in short axis diameter if the GTD is  
> 10 mm to ≤ 15 mm) 
Relapse 
(1) Any new lymph node > 15 mm in GTD or >10 mm in short axis if the GTD is > 10 mm to 
≤ 15 mm 
(2) Recurrence of any lymph node previously selected at baseline, which was previously assessed 
as a CR, but which has recurred and measures  > 15 mm in the GTD or > 10 mm in the short axis 
if the GTD is > 10 mm to ≤ 15 mm. 
Unable to 
Evaluate 
A lymph node present at baseline, but which was not measured or which subsequently became 
unevaluable, leading to an inability to determine the status of that particular node for the time 
point in question. 
a: Peripheral and central lymph nodes 
GTD=greatest transverse diameter; SPD=sum of the products of the diameters 
 
 


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Table 7.2.3-2 
Response in Viscera 
CR 
(1) 100% reduction in the SPD of all lesions selected at baseline. 
(2) Liver or spleen or any organ considered involved at baseline should be considered normal by 
imaging. 
(3) No nodules should be present on any imaging of liver or spleen. 
PR 
(1) ≥ 50% regression in all splenic or liver nodules, or in measurable disease (SPD) in all organs 
abnormal at baseline.  
(2) No increase in the size of liver or spleen consistent with disease progression and no new sites of 
involvement.  
SD 
Fails to attain the criteria for CR, PR, or PD 
PD 
Must meet any of the following: 
(1) > 50% increase in SPD of organs involved at baseline, or 
(2) New organ involvement, or 
(3) Loss of response, which is > 50% increase from nadir in the SPD of previous organ involvement 
in subjects previously assessed as PR, or 
(4) > 50% increase compared to nadir, but which does not meet the criteria for PR (i.e., up to a 50% 
reduction compared to baseline). 
Relapse 
(1) New organ involvement in subjects previously assessed as CR. 
(2) Recurrence of any lesion previously selected at baseline, which was previously assessed as a CR, 
but which has recurred and meets the measurement criteria (≥ 10 mm and/or 2× the reconstruction 
interval in the GTD). 
Unable 
to 
Evaluate 
An area of visceral disease present at baseline, but which was not measured or which subsequently 
became unevaluable, leading to an inability to determine the status of that particular area for the time 
point in question. 
GTD=greatest transverse diameter; SPD=sum of the products of the diameters 
 
7.2.4 
Global Composite Response Score 
Overall response will be based on response in each compartment (skin, blood, lymph nodes 
and viscera) as specified in Table 7.2.4-1.  


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Table 7.2.4-1 
Global Composite Scoring System 
Global 
Score 
Definition 
Skin 
Nodes 
Viscera 
Blood 
CR 
Complete disappearance of all 
clinical evidence of disease 
CR 
All categories have CR/NI 
PR 
Regression of measurable 
disease 
CR 
All categories do not have a CR/NI and no 
category has a PD  
PR 
No category has a PD and if any other category 
involved at baseline, at least one has a CR or 
PR  
SD 
Failure to attain CR, PR or PD 
PR 
No category has a PD and if any other category 
involved at baseline, no CR or PR in any 
SD 
CR/NI,PR,SD in any category and no category 
has a PD  
PD 
Progressive disease 
PD in any category 
Relapse 
Recurrence of disease in prior 
CR 
Relapse in any category  
NI=non-involved 
 
Node, viscera and blood response contributes towards global response only if disease present 
at baseline, unless defining global PD which is met by new disease in previously uninvolved 
compartment.  However, subjects who meet PD criteria in any compartment, or relapse in 
blood, lymph nodes or viscera, confirmed at 2 consecutive visits must be discontinued from 
study treatment due to disease progression/relapse. If subsequent assessment does not 
confirm PD in any compartment, or relapse in blood, lymph nodes or viscera, subject may 
continue on treatment. An unconfirmed PD/relapse would not preclude future responses (CR 
or PR). 
If PD is documented in any compartment at any point leading to subject’s discontinuation 
from treatment, the overall global composite score should be completed at that time even if 
all compartments have not been assessed. 
7.2.4.1 
Independent Review of Progression 
A blinded independent review of response data for each subject will be performed to make a 
determination regarding progression and the date of progression. The nodal and visceral 
compartments evaluation will be based upon radiologic data. The independent radiology 
review of radiographic exams will provide an assessment of tumor response and progression 
for all subjects. A separate radiology charter will detail the roles and responsibilities of the 
radiology reviewers and how the reads will be performed. An independent reviewer (IR) will 
assess PFS based on date of progression or death, whichever comes first. For this assessment 


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the independent reviewer will be supplied the results of the independent radiology review, the 
mSWAT score for each subject, as assessed by the investigator, and the results of central 
flow cytometry in order to assess blood response, and date of death for subjects who died 
before progression.  
Secondarily, the IR will review the date of any objective responses (CR or PR).  
7.3 
Pharmacokinetics (for subjects receiving KW-0761) 
Serum samples will be drawn in subjects who receive KW-0761 (as first assigned therapy or 
crossover) at the timepoints specified in the Study Procedures Tables (Table 1, Table 2, and 
Table 3) for determination of KW-0761 concentration, through Cycle 3 and at the 
End-of-treatment Visit. At selected sites, 4 additional samples will be drawn between 6 and 
8 hours, and at 24, 48, and 72 - 96 hours after the first infusion on Day 1/Cycle 1 in 
approximately 10 subjects, including crossover subjects. Blood samples obtained 
post-infusion should be obtained from the arm contralateral to that of study drug 
administration. The exact time of sample draw must be recorded in the eCRF.  
All samples will be sent to a central laboratory designated by the Sponsor. Specific directions 
for sample preparation and packaging will be provided in the Laboratory Manual. 
7.4 
Quality of Life Assessments 
Subjects with CTCL often suffer from the symptoms related to their disease (pain, sleep 
disturbance, etc.), the social and psychological problems related to sometimes unsightly skin 
lesions and the burden of living with a chronic disease. In an effort to assess some of these 
QoL issues, the Skindex-29 (see Appendix 6), FACT-G (see Appendix 7) and EQ-5D-3L (see 
Appendix 8) will be administered. 
7.5 
Follow-Up 
All subjects will be contacted by telephone every 30 days (± 7 days) up to 90 days after the 
last dose of study medication or initiation of alternative therapy, whichever comes first, to 
confirm any new onset AEs or toxicities. If a subject who has received KW-0761 undergoes a 
stem cell transplant at any time during or after the 90-day follow-up period, AEs/SAEs 
should be documented from the transplant procedure through 180 days post-transplant.  
During follow-up, medications used to treat an AE and those that are temporally associated 
with the AE and may have a causal relationship will be recorded. In all subjects who cross 


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over from vorinostat to KW-0761, the causality should be assessed for both drugs for 30 days 
after vorinostat was stopped (or later if the event is considered to be related to vorinostat).  
• 
After a subject who receives KW-0761 goes off study, if CD4 and CD8 counts are less 
than 200/mm3 at the End-of-treatment visit, they will be followed every 3 months 
(± 14 days) until they return to at least 200/mm3, initiation of alternative therapy or 
1 year, whichever comes first. 
• 
In the absence of disease progression, all subjects or their referring physicians will be 
contacted every 3 months (± 14 days) until documented disease progression or death, or 
initiation of alternative therapy. 
• 
All subjects or their referring physician will be contacted every 3 months (± 14 days) to 
ascertain survival status.  
• 
For all subjects who have received KW-0761, subsequent stem cell transplant information 
should be recorded in a separate CRF provided by the Sponsor. For subjects who undergo 
transplant, concomitant medications and AEs/SAEs should be documented through 
180 days post-transplant on the CRFs provided. 
• 
All follow up information and attempts to obtain follow up information should be 
documented in the subject’s source record. 
7.6 
Follow-Up for Subjects Achieving a Complete Response 
Those subjects who do not continue treatment after achieving a CR will undergo the 
following assessments every 8 weeks (± 14 days) for the first 6 months (if CR achieved prior 
to one year on study) and then every 16 weeks (± 14 days) thereafter until progression: 
• 
Chemistry/Hematology profile;  
• 
Skin photographs; 
• 
mSWAT; 
• 
Pruritus evaluation; 
• 
Blood sample for flow cytometric analysis; 
• 
CT;  
• 
Overall Disease Response; 
• 
Immunogenicity (for subjects receiving KW-0761).  
After progression of disease, subjects will be followed as applicable according to the 
procedures for post-treatment follow-up described in Section 7.5 including collection of 
transplant information for subjects who have received KW-0761. 


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7.7 
Study Procedures for Subjects Continuing Study Treatment at the Time 
of Primary Efficacy Analysis 
Subjects receiving study treatment at the time of the primary efficacy analysis may continue 
on study. For these subjects, administration of study drug(s) and data collection should 
continue as described below.  Note: Initiation of  disease evaluation assessments per 
institution/Investigator standard of care should not occur until notification by the Sponsor. 
Study Drug Administration 
• 
KW-0761 administration: KW-0761 may continue to be administered according to the 
protocol (as specified in Section 8.1) on Day 1 and Day 15 of each cycle until PD, drug 
intolerance or unacceptable toxicity, or until any of the other criteria for study removal 
are met (as defined in Section 5.5) or until KW-0761 is approved/not approved for 
marketing for the indication and regimen under study in the geographic region of study.  
• 
Vorinostat treatment will continue to be administered as described in Section 5.2.2. 
Vorinostat will be supplied by the Sponsor for a period of up to 1 year after the data 
cutoff for the primary efficacy analysis. During this year all study subjects are eligible to 
cross over to mogamulizumab as described in Sections 3.4 and 5.3.  
Safety: Safety data will continue to be collected as described in the protocol for as long as the 
subject receives study drug through 90 days after the last dose or initiation of alternative 
therapy whichever comes first (as described in Section 7.1). 
If a subject who has received KW-0761 undergoes a stem cell transplant at any time during or 
after the 90-day follow-up period, transplant information should be documented as described 
in Section 7.5 including recording of concomitant medications and AEs/SAEs from the 
transplant procedure through 180 days post-transplant. 
Efficacy: Efficacy data will be collected for 1 year after the time of the primary efficacy 
analysis. During that 1-year period, pending notification by the Sponsor, Investigators should 
follow study subjects in accordance with the standard of care at their Institution in order to 
assess subjects’ disease status. Required data collection will be limited to the following 
(additional data may be collected at the discretion of the Investigator): 
• 
At the time of disease progression or discontinuation from treatment for any other reason, 
sites are to perform the disease evaluation assessments per institution/Investigator 
standard of care. The method of assessment of PD, if applicable, should be recorded; 
• 
PRO - Itchy QoL, Skindex-29, EQ-SD-3L, Likert, and FACT-G will be collected every 
4 mos. (16 weeks) for as long as the subject receives study drug. 
In addition, all subjects or their referring physician will continue to be contacted every 
3 months (± 14 days) to ascertain survival status. 


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7.8 
Study Procedures for Subjects Ongoing at the Time of Initial Marketing 
Authorization 
For subjects who are continuing to receive KW-0761 at the time of initial marketing 
authorization, the Sponsor will supply study drug until KW-0761 becomes commercially 
available (reimbursable) in the country/region of the study site or until KW-0761 is not 
approved for marketing for the indication and regimen under study in the country/region of 
the study site.  
Procedures to be followed for all ongoing subjects, i.e., subjects who are continuing to 
receive KW-0761 or who are in safety or survival follow-up, at the time of initial marketing 
authorization are described below.  These procedures should be implemented upon 
notification by the Sponsor.  
Study Drug Administration 
KW-0761 may continue to be administered according to the protocol (as specified in 
Section 8.1) on Day 1 and Day 15 of each cycle until PD, drug intolerance or unacceptable 
toxicity, or until any of the other criteria for study removal are met (as defined in Section 5.5) 
or until KW-0761 becomes commercially available (reimbursable) or is not approved for 
marketing for the indication and regimen under study in the country/region of the study site. 
For subjects who experience an overall CR, the subject may continue treatment for up to 
12 months (as described in Section 5.2.1.4) or until KW-0761 becomes reimbursable or is not 
approved. 
KW-0761 should continue to be administered as described in Section 8.1.3. 
Study Drug Accountability 
Drug accountability must be maintained as described in Section 8.1.6.   
Efficacy and Safety Assessments 
Investigators should follow study subjects in accordance with the standard of care at their 
Institution with respect to assessments of disease status and safety/tolerability, including the 
use of local clinical laboratories.  There will be no further central laboratory requirements. 
Subjects who meet the protocol criteria for progression or relapse in one compartment but are 
clearly deriving benefit in other compartment(s), may remain on treatment at the discretion of 
the Investigator. 
Survival follow-up will be discontinued for all subjects.  


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Data Collection 
Electronic data capture will be terminated for all subjects at the time of implementation of 
Amendment 10.   
Required data collection will be limited to SAEs and treatment-related AEs.  These events 
will be reported only to the KKD Drug Safety Surveillance Department using the SAE form 
(see Section 9.4).   
8 
STUDY AGENTS 
8.1 
KW-0761 (mogamulizumab) 
8.1.1 
Description 
 
 
 
 
  
8.1.2 
Preparation of Dose 
 
 
 
  
 
 
  
 
 
 
 
 
8.1.3 
Study Drug Administration 
Subjects will receive KW-0761 as an iv infusion over at least 1 hour for all infusions. 
Subjects will be observed closely for 1 hour following each administration of KW-0761 for 


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any potential AEs in an area with resuscitation equipment. Vital signs will be checked and 
recorded prior to start of infusion, at the end of the infusion and at 1 hour after completion of 
infusion.  
Hematology results should be reviewed before each subsequent dose. Laboratory assessments 
may be performed the day prior to dosing to ensure results are available prior to dosing. The 
platelet count must be ≥ 100,000 / mm3 and the ANC must be ≥ 1,500/mm3 before a subject 
can receive study drug. If a scheduled dose cannot be given within the allowed window, the 
dose should be skipped and the subject should resume dosing with the next scheduled dose 
assuming the platelet count and ANC are within the parameters described above. If a subject 
misses 2 consecutive doses, contact the Medical Monitor or designee to determine if the 
subject should be withdrawn from the trial. 
Should a hypersensitivity reaction to KW-0761 occur, the subject must be treated according 
to the best available medical practices. Subjects should be instructed to report any delayed 
reactions to the investigator immediately. See Section 5.2.1.7 for additional information 
regarding the treatment of infusion reactions. 
8.1.4 
KW-0761 Formulation and Storage 
 
 
 
  
 
  
 
  
8.1.5 
Packaging and Labeling of KW-0761 
 will distribute the study drug to the 
pharmacies at the study sites in the US. 
 
 will distribute the study drug to the pharmacies at the 
study sites in Europe and Australia. 
 will distribute the study drug to 
the pharmacies at the study sites in Japan.  


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8.1.5.1 
Labeling 
Vial and carton labels will bear the appropriate text as required by each country’s regulatory 
agency requirements.  
8.1.6 
Drug Accountability 
The Principal Investigator and pharmacy at the study site are responsible for maintaining 
accurate records of the receipt, dispensing, and return of all investigational materials. The 
Investigator may dispense study drug only to subjects enrolled in the study. Under no 
circumstance will the Investigator allow study drug to be used other than as directed by the 
protocol. 
The pharmacy designated by the Investigator, must maintain an inventory of drug supplies 
received, dispensed, and destroyed. All used and unused study drug must be accounted for. 
When a shipment is received, the Investigator or pharmacist must verify the quantities 
received and return the acknowledgement to the study monitor or designee. The study drug 
accountability record includes the identification of the person to whom the drug is dispensed, 
the lot number on the vial, the date of dispensing, and any returned or unused drug. An 
account must be given of any discrepancies. This record is in addition to information 
regarding dose recorded on the eCRF. These records must be readily available for inspection 
by KKD monitor or designee and are open to FDA or other regulatory authority inspection at 
any time. Copies of this record will be provided to the sponsor by the Investigator at the 
conclusion of the study. 
8.1.7 
Return and Destruction 
Upon completion or termination of the study, all unopened vials of KW-0761 must be 
destroyed at the study site according to local regulations, unless other arrangements have 
been approved by KKD. 
8.2 
Vorinostat (ZOLINZA®) Capsules 
8.2.1 
Description 
Vorinostat will be supplied by the Sponsor for a period of up to 1 year after 255 PFS events 
are observed. Vorinostat is a white to light orange powder. Each 100 mg capsule for oral 
administration contains 100 mg vorinostat and the following inactive ingredients: 
microcrystalline cellulose, sodium croscarmellose and magnesium stearate. The capsule shell 
excipients are titanium dioxide, gelatin and sodium lauryl sulfate. This agent is approved for 


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marketing in the US, Japan and Australia and is indicated for the treatment of progressive, 
persistent or recurrent CTCL. Since vorinostat is not approved in the EU, it will be labeled as 
an investigational drug according to applicable regulations. Investigators will use the supplies 
provided and will follow the FDA approved US prescribing information (e.g., dosage and 
administration, warnings, precautions, adverse reactions, dose modifications and omissions 
and storage information).  
8.2.2 
Administration 
Subjects will receive 400 mg daily of vorinostat orally with food commencing on Day 1. 
8.2.3 
Vorinostat Adverse Events  
The most common AEs (≥ 20%) are diarrhea, fatigue, nausea, thrombocytopenia, anorexia 
and dysgeusia. Please refer to the US prescribing information for more complete information. 
8.2.4 
Return and Destruction 
Upon completion or termination of the study, all unopened containers of vorinostat must be 
destroyed at the study site according to local regulations, unless other arrangements have 
been approved by KKD. 
9 
ADVERSE EVENT REPORTING IN CLINICAL TRIALS 
The Investigator will inquire about AEs at all subject visits by asking the subject a question 
such as: “How have you been feeling since your last visit?” All AEs, whether observed by the 
Investigator or reported by the subject, must be collected and recorded on the appropriate AE 
page of the eCRF and as appropriate on the SAE form (see Section 9.2). (See Section 7.8 for 
reporting requirements/procedures for subjects who are ongoing in the study (i.e., subjects 
who are continuing to receive KW-0761 or who are in safety or survival follow-up) at the 
time of initial marketing authorization). 
The collection of AE information commences following the subject’s written Informed 
Consent to participate in the study. If a subject experiences an AE, the subject will receive 
appropriate treatment and supportive care as necessary, and the Investigator will continue to 
follow up until there is a return to the subject’s baseline condition, or until a clinically 
satisfactory resolution is achieved. 
Timely and complete reporting of all AEs assists the Sponsor in identifying any untoward 
medical occurrence, thereby allowing: (1) protection of safety of study subjects; (2) a greater 


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understanding of the overall safety profile of the study drug; (3) recognition of dose-related 
study drug toxicity; (4) appropriate modification of study protocols; (5) improvements in 
study design or procedures; and (6) adherence to worldwide regulatory requirements. Every 
effort should be made to enter the AE information in the eCRF within 7 days of when the 
information becomes available in order to ensure timely reporting to the Sponsor. 
9.1 
Definitions 
9.1.1 
Adverse Events 
An AE is any untoward medical occurrence in a clinical investigation subject administered an 
investigational product and which does not necessarily have to have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding, for example), symptom or disease temporally associated with 
the use of an investigational product, whether or not considered related to the investigational 
product. 
The description of each AE will identify the subject, date of onset, the date of resolution, the 
severity of the event, the action taken regarding study drug, the outcome of the event, and the 
relationship of the event to study drug. A medical condition present at screening that has 
increased in frequency or severity must be recorded on the AE page of the eCRF. 
Standard medical terminology should be used to document AEs on the eCRF. The subject’s 
exact description of the event will be recorded in the source documentation. In the case of 
signs and symptoms, the underlying illness or diagnosis will be recorded as the event when 
known. 
For this study, disease progression will not be considered as an AE. Lymphopenia is the 
pharmacologic effect of the drug and will also not be considered an AE for this study. 
Lymphocytes will be monitored and evaluated with the laboratory data. 


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9.1.2 
Adverse Event Severity 
All AEs will be graded using CTCAE Version 4.0 as:  
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADLa 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADLb 
Grade 4 
Life-threatening consequences; urgent intervention indicated 
Grade 5 
Death related to AE 
a: Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
b: Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
ADL=Activities of Daily Living 
 
For AEs not contained within CTCAE, Version 4.0, the Investigator will assess the 
severity/grade of an AE according to the five grades above. 
9.1.3 
Adverse Event Relationship to Study Drug 
The relationship of each AE to the study drug will be evaluated using the following 
guidelines: 
Definitely Related 
An AE that follows a reasonable temporal sequence from administration of the drug 
(including the course after withdrawal of the drug) and that satisfies any of the following: 
(1) reappearance of a similar reaction upon re-administration (positive re-challenge); 
(2) positive results in a drug sensitivity test (skin test, etc.); (3) toxic level of the drug as 
evidenced by measurement of drug concentrations in blood or other bodily fluid. 
Probably Related 
An AE that follows a reasonable temporal sequence from administration of the drug 
(including the course after withdrawal of the drug) and for which involvement of factors 
other than the drug, such as underlying diseases, complications, concomitant drugs and 
concurrent treatments, can reasonably be excluded. This may also include positive 
dechallenge (event abates upon discontinuation of the investigational agent). 


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Possibly Related 
An AE that follows a reasonable temporal sequence from administration of the drug 
(including the course after withdrawal of the drug) and for which possible involvement of the 
drug can be suggested (for example previous similar reports or pharmacologic actions of the 
drug) although factors other than the drug, such as underlying diseases, complications, 
concomitant drugs and concurrent treatments may also be responsible.  
Unlikely 
An AE that, while relationship to the drug cannot be definitively excluded, does not appear to 
follow a reasonable temporal sequence from administration of the drug or that appears to be 
reasonably explained by other factors, such as underlying diseases, complications, 
concomitant drugs and concurrent treatments. 
Not Related 
An AE that does not follow a reasonable temporal sequence from administration of the drug 
or that can reasonably be explained by other factors, such as underlying diseases, 
complications, concomitant drugs and concurrent treatments. 
As of Amendment 10, relationship to study drug will be reported as related/not related per 
SAE form requirements (see Section 7.8). 
9.2 
Serious Adverse Events 
Any AE that is initially considered serious or becomes serious should be reported on the SAE 
form.  
A SAE is any untoward medical occurrence which: 
• 
Results in death; 
• 
Is immediately life threatening;  
– The term “life-threatening” in the definition of “serious” refers to an event in which 
the subject was at risk of death at the time of the event; it does not refer to an event 
that hypothetically might have caused death if it were more severe.  
– If an event is Grade 4 by CTCAE version 4.0, it does not necessarily meet the 
definition for life-threatening. 
• 
Requires in-patient hospitalization/admission or prolongation of existing hospitalization; 
• 
Results in persistent or significant disability/incapacity;  
• 
Is a congenital anomaly/birth defect; or 
• 
Is an important medical event: 


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– Those events that may not be immediately life-threatening or result in death or 
hospitalization but based upon appropriate medical and scientific judgment may 
jeopardize the subject or may require intervention to prevent one of the serious 
outcomes listed above. Examples include intensive treatment in an emergency room 
or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not 
result in hospitalization; development of drug dependency or drug abuse. 
All AEs, whether non-serious or serious, must be recorded on the AE page of the eCRF. In 
addition, any AE that is initially considered serious or becomes serious must be reported on 
the SAE form. The SAE information entered on the eCRF must be consistent with the 
information entered on the SAE form. 
Serious adverse events require expeditious handling to comply with regulatory requirements. 
Any SAE occurring in a clinical study subject must be reported to the Sponsor or designee 
within 24 hours of the Investigator having knowledge of the SAE. 
The Investigator or other qualified individual at the investigative site must complete the SAE 
form and fax it to the Sponsor or designee. All telephone communication regarding an SAE 
must be followed by a written report. In addition, SAE reports may require subsequent 
notification of the IRB and/or Ethics Committee (EC), if appropriate. 
The Investigator is obligated to immediately report to the Sponsor or designee any SAE 
occurring at any time after the subject signs the Informed Consent Form and within 90 days 
after the last dose of study drug or initiation of alternative therapy whichever comes first, 
independent of the circumstances or suspected cause. In all subjects who cross over from 
vorinostat to KW-0761, the causality should be assessed for both drugs for 30 days after 
vorinostat was stopped (or later if the event is considered to be related to vorinostat). In 
addition, the Investigator must promptly report to the Sponsor any SAE occurring at any 
other time after completion of the study if a causal relationship to study drug is suspected. 
For all SAEs, the Investigator is obligated to pursue and provide information as requested by 
the Sponsor in addition to that requested on the SAE form. Information must include a 
description of the SAE in sufficient detail to allow for a complete medical assessment of the 
case and independent determination of causality. In the case of a subject death, a summary of 
autopsy findings, if available, must be submitted as soon as possible to the Sponsor. The 
Investigator will ensure that information reported immediately by telephone or other means 
and information entered on the SAE form is accurate and consistent.  


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9.3 
Other Safety Considerations 
Any clinically important changes noted during interim or final physical examinations, ECGs, 
x-rays, or any other potential safety assessments, whether or not these procedures are 
required by the protocol, must also be recorded on the appropriate eCRF page and SAE form, 
as appropriate, in order for the Sponsor to collect additional information about that 
abnormality, including information regarding relationship to study drug, any action taken, 
and resolution.  
9.4 
Adverse Event Contacts 
All non-emergency inquiries and general information regarding this study should be directed 
to the Sponsor or designee.  
Serious adverse event reports and follow-up SAE documentation for subjects in the US, UK, 
and Australia should be forwarded to the KKD Drug Safety Surveillance Department:  
 
 
 
 
Serious adverse event reports and follow-up SAE documentation for subjects in Japan should 
be forwarded to the KHK Drug Safety Surveillance Department: 
 
9.5 
Data Safety Monitoring Board 
A Data Safety Monitoring Board (DSMB), whose composition, roles and responsibilities are 
described in a separate DSMB charter, will oversee subject safety in the trial. The DSMB 
consists of at least 2 medical doctors and a statistician.  
10 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
The number of subjects enrolled and discontinued will be presented. A summary of reasons 
for discontinuation will be provided. The number of subjects in the Intent-to-Treat (ITT), 
Safety Analysis, and Efficacy Evaluable Sets (see Section 10.1) will be presented by 
treatment arm and combined.  


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Demographic and other baseline subject characteristics will be summarized by treatment arm 
for the ITT Set. These summaries will include demographics (including age, race, sex, height, 
weight, and body surface area) and baseline values for disease information. 
Descriptive statistics (mean, standard deviation, median, minimum, and maximum) for 
continuous variables and frequency distributions and percentages for discrete variables will 
be utilized. 
10.1 Populations to be Analyzed 
The following analysis sets will be used in the study: 
• 
Intent-to-Treat Set: Includes all subjects randomized to a therapy and assigned a study 
number. 
• 
Safety Analysis Set: Includes all subjects who received at least one dose of the assigned 
study agent (even a partial dose).  
• 
Efficacy Evaluable Set: Includes all subjects who receive the first cycle of treatment and 
who have baseline and the Day 26-28 on-study assessment for response.  
• 
Pharmacokinetic (PK) Analysis Set:  All subjects who provide at least one post-dose 
KW-0761 concentration measurement will be included in the PK analysis dataset.  
10.2 Analyses of Safety Data 
The safety and tolerability of KW-0761 and vorinostat is determined by reported AEs, 
physical examinations, ECGS, vital signs, and laboratory tests. All summaries for the Safety 
Analysis Set will be prepared for each treatment arm. For those subjects in the vorinostat arm 
who cross over to KW-0761 treatment arm, AEs with an onset date/time after the first dose of 
KW-0761 will be summarized separately within that KW-0761 crossover group. 
The World Health Organization (WHO) Drug Dictionary will be used to classify prior and 
concomitant medications by therapeutic class and Preferred Term. Prior medications include 
medications that were taken within 30 days prior to the Pre-treatment Visit. Concomitant 
medications include medications that started at any time and were taken at any time after the 
start of treatment until the end of the entire treatment period. 
Adverse events are collected from the time the subject signs the ICF until 90 days after the 
last dose or initiation of alternative therapy, whichever comes first. In all subjects who cross 
over from vorinostat to KW-0761, the causality should be assessed for both drugs for 30 days 
after vorinostat was stopped (or later if the event is considered to be related to vorinostat). 
The NCI-CTCAE v4.0 system will be used to grade AEs. Treatment-emergent AEs will be 
grouped and tabulated by MedDRA preferred terms and system organ class. AEs will be 


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classified by body system, incidence, severity, and causality. All treatment-emergent AEs 
will be summarized showing the number and percent of subjects for each outcome. 
The results from physical examination will be presented in the subject data listings. Vital sign 
measurements will be summarized at each time point. The incidence of clinically significant 
laboratory abnormalities will be presented, and laboratory data will be summarized at each 
time point by the NCI-CTCAE v4.0 toxicity grade. Laboratory data will be presented for 
subjects having Grade 3 or 4 changes from baseline by treatment arm.  
Pre- and post-treatment serum samples will be assayed for development of human antibodies 
to KW-0761 (anti-KW-0761). 
10.3 Analyses of Efficacy Data 
Disease status will be assessed every 4 weeks in skin and blood. In the first year of treatment, 
response in lymph nodes and viscera and the overall global composite score will be 
documented every 8 weeks. After the first year, response in the lymph nodes and viscera and 
the overall global composite score will be documented every 16 weeks. Additionally, if 
clinical progression is noted, efficacy assessments are performed to fully document disease 
progression.  
These assessments will be compared with the baseline assessment to determine response. 
Subjects will be evaluated for response in each compartment. Progressive-free survival, 
overall response, duration of response, and QoL will be analyzed. For any time-to-event 
endpoints, the date of disease progression will be determined by both the on-site 
investigator’s assessment and the IR. All efficacy analyses will be conducted on both the ITT 
and Efficacy Evaluable sets.  
The primary comparison of PFS between both arms will be performed on the ITT set based 
upon the results of the on-site investigator’s assessment using a stratified Log-rank test at the 
one-sided 2.5% significance level. Stratification is done by disease type, either SS or MF, and 
disease stage, either IB/II or III/ IV. A similar secondary analysis will be performed on the 
results based on the IR. Each analysis will also be conducted for the Efficacy Evaluable Set. 
Progressive-free survival, which will be analyzed using Kaplan-Meier survival analysis 
methods, is defined as the time from the day of randomization to a treatment arm until 
documented progression or death. For subjects who exhibit conditions of disease progression, 
but continue on the study due to a questionable clinical impression as described in Sections 
5.2.1.4 and 5.2.2.3, the subject is not considered to have progressed unless disease 


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progression is confirmed at least 4 weeks after the date of the initial questionable disease 
progression. In this case, the initial date will be used as the date of disease progression.  
For PFS events, all deaths will be attributed to progression and, hence, the TTP will equal the 
time to death and will be uncensored. Subjects who die without a reported prior progression 
will still be considered to have progressed on the day of their death. In the event that a 
randomized subject withdraws from the study for any reason before documented progression, 
the time from the day of randomization to the last tumor assessment (from any compartment) 
will be used as a censored time point. For all subjects randomized to a treatment arm but 
withdrawing prior to first tumor assessment for any reason other than disease progression, the 
PFS time will be censored at the last documented visit. Sensitivity analyses for PFS will be 
performed, with the details specified in the Statistical Analysis Plan. 
Frequency tables will be used to display best response. Best response will be presented for all 
subjects by treatment arm. The best overall response is the best response from the start of 
treatment until disease progression/recurrence. The subject’s best response assignment will 
depend on the achievement of both measurement and confirmation criteria. Response data 
will be analyzed for both the ITT and the Efficacy Evaluable Set for each treatment arm. 
Exact 95% confidence intervals for response rate will be calculated for each of these groups 
along with the difference in response rates between the 2 treatment arms. All 95% confidence 
intervals on individual rates will be computed using exact computational methods. Any 
confidence interval on the difference of proportions will be computed using exact 
unconditional confidence limits for the risk difference. These confidence intervals can be 
constructed using SAS version 9.2 with the FREQ procedure specifying the RISKDIFF 
option in the EXACT statement (Santner, 1980). ORR will be calculated as the proportion of 
subjects who are responders (CR and PR) and the 95% exact confidence interval for response 
will be calculated. 
The duration of response (DOR), which will be estimated using survival analysis methods, is 
measured from the time measurement criteria are met for CR/PR (whichever is first recorded) 
until the first date that PD or death is objectively documented (taking as a reference for PD 
that smallest measurement recorded since the treatment started). Subjects who do not relapse 
will be censored at the day of their last tumor assessment. The DOR will be estimated 
separately for each treatment arm. Because the DOR is a conditional estimate (conditional on 
having a response), comparison between KW-0761 and vorinostat would not be based on 
randomized groups and therefore will not be made. 


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The Pruritus Evaluation (Likert scale & Itchy QoL) and Skindex-29, FACT-G and EQ-5D-3L 
assessments will be summarized at baseline and at the timepoints specified in the study 
procedures tables for each arm. The improvement (change from baseline) for each of these 
measures will also be summarized and analyzed using repeated measures ANCOVA utilizing 
time points through the 6-month assessment.  
For those subjects who crossover from the vorinostat arm to the KW-0761 arm, these 
assessments within the second arm of the study will be measured at the end of the first cycle 
after the first day of dosing for KW-0761. Baseline measurements for crossover subjects are 
those documented closest to and before the first KW-0761 infusion. No statistical 
comparisons will be made for information gathered in the crossover from the vorinostat arm 
to the KW-0761 arm. All summaries for this arm will be purely descriptive. 
Progression-free survival is the primary endpoint in this study. There are four key secondary 
endpoints in this study that require a comparison between treatment arms: ORR, Skindex-29, 
FACT-G, and EQ-5D-3L. Comparisons of these four secondary endpoints between the 
2 treatment arms will be conducted using p-values that are adjusted to control the overall 
study-wise Type 1 error rate to be less than 0.05. Since these tests are not independent, the 
four secondary tests will be conducted using the Sidak adjusted p-value method defined as  
Adjusted p-value = 1-(1-p)4 where p is the original p-value of the individual test 
These adjusted p-values will then be compared to .05 for each test. 
Comparisons between treatment arms for all other secondary endpoints such as Likert scale, 
and Itchy QoL will be conducted with no adjustment for multiple comparisons used for those 
statistical tests. Exploratory subset analyses for PFS and any of the secondary endpoints by 
region, study site, compartment involvement, CCR4 expression status, disease subtypes, and 
medical history may be conducted. Details of such subset analyses will be provided in the 
Statistical Analysis Plan. Although overall survival (OS) is not a secondary endpoint, each 
subject will be followed in this study for a minimum of 2 years to generate information on 
OS. Using this follow-up information, a comparison between treatment arms for OS will also 
be conducted and considered exploratory. Statistical analyses on OS using follow-up data 
may take place after database lock for the study and will be reported as supplemental to the 
Clinical Study Report. 
Randomization will be stratified within the 2 disease types, SS and MF and 2 disease stages 
IB or II and III or IV. The efficacy analyses described in this section will be conducted as 
stratified tests but may also be conducted as a subset analysis within each of these 
disease-type groups and disease stages. Comparison of endpoints between these 2 groups and 


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stages will be conducted for each treatment assuming adequate sample sizes in the respective 
groups. 
Exploratory analyses based on other subject groupings and with other parameters may also be 
conducted. 
Since the primary endpoint is PFS, the reference median PFS for vorinostat is assumed to be 
169 days. The median PFS for KW-0761 therapy is targeted for 254 days, a 50% 
improvement over this reference median. For a 24-month accrual and 12 month follow-up on 
the last subject dosed, Table 10.3-1 gives the power and the number of PFS events required to 
show superior PFS for KW-0761 therapy over vorinostat at the one-sided 0.025 significance 
level. The ITT set is used for this primary analysis. The same analysis conducted using the 
Efficacy Evaluable set is considered secondary. 
Under these assumptions, for the ITT population, a total of 255 PFS events will give 90% 
power (row is in bold in Table 10.3-1). For this study, the final primary analysis comparing 
PFS between treatment groups will not be conducted until 255 PFS events occur or until a 
maximum of 24 months after the last randomized subject’s first dose, whichever comes first. 
In the event that the study is stopped prior to 255 PFS events are observed, the primary test 
will be performed at less than 90% power under the current assumptions according to 
Table 10.3-1. 
Each of these calculations uses a log-rank test to compare the 2 survival curves. Sample size 
calculations were computed using SAS software version 9.3 using PROC POWER, 
Twosamplesurvival test = logrank. 


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Table 10.3-1 Required PFS Events and Power for Comparison of PFS Kaplan-Maier 
Curves Between the Vorinostat and KW-0761 Arms at the 0.025 Level 
Vorinostat Median PFS = 169 Days, KW-0761 Median PFS = 254 Days 
Power 
Total Required PFS 
Events  
Expected Total Sample Size to Achieve The Required 
Events 
90 
255 
288 
89 
247 
280 
88 
239 
270 
87 
231 
262 
86 
225 
254 
85 
218 
248 
84 
212 
240 
83 
206 
234 
82 
201 
228 
81 
196 
222 
80 
191 
216 
The total sample size of 288 represents the approximate number of subjects that may be 
necessary for 255 PFS events to occur within the projected 36 months of the trial. If a 10% 
inflation factor is applied to this total (about 29 subjects) to take into account those subjects 
that may be lost to follow-up prior to documented progression, a total of 317 enrolled 
subjects may be necessary in order to observe 255 PFS events.  
The observed rates of PFS events, recruitment, and drop-outs will be monitored throughout 
the study and may be used to alter the number of sites, the accrual period, and the follow-up 
period to achieve the required 255 PFS events in a timely manner. If the 255 PFS events are 
not observed within 36 months from the start of enrollment the study will be stopped at 
approximately 24 months after the last randomized subject’s first dose.  
10.4 Exposure-Response Analysis 
Values for individual drug concentrations and descriptive statistics for each blood sample for 
PK assessment will be provided at each scheduled time point of collection. 
Exposure-response analysis using population-based methods will be presented in a separate 
report. 
11 
ETHICAL ASPECTS 
11.1 Ethics and Good Clinical Practice 
This study will be conducted in compliance with the International Conference on 
Harmonization (ICH) E6 Good Clinical Practice (GCP) guidance, and the most recent version 


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of the Declaration of Helsinki as amended in 2008. In addition, all applicable local laws and 
regulatory requirements relevant to the use of new therapeutic agents in the countries 
involved will be adhered to. 
11.2 Ethics Committee/Institutional Review Board 
Prior to implementation of the study, the protocol and the proposed informed consent form 
must be reviewed and approved by a properly constituted EC/IRB. A dated statement that the 
protocol and informed consent have been approved by the EC/IRB must be provided to the 
Sponsor prior to study initiation. Any amendments to the protocol will also require EC/IRB 
approval, except in the case of changes made to protect subject safety, which may be 
implemented immediately. The name and occupation of the chairperson and the members of 
the EC/IRB will be provided. 
The Investigator will provide progress reports to the EC/IRB as required by the EC/IRB. The 
Investigator will provide a final report to the EC/IRB within three months after completion of 
participation in the study.  
The Investigator will not start this study, nor will study drug be shipped to the Investigator’s 
site, before providing the Sponsor or designee with evidence of EC/IRB approval. 
11.3 Informed Consent 
The Investigator must explain to each subject the research nature of the study, its purpose, 
procedures, expected duration and the potential risks and benefits involved in study 
participation. Each subject must be informed that participation in the study is voluntary and 
that he/she may withdraw from the study at any time and that withdrawal of consent will not 
affect his/her right to the most appropriate medical treatment or affect the doctor/subject 
relationship. 
The informed consent should be given by means of a standard written statement. The 
informed consent document should be written so as to be easily understood by the subject or 
the subject’s legal representative. The subject or the subject’s legal representative should be 
given time to read and understand the information before signing the informed consent 
document. The subject should receive a copy of the written informed consent document once 
he/she has signed. 
If signed consent is not possible, then it is also possible to obtain consent orally, in which 
case, the act of informed consent should be established by an additional signed statement 
from an independent witness. The Investigator should explain in the chart why direct-signed 


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consent was not possible. Each investigator must provide a copy of the signed informed 
consent form to the subject. A subject may not be admitted to the study unless informed 
consent of the subject (or his/her legally authorized representative) has been obtained. 
Subjects will be asked to consent to allow the sponsor, sponsor representative or regulatory 
auditor to review their medical records to confirm compliance with GCP and the protocol. 
The standard written informed consent statement forms a part of the protocol that is 
submitted to the EC/IRB for approval. The Investigator must submit a specimen copy of the 
EC/IRB-approved informed consent document to be used in the study before the study is 
initiated.  


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12 
INVESTIGATOR OBLIGATIONS AND STUDY MANAGEMENT 
12.1 Administrative 
All references to KKD in this section include all designees e.g., Contract Research 
Organizations or Consultants acting on behalf of KKD. 
12.2 Changes in Protocol 
Any change to the protocol will be made by written amendment to the Investigational New 
Drug Application (IND) and Clinical Trial Authorization (CTA) (if required) and approved 
by KKD and the Principal Investigator(s) before the change is implemented. All amendments 
to the protocol and informed consent form, which require regulatory and/or EC/IRB 
approval/favorable opinion, must be reviewed and approved by KKD, the EC/IRB and/or 
local authorities before being implemented. Amendments should not be implemented until all 
necessary approvals have been obtained, except when necessary to eliminate an immediate 
hazard(s) to study subjects.  
12.3 Protocol Deviations  
KKD, as the protocol sponsor, is responsible for implementing and maintaining quality 
assurance and quality control to ensure that studies are conducted according to the protocol, 
GCPs and all applicable regulatory requirements. A protocol deviation is any noncompliance 
with the protocol. Noncompliance can be on the part of the study participant, the Investigator 
or the study site staff. Deviations to the protocol are not permitted except when necessary to 
eliminate an immediate hazard(s) to study subjects.  
12.4 Monitoring and Quality Assurance 
The Sponsor of this study, KKD, has responsibilities to health authorities to take all 
reasonable steps to ensure the proper conduct of the study as regards to ethics, protocol 
adherence, integrity, validity of the data recorded on the eCRF and adherence to regulations 
regarding GCP and the protection of human subjects.  
If the study site has not participated in a KKD sponsored trial within the past year, KKD or 
its designee will assess the study site prior to study initiation to verify the qualifications of the 
Investigator, inspect the study site’s facilities and inform the Investigator of his/her 
responsibilities and the procedures for ensuring adequate and correct documentation.  


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During the course of the study, the study monitor will make routine site visits to review 
protocol compliance, compare eCRFs with individual subject’s original source documents, 
assess drug accountability and ensure that the study is being conducted according to the 
pertinent regulatory requirements. The review of the subject’s medical record will be 
performed in a manner to ensure that the subject’s confidentiality is maintained. Monitoring 
visits will occur approximately every 6-8 weeks. Frequency of visits may be modified based 
on the rate of enrollment or as otherwise necessary to ensure GCP compliance. The 
Investigator agrees to cooperate with the monitor to ensure that any problems detected in the 
course of these monitoring visits, including delays in completing case report forms, are 
resolved. 
Regulatory authorities and/or the KKD staff may carry out source document verification 
visits and/or site inspections/audits. Direct access to original source data will be required for 
inspections/audits, which will be carried out giving due consideration to data protection and 
subject confidentiality. 
12.5 Electronic Case Report Forms (eCRFs) and Source Documentation 
The investigator is required to prepare and maintain adequate and accurate case histories (i.e., 
medical records) designed to record all observations and other data pertinent to the study for 
each study participant.  
It is the responsibility of the Principal Investigator to prepare and maintain adequate and 
accurate eCRFs that have been designed by the Sponsor to record all observations and other 
data pertinent to the clinical investigation.  
Electronic Case Report Forms are used to record information collected in the performance of 
this study and to transfer the data into the study database. These eCRFs are organized as an 
ordered series of electronic data entry modules specific for each scheduled and unscheduled 
study visit.  
The electronic data capture (EDC) users at the study site will exercise due diligence in 
ensuring that study subject data are entered accurately and in their entirety from the 
investigative site’s source documents and flow sheets into the appropriate data entry fields. 
Only staff listed on the “Delegation of Authority” page in the study file notebook and who 
have been appropriately trained will be issued a user ID enabling them to make entries and 
edits to the electronic trial database and to respond to queries. Only the Principal Investigator 
will be issued a user ID allowing the application of an electronic signature to a completed 


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study subject record signifying the data has been reviewed and verified as complete and 
accurate. 
Upon completion of the study, validated study subject records will be published 
electronically along with the Principal Investigator’s electronic signature in a Portable 
Document Format (PDF) file and transferred to a CD-ROM. The compact disc(s) will then be 
distributed to the Study Site to be retained by the Principal Investigator as a component of the 
required records for this study. 
At the time of implementation of Amendment 10, the electronic data capture system defined 
as the clinical database will be terminated for all subjects (see Section 7.8). 
12.6 Record Retention 
Study data and other essential documents should be retained by the study site for a minimum 
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 until at least 
2 years have elapsed since the formal discontinuation of clinical development of the 
investigational product. However, these documents should be retained for a longer period if 
required by the applicable legal requirements. KKD or its designee will inform the 
investigator, in writing, as to when these documents no longer need to be maintained. 
12.7 Confidentiality  
All personal data collected and processed for the purposes of this study should be managed 
by the investigator and his/her staff with adequate precautions to ensure the confidentiality of 
those data, and in accordance with applicable national and/or local laws and regulations on 
personal data protection. 
Monitors, auditors, and other authorized agents of KKD and/or its designee, the EC/IRBs 
approving this research, and the regulatory authorities, as well as that of any other applicable 
government agency(ies), will be granted direct access to the study subjects’ original medical 
records for verification of clinical trial procedures and/or data, without violating the 
confidentiality of the subjects, to the extent permitted by the law and regulations. In any 
presentations of the results of this study or in publications, the subjects’ identity will remain 
confidential. 


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12.8 Disclosure 
By conducting this study, the Investigator agrees that all information provided will be 
maintained by the Investigator and his/her staff in strict confidence. Such information may be 
communicated to the Scientific Committee and/or EC/IRB under a similar, appropriate 
understanding of the confidential nature of the information. Study documents provided 
(protocols, IBs, case report forms and other material) will be stored appropriately to ensure 
their confidentiality. It is understood that the confidential information provided to the 
Investigator will not be disclosed to others without written authorization from KKD, except 
to the extent necessary to obtain informed consent from those subjects who are eligible and 
choose to participate in the study.  
Such information will not be provided to potential subjects by telephone or to any other 
individual. 
12.9 Termination of Study 
The Sponsor reserves the right to terminate the study or individual study sites at any time. 
Reasons for study termination include, but may not be limited to, manufacturing problems, a 
request to discontinue the study from a regulatory authority, a corporate decision to 
discontinue development of KW-0761, AE incidence or severity not consistent with the 
potential benefit of the drug, poor enrollment or inadequate adherence to GCP guidances. In 
terminating the study, the Sponsor and the Principal Investigator will assure that adequate 
consideration is given to the protection of the subjects’ interest. If the trial is terminated 
prematurely, the EC/IRB and regulatory authorities (if required) will be notified.  
12.10 Final Report/Publications 
The study is part of a multicenter study; accordingly, the Institution and Principal Investigator 
of the study agree that the first publication of the results of the study shall be made in 
conjunction with the presentation of a joint, multicenter publication of the study results with 
the Investigators and the Institutions from all appropriate sites contributing data, analyses and 
comments. However, if such a multicenter publication is not submitted within 12 months 
after the database has been locked, abandonment or termination of the study at all sites, or 
after Sponsor confirms there will be no multicenter study publication, the Institution and/or 
such Principal Investigator may publish the results from the institution site individually in 
accordance with the following requirements. Prior to submission of any materials for 
publication or presentation, the Institution will provide such materials or manuscript to the 


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95 
 
Sponsor for review. Details of the Sponsor’s publication policy can be found in the Clinical 
Trial Agreement. 


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13 
REFERENCES 
1. 
Agar NS, Wedgeworth E, Crichton S, Mitchell TJ, Cox M, Ferreira S, et al. Survival 
outcomes and prognostic factors in mycosis fungoides/Sézary Syndrome: validation 
of the revised International Society for Cutaneous Lymphomas/European 
Organisation for Research and Treatment of Cancer Staging Proposal. J Clin Oncol. 
2010;28(31):4730-9. 
2. 
Campbell JJ, Clark RA, Watanabe R, Kupper TS. Sézary syndrome and mycosis 
fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct 
clinical behaviors. Blood. 2010;116:767-71. 
3. 
Criscione VD, Weinstock MA. Incidence of cutaneous T-cell lymphoma in the United 
States, 1973-2002. Arch Dermatol. 2007;143(7):854-9. 
4. 
Demierre MF, Kim YH, Zackheim HS. Prognosis, clinical outcomes and quality of 
life issues in cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 
2003;17:1485-507. 
5. 
Demierre MF, Tien A, Miller D. Health-related quality of life assessment in subjects 
with cutaneous T-cell lymphoma. Arch Dermatol. 2005;141:325-30. 
6. 
Demierre MF, Gan S, Jones J, Miller DR. Significant impact of cutaneous T-cell 
lymphoma on subjects’ quality of life. Cancer. 2006;107:2504-11. 
7. 
Demierre M, Whittaker S, Kim Y, Kim E, Piekarz R, Prince M, et al. Pooled analyses 
of two international, multicenter clinical studies of Romidepsin in 167 subjects with 
cutaneous T-cell lymphoma (CTCL). J Clin Oncol. 2009;27(15S);8546.  
8. 
Desai N, Poindexter G, Monthrope Y, Bendeck SE, Swerlick RA, Chen SC. A pilot 
quality of life instrument for pruritus. J Am Acad Dermatol. 2008;59:2:234-44. 
9. 
Diamendidou E, Cohen PR, Kurzrock R. Mycosis fungoides and Sézary syndrome. 
Blood. 1996;88(7):2385–409. 
10. 
Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, et al. 
Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous 
T-cell lymphoma: multinational Phase II-III trial results. J Clin Oncol. 
2001;19(9):2456-71. 


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11. 
Duvic M, Talpur R, Ni X, Zhang C, Hazarika P, Kelly C, et al. Phase 2 trial of oral 
vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell 
lymphoma (CTCL). Blood. 2007 Jan 1;109(1):31-9. Epub 2006 Sep 7. Erratum in: 
Blood. 2007 Jun 15;109(12):5086. 
12. 
Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P, et al. 
Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in 
previously treated patients with cutaneous T-cell lymphoma. Epub 2015 Jan 20 DOI 
10.1182/blood-2014-09-600924. 
13. 
Ferenczi K, Fuhlbrigge RC, Pinkus JL, Pinkus GS, Kupper TS. Increased CCR4 
expression in cutaneous T-cell lymphoma. J Invest Dermatol. 2002;119:1405-10. 
14. 
Fierro MT, Comessatti A, Quaglino P, Ortoncelli M, Abate SO, et al. Expression 
pattern of chemokine receptors and chemokine release in inflammatory erythroderma 
and Sézary syndrome. Dermatology. 2006;213:284-92. 
15. 
He LZ, Tolentino T, Grayson P, Zhong S, Warrell RP Jr, Rifkind RA, et al. Histone 
deacetylase inhibitors induce remission in transgenic models of therapy-resistant 
acute promyelocytic leukemia. J Clin Invest. 2001 Nov;108(9):1321-30. 
16. 
Horwitz S, Olsen E, Duvic M, Porcu P, Kim YH. Review of treatment of mycosis 
fungoides and Sézary syndrome: a stage-based approach. JNCCN. 2008;6(4):436-42. 
17. 
Ishida T, Iida S, Akatsuka Y, Ishii T, Miyazaki M, Komatsu H, et al. The CC 
chemokine receptor 4 as a novel specific target for immunotherapy in adult T-cell 
leukemia/lymphoma. Clin Can Res. 2004;10(22):7529-39. 
18. 
Istodax [package insert]. Summit, NJ: Celgene Corporation; 2011. 
19. 
Jones D, O’Hara C, Kraus MD, Perez-Atayde AR, Shahsafaei A, Wu L, et al. 
Expression pattern of T-cell associated chemokine receptors and their chemokines 
correlate with specific subtypes of T-cell non-Hodgkin’s lymphoma. Blood. 
2000;96(2):685-90. 
20. 
Kavanaugh SM, White LA, Kolesar JM. Vorinostat: A novel therapy for the treatment 
of cutaneous T-cell lymphoma. Am J Health Syst Pharm. 2010 May 15;67(10):793-7. 
Review. Erratum in: Am J Health Syst Pharm. 2010 Jul 15;67(14):1136. 


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21. 
Kelly WK, Richon VM, O’Connor O, Curley T, MacGregor-Curtelli B, Tong W, 
et al. Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide 
hydroxamic acid administered intravenously. Clin Cancer Res. 2003 Sep 1;9(10 Pt 
1):3578-88. 
22. 
Kelly WK, O’Connor OA, Krug LM, Chiao JH, Heaney M, Curley T, et al. Phase I 
study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in 
patients with advanced cancer. J Clin Oncol. 2005 Jun 10;23(17):3923-31. 
23. 
Kim YH, Liu HL, Mraz-Gernhard S, Vargheses A, Hoppe RT. Long-term outcome of 
525 subjects with mycosis fungoides and Sézary syndrome. Arch Dermatol. 
2003;139:857-66. 
24. 
Mann BS, Johnson JR, He K, Sridhara R, Abraham S, Booth B, et al. Vorinostat for 
treatment of cutaneous manifestations of advance primary cutaneous T-cell 
lymphoma. Clin Cancer Res. 2007:13(8):2318-22. 
25. 
Meyer N, Paul C, Misery L. Pruritus in cutaneous T-cell lymphomas: frequent, often 
severe and difficult to treat. Acta Derm Venereol. 2010;90:12-7. 
26. 
Narducci MG, Scala E, Bresin A, Gaprini E, Picchio MC, Remotti D, et al. Skin 
homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of 
CD26/dipeptidylpeptidase IV. Blood. 2006;107(3):1108-15. 
27. 
National Comprehensive Cancer Network, Inc., Clinical practice guidelines in 
oncology, version 1. 2013. Mycosis fungoides/Sézary syndrome of the cutaneous 
T-cell lymphomas. 
28. 
O’Connor OA, Heaney ML, Schwartz L, Richardson S, Willim R, 
MacGregor-Cortelli B, et al. Clinical experience with intravenous and oral 
formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic 
acid in patients with advanced hematologic malignancies. J Clin Oncol. 2006 Jan 
1;24(1):166-73. 
29. 
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. 
Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin 
Oncol. 1982;5(6):649-55. 
30. 
Olsen E, Duvic M, Frankel A, Kim Y, Martin A, Vonderheid E, et al. Pivotal phase 
III trial of two doses of Denileukin Diftitox for the treatment of cutaneous T-cell 
lymphoma. J Clin Oncol. 2001;19(2):376-88. 


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31. 
Olsen EA, Kim YH, Kuzel TM, Pacheco TR, Foss FM, Parker S, et al. Phase IIb 
multicenter trial of vorinostat in subjects with persistent, progressive, or treatment 
refractory cutaneous T-cell lymphoma. J Clin Oncol. 2007;25(21):3109-15. 
32. 
Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler, et al. Revisions 
to the staging and classification of mycosis fungoides and Sézary syndrome: a 
proposal of the International Society for Cutaneous Lymphomas (ISCL) and the 
cutaneous lymphoma task force of the European Organization of Research and 
Treatment of Cancer (EORTC). Blood. 2007;110:1713–22. 
33. 
Olsen E, Whittaker S, Kim YH, Duvic M, Prince HM, Lessin HR, et al. Clinical 
Endpoints and Response Criteria in Mycosis Fungoides and Sézary Syndrome: a 
Consensus Statement of the International Society for Cutaneous Lymphomas (ISCL), 
the United States Cutaneous Lymphoma Consortium (USCLC) and the Cutaneous 
Lymphoma Task Force of the European Organization for Research and Treatment of 
Cancer. J Clin Oncol. 2011;29:2598-607. 
34. 
Ontak [package insert]. Woodcliff Lake, NJ: Eisai Inc.; 2011. 
35. 
Richon VM. Cancer biology: mechanism of antitumour action of vorinostat 
(suberoylanilide hydroxamic acid), a novel histone deacetylase inhibitor. Br J Cancer. 
2006;95:S2-S6. 
36. 
Rizzo JD, Brouwers M, Hurley P, Seidenfeld J, Arcasoy MO, Spivak JL, et al. 
American Society of Clinical Oncology/American Society of Hematology Clinical 
Practice Guidelines update on the use of Epoetin and Darbepoetin in adult subjects 
with cancer. J Clin Oncol. 2010;28:4996-5010. 
37. 
Rubin EH, Agrawal NG, Friedman EJ, Scott P, Mazina KE, Sun L, et al. A study to 
determine the effects of food and multiple dosing on the pharmacokinetics of 
vorinostat given orally to patients with advanced cancer. Clin Cancer Res. 2006 
Dec;12(23):7039-45. 
38. 
Santner T, Snell MK. "Small-Sample Confidence Intervals for p1-p2 and p1/p2 in 
2 × 2 Contingency Tables," Journal of the American Statistical Association, 
1980;75:386–94. 
39. 
SEER Data, 2001- 2007. Available at: 
http://seer.cancer.gov/csr/1975_2007/results_merged/sect_19_nhl.pdf. Accessed 
December 3, 2010. 


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40. 
Stevens SR, Ke MS, Parry EJ, Mark J, Cooper KD. Quantifying skin disease burden 
in mycosis fungoides-type cutaneous T-cell lymphomas. Arch Dermatol. 
2002;138(1):42-8. 
41. 
Targretin capsules [package insert]. Woodcliff Lake, NJ: Eisai Inc.; 2011. 
42. 
Vose JM. Peripheral T-cell non-Hodgkin’s lymphoma. Hematol Oncol Clin North 
Amer. 2008;22:997–1005. 
43. 
Weber JS, Kähler KC, Hauschild A. Management of immune-related adverse events 
and kinetics of response with ipilimumab.JCO. 2012;30(21):2691-7.  
44. 
Wolchok JD, Hoos A, O'Day S , Weber JS, Hamid O, Lebbé C, et al. Guidelines for 
the evaluation of immune therapy activity in solid tumors: immune-related response 
criteria. Clin Cancer Res. 2009;15(23):7412-9. 
45. 
Yagi H, Naohiro S, Ohshima A, Itoh T, Itoh N, Horibe T, et al. Chemokine receptor 
expression in cutaneous T cell and NK/T-cell lymphomas: immunohistochemical 
staining and in vitro chemotactic assay. Am J Surg Pathol. 2006;30(9):1111-9. 
46. 
Zhang C, Richon V, Ni X, Talpur R, Duvic M. Selective induction of apoptosis by 
histone deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells: relevance to 
mechanism of therapeutic action. J Invest Dermatol. 2005 Nov;125(5):1045-52. 
47. 
ZOLINZA [package insert]. Whitehouse Station, NJ: Merck & Co.; 2011. 
 


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14 
APPENDICES 


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Appendix 1 
Modified ISCL/EORTC Revisions to the TNMB Classification of 
MF/SS 
 
 
 


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Appendix 2 
Eastern Cooperative Oncology Group (ECOG) Scale 


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Appendix 3 NYHA Classification 
 


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Appendix 4 
Autoimmune Screening Questionnaire 
 


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Appendix 5 
Itchy Quality of Life Questionnaire  
 


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Appendix 6 
Skindex-29  


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Appendix 7 
FACT-G 


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Appendix 8 
EQ-5D-3L 
 


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Appendix 9 
Likert Scale for Pruritus Evaluation 
 

SAP_001.pdf: 
 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 
(mogamulizumab) Versus Vorinostat in Subjects with Previously Treated Cutaneous T-Cell 
Lymphoma 
 
Statistical Analysis Plan Version Date: 22Nov2016 
 
NCT01728805 


 
CONFIDENTIAL 
1 
 
 
 
Statistical Analysis Plan 
 
 
Open-Label, Multi-Center, Randomized Study of Anti-CCR4 Monoclonal Antibody 
KW-0761 (mogamulizumab) Versus Vorinostat in Subjects with Previously Treated 
Cutaneous T-Cell Lymphoma 
 
Protocol Number: 0761-010 
 
US IND Number: 101,843 
 
Date:      FINAL-for review  
 
24 February 2014 
  
 
                 FINAL-for signature 
 
24 February 2014 
    
 
                 FINAL-Amended-for signature 
22 November 2016 
 
 
 
 
 
 
Confidentiality Statement 
The information disclosed in connection with this Statistical Analysis Plan is the trade secret, confidential, 
privileged and/or proprietary financial or commercial information of Kyowa Kirin Pharmaceutical 
Development, Inc. and is delivered in confidence and reliance that it will not be copied or made available to any 
third party without the prior written consent of Kyowa Kirin Pharmaceutical Development, Inc. except as may 
be required by federal, state, or local laws or regulations.  Kyowa Kirin Pharmaceutical Development, Inc. 
requests that this information be treated as privileged or confidential trade secret, commercial or financial 
information in accordance with 5 U.S. Code, sec. 552(b)(4), and that it be provided with prior written notice of 
any disclosure required by law. 
   




Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
CONFIDENTIAL 
3 
 
Summary of Revisions 
• 
Updated Sections 3 to 5 to reflect changes made in protocol amendments 5, 6, and 7. 
• 
Updated Section 6.11.1.1 to clarify that for the primary efficacy variable progression-free 
survival (PFS), documented progression include disease progression in any compartment 
based on Investigator’s assessment per CTCL response criteria or documented disease 
progression reported during the follow-up period. The date of progression will be the earliest 
date at which documented disease progression can be declared. 
• 
Updated Section 5 to show the global composite response score definitions.  Clarified the 
overall response rate is based on the global composite response score.  
• 
Changes were made to Section 6.11.1.2.1 to clarify that confirmation of complete response 
and partial response is required for the overall response rate.  In addition to the confirmed 
overall response rate, the confirmed and unconfirmed overall response rates will be 
summarized. Added summaries efficacy summaries by disease type. 
• 
Added clarifications in Section 6.11.1.2.2 on the scheduled time points for QoL evaluation.  
Added additional time points to summary table. 
• 
Updated Sections 6.11.1, 6.11.1.4, and 6.11.2.5 to include time to treatment failure as an 
exploratory efficacy variable.  
• 
Updated Section 6.11.1.4 to omit statement that each subject would be followed in the study 
for a minimum of two years to generate information on overall survival. 
• 
Updated Section 6.11.2.2 to add a sensitivity analysis for the primary efficacy variable PFS 
by including clinical progression from PFS events.  
• 
Updated Section 6.11.2.4 to clarify that duration of response and time to response are 
summarized only for subjects with confirmed complete response or partial response. Added 
concordance analysis between the investigators assessment and the independent review of 
best overall responses. 
• 
Updated Section 6.11.2.5 to include additional exploratory analysis for PFS between subjects 
with any exposure to KW-0761 versus subjects with vorinostat only. 
• 
Updated Sections 6.11.2.6, 6.11.2.7, and 6.15 to remove CCR4 related analysis and to 
indicate that a separate analysis plan will be prepared to detail the CCR4 analysis. 
• 
Updated Section 6.12.1 to include summary of exposure-adjusted incidence rate and 
exposure-adjusted event rate for special adverse events. 
• 
Changes were made to Section 6.14 to revise immunogenicity analysis. 
• 
Revised to reflect the current plan for presenting PK data. Descriptive statistics will be 
presented for the PK data. 
• 
Revised summary of ECOG performance status from worst score during randomized 
treatment to mean and mean change from baseline summaries every 8 weeks. 
• 
Added testing for quality of life assessment beyond the 6-month assessment period. 
• 
Added exploratory analyses of Overall Survival adjusting for crossover. 
• 
Updated company name. 
• 
Incorporate other minor clarifications and typographical corrections. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
CONFIDENTIAL 
4 
 
Table of Contents 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ................................................. 2 
SUMMARY OF REVISIONS ............................................................................................. 3 
TABLE OF CONTENTS ..................................................................................................... 4 
LIST OF ABBREVIATIONS .............................................................................................. 8 
1 
INTRODUCTION ................................................................................................... 10 
2 
OBJECTIVES .......................................................................................................... 10 
2.1 
Primary Objective .................................................................................................. 10 
2.2 
Secondary Objectives ............................................................................................. 10 
2.3 
Exploratory Objectives ........................................................................................... 11 
3 
STUDY DESIGN ..................................................................................................... 11 
3.1 
Overview of Study Design ...................................................................................... 11 
3.2 
Treatment Plan ....................................................................................................... 11 
3.2.1 
Assignment to Study ........................................................................................... 11 
3.2.2 
Study Treatments ................................................................................................ 12 
3.2.2.1 
Study Drug: KW-0761 (mogamulizumab) ....................................................... 12 
3.2.2.2 
Study Drug: Vorinostat (ZOLINZA®) .............................................................. 12 
3.2.2.3 
Duration of Treatment ..................................................................................... 12 
3.2.2.4 
Cross-over to Study Drug KW-0761 ................................................................ 13 
4 
SUBJECT SELECTION ......................................................................................... 13 
5 
STUDY ASSESSMENTS ........................................................................................ 14 
5.1 
Efficacy Evaluations ............................................................................................... 14 
5.1.1 
Evaluation of Skin Disease.................................................................................. 15 
5.1.1.1 
Skin Biopsy ..................................................................................................... 15 
5.1.1.2 
Skin Photographs ............................................................................................. 16 
5.1.1.3 
Modified Severity Weighted Assessment Tool (mSWAT) ............................... 16 
5.1.1.4 
Response Criteria for Skin ............................................................................... 16 
5.1.1.5 
Pruritus Evaluation .......................................................................................... 16 
5.1.2 
Evaluation of Blood Disease ............................................................................... 17 
5.1.2.1 
Flow Cytometric Analysis ............................................................................... 17 


Statistical Analysis Plan 
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22 November 2016 
 
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5.1.2.2 
Response Criteria in Blood .............................................................................. 17 
5.1.3 
Evaluation of Disease in Lymph Nodes and Viscera............................................ 17 
5.1.3.1 
Baseline Tumor Assessments ........................................................................... 17 
5.1.3.2 
Method of Tumor Response Assessment .......................................................... 17 
5.1.3.3 
Determination of Response in Lymph Nodes and Viscera ................................ 17 
5.1.4 
Global Composite Response Score ...................................................................... 18 
5.1.4.1 
Independent Review of Progression ................................................................. 18 
5.2 
Safety Assessments ................................................................................................ 19 
5.2.1 
Adverse Events ................................................................................................... 19 
5.2.2 
Clinical Laboratory Evaluations .......................................................................... 19 
5.2.3 
Vital Signs and Body Weight .............................................................................. 19 
5.2.4 
Physical Examination .......................................................................................... 19 
5.2.5 
Electrocardiograms ............................................................................................. 20 
5.2.6 
Blood Sample for Determination of Natural Ligands ........................................... 20 
5.2.7 
Genomic Sampling (For subjects receiving KW-0761 as first assigned 
therapy only) ....................................................................................................... 20 
5.2.8 
Immunogenicity (For subjects receiving KW-0761) ............................................ 20 
5.3 
Pharmacokinetic Assessments ................................................................................ 20 
5.4 
Quality of Life Assessments ................................................................................... 21 
5.5 
Follow-Up .............................................................................................................. 21 
5.6 
Follow-Up for Subjects Achieving a Complete Response ....................................... 21 
6 
STATISTICAL METHODOLOGY ....................................................................... 22 
6.1 
General Statistical Consideration ............................................................................ 22 
6.2 
Baseline Definition ................................................................................................. 22 
6.3 
Determination of Sample Size ................................................................................ 22 
6.4 
Analysis Sets .......................................................................................................... 23 
6.5 
Interim Analysis and Data Monitoring .................................................................... 24 
6.6 
Subject Disposition................................................................................................. 24 
6.7 
Demographic and Baseline Disease Characteristics ................................................ 25 
6.8 
Medical and Surgical History ................................................................................. 25 
6.9 
Prior/Concomitant Medications .............................................................................. 25 


Statistical Analysis Plan 
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6.10 
Study Drug Exposure and Compliance ................................................................... 26 
6.11 
Efficacy Analysis ................................................................................................... 27 
6.11.1 
Efficacy Variables for Analysis ........................................................................... 27 
6.11.1.1 
Definition of Primary Efficacy Variable........................................................... 28 
6.11.1.2 
Definition of Key Secondary Efficacy Variables .............................................. 29 
6.11.1.3 
Definition of Other Secondary Efficacy Variables............................................ 31 
6.11.1.4 
Definition of Exploratory Efficacy Variables ................................................... 31 
6.11.2 
Efficacy Analysis Methodology .......................................................................... 32 
6.11.2.1 
Analysis of Primary Efficacy Variable ............................................................. 32 
6.11.2.2 
Sensitivity Analyses of Primary Efficacy Variable ........................................... 33 
6.11.2.3 
Analyses of Key Secondary Efficacy Variables................................................ 34 
6.11.2.4 
Analyses of Other Secondary Efficacy Variables ............................................. 35 
6.11.2.5 
Analyses of Exploratory Efficacy Variables ..................................................... 37 
6.11.2.6 
Adjustment for Covariates ............................................................................... 37 
6.11.2.7 
Subgroup Analyses .......................................................................................... 38 
6.12 
Safety Analysis....................................................................................................... 38 
6.12.1 
Adverse Events ................................................................................................... 39 
6.12.2 
Clinical Laboratory Tests .................................................................................... 41 
6.12.3 
Vital Signs .......................................................................................................... 41 
6.12.4 
12-Lead Electrocardiogram (ECG) ...................................................................... 42 
6.12.5 
Physical Examinations ........................................................................................ 42 
6.12.6 
ECOG Performance Status .................................................................................. 42 
6.13 
Pharmacokinetics Analysis ..................................................................................... 42 
6.14 
Analysis of Immunogenicity Data........................................................................... 43 
6.15 
Analysis of CCR4 and Other Biomarkers ............................................................... 44 
6.16 
Other Data Considerations ...................................................................................... 44 
7 
REFERENCES ........................................................................................................ 45 
8 
PROGRAMMING CONSIDERATIONS ............................................................... 47 
8.1 
Table, Listing, and Figure Format ........................................................................... 47 
8.1.1 
General ............................................................................................................... 47 
8.1.2 
Headers ............................................................................................................... 47 


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8.1.3 
Display Titles ...................................................................................................... 48 
8.1.4 
Column Headers ................................................................................................. 48 
8.1.5 
Body of the Data Display .................................................................................... 48 
8.1.6 
Footnotes ............................................................................................................ 50 
8.2 
Data-Handling Rules .............................................................................................. 50 
8.2.1 
Visits .................................................................................................................. 50 
8.2.2 
Demographics and Baseline Characteristics ........................................................ 50 
8.2.3 
Prior and Concomitant Medications .................................................................... 51 
8.2.4 
Safety ................................................................................................................. 51 
8.2.5 
SAS® Procedures ................................................................................................ 52 
9 
LIST OF TABLES AND FIGURES ....................................................................... 53 
10 
LIST OF LISTINGS ................................................................................................ 61 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
CONFIDENTIAL 
8 
 
List of Abbreviations  
Abbreviations 
aCRF 
Annotated case report form 
AE 
Adverse Event 
ANC 
Absolute neutrophil count 
ANCOVA 
Analysis of Covariance 
ATC 
CCR4 
Anatomical Therapeutic Chemical 
CC chemokine receptor 4, chemokine (C-C motif) receptor 4 
BMI 
Body mass index 
BSA 
Body surface area 
CMH 
Cochran-Mantel-Haenszel 
CR 
Complete response 
CRF 
Case Report Form 
CS 
Clinically significant 
CSR 
CT 
Clinical Study Report 
Computerized Tomography 
CTCL 
cutaneous T-cell lymphoma 
CTIVRS 
ClinTrak Interactive Voice/Web Response System 
DOR 
DSMB 
Duration of response 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
ECOG 
EORTC 
Eastern Cooperative Oncology Group 
European Organization for Research and Treatment of Cancer 
EQ-5D-3L 
European quality of life 5 dimensions 3 levels 
EWB 
Emotional well-being 
FACT-G 
Functional Assessment of Cancer Therapy-General 
FWB 
Functional well-being 
ICH 
International Conference on Harmonisation 
IHC 
IPCW 
IR 
Immunohistochemistry 
Inverse probability of censoring weighting 
Independent Reviewer 
ISCL 
ITT 
International Society of Cutaneous Lymphomas 
Intent-to-Treat 
iv 
Intravenous 
KKD 
Kyowa Kirin Pharmaceutical Development, Inc. 
LOCF 
Last observation carried forward 
LS 
Least squares 
MedDRA 
Medical Dictionary for Regulatory Activities  
MF 
Mycosis fungoides 
mg 
Milligram 
msec 
Milliseconds 
mSWAT 
modified Severity Weighted Assessment Tool 
NCI-CTCAE  
National Cancer Institute- Common Terminology Criteria for Adverse Events 
NCS 
Not clinically significant 


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Abbreviations 
ORR 
Overall response rate 
OS 
Overall survival 
PD 
Progressive disease 
PFS 
Progression-free survival 
PK 
Pharmacokinetics 
PR 
Partial response 
PS 
Performance status 
PT 
Preferred Term 
PWB 
Physical well-being 
QoL 
QTcB 
QTcF 
RPSFT 
Quality of life 
QTc Bazett correction 
QTc Fridericia correction 
Rank-reserving structure failure time 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SAS® 
Statistical Analysis Software 
SD 
Standard Deviation or stable disease 
SOC 
System Organ Class 
SS 
Sézary Syndrome 
SWB 
Social/family well-being 
SWAT 
TBSA 
Severity Weighted Assessment Tool 
Total body surface area 
TEAE 
Treatment-Emergent Adverse Event 
TLFs 
Tables, data listings, figures 
TTF 
Time to treatment failure 
TTR 
Time to response 
US 
USCLC 
United States 
United States Cutaneous Lymphoma Consortium 
VAS 
Visual analog scale 
WBC 
White blood cell count 
WHO 
World Health Organization 
 


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1 
INTRODUCTION 
This Statistical Analysis Plan (SAP) has been developed after review of Kyowa Kirin 
Pharmaceutical Development, Inc. (KKD) Protocol 0761-010 (original version dated 19 June 
2012, Amendment No. 1 dated 09 July, 2012, Amendment No. 2 dated 19 February, 2013, 
Amendment No. 3 dated 03 April, 2013), Amendment No. 4 (dated 14 November, 2013), 
Amendment No. 5 (dated 05 March, 2014), Amendment No. 6 (dated 04 March, 2015), 
Amendment No. 7 (dated 09 March, 2016), the corresponding annotated case report form 
(aCRF), and the raw Statistical Analysis Software (SAS®) data schemas. This SAP describes 
the analysis sets and specific details for the statistical methods to be used for the analysis and 
reporting of all efficacy, safety, biomarker, and immunogenicity data collected during the 
conduct of Protocol 0761-010. This SAP supersedes the statistical considerations identified in 
Protocol 0761-010 and where considerations are substantially different, they will be 
identified as such in this document. This SAP has been developed and finalized prior to 
database lock of the clinical database for Protocol 0761-010. If additional analyses are 
required to supplement the planned analyses described in this SAP, they may be performed 
and will be identified in the Clinical Study Report (CSR). 
This SAP is being written with consideration of the recommendations outlined in the 
International Conference on Harmonisation (ICH) E9 Guideline entitled “Guidance for 
Industry: Statistical Principles for Clinical Trials”1 and the most recent ICH E3 Guideline 
entitled, “Guidance for Industry: Structure and Content of Clinical Study Reports”.2  
2 
OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study will be:  
• 
To compare the progression free survival (PFS) of KW-0761 versus vorinostat for 
subjects with relapsed or refractory cutaneous T-Cell Lymphoma (CTCL). 
2.2 
Secondary Objectives 
The secondary objectives will be:  
• 
To compare the overall response rate of KW-0761 versus vorinostat in subjects with 
relapsed or refractory CTCL; 
• 
To evaluate and compare improvements in Quality of Life (QoL) measurements 
Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European 


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Quality of Life 5 dimensions 3 levels (EQ-5D-3L) for subjects receiving KW-0761 versus 
vorinostat; 
• 
To evaluate and compare improvements in the Pruritus Evaluation (Likert scale & Itchy 
QoL) for subjects receiving KW-0761 versus vorinostat; 
• 
To estimate the duration of response (DOR) for both the KW-0761 and vorinostat arms 
for those subjects with relapsed or refractory CTCL responding to treatment; 
• 
To determine if subjects who relapse on vorinostat can achieve response upon cross over 
to treatment with KW-0761; 
• 
To further assess the safety of KW-0761;  
• 
To describe the immunogenicity of KW-0761. 
2.3 
Exploratory Objectives 
The exploratory objectives will be:  
• 
To compare the overall survival of KW-0761 versus vorinostat for subjects with relapsed 
or refractory CTCL; 
• 
To conduct exploratory evaluation of KW-0761exposure-response relationships. 
3 
STUDY DESIGN 
3.1 
Overview of Study Design 
This open-label, multi-center, randomized, Phase 3 study will enroll subjects with previously 
treated CTCL including mycosis fungoides (MF) and Sézary Syndrome (SS).  Approximately 
317 subjects may enroll in this study over a period of 24 months. The primary analysis will 
be conducted when 255 total progression-free survival events have been observed or 
24 months after the last randomized subject’s first dose, whichever comes first. It is 
anticipated that approximately 75 investigational centers in the US, Europe, Japan and 
Australia will participate in this study. 
3.2 
Treatment Plan 
3.2.1 
Assignment to Study 
After a subject signs consent, screening numbers should be assigned by the Investigator (or 
designee) using ClinTrak Interactive Voice/Web Response System (CTIVRS). Once 
assigned, numbers for any screen failures or non-treated, non-evaluable, or discontinued 
subjects will not be re-used.  


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A subject who meets all entry criteria will be randomized in a 1:1 ratio to receive KW-0761 
or vorinostat. The randomization to treatment groups will be stratified by disease type (MF or 
SS) and disease stage (IB/II or III/IV). When a subject is determined to be eligible for 
randomization the Investigator (or designee) will contact CTIVRS to obtain the 
randomization assignment for the subject.  
3.2.2 
Study Treatments 
In this protocol, study treatments are KW-0761 and vorinostat. Subjects will be randomized 
to the study drug, KW-0761 or comparator, vorinostat, in a 1:1 ratio.  
3.2.2.1 
Study Drug: KW-0761 (mogamulizumab) 
Treatment can be administered on an outpatient basis. Subjects will receive 1.0 mg/kg of 
KW-0761 as an intravenous (iv) infusion over at least 1 hour on Days 1, 8, 15 and 22 of the 
first cycle and on Days 1 and 15 of subsequent cycles. Each treatment cycle is 28 days.  
No dose modifications of the KW-0761 will be permitted in this study.  Subjects will not be 
replaced. 
3.2.2.2 
Study Drug: Vorinostat (ZOLINZA®) 
Treatment can be administered on an outpatient basis. Subjects will take 400 mg orally once 
daily with food. Each treatment cycle is 28 days. 
Management of severe or intolerable adverse reactions may require dose omission, reduction 
or interruption of vorinostat therapy. Subjects will not be replaced. 
3.2.2.3 
Duration of Treatment 
Subjects may remain in the treatment phase up until progressive disease (PD), drug 
intolerance or unacceptable toxicity, or until any of the other criteria for study removal are 
met. Except in cases of unacceptable toxicity or drug intolerance, every effort should be made 
to ensure the subject remains in the study until disease progression. 
In cases where the definition of PD or relapse is met but the clinical impression is 
questionable, subjects may remain on study until the next evaluation (4 weeks later if 
questionable finding in skin or blood; 8 weeks later in first year and 16 weeks later after Year 
1 if questionable finding in lymph nodes or viscera, with at least stable disease in other 
compartments) to avoid a subject being removed prematurely from the study. If PD is 
confirmed at this subsequent evaluation, subject should be discontinued from treatment. If 


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PD is not confirmed at this subsequent evaluation, the subject may remain on study. 
This course of action only applies to cases where the clinical impression is questionable; 
subjects in frank or obvious PD in any compartment should be discontinued from protocol 
therapy. 
If clinical progression is noted at any time prior to the scheduled assessments for efficacy, the 
assessments (CT, mSWAT, skin photographs and flow cytometry) should be done at that 
time to fully document disease progression. CT must be performed even if previously 
negative at baseline. 
If the subject experiences an overall complete response (CR), the subject may continue 
treatment for up to 12 months or until progression, whichever comes first. 
3.2.2.4 
Cross-over to Study Drug KW-0761 
Subjects who have received at least two full treatment cycles and demonstrate progression of 
disease on treatment with vorinostat at the 8 week (cycle 2, Day 26-28) assessment, or 
anytime thereafter, may cross over to treatment with KW-0761 after discussion with Medical 
Monitor or designee and receipt of approval for cross over from KKD. All subjects must 
undergo the full extent of disease evaluations (including computerized tomography (CT) 
scanning) to document PD prior to crossover. 
For subjects who are unable to tolerate the toxicities associated with vorinostat treatment, 
dose reduction should be initiated in an attempt to have the subject complete two full cycles 
of treatment. If the subject is unable to tolerate treatment with vorinostat despite attempts at 
dose reduction and has not had documented disease progression, the subject may receive 
KW-0761 after consultation with the Medical Monitor or designee and subsequent approval 
documentation from the Sponsor. 
Drug intolerance is defined as: 
• 
A serious adverse event (SAE) attributed to the drug; 
• 
≥  Grade 3 adverse events (AEs) excluding inadequately treated nausea, vomiting and 
diarrhea and alopecia. 
4 
SUBJECT SELECTION 
This study will enroll subjects with CTCL who have failed at least one prior course of 
systemic therapy. 
The detailed inclusion and exclusion criteria are defined in Section 3 of the protocol. 


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5 
STUDY ASSESSMENTS 
5.1 
Efficacy Evaluations 
Response in skin and blood will be evaluated every 4 weeks during treatment. In the first year 
of treatment, response in lymph nodes and viscera and the overall global composite response 
(including skin, blood, lymph nodes, and viscera) will be documented at 4 weeks after the 
start of study treatment (end of Cycle 1) and every 8 weeks thereafter (Cycle 3, 5, etc.). After 
the first year, response in the lymph nodes and viscera and the overall global composite 
response will be documented every 16 weeks (Cycle 17, 21, etc.).  
For those subjects who cross over from the vorinostat arm to KW-0761 treatment, response 
within the second arm of the study will be measured from the first day of dosing with KW-
0761. Baseline measurements for this arm are considered to be those taken at the last 
assessment which documented progression on vorinostat or if repeated, assessment 
completed closest to and before the first KW-0761 infusion (i.e., mSWAT done on Cycle 1, 
Day 1 is the new baseline). 
Prior to starting study treatment, visual inspection of the skin with photographs and 
measurements Severity Weighted Assessment Tool (SWAT), assessment of CT images and 
hematological examinations will be done to document extent of disease. Skin disease will be 
evaluated using a modification of the SWAT. Response for skin will be based on modified 
SWAT (mSWAT) scores. In addition, pruritus will be evaluated using a Likert scale and 
Itchy QoL. Lymph nodes and visceral disease will be evaluated by CT. The response in blood 
will be assessed by flow cytometry.  
The response in all compartments (skin, blood, lymph nodes and viscera, as applicable) and 
overall response will be assessed, except as otherwise noted, in accordance with the response 
criteria determined by consensus of the International Society of Cutaneous Lymphomas 
(ISCL), the United States Cutaneous Lymphoma Consortium (USCLC) and the Cutaneous 
Lymphoma Task Force of the European Organization for Research and Treatment of Cancer 
(EORTC) as noted in Table 5.1-1 below.3 


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Table 5.1-1 
Global Composite Scoring System 
Global 
Score 
Definition 
Skin 
Nodes 
Viscera 
Blood 
CR 
Complete disappearance of all 
clinical evidence of disease 
CR 
All categories have CR/NI 
PR 
Regression of measurable 
disease 
CR 
All categories do not have a CR/NI and no 
category has a PD  
PR 
No category has a PD and if any other category 
involved at baseline, at least one has a CR or 
PR  
SD 
Failure to attain CR, PR or PD 
PR 
No category has a PD and if any other category 
involved at baseline, no CR or PR in any 
SD 
CR/NI,PR,SD in any category and no category 
has a PD  
PD 
Progressive disease 
PD in any category 
Relapse 
Recurrence of disease in prior 
CR 
Relapse in any category  
NI=non-involved 
 
If clinical progression is noted at any time prior to the scheduled assessments for efficacy, the 
assessments (CT, mSWAT, skin photographs and flow cytometry) should be done at that 
time to fully document disease progression. CT must be performed even if previously 
negative at baseline. 
5.1.1 
Evaluation of Skin Disease 
5.1.1.1 
Skin Biopsy 
5.1.1.1.1 CCR4 Expression 
A skin biopsy will be taken at baseline for determination of CCR4 expression by 
immunohistochemistry (IHC). In the event it is not possible to obtain a skin biopsy, use of an 
archived sample (taken within 6 months prior to treatment) may be allowed with prior 
authorization from the Sponsor. To determine if vorinostat alters CCR4 expression, 
investigators are strongly encouraged to obtain an additional skin biopsy for the 
determination of CCR4 expression, prior to treatment with KW-0761, in subjects who cross 
over from treatment with vorinostat. 
5.1.1.1.2 Disease Status/Other Biopsy Recommendations 
Subjects with clinical features suggestive of large cell transformation must have a biopsy 
performed within 4 months prior to Cycle 1 Day 1 to rule out transformed disease. 


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Skin biopsies at the end of the cycle and to confirm a CR are optional and can be performed 
at the discretion of the investigator. Analysis of these biopsies will be done by the pathologist 
at the study site. 
Additional translational assessments may be performed to further characterize the response in 
skin on any biopsy samples obtained. 
5.1.1.2 
Skin Photographs 
All involved areas that are representative of the subject’s extent of disease, will be selected at 
baseline and measured and photographed using a digital camera provided by Canfield. In 
addition, half-body global photos (waist to feet, waist to top of head and sides) will also be 
obtained. 
Skin photographs should be obtained prior to administration of study drug on Day 1 of the 
first treatment cycle and then as specified in the Study Procedures tables in the protocol. 
5.1.1.3 
Modified Severity Weighted Assessment Tool (mSWAT) 
Skin lesions and erythema will be evaluated using the mSWAT.  
The mSWAT is an objective, quantitative, severity-weighted method to assess the extent of 
skin lesions. An mSWAT score is derived by measuring each lesion as a percentage of total 
body surface area (%TBSA) and multiplying it by a severity-weighting factor (1=patch, 
2=plaque, 4=tumor). All individual numbers are then added to produce a total score. 
5.1.1.4 
Response Criteria for Skin 
Response in skin will be determined by changes in mSWAT score as specified in the 
protocol. Responses (CR and PR) must be confirmed for a minimum of 4 weeks. 
5.1.1.5 
Pruritus Evaluation 
The extent of pruritus can have a significant impact on the subject’s QoL. A Likert scale will 
be completed by each subject to assess their degree of pruritus at the visits specified in the 
Study Procedures tables. The Itchy Quality of Life questionnaire will also be completed by 
the subjects at these visits to further evaluate the impact of pruritus on their QoL.  
Medications taken to treat pruritus will be documented. 


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5.1.2 
Evaluation of Blood Disease 
5.1.2.1 
Flow Cytometric Analysis 
A peripheral blood sample will be used to evaluate circulating malignant T-cells and further 
assess immune cells in the blood. Samples will be sent to a central laboratory designated by 
the Sponsor. 
5.1.2.2 
Response Criteria in Blood 
In subjects with blood involvement, response in blood will be determined based on criteria as 
specified in the protocol. All blood responses (CR and PR) must be confirmed for a minimum 
of 4 weeks. 
5.1.3 
Evaluation of Disease in Lymph Nodes and Viscera  
5.1.3.1 
Baseline Tumor Assessments  
The baseline tumor burden will be assessed by CT of the neck, chest, abdomen and pelvis 
within 30 days prior to the first dose of study drug. The Investigator will identify, 
prospectively, the lesions to be followed to evaluate the subject’s response to therapy. 
5.1.3.2 
Method of Tumor Response Assessment 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at Screening and at reassessment during treatment.  Imaging-
based evaluation is preferred to evaluation by clinical examination when both methods have 
been used to assess the anti-tumor effect of a treatment. Lesions evaluated clinically will only 
be considered measurable when they are superficial (e.g., skin nodules, palpable lymph 
nodes).  
Central review of radiologic images may be performed to confirm the date of disease 
progression. 
5.1.3.3 
Determination of Response in Lymph Nodes and Viscera 
The Investigator will make a determination of response based on criteria as specified in the 
protocol. In subjects with lymph node and/or visceral involvement, responses (CR and PR) 
must be confirmed for a minimum of 4 weeks. 


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5.1.4 
Global Composite Response Score 
Overall response will be based on response in each compartment (skin, blood, lymph nodes 
and viscera) as specified in the protocol. Node, viscera and blood response contributes 
towards global response only if disease was present at baseline, unless defining global PD 
which is met by new disease in a previously uninvolved compartment. 
Subjects who meet PD criteria in any compartment, or relapse in blood, lymph nodes or 
viscera, confirmed at two consecutive visits must be discontinued from study treatment due to 
disease progression/relapse. If subsequent assessment does not confirm PD in any 
compartment, or relapse in blood, lymph nodes or viscera, subject may continue on treatment. 
An unconfirmed PD/relapse would not preclude future responses (CR or PR). 
If PD is documented in any compartment at any point leading to subject’s discontinuation 
from treatment, the overall global composite score should be completed at that time even if 
all compartments have not been assessed. 
5.1.4.1 
Independent Review of Progression 
A blinded Independent Review of response data for each subject will be performed to make a 
determination regarding progression and the date of progression.  The nodal and visceral 
compartments evaluation will be based upon radiologic data. The independent radiology 
review of radiographic exams will provide an assessment of tumor response and progression 
for all subjects. A separate radiology charter will detail the roles and responsibilities of the 
radiology reviewers and how the reads will be performed. An independent reviewer (IR) will 
assess PFS based on date of progression or death, whichever comes first. For this assessment 
the independent reviewer will be supplied the results of the independent radiology review, the 
mSWAT score for each subject, as assessed by the investigator, and the results of central 
flow cytometry in order to assess blood response, and date of death for subjects who died 
before progression.  
Secondarily, the IR will review the date of any objective responses (CR or PR) for each 
subject.  
The independent review charter identifies the data package that the Independent Reviewer 
receives to review responses for each subject with baseline and at least on post-baseline 
measurement in the study. 
 


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5.2 
Safety Assessments 
The safety of KW-0761 and vorinostat will be determined by reported AEs, changes in 
physical examinations, vital sign measurements, electrocardiograms (ECGs) and laboratory 
analyses. Safety evaluations will be performed throughout the study. All subjects who 
received at least one dose, including a partial dose, of study drug will be evaluated for safety. 
5.2.1 
Adverse Events 
All subjects will be assessed regularly for potential occurrence of AEs from the time  of 
signing the informed consent  until 90 days after the last dose or initiation of alternative 
therapy whichever comes first. In all subjects who cross over from vorinostat to KW-0761, 
the causality of any reported AEs should be assessed for both drugs for 30 days after 
vorinostat was stopped (or later if the event is considered to be related to vorinostat).  
All AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA, version 
15.1). The National Cancer Institute-Common Terminology Criteria for Adverse Events 
(NCI-CTCAE) v4.0 system will be used to grade AEs, both clinical and laboratory. 
5.2.2 
Clinical Laboratory Evaluations 
Clinical laboratory assessments will be performed at the visits specified in the Study 
Procedures tables of the protocol. A pregnancy test (serum or urine) is to be performed for all 
women of childbearing potential prior to administration of study medication.  
Clinical laboratory assessments are specified in the protocol. 
5.2.3 
Vital Signs and Body Weight 
Vital signs (pulse, respiration rate, temperature, and blood pressure) will be measured, with 
the subject in the seated position, at the visits specified in the Study Procedures tables of the 
protocol. Additional vital signs will be obtained if clinically significant signs or symptoms 
occur. 
Weight will be included in vital sign assessments.  
5.2.4 
Physical Examination 
The Investigator will perform a full physical examination at the Pre-treatment (including 
height at only this visit) and End of Treatment visits and brief physical examinations at other 
visits specified in the Study Procedures Tables in the protocol.  


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Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) will be assessed at 
each exam according to the ECOG PS criteria.4 
5.2.5 
Electrocardiograms 
A baseline 12-lead ECG is to be obtained at the Pre-treatment Visit. Follow up ECGs should 
be performed during the study if clinically indicated and then at the End of Treatment visit. 
The Investigator will have the responsibility for evaluating the ECG interpretation in 
relationship to clinical signs and symptoms and for reaching a medical decision regarding the 
subject’s medical status. If not within normal limits, the ECG findings should be marked 
“clinically significant” or “not clinically significant” (i.e., “CS” or “NCS”) and the ECG 
should be initialed and dated by the Investigator. 
5.2.6 
Blood Sample for Determination of Natural Ligands 
Blood samples will be drawn to measure the concentration of natural ligands such as 
CCL17/TARC and CCL22/MDC at the visits specified in the Study Procedures Tables in the 
protocol. Analysis of samples will be performed by a central laboratory designated by the 
Sponsor. 
5.2.7 
Genomic Sampling (For subjects receiving KW-0761 as first assigned 
therapy only) 
A saliva sample will be collected to obtain baseline germline DNA sample to assess 
Fc-gamma receptor polymorphisms. Exploratory analysis of the effect of this genetic 
determinant on safety parameters may be performed. Analysis of samples will be performed 
by a central laboratory designated by the Sponsor. 
5.2.8 
Immunogenicity (For subjects receiving KW-0761) 
Serum samples will be drawn for the determination of anti-KW-0761 antibodies and 
concentration of KW-0761 at the visits specified in the Study Procedures Tables in the 
protocol. Analysis of samples will be performed by a central laboratory designated by the 
Sponsor. 
5.3 
Pharmacokinetic Assessments  
Serum samples will be drawn in subjects who receive KW-0761 (as first assigned therapy or 
crossover) at the timepoints specified in the Study Procedures Tables in the protocol for 


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determination of KW-0761 concentration, through Cycle 3 and at the End-of-Treatment Visit.  
At selected sites, 4 additional samples will be drawn between 6 and 8 hours, and at 24, 48, 
and 72 - 96 hours after the first infusion on Day 1/Cycle 1 in approximately 10 subjects. All 
samples will be sent to a central laboratory designated by the Sponsor. 
5.4 
Quality of Life Assessments 
Subjects with CTCL often suffer from the symptoms related to their disease (pain, sleep 
disturbance, etc.), the social and psychological problems related to sometimes unsightly skin 
lesions and the burden of living with a chronic disease. In an effort to assess some of these 
QoL issues, the Skindex-29, FACT-G, and EQ-5D-3L will be administered. 
5.5 
Follow-Up 
• 
All subjects will be contacted by telephone every 30 days (+/- 7 days) up to 90 days after 
the last dose of study medication or initiation of alternative therapy, whichever comes 
first, to confirm any new onset AEs or toxicities. In all subjects who cross over from 
vorinostat to KW-0761, the causality should be assessed for both drugs for 30 days after 
vorinostat was stopped (or later if the event is considered to be related to vorinostat).   
• 
After a subject who receives KW-0761 goes off study, if CD4 and CD8 counts are less 
than 200/mm3 at the End-of-treatment visit, they will be followed every 3 months (+/- 14 
days) until they return to at least 200/mm3, initiation of alternative therapy, or 1 year, 
whichever comes first. 
• 
In the absence of disease progression, all subjects or their referring physicians will be 
contacted every 3 months (+/- 14 days) until documented disease progression or death, or 
initiation of alternative therapy. 
• 
All subjects or their referring physician will be contacted every 3 months (+/- 14 days) to 
ascertain survival status. 
• 
All follow up information and attempts to obtain follow up information should be 
documented in the subject’s source record. 
5.6 
Follow-Up for Subjects Achieving a Complete Response 
Those subjects who do not continue treatment after achieving a CR will undergo the 
following assessments every 8 weeks (+/- 14 days) for the first 6 months (if CR achieved 
prior to one year on study) and then every 16 weeks (+/- 14 days) thereafter until progression: 
• 
Chemistry/Hematology profile; 
• 
Skin photographs; 
• 
mSWAT; 
• 
Pruritus evaluation; 


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• 
Blood sample for flow cytometric analysis; 
• 
CT; 
• 
Overall Disease Response; 
• 
Immunogenicity (for subjects receiving KW-0761).  
6 
STATISTICAL METHODOLOGY 
6.1 
General Statistical Consideration 
Summary statistics will be presented by treatment arm. For continuous variables, the number 
of available observations (n), mean, standard deviation (SD), median, minimum, and 
maximum will be provided. For categorical variables, the frequency and percentage in each 
category will be displayed. Additionally, the point estimates will be accompanied by the 
corresponding 2-sided 95% confidence intervals. 
For summary statistics, the mean and median will be displayed to one decimal place greater 
than the original value and the measure of variability (e.g., standard deviation) will be 
displayed to two decimal places greater than the original value.  
Unless otherwise specified, all efficacy and safety analyses will be performed based on the 
first assigned therapy. For those subjects in the vorinostat arm who cross over into the 
KW-0761 arm, efficacy and safety data collected during the crossover portion will be 
presented separately within the KW-0761 crossover group. 
All analyses will be performed using SAS® Version 9.3 or higher. 
6.2 
Baseline Definition 
For analyses of study variables based on the first assigned therapy, baseline is defined as the 
last measurement obtained prior to the first dose of study drug. For analyses of study 
variables in the crossover portion, baseline is defined as the last measurement obtained prior 
to the first dose of KW-0761. 
6.3 
Determination of Sample Size 
Since the primary endpoint is PFS, the reference median PFS for vorinostat is assumed to be 
169 days. 5   The median PFS for KW-0761 therapy is targeted for 254 days, a 50% 
improvement over this reference median. For a 24-month accrual and 12 month follow-up on 
the last subject dosed, Table 10.3-1 of the protocol gives the power and the number of PFS 
events required to show superior PFS for KW-0761 therapy over vorinostat at the one-sided 


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0.025 significance level. The Intent-to-Treat (ITT) set is used for this primary analysis. The 
same analysis conducted using the Efficacy Evaluable set is considered secondary. 
Under these assumptions, for the ITT population, a total of 255 PFS events will give 90% 
power. For this study, the final primary analysis comparing PFS between treatment groups 
will not be conducted until 255 PFS events occur or until a maximum of 24 months after the 
last randomized subject’s first dose, whichever comes first. In the event that the study is 
stopped prior to 255 PFS events being observed, the primary test will be performed at less 
than 90% power under the current assumptions according to Table 10.3-1 in the protocol. 
Each of these calculations used a log-rank test to compare the two survival curves. Sample 
size calculations were computed using SAS software version 9.3 using PROC POWER, 
Twosamplesurvival test = logrank. 
The total sample size of 288 represents the approximate number of subjects that may be 
necessary for 255 PFS events to occur within the projected 36 months of the trial. If a 10% 
inflation factor is applied to this total (about 29 subjects) to take into account those subjects 
that may be lost to follow-up prior to documented progression, a total of 317 enrolled 
subjects may be necessary in order to observe 255 PFS events.  
The observed rates of PFS events, recruitment, and drop-outs will be monitored throughout 
the study and may be used to alter the number of sites, the accrual period, and the follow-up 
period to achieve the required 255 PFS events in a timely manner. If the 255 PFS events are 
not observed within 36 months from the start of enrollment the study will be stopped at 
approximately 24 months after the last randomized subject’s first dose. 
6.4 
Analysis Sets 
• 
Intent-to-Treat (ITT) Set: Includes all subjects randomized to a therapy (KW-0761 or 
vorinostat) and assigned a study number.  
• 
Safety Analysis Set: Includes all subjects who received at least one dose (even a partial 
dose) of the assigned study agent (KW-0761 or vorinostat). 
• 
Efficacy Evaluable Set: Includes all subjects who receive the first cycle of treatment (at 
least one dose) and who have baseline tumor assessment and at least one post-baseline 
assessment for response. If a subject had baseline tumor assessment but progressed (died 
before progression or had documented progression in follow-up period) during the study 
without any post-baseline tumor assessment, that subject will still be considered as 
efficacy evaluable.  
• 
Pharmacokinetic (PK) Analysis Set: All subjects who provide at least one post-dose KW-
0761 concentration measurement will be included in the PK analysis set. 


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6.5 
Interim Analysis and Data Monitoring 
No formal interim analysis is planned for this study.  
A Data Safety Monitoring Board (DSMB) will be responsible for overseeing subject safety in 
the trial. The DSMB will be comprised of at least two medical doctors and a statistician.  A 
detailed DSMB charter will be developed prior to the safety review.   
6.6 
Subject Disposition 
Subject disposition will be summarized for each treatment arm and in total for all randomized 
subjects. The following subject disposition categories will be included: 
• 
Subjects who were randomized; 
• 
Subjects who were randomized and did not receive any assigned study drug; 
• 
Subjects who were randomized and treated; 
• 
Subjects who discontinued randomized study drug; and 
• 
Subjects who discontinued from the study. 
For subjects who discontinued randomized study drug and subjects who discontinued from 
the study, a summary of reasons for discontinuation will be provided. The number of subjects 
in the ITT, Safety Analysis and Efficacy Evaluable Sets will also be summarized. 
For subjects who were randomized to vorinostat arm but then cross over into KW-0761 arm, 
the following disposition categories will be presented for the crossover portion: 
• 
Subjects who were randomized to vorinostat and crossed over to KW-0761; 
• 
Subjects who were crossed over to KW-0761 but did not receive KW-0761;  
• 
Subjects who were crossed over to KW-0761 and received KW-0761; 
• 
Subjects who were crossed over to KW-0761 and discontinued KW-0761; and 
• 
Subjects who were crossed over to KW-0761 and discontinued from the study. 
The reasons for discontinuation of KW-0761 and discontinuation from the study during the 
crossover portion will be provided. 
All disposition data will be listed by subject corresponding to their first assigned therapy. A 
listing will be provided that indicates each subject’s inclusion/exclusion from the analysis set 
and the reason(s) for exclusion from the Efficacy Evaluable Set.  


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6.7 
Demographic and Baseline Disease Characteristics 
Demographic and baseline characteristics will be summarized descriptively for the ITT Set, 
Safety Analysis Set, and the Efficacy Evaluable Set by treatment arm and in total. Gender, 
race, ethnicity, region, and baseline ECOG performance status will be summarized with 
contingency tables. Age at screening (years), height, weight, body surface area (BSA), and 
body mass index (BMI) at baseline will be described with summary statistics (n, mean, 
standard deviation, median, minimum, and maximum). 
Baseline disease characteristics will be collected at screening and will be summarized 
descriptively for each treatment arm and in total. Time from initial diagnosis (months) will be 
summarized with descriptive statistics (n, mean, standard deviation, median, minimum, and 
maximum).  Histologically confirmed diagnosis type (MF or SS), clinical stage at diagnosis, 
current clinical stage, current sites of disease, CCR4 expression status, number of prior CTCL 
therapies, best response to the last CTCL therapy prior to study entry, and prior radiotherapy 
will be summarized to show the number and percentage of subjects in each category.   
All demographic data and baseline disease characteristics data will be listed by subject. 
6.8 
Medical and Surgical History 
Medical/surgical history will be listed by subject. 
6.9 
Prior/Concomitant Medications 
Prior and concomitant medications will be coded using the World Health Organization 
(WHO) Drug Dictionary (September 2012). Prior medications include medications that were 
taken within 30 days prior to study entry and stopped prior to start of randomized treatment. 
Concomitant medications during the randomized treatment period include medications that 
started at any time and were taken at any time after the start of treatment until the end of the 
entire randomized treatment period.  
The number and percentage of subjects taking concomitant medications during randomized 
treatment period (excluding crossover) will be summarized by anatomical therapeutic 
chemical (ATC) and preferred term (PT) for the Safety Analysis Set. Although a subject may 
have taken two or more medications, the subject is counted only once within an ATC 
classification. The same subject may contribute to two or more preferred terms in the same 
classification.   


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All prior and concomitant medications will be listed by subject. Pruritus medications will also 
be listed. 
6.10 Study Drug Exposure and Compliance 
Extent of exposure in days for each subject for the entire randomized treatment period will be 
calculated as the last dose date of study drug (KW-0761 or vorinostat) minus the first dose 
date of study drug plus 1. Extent of exposure and total number of cycles initiated during the 
randomized treatment period will be summarized using descriptive statistics by treatment arm 
and in total for the Safety Analysis Set. The number and percentage of subjects who initiated 
treatment for at least 1, 2, 3, 4, 5, and 6 or more cycles will be tabulated by treatment arm and 
in total. 
For the KW-0761 arm, the number of KW-0761 infusions administered, the planned dose 
(average of the planned dose per subject), the actual dose (average of the actual dose received 
per subject), and the % dose intensity (total actual dose/total duration of treatment/7) / (total 
planned dose/total planned weeks) of KW-0761 will be calculated and summarized 
descriptively.  Total planned weeks are based on a 28 day cycle.  The following categories of 
KW-0761 dosing status will be summarized: 
• 
Subjects with total planned dose not administered; 
• 
Subjects with a dose withheld for KW-0761; and 
• 
Subjects with a KW-0761 infusion temporarily interrupted. 
In addition, the reasons will be provided for subjects with total planned dose of KW-0761 not 
administered and for subjects with KW-0761 infusion temporarily interrupted.  
For the vorinostat arm, the number and percentage of subjects with dose modifications and 
the number and percentage of subjects who had non-compliance with dosing for vorinostat 
will be provided. 
For subjects who were randomized to vorinostat arm but then cross over into KW-0761 arm, 
the extent of exposure to KW-0761 and the total number of cycles initiated during the 
crossover portion will be summarized. In addition, the number of KW-0761 infusions 
administered, the % dose intensity, and the dosing status of KW-0761 during the crossover 
portion will also be summarized descriptively. 
All study drug administration data will be listed by subject.  


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6.11 Efficacy Analysis  
Efficacy evaluations will be performed based on both the Intent-to-Treat Set and the Efficacy 
Evaluable Set.   
6.11.1 
Efficacy Variables for Analysis 
The primary efficacy variable is: 
• 
Progression-free survival (PFS) as assessed by the Investigator 
The key secondary efficacy variables are as follows: 
• 
Overall response rate (ORR) as assessed by the Investigator;  
• 
Change in Skindex-29 score from baseline through the 6-month assessment; 
• 
Change in FACT-G total score from baseline through the 6-month assessment; 
• 
Change in EQ-5D-3L index score from baseline through the 6-month assessment. 
Other secondary efficacy variables include: 
• 
Progression-free survival (PFS) as assessed by IR; 
• 
Overall response rate (ORR) as assessed by IR;  
• 
Best overall response;  
• 
Duration of response (DOR); 
• 
Time to response (TTR);  
• 
Overall response rate in the crossover portion of the trial;  
• 
Changes from baseline in Skindex-29, FACT-G, and EQ-5D-3L at other timepoints;  
• 
Changes from baseline in Pruritus Evaluation (Likert scale & Itchy QoL).  
An overall response is defined as a CR or PR at any time during the treatment period prior to 
progression/relapse, if applicable. The best overall response is the best response reported 
across all visits during the treatment period prior to a progression/relapse, if applicable. 
The exploratory efficacy variables include: 
• 
Overall survival (OS); 
• 
Time to treatment failure (TTF)  
Disease status will be assessed every 4 weeks in skin and blood. In the first year of treatment, 
response in lymph nodes and viscera and the overall global composite score will be 
documented every 8 weeks. After the first year, response in the lymph nodes and viscera and 
the overall global composite score will be documented every 16 weeks. Additionally, if 


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clinical progression is noted, efficacy assessments are performed to fully document disease 
progression.  
These assessments will be compared with the baseline assessment to determine response. 
Subjects will be evaluated for response in each compartment and overall. For any time-to-
event endpoints (e.g., PFS), the date of disease progression will be determined by both the 
on-site Investigator’s assessment and the IR. 
6.11.1.1 
Definition of Primary Efficacy Variable 
The primary efficacy variable is progression-free survival (PFS) based upon the assessment 
by the Investigator, defined as the time from the day of randomization to a treatment arm 
until documented progression or death due to any cause.  
Documented disease progression includes disease progression in any compartment based on 
the Investigator’s assessment per CTCL response criteria or documented disease progression 
reported during the follow-up period. The date of progression will be the earliest date at 
which documented disease progression can be declared. 
For subjects who exhibit conditions of disease progression, but continue on the study due to a 
questionable clinical impression as described in Section 3.2.2.3, the subject is not considered 
to have progressed unless disease progression is confirmed at least 4 weeks after the date of 
the initial questionable disease progression.  In this case, the initial date will be used as the 
date of disease progression. 
Subjects who died without a reported prior progression will be considered to have progressed 
on the day of their death.  
The definition of censoring date will be as follows:  
• 
In the event that a randomized subject withdraws from the study for any reason before 
documented progression, the time from the day of randomization to the last post-baseline 
tumor assessment from any compartment (skin, blood, bone marrow, lymph node, and 
viscera) will be used as a censored time point.  
• 
For subjects who are randomized to a treatment arm but have an unknown baseline 
assessment for a compartment, the PFS time will be censored at the randomization date if 
there is no post-baseline tumor assessment for that compartment or if there is any 
evidence of lymphoma in that compartment at post-baseline evaluation. 


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• 
For subjects randomized to a treatment arm but withdrawing prior to the first 
post-baseline tumor assessment for any reason other than disease progression, the PFS 
time will be censored at the last documented visit. 
• 
For subjects who initiate a new anticancer therapy (including crossover to KW-0761) in 
the absence of a PFS event, the PFS time will be censored at the last tumor assessment 
(from any compartment) prior to the start of the new anticancer therapy. 
• 
For subjects not known to have died or have documented progression as of the end of the 
study, the PFS time will be censored at the date of the last post-baseline tumor assessment 
(from any compartment). 
6.11.1.2 
Definition of Key Secondary Efficacy Variables 
6.11.1.2.1 Objective Response Rate 
The overall response rate (ORR) is defined as the proportion of subjects who are responders 
(confirmed CR or PR) based on the Investigator’s assessment.  
Confirmed CR or PR is defined as documented CR or PR based on the Investigator’s 
assessment of overall response per Global Composite Response Score that is subsequently 
confirmed by two or more consecutive observations for a minimum of 4 weeks. In the case 
where a subject has visit responses of CR, N/A, CR, then, as long as the time between the 2 
visits of CR is greater than 4 weeks, the subject will be defined as a responder. 
Subjects lacking valid data to assign a response status will be included in the denominator for 
response rate calculation based on the ITT Set and, hence, are considered nonresponders. 
6.11.1.2.2 Changes in Skindex-29, FACT-G, and EQ-5D-3L from Baseline 
The Skindex-29 is a validated instrument to measure the effect of skin disease on 
health-related quality of life.6  It is composed of 29 items assessing three domains: emotions, 
symptoms, and functioning. The items are scored on a 5-point Likert-type scale (never, rarely, 
sometimes, often, all the time). Responses to each item are transformed to a linear scale of 
100 (never=0, rarely=25, sometimes=50, often=75, all the time=100) for the purpose of scale 
score calculation.  A scale score is the mean of a subject’s responses to the items in a given 
scale and the composite Skindex-29 score is calculated as the average of the 3 scale scores to 
measure the overall impact on quality of life. Higher scores indicate a higher impact of skin 
disease. 
The FACT-G is a validated instrument for assessing health-related quality of life in subjects 
with cancer.7  The FACT-G consists of 27 items in the following 4 domains: physical 


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well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), and 
functional well-being (FWB). The total FACT-G score is obtained by summing individual 
subscale scores. Response scores on negatively-phrased questions are reversed before 
summing. Higher scores for the scales and subscales indicate better quality of life.  
The EuroQol/EQ-5D is a standardized, reliable and validated instrument to measure 
health-related quality of life. The EQ-5D self-reported questionnaire includes the EQ-5D 
descriptive system and a visual analog scale (VAS). The EQ-5D 3 level version (EQ-5D-3L) 
descriptive system comprises the following dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some 
problems, extreme problems. The EQ-5D index score is calculated based on the descriptive 
system using a set of item weights (value sets) to derive a single score ranging from -0.109 to 
1, with 1 representing full health. The value sets for the US will be used for the calculation of 
the EQ-5D index score.8  The EQ-5D self-reported questionnaire also includes a visual analog 
scale (VAS), which records the respondent's self-rated health status on a graduated (0-100) 
scale, with 100 = best imaginable health state and 0 = worst imaginable health state. 
Skindex-29, FACT-G, and EQ-5D-3L will be evaluated at baseline (Cycle 1 Day 1), end of 
Cycle 1, then every 8 weeks (i.e., end of Cycle 3, 5, etc), and at the End of Treatment Visit. 
Measurements at end of cycle 1 are defined as the latest value obtained from Cycle 1 Day 26-
28 or Cycle 2 Day 1. Measurements at the end of Cycle x, where x = 3, 5, 7, …, etc, are 
defined as the latest value obtained from Cycle x Day 26-28, Cycle x Q8 weeks, or Cycle 
(x+1) Day 1. 
The improvement (change from baseline) for each of the quality of life measurements 
described above will be evaluated at each timepoint as specified in the study procedure tables 
for each arm.  
Missing data for Skindex-29 and FACT-G will be handled according to the questionnaires’ 
scoring guidelines. For Skindex-29, if responses to more than 25% of items are missing 
overall, the Skindex-29 score will be treated as missing. If any scale has more than 25% of 
the responses missing, the scale score is missing. The scale scores are the average of the 
non-missing items in a given scale. For FACT-G, if more than 50% of the items are 
responded for a subscale, the subscale scores will be prorated by multiplying the sum of the 
subscale by the number of items in the subscale and then dividing by the number of items 
actually responded. The total FACT-G score will be scored only if the overall item response 
rate is greater than 80%. For EQ-5D-3L, the EQ-5D index score will be treated as missing if 
not all five descriptors are responded.  


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6.11.1.3 
Definition of Other Secondary Efficacy Variables 
6.11.1.3.1 Best Overall Response 
Best overall response is defined as the best response recorded across all timepoints from the 
start of treatment until disease progression/recurrence or end of treatment. The subject’s best 
response assignment will depend on the achievement of both measurement and confirmation 
criteria.  
6.11.1.3.2 Duration of Response and Time to Response 
Duration of response (DOR) is defined as the time from the date criteria are met for CR/PR 
(whichever is first recorded) until the first date that PD or death is objectively documented. 
Subjects who do not relapse will be censored at the day of their last tumor assessment (from 
any compartment).  
Time to response (TTR) is defined as the time from the date of randomization to the date 
criteria are first met for CR/PR (whichever is first recorded).  Subjects who do not respond 
over the course of the study will have a missing value for TTR. 
6.11.1.3.3 Changes in Pruritus Evaluation 
Pruritus Evaluation includes the Likert Scale and the Itchy QoL. The Likert scale for pruritus 
evaluation uses a numbered scale from 0 to 10 to measure the level of itching for pruritus 
with 10 indicating worst itch imaginable and 0 indicating no itch. The Itchy QoL is a 
validated pruritus-specific quality of life instrument.9  It includes 22 pruritus-specific 
questions covering three major domains: symptoms, functioning, and emotions. The subscale 
scores consist of the average of the responses to the items in a given subscale.  The overall 
score is the average of the responses to all items. Higher Itchy QoL scores indicate worse 
quality of life. Missing data in Itchy QoL questionnaire will be handled according to the 
following rule: if responses to more than 25% of items are missing overall, the overall score 
will be treated as missing; if any scale has more than 25% of the responses missing, the scale 
score is missing.  
Pruritus Evaluation will be performed at each timepoint specified in the study procedure 
tables for each arm. 
6.11.1.4 
Definition of Exploratory Efficacy Variables 
6.11.1.4.1 Overall Survival (OS) 
Overall survival is defined as the time from the date of randomization until the date of death 
of the subject due to any cause. Subjects who are still alive at the end of the survival 


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follow-up period or are lost to follow-up at the time of analysis will be censored on the last 
date the subject is known to be alive. 
6.11.1.4.2 Time to Treatment Failure (TTF) 
Time to treatment failure is defined as the time from the day of randomization to a treatment 
arm until discontinuation of randomized treatment due to any reason except for those subjects 
who discontinued randomized treatment due to one year on treatment with a CR.  
Subjects who experienced an overall CR and discontinued randomized treatment after one 
year of treatment will be censored at the last dose date of the randomized treatment. Subjects 
who were randomized but did not take any study drug will be censored at the last documented 
visit date.  
6.11.2 
Efficacy Analysis Methodology 
6.11.2.1 
Analysis of Primary Efficacy Variable 
The primary comparison of progression-free survival between KW-0761 and vorinostat will 
be performed on the ITT set based upon the results of the on-site Investigator’s assessment 
using a stratified Log-rank test at the one-sided 2.5% significance level. Stratification is done 
by disease type (MF or SS), disease stage (IB/II or III/ IV), and region (U.S., Japan, and Rest 
of World). A Cox proportional hazard model with treatment, disease type, disease stage, and 
region (U.S., Japan, and Rest of World) as covariates will be used to assess the magnitude of 
the treatment difference in PFS. The hazard ratio along with the 95% confidence interval 
obtained from the Cox proportional hazard model will be presented. Additional analyses may 
be performed adjusting for treatment and other baseline characteristics. 
The median PFS and the 2-sided 95% confidence interval for each treatment will be 
estimated using the Kaplan-Meier survival analysis methods. Kaplan-Meier estimate of PFS 
rates and the corresponding 95% confidence interval will also be provided for each treatment 
arm by 6 months intervals. Plots of the Kaplan-Meier estimate of the survival distribution 
function over time for PFS will be presented by treatment arm.  
The primary analysis of PFS will be performed when 255 total PFS events have been 
observed or 24 months after the last randomized subject’s first dose, whichever comes first.  


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6.11.2.2 
Sensitivity Analyses of Primary Efficacy Variable 
Three sensitivity analyses will be performed for PFS during randomized treatment period 
based on the on-site Investigator’s assessment and the ITT Set using the following 
definitions: 
1) Sensitivity Analysis 1: PFS is defined as the time from the day of randomization to a 
treatment arm until documented progression in any compartment based on the 
Investigator’s assessment per CTCL response criteria or death due to any cause 
provided that death is not more than 8 weeks after the last post-baseline tumor 
assessment or the last dose of study drug (if the subject did not have any post-baseline 
tumor assessment).   
Using this definition, the disease progression reported during the follow-up period 
would not be considered as an event in the sensitivity analysis, but would be a 
censored value on the day of the last tumor assessment. 
2) Sensitivity Analysis 2: PFS is defined as the time from the day of randomization to a 
treatment arm until the earliest date of documented progression in any compartment 
based on the Investigator’s assessment per CTCL response criteria, or clinical 
progression at the end of the randomized treatment, or documented disease 
progression reported during the follow-up period, or death due to any cause. 
Using this definition, clinical progression noted at the end of the randomized 
treatment would be considered as an event in the sensitivity analysis. 
3) Sensitivity Analysis 3: An additional worst-case sensitivity analysis will be performed 
based on the ITT Set using the following definition: 
PFS is defined as the time from the day of randomization to a treatment arm until 
documented progression or death due to any cause. The date of documented disease 
progression will be the earliest date of disease progression in any compartment based 
on the Investigator’s assessment per CTCL response criteria or disease progression 
reported during the follow-up period. For assessments where progression is reported 
by the investigator but is not confirmed by the IR, the progression date will be set to 
the last tumor assessment plus one day in the KW-0761 treatment arm and will be 
censored in the Vorinostat treatment arm. 
The same censoring rules as described in Section 6.11.1.1 will be used for the sensitivity 
analyses. 


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6.11.2.3 
Analyses of Key Secondary Efficacy Variables 
There are four key secondary endpoints in this study that require a comparison between 
treatment arms: ORR as assessed by the Investigator, changes in Skindex-29 score, FACT-G 
total score, and EQ-5D-3L index score. All assessments up to 6-months will be of interest for 
this analysis.  
ORR as assessed by the Investigator will be compared between the 2 treatment arms using 
Cochran-Mantel-Haenszel (CMH) test adjusted for disease type, disease stage, and region. 
Additional analyses may be performed adjusting for treatment and other baseline 
characteristics. The exact 95% confidence intervals for ORR will be calculated for each 
treatment arm along with the difference in response rates between the two treatment arms. All 
95% confidence intervals on individual rates will be computed using exact computational 
methods. Any confidence interval on the difference of proportions will be computed using 
exact unconditional confidence limits for the risk difference. These confidence intervals can 
be constructed using SAS® version 9.3 with the FREQ procedure specifying the RISKDIFF 
option in the EXACT statement.10  In addition to the results described above, the number and 
percentage of subjects achieving objective response (CR or PR) will be presented for each 
treatment arm. 
The treatment differences in the mean change of Skindex-29 score from baseline across each 
planned timepoint (end of cycle 1, cycle 3, cycle 5) up to 6 months of assessments will be 
tested using a repeated measures mixed effects model with time, region, disease type, disease 
stage, treatment, and time-by-treatment interaction as factors and baseline score as a covariate.  
Restricted Maximum Likelihood (REML) method will be used. An unstructured covariance 
matrix will be employed to model the correlation among repeated measurements.  
Appropriate contrasts will be used to determine the difference between the Vorinostat 
treatment group and the KW-0761 treatment group across the end of Cycles 1, 3, and 5.  In 
case of convergence problems, another variance-covariance structure will be considered.  The 
selection of any of these structures will be determined after exploration of the observed 
correlation structure.  Least squares (LS) means, corresponding standard errors, 95% two-
sided confidence intervals will be presented for the within-group change for odd cycles. For 
the between-treatment group comparison, the difference in LS means, corresponding standard 
errors, 95% two-sided confidence intervals, and two-sided p-value will also be derived from 
this ANCOVA model and presented for the odd cycles. This mixed-effects model will also be 
used to compare the treatment differences in the mean changes in Skindex-29 score from 
baseline to each scheduled time point at end of cycle 1, cycle 3, and cycle 5.  In addition to 


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the Skindex-29 score, a Skindex score based on a subset of Skindex questions may be 
analyzed in a similar fashion.11 
Standard model diagnostics will be performed to assess the validity of the proposed 
ANCOVA model. These diagnostics will include an examination of the residuals for 
normality and homoscedasticity as well as testing for the significance of the treatment by 
baseline interaction term. If the residuals are not normally distributed, then the analysis will be 
carried out using Wilcoxon rank sum test instead. 
In addition to the analysis described above, summary statistics including n, mean, standard 
deviation, median, minimum, and maximum will be provided for Skindex-29 score at 
baseline and each scheduled time point and change in total score at each of these scheduled 
assessments for each treatment arm. 
The same methods described above for the analysis of change in Skindex-29 score will be 
performed for the analysis of change from baseline for the ends of cycle 1,3, and 5 in FACT-
G total score and EQ-5D-3L index score. 
Comparisons of these four key secondary endpoints between the two treatment arms will be 
conducted using p-values that are adjusted to control the overall study-wise Type 1 error rate 
to be less than 0.05. The four statistical tests that will be conducted are:  
• 
ORR as assessed by the Investigator,  
• 
Change in Skindex-29 score at  through the 6-month assessment,  
• 
Change in FACT-G total score at through the 6-month assessment, and  
• 
Change in EQ-5D-3L index score at through the 6-month assessment.  
Since these tests are not independent, the four key secondary tests will be conducted using the 
Sidak adjusted p-value method defined as: 
Adjusted p-value = 1-(1-p)4 where p is the original p-value of the individual test.  
These adjusted p-values will then be compared to .05 for each test. 
6.11.2.4 
Analyses of Other Secondary Efficacy Variables 
Comparisons between treatment arms for all other secondary endpoints such as Pruritus 
Evaluation (Likert scale and Itchy QoL) will be conducted with no adjustment for multiple 
comparisons used for those statistical tests. 
PFS and ORR as assessed by the IR will be analyzed using the same method described above 
for PFS and ORR as assessed by the Investigator.  


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Frequency tables will be used to display the best overall response as assessed by the 
Investigator and by the IR during the randomized treatment period for all subjects by 
treatment arm. The concordance between the investigators assessment and the IR assessment 
of best overall responses will be presented. 
For subjects who achieved a confirmed CR or PR during the randomized treatment period, 
the time to response will be summarized descriptively. The duration of response will be 
analyzed using survival analysis methods. The Kaplan-Meier estimate of the median duration 
of response and the associated 95% confidence intervals will be estimated and presented 
separately for each treatment arm. Because the DOR is a conditional estimate (conditional on 
having a confirmed response), comparison between KW-0761 and vorinostat would not be 
based on randomized groups and therefore will not be made.  
The same repeated measures ANCOVA model described above for the analysis of change in 
Skindex-29 score from baseline to end of cycles 1, 3, and 5 will be performed for the changes in 
Skindex-29 score, FACT-G total score and EQ-5D-3L index score at other time points up to 
end of cycle 11. Due to the relatively small sample size of subjects after cycle 11, QoL data 
beyond cycle 11 will only be summarized descriptively. In addition, for EQ-5D-3L 
descriptive system, frequency tables will be used to display the number and percentage of 
subjects with reported problems for each level and for each dimension at each scheduled 
timepoint.   
Other quality of life measurements including changes in Pruritus Evaluation (Itchy QoL 
score) and EQ-5D-3L VAS score from baseline at each scheduled timepoint up to the cycle 
11 assessment will also be analyzed using the same method. The assumptions of normality 
and homogeneity of variance of the ANCOVA analysis will be examined prior to fitting the 
models. When significant departure from the assumption is observed, the Wilcoxon rank sum 
test will be applied. 
For the Pruritus Evaluation Likert Scale data, the changes in the Likert Scale score from 
baseline at different timepoints up to the cycle 11 assessments during the randomized 
treatment period will be analyzed using Wilcoxon rank sum test. The treatment difference in 
the median change of the Likert Scale score from baseline will be estimated using the 
Hodges-Lehmann estimate and a two-sided 95% confidence interval for the treatment 
difference will be obtained using the method of Moses. 
All quality of life measurements and changes from baseline will be summarized descriptively 
at each scheduled time point. 


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For subjects who cross over from the vorinostat arm to the KW-0761 arm, ORR during the 
crossover portion of the trial will be estimated in a similar fashion as described above for 
ORR of the randomized therapy.  In addition, the quality of life assessments during the 
crossover portion will be measured at the end of the first cycle after the first day of dosing for 
KW-0761. Baseline measurements for the crossover portion are considered to be those taken 
at the last assessment point of the previous cycle. The quality of life measurements as well as 
the changes from baseline during the crossover portion of the trial will be summarized 
descriptively. All summaries for the crossover portion will be purely descriptive. No 
statistical comparisons will be made for data collected during the crossover portion.   
6.11.2.5 
Analyses of Exploratory Efficacy Variables 
Although not considered a secondary endpoint, a comparison between treatment arms for OS 
and TTF will be conducted using the same method as described above for the analysis of PFS 
based on the ITT set and will be considered exploratory.  
Additional exploratory analysis will be performed for comparison of PFS between subjects 
with any exposure to KW-0761 versus subjects with vorinostat only. For this analysis, the 
PFS for subjects who cross over from the vorinostat arm to KW-0761 will be calculated from 
the first dose of KW-0761. 
Statistical analyses on OS using follow-up data may take place after database lock for the 
study and will be reported as supplemental to the Clinical Study Report. 
The following exploratory analyses will be performed for OS to account for crossover effect:  
• 
The rank-preserving structural failure time (RPSFT) model will be applied to allow a 
direct comparison of the randomized treatment groups by adjusting the OS of subjects 
who crossed over so that it reflects the OS had they not received KW-0761. 12 
• 
The Inverse Probability of Censoring Weighting (IPCW) model will also be applied. 
In this method subjects who cross over from IC to KW-0761 will be censored and 
subjects remaining on IC will be weighted to compensate for missing data. The bias 
introduced by the crossover will be corrected by weighting each subject by the inverse 
of the predicted probability of not being censored at a given time. 12 
6.11.2.6 
Adjustment for Covariates 
Additional analysis of the treatment effect on PFS and ORR as assessed by the Investigator 
when adjusted for potential prognostic factors will be carried out using a multivariate Cox 
proportional hazard model for PFS and a multivariate logistic regression model for ORR.  
These analyses will be performed based on the PFS and ORR as assessed by the Investigator 
for the first assigned therapy and the ITT Set. Potential prognostic factors including disease 


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type (MF or SS), disease stage (IB and II versus III or IV), compartment involvement (blood 
involvement or no blood involvement), region (US, Japan, Rest of World), age group (<65 or 
≥65 years), gender (males or females), and race category (Black or African American, White, 
Other) will be included as covariates in the multivariate Cox proportional hazard model for 
PFS and the multivariate logistic regression model for ORR. Backward selection will be used 
to identify the final set of prognostic factors (exit p-value is set to be 0.1). The final model 
will then be used to assess treatment effect when adjusted for these important prognostic 
factors. 
6.11.2.7 
Subgroup Analyses 
Subgroup analyses will be performed for PFS as assessed by the Investigator based on the 
first assigned therapy for the ITT Set and the Efficacy Evaluable Set provided that there are 
adequate sample sizes in the respective groups. The following subgroup factors will be used: 
• 
Disease type (MF or SS); 
• 
Disease stage (IB and II versus III or IV); 
• 
Blood involvement (yes or no); 
• 
Region (US, Japan, Rest of World); 
• 
Age group (<65 years or ≥65 years ); 
• 
Gender (male or female); 
• 
Race category (Black or African American, White, Other).  
• 
LDH (normal versus elevated) 
Forest plot of hazard ratios by subgroups will be provided for PFS as assessed by the 
Investigator. Additional subgroup analyses may be performed. 
6.12 Safety Analysis 
The safety and tolerability of the study drugs are determined by reported AEs, physical 
examinations, ECGs, vital signs, and laboratory tests. Unless otherwise specified, safety 
analyses will be based on the safety data collected for the first assigned therapy. For those 
subjects in the vorinostat arm who cross over to KW-0761 treatment arm, the safety data 
collected during the crossover portion will be presented separately.  
All safety summaries will be based on the entire Safety Analysis Set. 


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6.12.1 
Adverse Events 
For subjects in the KW-0761 arm and subjects in the vorinostat arm who do not cross over to 
KW-0761, treatment-emergent adverse events (TEAEs) during the randomized treatment 
period are defined as adverse events with an onset date/time after the first dose of randomized 
study drug until 90 days after the last dose of randomized study drug or initiation of an 
alternative therapy whichever comes first. 
For subjects in the vorinostat arm who cross over to KW-0761 treatment arm, TEAEs during 
the randomized treatment period are defined as adverse events with an onset date/time after 
the first dose of randomized study drug and prior to the start of KW-0761. An adverse event 
with onset date/time after the start of KW-0761 will also be considered as a TEAE during the 
randomized treatment period if it is considered related to vorinostat. TEAEs during the 
crossover portion are defined as adverse events with an onset date/time after the first dose of 
KW-0761 and within 90 days after the last dose of KW-0761 or initiation of an alternative 
therapy whichever comes first.  
TEAEs during the randomized treatment period will be summarized by treatment arm and in 
total based on the Safety Analysis Set. For subjects who are initially assigned to vorinostat 
arm and are crossed over to KW-0761 arm, TEAEs during the crossover portion will be 
summarized separately. A drug-related AE is defined as any event with a relationship to 
study drug recorded as “definitely”, “probably” or “possibly”.  Any adverse events for which 
relationship to study drug are not recorded will be assumed to be probable. 
An overview of adverse events for the randomized treatment period will be provided which 
summarizes the subject incidence of the following information: 
• 
Any AEs, 
• 
Any TEAEs, 
• 
Drug-related TEAEs, 
• 
NCI/CTCAE grade III/IV/V AEs, 
• 
NCI/CTCAE grade III/IV/V TEAEs, 
• 
Drug-related NCI/CTCAE grade III/IV/V TEAEs, 
• 
Deaths, 
• 
Serious AEs, 
• 
Treatment-emergent SAEs, 
• 
Drug-related treatment-emergent SAEs, 
• 
Discontinuation due to AEs, 
• 
Discontinuation due to TEAEs, and  


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• 
Discontinuation due to drug-related TEAEs. 
The number and percentage of subjects with TEAEs during the randomized treatment period 
will be summarized for each treatment arm and in total by system organ class (SOC) and 
preferred term. Drug-related TEAEs, grade III/IV/V TEAEs, and drug-related grade III/IV/V 
TEAEs, treatment-emergent SAEs, drug-related treatment-emergent SAEs, TEAEs leading to 
discontinuation of study drug, and drug-related TEAEs leading to discontinuation of study 
drug will be summarized in the same manner. For these summaries, subjects with multiple 
adverse events will be counted only once per SOC and preferred term.  
In addition, summaries will be provided for the number and percentage of subjects with 
TEAEs and drug-related TEAEs by SOC and preferred term and by the highest NCI CTCAE 
grade. For these summaries, subjects with multiple adverse events will be counted only once 
by the highest NCI CTCAE grade within an SOC and preferred term.  
Adverse events during the crossover portion that are related to KW-0761 will be summarized 
separately in the same manner as described above for subjects who are randomized to 
vorinostat arm and then crossed over to KW-0761 treatment.  Another summary of adverse 
events related to Vorinostat may be presented if necessary. 
A summary will be provided for the number and percentage of subjects with TEAEs related 
to KW-0761 by SOC and preferred term for all subjects exposed to KW-0761 and separately 
for subjects who are initially randomized to KW-0761 and for subjects who are crossed over 
to KW-0761 treatment. 
The number and percentage of subjects with TEAEs during the randomized treatment period 
will also be summarized for each treatment arm and in total by system organ class (SOC) and 
preferred term for the following subgroups:  Gender and Age (< 65 years vs ≥ 65 years). 
In addition to the summaries described above, exposure-adjusted incidence rate and 
exposure-adjusted event rate will be summarized for each treatment arm and in total by 
preferred term for the following special TEAEs (system organ class): 
• 
Infections and infestations,  
• 
Respiratory, thoracic and mediastinal disorders,  
• 
Renal and urinary disorders, 
• 
Musculoskelatal and connective tissue disorders. 
The exposure-adjusted incidence rate per patient-months of exposure will be calculated as 
(the number of patients with AEs/sum of days at risk for AEs) * 30.42 days/month; the 


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exposure-adjusted event rate per patient-months of exposure will be calculated as (the 
number of AEs/sum of days at risk for AEs) * 30.42 days/month. 
Listings will be provided for SAEs, grade III/IV/V AEs, and AEs leading to discontinuation 
of study drug and AEs leading to death. All adverse events will be listed by subject. 
6.12.2 
Clinical Laboratory Tests 
Local laboratories were used for this study.  Shift tables from baseline to the worst post-
baseline values during the randomized treatment period according to the NCI-CTCAE v4.0 
toxicity grade will be provided for selected chemistry parameters and hematology parameters. 
The following categories will be used: ≤ Grade II and ≥ Grade III. Both scheduled and 
unscheduled post-baseline values during the randomized treatment period will be considered.  
Additionally, the number and percentage of subjects with Grade ≥ III will be presented for 
the following hematology tests:  White Blood Cell Count (WBC), Hemoglobin, Platelet 
Count and Absolute Neutrophil Count (ANC). 
Laboratory data during the crossover portion will be summarized separately in the same 
manner. 
All clinical laboratory data will be listed by subject. Values outside the normal ranges from 
local laboratories will be flagged and grades will be displayed for selected parameters.  
Additionally, the laboratory values will display clinical significance based on investigator 
judgement. 
6.12.3 
Vital Signs 
Vital signs measurements including pulse rate, respiratory rate, temperature, systolic blood 
pressure, diastolic blood pressure, and body weight will be summarized descriptively (n, 
mean, standard deviation, median, minimum, and maximum).  Baseline and changes from 
baseline to end of treatment will be presented during the randomized treatment period by 
treatment arm.  Additionally the maximum and minimum post-treatment values during the 
randomized treatment period will be summarized by treatment arm. Vital signs during the 
crossover portion will be summarized separately in the same manner.  
All vital signs measurements will be listed by subject.  


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6.12.4 
12-Lead Electrocardiogram (ECG) 
The QTc intervals are to be determined using the Fridericia correction (QTcF) and the Bazett 
correction (QTcB). The QTcF and QTcB intervals of the ECG measurements and changes 
from baseline to end of treatment during the randomized treatment period will be summarized 
by treatment arm. The number and percentage of subjects with elevated QTcF or QTcB 
values (> 450 msec, > 480 msec, and > 500 msec) at baseline and end of treatment during the 
randomized treatment period will be presented by treatment arm. In addition, the number and 
percentage of subjects with QTcF or QTcB values that increase by > 30 msec and > 60 msec 
from baseline to end of treatment will also be presented by treatment arm.   
A shift table from baseline to the worst post-baseline values during the randomized treatment 
period will be provided for QTcF and QTcB intervals. The following categories will be used: 
≤ 450 msec, > 450 and ≤ 480 msec, > 480 and ≤ 500 msec, and > 500 msec. 
All ECG measurements and the overall interpretation will be listed by subject. Abnormal 
QTcF or QTcB values will be flagged in the listing. 
6.12.5 
Physical Examinations 
Physical examination dates will be listed by subject. Clinically significant findings are 
recorded as adverse events. 
6.12.6 
ECOG Performance Status 
ECOG performance status mean and mean change from baseline during the randomized 
treatment period will be tabulated by treatment arm.  
All ECOG performance status data will be listed by subject. 
6.13 Pharmacokinetics Analysis 
Pharmacokinetic (PK) analysis will be conducted using population-based methods. Details of 
the Pharmacokinetic analysis will be provided in a separate PK analysis plan. 
 The KW-0761 concentrations at each scheduled time point of collection will be tabulated for 
subjects in the KW-0761 arm and for subjects who are randomized to vorinostat and crossed 
over into the KW-0761 arm.  If serum KW-0761 concentration is below the lower limit of 
quantification (BLQ, <1.25 ng/mL), the concentration will be shown as ‘BLQ’ in the data 
listing, and the data will be considered to be 0 ng/mL when calculating descriptive statistics. 


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If the mean, minimum, median, or maximum is calculated to be below the lower limit of 
quantification, it will be shown as ‘BLQ’ in the summary table. If the mean is below the 
lower limit of quantification, standard deviation will be shown as ‘-‘ in the summary table.  
All KW-0761 concentration data will be listed by subject. 
6.14 Analysis of Immunogenicity Data  
Samples to detect anti-KW-0761 antibodies for the analysis of immunogenicity will be taken 
at baseline (Cycle 1, Day 1), Day 26-28 of Cycle 1, every 8 weeks thereafter, and at the end 
of treatment.   
Anti-KW-0761 antibody status (positive, negative, and inconclusive) will be tabulated at each 
scheduled time point and overall at post-baseline for subjects in the KW-0761 arm and 
separately for those subjects who are randomized to vorinostat but crossed over into the KW-
0761 arm. Anti KW-0761 antibody status will be determined using anti-KW-0761 antibody 
assay result and KW-0761 concentration value as outlined below:  
• 
Positive: When the sample is positive in both screening assay and confirmatory assay, 
the sample status is considered to be Positive. 
• 
Negative: When the sample is negative in screening assay and KW-0761 
concentration at the same time point is equal to or less than drug tolerance limit 
(16000 ng/mL), or when the sample is positive in screening assay and negative in 
confirmatory assay, the sample status is considered to be Negative. 
• 
Inconclusive: When the sample is negative in screening assay and KW-0761 
concentration at the same time point is above the drug tolerance limit (>16000 ng/mL), 
the sample status is considered to be Inconclusive. When the sample is negative in 
screening assay and KW-0761 concentration is not measured, the sample status is 
considered to be inconclusive. 
 
 


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Anti KW-0761 Antibody Status 
-decision tree- 
 
 
The number and percentage of subjects with a positive neutralizing antibody test result will 
also be presented for each scheduled time point and overall at post-baseline. For each subject, 
overall is defined as positive if at least one post-baseline neutralization test result is positive. 
Additionally, a summary of subjects with a positive overall assay at any time post-baseline 
and who experienced infusion reaction will be presented. 
All immunogenicity data will be listed by subject. 
6.15 Analysis of CCR4 and Other Biomarkers 
CCR4 expression results will be listed by subject.  
A separate analysis plan will be prepared to detail the CCR4 and other biomarker analyses. 
6.16 Other Data Considerations 
All other information recorded in the Case Report Form (CRF) (e.g., inclusion and exclusion 
criteria, natural ligands assessment, genetic determinants (i.e., Fc-gamma receptor 
polymorphisms), results of serum pregnancy test, etc.) will be listed by subject. 


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7 
REFERENCES 
1. International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, 
Statistical Principles for Clinical Trials (E9), 5 February 1998. 
2. International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, 
Structure and Content of Clinical Study Reports (E3), 30 November 1995.   
3. Olsen E, Whittaker S; Kim YH, Duvic M, Prince HM, Lessin HR, et al. Clinical 
Endpoints and Response Criteria in Mycosis Fungoides and Sézary Syndrome: a 
Consensus Statement of the International Society for Cutaneous Lymphomas (ISCL), 
the United States Cutaneous Lymphoma Consortium (USCLC) and the Cutaneous 
Lymphoma Task Force of the European Organization for Research and Treatment of 
Cancer. J Clin Oncol. 2011;29:2598-607. 
4. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. 
Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin 
Oncol. 1982;5(6):649-55 
5. ZOLINZA [package insert]. Whitehouse Station, NJ: Merck & Co.; 2011. 
6. Chren MM, Lasek RJ, Quinn LM, Mostow EN, Zyzanski SJ. Skindex, a quality-of-life 
measure for patients with skin disease: reliability, validity and responsiveness. J Invest 
Dermatol. 1996;Nov 107(5):707-13. 
7. Webster K, Cella D, and Yost K. The Functional Assessment of Chronic Illness 
Therapy (FACIT) Measurement System: Properties, Applications, and Interpretation. 
Health and Quality of Life Outcomes. 2003;1(79):1-7. 
8. Shaw JW, Johnson JA, and Joel Coon S. US Valuation of the EQ-5D Health States 
Development and Testing of the D1 Valuation Model. Medical Care. 
2005;43(3):203-20. 
9. Desai N, Poindexter G, Monthrope Y, Bendeck SE, Swerlick RA, Chen SC. A pilot 
quality of life instrument for pruritus. J Am Acad Dermatol. 2008;59(2):234-44. 
10. Santner TJ, Snell MK Small-sample confidence intervals for p1-p2 and p1/p2 in 2 × 2 
contingency tables. Journal of the American Statistical Association. 1980;75:386-94. 


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11. Nijsten Tamar EC, Sampogna F, Chren M, and Abeni DD.  Testing and Reducing 
Skindex-29 Using Rasch Analysis:  Skindex-17.  Journal of Investigative Dermatology.  
2006;126:1244-1250. 
12. Jonsson L, Sandin R, Ekman M, Ramsberg J, Charbonneau C, Huang X, Jonsson B, 
Weinstein M, Drummond M. Analyzing Overall Survival in Randomized Controlled 
Trials with Crossover and Implications for Economic Evaluation. Value in Health. 
2014: 17: 707-713. 
 


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8 
PROGRAMMING CONSIDERATIONS 
All tables, data listings, figures (TLFs), and statistical analyses will be generated using SAS® 
Version 9.3 or higher. Computer-generated table output will adhere to the following 
specifications. 
8.1 
Table, Listing, and Figure Format 
8.1.1 
General 
1) All TLFs will be produced in landscape format. 
2) All TLFs will be produced using the Courier New font, size 8. 
3) The data displays for all TLFs will have a 1.5-inch binding margin on top of a 
landscape oriented page and a minimum 1-inch margin on the other 3 sides. 
4) Headers and footers for figures will be in Courier New font, size 8. 
5) Legends will be used for all figures with more than 1 variable, group, or item 
displayed. 
6) TLFs will be in black and white (no color). 
7) Specialized text styles, such as bolding, italics, borders, shading, and superscripted 
and subscripted text, will not be used in the TLFs. On some occasions, superscripts 1, 
2, or 3 may be used (see below). 
8) Only standard keyboard characters will be used in the TLFs. Special characters, such 
as non-printable control characters, printer-specific, or font-specific characters, will 
not be used. Hexadecimal-derived characters will be used, where possible, if they are 
appropriate to help display math symbols (e.g., μ). Certain superscripts (e.g., cm2) will 
be employed on a case-by-case basis. 
9) Mixed case will be used for all titles, footnotes, column headers, and programmer-
supplied formats. 
8.1.2 
Headers 
1) All output should have the following header at the top of the page: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Date: DD-MMM-YYYY 
Study: Protocol 0761-010 
Page n of N 
All output should have a date (date output was generated) and page number. TLFs should be 
internally paginated in relation to the total length (i.e., the page number should appear 
sequentially as page n of N, where N is the total number of pages in the table). 


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8.1.3 
Display Titles 
1) Each TLF should be identified by a numeral, and the designation (i.e., Table 1) should 
be centered above the title. A decimal system (x.y and x.y.z) should be used to 
identify TLFs with related contents. The title is centered in initial capital characters. 
The analysis set should be identified on the line immediately following the title. The 
title and table designation are single spaced. A solid line spanning the margins will 
separate the display titles from the column headers. There will be 1 blank line 
between the last title and the solid line. 
Table x.y.z 
First Line of Title 
Second Line of Title if Needed 
Safety Analysis Set 
8.1.4 
Column Headers 
1) Column headings should be displayed immediately below the solid line described 
above in initial upper-case characters. The variable (or characteristic) column will be 
on the far left followed by the treatment group columns, total column (if applicable), 
and p-value column (if applicable). 
2) For numeric variables, include “unit” in column or row heading when appropriate. 
3) Analysis set sizes will be presented for each treatment group in the column heading as 
(N=xx) (or in the row headings if applicable). This is distinct from the ‘n’ used for the 
descriptive statistics representing the number of subjects in the analysis set. 
4) The order of treatments in the mock-up tables and listings will be: Vorinostat and 
KW-0761, and Total (if applicable).   
8.1.5 
Body of the Data Display  
1) Listings will be sorted for presentation in order of treatment groups as above, subject 
number, collection day, and collection time. 
2) If the categories of a parameter are ordered, then all categories between the maximum 
and minimum category should be presented in the table, even if n=0 for all treatment 
groups in a given category that is between the minimum and maximum level for that 
parameter. For example, the frequency distribution for symptom severity would 
appear as: 
Severity Rating 
n 
severe 
0 
moderate 
8 
mild 
3 
Where percentages are presented in these tables, any counts of 0 will be presented as 
0 and not as 0 (0%). 


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3) If the categories are not ordered (e.g., Medical History, Reasons for Discontinuation 
from the Study, etc.), then only those categories for which there is at least 1 subject 
represented in 1 or more groups should be included. 
4) An Unknown or Missing category should be added to any parameter for which 
information is not available for 1 or more subjects. 
5) Unless otherwise specified, the estimated mean and median for a set of values should 
be printed out to 1 more significant digit than the original values, and standard 
deviations should be printed out to 2 more significant digits than the original values. 
The minimum and maximum should report the same significant digits as the original 
values. For example, for systolic blood pressure: 
N 
XX 
Mean 
XXX.X 
Std Dev 
X.XX 
Median 
XXX.X 
Minimum 
XXX 
Maximum 
XXX 
6) Data in columns of a table should be formatted as follows: 
• 
alphanumeric values are left-justified; 
• 
whole numbers (e.g., counts) are right-justified; and 
• 
numbers containing fractional portions are decimal aligned. 
8) Percentage values should be printed with 1 digit to the right of the decimal point in 
parentheses 1 space after the count (e.g., 7 (12.8), 13 (5.4)). Less-than-signs “<0.1” 
should be printed when values are >0.0 and <0.1 (not 0.0). Unless otherwise noted, 
for all percentages, the number of subjects in the analysis set for the treatment group 
who have an observation will be the denominator. 
9) Tabular display of data for concomitant medications and all tabular displays of 
adverse event data should be presented by the body system, drug class, or SOC with 
the highest occurrence in the total column in decreasing order. Within the body 
system, drug class and SOC, drugs (by ATC1 code) and adverse events (by preferred 
term) should be displayed in decreasing order. If incidence for more than 1 term is 
identical, they should then be sorted alphabetically. 
10) Missing data should be represented on subject listings as either a hyphen (“-”) with a 
corresponding footnote (“ - = unknown or not evaluated”), or as “N/A”, with the 
footnote “N/A = not applicable”, whichever is appropriate. Missing descriptive 
statistics due to non-estimability should be reported as “-”. 
11) Date should be printed in SAS® YYMMDD10.format (“YYYY-MM-DD”: 2000-07-
01). Missing portions of dates will not be presented on subject listings (2000-07). 
Dates that are missing because they are not applicable for the subject are output as 
“N/A”, unless otherwise specified. 


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12) All observed time values must be presented using a 24-hour clock HH:MM:SS format 
(e.g., 01:35:45, or 11:26). Time will only be reported if it was measured as part of the 
study. 
8.1.6 
Footnotes 
1) A solid line spanning the margins will separate the body of the data display from the 
footnotes.  
2) All footnotes will be left justified with single-line spacing immediately below the 
solid line underneath the data display. 
3) Footnotes should always begin with “Note:” if an informational footnote, or asterisks 
and other non-numeric symbols if an annotated footnote. Each new footnote starts on 
a new line. 
4) Footnotes will be present on the page where they are first referenced and thereafter on 
each page of the table, unless the footnote is specific only to certain pages. Subject 
specific footnotes should be avoided. 
5) Footnotes will be used sparingly and must add value to the table, figure, or data listing. 
If more than 4 footnotes are planned, then a cover page may be used to display 
footnotes, and only those essential to comprehension of the data will be repeated on 
each page. Footnotes should not repeat definitions already provided in the SAP. 
6) The last line of the footnote section will be a standard source line that indicates the 
data source called in by the program, the name of the program used to produce the 
data display, and the listing source (i.e., ‘Data source: xyzabc.sas7bdat    Program 
source: myprogram.sas    Listing source: 16.x.y.z’). 
8.2 
Data-Handling Rules 
This section describes naming conventions and rules for calculations that would be common 
to all applicable tables. Some rules specific to a table can be found in the relevant mock-ups. 
8.2.1 
Visits 
1) Relative Study Day: The first day of treatment is Day 1. A minus (-) sign indicates 
days prior to the start of treatment (e.g., Day -5 represents 5 days before start of 
therapy. There is no Day 0.). The relative study day for a specific visit is calculated as 
(Visit Date - Date of First Dose +1). 
2) Baseline: For all study variables, baseline is defined as the last measurement obtained 
prior to the first dose of the study medication. 
8.2.2 
Demographics and Baseline Characteristics 
1) Age = (Screening visit date - date of birth + 1) / 365.25 and truncated to complete 
years. 


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2) BSA (m²) = ( [Height(cm) x Weight(kg) ]/ 3600 )½         
3) BMI (kg/m²) = Weight(kg) /[Height(m)]2         
8.2.3 
Prior and Concomitant Medications 
1) Prior and concomitant medications will be coded and classified using the WHO Drug 
Dictionary (September 2012). The specific dictionary version will be provided in the 
actual tables/listings. 
2) Counting rules for prior and concomitant medications: Prior medications include 
medications that were taken within 30 days prior to study entry and stopped prior to 
start of randomized treatment. Concomitant medications during randomized treatment 
period include medications that started at any time and were taken at any time after 
the start of randomized treatment until the end of the entire randomized treatment 
period. Concomitant medications during the crossover portion include medications 
that started at any time and were taken at any time after the start of KW-0761 during 
the crossover portion until the end of the entire treatment period. 
3) Medications missing both start and stop dates, or having a start date prior to the last 
dose of study drug and missing the stop date, or having a stop date after the start of 
study drug and missing the start date, will be counted as concomitant. When partial 
dates are present in the data, both a partial start date and/or a partial stop date will be 
evaluated to determine whether it can be conclusively established that the medication 
either ended prior to the start of study drug or started after the end of study drug. If 
the above cannot be conclusively established based on the partial and/or present dates, 
then the medication will be counted as concomitant. 
8.2.4 
Safety 
1) If multiple results (e.g., lab test results) are reported at a study visit, then the most 
deviant lab result reported for that visit will be used in that visit summary. 
2) Adverse events will be coded and classified using the MedDRA dictionary. The 
specific dictionary version will be provided in the actual tables/listings. 
3) Counting rules for adverse events: Adverse events with missing start dates, but with 
stop dates either overlapping into the treatment period or missing, will be counted as 
treatment-emergent, taking the worst-case approach. Special care will be taken 
regarding partial dates with similar logic to that of the prior/concomitant medications 
applied. 
4) For purposes of flagging individual subject data listings, laboratory abnormalities are 
defined as values above or below the normal range.  


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8.2.5 
SAS® Procedures 
This section provides sample SAS® code to illustrate statistical tests specified in the statistical 
methods section. All computer output from SAS® statistical procedures serving as a basis for 
extracted results (e.g., LIFETEST) will be retained for quality control procedures and will be 
included in CSR appendices. 
1) Stratified Log Rank test for PFS between treatment: 
proc lifetest method=KM; 
time PFS*censor(1); 
strata type stage region/group=trt; 
run;  
2) Hazard ratio from Cox proportional hazard model for PFS: 
proc phreg; 
model PFS*censor(1)=trt type stage region/risklimits ties=efron; 
run;  
3) CMH test for ORR between treatment: 
proc freq; 
tables type*stage*region*trt*resp/cmh; 
run;  
4) Exact 95% confidence interval on ORR and exact 95% unconditional confidence 
interval for the risk difference: 
proc freq; 
tables trt*resp; 
exact riskdiff; 
run;  
5) ANCOVA for change in QoL score between treatment: 
proc mixed; 
class trt type stage region timept usubjid; 
model QoL_chng = trt type stage region base_QoL timept  
 trt*timept/solution; 
 
 
repeated timept / subject=usubjid type=un; 
lsmeans trt/pdiff cl; 
run;  
6) Wilcoxon Rank Sum test for change in Likert Scale score between treatment: 
proc npar1way wilcoxon hl; 
class trt; 
var QoL_chng; 
run;  
 


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9 
LIST OF TABLES AND FIGURES 
Disposition, Demographic, Baseline Characteristics, Concomitant Medications, and 
Exposure and Dosing Status 
Table 14.1.1.1 
Subject Disposition – Intent-to-Treat Set 
Table 14.1.1.2 
Subject Disposition – Crossover Portion – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.1.2.1 
Demographic and Baseline Disease Characteristics – Intent-to-Treat Set 
Table 14.1.2.2 
Demographic and Baseline Disease Characteristics – Safety Analysis Set 
Table 14.1.2.3 
Demographic and Baseline Disease Characteristics – Efficacy Evaluable Set 
Table 14.1.3 
Summary of Concomitant Medications During Randomized Treatment Period - 
Number (%) of Subjects – Safety Analysis Set 
Table 14.1.4 
Summary of Extent of Exposure to Randomized Study Drug – Safety Analysis Set 
Table 14.1.5 
Summary of Study Drug Dosing Status During Randomized Treatment Period – Safety 
Analysis Set 
Table 14.1.6 
Summary of Extent of Exposure to KW-0761 During Crossover Portion – Safety 
Analysis Set – Subjects Who Are Randomized to Vorinostat and Crossed Over to 
KW-0761 
Table 14.1.7 
Summary of KW-0761 Dosing Status During Crossover Portion – Safety Analysis 
Set – Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
Efficacy Data 
Table 14.2.1.1 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment – 
Intent-to-Treat Set 
Table 14.2.1.2 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment – 
Sensitivity Analysis 1 – Intent-to-Treat Set 
Table 14.2.1.3 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment – 
Sensitivity Analysis 2 – Intent-to-Treat Set 
Table 14.2.1.4 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment – 
Worst Case Sensitivity Analysis – Sensitivity Analysis 3 – Intent-to-Treat Set 
Table 14.2.1.5 
Multivariate Analysis of Progression-Free Survival (PFS) Based on Investigator’s 
Assessment – Intent-to-Treat Set 
Table 14.2.1.6.1 
Summary of Progression-Free Survival (PFS) – Efficacy Evaluable Set 
Table 14.2.1.6.2 
Summary of Progression-Free Survival (PFS) – Intent-to-Treat Set – Any Exposure 
to KW-0761 vs. Vorinostat Only 
Table 14.2.1.7.1 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment – 
Intent-to-Treat Set – By Pre-defined Subgroups 
Table 14.2.1.7.2 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment – 
Efficacy Evaluable Set – By Pre-defined Subgroups 
Table 14.2.1.8 
Summary of Progression-Free Survival (PFS) Based on Independent Review – 
Intent-to-Treat Set 
Table 14.2.2.1.1 
Summary of Confirmed Overall Response Rate (ORR) During Randomized 
Treatment Period – Intent-to-Treat Set 


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Table 14.2.2.1.2 
Logistic Regression Analysis of Confirmed Overall Response Rate (ORR) Based on 
Investigator’s Assessment – Intent-to-Treat Set 
Table 14.2.2.1.3 
Summary of Confirmed and Unconfirmed Overall Response Rate (ORR) During 
Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.2.1.4 
Summary of Confirmed Overall Response Rate (ORR) During Randomized 
Treatment Period by Disease Type – Intent-to-Treat Set 
Table 14.2.2.1.5 
Summary of Confirmed and Unconfirmed Overall Response Rate (ORR) During 
Randomized Treatment Period by Disease Type – Intent-to-Treat Set 
Table 14.2.2.2.1 
Summary of Best Overall Response During Randomized Treatment Period – Intent-
to-Treat Set  
Table 14.2.2.2.2 
Summary of Best Overall Response During Randomized Treatment Period by 
Disease Type – Intent-to-Treat Set  
Table 14.2.2.3.1 
Summary of Confirmed Overall Response Rate (ORR) During Randomized 
Treatment Period – Efficacy Evaluable Set  
Table 14.2.2.3.2 
Summary of Confirmed and Unconfirmed Overall Response Rate (ORR) During 
Randomized Treatment Period – Efficacy Evaluable Set  
Table 14.2.2.3.3 
Summary of Confirmed Overall Response Rate (ORR) During Randomized 
Treatment Period  by Disease Type – Efficacy Evaluable Set 
Table 14.2.2.3.4 
Summary of Confirmed and Unconfirmed Overall Response Rate (ORR) During 
Randomized Treatment Period  by Disease Type – Efficacy Evaluable Set 
Table 14.2.2.4.1 
Summary of Best Overall Response During Randomized Treatment Period – 
Efficacy Evaluable Set 
Table 14.2.2.4.2 
Summary of Best Overall Response During Randomized Treatment Period by 
Disease Type – Efficacy Evaluable Set 
Table 14.2.2.5 
 
Summary of Overall Response During Randomized Treatment Period by Selected 
Time Points, Investigator’s Assessment - Intent-to-Treat Set 
Table 14.2.2.6.1 
Summary of Duration of Response During Randomized Treatment Period – Intent-
to-Treat Set  
Table 14.2.2.6.2 
Summary of Duration of Response During Randomized Treatment Period by 
Disease Type – Intent-to-Treat Set  
Table 14.2.2.6.3 
Summary of Duration of Response During Randomized Treatment Period – Efficacy 
Evaluable Set  
Table 14.2.2.6.4 
Summary of Duration of Response During Randomized Treatment Period by 
Disease Type – Efficacy Evaluable Set  
Table 14.2.2.7.1 
Summary of Time to Response During Randomized Treatment Period – Intent-to-
Treat Set 
Table 14.2.2.7.2 
Summary of Time to Response During Randomized Treatment Period by Disease 
Type – Intent-to-Treat Set 
Table 14.2.2.7.3 
Summary of Time to Response During Randomized Treatment Period – Efficacy 
Evaluable Set 
Table 14.2.2.7.4 
Summary of Time to Response During Randomized Treatment Period by Disease 
Type – Efficacy Evaluable Set 
Table 14.2.2.8.1 
Summary of Best Overall Response Based on Investigator’s Assessment During 
Crossover Portion – Intent-to-Treat Set – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.2.2.8.2 
Summary of Best Overall Response Based on Investigator’s Assessment During 


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Crossover Portion by Disease Type – Intent-to-Treat Set – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Table 14.2.2.8.3 
Summary of Best Overall Response Based on Investigator’s Assessment During 
Crossover Portion – Efficacy Evaluable Set – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.2.2.8.4 
Summary of Best Overall Response Based on Investigator’s Assessment During 
Crossover Portion by Disease Type – Efficacy Evaluable Set – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Table 14.2.2.9 
Concordance Between Independent Review and Investigator’s Assessment for Best 
Overall Response During Randomized Treatment Period – Intent-to-Treat Set  
Table 14.2.3.1 
Summary of Skindex-29 Score and Change from Baseline by Visit During 
Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.3.2 
Analysis of Change in Skindex-29 Score from Baseline During Randomized 
Treatment Period – Intent-to-Treat Set 
Table 14.2.3.3 
Summary of Skindex-29 Score and Change from Baseline by Visit During 
Randomized Treatment Period – Efficacy Evaluable Set 
Table 14.2.3.4 
Analysis of Change in Skindex-29 Score from Baseline During Randomized 
Treatment Period – Efficacy Evaluable Set 
Table 14.2.3.5 
Summary of Skindex-29 Score and Change from Baseline by Visit During 
Crossover Portion – Intent-to-Treat Set – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.2.4.1 
Summary of FACT-G Total Score and Change from Baseline by Visit During 
Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.4.2 
Analysis of Change in FACT-G Total Score from Baseline  During Randomized 
Treatment Period – Intent-to-Treat Set 
Table 14.2.4.3 
Summary of FACT-G Total Score and Change from Baseline by Visit During 
Randomized Treatment Period – Efficacy Evaluable Set 
Table 14.2.4.4 
Analysis of Change in FACT-G Total Score from Baseline During Randomized 
Treatment Period – Efficacy Evaluable Set 
Table 14.2.4.5 
Summary of FACT-G Total Score and Change from Baseline by Visit During 
Crossover Portion – Intent-to-Treat Set – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.2.4.6 
Summary of FACT-G Physical Well-Being Score and Change from Baseline by 
Visit During Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.4.7 
Summary of FACT-G Social Well-Being Score and Change from Baseline by Visit 
During Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.4.8 
Summary of FACT-G Emotional Well-Being Score and Change from Baseline by 
Visit During Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.4.9 
Summary of FACT-G Functional Well-Being Score and Change from Baseline by 
Visit During Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.5.1 
Summary of EQ-5D-3L Index Score and Change from Baseline by Visit During 
Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.5.2 
Analysis of Change in EQ-5D-3L Index Score from Baseline During Randomized 
Treatment Period – Intent-to-Treat Set 
Table 14.2.5.3 
Summary of EQ-5D-3L Index Score and Change from Baseline by Visit During 
Randomized Treatment Period – Efficacy Evaluable Set 


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Table 14.2.5.4 
Analysis of Change in EQ-5D-3L Index Score from Baseline During Randomized 
Treatment Period – Efficacy Evaluable Set 
Table 14.2.5.5 
Summary of EQ-5D-3L Index Score and Change from Baseline by Visit During 
Crossover Portion – Intent-to-Treat Set – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.2.5.6 
Summary of EQ-5D-3L by Dimension and by Visit During Randomized Treatment 
Period – Number (%) of Subjects – Intent-to-Treat Set 
Table 14.2.5.7 
Summary of EQ-5D-3L by Dimension and by Visit During Randomized Treatment 
Period – Number (%) of Subjects – Efficacy Evaluable Set 
Table 14.2.5.8 
Summary of EQ-5D-3L by Dimension and by Visit During Crossover Portion – 
Number (%) of Subjects – Intent-to-Treat Set – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.2.6.1 
Summary of EQ-5D-3L VAS Score and Change from Baseline by Visit During 
Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.6.2 
Analysis of Change in EQ-5D-3L VAS Score from Baseline During Randomized 
Treatment Period – Intent-to-Treat Set 
Table 14.2.6.3 
Summary of EQ-5D-3L VAS Score and Change from Baseline by Visit – Efficacy 
Evaluable Set 
Table 14.2.6.4 
Analysis of Change in EQ-5D-3L VAS Score from Baseline During Randomized 
Treatment Period – Efficacy Evaluable Set 
Table 14.2.6.5 
Summary of EQ-5D-3L VAS Score and Change from Baseline by Visit During 
Crossover Portion – Intent-to-Treat Set – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.2.7.1 
Summary of Pruritus Evaluation Itchy Quality of Life Score and Change from 
Baseline by Visit During Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.7.2 
Analysis of Change in Pruritus Evaluation Itchy Quality of Life Score from Baseline 
During Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.7.3 
Summary of Pruritus Evaluation Itchy Quality of Life Score and Change from 
Baseline by Visit During Randomized Treatment Period – Efficacy Evaluable Set 
Table 14.2.7.4 
Analysis of Change in Pruritus Evaluation Itchy Quality of Life Score from Baseline 
During Randomized Treatment Period – Efficacy Evaluable Set 
Table 14.2.7.5 
Summary of Pruritus Evaluation Itchy Quality of Life Score and Change from 
Baseline by Visit During Crossover Portion – Intent-to-Treat Set – Subjects Who 
Are Randomized to Vorinostat and Crossed Over to KW-0761 
Table 14.2.8.1 
Summary of Pruritus Evaluation Likert Scale Score and Change from Baseline by 
Visit During Randomized Treatment Period – Intent-to-Treat Set 
Table 14.2.8.2 
Analysis of Change in Pruritus Evaluation Likert Scale Score from Baseline During 
Randomized Treatment Period – Intent-to-Treat Set  
Table 14.2.8.3 
Summary of Pruritus Evaluation Likert Scale Score and Change from Baseline by 
Visit During Randomized Treatment Period – Efficacy Evaluable Set 
Table 14.2.8.4 
Analysis of Change in Pruritus Evaluation Likert Scale Score from Baseline 
Assessment During Randomized Treatment Period – Efficacy Evaluable Set 
Table 14.2.8.5 
Summary of Pruritus Evaluation Likert Scale Score and Change from Baseline by 
Visit During Crossover Portion – Intent-to-Treat Set – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Table 14.2.9.1 
Summary of Overall Survival (OS) – Intent-to-Treat Set 


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Table 14.2.9.2 
Overall Survival (OS) Analysis Using RPSFT Model – Intent-to-Treat Set 
Table 14.2.9.3 
Overall Survival (OS) Analysis Using IPCW Model – Intent-to-Treat Set 
Table 14.2.10 
Summary of Time to Treatment Failure (TTF) – Intent-to-Treat Set 
Safety Data 
Table 14.3.1.1 
Overview of Adverse Events During Randomized Treatment Period – Safety Analysis 
Set 
Table 14.3.1.2 
Number (%) of Subjects with Treatment-Emergent Adverse Events During 
Randomized Treatment Period – By System Organ Class and Preferred Term – Safety 
Analysis Set 
Table 14.3.1.3 
Number (%) of Subjects with Drug-Related Treatment-Emergent Adverse Events 
During Randomized Treatment Period – By System Organ Class and Preferred Term – 
Safety Analysis Set 
Table 14.3.1.4 
Number (%) of Subjects with Treatment-Emergent Adverse (TEAEs) Events During 
Randomized Treatment Period – By System Organ Class, Preferred Term, and Highest 
CTCAE Grade – Safety Analysis Set 
Table 14.3.1.5 
Number (%) of Subjects with Drug-Related Treatment-Emergent Adverse Events 
(TEAEs) During Randomized Treatment Period – By System Organ Class, Preferred 
Term, and Highest CTCAE Grade – Safety Analysis Set 
Table 14.3.1.6 
Number (%) of Subjects with Grade III/IV/V Treatment-Emergent Adverse Events 
(TEAEs) During Randomized Treatment Period – By System Organ Class and 
Preferred Term – Safety Analysis Set 
Table 14.3.1.7 
Number (%) of Subjects with Drug-Related Grade III/IV/V Treatment-Emergent 
Adverse Events (TEAEs) During Randomized Treatment Period – By System Organ 
Class and Preferred Term – Safety Analysis Set 
Table 14.3.1.8 
Number (%) of Subjects with Treatment-Emergent Serious Adverse Events During 
Randomized Treatment Period – By System Organ Class and Preferred Term – Safety 
Analysis Set   
Table 14.3.1.9 
Number (%) of Subjects with Drug-Related Treatment-Emergent Serious Adverse 
Events During Randomized Treatment Period – By System Organ Class and Preferred 
Term – Safety Analysis Set 
Table 14.3.1.10 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) Leading 
to Discontinuation During Randomized Treatment Period – By System Organ Class 
and Preferred Term – Safety Analysis Set 
Table 14.3.1.11 
Number (%) of Subjects with Drug-Related Treatment-Emergent Adverse Events 
(TEAEs) Leading to Discontinuation During Randomized Treatment Period – By 
System Organ Class and Preferred Term – Safety Analysis Set 
Table 14.3.1.12 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) During 
Randomized Treatment Period – By Gender, System Organ Class and Preferred Term 
– Safety Analysis Set 
Table 14.3.1.13 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) During 
Randomized Treatment Period – By Age Group, System Organ Class and Preferred 
Term – Safety Analysis Set 
Table 14.3.2.1 
Overview of Adverse Events During Crossover Portion – Safety Analysis Set – 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 


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Table 14.3.2.2 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) Related 
to KW-0761 During Crossover Portion – By System Organ Class and Preferred Term – 
Safety Analysis Set – Subjects Who Are Randomized to Vorinostat and Crossed Over 
to KW-0761 
Table 14.3.2.3 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) Related 
to KW-0761 During Crossover Portion – By System Organ Class, Preferred Term, and 
Highest CTCAE Grade – Safety Analysis Set – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.3.2.4 
Number (%) of Subjects with Grade III/IV/V Treatment-Emergent Adverse Events 
(TEAEs) Related to KW-0761 During Crossover Portion – By System Organ Class 
and Preferred Term – Safety Analysis Set – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.3.2.5 
Number (%) of Subjects with Treatment-Emergent Serious Adverse Events Related to 
KW-0761 During Crossover Portion – By System Organ Class and Preferred Term – 
Safety Analysis Set – Subjects Who Are Randomized to Vorinostat and Crossed Over 
to KW-0761 
Table 14.3.2.6 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) Related 
to KW-0761 Leading to Discontinuation During Crossover Portion – By System Organ 
Class and Preferred Term – Safety Analysis Set – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Table 14.3.3.1 
Number(%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) Related to 
KW-0761 for Subjects Exposed to KW-0761 - By System Organ Class and Preferred 
Term - Safety Analysis Set 
Table 14.3.3.2 
Exposure-Adjusted Incidence Rate of Infections and Infestations During Randomized 
Treatment Period - By Preferred Term - Safety Analysis Set 
Table 14.3.3.3 
Exposure-Adjusted Event Rate of Infections and Infestations During Randomized 
Treatment Period - By Preferred Term - Safety Analysis Set 
Table 14.3.3.4 
Exposure-Adjusted Incidence Rate of Respiratory, Thoracic and Mediastinal Disorders 
During Randomized Treatment Period - By Preferred Term - Safety Analysis Set 
Table 14.3.3.5 
Exposure-Adjusted Event Rate of Respiratory, Thoracic and Mediastinal Disorders 
During Randomized Treatment Period - By Preferred Term - Safety Analysis Set 
Table 14.3.3.6 
Exposure-Adjusted Incidence Rate of Renal and Urinary Disorders During 
Randomized Treatment Period - By Preferred Term - Safety Analysis Set 
Table 14.3.3.7 
Exposure-Adjusted Event Rate of Renal and Urinary Disorders During Randomized 
Treatment Period - By Preferred Term - Safety Analysis Set 
Table 14.3.3.8 
Exposure-Adjusted Incidence Rate of Musculoskeletal and Connective Tissue 
Disorders During Randomized Treatment Period - By Preferred Term - Safety 
Analysis Set 
Table 14.3.3.9 
Exposure-Adjusted Event Rate of Musculoskeletal and Connective Tissue Disorders 
During Randomized Treatment Period - By Preferred Term - Safety Analysis Set 
Table 14.3.4.1 
Shift Table for Selected Laboratory Parameters During Randomized Treatment Period 
– Serum Chemistry – Safety Analysis Set 
Table 14.3.4.2 
Shift Table for Selected Laboratory Parameters During Randomized Treatment Period 
– Hematology  – Safety Analysis Set 
Table 14.3.4.3 
Shift Table for Selected Laboratory Parameters During Crossover Portion – Serum 
Chemistry  – Safety Analysis Set  – Subjects Who Are Randomized to Vorinostat and 


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Crossed Over to KW-0761 
Table 14.3.4.4 
Shift Table for Selected Laboratory Parameters During Crossover Portion – 
Hematology  – Safety Analysis Set  – Subjects Who Are Randomized to Vorinostat 
and Crossed Over to KW-0761 
Table 14.3.4.5 
Number (%) of Subjects with Grade >=III  Laboratory Values for Selected 
Hematology Parameters – Safety Analysis Set   
Table 14.3.5.1 
Summary of Vital Signs and Change from Baseline During Randomized Treatment 
Period – Safety Analysis Set 
Table 14.3.5.2 
Summary of Vital Signs and Change from Baseline During Crossover Portion – Safety 
Analysis Set – Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-
0761 
Table 14.3.6.1 
Summary of QTcB and QTcF and Change from Baseline During Randomized 
Treatment Period – Safety Analysis Set 
Table 14.3.6.2 
Number (%) of Subjects with Abnormal QTcB and QTcF During Randomized 
Treatment Period – Safety Analysis Set 
Table 14.3.6.3 
Shift Table for QTcB and QTcF (msec) from Baseline During Randomized Treatment 
Period – Safety Analysis Set 
Table 14.3.7 
ECOG Performance Status Mean and Mean Change from Baseline During 
Randomized Treatment Period by Selected Visits – Safety Analysis Set 
Biomarker, Immunogenicity, and Pharmacokinetic Data 
Table 14.3.8.1 
Anti-KW-0761 Antibody Response – Safety Analysis Set (Subjects Exposed to KW-
0761) 
Table 14.3.8.2 
Summary of Positive Anti-KW-0761 Antibody Response at Post-Baseline and Infusion 
Reaction – Safety Analysis Set (Subjects Exposed to KW-0761) 
Table 14.3.9 
Summary of Pharmacokinetic Concentrations of KW-0761 (ng/mL) – PK Analysis Set 
Figures 
Figure 14.2.1 
Plot of Kaplan-Meier Curve of Progression-Free Survival by Investigator’s 
Assessment – Intent-to-Treat Set 
Figure 14.2.2 
Plot of Kaplan-Meier Curve of Progression-Free Survival by Investigator’s 
Assessment – Efficacy Evaluable Set  
Figure 14.2.3 
 
Plot of Kaplan-Meier Curve of Progression-Free Survival by Independent Review – 
Intent-to-Treat Set 
Figure 14.2.4 
Plot of Kaplan-Meier Curve of Progression-Free Survival by Independent Review – 
Efficacy Evaluable Set  
Figure 14.2.5 
Forest Plot of Hazard Ratios for Progression-Free Survival Based on Investigator’s 
Assessment by Pre-defined Subgroups – Intent-to-Treat Set 
Figure 14.2.6 
Forest Plot of Hazard Ratios for Progression-Free Survival Based on Investigator’s 
Assessment by Pre-defined Subgroups – Efficacy Evaluable Set  
Figure 14.2.7.1 
Plot of Kaplan-Meier Curve of Overall Survival – Intent-to-Treat Set 
Figure 14.2.7.2 
Plot of Kaplan-Meier Curve of Time to Treatment Failure – Intent-to-Treat Set 
Figure 14.2.8 
Mean (±SE) Skindex-29 Score During Randomized Treatment Period – Intent-to-Treat 
Set 
Figure 14.2.9 
Mean (±SE) Change in Skindex-29 Score from Baseline During Randomized 


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Treatment Period – Intent-to-Treat Set 
Figure 14.2.10 
Mean (±SE) Skindex-29 Score During Randomized Treatment Period – Efficacy 
Evaluable Set 
Figure 14.2.11 
Mean (±SE) Change in Skindex-29 Score from Baseline During Randomized 
Treatment Period – Efficacy Evaluable Set 
Figure 14.2.12 
Mean (±SE) FACT-G Total Score During Randomized Treatment Period – Intent-to-
Treat Set 
Figure 14.2.13 
Mean (±SE) Change in FACT-G Total Score from Baseline During Randomized 
Treatment Period – Intent-to-Treat Set 
Figure 14.2.14 
Mean (±SE) FACT-G Total Score During Randomized Treatment Period – Efficacy 
Evaluable Set 
Figure 14.2.15 
Mean (±SE) Change in FACT-G Total Score from Baseline During Randomized 
Treatment Period – Efficacy Evaluable Set 
Figure 14.2.16 
Mean (±SE) EQ-5D-3L Index Score During Randomized Treatment Period – Intent-
to-Treat Set 
Figure 14.2.17 
Mean (±SE) Change EQ-5D-3L Index Score from Baseline During Randomized 
Treatment Period – Intent-to-Treat Set 
Figure 14.2.18 
Mean (±SE) EQ-5D-3L Index Score During Randomized Treatment Period – Efficacy 
Evaluable Set 
Figure 14.2.19 
Mean (±SE) Change in EQ-5D-3L Index Score from Baseline During Randomized 
Treatment Period – Efficacy Evaluable Set 
Figure 14.2.20 
Mean (±SE) Pruritus Evaluation Itchy Quality of Life Score During Randomized 
Treatment Period –Intent-to-Treat Set 
Figure 14.2.21 
Mean (±SE) Change in Pruritus Evaluation Itchy Quality of Life Score from Baseline 
During Randomized Treatment Period – Intent-to-Treat Set 
Figure 14.2.22 
Mean (±SE) Pruritus Evaluation Itchy Quality of Life Score During Randomized 
Treatment Period – Efficacy Evaluable Set 
Figure 14.2.23 
Mean (±SE) Change in Pruritus Evaluation Itchy Quality of Life Score from Baseline 
During Randomized Treatment Period – Efficacy Evaluable Set 
Figure 14.2.24 
Mean (±SE) Pruritus Evaluation Likert Scale Score During Randomized Treatment 
Period –Intent-to-Treat Set 
Figure 14.2.25 
Mean (±SE) Change in Pruritus Evaluation Likert Scale Score from Baseline During 
Randomized Treatment Period – Intent-to-Treat Set 
Figure 14.2.26 
Mean (±SE) Pruritis Likert Scale Pruritus Evaluation Likert Scale Score During 
Randomized Treatment Period – Efficacy Evaluable Set 
Figure 14.2.27 
Mean (±SE) Change in Pruritis Likert Scale Pruritus Evaluation Likert Scale Score 
from Baseline During Randomized Treatment Period – Efficacy Evaluable Set 
 


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10 
LIST OF LISTINGS 
Listing 16.2.1.1 
Disposition - End of Treatment 
Listing 16.2.1.2 
Subjects Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.1.3 
Disposition - End of Study  
Listing 16.2.2.1 
Protocol Deviations 
Listing 16.2.2.2 
Inclusion/Exclusion Criteria  
Listing 16.2.3 
Analysis Population  
Listing 16.2.4.1 
Demographics  
Listing 16.2.4.2 
Current CTCL History  
Listing 16.2.4.3 
Medical/Surgical History 
Listing 16.2.4.4 
Prior CTCL Therapy 
Listing 16.2.4.5 
Prior Radiotherapy 
Listing 16.2.4.6 
Prior Medications 
Listing 16.2.4.7 
Concomitant Medication During Randomized Treatment Period 
Listing 16.2.4.8 
Concomitant Medication During Crossover Portion – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.4.9 
Pruritus Medications During the Study 
Listing 16.2.5.1 
KW-0761 Administration During Randomized Treatment Period 
Listing 16.2.5.2 
KW-0761 Administration During Crossover Portion – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.5.3 
Vorinostat Administration 
Listing 16.2.5.4 
Blood Sampling and Results for Pharmacokinetic Assessment  
Listing 16.2.6.1 
mSWAT Assessment During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.6.2 
mSWAT Analysis During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.6.3 
mSWAT Assessment During Crossover Portion – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.4 
mSWAT Analysis During Crossover Portion – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.5 
Flow Cytometric Analysis During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.6.6 
Flow Cytometric Analysis During Crossover Portion – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.7 
Bone Marrow Aspirate/Biopsy Assessment During Pre-Treatment and Randomized 
Treatment Period 
Listing 16.2.6.8 
Bone Marrow Aspirate/Biopsy Assessment During Crossover Portion – Subjects 
Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.9 
Lymph Node Assessment During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.6.10 
Lymph Node Assessment During Crossover Portion – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.11 
Visceral Mass Assessment During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.6.12 
Visceral Mass Assessment During Crossover Portion – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.13 
CTCL Response During Randomized Treatment Period – By Investigator’s 
Assessment 
Listing 16.2.6.14 
CTCL Response During Crossover Portion – Subjects Who Are Randomized to 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
CONFIDENTIAL 
62 
 
Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.15.1 
CTCL Response During Randomized Treatment Period – By Independent Review  
Listing 16.2.6.15.2 
Lymph Node Assessment During Pre-Treatment and Randomized Treatment Period 
– By Independent Review  
Listing 16.2.6.15.3 
Visceral Assessment During Pre-Treatment and Randomized Treatment Period – By 
Independent Review  
Listing 16.2.6.16 
Progression-Free Survival (PFS) – By Investigator’s Assessment 
Listing 16.2.6.17 
Progression-Free Survival (PFS) – By Independent Review  
Listing 16.2.6.18 
Best Response During Randomized Treatment Period – By Investigator’s 
Assessment 
Listing 16.2.6.19 
Best Response During Randomized Treatment Period – By Independent Review  
Listing 16.2.6.20 
Best Response During Crossover Portion – By Investigator’s Assessment – Subjects 
Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.21 
Skindex-29 Assessment During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.6.22 
Skindex-29 Score During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.6.23 
Skindex-29 Assessment During Crossover Portion – Subjects Who Are Randomized 
to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.24 
Skindex-29 Score During Crossover Portion – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.25 
FACT-G Assessment During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.6.26 
FACT-G Subscale and Total Scores During Randomized Treatment Period 
Listing 16.2.6.27 
FACT-G Assessment During Crossover Portion – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.28 
FACT-G Subscale and Total Scores During Crossover Portion – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.29 
EQ-5D-3L Assessment and Score During Pre-Treatment and Randomized Treatment 
Period 
Listing 16.2.6.30 
EQ-5D-3L Assessment and Score During Crossover Portion – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.31 
Pruritus Evaluation – Itchy QoL Assessment  During Randomized Treatment Period 
Listing 16.2.6.32 
Pruritus Evaluation Score During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.6.33 
Pruritus Evaluation – Itchy QoL Assessment  During Crossover Portion – Subjects 
Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.34 
Pruritus Evaluation Score During Crossover Portion – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.35 
Skin Biopsy During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.6.36 
Skin Biopsy During Crossover Portion – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Listing 16.2.6.37 
Survival Status 
Listing 16.2.7.1 
Adverse Events During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.7.2 
Listing of Serious Adverse Events (SAEs) During Pre-Treatment and Randomized 
Treatment Period 
Listing 16.2.7.3 
Listing of Grade III/IV/V Adverse Events During Pre-Treatment and Randomized 
Treatment Period 
Listing 16.2.7.4 
Listing of Adverse Events Leading to Discontinuation of Study Medication During 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
CONFIDENTIAL 
63 
 
Randomized Treatment Period 
Listing 16.2.7.5 
Listing of Adverse Events Leading to Death During Randomized Treatment Period 
Listing 16.2.7.6 
Adverse Events During Crossover Portion – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Listing 16.2.7.7 
Listing of Serious Adverse Events (SAEs) During Crossover Portion – Subjects 
Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.7.8 
Listing of Grade III/IV/V Adverse Events During Crossover Portion – Subjects Who 
Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.7.9 
Listing of Adverse Events Leading to Discontinuation of Study Medication During 
Crossover Portion – Subjects Who Are Randomized to Vorinostat and Crossed Over 
to KW-0761 
Listing 16.2.7.10 
Listing of Adverse Events Leading to Death During Crossover Portion – Subjects 
Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.1 
Laboratory Assessment During Pre-Treatment and Randomized Treatment Period – 
Chemistry 
Listing 16.2.8.2 
Laboratory Assessment During Pre-Treatment and Randomized Treatment Period – 
Hematology 
Listing 16.2.8.3 
Laboratory Assessment During Pre-Treatment and Randomized Treatment Period – 
Coagulation Profile 
Listing 16.2.8.4 
Laboratory Assessment During Pre-Treatment and Randomized Treatment Period – 
Thyroid Function Test 
Listing 16.2.8.5 
Laboratory Assessment During Pre-Treatment and Randomized Treatment Period – 
T-cell Counts 
Listing 16.2.8.6 
Laboratory Assessment During Pre-Treatment and Randomized Treatment Period – 
Urinalysis 
Listing 16.2.8.7 
Laboratory Assessment During Pre-Treatment and Randomized Treatment Period – 
Pregnancy Test 
Listing 16.2.8.8 
Laboratory Assessment During Crossover Portion – Chemistry – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.9 
Laboratory Assessment During Crossover Portion – Hematology – Subjects Who 
Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.10 
Laboratory Assessment During Crossover Portion – Coagulation Profile – Subjects 
Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.11 
Laboratory Assessment During Crossover Portion – Thyroid Function Test – 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.12 
Laboratory Assessment During Crossover Portion – T-cell Counts – Subjects Who 
Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.13 
Laboratory Assessment During Crossover Portion – Urinalysis – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.14 
Laboratory Assessment During Crossover Portion – Pregnancy Test – Subjects Who 
Are Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.15 
Laboratory Assessment – Virus Testing 
Listing 16.2.8.16 
Vital Signs During Pre-Treatment and Randomized Treatment Period 
Listing 16.2.8.17 
Vital Signs During Crossover Portion – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.18 
Electrocardiogram During Pre-Treatment and Randomized Treatment Period  


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
CONFIDENTIAL 
64 
 
Listing 16.2.8.19 
Electrocardiogram During Crossover Portion – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.20 
ECOG Performance Status During Pre-Treatment and Randomized Treatment 
Period   
Listing 16.2.8.21 
ECOG Performance Status During Crossover Portion – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.22 
Physical Examination During Pre-Treatment and Randomized Treatment Period   
Listing 16.2.8.23 
Physical Examination During Crossover Portion – Subjects Who Are Randomized to 
Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.24 
Natural Ligands (MDC/TARC) During Pre-Treatment and Randomized Treatment 
Period   
Listing 16.2.8.25 
Natural Ligands (MDC/TARC) During Crossover Portion – Subjects Who Are 
Randomized to Vorinostat and Crossed Over to KW-0761 
Listing 16.2.8.26 
Saliva Sample for Genetic Analysis – KW-0761 Treatment Only 
Listing 16.2.8.27 
Anti-KW-0761 Antibody Response   
Listing 16.2.8.28 
Anti-KW-0761 Antibody Response for Subjects with Infusion Reactions  
Listing 16.2.8.29 
CCR4 Expression 
Listing 16.2.8.30 
General Comments 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
65 
 
Table 14.1.1.1 
Subject Disposition 
Intent-to-Treat Set 
 
 
Vorinostat 
n    (%) 
KW-0761 
n    (%) 
Total 
n    (%) 
Subjects Randomized  
 xx (100.0) 
 xx (100.0) 
 xx (100.0) 
 
 
 
 
Subjects Randomized and Did Not Receive Any Assigned Study Drug 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
 
 
 
 
Subjects Randomized and Treated 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
 
 
 
 
Subjects Discontinued Randomized Study Drug 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Study termination by sponsor 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Progressive disease per CTCL response criteria 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Progressive disease – Clinical 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Pregnancy 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Withdrawal of consent 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Subject requires prohibited concomitant medication 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Protocol noncompliance 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Investigator decision 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Adverse event 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Death 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
   Other 
 xx ( xx.x) 
 xx ( xx.x) 
 xx ( xx.x) 
 
 
 
 
Subjects Randomized to Vorinostat and Crossed Over to KW-0761 
xx ( xx.x) 
- 
xx ( xx.x) 
 
 
 
 
Subjects Discontinued from the Study 
xx ( xx.x) 
xx ( xx.x) 
xx ( xx.x) 
   Study termination by sponsor 
xx ( xx.x) 
xx ( xx.x) 
xx ( xx.x) 
   Withdrawal of consent 
xx ( xx.x) 
xx ( xx.x) 
xx ( xx.x) 
   Death 
xx ( xx.x) 
xx ( xx.x) 
xx ( xx.x) 
   Lost to Follow-up 
xx ( xx.x) 
xx ( xx.x) 
xx ( xx.x) 
   Subject did not meet Inc./Exc. criteria 
xx ( xx.x) 
xx ( xx.x) 
xx ( xx.x) 
   Other 
xx ( xx.x) 
xx ( xx.x) 
xx ( xx.x) 
 
 
 
 
Analysis Set 
 
 
 
   Intent-to-Treat Set 
xx ( xx.x) 
xx ( xx.x) 
xx ( xx.x) 
   Safety Analysis Set 
xx ( xx.x) 
xx ( xx.x) 
xx ( xx.x) 
   Efficacy Evaluable Set 
xx ( xx.x) 
xx ( xx.x) 
xx ( xx.x) 
Note: Percentage is calculated using the number of randomized subjects as the denominator. 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
66 
 
Table 14.1.1.2 
Subject Disposition – Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
 
Total 
n    (%) 
 
 
 
 
 
Subjects randomized to Vorinostat and crossed over to KW-0761  
 
 xx ( 100.0) 
 
    Due to Progression 
 
xx ( xx.x) 
 
    Due to Intolerance 
 
xx ( xx.x) 
 
 
 
 
 
Subjects who crossed over to KW-0761 but did not receive KW-0761 
 
xx ( xx.x) 
 
 
 
 
 
Subjects who crossed over to KW-0761 and received KW-0761 
 
xx ( xx.x) 
 
 
 
 
 
Subjects crossed over to KW-0761 and discontinued KW-0761 
 
xx ( xx.x) 
 
   Study termination by sponsor 
 
xx ( xx.x) 
 
   Progressive disease per CTCL response criteria 
 
xx ( xx.x) 
 
   Progressive disease - Clinical 
 
xx ( xx.x) 
 
   Pregnancy 
 
xx ( xx.x) 
 
   Withdrawal of consent 
 
xx ( xx.x) 
 
   Subject requires prohibited concomitant medication 
 
xx ( xx.x) 
 
   Protocol noncompliance 
 
xx ( xx.x) 
 
   Investigator decision 
 
xx ( xx.x) 
 
   Adverse event 
 
xx ( xx.x) 
 
   Death 
 
xx ( xx.x) 
 
   Other 
 
xx ( xx.x) 
 
 
 
 
 
Subjects crossed over to KW-0761 and discontinued from the study 
 
xx ( xx.x) 
 
    Study termination by sponsor 
 
xx ( xx.x) 
 
    Withdrawal of consent 
 
xx ( xx.x) 
 
    Death 
 
xx ( xx.x) 
 
    Lost to Follow-up 
 
xx ( xx.x) 
 
    Subject did not meet Inclusion/Exclusion Criteria 
 
xx ( xx.x) 
 
    Other 
 
xx ( xx.x) 
 
Note: Percentage is calculated using the number of subjects who are randomized to Vorinostat and then crossed over to KW-0761 as the 
denominator. 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
67 
 
Table 14.1.2.1 
Demographic and Baseline Disease Characteristics  
Intent-to-Treat Set 
 
Variable 
  Statistic/Category 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
Total 
N=xxx 
Age (years) at Screening 
 
 
 
n 
           xx 
             xx 
           xx 
Mean 
           xx.x 
             xx.x 
           xx.x 
Std Dev 
           xx.xx 
             xx.xx 
           xx.xx 
Median 
           xx.x 
             xx.x 
           xx.x 
Minimum 
           xx 
             xx 
           xx 
Maximum 
           xx 
             xx 
           xx 
 
 
 
 
Age Group (n, %) 
 
 
 
<65 years 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  >=65 years 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Gender (n, %) 
 
 
 
Male 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Female 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Race (n, %) 
 
 
 
White 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Asian 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Black or African American 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Native American or Alaska Native 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Native Hawaiian or Other Pacific Islander 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Not Applicable 
 
 
 
 
 
 
 
Ethnicity (n, %) 
 
 
 
Hispanic or Latino 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Not Hispanic or Latino  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Not Applicable 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
ECOG Performance Status [1] (n, %) 
 
 
 
0 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
[1] Baseline is defined as the last measurement obtained prior to the first dose of study drug. 
* Time from initial diagnosis (months) is calculated as (date of first dose of study medication – date of initial diagnosis + 1)/30.   
If the month and year of the diagnosis are provided but the day is missing, the missing day is imputed as 15. If only the year is 
provided, then the missing month and day are imputed as July 1 for the calculation.   


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
68 
 
Table 14.1.2.1 
Demographic and Baseline Disease Characteristics 
Intent-to-Treat Set 
 
Variable 
  Statistic/Category 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
Total 
N=xxx 
Region (n, %) 
 
 
 
  US 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Japan 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Rest of World 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Height (cm)   
 
 
 
n 
            xx 
         xx 
             xx 
Mean 
            xx.x 
         xx.x 
             xx.x 
Std Dev 
            xx.xx 
         xx.xx 
             xx.xx 
Median 
            xx.x 
         xx.x 
             xx.x 
Minimum 
            xx 
         xx 
             xx 
Maximum 
            xx 
         xx 
             xx 
 
 
 
 
Weight (kg) [1] 
 
 
 
n 
            xx 
         xx 
             xx 
Mean 
            xx.x 
         xx.x 
             xx.x 
Std Dev 
            xx.xx 
         xx.xx 
             xx.xx 
Median 
            xx.x 
         xx.x 
             xx.x 
Minimum 
            xx 
         xx 
             xx 
Maximum 
            xx 
         xx 
             xx 
 
 
 
 
Body Surface Area (m^2) [1] 
 
 
n 
            xx 
         xx 
             xx 
Mean 
            xx.x 
         xx.x 
             xx.x 
Std Dev 
            xx.xx 
         xx.xx 
             xx.xx 
Median 
            xx.x 
         xx.x 
             xx.x 
Minimum 
            xx 
         xx 
             xx 
Maximum 
            xx 
         xx 
             xx 
 
 
 
 
Body Mass Index (kg/m^2) [1] 
 
 
 
n 
            xx 
         xx 
             xx 
Mean 
            xx.x 
         xx.x 
             xx.x 
Std Dev 
            xx.xx 
         xx.xx 
             xx.xx 
Median 
            xx.x 
         xx.x 
             xx.x 
Minimum 
            xx 
         xx 
             xx 
Maximum 
            xx 
         xx 
             xx 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
[1] Baseline is defined as the last measurement obtained prior to the first dose of study drug. 
* Time from initial diagnosis (months) is calculated as (date of first dose of study medication – date of initial diagnosis + 1)/30.  
If the month and year of the diagnosis are provided but the day is missing, the missing day is imputed as 15. If only the year is 
provided, then the missing month and day are imputed as July 1 for the calculation.   


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
69 
 
Table 14.1.2.1 
Demographic and Baseline Disease Characteristics 
Intent-to-Treat Set 
 
Variable 
  Statistic/Category 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
Total 
N=xxx 
Time from Initial Diagnosis (months)*  
 
 
 
  n 
            xx 
         xx 
             xx 
  Mean 
            xx.x 
         xx.x 
             xx.x 
  Std Dev 
            xx.xx 
         xx.xx 
             xx.xx 
  Median 
            xx.x 
         xx.x 
             xx.x 
  Minimum 
            xx 
         xx 
             xx 
  Maximum 
            xx 
         xx 
             xx 
 
 
 
 
Disease Type (n, %) 
 
 
 
Mycosis Fungoides (MF) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Sézary Syndrome (SS) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Clinical Stage at Diagnosis (n, %) 
 
 
 
IA 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IB 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IIA 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IIB 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IIIA 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IIIB 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IVA 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IVB 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
I or II 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
III or IV 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Current Clinical Stage (n, %) 
 
 
 
IB 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IIA 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IIB 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IIIA 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IIIB 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IVA 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
IVB 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
IB or II 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
III or IV 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
[1] Baseline is defined as the last measurement obtained prior to the first dose of study drug. 
* Time from initial diagnosis (months) is calculated as (date of first dose of study medication – date of initial diagnosis + 1)/30.  
If the month and year of the diagnosis are provided but the day is missing, the missing day is imputed as 15. If only the year is 
provided, then the missing month and day are imputed as July 1 for the calculation.   


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
70 
 
Table 14.1.2.1 
Demographic and Baseline Disease Characteristics 
Intent-to-Treat Set 
 
Variable 
  Statistic/Category 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
Total 
N=xxx 
Current Sites of Disease (n, %) 
 
 
 
  Skin 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Nodes 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Viscera 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Blood 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Prior CTCL Therapy (n, %) 
 
 
 
  No 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Yes 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 Type of Prior Therapy Received (n, %) 
 
 
 
   Bexarotene-Oral  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Bexarotene-Topical 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Brentuximab Vedotin 
 
 
 
   Carmustine 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Chlorambucil 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Denileukin Diftitox 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Doxorubicin HCL Liposome 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   ECP 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Etoposide 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   IL-12 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Interferon-α 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Pralatrexate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Methotrexate 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Nitrogen Mustard 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   PUVA 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Romidepsin 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Topical Steroid 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
[1] Baseline is defined as the last measurement obtained prior to the first dose of study drug. 
* Time from initial diagnosis (months) is calculated as (date of first dose of study medication – date of initial diagnosis + 1)/30.  
If the month and year of the diagnosis are provided but the day is missing, the missing day is imputed as 15. If only the year is 
provided, then the missing month and day are imputed as July 1 for the calculation.   
 
 


Statistical Analysis Plan 
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71 
 
Table 14.1.2.1 
Demographic and Baseline Disease Characteristics 
Intent-to-Treat Set 
 
Variable 
  Statistic/Category 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
Total 
N=xxx 
Prior CTCL Therapy 
 
 
 
Number of Prior CTCL Therapies (n, %) 
 
 
 
  1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  4 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  >=6 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Best Response to Last CTCL Therapy Prior 
to Study Entry (n, %) 
 
 
 
Complete response 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Partial response 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Complete response or partial response 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Stable disease 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Progressive disease 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Not applicable 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Unknown 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
Prior Radiotherapy (n, %) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
No 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Yes 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
CCR4 Expression Status (n, %)  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Positive 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Negative 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Unknown 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
[1] Baseline is defined as the last measurement obtained prior to the first dose of study drug. 
* Time from initial diagnosis (months) is calculated as (date of first dose of study medication – date of initial diagnosis + 1)/30.  
If the month and year of the diagnosis are provided but the day is missing, the missing day is imputed as 15. If only the year is 
provided, then the missing month and day are imputed as July 1 for the calculation.   


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
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72 
 
Table 14.1.2.1 
Demographic and Baseline Disease Characteristics  
Intent-to-Treat Set 
 
Variable 
  Statistic/Category 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
Total 
N=xxx 
LDH (U/L) at Baseline 
 
 
 
n 
           xx 
             xx 
           xx 
Mean 
           xx.x 
             xx.x 
           xx.x 
Std Dev 
           xx.xx 
             xx.xx 
           xx.xx 
Median 
           xx.x 
             xx.x 
           xx.x 
Minimum 
           xx 
             xx 
           xx 
Maximum 
           xx 
             xx 
           xx 
 
 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
[1] Baseline is defined as the last measurement obtained prior to the first dose of study drug. 
* Time from initial diagnosis (months) is calculated as (date of first dose of study medication – date of initial diagnosis + 1)/30.   
If the month and year of the diagnosis are provided but the day is missing, the missing day is imputed as 15. If only the year is 
provided, then the missing month and day are imputed as July 1 for the calculation.   


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
73 
 
The following tables will have a similar layout as Table 14.1.2.1: 
Table 14.1.2.2 
Demographic and Baseline Disease Characteristics 
Safety Analysis Set  
 
Table 14.1.2.3 
Demographic and Baseline Disease Characteristics 
Efficacy Evaluable Set  
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
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74 
 
Table 14.1.3 
Summary of Concomitant Medications During Randomized Treatment Period – Number (%) of Subjects 
Safety Analysis Set 
 
ATC Classification 
  Preferred Term 
 
Vorinostat 
N=xxx 
n    (%) 
 
KW-0761 
N=xxx  
n    (%) 
 
 
Total 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
ATC Classification 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
Preferred Term 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
Preferred Term 2 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
Preferred Term 3 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
ATC Classification 1 
 
 
 
 
 
 
Preferred Term 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
Preferred Term 2 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
Preferred Term 3 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
Medications that started at any time and were taken at any time after the start of treatment until the end of the entire randomized 
treatment period are included. 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
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75 
 
Table 14.1.4 
Summary of Extent of Exposure to Randomized Study Drug 
Safety Analysis Set 
 
 
 
Vorinostat 
N=xxx 
 
KW-0761 
N=xxx 
 
 
Extent of Exposure (Days) 
 
 
 
 
 
 
n 
 
    xx 
 
    xx 
 
 
Mean 
 
    xx.x 
 
    xx.x 
 
 
Std Dev 
 
    xx.xx 
 
    xx.xx 
 
 
Median 
 
    xx.x 
 
    xx.x 
 
 
Minimum 
 
    xx 
 
    xx 
 
 
Maximum 
 
    xx 
 
    xx 
 
 
 
 
 
 
 
 
 
Number of KW-0761 Infusions Administered 
 
 
 
 
 
 
n 
 
 
 
    xx 
 
 
Mean 
 
 
 
    xx.x 
 
 
Std Dev 
 
 
 
    xx.xx 
 
 
Median 
 
 
 
    xx.x 
 
 
Minimum 
 
 
 
    xx 
 
 
Maximum 
 
 
 
    xx 
 
 
 
 
 
 
 
 
 
Total Number of Cycles Initiated 
 
 
 
 
 
 
n 
 
    xx 
 
    xx 
 
 
Mean 
 
    xx.x 
 
    xx.x 
 
 
Std Dev 
 
    xx.xx 
 
    xx.xx 
 
 
Median 
 
    xx.x 
 
    xx.x 
 
 
Minimum 
 
    xx 
 
    xx 
 
 
Maximum 
 
    xx 
 
    xx 
 
 
 
 
 
 
 
 
 
Subjects Who Initiated Treatment for at Least* 
 
 
 
 
 
 
1 Cycle 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
2 Cycles 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
3 Cycles 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
4 Cycles 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
5 Cycles 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
6 Cycles 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
Etc. 
 
 
 
 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
* A subject is considered initiated treatment for a cycle if the subject received any assigned study drug for that cycle.  
** % dose intensity is calculated as 100*(total actual dose/total duration of treatment/7)/(total planned dose/total planned weeks). 
 


Statistical Analysis Plan 
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22 November 2016 
 
 
 
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Table 14.1.4 
Summary of Extent of Exposure to Randomized Study Drug 
Safety Analysis Set 
 
 
 
Vorinostat 
N=xx 
 
KW-0761 
N=xx 
 
 
Average Planned Dose of KW-0761 (mg) 
 
 
 
 
 
 
n 
 
 
 
    xx 
 
 
Mean 
 
 
 
    xx.x 
 
 
Std Dev 
 
 
 
    xx.xx 
 
 
Median 
 
 
 
    xx.x 
 
 
Minimum 
 
 
 
    xx 
 
 
Maximum 
 
 
 
    xx 
 
 
 
 
 
 
 
 
 
Average Actual Dose of KW-0761 (mg)   
 
 
 
 
 
 
n 
 
 
 
    xx 
 
 
Mean 
 
 
 
    xx.x 
 
 
Std Dev 
 
 
 
    xx.xx 
 
 
Median 
 
 
 
    xx.x 
 
 
Minimum 
 
 
 
    xx 
 
 
Maximum 
 
 
 
    xx 
 
 
 
 
 
 
 
 
 
% Dose Intensity of KW-0761**  
 
 
 
 
 
 
n 
 
 
 
    xx 
 
 
Mean 
 
 
 
    xx.x 
 
 
Std Dev 
 
 
 
    xx.xx 
 
 
Median 
 
 
 
    xx.x 
 
 
Minimum 
 
 
 
    xx 
 
 
Maximum 
 
 
 
    xx 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
* A subject is considered initiated treatment for a cycle if the subject received any assigned study drug for that cycle. 
** % dose intensity is calculated as 100*(total actual dose/total duration of treatment/7)/(total planned dose/total planned weeks). 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
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Table 14.1.5 
Summary of Study Drug Dosing Status During Randomized Treatment Period 
Safety Analysis Set 
 
 
 
Vorinostat 
N=xx 
n    (%) 
 
KW-0761 
N=xx 
n    (%) 
 
 
Subjects with a Dose Withheld for KW-0761   
 
 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Subjects with Total Planned Dose of KW-0761 Not Administered  
  Reason: 
 
 
 
xx (xx.x) 
 
 
Infusion reaction 
 
 
 
xx (xx.x) 
 
 
Other adverse event 
 
 
 
xx (xx.x) 
 
 
Mechanical equipment issue 
 
 
 
xx (xx.x) 
 
 
Other 
 
 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Subjects with a KW-0761 Infusion Temporarily Interrupted  
  Reason: 
 
 
 
xx (xx.x) 
 
 
Infusion reaction 
 
 
 
xx (xx.x) 
 
 
Other adverse event 
 
 
 
xx (xx.x) 
 
 
Mechanical equipment issue 
 
 
 
xx (xx.x) 
 
 
Other 
 
 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Subjects with Dose Modifications for Vorinostat 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
Subjects with Non-compliance with Dosing for Vorinostat* 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
* Non-compliance is based on investigator assessment. 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
78 
 
The following tables will have similar layout as Table 14.1.4 and Table 14.1.5: 
Table 14.1.6 
Summary of Extent of Exposure to KW-0761 During Crossover Portion 
Safety Analysis Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Table 14.1.7 
Summary of KW-0761 Dosing Status During Crossover Portion 
Safety Analysis Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
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Table 14.2.1.1 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment 
Intent-to-Treat Set 
 
 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
  Number of Subjects with PFS Event (n, %) 
xx (xx.x) 
xx (xx.x) 
  Earliest Contributing Event: 
 
 
    Progressive Disease 
xx (xx.x) 
xx (xx.x) 
    Death 
xx (xx.x) 
xx (xx.x) 
 
 
 
  Number of Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
  Progression-Free Survival (months) 
 
 
  Kaplan-Meier Estimate of PFS 
 
 
    Q1 
xx.x 
xx.x 
    Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Q3 
xx.x 
xx.x 
  Mean 
xx.xx 
xx.xx 
  Standard Deviation 
xx.xxx 
xx.xxx 
  Median 
xx.xx 
xx.xx 
  Minimum 
xx.x 
xx.x 
  Maximum 
xx.x 
xx.x 
 ------ Treatment Comparison ------ 
  KW-0761 vs. Vorinostat** 
 
 
    Hazard Ratio (95% CI)     
 
xx.x (xx.x, xx.x) 
    Log rank p-value  
 
x.xxxx 
 
 
 
Rate (%) of Being Alive without 
Progression for at Least*** 
 
 
    6 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    12 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    18 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    24 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Etc. 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator.  
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
** Hazard ratio and 95% CI are based on Cox proportional hazards model with treatment, disease type, disease stage, and region as 
covariates. P-value (two-sided) is obtained from a stratified log rank test (one-sided test at 0.025 level or equivalently two-sided 
test at 0.05 level) with disease type, disease stage, and region as stratification factors. 
*** Kaplan-Meier estimate.    
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
80 
 
The following tables will have similar layout as Table 14.2.1.1: 
 
Table 14.2.1.2 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment 
Sensitivity Analysis 1 
Intent-to-Treat Set  
 
Table 14.2.1.3 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment  
Sensitivity Analysis 2 
Intent-to-Treat Set 
 
Table 14.2.1.4 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment – Worst Case Sensitivity Analysis 
Sensitivity Analysis 3 
Intent-to-Treat Set  
 
<<Programming Note: Add the corresponding PFS definition in the footnote for Tables 14.2.1.2 to 14.2.1.4 per SAP Section 6.11.2.2.>>  


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
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Table 14.2.1.5 
Multivariate Analysis of Progression-Free Survival (PFS) Based on Investigator’s Assessment 
Intent-to-Treat Set 
 
Prognostic Factors 
 
--------- Progression-Free Survival (Months) -------- 
   Hazard Ratio (95% CI)                  P-value 
 
 
 
Treatment     
 
 
 
 
 
 KW-0761 vs. Vorinostat 
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
 
 
 
 
 
 
Disease Type 
 
 
 
 
 
 MF vs. SS 
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
 
 
 
 
 
 
Disease Stage 
 
     
 
 
 
IB/II vs. III/IV 
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
 
 
 
 
 
 
Blood Involvement 
 
 
 
 
 
Yes vs. No  
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
  
 
 
 
 
 
Region 
 
 
 
 
 
US vs. Japan 
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
US vs. Rest of World 
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
Japan vs Rest of World 
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
 
 
 
 
 
 
Age Group 
 
 
 
 
 
 >=65 vs. <65 yrs  
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
 
 
 
 
 
 
Gender 
 
 
 
 
 
 Male vs. female  
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
 
 
 
 
 
 
Race Category 
 
 
 
 
 
 White vs. Black or African American 
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
 White vs. Other 
 
    xx.x (xx.x, xx.x)                     x.xxxx 
 
 
 
Note: Hazard ratio, 95% CI, and p-value are obtained from a Cox proportional hazard model with treatment, disease type, disease stage, 
Blood Involvement, region, age group, gender, and race category as explanatory variables. 
 
<<Programming Note: Backward selection method will be used to identify the final set of prognostic factors (exit p-value is set to be 0.1). 
Treatment will be fixed in the model, i.e., will not be eliminated.>> 
    


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
82 
 
The following table will have a similar layout as Table 14.2.1.1: 
Table 14.2.1.6.1 
Summary of Progression-Free Survival (PFS) 
Efficacy Evaluable Set  
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
83 
 
Table 14.2.1.6.2 
Summary of Progression-Free Survival (PFS) 
Intent-to-Treat Set 
Any Exposure to KW-0761 vs. Vorinostat Only 
 
 
 
 
Vorinostat 
N=xxx 
KW-0761# 
---------------------------------------------------------- 
  Crossover       Randomized to KW-0761        Any KW-0761 
N=xxx 
By Investigator’s Assessment 
 
 
  Number of Subjects with PFS Event (n, %) 
xx (xx.x) 
  xx (xx.x)              xx (xx.x)              xx (xx.x) 
  Earliest Contributing Event: 
 
 
    Progressive Disease 
xx (xx.x) 
  xx (xx.x)              xx (xx.x)              xx (xx.x) 
    Death 
xx (xx.x) 
  xx (xx.x)              xx (xx.x)              xx (xx.x) 
 
 
 
  Number of Subjects Censored (n, %) 
xx (xx.x) 
  xx (xx.x)              xx (xx.x)              xx (xx.x) 
 
 
 
  Progression-Free Survival (months) 
 
 
  Kaplan-Meier Estimate of PFS 
 
 
    Q1 
xx.x 
    xx.x                   xx.x                    xx.x 
    Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x)   xx.x (xx.x, xx.x)     xx.x (xx.x, xx.x) 
    Q3 
xx.x 
    xx.x                   xx.x                    xx.x 
  Mean 
xx.xx 
    xx.xx                  xx.xx                   xx.xx 
  Standard Deviation 
xx.xxx 
    xx.xxx                 xx.xxx                  xx.xxx 
  Median 
xx.xx 
    xx.xx                  xx.xx                   xx.xx 
  Minimum 
xx.x 
    xx.x                   xx.x                    xx.x 
  Maximum 
xx.x 
    xx.x                   xx.x                    xx.x 
 ------ Treatment Comparison ------ 
  KW-0761 vs. Vorinostat** 
 
 
    Hazard Ratio (95% CI)     
 
                                          xx.x (xx.x, xx.x) 
    Log rank p-value  
 
                                                x.xxxx 
 
 
 
Rate (%) of Being Alive without 
Progression for at Least*** 
 
 
    6 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x)
    12 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x) 
    18 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x) 
    24 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x) 
    Etc. 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator.  
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
** Hazard ratio and 95% CI are based on Cox proportional hazards model with treatment, disease type, disease stage, and region as 
covariates. P-value (two-sided) is obtained from a stratified log rank test (one-sided test at 0.025 level or equivalently two-sided 
test at 0.05 level) with disease type, disease stage, and region as stratification factors. 
*** Kaplan-Meier estimate.    
# For subjects who had KW-0761 treatment, PFS is calculated from the first dose of KW-0761. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
84 
 
Table 14.2.1.6.2 
Summary of Progression-Free Survival (PFS) 
Intent-to-Treat Set 
Any Exposure to KW-0761 vs. Vorinostat Only 
 
 
 
 
Vorinostat 
N=xxx 
KW-0761# 
---------------------------------------------------------- 
  Crossover       Randomized to KW-0761        Any KW-0761 
N=xxx 
By Independent Review Committee 
 
 
  Number of Subjects with PFS Event (n, %) 
xx (xx.x) 
  xx (xx.x)              xx (xx.x)              xx (xx.x) 
  Earliest Contributing Event: 
 
 
    Progressive Disease 
xx (xx.x) 
  xx (xx.x)              xx (xx.x)              xx (xx.x) 
    Death 
xx (xx.x) 
  xx (xx.x)              xx (xx.x)              xx (xx.x) 
 
 
 
  Number of Subjects Censored (n, %) 
xx (xx.x) 
  xx (xx.x)              xx (xx.x)              xx (xx.x) 
 
 
 
  Progression-Free Survival (months) 
 
 
  Kaplan-Meier Estimate of PFS 
 
 
    Q1 
xx.x 
    xx.x                   xx.x                    xx.x 
    Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x)   xx.x (xx.x, xx.x)     xx.x (xx.x, xx.x) 
    Q3 
xx.x 
    xx.x                   xx.x                    xx.x 
  Mean 
xx.xx 
    xx.xx                  xx.xx                   xx.xx 
  Standard Deviation 
xx.xxx 
    xx.xxx                 xx.xxx                  xx.xxx 
  Median 
xx.xx 
    xx.xx                  xx.xx                   xx.xx 
  Minimum 
xx.x 
    xx.x                   xx.x                    xx.x 
  Maximum 
xx.x 
    xx.x                   xx.x                    xx.x 
 ------ Treatment Comparison ------ 
  KW-0761 vs. Vorinostat** 
 
 
    Hazard Ratio (95% CI)     
 
                                          xx.x (xx.x, xx.x) 
    Log rank p-value  
 
                                                x.xxxx 
 
 
 
Rate (%) of Being Alive without 
Progression for at Least*** 
 
 
    6 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x)
    12 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x) 
    18 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x) 
    24 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x)    xx.x (xx.x, xx.x) 
    Etc. 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator.  
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
** Hazard ratio and 95% CI are based on Cox proportional hazards model with treatment, disease type, disease stage, and region as 
covariates. P-value (two-sided) is obtained from a stratified log rank test (one-sided test at 0.025 level or equivalently two-sided 
test at 0.05 level) with disease type, disease stage, and region as stratification factors. 
*** Kaplan-Meier estimate.    
# For subjects who had KW-0761 treatment, PFS is calculated from the first dose of KW-0761. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
85 
 
 Table 14.2.1.7.1 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment 
Intent-to-Treat Set 
By Pre-defined Subgroups 
Disease Type = MF 
 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
Number of Subjects with PFS Event (n, %) 
xx (xx.x) 
xx (xx.x) 
  Earliest Contributing Event: 
 
 
    Progressive Disease 
xx (xx.x) 
xx (xx.x) 
    Death 
xx (xx.x) 
xx (xx.x) 
 
 
 
Number of Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Progression-Free Survival (months) 
 
 
  Kaplan-Meier Estimate of PFS 
 
 
    Q1 
xx.x 
xx.x 
    Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Q3 
xx.x 
xx.x 
 
 
 
------ Treatment Comparison ------ 
   KW-0761 vs. Vorinostat** 
 
 
    Hazard Ratio (95% CI)     
 
xx.x (xx.x, xx.x) 
    Log rank p-value 
 
x.xxxx 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator.  
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
** Hazard ratio and 95% CI are based on Cox proportional hazards model with treatment, disease stage, and region as covariates. P-
value is obtained from a stratified log rank test with disease stage and region as stratification factors. 
 
 
 
<<Programming Note: Repeat for the following subgroups: Disease Type (SS), Disease Stage, Blood Involvement, Region, Age group, Gender, 
Race Category, and Baseline LDH.>> 
  


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
86 
 
The following table will have a similar layout as Table 14.2.1.7.1: 
Table 14.2.1.7.2 
Summary of Progression-Free Survival (PFS) Based on Investigator’s Assessment 
Efficacy Evaluable Set  
By Pre-defined Subgroups 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
87 
 
Table 14.2.1.8 
Summary of Progression-Free Survival (PFS) Based on Independent Review 
Intent-to-Treat Set 
 
 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
  Number of Subjects with PFS Event (n, %) 
xx (xx.x) 
xx (xx.x) 
  Earliest Contributing Event: 
 
 
    Progressive Disease 
xx (xx.x) 
xx (xx.x) 
    Death 
xx (xx.x) 
xx (xx.x) 
 
 
 
  Number of Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
  Progression-Free Survival (months) 
 
 
  Kaplan-Meier Estimate of PFS 
 
 
    Q1 
xx.x 
xx.x 
    Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Q3 
xx.x 
xx.x 
  Mean 
xx.xx 
xx.xx 
  Standard Deviation 
xx.xxx 
xx.xxx 
  Median 
xx.xx 
xx.xx 
  Minimum 
xx.x 
xx.x 
  Maximum 
xx.x 
xx.x 
 
 
 
 ------ Treatment Comparison ------ 
  KW-0761 vs. Vorinostat** 
 
 
    Hazard Ratio (95% CI)     
 
xx.x (xx.x, xx.x) 
    Log rank p-value 
 
x.xxxx 
 
 
 
Rate (%) of Being Alive without 
Progression for at Least*** 
 
 
    6 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    12 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    18 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    24 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Etc. 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator.  
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
**  Hazard ratio and 95% CI are based on Cox proportional hazards model with treatment, disease type, disease stage, and region as   
   covariates. P-value (two-sided) is obtained from a stratified log rank test (one-sided test at 0.025 level or equivalently two- 
   sided test at 0.05 level) with disease type disease stage, and region as stratification factors. 
*** Kaplan-Meier estimate.    


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
88 
 
Table 14.2.2.1.1 
Summary of Confirmed Overall Response Rate (ORR) During Randomized Treatment Period 
Intent-to-Treat Set 
 
 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
By Investigator’s Assessment 
 
 
  Overall response rate (confirmed CR + PR) (n, %) 
xx (xx.x) 
xx (xx.x) 
      95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
 
  ------ Treatment Comparison ------ 
  KW-0761 vs. Vorinostat 
 
 
 
 
      Risk Diff                                      
 
xx.x   
      95% CI* 
 
(xx.x, xx.x) 
      P-value** 
 
x.xxxx 
      Adjusted P-value** 
 
x.xxxx 
 
 
 
By Independent Review Committee 
 
 
Overall response rate (confirmed CR + PR) (n, %) 
xx (xx.x) 
xx (xx.x) 
    95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
 
  ------ Treatment Comparison ------ 
KW-0761 vs. Vorinostat 
 
 
 
 
      Risk Diff 
xx.x   
xx.x   
      95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
      P-value** 
 
x.xxxx 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. CR = complete response, PR = 
partial response. 
Overall Response Rate is based on Global Composite Response Score. 
* 95% CI for response rate is the exact 95% confidence interval. 95% CI for difference is the exact 95% unconditional confidence 
interval for the risk difference (KW-0761 – Vorinostat).  
** P-value is obtained from Cochran-Mantel-Haenszel test adjusting for disease type, disease stage, and region. Adjusted P-value is 
calculated using Sidak method. 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
89 
 
Table 14.2.2.1.2 
Logistic Regression Analysis of Confirmed Overall Response Rate (ORR) During Randomized Treatment Period 
Based on Investigator’s Assessment 
Intent-to-Treat Set 
 
Prognostic Factor 
 
Odds Ratio Estimate (SE) 
95% CI 
P-value 
 
Treatment     
 
 
 
 
 
 
 KW-0761 vs.  Vorinostat 
 
 
xx.x (xx.xx) 
(xx.x, xx.x) 
x.xxxx 
 
 
 
 
 
 
 
 
Disease Type 
 
 
 
 
 
 
 MF vs. SS 
 
 
xx.x (xx.xx) 
(xx.x, xx.x) 
x.xxxx 
 
 
 
 
 
 
 
 
Disease Stage 
 
 
 
 
 
 
IB/II vs. III/IV 
 
 
xx.x (xx.xx) 
(xx.x, xx.x) 
x.xxxx 
 
 
 
 
 
 
 
 
Blood Involvement 
 
 
 
 
 
 
Yes vs. No 
 
 
xx.x (xx.xx) 
(xx.x, xx.x) 
x.xxxx 
 
 
 
 
 
 
 
 
Region 
 
 
 
 
 
 
 US vs. Japan 
 US vs. Rest of World 
 Japan vs Rest of World 
 
 
xx.x (xx.xx) 
(xx.x, xx.x) 
x.xxxx 
 
 
 
 
 
 
 
 
Age Group 
 
 
 
 
 
 
 >=65 vs. <65 years old 
 
 
xx.x (xx.xx) 
(xx.x, xx.x) 
x.xxxx 
 
 
 
 
 
 
 
 
Gender 
 
 
 
 
 
 
 Male vs. female  
 
 
xx.x (xx.xx) 
(xx.x, xx.x) 
x.xxxx 
 
 
 
 
 
 
 
 
Race Category 
 
 
 
 
 
 
 White vs. Black or African America 
 
 
xx.x (xx.xx) 
(xx.x, xx.x) 
x.xxxx 
 
 White vs. Other 
 
 
xx.x (xx.xx) 
(xx.x, xx.x) 
x.xxxx 
 
Note: Odds ratio, SE, 95% CI, and p-value are obtained from a multivariate logistic regression model with treatment, disease type, 
disease stage, blood Involvement, region, age group, gender, and race category as explanatory variables. 
Overall Response is based on Global Composite Response Score. 
 
<<Programming Note: Backward selection method will be used to identify the final set of prognostic factors (exit p-value is set to be 0.1). 
Treatment will be fixed in the model, i.e., will not be eliminated.>> 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
90 
 
Table 14.2.2.1.3 
 
Summary of Confirmed and Unconfirmed Overall Response Rate (ORR) During Randomized Treatment Period 
Intent-to-Treat Set 
 
 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
By Investigator’s Assessment 
 
 
  Overall response rate (confirmed and unconfirmed CR + PR) (n, %) 
xx (xx.x) 
xx (xx.x) 
      95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
 
  ------ Treatment Comparison ------ 
  KW-0761 vs. Vorinostat 
 
 
 
 
      Risk Diff                                      
 
xx.x 
      95% CI* 
 
(xx.x, xx.x) 
      P-value** 
 
x.xxxx 
 
 
 
By Independent Review Committee 
 
 
Overall response rate (confirmed and unconfirmed CR + PR) (n, %) 
xx (xx.x) 
xx (xx.x) 
    95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
 
  ------ Treatment Comparison ------ 
KW-0761 vs. Vorinostat 
 
 
 
 
      Risk Diff 
xx.x 
xx.x 
      95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
      P-value** 
 
x.xxxx 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. CR = complete response, PR = 
partial response. 
Overall Response Rate is based on Global Composite Response Score. 
* 
95% CI for response rate is the exact 95% confidence interval. 95% CI for difference is the exact 95% unconditional confidence 
interval for the risk difference (KW-0761 – Vorinostat).  
** 
P-value is obtained from Cochran-Mantel-Haenszel test adjusting for disease type, disease stage, and region.  


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
91 
 
Table 14.2.2.1.4 
Summary of Confirmed Overall Response Rate (ORR) During Randomized Treatment Period by Disease Type 
Intent-to-Treat Set 
Disease Type = MF 
 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
By Investigator’s Assessment 
 
 
  Overall response rate (confirmed CR + PR) (n, %) 
xx (xx.x) 
xx (xx.x) 
      95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
 
  ------ Treatment Comparison ------ 
  KW-0761 vs. Vorinostat 
 
 
 
 
      Risk Diff                                      
 
xx.x   
      95% CI* 
 
(xx.x, xx.x) 
      P-value** 
 
x.xxxx 
      Adjusted P-value** 
 
x.xxxx 
 
 
 
By Independent Review Committee 
 
 
Overall response rate (confirmed CR + PR) (n, %) 
xx (xx.x) 
xx (xx.x) 
    95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
 
  ------ Treatment Comparison ------ 
KW-0761 vs. Vorinostat 
 
 
 
 
      Risk Diff 
xx.x   
xx.x   
      95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
      P-value** 
 
x.xxxx 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. CR = complete response, PR = 
partial response. 
Overall Response Rate is based on Global Composite Response Score. 
* 95% CI for response rate is the exact 95% confidence interval. 95% CI for difference is the exact 95% unconditional confidence 
interval for the risk difference (KW-0761 – Vorinostat).  
** P-value is obtained from Cochran-Mantel-Haenszel test adjusting for disease type, disease stage, and region. Adjusted P-value is 
calculated using Sidak method. 
 
 
 
<<Programming Note: Repeat for the following subgroup: Disease Type (SS).>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
92 
 
Table 14.2.2.1.5 
Summary of Confirmed and Unconfirmed Overall Response Rate (ORR) During Randomized Treatment Period by Disease Type 
Intent-to-Treat Set 
Disease Type = MF 
 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
By Investigator’s Assessment 
 
 
  Overall response rate (confirmed and unconfirmed CR + PR) (n, %) 
xx (xx.x) 
xx (xx.x) 
      95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
 
  ------ Treatment Comparison ------ 
  KW-0761 vs. Vorinostat 
 
 
 
 
      Risk Diff                                      
 
xx.x 
      95% CI* 
 
(xx.x, xx.x) 
      P-value** 
 
x.xxxx 
 
 
 
By Independent Review Committee 
 
 
Overall response rate (confirmed and unconfirmed CR + PR) (n, %) 
xx (xx.x) 
xx (xx.x) 
    95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
 
  ------ Treatment Comparison ------ 
KW-0761 vs. Vorinostat 
 
 
 
 
      Risk Diff 
xx.x 
xx.x 
      95% CI* 
(xx.x, xx.x) 
(xx.x, xx.x) 
      P-value** 
 
x.xxxx 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. CR = complete response, PR = 
partial response. 
Overall Response Rate is based on Global Composite Response Score. 
* 
95% CI for response rate is the exact 95% confidence interval. 95% CI for difference is the exact 95% unconditional confidence 
interval for the risk difference (KW-0761 – Vorinostat).  
** 
P-value is obtained from Cochran-Mantel-Haenszel test adjusting for disease type, disease stage, and region.  
 
 
<<Programming Note: Repeat for the following subgroup: Disease Type (SS).>> 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
93 
 
Table 14.2.2.2.1 
Summary of Best Overall Response During Randomized Treatment Period 
Intent-to-Treat Set 
 
  Best Overall Response 
Vorinostat 
N=xxx 
n    (%) 
KW-0761 
N=xxx 
n    (%) 
By Investigator’s Assessment 
 
 
Responders (CR + PR) 
 
 
xx (xx.x) 
 
 
 
 
xx (xx.x) 
 Complete response(CR) 
   Confirmed CR 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Partial response (PR) 
   Confirmed PR 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Stable disease 
xx (xx.x) 
xx (xx.x) 
 Progressive disease  
xx (xx.x) 
xx (xx.x) 
   Not Assessable*  
xx (xx.x) 
xx (xx.x) 
      Clinical Progression 
 
 
 
 
 
By Independent Review Committee 
 
 
 Responders (CR + PR) 
xx (xx.x) 
xx (xx.x) 
 Complete response (CR) 
   Confirmed CR 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Partial response (PR) 
   Confirmed PR 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Stable disease 
xx (xx.x) 
xx (xx.x) 
 Progressive disease 
xx (xx.x) 
xx (xx.x) 
   Not Assessable*  
xx (xx.x) 
xx (xx.x) 
      Clinical Progression 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
Overall Response is based on Global Composite Response Score. 
* If there is no post-baseline tumor assessment or the response for all post-baseline tumor assessments is not assessable or unable to 
  evaluate, the best overall response is classified as not assessable.  
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
94 
 
Table 14.2.2.2.2 
Summary of Best Overall Response During Randomized Treatment Period by Disease Type 
Intent-to-Treat Set 
 
Disease Type = MF 
   Best Overall Response 
Vorinostat 
N=xxx 
n    (%) 
KW-0761 
N=xxx 
n    (%) 
By Investigator’s Assessment 
 
 
 Complete response(CR) 
   Confirmed CR 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Partial response (PR) 
   Confirmed PR 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Stable disease 
xx (xx.x) 
xx (xx.x) 
 Progressive disease  
xx (xx.x) 
xx (xx.x) 
   Not Assessable*  
xx (xx.x) 
xx (xx.x) 
      Clinical Progression 
 
 
 
 
 
By Independent Review Committee 
 
 
 Complete response (CR) 
   Confirmed CR 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Partial response (PR) 
   Confirmed PR 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Stable disease 
xx (xx.x) 
xx (xx.x) 
 Progressive disease 
xx (xx.x) 
xx (xx.x) 
   Not Assessable*  
xx (xx.x) 
xx (xx.x) 
      Clinical Progression 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
* If there is no post-baseline tumor assessment or the response for all post-baseline tumor assessments is not assessable or unable to 
  evaluate, the best overall response is classified as not assessable.  
 
 
 
<<Programming Note: Repeat for the following subgroup: Disease Type (SS).>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
95 
 
The following tables will have similar layouts as Tables 14.2.2.1.1, 14.2.2.1.3, 14.2.2.1.4, 14.2.2.1.5 except the p-values will be 
removed. 
 
Table 14.2.2.3.1 
Summary of Confirmed Overall Response Rate (ORR) During Randomized Treatment Period  
Efficacy Evaluable Set 
 
Table 14.2.2.3.2 
Summary of Confirmed and Unconfirmed Overall Response Rate (ORR) During Randomized Treatment Period  
Efficacy Evaluable Set 
 
Table 14.2.2.3.3 
Summary of Confirmed Overall Response Rate (ORR) During Randomized Treatment Period by Disease Type 
Efficacy Evaluable Set 
 
Table 14.2.2.3 
Summary of Confirmed and Unconfirmed Overall Response Rate (ORR) During Randomized Treatment Period by Disease Type 
Efficacy Evaluable Set 
 
The following tables will have similar layout as Tables 14.2.2.2.1 and 14.2.2.2.2. 
 
Table 14.2.2.4.1 
Summary of Best Overall Response During Randomized Treatment Period 
Efficacy Evaluable Set 
 
 
Table 14.2.2.4.2 
Summary of Best Overall Response During Randomized Treatment Period by Disease Type 
Efficacy Evaluable Set 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
96 
 
Table 14.2.2.5 
Summary of Overall Response During Randomized Treatment Period by Selected Time Points 
Investigator’s Assessment 
Intent-to-Treat Set 
 
Overall Response 
Vorinostat 
N=xxx 
n    (%) 
KW-0761 
N=xxx 
n    (%) 
End of Cycle 3 
 
 
 Complete response(CR) 
xx (xx.x) 
xx (xx.x) 
 Partial response (PR) 
xx (xx.x) 
xx (xx.x) 
 Stable disease 
xx (xx.x) 
xx (xx.x) 
 Progressive disease  
xx (xx.x) 
xx (xx.x) 
   Not Assessable*  
xx (xx.x) 
xx (xx.x) 
 
 
 
End of Cycle 5 
 
 
 Complete response(CR) 
xx (xx.x) 
xx (xx.x) 
 Partial response (PR) 
xx (xx.x) 
xx (xx.x) 
 Stable disease 
xx (xx.x) 
xx (xx.x) 
 Progressive disease  
xx (xx.x) 
xx (xx.x) 
 Not Assessable*  
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
* If there is no post-baseline tumor assessment or the response for all post-baseline tumor assessments is not assessable or unable to 
  evaluate, the best overall response is classified as not assessable.  
 
 
 
<<Programming Note: Repeat for Cycles 7, 11, 13, 25).>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
97 
 
Table 14.2.2.6.1 
Summary of Duration of Response During Randomized Treatment Period 
Intent-to-Treat Set 
 
 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
By Investigator’s Assessment 
 
 
  Number of Subjects with Confirmed CR or PR 
N’=xx 
N’=xx 
     Subjects with Progressive Disease (n, %) 
xx (xx.x) 
xx (xx.x) 
   Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
  Duration of Response (months) 
 
 
   Kaplan-Meier Estimate  
 
 
     Q1 
xx.x 
xx.x 
     Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
     Q3 
xx.x 
xx.x 
   Mean 
xx.xx 
xx.xx 
   Standard Deviation 
xx.xxx 
xx.xxx 
   Median 
xx.xx 
xx.xx 
   Minimum 
xx.x 
xx.x 
   Maximum 
xx.x 
xx.x 
 
 
 
By Independent Review Committee 
 
 
Number of Subjects with Confirmed CR or PR 
N’=xx 
N’=xx 
   Subjects with Progressive Disease (n, %) 
xx (xx.x) 
xx (xx.x) 
   Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Duration of Response (months) 
 
 
   Kaplan-Meier Estimate  
 
 
     Q1 
xx.x 
xx.x 
     Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
     Q3 
xx.x 
xx.x 
     Mean 
xx.xx 
xx.xx 
   Standard Deviation 
xx.xxx 
xx.xxx 
   Median 
xx.xx 
xx.xx 
   Minimum 
xx.x 
xx.x 
   Maximum 
xx.x 
xx.x 
Note: Percentage is calculated using N’ as the denominator. CR = complete response, PR = partial response. 
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
98 
 
Table 14.2.2.6.2 
Summary of Duration of Response During Randomized Treatment Period by Disease Type 
Intent-to-Treat Set 
 
Disease Type = MF 
 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
By Investigator’s Assessment 
 
 
  Number of Subjects with Confirmed CR or PR 
N’=xx 
N’=xx 
     Subjects with Progressive Disease (n, %) 
xx (xx.x) 
xx (xx.x) 
   Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
  Duration of Response (months) 
 
 
   Kaplan-Meier Estimate  
 
 
     Q1 
xx.x 
xx.x 
     Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
     Q3 
xx.x 
xx.x 
   Mean 
xx.xx 
xx.xx 
   Standard Deviation 
xx.xxx 
xx.xxx 
   Median 
xx.xx 
xx.xx 
   Minimum 
xx.x 
xx.x 
   Maximum 
xx.x 
xx.x 
 
 
 
By Independent Review Committee 
 
 
Number of Subjects with Confirmed CR or PR 
N’=xx 
N’=xx 
   Subjects with Progressive Disease (n, %) 
xx (xx.x) 
xx (xx.x) 
   Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Duration of Response (months) 
 
 
   Kaplan-Meier Estimate  
 
 
     Q1 
xx.x 
xx.x 
     Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
     Q3 
xx.x 
xx.x 
     Mean 
xx.xx 
xx.xx 
   Standard Deviation 
xx.xxx 
xx.xxx 
   Median 
xx.xx 
xx.xx 
   Minimum 
xx.x 
xx.x 
   Maximum 
xx.x 
xx.x 
Note: Percentage is calculated using N’ as the denominator. CR = complete response, PR = partial response. 
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
 
 
<<Programming Note: Repeat for the following subgroup: Disease Type (SS).>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
99 
 
The following tables will have a similar layout as Table 14.2.2.6.1 and 14.2.2.6.2: 
Table 14.2.2.6.3 
Summary of Duration of Response During Randomized Treatment Period 
Efficacy Evaluable Set  
 
Table 14.2.2.6.4 
Summary of Duration of Response During Randomized Treatment Period by Disease Type 
Efficacy Evaluable Set  
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
100 
 
Table 14.2.2.7.1 
Summary of Time to Response During Randomized Treatment Period 
Intent-to-Treat Set 
  
 
Vorinostat 
N=xxx 
KW-0761 
N=xxx 
By Investigator’s Assessment 
 
 
  Time to Response (months)* 
 
 
n 
                     xx 
                  xx 
Mean 
                     xx.x 
                  xx.x 
Std Dev 
                     xx.xx 
                  xx.xx 
Median 
                     xx.x 
                  xx.x 
Minimum 
                     xx 
                  xx 
Maximum 
                     xx 
                  xx 
 
 
 
By Independent Review Committee 
 
 
  Time to Response (months)* 
 
 
n 
                     xx 
                  xx 
Mean 
                     xx.x 
                  xx.x 
Std Dev 
                     xx.xx 
                  xx.xx 
Median 
                     xx.x 
                  xx.x 
Minimum 
                     xx 
                  xx 
Maximum 
                     xx 
                  xx 
* For subjects with confirmed complete response or partial response.  
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
101 
 
Table 14.2.2.7.2 
Summary of Time to Response During Randomized Treatment Period by Disease Type 
Intent-to-Treat Set 
 
Disease Type = MF 
 
             Vorinostat 
            N=xxx 
KW-0761 
N=xxx 
By Investigator’s Assessment 
 
 
  Time to Response (months)* 
 
 
n 
                     xx 
xx 
Mean 
                     xx.x 
  xx.x 
Std Dev 
                     xx.xx 
   xx.xx 
Median 
                     xx.x 
  xx.x 
Minimum 
                     xx 
xx 
Maximum 
                     xx 
xx 
 
 
 
By Independent Review Committee 
 
 
  Time to Response (months)* 
 
 
n 
                     xx 
xx 
Mean 
                     xx.x 
  xx.x 
Std Dev 
                     xx.xx 
   xx.xx 
Median 
                     xx.x 
  xx.x 
Minimum 
                     xx 
xx 
Maximum 
                     xx 
xx 
* For subjects with confirmed complete response or partial response.  
 
<<Programming Note: Repeat for the following subgroup: Histologically Confirmed Diagnosis (SS).>> 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
102 
 
The following tables will have a similar layout as Table 14.2.2.7.1 and 14.2.2.7.2: 
Table 14.2.2.7.3 
Summary of Time to Response During Randomized Treatment Period 
Efficacy Evaluable Set  
 
Table 14.2.2.7.4 
Summary of Time to Response During Randomized Treatment Period by Disease Type 
Efficacy Evaluable Set 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
103 
 
Table 14.2.2.8.1 
Summary of Best Overall Response Based on Investigator’s Assessment During Crossover Portion 
Intent-to-Treat Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
 
Total 
(N=xx) 
n    (%) 
 
Overall response (confirmed CR + PR)  
 
xx (xx.x) 
 
   95% CI* 
 
(xx.x, xx.x) 
 
 
 
 
 
Best Overall Response 
 
 
 
 Complete response (CR) 
   Confirmed CR 
 
xx (xx.x) 
xx (xx.x) 
 
 Partial response (PR) 
   Confirmed PR 
 
xx (xx.x) 
xx (xx.x) 
 
 Stable disease 
 
xx (xx.x) 
 
 Progressive disease 
 
xx (xx.x) 
 
   Not Assessable  
 
xx (xx.x) 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
* 95% CI for response rate is the exact 95% confidence interval.   
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
104 
 
Table 14.2.2.8.2 
Summary of Best Overall Response Based on Investigator’s Assessment During Crossover Portion 
By Disease Type 
Intent-to-Treat Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
Disease Type = MF 
 
 
 
Total 
(N=xx) 
n    (%) 
 
Overall response (confirmed CR + PR)  
 
xx (xx.x) 
 
   95% CI* 
 
(xx.x, xx.x) 
 
 
 
 
 
Best Overall Response 
 
 
 
 Complete response (CR) 
   Confirmed CR 
 
xx (xx.x) 
xx (xx.x) 
 
 Partial response (PR) 
   Confirmed PR 
 
xx (xx.x) 
xx (xx.x) 
 
 Stable disease 
 
xx (xx.x) 
 
 Progressive disease 
 
xx (xx.x) 
 
   Not Assessable  
 
xx (xx.x) 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
* 95% CI for response rate is the exact 95% confidence interval.   
 
 
 
<<Programming Note: Repeat for the following subgroup: Disease Type (SS).>> 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
105 
 
The following tables will have a similar layout as Table 14.2.2.8.1 and 14.2.2.8.2: 
Table 14.2.2.8.3 
Summary of Best Overall Response Based on Investigator’s Assessment During Crossover Portion 
Efficacy Evaluable Set  
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761  
 
Table 14.2.2.8.4 
Summary of Best Overall Response Based on Investigator’s Assessment During Crossover Portion 
By Disease Type 
Efficacy Evaluable Set  
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
106 
 
                                                           Table 14.2.2.9 
    Concordance Between Independent Review and Investigator's Assessment for Best Overall Response During Randomized Treatment Period 
                                                        Intent-to-Treat Set 
______________________________________________________________________________________________________________________________________ 
                                                            Vorinostat                     KW-0761  
                                                               N=xx                         N=xx 
______________________________________________________________________________________________________________________________________ 
CR by Independent Review                                       N'=  xx                       N'=  xx 
  Agreement of CR by Investigator                             xx (xx.x)                     xx (xx.x) 
  PR by Investigator                                          xx (xx.x)                     xx (xx.x) 
 
PR by Independent Review                                       N'=  xx                        N'= xx 
  Agreement of PR by Investigator                             xx (xx.x)                     xx (xx.x) 
  SD by Investigator                                          xx (xx.x)                     xx (xx.x) 
  PD by Investigator                                          xx (xx.x)                     xx (xx.x) 
 
SD by Independent Review                                       N'=  xx                        N'= xx 
  Agreement of SD by Investigator                             xx (xx.x)                     xx (xx.x) 
  Unable to Evaluate                                          xx (xx.x)                     xx (xx.x) 
 
PD by Independent Review                                       N'=  xx                        N'= xx 
  Agreement of PD by Investigator                             xx (xx.x)                     xx (xx.x) 
  PR by Investigator                                          xx (xx.x)                     xx (xx.x) 
  SD by Investigator                                          xx (xx.x)                     xx (xx.x) 
  Unable to Evaluate                                          xx (xx.x)                     xx (xx.x) 
 
Unable to Evaluate by Independent Review                       N'=  xx                        N'= xx 
  Agreement by Investigator                                   xx (xx.x)                     xx (xx.x) 
  PR by Investigator                                          xx (xx.x)                     xx (xx.x) 
  SD by Investigator                                          xx (xx.x)                     xx (xx.x) 
  PD by Investigator                                          xx (xx.x)                     xx (xx.x) 
______________________________________________________________________________________________________________________________________ 
Percentage is calculated using N' as the denominator, where N' is the number of subjects with the specified best response 
by Independent Review. 
Note: If there is no post-baseline tumor assessment or the response for all post-baseline tumor assessments is not assessable or 
unable to evaluate, the best overall response is classified as unable to evaluate. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
107 
 
Table 14.2.3.1 
Summary of Skindex-29 Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
Scale 
  Time Point 
    Statistic 
Vorinostat (N=xx) 
--------------------------------------------- 
    Base           Post            Change 
KW-0761 (N=xx) 
------------------------------------------- 
    Base            Post           Change 
Skindex-29 Score 
 
 
 
 
 
 
  Baseline 
 
 
 
 
 
 
  n 
    xx 
 
 
    xx 
 
 
  Mean 
    xx.x 
 
 
    xx.x 
 
 
  Std Dev 
    xx.xx 
 
 
    xx.xx 
 
 
  Median 
    xx.x 
 
 
    xx.x 
 
 
  Minimum 
    xx 
 
 
    xx 
 
 
  Maximum 
    xx 
 
 
    xx 
 
 
 
 
 
 
 
 
 
  End of Cycle 1 
 
 
 
 
 
 
  n 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
  Mean 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
  Std Dev 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
  Median 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
  Minimum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
  Maximum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
 
 
 
 
 
 
 
  End of Cycle 3 
 
 
 
 
 
 
  n 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
  Mean 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
  Std Dev 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
  Median 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
  Minimum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
  Maximum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
 
 
 
 
 
 
 
 Etc. 
 
 
 
 
 
 
    
<<Programming Note: Repeat for each schedule visit for Symptoms Scale Score, Emotions Scale Score, and Functioning Scale Score.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
108 
 
Table 14.2.3.2 
Analysis of Change in Skindex-29 Score from Baseline During Randomized Treatment Period 
Intent-to-Treat Set 
 
Scale 
  Time Point 
   Treatment 
N* 
--Baseline-- 
Mean (SD) 
--Endpoint-- 
Mean (SD) 
-----------------------------Change from Baseline----------------------------- 
                             --Treatment Difference (KW-0761 vs. Vorinostat)-- 
LS                           LS                                      Adjusted  
Mean (SE)      95% CI        Mean (SE)       95% CI      P-value     P-Value 
Skindex-29 Score 
 
 
 
 
 
  End of Cycle 1 
 
   
 
 
xx.x (xx.xx)  (xx.x, xx.x)   x.xxxx 
   
 Vorinostat 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 KW-0761 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 
 
 
 
 
 
 
  End of Cycle 3 
 
 
 
 
xx.x (xx.xx)  (xx.x, xx.x)   x.xxxx 
 
 Vorinostat 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 KW-0761 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 
 
 
 
 
 
 
  End of Cycle 5 
 
 
 
 
xx.x (xx.xx)  (xx.x, xx.x)   x.xxxx 
 
 Vorinostat 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 KW-0761 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 
 
 
 
 
 
 
Overall Across 6-Month Assessment 
 
 
xx.x (xx.xx)  (xx.x, xx.x)   x.xxxx 
x.xxxx 
  Vorinostat 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
  KW-0761 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 
 
 
 
 
 
 
End of Cycle 7 
 
 
 
 
xx.x (xx.xx)  (xx.x, xx.x)   x.xxxx 
 
 Vorinostat 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 KW-0761 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
* N is the number of subjects with values at baseline and post-baseline. 
Note: LS mean, SE, 95% CI and P-value are from MMRM with treatment, disease type, disease stage, and region as fixed effects and 
baseline score as a covariate. Adjusted P-value is calculated using Sidak method for the overall difference across time points through 
6-month assessment (including End of Cycles 1, 3, and 5 timepoints only). Time points beyond Cycle 11 are not included due to the 
small number of subjects on study after cycle 11. 
         
<<Programming Note: Repeat for Symptoms Scale Score, Emotions Scale Score, and Functioning Scale Score. Adjusted p-value is only presented 
for the overall treatment difference through 6-month assessment for the Skindex-29 score including the End of Cycle 1, End of Cycle 3, and End of 
Cycle 5 time points.>>


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
109 
 
The following tables will have similar layout as Table 14.2.3.1 and Table 14.2.3.2: 
 
Table 14.2.3.3 
Summary of Skindex-29 Score and Change from Baseline by Visit During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Table 14.2.3.4 
Analysis of Change in Skindex-29 Score from Baseline During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Table 14.2.3.5 
Summary of Skindex-29 Score and Change from Baseline by Visit During Crossover Portion 
Intent-to-Treat Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
<<Programming Note: For tables 14.2.3.3 and 14.2.3.5, all scheduled timepoints according to the study procedures will be presented. >> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
110 
 
The following tables will have similar layout as Table 14.2.3.1 and Table 14.2.3.2: 
Table 14.2.4.1 
Summary of FACT-G Total Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
Table 14.2.4.2 
Analysis of Change in FACT-G Total Score from Baseline During Randomized Treatment Period 
Intent-to-Treat Set 
 
Table 14.2.4.3 
Summary of FACT-G Total Score and Change from Baseline by Visit During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Table 14.2.4.4 
Analysis of Change in FACT-G Total Score from Baseline During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Table 14.2.4.5 
Summary of FACT-G Total Score and Change from Baseline by Visit During Crossover Portion 
Intent-to-Treat Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
Table 14.2.4.6 
Summary of FACT-G Physical Well-Being Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
Table 14.2.4.7 
Summary of FACT-G Social Well-Being Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
Table 14.2.4.8 
Summary of FACT-G Emotional Well-Being Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
Table 14.2.4.9 
Summary of FACT-G Functional Well-Being Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
<<Programming Note:   For tables 14.2.4.1, 14.2.4.3, and  14.2.4.5-14.2.4.9, all scheduled timepoints according to the study procedures will be 
presented.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
111 
 
The following tables will have similar layout as Table 14.2.3.1: 
 
Table 14.2.5.1 
Summary of EQ-5D-3L Index Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
Table 14.2.5.2 
Analysis of Change in EQ-5D-3L Index Score from Baseline During Randomized Treatment Period 
Intent-to-Treat Set 
 
Table 14.2.5.3 
Summary of EQ-5D-3L Index Score and Change from Baseline by Visit During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Table 14.2.5.4 
Analysis of Change in EQ-5D-3L Index Score from Baseline During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Table 14.2.5.5 
Summary of EQ-5D-3L Index Score and Change from Baseline by Visit During Crossover Portion 
Intent-to-Treat Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
<<Programming Note: For tables 14.2.5.1,  14.2.5.3, and 14.2.5.5, all scheduled timepoints according to the study procedures will be presented. 
>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
112 
 
Table 14.2.5.6 
Summary of EQ-5D-3L by Dimension and by Visit During Randomized Treatment Period – Number (%) of Subjects  
Intent-to-Treat Set 
 
Dimension 
   Time Point 
Vorinostat (N=xx) 
----------------------------------------------- 
No Problem     Some Problem    Extreme Problem    
KW-0761 (N=xx) 
----------------------------------------------- 
   No Problem     Some Problem    Extreme Problem 
Mobility 
 
 
 Baseline (n/N’, %) 
  xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
   xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
 
 
 
 End of Cycle 1(n/N’, %) 
  xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
   xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
 
 
 
 End of Cycle 3 (n/N’, %) 
  xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
   xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
 
 
 
 End of Cycle 5 (n/N’, %) 
  xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
   xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
 
 
 
 End of Cycle 7 (n/N’, %) 
  xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
   xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
 
 
 
 End of Cycle 9 (n/N’, %) 
  xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
   xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
 
 
 
 End of Cycle 11 (n/N’, %) 
  xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
   xx/xx (xx.x)    xx/xx (xx.x)     xx/xx (xx.x) 
Etc. 
 
 
Note: Percentage is calculated using N’ as the denominator, where N’ is the number of subjects with valid measurement at the specified 
time point.  
 
<<Programming Note: Dimensions also to be included: Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
113 
 
The following tables will have similar layout as Table 14.2.5.6: 
Table 14.2.5.7 
Summary of EQ-5D-3L by Dimension and by Visit During Randomized Treatment Period – Number (%) of Subjects 
Efficacy Evaluable Set 
 
 
Table 14.2.5.8 
Summary of EQ-5D-3L by Dimension and by Visit During Crossover Portion – Number (%) of Subjects 
Intent-to-Treat Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
  
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
114 
 
The following tables will have similar layout as Table 14.2.3.1 and Table 14.2.3.2: 
 
Table 14.2.6.1 
Summary of EQ-5D-3L VAS Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
Table 14.2.6.2 
Analysis of Change in EQ-5D-3L VAS Score from Baseline During Randomized Treatment Period  
Intent-to-Treat Set 
 
Table 14.2.6.3 
Summary of EQ-5D-3L VAS Score and Change from Baseline by Visit During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Table 14.2.6.4 
Analysis of Change in EQ-5D-3L VAS Score from Baseline During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Table 14.2.6.5 
Summary of EQ-5D-3L VAS Score and Change from Baseline by Visit During Crossover Portion 
Intent-to-Treat Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
<<Programming Note: For tables 14.2.6.1, 14.2.6.3, and14.2.6.5, all scheduled timepoints according to the study procedures will be 
presented.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
115 
 
The following tables will have similar layout as Table 14.2.3.1 and Table 14.2.3.2: 
 
Table 14.2.7.1 
Summary of Pruritus Evaluation Itchy Quality of Life Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
Table 14.2.7.2 
Analysis of Change in Pruritus Evaluation Itchy Quality of Life Score from Baseline During Randomized Treatment Period 
Intent-to-Treat Set 
 
Table 14.2.7.3 
Summary of Pruritus Evaluation Itchy Quality of Life Score and Change from Baseline by Visit During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Table 14.2.7.4 
Analysis of Change in Pruritus Evaluation Itchy Quality of Life Score from Baseline During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Table 14.2.7.5 
Summary of Pruritus Evaluation Itchy Quality of Life Score and Change from Baseline by Visit During Crossover Portion 
Intent-to-Treat Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
<<Programming Note: 
(1) Only the overall score will be presented for Itchy Quality of Life. 
(2) For tables 14.2.7.1,  14.2.7.3, and 14.2.7.5, all scheduled timepoints according to the study procedures will be presented.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
116 
 
The following table will have a similar layout as Table 14.2.3.1: 
Table 14.2.8.1 
Summary of Pruritus Evaluation Likert Scale Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
<<Programming Note: For Table 14.2.8.1, add a row in each time point to display interquartile range after median.>> 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
117 
 
Table 14.2.8.2 
Analysis of Change in Pruritus Evaluation Likert Scale Score from Baseline  
During Randomized Treatment Period 
Intent-to-Treat Set 
 
Time Point 
  Treatment 
N* 
--Baseline-- 
Median (IQR) 
--Endpoint-- 
Median (IQR) 
------------------------------Change from Baseline----------------------------- 
                             --Treatment Difference (KW-0761 vs. Vorinostat)-- 
Median (IQR)    95% CI        Median (IQR)       95% CI           P-value        
End of Cycle 1 
 
 
 
 
xx.x (xx.xx)     (xx.x, xx.x)       x.xxxx 
  
Vorinostat 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
KW-0761 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 
 
 
 
 
 
 
End of Cycle 3 
 
 
 
 
xx.x (xx.xx)     (xx.x, xx.x)       x.xxxx 
 
Vorinostat 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
KW-0761 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 
 
 
 
 
 
 
End of Cycle 5 
 
 
 
 
xx.x (xx.xx)     (xx.x, xx.x)       x.xxxx 
 
Vorinostat 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
KW-0761 
xxx 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx)  (xx.x, xx.x) 
 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
* N is the number of subjects with values at baseline and post-baseline. 
Note: Treatment difference (KW-0761 - Vorinostat) and its 95% CI are estimated using Hodges-Lehmann estimator and Moses method.  
P-values are obtained from Wilcoxon Rank Sum test. Time points beyond Cycle 11 are not included due to the small number of subjects on 
study after cycle 11. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
118 
 
The following tables will have similar layout as Table 14.2.8.1 and Table 14.2.8.2: 
 
Table 14.2.8.3 
Summary of Pruritus Evaluation Likert Scale Score and Change from Baseline by Visit During Randomized Treatment Period 
Intent-to-Treat Set 
 
 
Table 14.2.8.4 
Analysis of Change in Pruritus Evaluation Likert Scale Score from Baseline  
During Randomized Treatment Period 
Intent-to-Treat Set 
 
 
Table 14.2.8.5 
Summary of Pruritus Evaluation Likert Scale Score and Change from Baseline by Visit During Randomized Treatment Period 
Efficacy Evaluable Set 
 
 
Table 14.2.8.6 
Analysis of Change in Pruritus Evaluation Likert Scale Score from Baseline  
During Randomized Treatment Period 
Efficacy Evaluable Set 
 
 
Table 14.2.8.7 
Summary of Pruritus Evaluation Likert Scale Score and Change from Baseline by Visit During Crossover Portion 
Intent-to-Treat Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
<<Programming Note: For tables 14.2.8.3,  14.2.8.5, and 14.2.8.7, the scheduled timepoint according to the study procedures will be 
presented.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
119 
 
Table 14.2.9.1 
Summary of Overall Survival (OS) 
Intent-to-Treat Set 
 
 
Vorinostat  
N=xxx 
KW-0761 
N=xxx 
Subjects Died (n, %) 
xx (xx.x) 
xx (xx.x) 
Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Overall Survival (months) 
 
 
 Kaplan-Meier Estimate of OS 
 
 
    Q1 
xx.x 
xx.x 
    Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Q3 
xx.x 
xx.x 
 Mean 
xx.xx 
xx.xx 
 Standard Deviation 
xx.xxx 
xx.xxx 
 Median 
xx.xx 
xx.xx 
 Minimum 
xx.x 
xx.x 
 Maximum 
xx.x 
xx.x 
 
 
 
   ------ Treatment Comparison ----- 
   KW-0761 vs. Vorinostat 
 
 
    Hazard Ratio (95% CI)**     
 
xx.x (xx.x, xx.x) 
    Log rank p-value* 
 
x.xxxx 
 
 
 
 Rate (%) of Being Alive for at Least*** 
 
 
    6 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    12 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    18 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    24 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Etc. 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator.  
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
** Hazard ratio and 95% CI are based on Cox proportional hazards model with treatment, disease type, disease stage, and region as 
factors. P-values is obtained from a stratified log rank test with disease type, disease stage, and region as the stratification 
factors. 
*** Kaplan-Meier estimate.    
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
120 
 
Table 14.2.9.2 
Overall Survival (OS) Analysis Using RPSFT Model 
Intent-to-Treat Set 
 
 
Vorinostat  
N=xxx 
KW-0761 
N=xxx 
Subjects Died (n, %) 
xx (xx.x) 
xx (xx.x) 
Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Overall Survival (months) 
 
 
 Kaplan-Meier Estimate of OS 
 
 
    Q1 
xx.x 
xx.x 
    Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Q3 
xx.x 
xx.x 
 Mean 
xx.xx 
xx.xx 
 Standard Deviation 
xx.xxx 
xx.xxx 
 Median 
xx.xx 
xx.xx 
 Minimum 
xx.x 
xx.x 
 Maximum 
xx.x 
xx.x 
 
 
 
   ------ Treatment Comparison ----- 
   KW-0761 vs. Vorinostat 
 
 
    Hazard Ratio (95% CI)**     
 
xx.x (xx.x, xx.x) 
    p-value** 
 
x.xxxx 
 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. RPSFT = rank-preserving 
structural failure time. 
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
** Hazard ratio, 95% CIs and p-value are obtained from RPSFT model. 
    
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
121 
 
Table 14.2.9.3 
Overall Survival (OS) Analysis Using IPCW Model 
Intent-to-Treat Set 
 
 
Vorinostat  
N=xxx 
KW-0761 
N=xxx 
Subjects Died (n, %) 
xx (xx.x) 
xx (xx.x) 
Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Overall Survival (months) 
 
 
 Kaplan-Meier Estimate of OS 
 
 
    Q1 
xx.x 
xx.x 
    Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Q3 
xx.x 
xx.x 
 Mean 
xx.xx 
xx.xx 
 Standard Deviation 
xx.xxx 
xx.xxx 
 Median 
xx.xx 
xx.xx 
 Minimum 
xx.x 
xx.x 
 Maximum 
xx.x 
xx.x 
 
 
 
   ------ Treatment Comparison ----- 
   KW-0761 vs. Vorinostat 
 
 
    Hazard Ratio (95% CI)**     
 
xx.x (xx.x, xx.x) 
    p-value** 
 
x.xxxx 
 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. IPCW = inverse probability of 
censoring weighting. 
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
** Hazard ratio, 95% CIs and p-value are obtained from the IPCW model.  
    
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
122 
 
 
Table 14.2.10 
Summary of Time to Treatment Failure (TTF) 
Intent-to-Treat Set 
 
 
Vorinostat  
N=xxx 
KW-0761 
N=xxx 
Subjects with Treatment Failure (n, %) 
xx (xx.x) 
xx (xx.x) 
  Earliest Contributing Events: 
 
 
    Discontinuation of Randomized Treatment Due to 
xx (xx.x) 
xx (xx.x) 
       PD per CTCL response criteria 
xx (xx.x) 
xx (xx.x) 
       Clinical progression 
xx (xx.x) 
xx (xx.x) 
       Adverse event 
xx (xx.x) 
xx (xx.x) 
       Death 
xx (xx.x) 
xx (xx.x) 
    Initiation of Another New Anti-cancer Therapy  
xx (xx.x) 
xx (xx.x) 
 
 
 
Subjects Censored (n, %) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Time to Treatment Failure (months) 
 
 
 Kaplan-Meier Estimate of TTF 
 
 
    Q1 
xx.x 
xx.x 
    Median (95% CI)* 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Q3 
xx.x 
xx.x 
 Mean 
xx.xx 
xx.xx 
 Standard Deviation 
xx.xxx 
xx.xxx 
 Median 
xx.xx 
xx.xx 
 Minimum 
xx.x 
xx.x 
 Maximum 
xx.x 
xx.x 
 
 
 
   ------ Treatment Comparison ----- 
   KW-0761 vs. Vorinostat 
 
 
    Hazard Ratio (95% CI)**     
 
xx.x (xx.x, xx.x) 
    Log rank p-value* 
 
x.xxxx 
 
 
 
 Rate (%) of Being Alive without Treatment  
 Failure for at Least*** 
 
 
    6 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    12 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    18 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    24 months (95% CI) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
    Etc. 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator.  
* 95% CIs are obtained from SAS proc lifetest using loglog transformation. 
** Hazard ratio and 95% CI are based on Cox proportional hazards model with treatment, disease type, disease stage, and region as 
factors. P-values is obtained from a stratified log rank test with disease type, disease stage, and region as the stratification 
factors. 
*** Kaplan-Meier estimate.    


Statistical Analysis Plan 
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123 
 
Table 14.3.1.1 
Overview of Adverse Events During Randomized Treatment Period 
Safety Analysis Set 
  
Adverse Event Category 
 
Vorinostat  
N=xx 
n    (%) 
 
KW-0761 
N=xx 
n    (%) 
 
 
Adverse Events (AEs) 
 
 
 
 
 
 
   Any AEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
   Any TEAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
   Drug-related TEAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
NCI/CTCAE Grade III/IV/V AEs 
 
 
 
 
 
 
 Any Grade III/IV/V AEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 Any Grade III/IV/V TEAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 Drug-related Grade III/IV/V TEAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Deaths 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Serious Adverse Events (SAEs) 
 
 
 
 
 
 
 Any SAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 Treatment-emergent SAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 Drug-related Treatment-emergent SAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Discontinuation Due to AEs 
 
 
 
 
 
 
 Any AEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 Any TEAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 Drug-related TEAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
 
 


Statistical Analysis Plan 
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Table 14.3.1.2 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) During Randomized Treatment Period 
By System Organ Class and Preferred Term 
Safety Analysis Set  
 
System Organ Class* 
   Preferred Term* 
 
Vorinostat  
N=xx 
n    (%) 
 
KW-0761 
N=xx 
n    (%) 
 
 
Subjects with Any TEAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
   Preferred Term 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
   Preferred Term 2 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
   Preferred Term 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
   Preferred Term 2 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 Etc. … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
* MedDRA Version 15.1 was used for coding. 


Statistical Analysis Plan 
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The following table will have a similar layout as Table 14.3.1.2: 
Table 14.3.1.3 
Number (%) of Subjects with Drug-Related Treatment-Emergent Adverse Events (TEAEs) During Randomized Treatment Period 
By System Organ Class and Preferred Term 
Safety Analysis Set  
 


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Table 14.3.1.4 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) During Randomized Treatment Period 
By System Organ Class, Preferred Term, and Highest CTCAE Grade 
Safety Analysis Set  
 
System Organ Class* 
   Preferred Term* 
      Highest CTCAE Grade 
 
Vorinostat  
N=xx 
n    (%) 
 
KW-0761 
N=xx 
n    (%) 
 
 
Subjects with Any TEAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade I 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade II 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade III 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade IV 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade V 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade I 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade II 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade III 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade IV 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade V 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
   Preferred Term 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade I 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade II 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
    Grade III 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade IV 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
      Grade V 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
Etc.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. If a subject experienced more 
than one adverse event within a preferred term, the subject will be counted once in that preferred term at the highest CTCAE grade. If 
a subject experienced more than one adverse event within an SOC, the subject will be counted once for that SOC at the highest CTCAE 
grade. 
* MedDRA Version 15.1 was used for coding. 


Statistical Analysis Plan 
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The following tables will have similar layout as Table 14.3.1.2 and Table 14.3.1.4: 
 
Table 14.3.1.5 
Number (%) of Subjects with Drug-Related Treatment-Emergent Adverse Events (TEAEs) During Randomized Treatment Period 
By System Organ Class, Preferred Term, and Highest CTCAE Grade 
Safety Analysis Set  
 
Table 14.3.1.6 
Number (%) of Subjects with Grade III/IV/V Treatment-Emergent Adverse Events (TEAEs) During Randomized Treatment Period 
By System Organ Class and Preferred Term 
Safety Analysis Set  
 
Table 14.3.1.7 
Number (%) of Subjects with Drug-Related Grade III/IV/V Treatment-Emergent Adverse Events (TEAEs) During Randomized Treatment Period 
By System Organ Class and Preferred Term 
Safety Analysis Set  
 
Table 14.3.1.8 
Number (%) of Subjects with Treatment-Emergent Serious Adverse Events During Randomized Treatment Period 
By System Organ Class and Preferred Term 
Safety Analysis Set  
 
Table 14.3.1.9 
Number (%) of Subjects with Drug-Related Treatment-Emergent Serious Adverse Events During Randomized Treatment Period 
By System Organ Class and Preferred Term 
Safety Analysis Set  
 
Table 14.3.1.10 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation During Randomized Treatment Period 
By System Organ Class and Preferred Term 
Safety Analysis Set  
 
Table 14.3.1.11 
Number (%) of Subjects with Drug-Related Treatment-Emergent Adverse Events (TEAEs) Leading to Discontinuation During Randomized 
Treatment Period 
By System Organ Class and Preferred Term 
Safety Analysis Set  
 
Table 14.3.1.12 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) During Randomized Treatment Period 
By Gender, System Organ Class and Preferred Term 
Safety Analysis Set  
 


Statistical Analysis Plan 
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Table 14.3.1.13 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) During Randomized Treatment Period 
By Age Group, System Organ Class and Preferred Term 
Safety Analysis Set  
 
<<Programming Note: Table 14.3.1.12 and Table 14.3.1.13 will have similar format as Table 14.3.1.2 but paging by subgroup. For Table 
14.3.1.13, the following Age Group will be used: <65 years vs. >=65 years.>> 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
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The following tables will have similar layout as Table 14.3.1.1, Table 14.3.1.2, and Table 14.3.1.4: 
Table 14.3.2.1 
Overview of Adverse Events During Crossover Portion 
Safety Analysis Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
Table 14.3.2.2 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) Related to KW-0761 During Crossover Portion  
By System Organ Class and Preferred Term 
Safety Analysis Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Table 14.3.2.3  
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) Related to KW-0761 During Crossover Portion 
By System Organ Class, Preferred Term, and Highest CTCAE Grade 
Safety Analysis Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Table 14.3.2.4 
Number (%) of Subjects with Grade III/IV/V Treatment-Emergent Adverse Events (TEAEs) Related to KW-0761 During Crossover Portion 
By System Organ Class and Preferred Term 
Safety Analysis Set  
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Table 14.3.2.5 
Number (%) of Subjects with Treatment-Emergent Serious Adverse Events Related to KW-0761 During Crossover Portion 
By System Organ Class and Preferred Term 
Safety Analysis Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Table 14.3.2.6 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) Related to KW-0761 Leading to Discontinuation  
During Crossover Portion By System Organ Class and Preferred Term 
Safety Analysis Set  
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
<<Programming Note: For Table 14.3.2.1 to 14.3.2.6, only display the total column.>> 


Statistical Analysis Plan 
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Table 14.3.3.1 
Number (%) of Subjects with Treatment-Emergent Adverse Events (TEAEs) Related to KW-0761 for Subjects Exposed to KW-0761 
By System Organ Class and Preferred Term 
Safety Analysis Set  
 
System Organ Class* 
   Preferred Term* 
 
Initially Randomized 
to KW-0761 
N=xx 
n    (%) 
 
Crossed Over to 
KW-0761**  
N=xx 
n    (%) 
 
All Subjects Exposed 
to KW-0761** 
N=xx 
n    (%) 
Subjects with Any TEAEs 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
System Organ Class 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
   Preferred Term 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
   Preferred Term 2 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
System Organ Class 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
   Preferred Term 1 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
   Preferred Term 2 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 Etc. … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Percentage is calculated using the number of subjects in the column heading as the denominator. 
* MedDRA Version 15.1 was used for coding. 
** For subjects who are randomized to Vorinostat and crossed over to KW-0761, the TEAEs during the crossover portion are summarized. 
 
 


Statistical Analysis Plan 
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                                                           Table 14.3.3.2 
                 Exposure-Adjusted Incidence Rate of Infections and Infestations During Randomized Treatment Period 
                                                         By Preferred Term 
                                                        Safety Analysis Set 
______________________________________________________________________________________________________________________________________ 
                                                    Number(%) of AE                  Incidence Rates Per Patient-months of Exposure[a] 
                                              ---------------------------------      ------------------------------------------------ 
                                                Vorinostat          KW-0761               Vorinostat                 KW-0761 
System Organ Class*                               N=xx               N=xx 
  Preferred Term*                               n    (%)            n    (%) 
______________________________________________________________________________________________________________________________________ 
INFECTIONS AND INFESTATIONS                     xx (xx.x)          xx (xx.x)                #.##                      #.## 
  Preferred Term 1                              xx (xx.x)          xx (xx.x)                #.##                      #.## 
  Preferred Term 2                                      
  Preferred Term 3                                         
  Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Percentage is calculated using the number of subjects in the column heading as the denominator. 
If a subject experienced more than one adverse event within an SOC, the subject will be counted once for that SOC. If a subject 
experienced more than one adverse event within a preferred term, the subject will be counted once for that preferred term. 
* MedDRA Version xx.x was used for coding. 
[a] Incidence Rates per Patient-months of Exposure = (Number of patients with AEs/sum of days at risk for AEs) * 30.42 days/month,   
where days at risk is defined as the last dose date of randomized treatment - first dose date of randomized treatment + 90 for 
subjects who did not crossover and first dose date of KW-0761 - first dose date of randomized treatment for subjects who crossed over. 
 
 


Statistical Analysis Plan 
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                                                           Table 14.3.3.3 
                 Exposure-Adjusted Event Rate of Infections and Infestations During Randomized Treatment Period 
                                                         By Preferred Term 
                                                        Safety Analysis Set 
______________________________________________________________________________________________________________________________________ 
                                                    Number(%) of AE                  Event Rates Per Patient-months of Exposure[a] 
                                              ----------------------------------   -------------------------------------------------- 
                                                Vorinostat          KW-0761               Vorinostat                 KW-0761 
System Organ Class*                               N=xx               N=xx 
  Preferred Term*                               n    (%)            n    (%) 
______________________________________________________________________________________________________________________________________ 
INFECTIONS AND INFESTATIONS                     xx (xx.x)          xx (xx.x)                #.##                      #.## 
  Preferred Term 1                              xx (xx.x)          xx (xx.x)                #.##                      #.## 
  Preferred Term 2                                      
  Preferred Term 3                                         
  Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Percentage is calculated using the number of subjects in the column heading as the denominator. 
If a subject experienced more than one adverse event within an SOC, the subject will be counted once for that SOC. If a subject 
experienced more than one adverse event within a preferred term, the subject will be counted once for that preferred term. 
* MedDRA Version xx.x was used for coding. 
[a] Event Rates per Patient-months of Exposure = (Number of AEs/sum of days at risk for AEs) * 30.42 days/month, where days at risk is 
defined as the last dose date of randomized treatment - first dose date of randomized treatment + 90 for subjects who did not 
crossover and first dose date of KW-0761 - first dose date of randomized treatment for subjects who crossed over. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
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The following tables will have similar layout as Table 14.3.3.2 and Table 14.3.3.3: 
Table 14.3.3.4 
        Exposure-Adjusted Incidence Rate of Respiratory, Thoracic and Mediastinal Disorders During Randomized Treatment Period 
                                                         By Preferred Term 
                                                        Safety Analysis Set 
 
Table 14.3.3.5 
          Exposure-Adjusted Event Rate of Respiratory, Thoracic and Mediastinal Disorders During Randomized Treatment Period 
                                                         By Preferred Term 
                                                        Safety Analysis Set 
 
Table 14.3.3.6 
                 Exposure-Adjusted Incidence Rate of Renal and Urinary Disorders During Randomized Treatment Period 
                                                         By Preferred Term 
                                                        Safety Analysis Set 
 
Table 14.3.3.7 
                 Exposure-Adjusted Event Rate of Renal and Urinary Disorders During Randomized Treatment Period 
                                                         By Preferred Term 
                                                        Safety Analysis Set 
  
Table 14.3.3.8 
         Exposure-Adjusted Incidence Rate of Musculoskeletal and Connective Tissue Disorders During Randomized Treatment Period 
                                                         By Preferred Term 
                                                        Safety Analysis Set 
 
Table 14.3.3.9 
                 Exposure-Adjusted Event Rate of Musculoskeletal and Connective Tissue During Randomized Treatment Period 
                                                         By Preferred Term 
                                                        Safety Analysis Set 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
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Table 14.3.4.1 
Shift Table for Selected Laboratory Parameters During Randomized Treatment Period – Serum Chemistry 
Safety Analysis Set 
 
Parameter (Unit) 
   Treatment Arm 
 
 
Baseline 
---- Highest CTCAE Grade During Randomized Treatment Period ---- 
N’ 
<=Grade II 
 
>=Grade III 
 
Total 
 
XXX (Unit) 
 
 
 
 
 
 
 
 
   Vorinostat 
 
 
 
 
 
 
 
 
  (N=xx) 
xx 
<=Grade II 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
>=Grade III 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
Total 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
   KW-0761 
 
 
 
 
 
 
 
 
  (N=xx) 
xx 
<=Grade II 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
>=Grade III 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
Total 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
Etc. 
 
 
 
 
 
 
 
 
Note: Percentage is calculated using N’ as the denominator where N’ is the number of subjects with both baseline and post baseline 
measurements for the specified parameter. 
 
<<Programming Note: parameters in this table include: AST, ALT, Alkaline Phosphatase, Albumin, Creatinine, Glucose, Total Bilirubin, 
Phosphorus, and Magnesium. High shifts and low shifts will be summarized for parameters with separate CTC grade criteria for low values and 
high values (i.e., Glucose and Magnesium).>>  


Statistical Analysis Plan 
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Table 14.3.4.2 
Shift Table for Selected Laboratory Parameters During Randomized Treatment Period – Hematology 
Safety Analysis Set  
 
Parameter (Unit) 
   Treatment Arm 
 
 
Baseline 
----  Highest CTCAE Grade During Randomized Treatment Period ---- 
N’ 
<=Grade II 
 
>=Grade III 
 
Total 
 
XXX (Unit) 
 
 
 
 
 
 
 
 
   Vorinostat 
 
 
 
 
 
 
 
 
  (N=xx) 
xx 
<=Grade II 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
>=Grade III 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
Total 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
   KW-0761 
 
 
 
 
 
 
 
 
  (N=xx) 
xx 
<=Grade II 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
>=Grade III 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
Total 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
Etc. 
 
 
 
 
 
 
 
 
Note: Percentage is calculated using N’ as the denominator where N’ is the number of subjects with both baseline and post baseline 
measurements for the specified parameter. 
 
<<Programming Note: parameters in this table include: Hemoglobin, WBC, Platelet Count, Lymphocytes, ANC, and CD4. >>  


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
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The following tables will have similar layout as Tables 14.3.4.1 and 14.3.4.2: 
Table 14.3.4.3 
Shift Table for Selected Laboratory Parameters During Crossover Portion – Serum Chemistry 
Safety Analysis Set  
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
Table 14.3.4.4 
Shift Table for Selected Laboratory Parameters During Crossover Portion – Hematology 
Safety Analysis Set  
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
<<Programming Note: For tables 14.3.4.3 and 14.3.4.4, the highest CTCAE Grade during Crossover Period will be presented.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
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Table 14.3.4.5 
Number (%) of Subjects with Grade >=III Laboratory Values for Selected Hematology Parameters 
Safety Analysis Set 
  
Period  
  Parameter 
 
Vorinostat  
N=xx 
n/N’   (%) 
 
KW-0761 
N=xx 
n/N’    (%) 
 
 
During Randomized Treatment Period 
 
 
 
 
 
 
  White Blood Cell Count 
 
xx/xx (xx.x) 
 
xx/xx (xx.x) 
 
 
  Hemoglobin 
 
xx/xx (xx.x) 
 
xx/xx (xx.x) 
 
 
  Platelet Count 
 
xx/xx (xx.x) 
 
xx/xx (xx.x) 
 
 
  Absolute Neutrophil Count (ANC) 
 
xx/xx (xx.x) 
 
xx/xx (xx.x) 
 
 
 
 
 
 
 
 
 
During Crossover Period 
 
 
 
 
 
 
  White Blood Cell Count 
 
xx/xx (xx.x) 
 
 
 
 
  Hemoglobin 
 
xx/xx (xx.x) 
 
 
 
 
  Platelet Count 
 
xx/xx (xx.x) 
 
 
 
 
Absolute Neutrophil Count (ANC) 
 
xx/xx (xx.x) 
 
 
 
 
Note: Percentage is calculated using N’ as the denominator, where N’ is the number of subjects with valid post-baseline values for the 
specified period and parameter. 


Statistical Analysis Plan 
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Table 14.3.5.1 
Summary of Vital Signs and Change from Baseline During Randomized Treatment Period 
Safety Analysis Set  
 
Parameter 
   Time Point 
     Statistic 
Vorinostat (N=xx) 
----------------------------------------- 
    Base        Post          Change 
KW-0761 (N=xx) 
---------------------------------------- 
    Base           Post          Change 
Pulse Rate (bpm)  
 
 
 
 
 
 
  Baseline  
 
 
 
 
 
 
   n  
    xx 
 
 
    xx 
 
 
   Mean 
    xx.x 
 
 
    xx.x 
 
 
   Std Dev 
    xx.xx 
 
 
    xx.xx 
 
 
   Median 
    xx.x 
 
 
    xx.x 
 
 
   Minimum 
    xx 
 
 
    xx 
 
 
   Maximum 
    xx 
 
 
    xx 
 
 
 
 
 
 
 
 
 
   Maximum Post-baseline Value  
 
 
 
 
 
 
   n  
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
   Mean 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
   Std Dev 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
   Median 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
   Minimum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
   Maximum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
 
 
 
 
 
 
 
   Minimum Post-baseline Value  
 
 
 
 
 
 
   n  
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
   Mean 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
   Std Dev 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
   Median 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
   Minimum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
   Maximum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
 
 
 
 
 
 
 
 End of Treatment* 
 
 
 
 
 
 
   n  
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
   Mean 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
   Std Dev 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
   Median 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
   Minimum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
   Maximum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
* End of Treatment is defined as the measurement obtained at the End of Treatment Visit during the randomized treatment period. If 
missing, the last post-baseline measurement during randomized treatment period is used.  
<<Programming Note: Parameters also to be included in the table: Systolic blood pressure, Diastolic blood pressure, Temperature, Respiratory 
Rate, and Body Weight.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
139 
 
The following tables will have similar layout as Table 14.3.5.1: 
Table 14.3.5.2 
Summary of Vital Signs and Change from Baseline During Crossover Portion 
Safety Analysis Set 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
Table 14.3.6.1 
Summary of QTcB and QTcF and Change from Baseline During Randomized Treatment Period 
Safety Analysis Set  
 
 
<<Programming Note: For table 14.3.6.1, only include timepoints of baseline and end of treatment.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
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Table 14.3.6.2 
Number (%) of Subjects with Abnormal QTcB and QTcF During Randomized Treatment Period 
Safety Analysis Set  
 
Parameter  
  Visit  
    Criteria 
 
Vorinostat  
N=xx 
n    (%) 
 
KW-0761 
N=xx 
n    (%) 
 
 
QTcB (msec)  
 
N’=xx 
 
N’=xx 
 
 
  Baseline 
 
 
 
 
 
 
    >450 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
    >480 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
    >500 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
  End of Treatment Visit 
 
N’=xx 
 
N’=xx 
 
 
    >450 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
    >480 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
    >500 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
    Increase >30 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
  Increase >60 msec  
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
  Overall for Post-baseline* 
 
N’=xx 
 
N’=xx 
 
 
    >450 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
    >480 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
    >500 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
    Increase >30 msec 
 
xx (xx.x) 
 
xx (xx.x) 
 
 
  Increase >60 msec  
 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Note: Percentage is calculated using N’ as the denominator, where N’ is the number of subjects with valid ECG measurement at the 
specified visit (time point). 
* Any post-baseline measurement including both scheduled and unscheduled measurements.  
 
<<Programming Note: Repeat for QTcF.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
141 
 
Table 14.3.6.3 
Shift Table for QTcB and QTcF (msec) from Baseline During Randomized Treatment Period 
Safety Analysis Set  
 
Parameter 
  Treatment Arm 
N’ 
Baseline 
-------------- Most Severe Value During Randomized Treatment Period ------------- 
<=450 
>450 and <=480 
>480 and <=500 
>500 
Total 
 
QTcB (msec) 
 
 
 
 
 
 
 
 
  Vorinostat  
 
 
 
 
 
 
 
 
   (N=xx) 
xxx 
<=450 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>450 and <=480 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>480 and <=500 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>500 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
  KW-0761 
 
 
 
 
 
 
 
 
   (N=xx) 
xxx 
<=450 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>450 and <=480 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>480 and <=500 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>500 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
QTcF (msec) 
 
 
 
 
 
 
 
 
Vorinostat  
 
 
 
 
 
 
 
 
 (N=xx) 
xxx 
<=450 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>450 and <=480 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>480 and <=500 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>500 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
KW-0761 
 
 
 
 
 
 
 
 
 (N=xx) 
xxx 
<=450 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>450 and <=480 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>480 and <=500 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
>500 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Note: Percentage is calculated using N’ as the denominator, where N’ is the number of subjects with both baseline and post baseline 
QTcB or QTcF measurements. 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
142 
 
 Table 14.3.7 
ECOG Performance Status Mean and Mean Change from Baseline by Selected Visits During Randomized Treatment Period 
Intent-to-Treat Set 
 
Scale 
  Time Point 
    Statistic 
Vorinostat (N=xx) 
--------------------------------------------- 
    Base           Post            Change 
KW-0761 (N=xx) 
------------------------------------------- 
    Base            Post           Change 
ECOG Performance Status 
 
 
 
 
 
 
  Baseline 
 
 
 
 
 
 
  n 
    xx 
 
 
    xx 
 
 
  Mean 
    xx.x 
 
 
    xx.x 
 
 
  Std Dev 
    xx.xx 
 
 
    xx.xx 
 
 
  Median 
    xx.x 
 
 
    xx.x 
 
 
  Minimum 
    xx 
 
 
    xx 
 
 
  Maximum 
    xx 
 
 
    xx 
 
 
 
 
 
 
 
 
 
  End of Cycle 1 
 
 
 
 
 
 
  n 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
  Mean 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
  Std Dev 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
  Median 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
  Minimum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
  Maximum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
 
 
 
 
 
 
 
  End of Cycle 3 
 
 
 
 
 
 
  n 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
  Mean 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
  Std Dev 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
    xx.xx 
  Median 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
    xx.x 
  Minimum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
  Maximum 
    xx 
    xx 
    xx 
    xx 
    xx 
    xx 
 
 
 
 
 
 
 
 Etc. 
 
 
 
 
 
 
    
<<Programming Note: Present for odd cycles..>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
143 
 
Table 14.3.8.1 
Anti-KW-0761 Antibody Response 
Safety Analysis Set (Subjects Exposed to KW-0761) 
 
 
 
Treatment Arm 
 
 
 
Visit* 
 
Anti-KW-0761 Antibody Status n/N’  (%) 
------------------------------------------ 
Positive        Negative    Inconclusivea)        
 
Neutralizing n/N’  (%) 
------------------------ 
Positive 
Initially Randomized to KW-0761 (N=xx) 
 
Baseline 
x/xx (xx.x) 
x/xx (xx.x) 
x/xx (xx.x) 
 
x/xx (xx.x) 
 
End of Cycle 1 
x/xx (xx.x) 
x/xx (xx.x) 
x/xx (xx.x) 
 
x/xx (xx.x) 
 
End of Cycle x 
x/xx (xx.x) 
x/xx (xx.x) 
x/xx (xx.x) 
 
x/xx (xx.x) 
 
End of Cycle x 
x/xx (xx.x) 
x/xx (xx.x) 
x/xx (xx.x) 
 
x/xx (xx.x) 
 
. 
 
 
 
 
 
 
. 
 
 
 
 
 
 
. 
 
 
 
 
 
 
EOT 
x/xx (xx.x) 
x/xx (xx.x) 
x/xx (xx.x) 
 
x/xx (xx.x) 
 
Overall 
x/xx (xx.x) 
 
 
 
 
Crossed Over to KW-0761 (N=xx) 
 
. 
 
 
 
 
 
 
. 
 
 
 
 
 
 
All Subjects Exposed to KW-0761 (N=xx) 
 
. 
 
 
 
 
 
 
. 
 
 
 
 
 
 
* For subjects who cross over, the cycle number corresponds to the treatment cycle of KW-0761. 
a) Inconclusive because KW-0761 concentration is higher than drug tolerance limit (16000 ng/mL) or KW-0761 concentration is not  
   determined. 
Note: Percentage is calculated using N’ as the denominator, where N’ is the number of subjects with valid measurements for anti- 
KW-0761 antibody at the specified visit. Overall is positive if at least one post-baseline assessment (including unscheduled) is 
positive.  
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
144 
 
Table 14.3.8.2 
                     Summary of Positive Anti-KW-0761 Antibody Response at Post-Baseline and Infusion Reaction 
                                                        Safety Analysis Set(Subjects Exposed to KW-0761) 
 
______________________________________________________________________________________________________________________________________ 
                                                                     All Subjects Exposed to KW-0761 
                                                                                  N=xx 
______________________________________________________________________________________________________________________________________ 
Number of Infusion Reactions (Events)                                              xx 
Number of Subjects who Experienced Infusion Reactions (n, %)*                  xx ( xx.x) 
Number of Subjects who Experienced Infusion Reaction and who had 
Overall Assay at Any Time Post-Baseline                                           N'=xx 
Number of Subjects who Experienced Infusion Reaction and who had a 
Positive Overall Assay at Any Time Post-Baseline (n, %)**                       xx ( xx.x) 
    Anti KW-0761 antibody                                                       xx ( xx.x) 
    Neutralizing                                                                xx ( xx.x) 
______________________________________________________________________________________________________________________________________ 
Note: Overall assay is positive if at least one of the two assays (Anti KW-0761 antibody or neutralizing) is positive. 
* Percentage is calculated using the number of subjects exposed to KW-0761 as the denominator. 
** Percentage is calculated using N' as the denominator. 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
145 
 
 Table 14.3.9 
Summary of Pharmacokinetic Concentrations of KW-0761 (ng/mL)  
PK Analysis Set 
 
 
 
 
 
 
 
 
 
                                       Cycle 1 
 
 
 
 
 
                           Day 1        
 
Day 8 
 
Day 15 
 
Day 22 
Day 28 
 
 
Pre-dose 
End of 
Infusion 
6-8 
Hrs 
 
24 Hrs 
 
48 Hrs 
72-96 
Hrs 
 
 
Pre-dose 
 
 
Pre-dose 
 
 
Pre-dose 
 
 
 
 
N 
Mean 
Std Dev 
Median 
Minimum 
Maximum 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: BLQ values (<12.5) are set to 0 for the summary. If a subject had multiple concentrations at a single time point, the average value  
      is used. 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
146 
 
Table 14.3.9 
Summary of Pharmacokinetic Concentrations of KW-0761 (ng/mL) 
PK Analysis Set 
 
 
              Cycle 2                             Cycle 3               
 
 
 
 
Day 1 
 
Day 15 
 
Day 1 
 
Day 15 
 
 
 
 
 
 
 
 
Subject 
Pre-dose 
 
Pre-dose 
 
    Pre-dose      
Pre-dose 
 
End of Treatment Visit 
 
 
 
 
N 
Mean 
Std Dev 
Median 
Minimum 
Maximum 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: BLQ values (<12.5) are set to 0 for the summary. If a subject had multiple concentrations at a single time point, the average value  
      is used. 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
147 
 
Figure 14.2.1 
Plot of Kaplan-Meier Curve of Progression-Free Survival by Investigator’s Assessment 
Intent-to-Treat Set 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
148 
 
The following figures will have similar layout as Figure 14.2.1: 
Table 14.2.2 
Plot of Kaplan-Meier Curve of Progression-Free Survival by Investigator’s Assessment 
Efficacy Evaluable Set 
 
 
Table 14.2.3 
Plot of Kaplan-Meier Curve of Progression-Free Survival by Independent Review  
Intent-to-Treat Set 
 
 
Table 14.2.4 
Plot of Kaplan-Meier Curve of Progression-Free Survival by Independent Review  
Efficacy Evaluable Set 
 
 
 
 
  
  
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
149 
 
Table 14.2.5 
Forest Plot of Hazard Ratios for Progression-Free Survival Based on Investigator’s Assessment by Pre-defined Subgroups 
Intent-to-Treat Set  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW = KW-0761; VOR = Vorinostat; HR = Hazard Ratio 
Hazard ratio (KW-0761 vs. Vorinostat) and 95% CI are based on Cox proportional hazards model with treatment as a covariate for  
each subgroup. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
150 
 
The following figure will have a similar layout as Figure 14.2.5: 
 
Table 14.2.6 
Forest Plot of Hazard Ratios for Progression-Free Survival Based on Investigator’s Assessment by Pre-defined Subgroups 
Efficacy Evaluable Set 
 
The following figures will have a similar layout as Figure 14.2.1: 
 
Table 14.2.7.1 
Plot of Kaplan-Meier Curve of Overall Survival 
Intent-to-Treat Set 
 
Table 14.2.7.2 
Plot of Kaplan-Meier Curve of Time to Treatment Failure 
Intent-to-Treat Set 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
151 
 
Figure 14.2.8 
Mean (±SE) Skindex-29 Score During Randomized Treatment Period 
Intent-to-Treat Set 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
152 
 
Figure 14.2.9 
Mean (±SE) Change in Skindex-29 Score from Baseline During Randomized Treatment Period 
Intent-to-Treat Set 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
153 
 
The following figures will have similar layout as Figure 14.2.8 and Figure 14.2.9: 
Figure 14.2.10 
Mean (±SE) Skindex-29 Score During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Figure 14.2.11 
Mean (±SE) Change in Skindex-29 Score from Baseline During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Figure 14.2.12 
Mean (±SE) FACT-G Total Score During Randomized Treatment Period 
Intent-to-Treat Set  
 
Figure 14.2.13 
Mean (±SE) Change in FACT-G Total Score from Baseline During Randomized Treatment Period 
Intent-to-Treat Set 
 
Figure 14.2.14 
Mean (±SE) FACT-G Total Score During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Figure 14.2.15 
Mean (±SE) Change in FACT-G Total Score from Baseline During Randomized Treatment Period 
Efficacy Evaluable Set 
  
Figure 14.2.16 
Mean (±SE) EQ-5D-3L Index Score During Randomized Treatment Period 
Intent-to-Treat Set  
 
Figure 14.2.17 
Mean (±SE) Change in EQ-5D-3L Index Score from Baseline During Randomized Treatment Period 
Intent-to-Treat Set 
 
Figure 14.2.18 
Mean (±SE) EQ-5D-3L Index Score During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Figure 14.2.19 
Mean (±SE) Change in EQ-5D-3L Index Score from Baseline During Randomized Treatment Period 
Efficacy Evaluable Set  
 
Figure 14.2.20 
Mean (±SE) Pruritus Evaluation Itchy Quality of Life Score During Randomized Treatment Period 
Intent-to-Treat Set  
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
154 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
155 
 
Figure 14.2.21 
Mean (±SE) Change in Pruritus Evaluation Itchy Quality of Life Score from Baseline During Randomized Treatment Period 
Intent-to-Treat Set 
 
Figure 14.2.22 
Mean (±SE) Pruritus Evaluation Itchy Quality of Life Score During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Figure 14.2.23 
Mean (±SE) Change in Pruritus Evaluation Itchy Quality of Life Score from Baseline During Randomized Treatment Period 
Efficacy Evaluable Set  
 
Figure 14.2.24 
Mean (±SE) Pruritus Evaluation Likert Scale Score During Randomized Treatment Period 
Intent-to-Treat Set  
 
Figure 14.2.25 
Mean (±SE) Change in Pruritus Evaluation Likert Scale Score from Baseline During Randomized Treatment Period 
Intent-to-Treat Set 
 
Figure 14.2.26 
Mean (±SE) Pruritus Evaluation Likert Scale Score During Randomized Treatment Period 
Efficacy Evaluable Set 
 
Figure 14.2.27 
Mean (±SE) Change in Pruritus Evaluation Likert Scale Score from Baseline During Randomized Treatment Period 
Efficacy Evaluable Set 
 
 
 
 
 
 
  
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
156 
 
Listing 16.2.1.1 
Disposition - End of Treatment 
 
Trt Arm 
   Subject 
First Dose 
Date/Last Dose 
Date* 
Crossed 
Over to 
KW-0761? 
First/Last Dose 
Date of KW-0761 
after Crossover 
Reason for Study Drug Discontinuation 
 
Date of 
Progression 
Date of 
Death 
Vorinostat 
 
xxx-xxx 
   YYYY-MM-DD/ 
   YYYY-MM-DD    
Yes 
   YYYY-MM-DD/ 
   YYYY-MM-DD 
Subject withdrawal of consent 
 
 
 
   xxx-xxx 
   YYYY-MM-DD/ 
YYYY-MM-DD     
No 
 
Progressive disease per CTCL response 
criteria 
 
YYYY-MM-DD 
 
   xxx-xxx 
   YYYY-MM-DD/ 
YYYY-MM-DD     
No 
 
Progressive disease – Clinical: xxxx 
xxxxxxxxxxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
   xxx-xxx 
 
   YYYY-MM-DD/ 
YYYY-MM-DD     
Yes 
   YYYY-MM-DD/ 
YYYY-MM-DD 
Death: xxxxxxx 
 
 
 
YYYY-MM-DD 
   xxx-xxx 
   YYYY-MM-DD/ 
YYYY-MM-DD     
No 
 
Withdrawal of consent 
 
 
 
 
 
 
KW-0761 
 
   xxx-xxx 
 
   YYYY-MM-DD/ 
YYYY-MM-DD     
 
 
Other: xxxxxxxxxxxxxxxxxxxxxx  
 
 
 
   xxx-xxx 
 
   YYYY-MM-DD/ 
YYYY-MM-DD     
 
 
Adverse Event: xxxxxxxxxxxxxxxxxxxx 
 
 
 
   Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* First dose date/last dose date of randomized study drug. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
157 
 
 Listing 16.2.1.2 
Subjects Randomized to Vorinostat and Crossed Over to KW-0761 
 
Subject 
Subject Crossed Over to  
KW-0761 Due to  
Date of Approval  
of Cross-over 
By Whom 
 
xxx-xxx 
Progression 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxx 
 
xxx-xxx 
Intolerance 
 
 
 
xxx-xxx 
Progression 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxxxx 
 
xxx-xxx 
Progression 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxx 
 
xxx-xxx 
Progression 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxx 
 
xxx-xxx 
Progression 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxxxx 
 
xxx-xxx 
Progression 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxx 
 
xxx-xxx 
Progression 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxx 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
158 
 
Listing 16.2.1.3 
Disposition - End of Study 
 
Trt Arm 
   Subject 
 Date of  Study 
Termination   
Reason for Study Termination  
 
Date of Death 
 
Vorinostat 
   xxx-xxx 
YYYY-MM-DD 
Withdrawal of consent 
 
 
 
   xxx-xxx 
YYYY-MM-DD 
Lost to Follow-up 
 
 
 
   xxx-xxx 
YYYY-MM-DD 
Death: xxxxxx 
 
YYYY-MM-DD 
 
   xxx-xxx 
YYYY-MM-DD 
Withdrawal of consent 
 
 
 
   xxx-xxx 
YYYY-MM-DD 
Lost to Follow-up 
 
 
 
   xxx-xxx 
YYYY-MM-DD 
Lost to Follow-up 
 
 
 
 
KW-0761  
   xxx-xxx 
YYYY-MM-DD 
Other: xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
   xxx-xxx 
YYYY-MM-DD 
Withdrawal of consent 
 
 
 
   Etc. 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
159 
 
Listing 16.2.2.1 
Protocol Deviations 
 
Trt Arm 
   Subject 
Category 
Description 
Occurrence 
Date 
Discovery 
Date 
Action Taken 
 
Vorinostat 
 
 
 
   xxx-xxx 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxx 
 
   xxx-xxx 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxx 
 
   xxx-xxx 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxx 
 
   xxx-xxx 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxx 
 
   xxx-xxx 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxx 
 
   xxx-xxx 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxx 
 
   xxx-xxx 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
KW-0761  
 xxx-xxx 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxx 
 
 xxx-xxx 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
160 
 
Listing 16.2.2.2 
Inclusion/Exclusion Criteria 
 
Trt Arm 
   Subject 
All Elig. 
Criteria 
Satisfied? 
Inc. Criteria*  
   Not Met 
Exc. Criteria* 
  Not Met 
Waiver 
Granted?/ 
Date of Waiver 
Waiver Authorized 
by Whom? 
Protocol Version 
Subject 
Consented 
Vorinostat 
 
 
 
   xxx-xxx 
Yes 
 
 
 
 
Amendment 1 
   xxx-xxx 
Yes 
 
 
 
 
Amendment 1 
   xxx-xxx 
No 
xx, xx 
 
Yes/YYYY-MM-DD 
xxxxxxxxxxxxxxxxxxx 
Amendment 1 
   xxx-xxx 
Yes 
 
 
 
 
Amendment 2 
   xxx-xxx 
Yes 
 
 
 
 
Amendment 2 
   xxx-xxx 
Yes 
 
 
 
 
Amendment 2 
   xxx-xxx 
Yes 
 
 
 
 
Amendment 2 
 
 
 
 
 
 
 
KW-0761  
 xxx-xxx 
Yes 
 
 
 
 
Amendment 2 
 xxx-xxx 
Yes 
 
 
 
 
Amendment 2 
 
 
 
 
 
 
 
* See the last pages of the listing for a complete list of the inclusion and exclusion criteria.   
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
161 
 
Listing 16.2.3 
Analysis Population 
 
Trt Arm 
   Subject 
Intent-to-Treat 
Set 
Safety  
Analysis Set 
  Efficacy  
Evaluable Set 
Reasons for Exclusion from   
Efficacy Evaluable Set   
Vorinostat 
   xxx-xxx 
Yes 
        Yes 
    No 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
   xxx-xxx 
Yes 
        Yes 
    Yes 
 
   xxx-xxx 
Yes 
        Yes 
    Yes 
 
   xxx-xxx 
Yes 
        Yes 
    No 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
   xxx-xxx 
Yes 
        No 
    No 
xxxxxxxxxxxxxx 
   xxx-xxx 
Yes 
        Yes 
    Yes 
 
   xxx-xxx 
Yes 
        Yes 
    No 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 xxx-xxx 
Yes 
        No 
    No 
xxxxxxxxxxxxxx 
 
 
 
 
 
KW-0761   
 
 
 
 
 xxx-xxx 
Yes 
        Yes 
    No 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 xxx-xxx 
Yes 
        Yes 
    Yes 
 
 xxx-xxx 
Yes 
        Yes 
    Yes 
 
 xxx-xxx 
Yes 
        Yes 
    Yes 
 
 
 
 
 
 
Subjects Crossed over 
to KW-0761 (Crossover 
Portion) 
 
 
 
 
   xxx-xxx 
Yes 
        Yes 
    Yes 
 
   xxx-xxx 
Yes 
        Yes 
    Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
162 
 
Listing 16.2.4.1 
Demographics 
 
Trt Arm 
   Subject 
Date of 
Informed 
Consent 
Date of 
Randomization 
 
Age 
(yrs)* 
Gender 
Race 
Ethnicity 
Child-
bearing 
Potential** 
BSA 
(m^2) 
 
BMI 
(kg/m^2) 
Non-Randomized 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
YYYY-MM-DD 
 
 
xx 
Male 
xxxxxxxxx 
xxxxxxx 
 
xx.x 
xx.x 
   xxx-xxx 
YYYY-MM-DD 
 
 
xx 
Female  
Other: xxxxxxxxx 
xxxxxxxx 
Yes 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
Vorinostat 
 
 
 
   xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Male 
xxxxxxxxx 
xxxxxxx 
 
xx.x 
xx.x 
   xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Female  
Other: xxxxxxxxx 
xxxxxxxx 
No 
xx.x 
xx.x 
   xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Male 
xxxxxxxxx 
xxxxxxx 
 
xx.x 
xx.x 
   xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Male 
xxxxxxxxx 
xxxxxxx 
 
xx.x 
xx.x 
   xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Female  
Other: xxxxxxxxx 
xxxxxxxx 
Yes 
xx.x 
xx.x 
   xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Female  
Other: xxxxxxxxx 
xxxxxxxx 
No 
xx.x 
xx.x 
 xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Male 
xxxxxxxxx 
xxxxxxx 
 
xx.x 
xx.x 
 xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Female  
Other: xxxxxxxxx 
xxxxxxxx 
No 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Male 
xxxxxxxxx 
xxxxxxx 
 
xx.x 
xx.x 
   xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Female  
Other: xxxxxxxxx 
xxxxxxxx 
No 
xx.x 
xx.x 
   xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
xx 
Female  
Other: xxxxxxxxx 
xxxxxxxx 
No 
xx.x 
xx.x 
Note: BSA = body surface area at baseline; BMI = body mass index at baseline. 
* Age at screening.  
** For Female only.  
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
163 
 
Listing 16.2.4.2 
Current CTCL History 
 
Trt Arm 
Subject  
Date of 
Initial  
Diagnosis 
Histologically 
Confirmed 
Diagnosis 
Clinical 
Stage at 
Diagnosis 
Current 
Clinical 
Stage 
Current T,N,M,B 
Classification 
--------------------- 
T    N    M    B 
Current Sites 
of Disease 
CCR4 
Expression 
Status 
Vorinostat 
   xxx-xxx 
YYYY-MM-DD 
MF 
   IA 
   IIA 
  xx   xx   xx   xx 
xxxxxxx, xxxxx 
Positive 
   xxx-xxx 
YYYY-MM-DD 
MF 
   IB 
   IIB 
  xx   xx   xx   xx 
xxxxxxx 
Positive 
   xxx-xxx 
YYYY-MM-DD 
MF 
   IIA 
   IIIA 
  xx   xx   xx   xx 
xxxxxxx, xxxx 
Negative 
   xxx-xxx 
YYYY-MM-DD 
SS 
   IIB 
   IIIB 
  xx   xx   xx   xx 
xxxxxxx, xxxxx 
Positive 
   xxx-xxx 
YYYY-MM-DD 
SS 
   IIIA 
   IVA1 
  xx   xx   xx   xx 
xxxxxxx 
Positive 
   xxx-xxx 
YYYY-MM-DD 
MF 
   IIIB 
   IVA2 
  xx   xx   xx   xx 
xxxxxxx, xxxx 
Negative 
 xxx-xxx 
YYYY-MM-DD 
SS 
   IVA1 
   IVB 
  xx   xx   xx   xx 
xxxxxxx, xxxxx 
Positive 
 xxx-xxx 
YYYY-MM-DD 
MF 
   IVA2 
   IVB 
  xx   xx   xx   xx 
xxxxxxx 
Positive 
 xxx-xxx 
YYYY-MM-DD 
SS 
   IVB 
   IVB 
  xx   xx   xx   xx 
xxxxxxx, xxxx 
Negative 
 
 
 
 
 
  xx   xx   xx   xx 
 
 
KW-0761  
   xxx-xxx 
YYYY-MM-DD 
MF 
   IIA 
IVB 
  xx   xx   xx   xx 
xxxxxxx, xxxxx 
Positive 
   xxx-xxx 
YYYY-MM-DD 
SS 
   IIB 
IVB 
  xx   xx   xx   xx 
Other: xxxxxxx 
Positive 
   xxx-xxx 
YYYY-MM-DD 
MF 
   IB 
IVB 
  xx   xx   xx   xx 
xxxxxxx, xxxx 
Negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
164 
 
Listing 16.2.4.3 
Medical/Surgical History 
 
Trt Arm 
   Subject 
Any Medical or 
Surgical History? 
Condition/Diagnosis 
Start Date 
Ongoing? 
 
 
Vorinostat 
   xxx-xxx 
    Yes 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
Yes 
 
 
 
 
xxxxxxxxxxxxxxxxxxx 
YYYY-MM 
No 
 
 
   xxx-xxx 
    Yes 
xxxxxxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
Yes 
 
 
    
 
xxxxxxxxxxxxxxxxxxxx 
YYYY-MM 
No 
 
 
   xxx-xxx 
    Yes 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
Yes 
 
 
 
 
xxxxxxxxxxxxxxxxxxx 
YYYY-MM 
No 
 
 
   xxx-xxx 
    Yes 
xxxxxxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
Yes 
 
 
    
 
xxxxxxxxxxxxxxxxxxxx 
YYYY-MM 
No 
 
 
 xxx-xxx 
    Yes 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
Yes 
 
 
 
 
xxxxxxxxxxxxxxxxxxx 
YYYY-MM 
No 
 
 
 xxx-xxx 
    Yes 
xxxxxxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
Yes 
 
 
    
 
xxxxxxxxxxxxxxxxxxxx 
YYYY-MM 
No 
 
 
 
KW-0761  
   xxx-xxx 
    Yes 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
Yes 
 
 
 
 
xxxxxxxxxxxxxxxxxxx 
YYYY-MM 
No 
 
 
 xxx-xxx 
    Yes 
xxxxxxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
Yes 
 
 
    
 
xxxxxxxxxxxxxxxxxxxx 
YYYY-MM 
No 
 
 
 Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
165 
 
Listing 16.2.4.4 
Prior CTCL Therapy 
 
Trt Arm 
   Subject 
Treatment Administered 
Start Date 
Stop Date 
Best Response 
to Therapy 
 
Vorinostat 
   xxx-xxx 
xxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxx 
 
 
xxxxxxxxxxxxxx 
YYYY-MM 
YYYY-MM-DD 
xxxxxxxx 
 
 
 
 
 
 
 
   xxx-xxx 
xxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxx 
 
     
Other: xxxxxxxxxxxxxx 
YYYY-MM 
YYYY-MM-DD 
xxxxxxxx 
 
   xxx-xxx 
xxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxx 
 
 
xxxxxxxxxxxxxx 
YYYY-MM 
YYYY-MM-DD 
xxxxxxxx 
 
 
 
 
 
 
 
   xxx-xxx 
xxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxx 
 
     
xxxxxxxxxxxxxxxxxxx 
YYYY-MM 
YYYY-MM-DD 
xxxxxxxx 
 
 xxx-xxx 
xxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxx 
 
 
xxxxxxxxxxxxxx 
YYYY-MM 
YYYY-MM-DD 
xxxxxxxx 
 
 
 
 
 
 
 
KW-0761   
   xxx-xxx 
xxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxx 
 
 
xxxxxxxxxxxxxx 
YYYY-MM 
YYYY-MM-DD 
xxxxxxxx 
 
 
 
 
 
 
 
 xxx-xxx 
xxxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxx 
 
     
Other: xxxxxxxxxxxxxxxxxxx 
YYYY-MM 
YYYY-MM-DD 
xxxxxxxx 
 
 
 
 
 
 
 
 Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
166 
 
Listing 16.2.4.5 
Prior Radiotherapy 
 
Trt Arm 
   Subject 
Any Prior 
Radiotherapy? 
Method 
Site Irradiated 
Total Dose  
Unit 
Start Date 
Stop Date 
Vorinostat 
 
 
 
 
 
 
 
   xxx-xxx 
  Yes 
External 
xxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxx 
xxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxx 
xxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
 
 
 
 
 
   xxx-xxx 
  Yes 
Systemic 
xxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxx 
xxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
     
 
 
xxxxxxxxxxxxxx 
xxxxxxxx 
xxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
   xxx-xxx 
  Yes 
External 
xxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxx 
xxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxx 
xxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
 
 
 
 
 
   xxx-xxx 
  No 
 
 
 
 
 
 
     
 
 
 
 
 
 
 
 xxx-xxx 
  Yes 
External 
xxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxx 
xxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxx 
xxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
 
 
 
 
 
KW-0761  
 
 
 
 
 
 
 
   xxx-xxx 
  Yes 
External 
xxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxx 
xxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxx 
xxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
 
 
 
 
 
   xxx-xxx 
  Yes 
External 
xxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxx 
xxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
     
 
 
xxxxxxxxxxxxxx 
xxxxxxxx 
xxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
 Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
167 
 
Listing 16.2.4.6 
Prior Medications 
 
Trt Arm 
   Subject 
VT: Verbatim Term 
PT: Preferred Term* 
ATC:ATC Class* 
Start Date/ 
Stop Date 
Indication 
Taken to  
Treat AE?  
If Yes,  
Specify AE 
 
Vorinostat 
   xxx-xxx 
VT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD/ 
xxxxxxxx 
 Yes 
xxxxxxxxxxxxxx 
     
 
PT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
 
 
 
 
 
ATC:xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
VT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD/ 
xxxxxxxx 
 No 
 
 
 
PT: xxxxxxxxxxxxxxxxxxxxxx 
Ongoing 
 
 
 
 
 
ATC:xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 xxx-xxx 
VT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD/ 
xxxxxxxx 
 Yes 
xxxxxxxxxxxxxx 
 
 
PT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
 
 
 
 
 
ATC:xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
VT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD/ 
xxxxxxxx 
 Yes 
xxxxxxxxxxxxxx 
 
 
PT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
 
 
 
 
 
ATC:xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
VT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD/ 
xxxxxxxx 
 No 
 
     
 
PT: xxxxxxxxxxxxxxxxxxxxxx 
Ongoing 
 
 
 
 
 
ATC:xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
   xxx-xxx 
VT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD/ 
xxxxxxxx 
 Yes 
xxxxxxxxxxxxxx 
 
 
PT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD 
 
 
 
 
 
ATC:xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
VT: xxxxxxxxxxxxxxxxxxxxxx 
YYYY-MM-DD/ 
xxxxxxxx 
 No 
 
     
 
PT: xxxxxxxxxxxxxxxxxxxxxx 
Ongoing 
 
 
 
 
 
ATC:xxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
* WHO Drug Dictionary (September 2012) was used for coding. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
168 
 
The following listings will have similar layout as Listing 16.2.4.6: 
Listing 16.2.4.7 
Concomitant Medication During Randomized Treatment Period 
 
 
Listing 16.2.4.8 
Concomitant Medication During Crossover Portion  
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
   


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
169 
 
Listing 16.2.4.9 
Pruritus Medications During the Study 
 
Trt Arm 
   Subject 
Any Medications  
Taken for Pruritus? 
Drug Name 
Dose 
Start Date 
Stop Date 
 
Vorinostat 
   xxx-xxx 
Yes 
xxxxxxxxxxxxxxxxxxx 
xxxx 
YYYY-MM-DD 
Ongoing 
     
 
 
xxxxxxxxxxxxxxx 
xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
 
 
 
 
 
 xxx-xxx 
No 
 
 
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
Yes 
xxxxxxxxxxxxxxxxxxx 
xxxx 
YYYY-MM-DD 
Ongoing 
 
 
 
xxxxxxxxxxxxxxx 
xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
xxxxxxxxxxxxxxxxxxx 
xxxx 
YYYY-MM-DD 
Ongoing 
 
 
 
xxxxxxxxxxxxxxxxxxx 
xxxx 
YYYY-MM-DD 
Ongoing 
 
 
 
 
 
 
 
 
KW-0761  
   xxx-xxx 
Yes 
xxxxxxxxxxxxxxxxxxx 
xxxx 
YYYY-MM-DD 
Ongoing 
 
 
 
xxxxxxxxxxxxxxx 
xxx 
YYYY-MM-DD 
YYYY-MM-DD 
 
 
 
xxxxxxxxxxxxxxxxxxx 
xxxx 
YYYY-MM-DD 
Ongoing 
 
 
 
xxxxxxxxxxxxxxxxxxx 
xxxx 
YYYY-MM-DD 
Ongoing 
 
 
 
 
 
 
 
     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
170 
 
Listing 16.2.5.1 
KW-0761 Administration During Randomized Treatment Period 
 
Trt Arm 
Subject 
Infusion Date/ 
Start Time/ 
Stop Time 
Planned/ 
Actual 
Dose 
(mg) 
% Dose 
Intensity 
Actual 
Volume 
(mL) 
Reason Total Planned 
Dose Not Administered 
Infusion 
Interrupted?/ 
Reason 
Time of 
Interruption/ 
Restart Time 
Symptom of 
Infusion 
Reaction* 
Any 
IR** 
KW-0761 (1.0 mg/kg) 
 
   xxx-xxx 
YYYY-MM-DD/ 
HH:MM/HH:MM 
xx.x/xx.x 
xx.x 
xx 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YYYY-MM-DD/ 
HH:MM/HH:MM 
xx.x/xx.x 
xx.x 
xx 
xxxxxxxxxxxxxxxxxxxxx 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YYYY-MM-DD/ 
HH:MM/HH:MM 
xx.x/xx.x 
xx.x 
xx 
 
Yes/Infusion 
Reaction 
HH:MM/HH:MM 
xxx, xxxxx 
 
 
 
 
 
 
 
 
 
 
 
   Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Symptoms of infusion reaction if interrupted for infusion reaction. 
** Any Infusion reaction (IR) that did not interrupt or stop the infusion. 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
171 
 
The following listing will have a similar layout as Listing 16.2.5.1: 
Listing 16.2.5.2 
KW-0761 Administration During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
172 
 
Listing 16.2.5.3 
Vorinostat Administration 
 
Trt Arm 
   Subject 
 
 
Dose Administered 
(mg) 
Start Date 
End Date 
Dose Modified?/ 
Reason 
Compliant with  
Dosing?/Reason 
 
 
Vorinostat 
   xxx-xxx 
 
 
xx.x 
YYYY-MM-DD 
YYYY-MM-DD 
 Yes/xxxxxxxxx 
 
No/xxxxxxxxxxxxxxxxx 
 
 
 
 
 
xx.x 
YYYY-MM-DD 
YYYY-MM-DD 
 No 
 
Yes 
 
 
 
 
 
xx.x 
YYYY-MM-DD 
YYYY-MM-DD 
 No 
 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
 
 
xx.x 
YYYY-MM-DD 
YYYY-MM-DD 
 Yes/xxxxxxxxx 
 
No/xxxxxxxxxxxxxxxxx 
 
 
 
 
 
xx.x 
YYYY-MM-DD 
YYYY-MM-DD 
 No 
 
Yes 
 
 
 
 
 
xx.x 
YYYY-MM-DD 
YYYY-MM-DD 
 No 
 
Yes 
 
 
   Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
173 
 
Listing 16.2.5.4 
Blood Sampling and Results for Pharmacokinetic Assessment 
 
 
Trt Arm 
   Subject 
Visit 
 
Analysis 
Visit 
Time Point 
 
Sample  
Collected? 
Sample Date/Time 
KW-0761 
Concentration 
(ng/mL) 
 
 
Initially Randomized KW-0761  
   xxx-xxx 
xxxxxxxxxx 
xxxxxxxxxx 
Pre-infusion 
Yes 
YYYY-MM-DD/HH:MM 
    xxxxxx 
 
 
 
 
 
End of Infusion 
No 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxxxx 
xxxxxxxxxx 
Pre-infusion 
Yes 
YYYY-MM-DD/HH:MM 
    xxxxxx 
 
 
    
 
 
End of Infusion 
Yes 
YYYY-MM-DD/HH:MM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
xxxxxxxxxx 
xxxxxxxxxx 
Pre-infusion 
Yes 
YYYY-MM-DD/HH:MM 
    xxxxxx 
 
 
 
 
 
End of Infusion 
Yes 
YYYY-MM-DD/HH:MM 
    xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cross Over to KW-0761 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
174 
 
Listing 16.2.6.1 
mSWAT Assessment During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
 
Visit 
mSWAT 
Completed? 
Assessment 
Date 
Area 
%BSA for 
Region 
--------%BSA-------
Patch Plaque Tumor 
Total BSA 
Involvement 
(%) 
 
 
Vorinostat 
   xxx-xxx 
 
xxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
xxxxxx 
xx 
 xx     xx    xx 
 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
xxxxx 
xx 
 xx     xx    xx 
 
 
 
 
 
 
xxxxxxxx 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
 
xxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
xxxxxx 
xx 
 xx     xx    xx 
 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
xxxxx 
xx 
 xx     xx    xx 
 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
 
xxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
xxxxxx 
xx 
 xx     xx    xx 
 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
xxxxx 
xx 
 xx     xx    xx 
 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
xxxxx 
xx 
 xx     xx    xx 
 
 
 
 
 
KW-0761 1.0 mg/kg 
   xxx-xxx 
 
xxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
xxxxxx 
xx 
 xx     xx    xx 
 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
xxxxx 
xx 
 xx     xx    xx 
 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxxxx 
xx 
 xx     xx    xx 
xx 
 
 
 
 
 
 
 
 
xxxxx 
xx 
 xx     xx    xx 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
175 
 
Listing 16.2.6.2 
mSWAT Analysis During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
 
 
 Visit 
Assessment 
Date 
--------- mSWAT Analysis* --------- 
%Patch   %Plaque   %Tumor    Total 
 
 
 
  
Vorinostat 
   xxx-xxx 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
   xxx-xxx 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
   xxx-xxx 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
 xxx-xxx 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD 
  xx       xx        xx       xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* mSWAT Analysis: %BSA patch x 1, %BSA plaque x 2, %BSA tumor x 4. 
Note: CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; NA = not assessable. 
   
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
176 
 
The following listings will have similar layout as Listing 16.2.6.1 and Listing 16.2.6.2: 
Listing 16.2.6.3 
mSWAT Assessment During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.6.4 
mSWAT Analysis During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
177 
 
Listing 16.2.6.5 
Flow Cytometric Analysis During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
Blood 
Involvement? 
Visit 
Sample Date/Time 
Parameter 
Unit 
Result 
   
 
Vorinostat 
xxx-xxx 
Yes 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
xxxxxxxx  
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
xxxxxxxx  
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx  
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
xxx-xxx 
Yes 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
xxxxxxxx  
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
xxx-xxx 
Yes 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
xxxxxxxx  
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
xxxxxxxx  
xxx 
xx.x 
 
 
 
 
 
 
 
xxxxxxxx 
xxx 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; NA = not assessable. 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
178 
 
The following listing will have a similar layout as Listing 16.2.6.5: 
Listing 16.2.6.6 
Flow Cytometric Analysis During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
179 
 
Listing 16.2.6.7 
Bone Marrow Aspirate/Biopsy Assessment During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
 
Visit 
Collection 
Method 
Collection 
Date 
Evidence of 
Lymphoma? 
 
 
 
 
 
 
Vorinostat 
    xxx-xxx 
 
xxxxxxxxxxxxx 
 Aspirate 
YYYY-MM-DD 
Yes 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxx 
 
Not Done 
 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxx 
 Aspirate 
YYYY-MM-DD 
Yes 
 
 
 
 
 
 
  xxx-xxx 
 
xxxxxxxxxxxxx 
 Aspirate 
YYYY-MM-DD 
Yes 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxx 
 Aspirate 
YYYY-MM-DD 
Yes 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxx 
 Aspirate 
YYYY-MM-DD 
No 
 
 
 
 
 
 
  xxx-xxx 
 
xxxxxxxxxxxxx 
 Aspirate 
YYYY-MM-DD 
Yes 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxx 
 Aspirate 
YYYY-MM-DD 
Yes 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxx 
 Aspirate 
YYYY-MM-DD 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
    xxx-xxx 
 
xxxxxxxxxxxxx 
 Biopsy 
YYYY-MM-DD 
Yes 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxx 
 Biopsy 
YYYY-MM-DD 
Yes 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxx 
 Biopsy 
YYYY-MM-DD 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
180 
 
The following listing will have a similar layout as Listing 16.2.6.7: 
Listing 16.2.6.8 
Bone Marrow Aspirate/Biopsy Assessment During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
181 
 
Listing 16.2.6.9 
Lymph Node Assessment During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
Subject 
 
Visit 
 
Date of 
Assessment 
Enlarged 
Lymph Nodes? 
Lesion 
No. 
Location 
Measurement 
(mm) 
Sum of the 
Product of 
Diameters 
(mm) 
 
 
Vorinostat 
    xxx-xxx  
xxxxxxxxx 
 
YYYY-MM-DD  
Yes 
xx 
xxxxx 
xxx/xxx 
xxx 
 
 
 
 
 
 
 
 
xx 
xxxxx 
xxx/xxx 
 
 
 
 
 
xxxxxxxxx 
 
YYYY-MM-DD  
Yes 
xx 
xxxxx 
xxx/xxx 
xxx 
 
 
 
 
 
 
 
 
xx 
xxxxx 
xxx/xxx 
 
 
 
 
 
xxxxxxxxx 
 
YYYY-MM-DD  
Yes 
xx 
xxxxx 
xxx/xxx 
xxx 
 
 
  xxx-xxx 
 
xxxxxxxxx 
 
YYYY-MM-DD  
Yes 
xx 
xxxxx 
xxx/xxx 
xxx 
 
 
 
 
 
 
 
 
xx 
xxxxx 
xxx/xxx 
 
 
 
 
 
xxxxxxxxx 
 
YYYY-MM-DD  
Yes 
xx 
xxxxx 
xxx/xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
  xxx-xxx 
 
xxxxxxxxx 
 
YYYY-MM-DD  
Yes 
xx 
xxxxx 
xxx/xxx 
xxx 
 
 
 
 
 
 
 
 
xx 
xxxxx 
xxx/xxx 
 
 
 
 
 
xxxxxxxxx 
 
YYYY-MM-DD  
Yes 
xx 
Other: 
xxxxx 
xxx/xxx 
xxx 
 
xx 
 
 
 
 
 
 
xx 
xxxxx 
xxx/xxx 
 
 
 
 
 
xxxxxxxxx 
 
YYYY-MM-DD  
No 
 
 
 
 
 
 
Note: CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; NA = not assessable. 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
182 
 
The following listing will have a similar layout as Listing 16.2.6.9: 
Listing 16.2.6.10 
Lymph Node Assessment During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
183 
 
Listing 16.2.6.11 
Visceral Mass Assessment During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
  Subject 
 
Visit 
Method 
Date of 
Assessment 
Abnormal 
Lesions? 
Lesion 
No. 
Location 
Measure-
ment 
(mm) 
Sum 
of 
Diam. 
(mm)* 
Non-
Measur-
able 
Disease 
Description 
 
Vorinostat 
 
 
  xxx-xxx 
 
xxxxxxx 
xxxxxxxx 
YYYY-MM-DD 
Yes 
xx 
xxxxxxxx  xxx/xxx 
xxx 
Yes 
xxxxxxxxxxx 
 
 
 
 
 
 
 
xx 
xxxxxxxx  xxx/xxx 
 
 
 
 
 
 
xxxxxxx 
xxxxxxxx 
YYYY-MM-DD 
Yes 
xx 
xxxxxxxx  xxx/xxx 
xxx 
No 
 
 
 
 
 
 
 
 
xx 
xxxxx 
 xxx/xxx 
 
 
 
 
 
 
xxxxxxx 
xxxxxxxx 
YYYY-MM-DD 
Yes 
xx 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
 
 
  xxx-xxx 
 
xxxxxxx 
xxxxxxxx 
YYYY-MM-DD 
Yes 
xx 
xxxxx 
 xxx/xxx 
xxx 
No 
 
 
 
 
 
 
 
 
xx 
xxxxx 
 xxx/xxx 
 
 
 
 
 
 
xxxxxxx 
xxxxxxxx 
YYYY-MM-DD 
Yes 
xx 
xxxxx 
 xxx/xxx 
xxx 
No 
 
 
 
 
 
 
 
 
xx 
xxxxx 
 xxx/xxx 
 
 
 
 
 
 
xxxxxxx 
Other: 
xxxxxxxx 
YYYY-MM-DD 
Yes  
xx 
Other: 
xxxxx 
 xxx/xxx 
xxx 
No 
Other: xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Sum of the Product of Diameters. 
Note: CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; NA = not assessable. 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
184 
 
The following listing will have a similar layout as Listing 16.2.6.11: 
Listing 16.2.6.12 
Visceral Mass Assessment During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
185 
 
Listing 16.2.6.13 
CTCL Response During Randomized Treatment Period - By Investigator’s Assessment 
 
Trt Arm 
   Subject 
 
 
Visit 
Compartment 
Date of 
Assessment 
Response 
 
 
 
 
 
 
 
 
Vorinostat 
    xxx-xxx xxxx 
xxxxxxxxxx 
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
 
xxxx 
xxxxxxxxxx  
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
 
xxxx 
Overall 
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
  xxx-xxx 
xxxx 
xxxxxxxxxx  
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
 
xxxx 
xxxxxxxxxx  
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
 
xxxx 
xxxxxxxxxx  
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
  xxx-xxx 
xxxx 
xxxxxxxxxx  
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
 
xxxx 
xxxxxxxxxx  
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
 
xxxx 
xxxxxxxxxx  
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
    xxx-xxx xxxx 
xxxxxxxxxx  
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
 
xxxx 
xxxxxxxxxx  
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
 
xxxx 
xxxxxxxxxx  
YYYY-MM-DD 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; NA = not assessable. 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
186 
 
The following listing will have similar layout as Listing 16.2.6.13: 
Listing 16.2.6.14 
CTCL Response During Crossover Portion - By Investigator’s Assessment 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
187 
 
Listing 16.2.6.15.1 
CTCL Response During Randomized Treatment Period - By Independent Review 
______________________________________________________________________________________________________________________________________ 
                                          Response* 
                         ------------------------------------------------- 
Trt Arm     Date of                       Lymph     
  Subject   Exam         Skin    Blood    Nodes  Visceral  Overall 
______________________________________________________________________________________________________________________________________ 
Vorinostat 
  xxx-xxx   2013-12-03   -        SD      -        -          -          
            2013-12-17   CR       SD      PD       SD         NA         
            2013-12-27   -        SD      -        -          -          
               BEST      CR       SD      PD       SD         NA         
 
  xxx-xxx   2013-06-19   -        SD      -        -          -          
            2013-07-01   -        -       PD       NA         NA         
 
KW-0761 
  xxx-xxx   2013-10-17   NA       -       NA       NA         NA         
            2013-10-21   NA       NA      -        -          -          
               BEST      NA       NA      NA       NA         NA         
 
 
 
 
 
 
 
 
 
* CR = complete response; CRu = uncertified complete response; PR = partial response; SD = stable disease; PD = relapsed disease or 
  progressive disease; NA = not assessable. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
188 
 
Listing 16.2.6.15.2 
Lymph Node Assessment During Pre-Treatment and Randomized Treatment Period - By Independent Review  
 
Note: CR = complete response; CRu = uncertified complete response, PR = partial response; SD = stable disease; PD = relapsed disease 
or progressive disease; NA = not assessable. 
 
 
Trt Arm 
   Subject 
 
 
 
 
Timepoint 
 
 
Date of  
Exam 
Sum of Products 
of Diameters 
(mm^2) 
 
% Change from 
Baseline 
 
% Change 
from Nadir 
New 
Lymph 
Lesion 
 
Vorinostat 
    xxx-xxx 
 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 
 
 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 
 
 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
    xxx-xxx 
 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 
 
 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 
 
 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
189 
 
Listing 16.2.6.15.3 
Visceral Assessment During Pre-Treatment and Randomized Treatment Period - By Independent Review  
 
Note: CR = complete response; CRu = uncertified complete response, PR = partial response; SD = stable disease; PD = relapsed disease 
or progressive disease; NA = not assessable. 
 
Trt Arm 
   Subject 
 
 
 
Timepoint 
 
 
 
Date of  
Exam 
Sum of Products 
of Diameters 
(mm^2) 
 
% Change from 
Baseline 
 
% Change 
from Nadir 
 
New  
Lesion 
 
Vorinostat 
    xxx-xxx 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 
 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 
 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 
KW-0761  
    xxx-xxx 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 
 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 
 
 
xxxxxxxxxx 
 
YYYY-MM-DD  
xxx 
xx.x 
xx.x 
No 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
190 
 
Listing 16.2.6.16 
Progression-Free Survival (PFS) – By Investigator’s Assessment 
 
Trt Arm 
   Subject 
Disease 
Type 
CCR4 
Status 
Disease 
Stage 
Age/ 
Gender/ 
Race* 
Blood 
Involve-
ment 
Date of 
Randomi- 
zation 
Progressive 
Disease?/ 
Date of 
Progression 
Death?/Date of 
Death 
Date of Last 
Tumor 
Assessment 
PFS 
(Days) 
Vorinostat 
    xxx-xxx 
MF 
Positive 
   IB 
xx/M/W 
Yes 
YYYY-MM-DD 
Yes/YYYY-MM-DD 
Yes/YYYY-MM-DD 
YYYY-MM-DD 
xxx  
    xxx-xxx 
SS 
Negative 
   IIA 
xx/F/B 
No 
YYYY-MM-DD 
No 
No 
YYYY-MM-DD** 
xxx (C) 
    xxx-xxx 
MF 
Positive 
   IB 
xx/F/W 
No 
YYYY-MM-DD 
Yes/YYYY-MM-DD 
No 
YYYY-MM-DD 
xxx 
    xxx-xxx 
SS 
Negative 
   IIA 
xx/F/B 
Yes 
YYYY-MM-DD 
No 
Yes/YYYY-MM-DD 
YYYY-MM-DD 
xxx 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
    xxx-xxx 
MF 
Positive 
   IB 
xx/M/W 
Yes 
YYYY-MM-DD 
Yes/YYYY-MM-DD 
Yes/YYYY-MM-DD 
YYYY-MM-DD 
xxx  
    xxx-xxx 
SS 
Negative 
   IIA 
xx/F/B 
No 
YYYY-MM-DD 
No 
No 
YYYY-MM-DD** 
xxx (C) 
    xxx-xxx 
MF 
Positive 
   IB 
xx/F/W 
No 
YYYY-MM-DD 
Yes/YYYY-MM-DD 
No 
YYYY-MM-DD 
xxx 
    xxx-xxx 
SS 
Negative 
   IIA 
xx/F/B 
Yes 
YYYY-MM-DD 
No 
Yes/YYYY-MM-DD 
YYYY-MM-DD 
xxx 
Note: (C) = censored observation.  
* Gender: M = male; F = female. Race: W = White; A = Asian; B = Black or African American; AI = American Indian or Alaska Native; NH = 
Native Hawaiian or Other Pacific Islander; O = Other; NA = Not applicable. 
** If subjects withdraw prior to first tumor assessment, the last documented visit date is provided.    


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
191 
 
The following listing will have a similar layout as Listing 16.2.6.16: 
Listing 16.2.6.17 
Progression-Free Survival (PFS) - By Independent Review 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
192 
 
Listing 16.2.6.18 
Best Response During Randomized Treatment Period – By Investigator’s Assessment 
 
Trt Arm 
   Subject 
Disease 
Type 
CCR4 
Status 
Disease 
Stage 
Age/ 
Gender/ 
Race* 
Blood 
Involvement 
Compartment 
Best 
Response 
Date of First 
Response 
(Study Day) 
Duration of 
Response** 
(Days) 
Vorinostat 
    xxx-xxx 
MF 
Positive 
   IB 
xx/M/W 
Yes 
Overall 
PD 
YYYY-MM-DD (xx) 
 
 
 
 
 
 
 
Skin 
PD 
YYYY-MM-DD (xx) 
 
 
 
 
 
 
 
Lymph Nodes 
SD 
YYYY-MM-DD (xx) 
 
 
 
 
 
 
 
Blood 
PD 
YYYY-MM-DD (xx) 
 
    xxx-xxx 
SS 
Negative 
   IIA 
  xx/F/B 
No 
Overall 
SD 
YYYY-MM-DD (xx) 
 
 
 
 
 
 
 
Skin 
SD 
YYYY-MM-DD (xx) 
 
 
 
 
 
 
 
Lymph Nodes 
SD 
YYYY-MM-DD (xx) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
    xxx-xxx 
MF 
Positive 
   IB 
xx/M/W 
Yes 
Overall 
 CR* 
YYYY-MM-DD (xx) 
   xxx(C) 
 
 
 
 
 
 
Skin 
CR 
YYYY-MM-DD (xx) 
 
 
 
 
 
 
 
Lymph Nodes 
CR 
YYYY-MM-DD (xx) 
 
 
 
 
 
 
 
Blood 
CR 
YYYY-MM-DD (xx) 
 
    xxx-xxx 
SS 
Negative 
   IIA 
xx/F/B 
No 
Overall 
SD 
YYYY-MM-DD (xx) 
 
 
 
 
 
 
 
Skin 
SD 
YYYY-MM-DD (xx) 
 
 
 
 
 
 
 
Lymph Nodes 
SD 
YYYY-MM-DD (xx) 
 
Note: CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, NE = not evaluable; * = confirmed 
response; (C) = censored observation. 
Study day is calculated relative to the date of randomization. 
* Gender: M = male; F = female. Race: W = White; A = Asian; B = Black or African American; AI = American Indian or Alaska Native; NH = 
  Native Hawaiian or Other Pacific Islander; O = Other; NA = Not applicable. 
** Only calculated for subjects who achieved confirmed CR or PR during randomized treatment period.    
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
193 
 
The following listings will have similar layout as Listing 16.2.6.18: 
Listing 16.2.6.19 
Best Response During Randomized Treatment Period – By Independent Review 
 
 
Listing 16.2.6.20 
Best Response During Crossover Portion – By Investigator’s Assessment 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
194 
 
Listing 16.2.6.21 
Skindex-29 Assessment During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
  Subject 
    Visit 
Assessment 
Date 
-------------------------------------------Question Number*-------------------------------------------------- 
1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29 30 
Vorinostat 
  xxx-xxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
 
 
 
 
 
 
 
 
 
xxx-xxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
    xxxxx 
 
 
 
 
 
 
 
 
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
 
 
 
 
 
 
 
 
 
KW-0761  
  xxx-xxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
  xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
  xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x  x 
 
 
 
 
 
 
 
 
 
Note: 1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, 5 = All the Time.  
* See the first pages of the listing for a complete list of the questions for Skindex-29.  


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
195 
 
Listing 16.2.6.22 
Skindex-29 Score During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
Visit 
Assessment 
Date 
 
-------------------Score--------------------  
Overall   Symptoms  Emotions  Functioning 
 
 
 
 
 
Vorinostat 
    xxx-xxx xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x      
 
 
 
 
 
 
xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  xxx-xxx 
xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    xxx-xxx xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
    xxx-xxx xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
xxxxx 
YYYY-MM-DD 
 
   xx.x       xx.x      xx.x       xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  Raw responses were transformed to a linear scale of 0 (no effect) to 100 (effect experienced all the time). Each subscale score 
is the mean of a subject’s responses to the items in the specified subscale.  Overall score is the average of the 3 subscale scores. 
 
<<Programming Note: Symptoms scale includes questions 1, 7, 10, 16, 19, 24, 27; Functioning scale includes questions 2, 4, 5, 8, 11, 14, 17, 20, 
22, 25, 29, 30; Emotions scale includes questions 3, 6, 9, 12, 13, 15, 21, 23, 26, 28.>>


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
196 
 
The following listing will have similar layout as Listing 16.2.6.21 and Listing 16.2.6.22: 
Listing 16.2.6.23 
Skindex-29 Assessment During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.6.24 
Skindex-29 Score During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
<<Programming Note: Time Point will not be presented for listing 16.2.23 and Listing 16.2.6.24.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
197 
 
Listing 16.2.6.25 
FACT-G Assessment During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
  Subject 
    Visit 
Assessment 
Date 
-------------------------------------------Question Number*----------------------------------------- 
1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27 
Vorinostat 
  xxx-xxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
 
 
 
 
 
 
 
 
 
xxx-xxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
 
 
 
 
 
 
 
 
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
 
 
 
 
 
 
 
 
 
KW-0761  
  xxx-xxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
  xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
  xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x   x    
 
 
 
 
 
 
 
 
 
Note: 1 = Not at all, 2 = A little bit, 3 = Some-what, 4 = Quite a bit, 5 = Very much. 
* See the first pages of the listing for a complete list of the questions for FACT-G.  


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
198 
 
Listing 16.2.6.26 
FACT-G Subscale and Total Scores During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
Visit 
Assessment 
Date 
 
PWB 
SWB 
EWB 
FWB 
Total 
 
Vorinostat 
    xxx-xxx xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
  xxx-xxx 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
    xxx-xxx xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
    xxx-xxx xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
    xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
    xxx 
 
 
 
 
 
 
 
 
 
 
 
Note: PWB = physical well-being, SWB = social/family well-being, EWB = emotional well-being, FWB = functional well-being. 
Score Ranges: PWB, SWB and FWB: 0 to 28; EWB: 0 to 24; Total Score: 0 to 108. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
199 
 
The following listings will have similar layout as Listing 16.2.6.25 and Listing 16.2.6.26: 
 
Listing 16.2.6.27 
FACT-G Assessment During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
Listing 16.2.6.28 
FACT-G Subscale and Total Scores During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
200 
 
Listing 16.2.6.29 
EQ-5D-3L Assessment and Score During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
Visit 
Assessment 
Date 
 
Mobility 
Self-
Care 
Usual 
Activities 
Pain/ 
Discomfort 
Anxiety/ 
Depression 
Index 
Score 
VAS 
Score 
 
Vorinostat 
 
 
    xxx-xxx xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
  xxx-xxx 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
    xxx-xxx xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
 
 
    xxx-xxx xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
xxxxx 
YYYY-MM-DD 
 
xxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 1 = no problems, 2 = some problems, 3 = extreme problems. VAS = visual analog scale. See the first pages of the listing for a 
complete list of the questions for EQ-5D-3L.  


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
201 
 
The following listing will have a similar layout as Listing 16.2.6.29: 
Listing 16.2.6.30 
EQ-5D-3L Assessment and Score During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
202 
 
Listing 16.2.6.31 
Pruritus Evaluation - Itchy QoL Assessment During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
  Subject 
    Visit 
Assessment 
Date 
----------------------------Question Number*---------------------------------- 
 1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22   
Vorinostat 
  xxx-xxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
 
 
 
 
 
 
 
 
 
xxx-xxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
 
 
 
 
 
 
 
 
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
 
 
 
 
 
 
 
 
 
KW-0761  
  xxx-xxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
    xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
  xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
  xxxxx 
YYYY-MM-DD 
 x  x  x  x  x  x  x  x  x  x   x   x   x   x   x   x   x   x   x   x   x   x    
 
 
 
 
 
 
 
 
 
Note: 1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, 5 = All the time. 
* See the first pages of the listing for a complete list of the questions for Itchy QoL.  
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
203 
 
Listing 16.2.6.32 
Pruritus Evaluation Score During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
Does 
Subject 
have 
Pruritus? 
Visit 
Assessment 
Date 
-------------Itchy QoL Score-------- 
Total   Symptom  Function  Emotion 
Likert Scale 
of Pruritus 
 
Any 
Medication 
Taken? 
Vorinostat 
    xxx-xxx Yes 
xxxxx 
YYYY-MM-DD 
  xx.x    xx.x      xx.x      xx.x 
xxx 
 
Yes 
 
 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
No 
 
 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
Yes 
 
 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
No 
 
 
 
 
 
 
 
 
 
  xxx-xxx 
Yes 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
No 
 
 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
No 
 
 
 
 
 
 
 
 
 
    xxx-xxx Yes 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
Yes 
 
 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
Yes 
 
 
 
 
 
 
 
 
 
KW-0761  
    xxx-xxx Yes 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
Yes 
 
 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
No 
 
 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
Yes 
 
 
xxxxx 
YYYY-MM-DD 
xx.x    xx.x      xx.x      xx.x 
xxx 
 
No 
 
 
 
 
 
 
 
 
 
Note:  For Itchy QoL, item responses for frequency were scored on a 1 (never) to 5 (all of the time) scale.  Each subscale score is 
the mean of a subject’s responses to the items in the specified subscale.  Total score is the average of the 3 subscale scores.   
 
<<Programming Note: For Itchy QoL, Symptoms scale includes questions 1 to 6; Functioning scale includes questions 7 to 13; Emotions scale 
includes questions 14 to 22.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
204 
 
The following listings will have similar layout as Listing 16.2.6.31 and Listing 16.2.6.32: 
Listing 16.2.6.33 
Pruritus Evaluation - Itchy QoL Assessment During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.6.34 
Pruritus Evaluation Score During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
205 
 
Listing 16.2.6.35 
Skin Biopsy During Randomized During Pre-Treatment and Treatment Period 
 
Trt Arm 
   Subject 
 
Visit 
Biopsy 
Performed? 
Collection 
Date 
Result 
Reason for Skin Biopsy 
 
 
 
Vorinostat 
    xxx-xxx  
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
  xxx-xxx 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
    xxx-xxx  
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
    xxx-xxx  
xxxxxxxx 
Yes 
YYYY-MM-DD 
xxxxxxx 
Other: xxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
xxxxxxxx 
Yes 
YYYY-MM-DD 
Other: 
xxxxxxx 
Skin Rash: xxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
206 
 
The following listing will have a similar layout as Listing 16.2.6.35: 
Listing 16.2.6.36 
Skin Biopsy During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
207 
 
Listing 16.2.6.37 
Survival Status 
 
Trt Arm 
   Subject 
 
Date of 
Contact 
Method of 
Contact 
New Anti-
Cancer 
Therapy? 
Date of 
Therapy 
Disease 
Progression?/ 
Date 
Method 
of 
Confir-
mation 
Subject 
Alive?/Date 
of Death 
Primary 
Cause of 
Death 
Autopsy 
Conducted?/ 
Sig. Findings 
Vorinostat 
 
    xxx-xxx  
xxxxxxxx 
xxxxxxxx 
Yes/Specify 
YYYY-MM-DD 
Yes/YYYY-MM-DD 
xxxxxx 
Yes  
 
 
 
 
xxxxxxxx 
xxxxxxxxx 
No 
 
No 
 
No/YYYY-MM-DD 
xxxxxxxx 
No 
  xxx-xxx 
 
xxxxxxxx 
xxxxxxxx 
No 
 
No 
 
Yes 
 
 
 
 
xxxxxxxx 
xxxxxxxxx 
No 
 
Yes/YYYY-MM-DD 
xxxxx 
Yes  
 
 
    xxx-xxx  
xxxxxxxx 
xxxxxxxxx 
No 
 
No 
 
Yes 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
No 
 
No 
 
No/YYYY-MM-DD 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
 
    xxx-xxx  
xxxxxxxx 
xxxxxxxxx 
Yes/Specify 
YYYY-MM-DD 
Yes/YYYY-MM-DD 
xxxxxx 
Yes 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
No 
 
 
No 
 
 
No/YYYY-MM-DD 
Other: 
xxxxxxxx 
Yes/xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
208 
 
Listing 16.2.7.1 
Adverse Events During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
 
 
VT: Verbatim Term 
PT: MedDRA Preferred Term 
SOC:System Organ Class 
Start Date/Day 
Stop Date/Day 
Duration (days) 
 
CTCAE 
Grade 
 
TEAE  
Serious 
Relationship 
Action Taken/ 
Outcome 
Trt.  
for AE? 
Vorinostat 
   xxx-xxx 
  VT: xxxxxxxxxxxxxxxx 
YYYY-MM-DD/xx 
 
x 
Yes 
No 
Not related 
xxxxxxxxxx/ 
Yes 
    
 
PT: xxxxxx 
YYYY-MM-DD/xx 
 
 
 
 
 
xxxxxxxxxx 
 
 
 
SOC:xxxxxxxxxxx 
xx 
 
 
 
 
 
 
 
   xxx-xxx 
  VT: xxxxxxxxxxxxxxxx 
YYYY-MM-DD/xx 
 
x 
Yes 
Yes 
Probably 
xxxxxxxxxxxx/ 
No 
    
 
PT: xxxxxx 
YYYY-MM-DD/xx 
 
 
 
 
 
xxxxxxxxxx 
 
 
 
SOC:xxxxxxxxxxx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  VT: xxxxxxxxxxxxxxxx 
YYYY-MM-DD/xx 
 
x 
Yes 
Yes 
Probably 
xxxxxxxxxxxx/ 
No 
 
 
PT: xxxxxx 
YYYY-MM-DD/xx 
 
 
 
 
 
xxxxxxxxxx 
 
 
 
SOC:xxxxxxxxxxx 
xx 
 
 
 
 
 
 
 
   xxx-xxx 
  VT: xxxxxxxxxxxxxxxx 
YYYY-MM-DD/xx 
 
x 
Yes 
No 
Not related 
xxxxxxxxxx/ 
No 
    
 
PT: xxxxxx 
YYYY-MM-DD/xx 
 
 
 
 
 
xxxxxxxxxx 
 
 
 
SOC:xxxxxxxxxxx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
  VT: xxxxxxxxxxxxxxxx 
YYYY-MM-DD/xx 
 
x 
Yes 
No 
Unlikely 
xxxxxxxxxxxx/ 
Yes 
    
 
PT: xxxxxx 
YYYY-MM-DD/xx 
 
 
 
 
 
xxxxxxxxxx 
 
 
 
SOC:xxxxxxxxxxx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
   xxx-xxx 
  VT: xxxxxxxxxxxxxxxx 
YYYY-MM-DD/xx 
 
x 
Yes 
No 
Not related 
xxxxxxxxxx/ 
No 
    
 
PT: xxxxxx 
Ongoing 
 
 
 
 
 
xxxxxxxxxx 
 
 
 
SOC:xxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
  VT: xxxxxxxxxxxxxxxx 
YYYY-MM-DD/xx 
 
x 
Yes 
 No 
Unlikely 
xxxxxxxxxxxx/ 
Yes 
    
 
PT: xxxxxx 
YYYY-MM-DD/xx 
 
 
 
 
 
xxxxxxxxxx 
 
 
 
SOC:xxxxxxxxxxx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: MedDRA Version 15.1 was used for coding. Study day is calculated as start date or stop date of adverse event – date of first 
dose of study medication + 1. Duration is calculated as stop date of adverse event – start date of adverse event + 1.  
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
209 
 
The following listings will have similar layout as Listing 16.2.7.1: 
Listing 16.2.7.2 
Listing of Serious Adverse Events (SAEs) During During Pre-Treatment and Randomized Treatment Period 
 
 
Listing 16.2.7.3 
Listing of Grade III/IV/V Adverse Events During During Pre-Treatment and Randomized Treatment Period 
 
 
Listing 16.2.7.4 
Listing of Adverse Events Leading to Discontinuation of Study Medication During Randomized Treatment Period 
 
 
Listing 16.2.7.5 
Listing of Adverse Events Leading to Death During Randomized Treatment Period 
 
 
Listing 16.2.7.6 
Adverse Events During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.7.7 
Listing of Serious Adverse Events (SAEs) During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.7.8 
Listing of Grade III/IV/V Adverse Events During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.7.9 
Listing of Adverse Events Leading to Discontinuation of Study Medication During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.7.10 
Listing of Adverse Events Leading to Death During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
<<Programming Note: For adverse events during the crossover portion, Relationship and Action Taken should be displayed for each study 
medication.>> 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
210 
 
Listing 16.2.8.1 
Laboratory Assessment During During Pre-Treatment and Randomized Treatment Period – Chemistry 
 
Trt Arm 
   Subject 
 
Lab Test 
Unit 
Normal Range 
Low-High 
Visit 
 Sample Date/Time 
Lab Value 
Flag* 
CTCAE 
Grade 
CS? 
 
Vorinostat 
 
   xxx-xxx 
 
xxxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x   
H 
2 
No 
 
 
 
 
 
 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x   
H 
3 
Yes 
 
    
 
 
 
 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
 
 
xxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x   
L 
1 
No 
 
 
 
 
 
 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x   
H 
1 
No 
 
 
 
 
 
 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
xxx-xxx 
 
xxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x   
H 
0 
No 
 
 
 
 
 
 
xxxxxxxx 
Not Done 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x   
H 
1 
No 
 
 
 
 
 
 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
xxx-xxx 
 
xxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
 
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x   
H 
2 
No 
 
 
 
 
 
 
xxxxxxxx 
Not Done 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
 
 
 
 
 
 
 
xxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x   
H 
1 
No 
 
 
 
 
 
 
xxxxxxxx 
YYYY-MM-DD/HH:MM 
  xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CS = clinically significant. CTCAE grade is assigned for selected parameters based on NCI CTCAE criteria (version 4.0). 
* H = above upper limit of normal reference range; L = below lower limit of normal reference range. 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
211 
 
The following listings will have similar layout as Listing 16.2.8.1: 
Listing 16.2.8.2 
Laboratory Assessment During During Pre-Treatment and Randomized Treatment Period – Hematology 
 
 
Listing 16.2.8.3 
Laboratory Assessment During During Pre-Treatment and Randomized Treatment Period – Coagulation Profile 
 
 
Listing 16.2.8.4 
Laboratory Assessment During During Pre-Treatment and Randomized Treatment Period – Thyroid Function Test 
 
 
Listing 16.2.8.5 
Laboratory Assessment During During Pre-Treatment and Randomized Treatment Period – T-cell Counts 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
212 
 
Listing 16.2.8.6 
Laboratory Assessment During During Pre-Treatment and Randomized Treatment Period - Urinalysis  
 
Trt Arm 
   Subject 
 
Test 
Visit 
Urine 
Sample 
Collected 
Sample Date/Time 
Result 
Any CS 
Result? 
 
 
Vorinostat 
   xxx-xxx 
 
xxxxxxxxx 
xxxxxxx 
Yes 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
xxxxxxx 
Yes 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
  xxx-xxx 
 
xxxxxxxxx 
xxxxxxx 
Yes 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
xxxxxxx 
Yes 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
  xxx-xxx 
 
xxxxxxxxxx 
xxxxxxx 
Yes 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
    
 
 
xxxxxxx 
Yes 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
 xxx-xxx 
 
xxxxxxxxxx 
xxxxxxx 
Yes 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxx 
No 
 
 
 
 
 
 
 
YYYY-MM-DD/HH:MM 
xxxxxxxx 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CS = clinically significant. 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
213 
 
Listing 16.2.8.7 
Laboratory Assessment During During Pre-Treatment and Randomized Treatment Period – Pregnancy Test 
 
Trt Arm 
   Subject 
 
 
 
Pregnancy Test 
Performed? 
Date Performed 
Type of 
Test 
Result 
 
Vorinostat 
   xxx-xxx 
 
 
Yes 
YYYY-MM-DD 
Urine 
xxxxxxx 
 
 
 
 
Yes 
YYYY-MM-DD 
Serum 
xxxxxxx 
 
 
 
 
Yes 
YYYY-MM-DD 
Urine 
xxxxxxx 
 
   xxx-xxx 
 
 
Yes 
YYYY-MM-DD 
Urine 
xxxxxxx 
 
    
 
 
No 
 
 
 
 
 
 
 
Yes 
YYYY-MM-DD 
Serum 
xxxxxxx 
 
 
 
 
 
 
 
 
 
KW-0761 
   xxx-xxx 
 
 
Yes 
YYYY-MM-DD 
Urine 
xxxxxxx 
 
 
 
 
No 
 
 
 
 
 
 
 
Yes 
YYYY-MM-DD 
Urine 
xxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
214 
 
The following listings will have similar layout as Listings 16.2.8.1 to 16.2.8.7: 
Listing 16.2.8.8 
Laboratory Assessment During Crossover Portion – Chemistry 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.8.9 
Laboratory Assessment During Crossover Portion – Hematology 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.8.10 
Laboratory Assessment During Crossover Portion – Thyroid Function Test 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.8.11 
Laboratory Assessment During Crossover Portion – T-cell Counts 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.8.12 
Laboratory Assessment During Crossover Portion – Coagulation Profile 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.8.13 
Laboratory Assessment During Crossover Portion – Urinalysis 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 
Listing 16.2.8.14 
Laboratory Assessment During Crossover Portion – Pregnancy Test 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
215 
 
Listing 16.2.8.15 
Laboratory Assessment – Virus Testing 
 
Trt Arm 
   Subject 
 
 
Sample 
Collected? 
Date/Time of 
Sample 
HBsAG 
HBcAB-IgM 
HC Ab 
HIV 
HTLV-1 
Vorinostat 
 
 
   xxx-xxx 
 
 
Yes 
YYYY-MM-DD/HH:MM 
negative 
negative 
negative 
negative 
negative 
   xxx-xxx 
 
 
Yes 
YYYY-MM-DD/HH:MM 
negative 
positive 
negative 
negative 
negative 
 
 
 
 
 
 
 
 
 
 
KW-0761  
 
 
   xxx-xxx 
 
 
Yes 
YYYY-MM-DD/HH:MM 
negative 
negative 
negative 
negative 
negative 
   xxx-xxx 
 
 
Yes 
YYYY-MM-DD/HH:MM 
negative 
negative 
negative 
negative 
negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
216 
 
Listing 16.2.8.16 
Vital Signs During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
 
Visit 
Assessment 
Date/Time 
Time 
Point* 
Height 
(cm) 
Weight 
(kg) 
Blood 
Pressure 
SBP/DBP 
(mmHg) 
Pulse 
Rate 
(bpm) 
Temperature 
(C) 
Respiratory 
Rate 
(rpm) 
Vorinostat 
   xxx-xxx 
 
xxxxxxxxxx 
YYYY-MM-DD/HH:MM 
 
xxx 
xx.x 
xxx/xxx  
xx 
xx.x 
xx 
 
 
xxxxxxxxxx 
YYYY-MM-DD/HH:MM 
 
 
xx.x 
xxx/xxx 
xx  
xx.x 
xx 
 
 
xxxxxxxxxx 
YYYY-MM-DD/HH:MM 
 
    
 
xxx/xxx 
xx 
xx.x 
xx 
 
 
xxxxxxxxxx 
YYYY-MM-DD/HH:MM 
 
 
 
xxx/xxx 
xx 
xx.x 
xx 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
   xxx-xxx 
 
xxxxxxxxxx 
YYYY-MM-DD/HH:MM 
 
xxx 
xx.x 
xxx/xxx  
xx 
xx.x 
xx 
 
 
xxxxxxxxxx 
YYYY-MM-DD/HH:MM 
1 
 
xx.x 
xxx/xxx 
xx  
xx.x 
xx 
 
 
 
YYYY-MM-DD/HH:MM 
2 
    
 
xxx/xxx 
xx 
xx.x 
xx 
 
 
 
YYYY-MM-DD/HH:MM 
3 
 
 
xxx/xxx 
xx 
xx.x 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Time point: 1 = Pre-infusion, 2 = end of infusion, 3 = 1 hour post-infusion.   
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
217 
 
The following listing will have a similar layout as Listing 16.2.8.16: 
Listing 16.2.8.17 
Vital Signs During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
218 
 
Listing 16.2.8.18 
Electrocardiogram During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
 
Visit 
 
 
Date/Time Performed 
Heart 
Rate 
(bpm) 
PR 
 (msec) 
QRS 
 (msec) 
QT 
 (msec) 
QTcB 
 (msec) 
QTcF 
(msec) 
Rhythm 
Overall 
Interpretation 
Vorinostat 
 
 
 
   xxx-xxx 
 
xxxxxxxx 
 
 
YYYY-MM-DD/HH:MM 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxx 
Normal 
 
 
xxxxxxxx 
 
 
YYYY-MM-DD/HH:MM 
xxx 
xxx 
xxx 
xxx 
 xxx* 
 xxx* 
xxxxxx 
Abnormal, NCS 
 
 
xxxxxxxx 
 
 
YYYY-MM-DD/HH:MM 
xxx 
xxx 
xxx 
xxx 
 xxx* 
 xxx* 
xxxxxx 
Abnormal, CS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
 
xxxxxxxx 
 
 
YYYY-MM-DD/HH:MM 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxx 
Normal 
 
 
xxxxxxxx 
 
 
YYYY-MM-DD/HH:MM 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxx 
Normal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
 
 
 
 xxx-xxx 
 
xxxxxxxx 
 
 
YYYY-MM-DD/HH:MM 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxx 
Normal 
 
 
xxxxxxxx 
 
 
YYYY-MM-DD/HH:MM 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Other:x
xxxxx 
Normal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: for QTcB and QTcF: * = >450, ** = >480, *** = >500 msec. CS = clinically significant, NCS = not clinically significant. 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
219 
 
The following listing will have a similar layout as Listing 16.2.8.18: 
Listing 16.2.8.19 
Electrocardiogram During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
220 
 
Listing 16.2.8.20 
ECOG Performance Status During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
 
Visit 
Date of Evaluation 
ECOG 
Performance  
Status 
 
 
Vorinostat 
   xxx-xxx 
 
xxxxxxxxx 
YYYY-MM-DD 
x 
 
 
 
 
xxxxxxxxx 
YYYY-MM-DD 
x 
 
 
 
 
xxxxxxxxx 
Not Done 
 
 
 
 
 
xxxxxxxxx 
YYYY-MM-DD 
x 
 
 
 
 
 
 
 
 
 
KW-0761 1.0 mg/kg 
   xxx-xxx 
 
xxxxxxxxx 
YYYY-MM-DD 
x 
 
 
 
 
xxxxxxxxx 
YYYY-MM-DD 
x 
 
 
 
 
xxxxxxxxx 
YYYY-MM-DD 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
221 
 
The following listing will have a similar layout as Listing 16.2.8.20: 
Listing 16.2.8.21 
ECOG Performance Status During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
222 
 
Listing 16.2.8.22 
Physical Examination During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
 
Visit 
Physical  
Exam  
Performed? 
Date 
Performed 
 
 
Findings*  
Any Changes Since  
Previous Exam? 
Vorinostat 
 
   xxx-xxx 
 
xxxxxxxxx 
Yes 
YYYY-MM-DD 
 
 
Abnormal, not CS 
 
 
 
xxxxxxxxx 
Yes 
YYYY-MM-DD 
 
 
 
No 
 
 
xxxxxxxxx 
Yes 
YYYY-MM-DD 
 
 
 
Yes, not CS 
 
 
 
 
 
 
 
 
 
KW-0761 
 
     xxx-xxx 
 
xxxxxxxxx 
Yes 
YYYY-MM-DD 
 
 
Normal 
 
 
 
xxxxxxxxx 
Yes 
YYYY-MM-DD 
 
 
 
No 
 
 
xxxxxxxxx 
Yes 
YYYY-MM-DD 
 
 
 
No 
      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CS = clinically significant. 
* Only applies to pre-treatment visit.    
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
223 
 
The following listing will have a similar layout as Listing 16.2.8.22: 
Listing 16.2.8.23 
Physical Examination During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
224 
 
Listing 16.2.8.24 
Natural Ligands (MDC/TARC) Assessment During During Pre-Treatment and Randomized Treatment Period 
 
Trt Arm 
   Subject 
 
Visit 
Sample Collected?/ 
Reason Not Collected 
Sample Date 
 
MDC 
(ng/L) 
TARC 
(ng/L) 
 
Vorinostat 
 
   xxx-xxx 
 
xxxxxx 
Yes 
YYYY-MM-DD 
 
xxxxxxxx 
xxxxxxxx 
 
 
 
xxxxxx 
No/xxxxxxxxx 
 
 
 
 
 
 
 
xxxxxx 
Yes 
YYYY-MM-DD 
 
xxxxxxxx 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
KW-0761  
   xxx-xxx 
 
xxxxxx 
Yes 
YYYY-MM-DD 
 
xxxxxxxx 
xxxxxxxx 
 
 
 
xxxxxx 
No/xxxxxxxxx 
 
 
 
 
 
 
 
xxxxxx 
Yes 
YYYY-MM-DD 
 
xxxxxxxx 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
225 
 
The following listing will have a similar layout as Listing 16.2.8.24: 
Listing 16.2.8.25 
Natural Ligands (MDC/TARC) Assessment During Crossover Portion 
Subjects Who Are Randomized to Vorinostat and Crossed Over to KW-0761 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
226 
 
Listing 16.2.8.26 
Saliva Sample for Genetic Analysis – KW-0761 Treatment Only 
 
Trt Arm 
   Subject 
 
 
 
Sample Collected?/ 
Reason Not Collected 
Sample Date 
Result 
 
 
KW-0761  
   xxx-xxx 
 
 
Yes 
YYYY-MM-DD 
xxxxxxx 
 
 
 
   xxx-xxx 
 
 
No/xxxxxxxxx 
 
 
 
 
 
   xxx-xxx 
 
 
Yes 
YYYY-MM-DD 
xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
227 
 
 Listing 16.2.8.27 
Anti-KW-0761 Antibody Response 
Subjects Exposed to KW-0761  
 
Trt Arm 
   Subject 
 
Visit 
Sample 
Collected?/ 
Reason Not 
Collected 
Sample Date 
      Assay – Anti KW-0761 Antibody 
---------------------------------------------- 
Screen-   Confirm-         
ing       atory     Result   Status*   Titer   
Neutrali
zing  
-------- 
Result 
KW-0761 
Concentr
ation 
(ng/mL) 
Initially Randomized to KW-0761  
 
   xxx-xxx 
 
Pre-Trt 
Yes 
YYYY-MM-DD 
xxxxxxxx  xxxxxxxx   xxxx     xxxx      xxxx 
 
 
 
 
End of Cycle 1 
No/xxxxxxxxx 
 
 
 
 
 
 
 
End of Cycle x 
Yes 
YYYY-MM-DD 
xxxxxxxx  xxxxxxxx   xxxx     xxxx      xxxx 
 
 
 
 
. 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
End of Treatment 
Yes 
YYYY-MM-DD 
 
 
 
 
 
   xxx-xxx 
 
Pre-Trt 
Yes 
YYYY-MM-DD 
xxxxxxxx  xxxxxxxx   xxxx     xxxx      xxxx 
 
 
 
 
End of Cycle 1 
No/xxxxxxxxx 
 
 
 
 
 
 
 
End of Cycle x 
Yes 
YYYY-MM-DD 
xxxxxxxx  xxxxxxxx   xxxx     xxxx      xxxx 
 
 
 
 
. 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
End of Treatment 
Yes 
YYYY-MM-DD 
xxxxxxxx  xxxxxxxx   xxxx     xxxx      xxxx 
 
 
 
 
 
 
 
 
 
Cross Over to KW-0761 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: When Anti-KW-0761 antibody result is positive (the sample is positive in both screening assay and confirmatory assay), titer 
will be measured; - = not applicable or not evaluated; ** = calculated mean. 
[1] Visit (cycle number) is continuous of initial treatment for subject who crossed over. 
* Inconclusive because the sample is negative in screening assay and KW-0761 concentration is higher than drug tolerance limit (16000 
  ng/mL) or KW-0761 concentration is not determined. 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
228 
 
Listing 16.2.8.28 
   Anti-KW-0761 Antibody Response for Subjects with Infusion Reactions  
Subjects Exposed to KW-0761 
 
Trt Arm 
   Subject 
 
Adverse Event 
Reported 
Grade 
Onset Date/ 
Study Day 
 
 
Duration 
(Days) 
Discontinued 
or Dose 
Interrupted? 
 Assay Positive at Any Time Post-Baseline 
 ---------------------------------------- 
 Anti KW-0761          Neutralizing 
 Antibody Result          Result 
 
Initially Randomized to KW-0761 
 
   xxx-xxx 
 
Infusion Reaction 
  1 
YYYY-MM-DD/xx 
  4 
    No 
    Yes                    No 
 
 
 
xxxxxxxxx 
  2 
YYYY-MM-DD/xx 
  2 
    Yes 
 
 
 
 
 
 
 
 
 
 
 
   xxx-xxx 
 
Infusion Reaction 
  1 
YYYY-MM-DD/xx 
  1 
    No 
    Yes                    No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Crossed Over to KW-0761 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study day is calculated using start of adverse event - date of first dose of study medication + 1. Duration is calculated as stop date 
of adverse event - start date of adverse event + 1. 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
229 
 
Listing 16.2.8.29 
CCR4 Expression 
 
Trt Arm 
   Subject 
 
Visit 
Sample 
Submitted? 
Biopsy Type 
Collection Date 
Date Sent to 
Central Lab 
Result 
 
Vorinostat 
 
   xxx-xxx 
 
xxxxxx 
Yes 
Fresh:xxxxxxxx
xxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxx 
 
   xxx-xxx 
 
xxxxxx 
Yes 
Archived:xxxxx
xxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxx 
 
   xxx-xxx 
 
xxxxxx 
Yes 
xxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxx 
 
 
 
 
 
 
 
 
 
 
KW-0761   
   xxx-xxx 
 
xxxxxx 
Yes 
xxxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxx 
 
   xxx-xxx 
 
xxxxxx 
Yes 
xxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxx 
 
   xxx-xxx 
 
xxxxxx 
Yes 
xxxxxxxxxxxxx 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol 0761-010 
 
22 November 2016 
 
 
 
CONFIDENTIAL 
230 
 
Listing 16.2.8.30 
General Comments 
 
Trt Arm 
   Subject 
 
Visit 
Cycle/Day 
Page Name 
Comment 
 
 
 
Vorinostat 
 
   xxx-xxx 
 
xxxxxx 
xx/xx 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
 
 
 
   xxx-xxx 
 
xxxxxx 
xx/xx 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
   xxx-xxx 
 
xxxxxx 
xx/xx 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
KW-0761  
   xxx-xxx 
 
xxxxxx 
xx/xx 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
 
 
 
   xxx-xxx 
 
xxxxxx 
xx/xx 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
   xxx-xxx 
 
xxxxxx 
xx/xx 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxx