Clinical trial NCT02931838
Conditions: Psoriasis
Sponsor: Bristol-Myers Squibb
Start date: 2016-11-15; Completion date: 2017-11-16
Enrollment: 268 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A Study to evaluate efficacy and safety in subjects with moderate to severe Psoriasis treated with BMS-986165

Detailed description:

Arms: arm 1: Specified dose of BMS-986165 on specified days. arm 2: Specified dose of BMS-986165 on specified days. arm 3: Specified dose of BMS-986165 on specified days. arm 4: Specified dose of BMS-986165 on specified days. arm 5: Specified dose of BMS-986165 on specified days. arm 6: Specified dose of Placebo for BMS-986165 on specified days.
Interventions: intervention 1: BMS-986165 intervention 2: Placebo for BMS-986165
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_000.pdf: 
Page: 1
Protocol Number: IM011011
IND Number: 131,993
Ex-US Non-IND
EUDRACT Number 2016-002481-31
Date: 23-Aug-2016
CLINICAL PROTOCOLIM011011
A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Phase 2 Study 
to Evaluate the Clinical Efficacy and Safety of BMS-986165 in Subjects with Moderate to 
Severe Psoriasis
Study Director / Medical Monitor
Lars Hansen, M.D., PhD
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This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS-sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, 
copying, disclosure or dissemination of this information is strictly prohibited unless 
expressly authorized in writing by BMS. Any supplemental information (e.g.,amendments) 
that may be added to this document is also confidential and proprietary to BMS and must 


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be kept in confidence in the same manner as the contents of this document. Any person 
who receives this document without due authorization from BMS is requested to return it 
to BMS or promptly destroy it. All other rights reserved.References to BMS in this 
protocol may apply to partners to which BMS has transferred obligations, e.g.,a Contract 
Research Organization (CRO).
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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Original 
Protocol
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Not applicable
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SYNOPSIS
Clinical ProtocolIM011011
Protocol Title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Phase 2 Study to 
Evaluate the Clinical Efficacy and Safety of BMS-986165 in Subjects with Moderate to Severe Psoriasis
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): Subjects will be randomized to 1 of 6dosing arms: BMS-986165 at 3mg Q2D, 3mg QD, 3mg BID, 
6mg BID, 12mg QD or matching placebo capsule taken for the 12 week double-blind period.
Study Phase:  II
Research Hypothesis: The proportion of subjects with moderate to severe psoriasis experiencing a 75% reduction 
in psoriasis area and severity index score (PASI) after 12 weeks of treatment with BMS-986165 willbe higher than 
after 12 weeks of treatment with placebo
Objectives: 
The primary objectives are as follows:

Tocompare the proportion of subjects with moderate to severe psoriasis is experiencing a 75% improvementas 
measured byreduction in psoriasis area and severity index (PASI-75) score after 12 weeks of treatmentbetween 
doses of BMS-986165 and placebo.

To assess the safety and tolerabilityof multiple oral doses of BMS-986165 in subjects with moderate to severe 
psoriasis
The secondary objectivesare as follows:

To assessthat the proportion of subjects experiencing a 75% reduction in psoriasis area and severity index 
(PASI) score in the most efficacious treatment group 

To compare the proportionsof subjects experiencing a 75% reduction in psoriasis area and severity index 
(PASI) score between treatment groups

To assess a positive trend between treatment groups of BMS-986165 and proportion of subjects experiencing a 
75% reduction in PASI score after 12 weeks of treatment

To assess clinical efficacy of BMS-986165 as measured by improvement in skin disease area and severity 
indices PASI 50, 75, 90 and 100 over time in subjects with moderate to severe psoriasis 

To assess a significantly higher proportion of subjects achieving astaticphysician’s global assessment (sPGA) 
score of “0” (“cleared”) or “1” (“minimal”) after 12 weeks of treatment with BMS-986165 than after 12 weeks 
of treatment with placebo 

To assess improvement by BMS-986165 in quality of life assessments (DLQI)

To assessthe trough concentrations of BMS-986165 in subjects with moderate to severe psoriasis 
 
 
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Study Design:This is a 12 week, multi-center, randomized double-blind, placebo-controlled, multiple oral dose
study in subjects with psoriasis. Subjects will be randomly assigned to receive BMS-986165(3mg Q2D, 3mg QD, 
3mg BID, 6mg BID, 12mg QD)or placebo. Subjects will undergo screening evaluations to determine eligibility 
within 28 days prior to administration of study medication. 
This will be an outpatient study. Subjects will receive BMS-986165 or placebo capsules to be taken at home. 
Subjects will be provided by the Investigator Site with enough capsules to cover the treatment interval between 
study visits beginning on Study Day 1. Additional capsules covering the treatment interval between study visits 
should be supplied by the Investigator Site during each follow up visit. To facilitate PK analyses, certain doses of 
BMS-986165 or placebo capsules will be administered in the clinic (See Section 4.5). 
Subjects will be reporting to the clinic for study visits on study Days 1, 8, 15, 29, 57, 85and on a follow-up Day 
115.
Physical examinations, clinical disease activity assessments (Psoriasis Area and Severity Index [PASI], Body 
Surface Area assessment [BSA],staticPhysician’s Global Assessment sPGA), vital sign measurements, PK 
evaluations, clinical laboratory evaluations, ECG, skin biopsies, subject reported quality of life measures (DLQI), 
and PD evaluations will be performed at selected times throughout the dosing interval. Subjects will be closely 
monitored for adverse events throughout the study. Subjects will be required to return to the clinic for additional 
(unscheduled) safety follow up visitsas deemed necessary by the investigator. 
Since BMS-986165 is a novel investigational agent with immunomodulatory effects, immunosuppressant agents will 
be discontinued prior to dosing in order to maximize subject safety. Further, in order to determine whether 
BMS-986165 exerts a potent anti-psoriatic effect in the absence of background therapy, participation requires that 
subjects discontinue therapy (with the exception of topical emollients for symptomatic relief, including topical 
steroids for sensitive areas like groin etc.) prior to dosing as describedin Sections 3.4.1. 
The study design schematic is shown in Figure -1below.
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Figure -1:
Study Design Schematic for IM011011
Q2D=every other day,QD=every day, BID=twice daily
Study Population: Male and female subjects diagnosed with plaque psoriasis vulgaris for ≥ 6 months, eligible for 
phototherapy or systemic therapy, having plaques covering ≥ 10% BSA and with PASI score of ≥ 12, between 18-70 
years of age with a BMI of 18-40 kg/m2, inclusive,will be eligible to participate in the study. 
Women of childbearing potential (WOCBP) must not be nursing or pregnant and must be using an acceptable 
method of contraception. WOCBP must have a negative pregnancy test within 24 hours prior to dosing with study 
drug.
Key Inclusion Criteria

Men and women age 18-70, inclusive

Body mass index (BMI) 18-40 kg/m2and total body weight > 50 kg (110 lb)

Diagnosis of plaque psoriasis for ≥ 6 months

Deemed by Investigator to be eligible for phototherapy or systemic therapy

Plaques covering ≥ 10% of Body Surface Area (BSA) 

Psoriasis Area and Severity Index (PASI) score ≥ 12and sPGA 3

Women must not be pregnant, lactating, or planning pregnancy during the study period

WOCBP and men who are sexually active with WOCBP must follow instructions on birth control

Willing to discontinue topical and/or systemic therapies, with the exception of topical emollients and low 
potency topical steroids (rescue) prior to dosing
Key Exclusion Criteria

Diagnosis of non-plaque psoriasis(guttate, inverse, pustular, erythrodermic)

History of lack of response to ustekinumab, secukinumab or ixikizumab (any therapeutic agent targeted to IL-
12, IL-17 or IL-23) at approved doses after at least 3 months of therapy
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
Has received ustekinumab, secukinumab or ixikizumab (any therapeutic agent targeted to IL-12, IL-17 or IL-
23) within 6 months of first administration of study medication

Has received anti-TNFinhibitor(s) within 2 months of first administration of study medication

Has received natalizumab, efalizumab, or agents that modulate B cells or T cells (eg, alemtuzumab, abatacept, 
alefacept, or visilizumab) within 3 months of first administration of study medication

Has received Rituximab within 6 months of first administration of study medication

Has received any systemic immunosuppressants (eg, MTX, azathioprine, cyclosporine, 6-thioguanine, 
mercaptopurine, mycophenolate mofetil, hydroxyurea, and tacrolimus) or anakinra within 4 weeks of the first 
administration of study medication

Has received phototherapy or any systemic medications/treatments that could affect psoriasis or PGA 
evaluation (including, but not limited to, oral or injectable corticosteroids, retinoids, 1,25-dihydroxy vitamin D3 
and analogues, psoralens, sulfasalazine, hydroxyurea, or fumaric acid derivatives) within 4 weeks of the first 
administration of study medication

Has used topical medications/treatments that could affect psoriasis or PGA evaluation (including, but not 
limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, 
methoxsalen, trimethylpsoralens, picrolimus, aprimilast and tacrolimus) within 2 weeks of the first 
administration of study medication

Is currently receiving lithium, antimalarials, leflunomide, or IM gold, or have received lithium, antimalarials, 
IM gold within 4 weeks or leflunomide within 12 weeks of the first administration of any study medication

Has received an experimental antibody or biologic therapy within the previous 6 months, or received any other 
experimental therapy or new investigational agent within 30 days or 5 half-lives (whichever is longer) of any 
study agent administration or is currently enrolled in an investigational study

History or evidence of active infection and/or febrile illness within 7 days; or serious infections that led to 
hospitalization and IV antibiotic treatment within 90 days; or serious infection requiring antibiotic treatment 
within 30 days 

Active herpes infection, including herpes simplex 1 and 2 and herpes zoster identified on examination and/or 
medical history within 2 months of administration of study medication

Hepatitis C virus (HCV): subjects known to be positive for anti-HCV antibody or for HCV RNA detectable by 
polymerase chain reaction (PCR)

Hepatitis B virus (HBV): subjects known to be positive for hepatitis B surface antigen or for HBV DNA 
detectable by PCR

Human Immunodeficiency Virus (HIV) infection: subjects known to be HIV positive

History of active or inadequately treated latent TB

Known or suspected systemic or skin autoimmune disorder other than psoriasis and psoriatic arthritis

Any major illness or evidence of unstable condition of major organ systems including psychiatric

Cancer or history of lymphoproliferative disease within last 5 years; exception is resected cutaneous basal cell 
or squamous cell carcinoma that has been treated without recurrence

Class III or IV congestive heart failure by New York Heart Association Criteria

Unstable cardiovascular disease, defined as a recent clinical deterioration (e.g., unstable angina, rapid atrial 
fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months

Major surgery within the last 4 weeks

Live vaccines within the last 60 days

Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital 
signs, ECG, chest x-ray or clinical laboratory determinations beyond what is consistent with the target 
population

Leukopenia (absolute WBC count < 3000/mm3); Lymphopenia (ALC < 500/mm3); Neutropenia (ANC < 
1000/mm3)

Thrombocytopenia (platelet count < 100,000/mm3; Anemia (hemoglobin <9.0 g/dL)
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
ALT/AST > 3 X ULN and/or Total, unconjugated, and/or conjugated bilirubin > 2 X ULN within 28 days of 
dosing
Study Drug: includes both investigational [medicinal] products (IP/IMP) and non-investigational [medicinal] 
products (Non-IP/Non-IMP) as listed:
Study Drug for IM011011
Medication 
Potency 
IP/Non-IP 
BMS-986165-02 Capsules
3 mg (as the free base)
IP
Study Assessments: 

Efficacy Measures: Efficacy will be assessed using the PASI scores, as well as sPGA and DLQIas listed 
under the objectives and endpoints.

Safety Outcome Measures:  Safety assessments will be based on medical reviewof adverse event reports 
and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests. The 
incidence of observed adverse events will be tabulated and reviewed for potential significance and clinical 
importance.

Pharmacokinetic Measures: Pharmacokinetic parameters Ctrough, plasma concentration versus time data
  
 
 
 
 
Statistical Considerations:
Sample Size: The sample size calculation is driven by several considerations.  
The first consideration is to compare the response rate in PASI-75, the proportion of subjects with moderate to
severe psoriasis experiencing a 75% improvement reduction in psoriasis area and severity index (PASI) score after 
12 weeks, between BMS-986165 and placebo arms. With a one-sided, two-sample Fisher’s exact test at significant 
level 0.05, a sample size of 42 per arm will provide at least 99% power to detect 50% increase in the PASI-75 
response rate in an active arm (i.e., 60% response rate) compared to the placebo assuming the response rate is 10% 
in the placebo arm.  
The second consideration is to assess the response rate in PASI-75 in active dose arms. Data from 42 treated 
subjects per arm will produce a two-sided 95% confidence interval with a margin of error at most 15.1% (half 
width)  using normal approximation. 
The third consideration is to compare the response rates in PASI-75 in two active arms. With one-sided, two-sample 
Fisher’s exact test at significant level 0.05, 42 subjects per arm will provide at least 82% power to detect at least 
30% difference in the response rate in PASI-75 between any two active dose arms.  
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The proposed sample size is mainly driven by the third consideration. In addition, administration of BMS-986165 to 
42 subjects in each active treatment group provides 34%, 88%, and 99% probability of observing at least one 
occurrence ofany adverse event that would occur with 1%, 5%, or 10% incidence rate respectively.
Endpoints:  Primary Endpoint
The primary endpoint is the response rate in PASI-75: the proportion of subjects with moderate to severe psoriasis 
experiencing a 75% improvement reduction in psoriasis area and severity index (PASI) score after 12 weeks.
Secondary Endpoints
The secondary endpoints include efficacy endpoints (PASI-50, PASI-75, PASI-90, PASI-100, sPGA score, DLQI, 
etc) after week 12 of treatment and PK parameter,Ctrough.
The secondary endpoints to assessthe safety and tolerability of BMS-986195 are the incidence, potential 
significance, and clinical importance of adverse events measured during multiple doses of BMS-986195 and up to 
30 days after the last dose, as determined by medical review of adverse event reports, vital sign measurements, 
electrocardiograms (ECGs), and results of physical examination and laboratory tests.
 
Analyses:  
Demographics and Baseline Characteristics
Demographics and baseline characteristics including baseline disease activities will be tabulated by treatments using 
descriptive statistics. 
Efficacy Analyses
Primary Efficacy Analyses
The primary endpoint, the proportion of subjects with moderate to severe psoriasis experiencing a 75% 
improvement reduction in PASI score after 12 weeks, will be analyzed by two-sample Fisher’s exacttestor Chi-
square testto compare the response ratesineachtreatment groupand placebo. Cochran–Mantel–Haenszel Chi-
squaretest, stratified according to previous treatment with a biologicand/or region(Japanese vs rest of world), will 
be performed. The odds ratio (odd in atreatment group/odd in placebo)in the response rates and its corresponding 
two-sided 90% confidence interval (CI) will be providedwhen using Fisher’s exact testor Cochran-Matel-Haenszel 
Chi-square test.If Chi-square test is performed, the difference in the response rates and its corresponding two-sided 
90% confidence interval (CI) will be provided.
Inaddition, point estimate and 90% asymptotic and exact two-sided confidence intervals will be provided for the 
proportion of subjects in PASI-75 in each group. A logistic regression model may be performed to incorporate some 
of thecovariates if these covariate are assumed to impactthe response rates. Details of the tests and models will be 
given in the statistical analysis plan.
Secondary Efficacy Analyses
Similar analyses as in primary efficacy analyses will be performed to compare any two active arms.  
A logistic model will be conducted to detect a positive trend between treatment groups of BMS-986165.
The response rate in PASI-50, PASI-75, PASI-90, and PASI-100 will be summarized by treatment and time and will 
be analyzed using a repeated measure model when applicable.The same analyses will be conducted stratified by 
previous biologic treatmentand/or region. The proportion of subjects with asPGA score of “0” or “1” will be 
analyzed similarly to the primary analyses. sPGA, and DLQI Score from psoriasis subjects will be tabulated by 
treatment and time; the corresponding changes from baseline and percent change from baseline will be calculated 
and summarized. 
For continuous secondary endpoints (e.g. PASI, etc), point estimates andtwo-sided90% confidence intervals for 
mean change from baseline within each treatment group will be provided. For binary endpoints (response rate in 
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PASI, sPGA, etc.), point estimates of the response rate and two-sided 90% confidence intervals will be provided 
using normal approximation within each treatment group. 
In addition, a two-sided 90% confidence interval will be providedfor the difference in the secondary efficacy 
endpoints between each active arm and the placebo arm at each visit. More analyses, such as analysis of covariance 
models with treatment group, use of previous biologic treatment, and baseline value included as covariates, may be 
performed on endpoints such as PASI score, sPGA score, DLQI, etc. 
There will be no adjustment for multiplicity.  All comparisonswill be performed in apre-specifiedhierarchical 
procedure starting from the highest dosearmto the lowest dose arm. If a comparison is not significant at level 0.05, 
all P-values in subsequent comparisons will be considered to benominalandmay be provided if applicable.
 
Safety Analyses
All recorded adverse events will be listed and tabulated by system organ class, preferred term and treatment. Vital 
signs and clinical laboratory test results will be listed and summarized by treatment. Any significant physical 
examination findings, and clinical laboratory results will be listed. ECG readings will be evaluated by the 
investigator and abnormalities, if present, will be listed.
Pharmacokinetic Analyses
Summary statistics will be tabulated for Ctrough. Additional details will be provided in the statistical analysis plan 
(SAP) as necessary.
 
 
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TABLE OF CONTENTS 
TITLE PAGE 
................................................................................................................ 
DOCUMENT HISTORY 
.............................................................................................. 
SYNOPSIS
 ....................................................................................................................
 
TABLE OF CONTENTS 
.............................................................................................. 
1 
 
 
 
 
 
1.3 Objectives(s) 
..................................................................................................... 
1.3.1 Primary Objectives 
.................................................................................. 
1.3.2 Secondary Objectives 
............................................................................... 
 
 
 
 
 
 
 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
2 ETHICAL CONSIDERATIONS 
............................................................................... 
2.1 Good Clinical Practice 
...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee 
............................. 
2.3 Informed Consent.............................................................................................. 
3 INVESTIGATIONAL PLAN 
.................................................................................... 
3.1 Study Design and Duration 
............................................................................... 
3.2 Post Study Access to Therapy 
........................................................................... 
3.3 Study Population 
............................................................................................... 
3.3.1 Inclusion Criteria 
..................................................................................... 
3.3.2 Exclusion Criteria 
.................................................................................... 
3.3.3 Women of Childbearing Potential ........................................................... 
3.4 Concomitant Treatments 
................................................................................... 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
3.4.2 Other Prohibited and/or Restricted Concomitant Medications: ............. 
3.4.3 Other Restrictions and Precautions 
......................................................... 
3.5 Discontinuation of Subjects following any Treatment with Study Drug 
.......... 
3.6 Post Study Drug Follow up 
............................................................................... 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up 
.................................................................................... 
4 STUDY DRUG 
.......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.2 Non-investigational Product 
............................................................................. 
4.3 Storage of Study Drug ...................................................................................... 
4.4 Method of Assigning Subject Identification 
..................................................... 
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4.5 Selection and Timing of Dose for Each Subject 
............................................... 
4.6 Blinding/Unblinding 
......................................................................................... 
4.7 Treatment Compliance 
...................................................................................... 
4.8 Destruction or Return of Investigational Product 
............................................. 
4.9 Retained Samples for Bioavailability / Bioequivalence ................................... 
5 STUDY ASSESSMENTS AND PROCEDURES 
..................................................... 
5.1 Flow Chart/Time and Events Schedule 
............................................................. 
5.1.1 Retesting During Screening or Lead-in Period 
....................................... 
5.2 Study Materials 
................................................................................................. 
5.3 Safety Assessments 
........................................................................................... 
5.3.1 Imaging Assessment for the Study............................................................ 
5.3.2 Laboratory Test Assessments 
................................................................... 
5.3.3 Physical Exams 
........................................................................................ 
5.3.4 Tuberculosis Screening and Chest X-Ray 
................................................ 
5.3.5 ECG.......................................................................................................... 
5.3.6 Medical Photography (Optional) 
............................................................. 
5.3.7 Skin Biopsy 
............................................................................................... 
5.4 Efficacy Assessments 
........................................................................................ 
5.4.1 Primary Efficacy Assessment 
................................................................... 
5.4.1.1 Psoriasis Area and Severity Index (PASI) 
...................................... 
5.4.2 Secondary Efficacy Assessments 
.............................................................. 
5.4.2.1 Body Surface Area (BSA) 
................................................................ 
5.4.2.2 static Physician Global Assessment (sPGA) 
................................... 
5.4.2.3 Dermatology Life Quality Index (DLQI) ........................................ 
 
 
5.5 Pharmacokinetic Assessments 
.......................................................................... 
5.5.1 Pharmacokinetics: Collection and Processing 
........................................ 
5.5.2 Pharmacokinetic Sampling Window 
........................................................ 
5.5.3 Pharmacokinetic Sample Analyses 
.......................................................... 
5.5.4 Labeling and Shipping of Biological Samples 
......................................... 
 
 
5.7 Outcomes Research Assessments 
..................................................................... 
5.8 Other Assessments 
............................................................................................ 
5.9 Additional Research Collection 
........................................................................ 
6 ADVERSE EVENTS 
................................................................................................. 
6.1 Serious Adverse Events 
.................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting 
.................................... 
6.2 Nonserious Adverse Events 
.............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting 
.............................. 
6.3 Laboratory Test Result Abnormalities 
.............................................................. 
6.4 Pregnancy 
.......................................................................................................... 
6.5 Overdose 
........................................................................................................... 
6.6 Potential Drug Induced Liver Injury 
................................................................. 
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6.7 Other Safety Considerations 
............................................................................. 
7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
................................................................................................................................. 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination 
............................................................................... 
8.2 Populations for Analyses 
.................................................................................. 
8.3 Endpoints 
.......................................................................................................... 
8.3.1 Primary Endpoint(s) ................................................................................ 
8.3.2 Secondary Endpoint(s) 
............................................................................. 
 
8.4 Analyses 
............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses 
..................................................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses 
....................................................................... 
 
. 
8.4.7 Outcomes Research Analyses .................................................................. 
8.4.8 Other Analyses 
......................................................................................... 
8.4.8.1 Population PK and Exposure Response Analysis 
........................... 
8.5 Interim Analyses 
............................................................................................... 
9 STUDY MANAGEMENT 
........................................................................................ 
9.1 Compliance 
....................................................................................................... 
9.1.1 Compliance with the Protocol and Protocol Revisions 
........................... 
9.1.2 Monitoring 
............................................................................................... 
9.1.2.1 Source Documentation 
.................................................................... 
9.2 Records ............................................................................................................. 
9.2.1 Records Retention 
.................................................................................... 
9.2.2 Study Drug Records 
................................................................................. 
9.2.3 Case Report Forms 
.................................................................................. 
9.3 Clinical Study Report and Publications 
............................................................ 
10 GLOSSARY OF TERMS 
........................................................................................ 
11 LIST OF ABBREVIATIONS 
.................................................................................. 
12 REFERENCES ........................................................................................................ 
APPENDIX 1 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION 
..................................................................... 
APPENDIX 2 PSORIASIS AREA AND SEVERITY INDEX (PASI) 
....................... 
APPENDIX 3 STATIC PHYSICIAN’S GLOBAL ASSESSMENT (SPGA) 
............. 
 
APPENDIX 5 AMERICAN COLLEGE OF RHEUMATOLOGY SUBJECT 
ASSESSMENT OF PAIN VISUAL ASSESSMENT SCALE 
............................... 
APPENDIX 6 SUSTAINED ELEVATED LIVER SAFETY ABNORMALITIES 
FLOW CHART 
....................................................................................................... 
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1.2
Research Hypothesis 
The proportion of subjects with moderate to severe psoriasis experiencing a 75% reduction in 
psoriasis area and severity index score (PASI) after 12 weeks of treatment with BMS-986165 
will be higher than after 12 weeks of treatment with placebo
1.3
Objectives(s)
1.3.1
Primary Objectives
To compare the proportion of subjects with moderate to severe psoriasis is experiencing a 
75% improvement as measured by reduction in psoriasis area and severity index (PASI-75) 
score after 12 weeks of treatment between doses of BMS-986165 and placebo
To assess the safety and tolerability of multiple oral doses of BMS-986165 in subjects with 
moderate to severe psoriasis
1.3.2
Secondary Objectives
To assess that the proportion of subjects experiencing a 75% reduction in psoriasis area and 
severity index (PASI) score in the most efficacious treatment group 
To compare the proportion of subjects experiencing a 75% reduction in psoriasis area and 
severity index (PASI) score between treatment groups
To assess a positive trend between treatment groups of BMS-986165 and proportion of 
subjects experiencing a 75% reduction in PASI score after 12 weeks of treatment
To assess clinical efficacy of BMS-986165 as measured by improvement in skin disease area 
and severity indicesPASI50, 75, 90 and 100 over time in subjects with moderate to severe 
psoriasis 
To assess a significantly higher proportion of subjects achieving a static physician global 
assessment (sPGA) score of “0” (“cleared”) or “1” (“minimal”) after 12 weeks of treatment 
with BMS-986165 than after 12 weeks of treatment with placebo 
To assess improvement by BMS-986165 in quality of life assessments (DLQI)
To assess the trough concentrations of BMS-986165in subjects with moderate to severe 
psoriasis 
 
 
 
 
 
 
 
 
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2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Council on Harmonisation (ICH) and in accordance with the ethical principles 
underlying European Union Directive 2001/20/EC and the United States Code of Federal 
Regulations, Title 21, Part 50 (21CFR50)and applicable local requirements.
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) and local health authority, if applicable, approval/favorable opinion prior 
to initiation of the study.
All potential serious breaches must be reported to Sponsor or designateimmediately. A serious 
breach is a breach of the conditions and principles of GCP in connection with the study or the 
protocol, which is likely to affect, to a significant degree, the safety or physical or mental 
integrity of the subjects of the study or the scientific value of the study.
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or 
where there has been scientific misconduct or fraud (e.g., loss of medical licensure, debarment). 
2.2
Institutional Review Board/Independent Ethics Committee 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, subject recruitment materials (e.g., 
advertisements), and any other written information to be provided to subjects. The investigator or 
BMSshould also provide the IRB/IEC with a copy of the Investigator Brochure or product 
labelinginformation to be provided to subjects and any updates. 
The investigator, Sponsoror designateshould provide the IRB/IEC with reports, updates and 
other information (e.g., expedited safety reports, amendments,and administrative letters) 
according to regulatory requirements or institution procedures.
2.3
InformedConsent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
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In situations where consent cannot be given tosubjects, their legally acceptable representatives
(as per country guidelines) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the subject volunteers to participate. 
Sponsoror designatewill provide the investigator with an appropriate (i.e., Global or Local) 
sample informed consent form(s)which will include all elements required by ICH, GCP and 
applicable regulatory requirements. The sample informed consent form will adhere to the ethical 
principles that have their origin in the Declaration of Helsinki.
Investigators must:
Provide a copy of the consent form(s)and written information about the study in the 
language in which the subject is most proficient prior to clinical study participation. The 
language must be non-technical and easily understood. 
Allow time necessary for subject or subject
's legally acceptable representative to inquire 
about the details of the study.
Obtain an informed consent signed and personally dated by the subject or the subject
's 
legally acceptable representative and by the person who conducted the informed consent
discussion. 
Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent 
form(s)and any other information to be provided to the subjects, prior to the beginning of the 
study, and after any revisions are completed for new information.
If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his 
or herinformedconsent during the study, consent must additionally be obtained from the 
subject.
Revise the informed consent whenever important new information becomes available that is 
relevant to the subject
's consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject
's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
subject
's willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the subjects
' signed ICF 
and, in the US, the subjects’ signed HIPAA Authorization.
The consent form(s)must also include a statement that BMS and regulatory authorities have 
direct access to subject records. 
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
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3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a 12 week, multi-center, randomized double-blind, placebo-controlled,parallel-group
multiple oral dose study in subjects with moderate to severe psoriasis. Subjects will be randomly 
assigned to receive BMS-986165(3mg Q2D, 3mg QD, 3mg BID, 6mg BID, 12mg QD) or 
placebo. Subjects will undergo screening evaluations to determine eligibility within 28 days prior 
to administration of study medication. 
This will be an outpatient study. Subjects will receive BMS-986165 or placebo capsules to be 
taken at home. Subjects will be provided by the Investigator Site with enough capsules to cover 
the treatment interval between study visits beginning on Study Day 1. Additional capsules 
covering the treatment interval between study visits should be supplied by the Investigator Site
during each follow up visit. To facilitate PK analyses, certain doses of BMS-986165 or placebo 
capsules will be administered in the clinic (see Section4.5). 
Subjects will be reporting to the clinic for study visits on study Days 1, 8, 15, 29, 57, 85and 
115.
Physical examinations, clinical disease activity assessments (Psoriasis Area and Severity Index 
[PASI], Body Surface Area assessment [BSA], static Physician’s Global Assessment sPGA), 
vital sign measurements, PK evaluations, clinical laboratory evaluations, ECG, skin biopsies, 
subject reported quality of life measures (DLQI), and PD evaluations will be performed at 
selected times throughout the dosing interval.Adverse events will be recorded and assessed by 
the Investigator (or designee as documented in the DOA) at study visits and throughout the study 
period.Subjects will be required to return to the clinic foradditional (unscheduled)safety follow 
up visitsas deemed necessary by the investigator. 
Since BMS-986165 is a novel investigational agent with immunomodulatory effects, 
immunosuppressant agents will be discontinued prior to dosing in order to maximize subject 
safety. Further, in order to determine whether BMS-986165 exerts a potent anti-psoriatic effect 
in the absence of background therapy, participation requires that subjects discontinue therapy 
(with the exception of topical emollients for symptomatic relief) prior to dosing as describedin 
Sections 3.4.1.
The study design schematic is presented in Figure 3.1-1.
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Figure 3.1-1:
Study Design Schematic
Q2D=every otherday, QD=every day, BID=twice daily
The approximate duration of the study is20 weeks (143days), this includes,a 4-week screening 
period (28 days), a 12-week treatment period (85days) and 4 weeksof follow-up period (30 
days).
The start of the trial is defined as the date of the first Screening Visit (date of signing the 
informed consent) for the first subject screened. End of trial is definedasthe last visit or 
scheduled procedure shown in the Time & Events schedule for the last subject.Study completion 
is defined as the final date on which data for the primary endpoint was or is expected to be 
collected, if this is not the same.
3.2
Post StudyAccess to Therapy
At the end of the study, BMS will not continue to provide BMS suppliedstudy drug to 
subjects/investigators unless BMSchooses to extend the study. The investigator should ensure 
that the subject receives appropriate standard of care to treat the condition under study.
3.3
Study Population
For entry into the study, the following criteria MUST be met prior to dosing on Day 1. No 
exceptions will be granted.
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3.3.1 
Inclusion Criteria
1. Signed Written Informed Consent
a) Subjects is willing to participate inthe study and has signed the informed consent 
2. Target Population
a) Male and female subjects with a diagnosis of plaque psoriasis for 6 months 
b) Body mass index (BMI) 18-40 kg/m2and total body weight > 50 kg (110 lb)
c) Deemed by Investigator to be eligible for phototherapy or systemic therapy
d) Psoriatic plaques must cover 10% of body surface area (BSA)
e) Psoriasis Area and Severity Index (PASI) score 12and sPGA 3
3. Age and Reproductive Status
a) Males and Females, ages 18 or age of majorityto 70years, inclusive
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 
hours prior to the start of study drug.
c) Women must not be pregnant, lactating, breastfeeding or planning pregnancy during the 
study period
d) Women of childbearing potential (WOCBP) must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug(s) BMS-986165
plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 33
days post-treatment completion
e) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug(s) BMS-986165
plus 5 half-lives of the study drug plus 90 days (duration of sperm turnover) for a total of 
93days post-treatment completion. In addition, male subjects must be willing to refrain 
from sperm donation during this time.
f) Azoospermic males are exempt from contraceptiverequirements.WOCBP who are 
continuously not heterosexually active are also exempt from contraceptive requirements, 
andstill undergo pregnancy testing as described in this section.
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy.
Investigators shall advise on the use of highly effective methods of contraception(Appendix 1)
which have a failure rate of < 1% when used consistently and correctly.
3.3.2
Exclusion Criteria
4. Target Disease Exceptions
a) Diagnosis of non-plaque psoriasis (guttate, inverse, pustular, erythrodermic)
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b) Diagnosis of psoriatic arthritis, uveitis, inflammatory bowel disease, or other 
immune-mediated conditions that are commonly associated with psoriasis for which a 
subject requires current systemic (oral, SC, or IV) (including corticosteroids, 
immunosuppressants, biologics) immunosuppressant medical treatment. Certain therapies 
such as NSAIDs may be permitted, but should be discussed with the BMS Medical 
Monitor prior to determination of subject eligibility. 
5. Infectious/Immune-related Exclusions
a) History or evidence of active infection and/or febrile illness within 7 days of Study Day 1 
(e.g., bronchopulmonary, urinary, gastrointestinal, etc.)
b) History of serious bacterial, fungal, or viral infections that let to hospitalization and IV 
antibiotic treatment within 90 days prior to screening, or any recent serious infection 
requiring antibiotic treatment within 30 days of Study Day 1
c) Live vaccines within 60 days of first dose of study medication
d) Has a history of an infected joint prosthesis, or has received antibiotics for a suspected 
infection of a joint prosthesis, if that prosthesis has not been removed or replaced
e) Active herpes infection, including herpes simplex 1 and 2 and herpes zoster 
(demonstrated on physical examination and/or medical historywithin 2 months of 
administration of study medication)
f) Positive hepatitis-B (HBV) surface antigenor HBV DNA by Polymerase Chain Reaction 
(PCR)
g) Positive hepatitis-C(HCV) antibody with positive Recombinant ImmunoBlot Assay 
(RIBA) or HCV RNA by or Polymerase Chain Reaction (PCR)
3. Subjects with any history or risk for tuberculosis (TB), specifically subjects with:
a) Current clinical radiographic or laboratory evidence of active TB
b) History of active TB within the last 3 years, unless there is documentation that prior 
anti-TB treatment was appropriate in duration and type according to current World 
Health Organization Guidelines.
c) Latent TB defined as Positive QFG or other diagnostic test in the absence of clinical 
manifestations, unless subject has received at least 1 month treatment with Isoniazid, or 
other agents recommended by local Health Authority guidelines, and an interferon 
gamma release assay (IGRA) test, eg, QFG or T-Spot, is negative before Day 1
d) Anyhistory of known or suspected congenital or acquired immunodeficiency state or 
condition that would compromise the subject’s immune status (e.g., history of 
splenectomy, primary immunodeficiency, HIV infection, etc.)
6. Medical History and Concurrent Diseases
a) Any significant acute or chronic medical illness
b) Any major surgery within 4 weeks of study drug administration
c) Blood transfusion within 4 weeks of studydrug administration
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d) Recent (within 6 months of study drug administration) drug or alcohol abuse as 
determined by the Investigator 
e) Any major illness/condition or evidence of an unstable clinical condition (e.g., renal, 
hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic, or local 
active infection/infectious illness) that, in the Investigator’s judgment will substantially 
increase the risk to the subject if he or she participates in the study
f) Has unstable cardiovascular disease, defined as a recent clinical deterioration (e.g., 
unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization 
within the last 3 months. 
g) Class III or IV congestive heart failure by New York Heart Association Criteria
h) Has been hospitalized in the past 3 months for asthma, ever required intubation for 
treatment of asthma, currently require oral corticosteroids for the treatment of asthma, or 
required more than one short-term (≤ 2 weeks) course of oral corticosteroids for asthma 
within the previous 6 months
i) History of cancer (solid organ or hematologic including myelodysplastic syndrome) or 
lymphoproliferative disease within the previous 5 years (other than resected cutaneous 
basal cell or squamous cell carcinoma that has been treated with no evidence of 
recurrence)
j) Inability to tolerate oral medication
k) Inability to be venipunctured and/or tolerate venous access
l) Any other sound medical, psychiatric and/or social reason as determined by the 
Investigator
m) History of lack of response toustekinumab, secukinumab or ixikizumab (any therapeutic 
agent targeted to IL-12, IL-17 or IL-23) at approved doses after at least 3 months of 
therapy
n) Has received ustekinumab, secukinumab or ixikizumab (any therapeutic agent targeted to 
IL-12, IL-17 or IL-23) within 6 months of first administration of study medication
o) Has received anti-TNFinhibitor(s) within 2 months of first administration of study 
medication
p) Has received natalizumab, efalizumab, or agents that modulate B cells or T cells (eg, 
alemtuzumab, abatacept, alefacept, or visilizumab) within 3 months of first 
administration of study medication
q) Has received Rituximab within 6 months of first administration of study medication.
r) Has received any systemic immunosuppressants (eg, MTX, azathioprine, cyclosporine, 
6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, and tacrolimus) or 
anakinra within 4 weeks of the first administration of study medication
s) Has received phototherapy or any systemic medications/treatments that could affect 
psoriasis or PGA evaluation (including, but not limited to, oral or injectable 
corticosteroids, retinoids, 1,25-dihydroxy vitamin D3 and analogues, psoralens, 
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sulfasalazine, hydroxyurea, or fumaric acid derivatives) within 4 weeks of the first 
administration of any study medication
t) Has used topical medications/treatments that could affect psoriasis or PGA evaluation 
(including, but not limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D 
derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens, picrolimus, and 
tacrolimus) within 2 weeks of the first administration of any study medication
u) Is currently receiving lithium, antimalarials, or IM gold, or have received lithium, 
antimalarials, or IM gold within 4 weeks of the first administration of any study 
medication
v) Has received an experimental antibody or biologic therapy within the previous 6 months, 
or received any other experimental therapy or new investigational agent within 30 days or 
5 half-lives (whichever is longer) of any study medication administration or is currently 
enrolled in an investigational study
7. Physical and Laboratory Test Findings
a) Evidence of organ dysfunction or any clinically significant deviation from normal in 
physical examination, vital signs, ECG or clinical laboratory determinations beyond what 
is consistent with the target population
b) Urinalysis findings suspicious of infection (e.g. pyuria, bacteriuria) in a non-
contaminated sample collected at screening. Subjects may be rescreened and if deemed 
eligible may be randomized within 14 days of completing an appropriate course of 
antibiotic treatment for urinary tract infection.
c) Chest X-ray findings suspicious of infection at screening. Subjects may be rescreened if 
deemed eligible may be randomized within 28 days of completing an appropriate course 
of antibiotic treatment for pulmonary infection.
d) Leukopenia defined as absolute WBC count < 3000/mm3 within 28 days of dosing with 
study drug on Day 1
e) Lymphopenia defined as absolute lymphocyte count < 500/mm3 within 28 days of dosing 
with study drug on Day 1
f) Neutropenia defined as absolute neutrophil count < 1000/mm3 within 28 days of dosing 
with study drug on Day 1
g) Moderate to severe thrombocytopenia defined as platelet count < 100,000/mm3 within 28 
days of dosing with study drug on Day 1
h) Moderate to severe anemia defined as hemoglobin < 9 g/dL within 28 days of dosing 
with study drug on Day 1
i) ALTand/or AST> 3X ULN within 28 days of dosing with study drug on Day 1 
j) Total, unconjugated, and/or conjugated bilirubin > 2X ULN within 28 days of dosing 
with study drug on Day 1 
k) Any other significant laboratory or procedure abnormalities that, in the opinion of the 
Investigator, might place the subject at unacceptable risk for participation in this study
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8. Allergies and Adverse Drug Reaction
a) History of any significant drug allergy (such asanaphylaxis or hepatotoxicity)
9. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific 
circumstances a person who has been imprisoned may be included or permitted to 
continue as a subject. Strict conditions apply and Bristol-Myers Squibb approval is 
required.
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(e.g., infectious disease) illness
c) Inability to comply with restrictions and prohibited activities/treatments as listed in 
Section 3.4
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects andthat the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
3.3.3
Women of Childbearing Potential
Women of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) andis not postmenopausal. Menopause is defined as 12 months of amenorrhea in 
a woman over age 45 in the absence of other biological or physiological causes. In addition, 
femalesunder the age of 55 yearsmust have a documented serum follicle stimulating hormone 
(FSH) level > 40mIU/mLto confirm menopause.
Femalestreated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgmentin checking serum FSH levels. 
1 week minimum for vaginal hormonal products (e.g., rings, creams, gels)
4 week minimum for transdermal products
8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months.If the serum FSH 
level is >40 mIU/ml at any time during the washout period, the woman can be considered 
postmenopausal.
3.4
Concomitant Treatments
3.4.1
Prohibited and/or Restricted Treatments
Prohibited and/or restricted medications taken prior to study drug administration in the study are 
described below in Table 3.4.1-1. Medications taken within 4 weeks prior to study drug 
administration must be recorded on the CRF.
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Table 3.4.1-1:
Prohibitedand or Restricted Treatments
Prohibited Treatments
Washout Period 
(before randomization)
Ustekinumab, secukinumab or ixikizumab 
(any therapeutic agent targeted to IL-12, IL-17, or IL-23)
6 months
TNFαinhibitors
2 months
Natalizumab, efalizumab, or agents that modulate B cells or T cells
(e.g. alemtuzumab, abatacept, alefacept, visilizumab)
3 months
Rituximab
6 months  
Systemic immunosuppressants 
(e.g. MTX, Azahiopine, cyclosporine, 6-thiouganine, mercaptopurine, 
mycophenolate mofetil, hydroxyurea, tacrolimus) or anakinara
4 weeks
Phototherapy 
4 weeks
Systemic medications/treatments 
(including but not limited to oral or injectable corticosteroids, retinoids, 1,25-
dihydroxy vitamin D3 and analogues, psoralens, sulfasalazine, hydroxyurea, 
fumaric acid derivative)
4 weeks
Topical Treatments 
(e.g. corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, 
retinoids, tazarotene, methoxsalen, trimethylpsoralens, picrolimus, tacrolimus)
2 weeks
Lithium, antimalarias, IM gold
4 weeks
Any biological therapy
6 months
Any experimental therapy or new investigational agentor participation in any 
other experimental/investigational trial 
30 days or 5 half-life 
(whichever is longer)
3.4.2
Other Prohibitedand/or Restricted Concomitant Medications:
Due to potential pharmacokinetic interactions with the transporters BCRP (as inhibitor) and 
P-gp (as substrate), the following medications that are restricted or prohibited:
Breast cancer resistance protein (BRCP) substrates, such as rosuvastatin should be used 
with caution. If a subject is taking rosuvastatin during the study duration,the following 
guidelines should be used :
Monitor of LFTs & CPK for duration of study:
If 2x baseline and <3 ULN increase, consider lowering statin dose by ½ 
If > 3 ULN, stop statin for duration of study
If > 5 ULN, stop statin and discontinue study medication
If myopathy and CPK<10 ULN are observed consider lowering statin dose by ½ 
If CPK ≥10 ULN or rhabdomyolysis, stop statin and discontinue study medication 
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Strong inhibitors of P-gp such as quinidine, cyclosporine, cobicistat, conivaptan, 
indinavir, itraconazole, ketoconazole, nefazodone, posaconazole, ritonavir, saquinavir, 
telaprevir, telithromycin, voriconazole are prohibited for the duration of the study.
Additional references24,25and individual drug labels should be referred to for further information 
on pharmacokinetic DDIs
In addition, the use of concomitant medications (prescription, over-the-counter or herbal) should 
be limited during the study unless they are prescribed by the investigator for treatment of specific 
clinical events and after consultation with the medical monitor. Any changes to or new 
concomitant therapies must be recorded on the CRF.
3.4.3
Other Restrictions and Precautions
Subjects are advised to protect against sun exposure through sun avoidance, use of protective 
clothing (long sleeves, pants, hats, etc.), and use of sunscreen from at least 1weekprior to 
the first doseof study medicationuntil the safety follow-up visit.
3.5
Discontinuation of Subjects following any Treatmentwith Study Drug
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:
Subject’s request to stop study treatmentand/or participation in the study
Any clinical adverse event (AE), laboratoryabnormalityor intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the 
best interest of the subject
Termination of thestudy by Bristol-Myers Squibb (BMS)
Loss of ability to freely provide consent through imprisonment or involuntarilyincarceration 
for treatment of either a psychiatric or physical (e.g., infectious disease) illness
Inability to comply with protocol
Discretion of the investigator
In the case of pregnancy, the investigator must immediately notify the Sponsor or designateof 
this event. In the event a normal healthy female subject becomes pregnant during a clinical trial, 
the study drug must be discontinued immediately. In most cases, the study drug will be 
permanently discontinued in an appropriate manner(e.g., dose tapering if necessary for subject 
safety). Please contactthe Sponsor or designatewithin 24 hours of awareness of the pregnancy.
If the investigator determines a possible favorable benefit/risk ratio that warrants continuation of 
study drug, a discussion between the investigator and the Sponsor or designatemust occur.
All subjects who discontinue investigationalproduct should comply with protocol specified
follow-up procedures as outlined in Section5. The only exception to this requirement is when a 
subject withdraws consent for all study procedures including post-treatment study follow-up or 
loses the ability to consent freely (i.e.,is imprisoned or involuntarily incarcerated for the 
treatment of either a psychiatric or physical illness).
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If study drugis discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate case report form (CRF) page.
3.6
Post Study DrugFollow up
In this study,PASI-75is a key endpoint of the study. Post study follow-up is of critical 
importance and is essential to preserving subject safety and the integrity of the study. Subjects 
who discontinue study drugmust continue to be followed for collection of outcome and/or 
survival follow-up data as required and in line with Section5until death or the conclusion of the 
study.
3.6.1
Withdrawal of Consent
Subjects who request todiscontinue study drugwill remain in the study and must continue to be 
followed for protocol specified follow-up procedures. The only exception to this is when a 
subject specifically withdraws consent for any further contact with him/her or persons previously 
authorized by the subject to provide this information. Subjects should notify the investigator of 
the decision to withdraw consent from future follow-up in writing, ifpossible. The withdrawal 
of consent should be explained in detailin the medical records by the investigator, as to whether 
the withdrawal is from further treatment with study drug only or also from study procedures 
and/or post treatment study follow-up, and entered on the appropriate CRF page. In the event 
that vital status (whether the subject is alive or dead) is being measured, publicly available 
information should be used to determine vital status only as appropriately directed in accordance 
with local law.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost to 
follow-up is defined by the inability to reach the subject after a minimum of three documented 
phone calls, faxes,texts,or emails as well as lack of response by subject to one registered mail 
letter. All attempts should be documented in the subject’s medical records. If it is determined 
that the subject has died, the site will use permissible local methods to obtain the date and cause 
of death.
If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the subject’s informed consent, then the investigator may use a sponsor-
retained third-party representative to assistsite staff with obtaining subject’s contact information 
or other public vital status data necessary to complete the follow-up portion of the study.The site 
staff and representative will consult publicly available sources, such as public health registries
and databases, in order to obtain updated contact information.If after all attempts, the subject 
remains lost to follow-up, then the last known alive date as determined by the investigator should 
be reported and documented in the subject’s medical records.
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4
STUDY DRUG
Study drug includes both investigational [medicinal] product (IP/IMP) and non-investigational 
[medicinal] product (Non-IP/Non-IMP) and can consist of the following:
All products, active or placebo, being tested or used as a comparator in a clinical trial.
Study required premedication, and
Other drugs administered as part of the study that are critical to claims of efficacy (eg, 
background therapy, rescue medications)
Diagnostic agents: (such as glucose for glucose challenge) given as part of the protocol 
requirements must also be included in the dosing data collection
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Table 4-1:
Study Drugs for IM011011
Product Description 
Class and Dosage Form
Potency
IP/Non-IMP
Blinded or Open 
Label
Packaging/Appearance
Storage Conditions
(per label)
BMS-986165 capsule
3 mg (asthe free base)
IP
Blinded
Blister Card containing 
48 active (3mg) and/or 
placebo capsules to 
equal required subject 
daily dosing/Size #1 
hard gelatin capsule 
Store 2 to 8°C ; 
Protected from light
Placebo Matching BMS-
986165 capsule
N/A
IP
Blinded
Blister Card containing 
48 active (3mg) and/or 
placebo capsules to 
equal required subject 
daily dosing/Size #1 
hard gelatin capsule 
Store 2 to 8°C ; 
Protected from light
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4.1
Investigational Product
An investigational product, also known as investigational medicinal product in someregions, is 
definedasa pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
orassembled (formulated or packaged) differently thanthe authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according tolocal regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
4.2
Non-investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or 
therapeutic reasons, as components of the standard of care for a given diagnosis, may be
considered as non-investigational products. Not applicable for this study.
4.3
Storageof Study Drug
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS(see Table 4-
1). If concerns regarding the quality or appearance of the study drug arise,the study drug should 
not be dispensedand contact BMSimmediately.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Please refer to Section 9.2.2for guidance on IP records and documentation.
4.4
Method of Assigning Subject Identification
Within each panel, subjects will be randomized to receive either BMS-986165at one of the 
doses being evaluated (3mg every other day, 3mg every day, 3 mg twice daily, 6mg twice daily, 
12mg every day) or placebo according to a computer-generated randomization scheme prepared 
by a Randomization Coordinator within the Drug Supply Management Department of BMS 
Research and Development. Randomization will be stratified by previous treatment with a 
biologic and region (Japanese vs rest of world).
Enrolled subjects, including those not dosed, will be assigned sequential subject numbers starting 
with00001, (e.g., 00001,00002,00003.... 00010). Sequential numbering may restart at 00001 
for each participating site as the distinct patient identification number (PID) will ultimately be 
comprised of the site number and subject number, (e.g., 0002 00001). Those enrolledsubjects 
meeting inclusion and exclusion criteria will be eligible to be randomized. Randomization 
numbers will be assigned prior to dosing. 
During the screening visit, the investigative site will call into the enrollment option of the 
Interactive Web Response System (IWRS) designated by BMS for assignment of a 5-digit 
subject number that will be unique across all sites. Enrolled subjects, including those not dosed, 
will be assigned sequential subject numbers starting with00001, (e.g., 00001,00002,00003.... 
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00010). The patient identification number (PID) will ultimately be comprised of the site number 
and subject number. For example, the first subject screened (i.e., enrolled) at site number 1, will 
have a PID of 0001 00001.Once it is determined that the subject meets the eligibility criteria 
following the screening visit, the investigative site will call the IWRS to randomize thesubject. 
4.5
Selection and Timing of Dose for Each Subject
The BMS-986165 capsules (active or placebo) are provided in blister card kits which contain 48 
capsules and will treat the patients for 8 days. The capsules will be arranged in 8 rows each 
containing four capsules to be taken each morning and two capsules to be taken at night, 
approximately 12 hours after the morning doseand will contain the appropriate combination of 
active and placebo to provide the subjects required daily dose (3mg every other day, 3mg every 
day, 3 mg twice daily, 6 mg twice daily,12 mg every day, or placebo).  It is essential that all 
patients finish all 8 days of treatment prior to starting a new blister card kit to ensure appropriate 
doses as identified above.If the subject forgets to take the dose, but remembers within 4 hours of 
the scheduled dose, then they should take it. If it is past 4 hours, they should miss that dose and 
take the next scheduled dose.Fasting is not required for drug administration, except on the days 
scheduled for blood collection under fasting conditions (Days 1,8,15, 29, 57and 85).On these 
days, the morning dose should be administeredat the investigator’s site.
4.6
Blinding/Unblinding
Blinding of treatment assignment is critical to the integrity of this clinical study. However, in the 
event of a medical emergency or pregnancy in an individual subject in which knowledge of the 
investigational product is critical to the subject’s management, the blind for that subject may be 
broken by the investigator. The subject’s safety takes priority over any other considerations in 
determining if a treatment assignment should be unblinded.
Before breaking the blind of an individual subject’s treatment, the investigator should determine 
that the unblinded information is necessary, (i.e., that it will alter the subject’simmediate 
management). In many cases, particularly when the emergency is clearly not related to the 
investigational product, the problem may be properly managed by assuming that the subject is 
receiving active product. It is highly desirablethat the decision to unblind treatment assignment 
be discussed with the medical monitor, but the investigatory always has ultimate authority for the 
decision to unblind. The principal investigator should only call in for emergency unblinding 
AFTER the decision to discontinue the subject has been made.
In cases of accidental unblinding, contact the medical monitor and ensure every attempt is made 
to preserve the blind.
Any request to unblind a subject for non-emergency purposes should be discussed with the 
medical monitor.
In case of an emergency, the investigator(s) has unrestricted access to randomization information 
via the IWRS and is capable of breaking the blind through the IWRS system without prior 
approval from sponsor. Following the unblinding the Investigator shall notify the medical 
monitor and/or study director.
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4.7
Treatment Compliance
At each study visit compliance with study drug will be reinforced. Subject diaries will be used to 
assist subjects in maintaining an accurate assessment of daily pill intake. Subject diaries and 
study blister packwill be required to be returned at every visit throughout the study.
4.8
Destruction or Return of Investigational Product
For this study, IP(those supplied by BMS, a vendoror sourced by the investigator) such as 
partially used study drug containers, vials and syringes may be destroyed on site. 
If...
Then...
IP supplied by BMS (including its vendors)
Any unused IP supplied by BMS can only be 
destroyed after being inspected and reconciled 
by the responsible Study Monitor unless IP 
containers must be immediately destroyed as 
required for safety, or to meet local regulations 
(e.g., cytotoxics or biologics).
If IP will be returned, the return will be 
arranged by the responsible Study Monitor.
IP sourced by site, not supplied by BMS (or its 
vendors) (examples include IP sourced from 
the sites stock or commercial supply, or a 
specialty pharmacy)
It is the investigator’s or designate’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
It is the investigator’s or designate’s responsibility to arrange for disposal, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept. The following minimal standards must be met:
On-site disposal practices must not expose humans to risks from the drug.
On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.
Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.
Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, (i.e.,incinerator, licensed sanitary landfill, or licensed waste disposal 
vendor)must be documented.
Accountability and disposal records are complete, up-to-date, and available for the monitor to 
review throughout the clinical trial period.
It is the investigator’s or designate’s responsibility to arrange for disposal of all empty 
containers.
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If conditions for destruction cannot be met the responsible BMS study monitor will make 
arrangements for return of IP provided by BMS (or its vendors). Destruction of non-IP sourced 
by the site, not supplied by BMS, is solely the responsibility of the investigator or designate.
Please refer to Section 9.2.2 for additional guidance on IP records and documentation
4.9
Retained Samples for Bioavailability / Bioequivalence
Not Applicable.
5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Study assessments and procedures are presented in Table 5.1-1andTable 5.1-2.
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Table 5.1-1:
Screening Procedural Outline (IM011011)
Procedure
Screening
Visit
Notes
Eligibility Assessments
Informed Consent
X
A subject is considered enrolled only when a protocol specific informed consent is signed.
Inclusion/Exclusion Criteria
X
Medical History
X
Include any toxicities or allergy related to previous treatments. 
Safety Assessments
Physical Examination (PE)
X
Physical Measurements
X
Includes height, weight, and BMI. 
Vital Signs
X
Includes (ear or oral) body temperature, respiratory rate, seated blood pressure and heart 
rate. Blood pressure and heart rate should be measured after the subject has been resting 
quietly for at least 5 minutes. 
Electrocardiogram (ECGs)
X
ECGs should berecorded after the subject has been supine for at least 5 minutes. See 
Section 5.3.5
Chest X-ray
X
Chest x-ray is required if not performed within 6 months of Screening visit, documentation 
must be on file. See Section 5.3.4
Laboratory Tests
Urinalysis 
X
Subjects are required to fast for at least 10 hours prior to the collection of specimens for 
clinical laboratory tests. See Section 5.3.2
Hematology
X
Complete Blood Count(CBC)with differential Subjects are required to fast for at least 10
hours prior to the collection of specimens for clinical laboratory tests. See Section  5.3.2
Chemistry Panel
X
Subjects are required to fast for at least 10 hours prior to the collection of specimens for 
clinical laboratory tests. See Section  5.3.2
Serology
X
Includes Hepatitis C antibody, Hepatitis B surface antigen, Hepatitis B core antibody, and 
HIV-1 and HIV-2 antibodies. See Section  5.3.2
Tuberculosis Test
X
In accordance with BMS standard testing. See Section 5.3.4of the protocol for more 
details. 
Pregnancy Test (urine)
X
For WOCBP only. 
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Table 5.1-1:
Screening Procedural Outline (IM011011)
Procedure
Screening
Visit
Notes
Follicle Stimulating Hormone (FSH)
X
Women only, Refer to Section 3.3.3.
Study Procedures
PASI Score Assessment
X
See Section 5.4
BSA Assessment
X
See Section 5.4
AdverseEvent Reporting
Monitor for Serious Adverse Events
X
All SAEs must be collected from the date of subject’s written consent until 28 days post 
discontinuation of dosing or subject’s participation in the study if the last scheduled visit 
occurs at a later time.
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Table 5.1-2:
On Treatment Procedural Outline for IM011011
Procedure
D1
D8
day
D15
day
D29
3 day
D57
3 day 
D85
daysa
Follow-Up  
visit 
D115
Notes
Safety Assessments
Full Physical Examination 
(PE)
X
X 
X 
X 
X
See Section5.3.3
Targeted Physical 
Examination
X 
X
See Section  5.3.3
Physical Measurements 
X
X 
X
X
Weight only
Vital Signs
X 
X 
X 
X 
X 
X 
X
Includes (ear or oral) body temperature, 
respiratory rate, seated blood pressure 
and heart rate. Blood pressure and heart 
rate should be measured after the 
subject has been resting quietly for at 
least 5 minutes.
Electrocardiograms (ECGs)
X 
X 
X 
X 
X 
X 
X
See Section5.3.5
Laboratory Tests
Hematology 
X*
X 
X 
X 
X 
X 
X
Including CBC with differential See 
Section 5.3.2
*predose(Subjects are required to fast 
for at least 10 hours prior to the 
collection of specimens for clinical 
laboratory testsDay 1)
Chemistry Panel
X*
X 
X 
X 
X 
X 
X
See Section 5.3.2
*predose(Subjects are required to fast 
for at least 10 hours prior to the 
collection of specimens for clinical 
laboratory testsDay 1)
High sensitivity CRP 
X*
X 
X 
X
See Section  5.3.2
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Table 5.1-2:
On Treatment Procedural Outline for IM011011
Procedure
D1
D8
day
D15
day
D29
3 day
D57
3 day 
D85
daysa
Follow-Up  
visit 
D115
Notes
(hsCRP)
*predose
Fasting LipidPanel
X*
X
Subjects are required to fast for at least 
10 hours prior to the collection of 
specimens for clinical laboratory tests 
See Section  5.3.2
*predose
Fasting Plasma Glucose
X*
X
Subjects are required to fast for at least 
10 hours prior to the collectionof 
specimens for clinical laboratory tests
See Section  5.3.2
*predose
Fasting C-peptide
X*
X
Subjects are required to fast for at least 
10 hours prior to the collection of 
specimens for clinical laboratory tests 
See Section  5.3.2
*predose
Urinalysis
X*
X 
X 
X 
X 
X 
X
See Section 5.3.2
*predose(Subjects are required to fast 
for at least 10 hours prior to the 
collection of specimens for clinical 
laboratory testson Day 1)
Serum Immunoglobulin 
Levels(IgM, IgG, IgA, 
IgE)
X*
X 
X 
X
See Section5.3.2.
*predose
Pregnancy Test(Urine)
X*
X 
X 
X 
X
Female subjects only. *All women must 
have a negative pregnancy prior to 
dosing on Day 1. 
Adverse Event Reporting
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Table 5.1-2:
On Treatment Procedural Outline for IM011011
Procedure
D1
D8
day
D15
day
D29
3 day
D57
3 day 
D85
daysa
Follow-Up  
visit 
D115
Notes
Monitor for non-Serious 
Adverse Events
X 
X 
X 
X 
X 
X 
X
See Section6.2.
Monitor for Serious 
Adverse Events
X 
X 
X 
X 
X 
X 
X
See Section6.1
Pharmacokinetic (PK) 
Assessments
Blood PK Sampling
X*
X 
X 
X 
X 
X
*Pre and post-dose. See Section 5.5and 
Study Procedure
PASI Score Assessment
X 
X 
X 
X 
X 
X 
X
See Section5.4
BSA Assessment 
X 
X 
X 
X 
X 
X 
X
See Section 5.4
sPGA
X 
X 
X 
X 
X 
X 
X
See Section 5.4
Subject Global Assessment 
of Pain VAS
X 
X 
X 
X 
X 
X 
X
See Section 5.4
Medical Photography (skin)
X
X
X
At selected sites only. 
See Section 5.3.6
Skin Biopsy 
X
X
X
See Section 5.3.7
Biomarker Assessments
Target Engagement
X 
X 
X
See Section 5.6(TE samples will be 
collected in the 1st 100 dosed subjects)
Blood PD Sampling
X 
X 
X 
X 
X 
X 
X
See Section 5.6
TBNK
X
X
X
See Section 5.6
Blood PaxGene RNA
X
X 
X 
X 
X
See Section 5.6
CV/Metabolic blood 
sample (Serum)
X
X
X
See Section 5.6
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Table 5.1-2:
On Treatment Procedural Outline for IM011011
Procedure
D1
D8
day
D15
day
D29
3 day
D57
3 day 
D85
daysa
Follow-Up  
visit 
D115
Notes
CV/Metabolic blood 
sample (Plasma)
X
X
X
See Section 5.6
Other Assessments
DLQI
X
X 
X 
X 
X
See Section 5.4
Clinical Drug Supplies
Dispense Study Drug
X 
X 
X 
X 
X
Subjects will be supplied with enough 
oral study drug (or placebo) to cover 
the intervals between study visits. See 
Section 4
a Evaluations performed prior to study discharge, or for subjects who are prematurely discontinued. In addition for subjects who are prematurely discontinued, 
the following should also be performed prior to study discharge: D85procedure
Abbreviations: D = Day
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5.1.1
Retesting During Screening or Lead-in Period
Retesting of laboratory parameters and/or other assessments within any single Screening or 
Lead-in period will be permitted (in addition to any parameters that require a confirmatory 
value).
Any new result will override the previous result (i.e., the most current result prior to 
Randomization) and is the value by which study inclusion will be assessed, as it represents the 
subject’s most current, clinical state.
Laboratory parameters and/or assessments that are included inTable 5.1-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified subjects.  Consultation 
with the medical monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant.
5.2
Study Materials
The site will provide all required materials for the tests performed locally (i.e., relevant clinical 
laboratory tests and urine drug screens). The site will have available a well-calibrated scale for 
recording body weight, a 12-lead ECG machine, and a calibrated sphygmomanometer and 
thermometer for vital signs assessments. A current and fully-stocked basic cardiac life support 
(BCLS)] cart will be immediately available on the premises. The site will have urine collection 
containers, a refrigerated centrifuge, a monitored and alarmed refrigerator, and freezer (-20°C or 
below), as well as containers and dry ice for shipment and storage of blood and urine samples. 
The site will provide all materials required for accurate source documentation of study activities 
and for housing the subjects during the study. 
Subjects will be provided with cooler bags and gel packs for transporting BMS-986165/matched 
placebo as it needs to be kept refrigerated,
BMS will provide a BMS-approved protocol and any amendments or administrative letters (if 
required), and investigator brochure. Case report forms (electronic or hard copy) will be 
provided by BMS. The Central Laboratory will provide labels and tubes for the collection of 
blood samples forPK and biomarkersamples.
Study supplies and documents (eg, electronic Case Reports Forms, patient drug logs, etc.) will be 
provided to the study center by BMS. Subject dosing diaries will be provided for each subject for 
completion throughout the study. IVRS/IWRS worksheets and instruction manuals will be 
provided by the IVRS/IWRS vendor.
5.3 
Safety Assessments
On Day 1, the results of all assessments must be reviewed to assure that eligibility requirements 
are met before contacting the Central Randomization System forthe subject’s randomization 
assignment.
Subjects who terminate early will complete the Day 85/Early Termination (ET) Visit 
assessments. The Early Termination Visit should be as soon as possible after the last dose of 
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study medication (investigational product) and prior to the subject receiving a prohibited 
concomitant medication.
All assessments should be performed or administered prior to study drug administration unless 
otherwise indicated.
Every effort must be made to ensure the same evaluator will complete the assessments for each 
subject at all visits.
Only data for the procedures and assessments specified in this protocol should be submitted to 
BMS on a case report form. Additional procedures and assessments may be performed as part of 
your institutional or medical practice standard of care; however, data for these assessments 
should remain in the subject’s medical record and should not be provided to BMS, unless 
specifically requested from the sponsor.
5.3.1
Imaging Assessment for the Study
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the study investigator as per 
standard medical/clinical judgment.
5.3.2 
Laboratory Test Assessments
All laboratory assessments will be analyzed centrally with exception of pregnancy test.
The following clinical laboratory tests will be performed:
Hematology
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
Serum Chemistry
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Total bilirubin
Direct bilirubin
Alkaline phosphatase
Lactate dehydrogenase (LDH)
Creatinine
Blood Urea Nitrogen (BUN)
Uric acid
Fasting glucose(Day 1 and Day 85only)
FastingC-peptide(Day 1 and Day 85only)
Total Protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatine kinase
Creatinine clearance (CLcr)-screening only
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Fasting Lipid Panel 
Total C (mg/dL, mmol/L)
Reflex testing will occur for direct LDL-C ifTG > 400 mg/dL (4.52 mmol/L)
HDL-C (mg/dL, mmol/L)
TG (mg/dL, mmol/L)
Note: A subject should be fasting at least 10hours.
Urinalysis
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, protein or leukocytes esterase are positive 
on the dipstick
Serology
Serum for hepatitis C antibody, hepatitis B surface antigen, Hepatitis B core antibody, HIV-1
and-2 antibody (screening only)
Other Analyses
Confirmatory Hepatitis B, C virus testing if positive serology: quantitative Hepatitis B viral 
load by PCR, quantitative Hepatitis C viral load by PCR (screening only)
TBNK flow cytometry panel -abnormalities in T, B, and NK cell subsets present at baseline 
do not necessarily warrant subject exclusion. 
High sensitivity CRP (hsCRP) -abnormalities in hsCRP levels present at baseline do not 
necessarily warrant subject exclusion. Please discuss with the Medical Monitor. 
Serum immunoglobulin levels: Total, IgA, IgE, IgG, IgM levels -abnormalities in serum 
immunoglobulin levels present at baseline do not necessarily warrant subject exclusion. 
Tuberculosis test (at screening only)
Pregnancy test -WOCBP only: Urine pregnancy test 
Follicle stimulating hormone (FSH) (screening only for women only) 
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Specialized Liver Laboratory Panel -(should only be done for elevated liver enzymes (see 
Appendix 6) 
Results of alllaboratory tests required by this protocol must be provided to BMS, either recorded 
on the laboratory pages of the CRF or by another mechanism as agreed upon between the 
investigator and BMS (e.g., provided electronically). If the units of a test result differ from those 
printed on the CRF, the recorded laboratory values must specify the correct units. Any abnormal 
laboratory test result considered clinically significant by the investigator must be recorded on the 
appropriate AE page of the CRF (see Section6.3).
5.3.3
Physical Exams
A complete physical examination will be obtained at specified timepoints as outlined in Table 
5.1-1andTable 5.1-2. The complete physical examination will consist of evaluation of the 
following systems: general, head, eyes, ears, nose, throat, neck, cardiovascular, lungs, 
abdominal, extremities, neurologic, psychiatric, skin, and musculoskeletal. A targeted physical 
examination will be performed at other study visits. The targeted physical exam will consist of 
evaluation of the following systems: general, eyes, throat, cardiovascular, lungs, abdominal, 
extremities, and skin, musculoskeletal. Complete and targeted physical examinations may be 
performed by a Doctor of Medicine (MD), Doctor of Osteopathy (DO), Physician’s Assistant 
(PA), or a Nurse Practitioner (NP). A targeted physical examination may note any changes in the 
subject’s condition since the last assessment and does not preclude examination of any of the 
body systems as clinically indicated
5.3.4
Tuberculosis Screening and Chest X-Ray 
A chest x-ray (CXR) and physical examination (PE) are considered part of the process to assess a 
subject’s eligibility as outlined in Section 3.3.2. CXR at the screening visit is required if not 
already performed within 6 months of obtaining written informed consent or if documentation is 
not on file.
In addition to a complete physical examination and medical history to evaluate exposure to 
tuberculosis, all subjects will have a screening test, an interferon gamma release assay [(IGRA) 
eg, T-spot®, QuantiFERON®], preferably performed centrally. If unable to obtain central lab 
results (eg, repeated test due to indeterminate result), an IGRA test could be obtained locally, 
after consultation with the study medical monitor.
Subjects with a positive screening test will not be eligible for the study unless they have 
completed at least four (4) weeks of treatment for latent TB prior to dosing of study drug, and the 
subject has a negative chest X-ray done at screening that reveals no evidence of active TB and a 
negative IGRA test (Quantiferon or T-Spot) is confirmed prior to Day 1.
5.3.5
ECG
12-lead ECGs should be collected at times specified in Table5.1-1and Table 5.1-2. All 
scheduled ECGs should be performed after the subject has rested quietly for at least 5 minutes in 
a supine position. When the timing of the measurements coincides with a blood collection, the 
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ECG should be obtained prior to the nominal time of the blood collection, blood pressure, and 
pulse rate. 
5.3.6
Medical Photography(Optional)
Standard medical dermatology photographs of the affected areas of psoriasis will be takenat 
selected sites. BMS will host a training session prior to study initiation to demonstrate proper 
photographic technique of subjects with psoriasis. Subjects can request to have sensitive areas 
covered.  Detailed instructions on the collection and transmission of digital images will be 
provided to the Investigator in a separate manual at or before the time of study initiation
5.3.7
Skin Biopsy
Skin biopsy is a standard diagnostic test performed for skin diseases, and has been used to 
characterize responses to therapeutic agents in patients diagnosed with psoriasis. Skin biopsy 
will be performed at 3 timepoints: Study Days 1 (for baseline evaluation), 15and 85.The skin 
biopsies are voluntary, but subjects should be encouraged to participate. Four 4 mm punch skin 
biopsies will be collected prior to dosing at the baseline study visit (Day 1). Two skin biopsies 
will obtain involved skin tissue at approximately 3 mm from the edge of an active psoriatic 
plaque (lesional skin biopsy), and two biopsies will obtain uninvolved skin tissue (non-lesional 
skin biopsy). One of each type of skin biopsy, will be used for histolopathology analyses and the 
other will be used for RNA analyses. On Days 15 and 85two 4mm punch biopsieswill be 
obtained from the same skin plaque as the original lesional skin biopsies, and utilized for RNA 
and histopathologic analyses. The serial biopsies should avoid the scar tissue at the same location 
where previous biopsies have been taken. One of the biopsies should be placed in formalin as 
described in the study manual and the other half should be stored in RNA Later as described in 
the laboratory manual and shipped to the centrallaboratory. Complete details for the collection, 
processing, storage, shipment and analysis of samples will be provided in a separate Laboratory 
Manual. Skin biopsies should be performed by a qualified health care provider who has 
experience in biopsying psoriatic skin lesions.
5.4 
Efficacy Assessments
5.4.1
Primary Efficacy Assessment
5.4.1.1
Psoriasis Area and Severity Index (PASI)
The PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions 
(each graded on a 0–4 scale), weighted by thearea of involvement (head, arms, trunk to groin, 
and legs to top of buttocks).26The PASI produces a numeric score that can range from 0 to 72, 
with higher PASI scores denoting more severe disease activity. PASI can also be used to assess 
response to treatment. The PASI-50 is the proportion of subjects who experience at least a 50% 
improvement in PASI score as compared with baseline value. The PASI-75, PASI-90, and 
PASI-100 are defined similarly. BMS will host a training session prior to initiation of the study 
to demonstrate proper PASI scoring. PASI assessments should be performed by a dermatologist 
or appropriately trained investigator who is experienced in the assessment of psoriasis patients
(see Appendix 2).
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5.4.2 
Secondary Efficacy Assessments
5.4.2.1
Body Surface Area (BSA) 
Measurement of psoriasis body surface area involvement is estimated using the handprint 
method with the size of a patient’s handprint representing ~1% of body surface area 
involved.
27,28,29The total BSA = 100% with breakdown by body region as follows: head and 
neck = 10% (10 handprints), upper extremities = 20% (20 handprints), trunk including axillae 
and groin = 30% (30 handprints), lower extremities including buttocks = 40% (40handprints). 
BSA assessments should be performed by a dermatologist or appropriately trained investigator 
who is experienced in the assessment of psoriasis patients.
5.4.2.2
static Physician Global Assessment (sPGA)
The sPGA30is an average assessment of all psoriatic lesions based on erythema, scale, and 
induration. The static PGA determines psoriasis severity at a single point in time, without taking 
the baseline disease condition into clear (0), minimal (1), mild (2), moderate (3), severe (4), or 
very severe (5). PGA assessments should be performed by a dermatologist or appropriately 
trained investigator who is experienced in the assessment of psoriasis patients. Every effort 
should be made to ensure that the physician or designee who performed the sPGA evaluations 
for a subject at randomization performs the sPGA for that subject at all subsequent visits(see 
Appendix 3).
5.4.2.3
Dermatology Life Quality Index (DLQI)
The DLQI31is a subject reported quality of life index which consists of 10 questions concerning 
symptoms and feelings, daily activities, leisure, work, school, personal relationships, and 
treatment during the last week. Each question is scored on a scale of 0 to 3 by a tick box: "not at 
all", "a little", "a lot", or "very much". The scores are summed, giving a range from 0 (no 
impairment of life quality) to 30 (maximum impairment)(see Appendix 4).
 
 
 
 
5.5
Pharmacokinetic Assessments
Pharmacokinetics of BMS-986165will be derived from plasma concentration versus time data. 
The pharmacokinetic parameters to be assessed include:
Ctrough
Trough observed plasma concentration
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5.5.1
Pharmacokinetics:  Collection and Processing
Table 5.5.1-1lists the sampling scheduleto be followed for the assessment of pharmacokinetics. 
Further details of blood collection and processing will be provided to the site in the procedure 
manual.
Table 5.5.1-1:
Pharmacokinetics Sampling Schedule
Study Day of 
Sample Collection
Event
Time 
(Relative To 
BMS-986165
Dose)
Hour: Min
BMS-986165
Blood Sample for PK
Notes
1
predosea
00:00
X
1
00:30
X
1
01:00
X
8
Predosea
00:00
X
15
Predosea
00:00
X
15*
00:30
X
*These post-dose 
samples maybe drawn 
at any scheduled visit
day after Day 15 (i.e 
On Day 29, 57 or 85)
15*
01:00
X
15*
04:00
X
15*
06:00
X
29
Predosea
00:00
X
57
predosea
00:00
X
85
predosea
00:00
X
apredose samples must be drawn before the morning dose on the Visit Day
5.5.2
Pharmacokinetic Sampling Window
It is expected that every effort is made to collect PK samples at the times indicated. However for 
flexibility in PK sampling, the following windows serve as a guideline for PK sample collection:
Pre-dose samples must be drawn before the morning dose on the Visit Day
For other samples:
+/-1 hour for the samples within the first two hours of dosing
+/-3 hours for the 4 and 6 hour sample. 
The samples should be collected using the time point labels provided even if outside suggested 
window.Any missed PK sample collections should be noted in the source documents.
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5.5.3
Pharmacokinetic Sample Analyses
The plasma samples will be analyzed for BMS-986165by a validated LC/MS/MSassay. 
Pharmacokinetic samples collected from a subject who received placebo will not be analyzed.
In addition, plasma samples will be archived for potential metabolite analysis, if the need arises 
and to the extent possible.
5.5.4
Labeling and Shipping of Biological Samples
Detailed instructions for the pharmacokinetic blood collection, labeling, processing, storage, and 
shipping will be provided to the site in the procedure manual.
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
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5.7
Outcomes Research Assessments
Not applicable.
5.8
Other Assessments 
Not applicable.
5.9
AdditionalResearchCollection
This protocol will include residual sample storage for additional research (AR). This collection 
for additional research is intended to expand the translational R&D capability at Bristol-Myers 
Squibb, and will support as yet undefined research aims that will advance our understanding of 
disease and options for treatment. It may also be used to support health authority requests for 
analysis, and advancement of pharmacodiagnostic development to better target drugs to the right 
patients. This may also include genetic/genomic exploration aimed at exploring disease 
pathways, progression and response to treatment etc. All requests for access to samples or data 
for additional research will be vetted through a diverse committee of the study sponsor’s senior 
leaders in Research and Development to ensure the research supports appropriate and well-
defined scientific research activities.
Residual serum, plasma, RNA and skin biopsy samples from skin biopsy, skin biopsy RNA, 
blood for PD assessments and blood RNA collections (seeTable 5.9-1) will also be retained by 
the BMS Biorepository in Hopewell, NJ or at a BMS approved third party storage management 
facility for additional research purposes. Additional research samples will be retained for 15 
years or the maximum allowed by applicable law. No additional sampling is required for residual 
collections. 
Table 5.9-1:
Residual Sample Retention for Additional Research Schedule
Sample
Timepoints for which residual samples will be retained
Blood for PD
All
Skin Biopsy histology
All
Skin Biopsy RNA
All
Blood RNA
All
CV/Metabolic (Plasma)
All
CV/Metabolic (Serum)
All
6
ADVERSE EVENTS
An Adverse Event(AE)is defined as any new untoward medical occurrence or worsening of a 
pre-existing medical condition in aclinical investigation subject administered study drugand that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such asan abnormallaboratory finding), symptom, or disease 
temporally associated with the use of study drug, whether or not considered related to the study 
drug.
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The causal relationship to study drug is determined by a physician and should be used to assess 
all adverse events (AE).The causal relationship can be one of the following:
Related: There is a reasonable causal relationship between study drug administration and 
the AE.
Not related: There is not a reasonable causal relationship between study drug 
administration and the AE.
The term "reasonable causal relationship" means there is evidence to suggest a causal 
relationship. 
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be
questioned regarding the specific occurrence of one or more AEs.)
Sponsor or designatewill be reporting adverse events to regulatory authorities and ethics 
committees according to local applicable laws including European Directive 2001/20/EC and 
FDA Codeof Federal Regulations 21 CFR Parts 312 and 320.
6.1
Serious Adverse Events
A Serious Adverse Event(SAE)is any untoward medical occurrence that at any dose: 
results in death
is life-threatening (defined as an event inwhich the subject was at risk ofdeath at the time of 
the event; it does not refer to an event which hypothetically might have caused death if it 
were more severe)
requires inpatient hospitalization or causes prolongation of existing hospitalization (see 
NOTEbelow)
results in persistentor significant disability/incapacity
is a congenital anomaly/birth defect 
is an important medical event (defined as a medical event(s) 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 [e.g., medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) 
Examples of such events include, but are not limited to, intensive treatment in an emergency 
room or at home for allergic bronchospasm,blood dyscrasias or convulsions that do not 
result in hospitalization.)Potential drug induced liver injury (DILI) is also considered an 
important medical event.(See Section 6.6for the definition of potential DILI.)
Suspected transmission of an infectious agent (e.g., pathogenic or nonpathogenic) via the study 
drug is an SAE.
Although pregnancy, overdose, cancer, and potential drug induced liver injury (DILI) are not 
always serious by regulatory definition, these events must be handled as SAEs. (See 
Section6.1.1for reporting pregnancies).
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Any component of a study endpoint that is considered related to study therapy (e.g.,death is an 
endpoint, if death occurred due to anaphylaxis, anaphylaxis must be reported) should be reported 
as an SAE (see Section6.1.1for reporting details.
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 
a visit to the emergency room or other hospital department < 24 hours, that does not 
result in admission (unless considered an important medical or life-threatening event)
elective surgery, planned prior to signing consent
admissions as per protocol for a planned medical/surgical procedure
routine health assessment requiring admission for baseline/trending of health status (e.g., 
routine colonoscopy)
medical/surgical admission other thanto remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases
admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (e.g., lack of housing,economic 
inadequacy, caregiverrespite, family circumstances, administrativereason)
Admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
6.1.1 
Serious Adverse EventCollection and Reporting
Sections 5.6.1 and 5.6.2 in the Investigator Brochure (IB) represent the Reference Safety 
Information to determine expectedness of serious adverse events for expedited reporting. 
Following the subject’s written consent to participate in the study, all SAEs, whether related or 
not related to study drug, must be collected, including those thought to be associated with 
protocol-specified procedures. All SAEs must be collected that occur during the screening period 
and within 30 days of discontinuation of dosing.
The investigator mustreportany SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure. 
An SAE report mustbe completed for any event where doubt exists regarding its seriousness. 
If the investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship mustbe specified in the narrative section of the SAE Report Form.
SAEs, whether related or not related to study drug, and pregnancies must be reported to Sponsor 
ordesignatewithin 24 hoursof awareness of the event. SAEs must be recorded on the SAE 
Report Form; pregnancies on a Pregnancy Surveillance Form (electronic or paper forms).The 
preferred method for SAE data reporting collection is through the eCRF.  The paper 
SAE/pregnancy surveillance forms are only intended as a back-up option when the eCRF system 
is not functioning. In this case, the paper forms are to be transmitted via email or confirmed 
facsimile (fax) transmission to:
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SAE Email Address: Refer toContact Information list.
SAE Facsimile Number:Refer toContact Information list.
For studies capturing SAEs throughelectronic data capture (EDC), electronic submission is the 
required method for reporting.  In the event the electronic system is unavailable for transmission, 
paper forms must be used and submitted immediately.  When paper forms are used, the original 
paper forms are to remain on site
SAE Telephone Contact (required forSAE andpregnancy reporting):Refer toContact 
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports mustinclude the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, the SAE report must be updated and submitted within 24 hours to Sponsor or 
designateusing the same procedure used for transmitting the initial SAE report.
All SAEs mustbe followed to resolution or stabilization.
BMS will be reporting adverse events to regulatory authorities and ethics committees according 
to local applicable laws including European Directive 2001/20/EC and FDA Code of Federal 
Regulations 21 CFR Parts 312 and 320. A SUSAR (Suspected, Unexpected Serious Adverse 
Reaction) is a subset of SAEs and will be reported to the appropriate regulatory authorities and 
investigatorsfollowing local and global guidelines and requirements.
6.2
Nonserious Adverse Events
Anonserious adverse eventis an AE not classified as seriousadverse event.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. Nonserious 
AE information should also be collected from the start of a placebo lead-in period or other 
observational period intended to establish a baseline status for the subjects.
Nonserious AEs should be followedto resolution or stabilization, or reported as SAEs if they 
become serious (see Section6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug andfor those present at the end of study treatment 
as appropriate.All identified nonserious AEs must be recorded and described on the nonserious 
AE page of the CRF (paper or electronic). 
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (electronic) as appropriate. Paper forms are only intended as a back-
up option when the electronic system is not functioning.
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Any laboratory test result that is clinically significant or meets the definition of an SAE 
Any laboratorytest resultabnormality that required the subject to have study drug 
discontinued or interrupted
Any laboratorytest resultabnormality that required the subject to receive specific corrective 
therapy
It is expected that wherever possible, the clinicalrather than laboratory term would be used by 
the reporting investigator (e.g., anemia versus low hemoglobin value).
6.4
Pregnancy
If, following initiation of the investigational product, it is subsequently discovered that a study 
subject is pregnant or may have been pregnant at the time of studyexposure, including during at 
least 5half-livesafter product administration, the investigator must immediately notify the 
Sponsor or designateof this event and complete and forward a Pregnancy Surveillance Form to 
the BMS designatewithin 24 hours of awareness of the event and in accordance with SAE 
reporting procedures described in Section6.1.1.
In most cases, the study drug will be permanently discontinued in an appropriate manner (e.g., 
dose tapering if necessary for subject safety).Please call the Sponsor or designatewithin 24 
hours of awareness of the pregnancy.
The investigator must immediately notify the Sponsoror designateof this event and complete 
and forward a Pregnancy Surveillance Form to Sponsoror designatewithin 24 hoursof 
awareness of the eventand in accordance with SAE reporting procedures described in 
Section6.1.1. 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome,and where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
Sponsor or designate.In order for BMS to collect any pregnancy surveillance information from 
the female partner, the female partner must sign an informed consent form for disclosure of this 
information.Information on this pregnancy will be collected on the Pregnancy Surveillance 
Form.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important. All occurrences of overdose must be 
reported as an SAE (see Section6.1.1for reporting details.).
6.6
Potential Drug Induced Liver Injury
Wherever possible, timely confirmation of initial liver-relatedlaboratory abnormalities should 
occur prior to the reporting of a potential DILI event(see Appendix6 flow chart for sustained 
elevated liver safety abnormalities). All occurrences of potential DILIs, meeting the defined 
criteria, must be reported as SAEs (see Section6.1.1for reporting details).
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Potential drug induced liver injury is defined as: 
1. Aminotransaminases (AT) (ALT or AST) elevation > 3 times upper limit of normal (ULN)
AND 
2. Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND 
3. No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic. 
6.7
Other SafetyConsiderations
Any significant worsening noted during interim or final physical examinations, 
electrocardiogram, x-ray filming,or any other potential safety assessment required or not 
required by protocol should also be recorded as a nonserious or serious AE, as appropriate, and 
reported accordingly. 
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
An Independent Data Monitoring Committee (IDMC) will be established to monitor data on an 
ongoing basis to ensure the continuing safety of patients enrolled in this study, to ensure the 
integrity of the blinded nature of the study, and to oversee the planned interim analyses.  An 
IDMC charter will be developed which will specify the roles and responsibilities of the members 
and interim decision rules.  Sponsor Steering Committee will receive and act on the 
recommendations from the IDMC.  A firewall will be established to ensure the maintenance of 
the study blind for the Sponsor, the investigational site staff, and study patients and their study 
partners.
Data summaries and listings will be provided to the IDMC to facilitate their safety assessment at 
the regularly scheduled times on an ad hoc basis if needed. The safety review includesserious 
adverse events and events of special interest, focusing on early signal detection. Further details 
on the frequency, content and methods of data reports to the IDMC will be outlined in the 
Charter of that Committee along with the processes and procedures the committee will follow.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
The sample size calculation is driven by several considerations. 
The first consideration is to compare the response rate in PASI-75, the proportion of subjects 
with moderate to severe psoriasis experiencing a 75% improvement reduction in psoriasis area 
and severity index (PASI) score after 12 weeks, between BMS-986165 and placebo arms. With a 
one-sided, two-sample Fisher’s exact test at significant level 0.05, a sample size of 42 per arm 
will provide at least 99% power to detect 50% increase in the PASI-75 response rate in an active 
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arm (i.e., 60% response rate) compared to the placebo assuming the response rate is 10% in the 
placebo arm.  
The second consideration is to assess the response rate in PASI-75 in active dose arms. Data 
from 42 treated subjects per arm will produce a two-sided 95% confidence interval with a margin 
of error at most 15.1% (half width)  using normal approximation. 
The third consideration is to compare the response rates in PASI-75 in two active arms. With 
one-sided, two-sample Fisher’s exact test at significant level 0.05, 42 subjects per arm will 
provide at least 82% power to detect at least 30% difference in the response rate in PASI-75 
between any two active dose arms.  
The proposed sample size is mainly driven by the third consideration. In addition, administration 
of BMS-986165 to 42 subjects in each active treatment group provides 34%, 88%, and 99% 
probability of observing at least one occurrence of any adverse event that would occur with 1%, 
5%, or 10% incidence rate respectively.
8.2
Populations for Analyses
All Enrolled Subjects: All subjects who sign an informed consent.
All Randomized Subjects: All subjects who are randomized to a treatment. Subjects will 
be analyzed as per randomized treatment.  All efficacy analyses will be performed using 
this population.
All Treated Subjects: All subjects who have received at least one dose of study treatment.  
This population will be used for safety analyses and will be analyzed as per actual 
treatment received.
Biomarker Analysis Population: All subjects that receive any study medication and have 
at least 1 post-treatment biomarker measurement. 
Pharmacokinetic Population: All subjects who receive any study medication and have 
any available concentration-time data. 
All subjects who receive study drugwill be included in the safety data set. All available data 
from subjects who receive BMS-986165will be included in the pharmacokinetic data set.All 
available data from subjects for whom pharmacodynamic measurements are available at baseline 
and at least one other time will be included in the pharmacodynamic data set.
Summary analyses of safety, pharmacokinetic, pharmacodynamic, biomarker, and efficacy data 
will be based on all treated subjects. For analyses such as PK parameter estimations, the analyses 
will be based on all treated subjects with adequate data.
8.3
Endpoints
8.3.1
Primary Endpoint(s)
The primary efficacy endpoint is the proportion of subjects in thestudy experiencing a 75% 
reduction from baseline in the PASI score after 12 weeks.
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The safety and tolerability of BMS-986195 will be assessed by the incidence, potential 
significance, and clinical importance of adverse events measured during multiple doses of BMS-
986195 and up to 30 days after the last dose, as determined by medical review of adverse event 
reports, vital sign measurements, electrocardiograms (ECGs), and results of physical 
examination and laboratory tests.
8.3.2
Secondary Endpoint(s)
The secondary efficacy endpoints are
the proportion of subjects at week 12 with PASI-50, PASI-75, PASI-90, PASI-100
sPGA score, DLQIscoreand the proportion of subjects with moderate to severe psoriasis 
in each categoryof these endpoints after week 12 of treatment 
The secondary endpoint to assess PK isCtrough.
 
 
 
 
 
8.4
Analyses
8.4.1
Demographics and Baseline Characteristics
Frequency distributions of gender and race will be tabulated. Summary statistics for age, body 
weight, height, and Body Mass Index (BMI) will be tabulated.In addition, baseline disease 
activities will be tabulated by treatments using descriptive statistics.
8.4.2
EfficacyAnalyses
Primary Efficacy Analyses
The primary endpoint, the proportion of subjects with moderate to severe psoriasis experiencing 
a 75% improvement reduction in PASI score after 12 weeks, will be analyzed by two-sample 
Fisher’s exact test or Chi-square test to compare the response rates betweeneach treatment group 
and placebo. Cochran–Mantel–Haenszel Chi-square test, stratified according to previous 
treatment with a biologic and/or region(Japanese vs rest of world), will be performed. The odds 
ratio (odd in a treatment group/odd in placebo) inthe response rates and its corresponding two-
sided 90% confidence interval (CI) will be provided when using Fisher’s exact test or 
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Cochran-Matel-Haenszel Chi-square test. If Chi-square test is performed, the difference in the 
response rates and its corresponding two-sided 90% confidence interval (CI) will be provided.
In addition, point estimate and 90% asymptotic and exact two-sided confidence intervals will be 
provided for the proportion of subjects in PASI-75 in each group.  A logistic regression model
may be performed to incorporate some of the covariates if these covariate are assumed to impact 
the response rates. Details of the tests and models will be given in the statistical analysis plan.
Secondary Efficacy Analyses
Similar analyses as in primaryefficacy analyses will be performed to compare any two active 
arms. 
A logistic model will be conducted to detect a positive trend between treatment groups of 
BMS-986165. 
The response rate in PASI-50, PASI-75, PASI-90, and PASI-100 will be summarized by 
treatment and time and will be analyzed using a repeated measure model when applicable. The 
same analyses will be conducted stratified by previous biologic treatmentand/or region. The 
proportion of subjects with a sPGA score of “0” or “1” will be analyzedsimilarly to the primary 
analyses. sPGA, and DLQI Score from psoriasis subjects will be tabulated by treatment and time; 
the corresponding changes from baseline and percent change from baseline will be calculated 
and summarized. 
For continuous secondary endpoints (e.g. PASI, etc), point estimates and two-sided 90% 
confidence intervals for mean change from baseline within each treatment group will be 
provided. For binary endpoints (PASI, sPGA, etc.), point estimates of the response rate and two-
sided 90% confidence intervals will be provided using normal approximation within each 
treatment group. 
In addition, a two-sided 90% confidence interval will be provided for the difference in the 
secondary efficacy endpoints between each active arm and the placebo arm at each visit. More 
analyses, such as analysis of covariance models with treatment group, use of previous biologic 
treatment, and baseline value included as covariates,  may be performed on endpoints such as 
PASI score, sPGA score, DLQI, etc. 
There will be no adjustment for multiplicity.  All comparisons will be performed in a pre-
specified hierarchical procedure starting from the highest dose arm to the lowest dose arm. If a 
comparison is not significant at level 0.05, all P-values in subsequent comparisons will be 
considered to be nominal and may be provided if applicable.
 
 
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8.4.3
Safety Analyses
All recorded adverse events will be listed and tabulated by system organ class, preferred term 
and treatment. Vital signs and clinical laboratory test results will be listed and summarized by 
treatment. Any significant physical examination findings, and clinical laboratory results will be 
listed. ECG readings will be evaluated by the investigator and abnormalities, if present, will be 
listed.
8.4.4
Pharmacokinetic Analyses
Ctroughwill be summarized by time for BMS-986165 in subjects with moderate to severe 
psoriasis. Additional details will be provided in the statistical analysis plan (SAP) as necessary.
 
 
 
8.4.7
Outcomes Research Analyses
Not applicable.
8.4.8
Other Analyses 
8.4.8.1
Population PK and Exposure Response Analysis
Analysisof PK and exposure-response relationships of BMS-986165 will be conducted using a 
population approach as appropriate and reported separately from the clinical study report.
8.5
Interim Analyses
There are no planned interim analyses for the current study.
9 
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local health authority)except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior 
to obtaining relevantapproval/favorable opinion(s)the deviation or change will be submitted as 
soon as possible to:
IRB/IEC
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Regulatory Authority(ies), if applicableby local regulationsper national requirements
Documentation of approval/favorable opinionsigned by the chairperson or designateof the 
IRB(s)/IEC(s)and if applicable, also by local health authority, must be sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
subject: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS or designaterepresentatives will review data centrally to identify potential issues to 
determine a schedule of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare 
them with source documents, discuss the conduct of the study with the investigator, and verify 
that the facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the 
source documents:.
In addition, the study may be evaluated by BMS or designateinternal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory 
authorities and promptly forward copies of inspection reports to BMSor designate. 
9.1.2.1
Source Documentation
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or 
entered electronically. If source data are created (first entered), modified, maintained, archived, 
retrieved, or transmitted electronically via computerized systems (and/or any other kind of 
electronic devices) as part of regulated clinical trial activities, such systems must be compliant 
with all applicable laws and regulations governing use of electronic records and/or electronic 
signatures. Such systems may include, but are not limited to, electronic medical/health records 
(EMRs/EHRs), adverse event tracking/reporting, protocol required assessments, and/or drug 
accountability records).
When paper records from such systems are used in place of electronic format to perform 
regulated activities, suchpaper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original. 
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9.2
Records
9.2.1
Records Retention
The investigator (or head of the study site in Japan) must retain all study recordsand source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designate, whichever is longer. The 
investigator(or head of the study site in Japan) must contact BMS or designateprior to 
destroying any records associated with the studyand BMS or designatewill notify the 
investigator when the study records are no longer needed.
If the investigator withdraws from the study (e.g., relocation, retirement), the records shall be 
transferred to a mutually agreed upon designate(e.g., another investigator, study site, IRB). 
Notice of such transfer will be given in writing to BMSor designate.
9.2.2
Study Drug Records 
Records for IP(whether supplied by BMS, its vendors, or the site) must substantiate IP integrity 
and traceability from receipt, preparation, administration, and through destruction or return. 
Records must be made available for review at the request of BMS/designateor a Health 
Authority.
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If...
Then...
Supplied by BMS (or its vendors):•
Records or logs must comply with applicable 
regulations and guidelines and should include:
amount received and placed in storage area
amount currently in storage area
label identification number or batch 
number
amount dispensed to and returned by each 
subject, including unique subject identifiers
amount transferred to another area/site for 
dispensing or storage
nonstudy disposition (e.g., lost, wasted) 
amount destroyed at study site, if 
applicable
amount returned to BMS
retain samples for 
bioavailability/bioequivalence, if 
applicable 
dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the 
Delegation of Authority Form.
Sourced by site, and not supplied by BMS or 
its vendors (examples include IP sourced from 
the sites stock or commercial supply, or a 
specialty pharmacy)
The investigator or designateaccepts 
responsibility for documenting traceability and 
study drug integrity in accordance with 
requirements applicable under law and the 
SOPs/standards of the sourcing pharmacy.
These records should include:
label identification number or batch 
number 
amount dispensed to and returned by each 
subject, including unique subject identifiers
dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the 
Delegation of Authority Form.
BMS or designatewill provide forms to facilitate inventory control if the investigational site 
does not have an established system that meets these requirements.
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9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the Sponsor or designateelectronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which 
will be reported on the or electronic SAEform and Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used.Spaces may be left blank 
only in those circumstances permitted by study-specific CRF completion guidelines provided by 
BMS. 
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signaturesand initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by 
the investigator or qualified physician who is a subinvestigatorand who is delegated this task on 
the Delegation of Authority Form Subinvestigators in Japan may not be delegated the CRF 
approval task. .For electronic CRFs, review and approval/signature is completed electronically 
through the BMS electronic data capture tool. The investigator must retain a copy of the CRFs 
including records of the changes and corrections.
Each individual electronically signing electronic CRFs must meet Sponsor or designatetraining 
requirements and must only access the BMS electronic data capture tool using the unique user
account provided by Sponsor or designate.User accounts are not to be shared or reassigned to 
other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report. 
For this protocol, the signatory investigator will be selected as appropriate based on the 
following criteria:
External principal investigator designated at protocol development
National coordinating investigator 
Study steering committee chair or their designate
Subject recruitment (e.g., among the top quartile of enrollers)
Involvement in trial design
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Regional representation (e.g., among top quartile of enrollers from a specified region or country)
Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTA) governing [Study site or Investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
BMS or designate at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTA.
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10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
Complete Abstinence is defined as complete avoidance of 
heterosexual intercourse and is an acceptable form of 
contraception for all study drugs. This also means that 
abstinence is the preferred and usual lifestyle of the patient. 
This does not mean periodic abstinence (e.g., calendar, 
ovulation, symptothermal, profession of abstinence for entry 
into a clinical trial, post-ovulation methods) and withdrawal, 
which are not acceptable methods of contraception.Women
must continue to have pregnancy tests. Acceptable alternate 
methods of highly or less effective contraception’s must be 
discussed in the event that the subject chooses to forego 
complete abstinence.
AdditionalResearch
Those scientific activities which cannot be reasonably 
anticipated at the time of trial design, for which we would 
like to collect and/or retain samples from study participants.  
Examples of additional research include, but are not limited 
to, new assay development and validation, companion 
diagnostic development, new hypotheses in the interaction of 
drug and the human body, and exploration of emerging 
science in the understanding of disease.
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11
LIST OF ABBREVIATIONS
Term
Definition
AE
adverse event
ACLS
advanced cardiac life support
AI
accumulation index
AI_AUC
AUC Accumulation Index; ratio of AUC(TAU) at steady state to 
AUC(TAU) after the first dose
AI_Cmax
Cmax Accumulation Index; ratio of Cmax at steady state to Cmax after 
the first dose
AI_Ctau
Ctau Accumulation Index; ratio of Ctau at steady state to Ctau after the 
first dose
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ANOVA
analysis of variance
aPTT
activated partial thromboplastin time
AR
Additional research
AST
aspartate aminotransferase
AT
aminotransaminases
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-T)
area under the concentration-time curve from time zero to the timeof the 
last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in one dosing interval
A-V
atrioventricular
BA/BE
bioavailability/bioequivalence
BID, bid
bis in die, twice daily
BLQ
below limit of quantification 
BMI
body mass index
BMS
Bristol-Myers Squibb
BP
blood pressure
BSA
Body Surface Area
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Term
Definition
BUN
blood urea nitrogen
C
Celsius
C12
concentration at 12 hours
C24
concentration at 24 hours
Ca++
calcium
Cavg
average concentration
CBC
complete blood count
Cexpected-tau
expected concentration in a dosing interval
CFR
Code of Federal Regulations 
CI
confidence interval
C1-
chloride
CLcr
creatinine clearance
cm
centimeter
Cmax, CMAX
maximum observed concentration
Cmin, CMIN
trough observed concentration
CNS
Central nervous system
CRC
Clinical Research Center
CRF
Case Report Form, paper or electronic
Ct
Expected concentration at a certain time, usually at the end of an 
expected future dosing interval (e.g., concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctau
Concentration in a dosing interval (e.g., concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctrough
Trough observed plasma concentration
CV
coefficient of variation
CYP
cytochrome p-450
D/C
discontinue
dL
deciliter
DMC
Data monitoring committee
DLQI
Dermatology Quality Life Index
DSM IV
Diagnostic and Statistical Manual of Mental Disorders (4thEdition)
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Term
Definition
EA
extent of absorption
ECG
electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EEG
electroencephalogram
e.g.
exempli gratia (for example)
ESR
Expedited Safety Report
F
bioavailability
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
g
gram
GC
gas chromatography
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GFR
glomerular filtration rate
h
hour
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCO3
-
bicarbonate
HIV
Human Immunodeficiency Virus
HR
heart rate
HRT
hormone replacement therapy
ICD
International Classification of Diseases
ICH
International Councilon Harmonisation 
i.e.
id est (that is)
IEC
Independent Ethics Committee
IMP
investigational medicinal products
IND
Investigational New Drug Exemption
IRB
Institutional Review Board
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Term
Definition
IU
International Unit
IV
intravenous
K
slope of the terminal phase of the log concentration-time curve
K3EDTA
potassium ethylenediaminetetraacetic acid
K+
potassium
kg
kilogram
L
liter
LAM
Lactation amenorrhea method
LC
liquid chromatography
LDH
lactate dehydrogenase
ln
natural logarithm
mg
milligram
Mg++
magnesium
min
minute
mL
milliliter
mmHg
millimeters of mercury
MTD
maximum tolerated dose
g
microgram
N
number of subjects or observations
Na+
sodium
N/A
not applicable
ng
nanogram
NIMP
non-investigational medicinal products 
NSAID
nonsteroidal anti-inflammatory drug
PASI
Psoriasis Area and Severity Index
PD
pharmacodynamics
PK
pharmacokinetics
PO
per os (by mouth route of administration)
PT
prothrombin time
PTT
partial thromboplastin time
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Term
Definition
Pu
percent of unbound drug
Q2D
Every other day
QC
quality control
QD, qd
quaque die, once daily
R2
coefficient of determination
RBC
red blood cell
SAE
serious adverse event
SD
standard deviation
SOP
Standard Operating Procedures
sPGA
Static Physician’s Global Assessment
Subj
subject
t
temperature
T
time
TAO
Trial Access Online, the BMS implementation of an EDC capability
T-HALF
Half life
T-HALFeff_AUC
Effective elimination half life that explains the degree of AUC 
accumulation observed
T-HALFeff_Cmax Effective elimination half life that explains the degree of Cmax 
accumulation observed)
TID, tid
ter in die, three times a day
Tmax, TMAX
time of maximum observed concentration
TR_AUC(0-T)
AUC(0-T) treatment ratio
TR_AUC(INF)
AUC(INF) treatment ratio
TR_Cmax
Cmax treatment ratio
W
washout
WBC
white blood cell
WHO
World Health Organization
WOCBP
women of childbearing potential
x g
times gravity
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APPENDIX 1
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND
METHODS OF CONTRACEPTION
DEFINITIONS
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Women in the following categories are not considered WOCBP
Premenarchal
Premenopausal female with 1 of the following:
Documented hysterectomy
Documented bilateral salpingectomy
Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.
Postmenopausal female
A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 45 
years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum folliclestimulating hormone, (FSH) level > 
40 mIU/mL to confirm menopause.
Note: Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgement in checking serum FSH levels. 
1 week minimum for vaginal hormonal products (rings, creams, gels)
4 week minimum for transdermal products
8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/ml at any time during the washout period, the woman can be considered 
postmenopausal.
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CONTRACEPTION GUIDANCE FOR FEMALE PARTICIPANTS OF CHILD BEARING 
POTENTIAL
One of the highly effective methods of contraception listed below is required during study 
duration and until the end of relevant systemic exposure, defined as 3 daysafter the end of study 
treatment, plus 30 days 
Local laws and regulations may require use of alternative and/or additional contraception 
methods.
Highly Effective Contraceptive Methods That Are User Dependent 
Failurerate of <1% per year when used consistently and correctly.
a
Combined (estrogen-and progestogen-containing) hormonal contraception associated with
inhibition of ovulationb
oral
intravaginal
transdermal
Progestogen-only hormonal contraception associated with inhibition of ovulationb
oral
injectable
Highly EffectiveMethods That Are User Independent
Implantable progestogen-only hormonal contraception associated with inhibition of
ovulationb
Intrauterine device (IUD)
c
Intrauterine hormone-releasing system (IUS)
c
Bilateral tubal occlusion
Vasectomizedpartner
A vasectomized partner is a highly effective contraception method provided that the partner 
is the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. 
If not, an additional highly effective method of contraception should be used. 
Sexual abstinence
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant.
It is not necessaryto use any other method of contraception when complete abstinence is
elected.
WOCBP participantswho choose complete abstinence must continue to have pregnancy
tests, as specified in Section 5.
Acceptable alternate methods of highly effective contraception must be discussed in the
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event that the WOCBP participantschooses to forego complete abstinence 
NOTES: 
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants participating in clinical 
studies. 
b Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy 
of the contraceptive method.  Hormonal contraception is permissible only when there is sufficient evidence 
that the IMP and other study medications will not alter hormonal exposures such that contraception would be 
ineffective or result in increased exposures that could be potentially hazardous.  In this case, alternative 
methods of contraception should be utilized. 
c Intrauterine devices and intrauterine hormone releasing systems are acceptable methods of contraception in the 
absence of definitive drug interaction studies when hormone exposures from intrauterine devices do not alter 
contraception effectiveness
Less Than Highly Effective Contraceptive Methods That Are User Dependent
Failure rate of >1% per year when used consistently and correctly.
Male or female condom with or without spermicide.  Male and female condoms cannot be 
used simultaneously
Diaphragm with spermicide
Cervical cap with spermicide
Vaginal Sponge with spermicide
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action
Unacceptable Methods of Contraception
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
Withdrawal(coitus interruptus).
Spermicide only
Lactation amenorrhea method (LAM)
CONTRACEPTION GUIDANCE FOR MALE PARTICIPANTS WITH PARTNER(S)OF 
CHILD BEARING POTENTIAL.
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to the following during the treatment and until the end of relevant systemic exposure.
Inform any and all partner(s) of their participation in a clinical drug study and the need to 
comply with contraception instructions as directed by the investigator.
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Male participants are required to use a condom for study duration and until end of relevant
systemic exposure defined as 3 days after the end of treatment plus an additional 90 days.
Female partners of males participating in the study to consider use of effective methods of
contraception until the end of relevant systemic exposure, defined as 3 daysafter the end of
treatment in the male participant.
Male participants with a pregnant or breastfeeding partner must agree to remain abstinent
from penile vaginal intercourse or use a male condom during each episode of penile
penetration during the treatment and until 3 daysafter the end of treatment.
Refrain from donating sperm for the duration of the study treatment and until 3 daysafter the
end oftreatment.
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 6.4 and the Appendix for Adverse Events and Serious 
Adverse Events Definitions and procedures for Evaluating, Follow-up and Reporting
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APPENDIX 2
PSORIASIS AREA AND SEVERITY INDEX (PASI)
The PASI is a grading system used for the evaluation of the severity of psoriatic lesions and their 
response to treatment. The PASI produces a numeric score that can range from 0 to 72. The 
severity of a subject’s disease is calculated as described below:
In the PASI system, the body is divided into 4 regions: the head (h), trunk (t), upper extremities 
(ux) and lower extremities (lx), which account for 10%, 30%, 20%, and 40% respectively of the 
total body surface area (BSA). Each of these areas are evaluated for erythema, induration and 
scaling, which are rated on a scale from 0 to 4.
The scoring system for the signs of disease (erythema, in duration and scaling) is below:
0 = none
1 = slight
2 = moderate
3 = severe
4 = very severe
The scoring system for estimating the area of involvement for psoriatic lesions is outlined below:
0 = no involvement
1 = 1% to 9% involvement
2 = 10% to 29% involvement
3 = 30% to 49% involvement
4 = 50% to 69% involvement
5 = 70% to 89% involvement
6 = 90% to 100% involvement
To aid in the area assessments, the following conventions are followed:
a.
the neck is considered part of the head
b.
the axilla and groin are considered part of the trunk
c.
the buttocks are considered part of the lower extremities
The PASI formula is:
PASI = 0.1(E
h+ Sh+ I
h)A
h+ 0.3(Et+ St+ I
t)At + 0.2(Eux+ Sux+ I
ux)A
ux+ 0.4(Elx+ Slx
+ Ilx)A
lx
Clinical assessments of response should be performed by the same assessor(s).
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APPENDIX 3
STATIC PHYSICIAN’S GLOBAL ASSESSMENT (SPGA)
The Physician Global Assessment (PGA) is used to determine the subject’s psoriasis lesions 
overall at a given time point. Overall lesions will begraded for induration, erythema, and scaling 
based on the scales below. The sum of the 3 scales will be divided by 3 to obtain a final PGA 
score.
Induration (I) (averaged over all lesions; use the National Psoriasis Foundation Reference card 
for measurement)
0 = no evidence of plaque elevation
1 = minimal plaque elevation, = 0.25 mm
2 = mild plaque elevation, = 0.5 mm
3 = moderate plaque elevation, = 0.75 mm
4 = marked plaque elevation, = 1 mm
5 = severe plaque elevation, = 1.25 mm or more
Erythema (E) (averaged over all lesions)
0 = no evidence of erythema, hyperpigmentation may be present
1 = faint erythema
2 = light red coloration
3 = moderate red coloration
4 = bright red coloration
5 = dusky to deep red coloration
Scaling (S) (averaged over all lesions)
0 = no evidence of scaling
1 = minimal; occasional fine scale over less than 5% of the lesion
2 = mild; fine scale dominates
3 = moderate; coarse scale predominates
4 = marked; thick, nontenacious scale dominates
5 = severe; very thick tenacious scalepredominates
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Add I + E + S = / 3 = (Total Average)
Physician’s Static Global Assessment based upon above Total Average
0 = Cleared, except for residual discoloration
1 = Minimal -majority of lesions have individual scores for I + E + S / 3 that averages 1
2 = Mild -majority of lesions have individual scores for I + E + S / 3 that averages 2
3 = Moderate -majority of lesions have individual scores for I + E + S / 3 that averages 3
4 = Marked -majority of lesions have individual scores for I + E + S / 3 that averages 4
5 = Severe -majority of lesions have individual scores for I + E + S / 3 that averages 5
Note: Scores should be rounded to the nearest whole number. If total ≤1.49, score = 1; if total ≥
1.50, score = 2.
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APPENDIX 5
AMERICAN COLLEGE OF RHEUMATOLOGY SUBJECT
ASSESSMENT OF PAIN VISUAL ASSESSMENT SCALE
Measure with a metric ruler. Line on Case Report Form is exactly 10 cm long.  Scores should be recorded in 
millimeter format.  DO NOT USE THIS APPENDIX AS SOURCE DOCUMENT OR CASE REPORT FORM. 
How much pain have you had because of your condition over the past week?  Place a mark on the line below to 
indicate how severely your pain has been:
No Pain
Pain as 
Bad as it 
Could be
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APPENDIX 6
SUSTAINED ELEVATED LIVER SAFETY ABNORMALITIES FLOW CHART
Obtain confirmatory repeat AST, ALT, ALK-P and TB 
within 3 days. Do NOThold study medication
Step 1: Central Laboratory Alert Criteria
ALT and/or AST 3X ULN
. 
.
Step 2a:
If repeat ALT AND
AST 3X ULN
Step 2b:
If repeat ALT and/or AST 
3X ULN BUT 5X ULN 
AND TB2.0X ULNa
Step 2c:
If repeat ALT and/or AST 
5X ULN BUT 10X 
ULN and TB 2.0X ULN
Step 2d:
If repeat ALT and/or AST 
3X ULN with a second 
confirmed TB 2.0XULNa
Step 2e:
If repeat ALT and/or 
AST 10XULN
-Continue the subject 
in the treatment period 
according to the 
original visit schedule, 
unless otherwise 
contraindicated.
-Discontinue the subject immediately.
-Notify the Sponsor.
-Perform the end-of-treatment visit and additional 
assessments, including the liver discontinuation panel.
b
-Obtain confirmatory repeat AST, ALT, ALK-P and 
TB every 3 days.c
-Continue study medication.
-Perform additional 
assessments, including the 
specialized liver panel.b
-Obtain confirmatory 
repeat AST, ALT, ALK-P 
and TB every 3 days.c

Each time AST, ALT, ALK-P and TB results are 
received, go back to Step 2to review and implement the 
-Continue study medication.
-Perform additional 
assessments, including the 
specialized liver panel.b
-Obtain confirmatory 
repeat AST, ALT, ALK-P 
and TB every 3 days.
c

If repeat ALT and/or AST 5X ULN for 14 
consecutive days, at any time after initial confirmatory 
results
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Specialized Liver Panel:
For subjects who are being monitored frequently as a result of confirmed AST and/or ALT > 3X 
ULN, additional central laboratory tests will be performed within 3 days of receipt of 
confirmatory results. These laboratory tests will study the possible causes of the increased ALT 
and/orAST and/or TB, and may include, but are not limited to, the following tests:
Hepatitis A IgM
Hepatitis BsAg
Hepatitis B Core Ab IgM
Hepatitis C virus RNA or RIBA
Hepatitis C Ab
Hepatitis E IgM
Epstein-Barr Virus (EBV) IgM Ab
Lactate Dehydrogenase (LDH)
Gamma-glutamyl-transpeptidase (GGT)
Carbohydrate deficient transferrin (CDT)
Prothrombin time (PT/INR)
Iron Panel -iron, ferritin, total iron binding capacity (TIBC)
Immunology Panel including Antinuclear Antibody (ANA), Anti-Smooth Muscle Antibody 
(SMA) and Anti-Liver/Kidney Microsomal Antibody (Anti-LKM)
Anti-tissue Transglutaminase Antibody
Liver Discontinuation Panel:
For subjects who are discontinued from the study as a result of sustained elevated liver safety 
abnormalities, additional central laboratory tests will be performed at the time of Early 
Termination (End-of-Treatment) visit. Similar to the Specialized Liver Panel, these laboratory 
tests will study the possible causes of the increased ALT and/or AST and/or TB, and may 
include, but are not limited to, the following tests:
Cytomegalovirus (CMV) IgM Ab
Herpes Simplex Virus (HSV) 1 and 2
Ceruloplasmin
Toxoplasmosis
Alpha-1 antitrypsin
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SAP_001.pdf: 
Official Title of Study:  
A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
PARALLEL GROUP PHASE 2 STUDY TO EVALUATE THE CLINICAL EFFICACY 
AND SAFETY OF BMS-986165 IN SUBJECTS WITH MODERATE TO SEVERE 
PSORIASIS 
 
NCT Number: NCT02931838 
 
Document Date (Date in which document was last revised):  June 6, 2017 
 






STATISTICAL ANALYSIS PLAN 
FOR CLINICAL STUDY REPORT 
 
A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
PARALLEL GROUP PHASE 2 STUDY TO EVALUATE THE CLINICAL EFFICACY 
AND SAFETY OF BMS-986165 IN SUBJECTS WITH MODERATE TO SEVERE 
PSORIASIS 
 
PROTOCOL IM011011 
 
VERSION # 2.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Statistical Plan Prepared by:   
 
   
 
Signature/Date:  _______________________________________________________ 
 
 
 
 
Statistical Plan Reviewed by:   
 
   
 
Signature/Date:  _______________________________________________________ 
 
 
 
 
Statistical Plan Approved by:   
 
 
 
 
 
 
 
 
 
Signature/Date:  _______________________________________________________ 
 
 
 
 
 
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TABLE OF CONTENTS 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF TABLES ...........................................................................................................................6 
LIST OF FIGURES .........................................................................................................................6 
1 
 
2 
STUDY DESCRIPTION ..............................................................................................7 
2.1 
Study Design .................................................................................................................7 
2.2 
Treatment Assignment ..................................................................................................8 
2.3 
Blinding and Unblinding ..............................................................................................9 
2.4 
Protocol Amendments ..................................................................................................9 
2.5 
Data Monitoring and Other External Committees ......................................................10 
3 
OBJECTIVES .............................................................................................................10 
3.1 
Primary .......................................................................................................................10 
3.2 
Secondary ...................................................................................................................10 
3.3 
 
4 
ENDPOINTS ..............................................................................................................11 
4.1 
Primary Efficacy Endpoint .........................................................................................11 
4.2 
Secondary Endpoints ..................................................................................................11 
4.3 
Primary Safety Endpoint .............................................................................................11 
4.4 
 
5 
SAMPLE SIZE AND POWER ..................................................................................12 
6 
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS 
FOR ANALYSES .......................................................................................................12 
6.1 
Study Periods ..............................................................................................................12 
6.2 
Treatment Regimens ...................................................................................................13 
6.3 
Populations for Analyses ............................................................................................13 
7 
STATISTICAL ANALYSES .....................................................................................13 
7.1 
General Methods .........................................................................................................13 
7.2 
Study Conduct ............................................................................................................14 
7.2.1 
Relevant Protocol Deviations .....................................................................................14 
7.3 
Study Population .........................................................................................................14 
7.3.1 
Subject Disposition .....................................................................................................14 
7.3.2 
Demographic Characteristics .....................................................................................14 
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7.3.3 
Physical Measurement Summary ................................................................................15 
7.3.4 
Medical History ..........................................................................................................15 
7.3.5 
Prior and Concomitant Therapy .................................................................................15 
7.4 
Extent of Exposure .....................................................................................................15 
7.4.1 
Administration of Study Therapy ................................................................................15 
7.4.2 
Treatment Compliance ................................................................................................16 
7.5 
Efficacy .......................................................................................................................16 
7.5.1 
Primary Efficacy Analysis ..........................................................................................16 
7.5.2 
Secondary Efficacy Analyses ......................................................................................17 
7.5.2.1 
PASI-75 .......................................................................................................................17 
7.5.2.2 
PASI Score ..................................................................................................................17 
7.5.2.3 
PASI-50, PASI-90, and PASI-100 ...............................................................................18 
7.5.2.4 
sPGA ...........................................................................................................................18 
7.5.2.5 
DLQI ...........................................................................................................................19 
7.5.2.6 
BSA .............................................................................................................................19 
7.5.3 
 
7.5.3.1 
VAS .............................................................................................................................20 
7.5.4 
Subgroup Analyses ......................................................................................................20 
7.5.5 
Sensitivity Analyses .....................................................................................................20 
7.5.6 
Per-Protocol Analyses ................................................................................................20 
7.6 
Safety ..........................................................................................................................21 
7.6.1 
Deaths .........................................................................................................................21 
7.6.2 
Serious Adverse Events ...............................................................................................21 
7.6.3 
Adverse Events Leading to Discontinuation of Study Therapy ..................................21 
7.6.4 
Adverse Events Leading to Dose Modification ...........................................................21 
7.6.5 
Adverse Events ............................................................................................................21 
7.6.6 
Clinical Laboratory Evaluations ................................................................................21 
7.6.7 
Electrocardiogram ......................................................................................................22 
7.6.8 
Vital Signs and Physical Findings ..............................................................................22 
7.6.9 
Other Observations Related to Safety .........................................................................23 
7.7 
Pharmacokinetic Results .............................................................................................23 
7.8 
 
 
 
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8 
CONVENTIONS ........................................................................................................24 
8.1 
Calculations of Key Measures ....................................................................................24 
8.1.1 
Evaluation of PASI .....................................................................................................24 
8.1.2 
Evaluation of sPGA ....................................................................................................25 
8.2 
Baseline Measures ......................................................................................................26 
8.3 
Missing Measurements ...............................................................................................26 
8.3.1 
Imputation of Missing Data for Binary Variables ......................................................26 
8.3.2 
Imputation of Missing Data for Continuous Variables ..............................................27 
8.4 
Missing, Unknown or Partial Dates ............................................................................27 
8.5 
Day Ranges for Analysis of Time Points ...................................................................28 
9 
CONTENT OF REPORTS .........................................................................................28 
 
 
11 
DOCUMENT HISTORY ...........................................................................................29 
APPENDIX 1 
RELEVANT RROTOCOL DEVIATIONS ...............................................29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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LIST OF TABLES 
Table 7.4-1: 
Administration of Study Therapy: Definition of Parameters .....................16 
Table 7.6.8-1: 
Vital Sign Parameter Cut-Off Values ........................................................23 
Table 8.5-1: 
Day Ranges for Efficacy Assessments ......................................................28 
Table 10-1: 
Document History ......................................................................................29 
 
 
LIST OF FIGURES 
Figure 1:   Study Design Schematic .................................................................................................8 
 
 
 
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2 
STUDY DESCRIPTION 
2.1 
Study Design 
This is a 12 week, multi-center, randomized double-blind, placebo-controlled, parallel-group 
multiple oral dose study in subjects with moderate to severe psoriasis. Subjects will be randomly 
assigned to one of six treatment groups, i.e., to receive BMS-986165 (3mg every other day (Q2D); 
3mg every day (QD); 3mg twice daily (BID); 6mg BID; 12mg QD) or placebo. Subjects will 
undergo screening evaluations to determine eligibility within 28 days prior to administration of 
study medication. 
This is an outpatient study. Subjects will receive BMS-986165 or placebo capsules to be taken at 
home. 
The study design schematic is presented in Figure 1. 
 
 
 
 
 
 
 
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Figure 1:   Study Design Schematic 
  
 
Q2D=every other day, QD=every day, BID=twice daily  
The approximate duration of the study is 20 weeks (143 days). This includes a 4-week screening 
period (28 days), a 12-week treatment period (85 days), and a 4-week follow-up period (30 days). 
The start of the trial is defined as the date of the first Screening Visit (date of signing the informed 
consent) for the first subject screened. The end of trial is defined as the last visit or scheduled 
procedure shown in the Time & Events schedule (Table 5.1-1 and Table 5.1-2 of the study 
protocol) for the last subject. Study completion is defined as the final date on which data for the 
primary endpoint was or is expected to be collected, if this is not the same. 
2.2 
Treatment Assignment 
After completion of all screening evaluations, on Day 1, all eligible subjects will be randomly 
assigned to 1 of 6 treatment arms (BMS-986165, 3mg Q2D; BMS-986165, 3mg QD; BMS-
986165, 3 mg BID; BMS-986165, 6mg BID; BMS-986165, 12mg QD; and Placebo) in an equal 
ratio.  
Enrolled subjects meeting inclusion and exclusion criteria will be eligible to be randomized. 
Randomization numbers will be assigned prior to dosing. During the screening visit, the 
investigative site will call into the enrollment option of the Interactive Web Response System 
(IWRS) designated by BMS for assignment of a 5-digit subject number that will be unique across 
all sites. Enrolled subjects, including those not dosed, will be assigned sequential subject numbers 
starting with 00001, (e.g., 00001, 00002, 00003....00010). The patient identification number (PID) 
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will ultimately be comprised of the site number and subject number. Once it is determined that the 
subject meets the eligibility criteria following the screening visit, the investigative site will call the 
IWRS to randomize the subject. Randomization will be stratified by the use of previous treatment 
with a biologic (yes/no) and region (Japan vs rest of world).   
Specific instructions (including an enrollment/randomization worksheet) for the central enrollment 
and randomization procedure using an IWRS will be provided to the site. 
2.3 
Blinding and Unblinding 
This is a double-blinded study. The subjects and all site personnel, including the investigator, the 
site monitor, and the study team, will be blinded. The study will be kept in the blinded nature until 
the last patient last visit, after which the database undergoes a final lock and unblinding for the 
final analysis. 
Blinding of treatment assignment is critical to the integrity of this clinical study. However, in the 
event of a medical emergency or pregnancy in an individual subject in which knowledge of the 
investigational product is critical to the subject’s management, the blind for that subject may be 
broken by the investigator. The subject’s safety takes priority over any other considerations in 
determining if a treatment assignment should be unblinded. 
Before breaking the blind of an individual subject’s treatment, the investigator should determine 
that the unblinded information is necessary, (i.e., that it will alter the subject’s immediate 
management). In many cases, particularly when the emergency is clearly not related to the 
investigational product, the problem may be properly managed by assuming that the subject is 
receiving active product. It is highly desirable that the decision to unblind treatment assignment 
be discussed with the medical monitor, but the investigator always has ultimate authority for the 
decision to unblind. The principal investigator should only call in for emergency unblinding 
AFTER the decision to discontinue the subject has been made. 
In cases of accidental unblinding, contact the medical monitor and ensure every attempt is made 
to preserve the blind. 
Any request to unblind a subject for non-emergency purposes should be discussed with the medical 
monitor. 
In case of an emergency, the investigator(s) has unrestricted access to randomization information 
via the IWRS and is capable of breaking the blind through the IWRS system without prior approval 
from sponsor. Following the unblinding the Investigator shall notify the medical monitor and/or 
study director. 
For analyses for the Independent Data Monitoring Committee (IDMC), a separate unblinded study 
team, comprising an unblinded biostatistician(s) and unblinded programmer(s), will be performing 
the required analyses. 
2.4 
Protocol Amendments 
Not applicable. 
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2.5 
Data Monitoring and Other External Committees 
An Independent Data Monitoring Committee (IDMC) will be established to monitor data on an 
ongoing basis to ensure the continuing safety of subjects enrolled in this study, to ensure the 
integrity of the blinded nature of the study. An IDMC charter will be developed which will specify 
the roles and responsibilities of the members and interim decision rules. The Sponsor Steering 
Committee will receive and act on the recommendations from the IDMC. A firewall will be 
established to ensure the maintenance of the study blind for the Sponsor, the investigational site 
staff, and study subjects and their study partners. 
Data summaries and listings will be provided to the IDMC to facilitate their safety assessment at 
the regularly scheduled times and on an ad hoc basis if needed. The safety review includes serious 
adverse events and events of special interest, focusing on early signal detection. Further details on 
the frequency, content and methods of data reports to the IDMC are outlined in the IDMC charter 
and IDMC Statistical Analysis Plan (SAP). 
3 
OBJECTIVES 
3.1 
Primary 
• To compare the proportion of subjects with moderate to severe psoriasis experiencing a 
75% improvement as measured by a reduction in PASI score (PASI-75) after 12 weeks of 
treatment between doses of BMS-986165 and placebo  
• To assess the safety and tolerability of multiple oral doses of BMS-986165 in subjects with 
moderate to severe psoriasis 
3.2 
Secondary 
• To assess that the proportion of subjects experiencing a 75% reduction in PASI score in 
the most efficacious treatment group 
• To compare the proportions of subjects experiencing a 75% reduction in PASI score 
between treatment groups 
• To assess a positive trend between treatment groups of BMS-986165 and proportion of 
subjects experiencing a 75% reduction in PASI score after 12 weeks of treatment 
• To assess clinical efficacy of BMS-986165 as measured by improvement in skin disease 
area and severity indices PASI-50, -75, -90 and -100 over time in subjects with moderate 
to severe psoriasis 
• To assess a significantly higher proportion of subjects achieving Static Physician’s Global 
Assessment (sPGA) score of “0” (“cleared”) or “1” (“minimal”) after 12 weeks of 
treatment with BMS-986165 than after 12 weeks of treatment with placebo 
• To assess improvement by BMS-986165 in Dermatology Life Quality Index (DLQI) 
• To assess the trough concentrations of BMS-986165 in subjects with moderate to severe 
psoriasis 
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4 
ENDPOINTS 
4.1 
Primary Efficacy Endpoint  
The primary endpoint is the response rate in PASI-75: the proportion of subjects with moderate to 
severe psoriasis experiencing a 75% improvement (reduction from baseline) in PASI score at Day 
85.  
4.2 
Secondary Endpoints 
The following secondary endpoints will be evaluated in this trial: 
• Proportion of subjects at Day 85 with PASI-50, PASI-75, PASI-90, PASI-100 
• Change from baseline in DLQI scores at Day 85  
• Change from baseline in body surface area (BSA) at Day 85 
• Proportion of subjects at Day 85 with sPGA score of 0 or 1 
• Pharmacokinetics (PK) parameter: Ctrough 
4.3 
Primary Safety Endpoint 
• The safety and tolerability of BMS-986195 will be assessed by the incidence, potential 
significance, and clinical importance of adverse events measured during multiple doses of 
BMS- 986195 and up to 30 days after the last dose, as determined by medical review of 
adverse event reports, vital sign measurements, electrocardiograms (ECGs), and results of 
physical examination and laboratory tests. 
 
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5 
SAMPLE SIZE AND POWER 
The sample size calculation is driven by several considerations. 
The first consideration is to compare the response rate in PASI-75, the proportion of subjects with 
moderate to severe psoriasis experiencing a 75% improvement in PASI score after 12 weeks, 
between BMS-986165 and placebo arms. With a one-sided, two-sample Fisher’s exact test at 
significant level 0.05, a sample size of 42 per arm will provide at least 99% power to detect 50% 
increase in the PASI-75 response rate in an active arm (i.e., 60% response rate) compared to the 
placebo assuming the response rate is 10% in the placebo arm. 
The second consideration is to assess the response rate in PASI-75 in active dose arms. Data from 
42 treated subjects per arm will produce a two-sided 95% confidence interval (CI) with a margin 
of error at most 15.1% (half width) using normal approximation. 
The third consideration is to compare the response rates in PASI-75 in two active arms. With a 
one-sided, two-sample Fisher’s exact test at significant level 0.05, 42 subjects per arm will provide 
at least 82% power to detect at least 30% difference in the response rate in PASI-75 between any 
two active dose arms. 
The proposed sample size is mainly driven by the third consideration. In addition, administration 
of BMS-986165 to 42 subjects in each active treatment group provides 34%, 88%, and 99% 
probability of observing at least one occurrence of any adverse event that would occur with 1%, 
5%, or 10% incidence rate respectively. 
6 
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS FOR 
ANALYSES 
6.1 
Study Periods 
The following periods are defined in this SAP for the purpose of analyses and reporting. 
Screening period: Covers the time period which starts from the day of enrollment and lasts until 
the initiation of randomized double-blind treatment. 
Treatment period: Starts at the time of the first dose of blinded treatment (BMS-986165 or placebo) 
and lasts until the date of the last dose of double-blinded treatment. 
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Follow-up period: Starts at the date of the last dose of blinded treatment and lasts 30 days post. 
6.2 
Treatment Regimens 
Subjects will receive one of the following treatments for 12 weeks: 
• BMS-986165 3mg Every Other Day (Q2D) 
• BMS-986165 3mg Every Day (QD) 
• BMS-986165 3mg Twice Daily (BID) 
• BMS-986165 6mg BID 
• BMS-986165 12mg QD 
• Placebo 
6.3 
Populations for Analyses 
The following subject populations will be considered in this trial: 
• All Enrolled Subjects: All subjects who sign an informed consent. 
• All Randomized Subjects: All subjects who are randomized to a treatment.  
• All Randomized and Treated Subjects: All randomized subjects who receive at least one 
dose of the study medication. Subjects will be grouped according to the treatment to which 
they are randomized by IWRS at the start of the study.   
• As-Treated Analysis Population: All subjects who have received at least one dose of study 
medication. Subjects will be grouped according to the treatment that they actually receive 
as opposed to the treatment to which they are randomized. Subjects will be grouped on an 
as-randomized basis unless the subject received the incorrect medication for the entire 
treatment period. In that case, the subject will be analyzed in the treatment group associated 
with the incorrect medication he/she receives.   
• Efficacy Analysis Population: All Randomized and Treated Subjects.  
• Biomarker Analysis Population: All subjects that receive any study medication and have 
at least 1 post-treatment biomarker measurement. 
• Pharmacokinetic Population: All subjects who receive any study medication and have any 
available concentration-time data. 
• Per-Protocol Population: All randomized subjects without relevant protocol deviations 
(Section 7.2.1). The primary efficacy analysis will be performed using this population if 
there are more than 10% of the study subjects with relevant protocol deviations. 
7 
STATISTICAL ANALYSES 
7.1 
General Methods 
Categorical variables will be summarized using counts and percentages of subjects falling into 
each category by treatment group and visit. Percentages given in these tables will be rounded and, 
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therefore, may not always sum to 100%. Continuous variables will be summarized by treatment 
group using the mean, standard deviation, median, Q1, Q3, minimum and maximum values.  
SAS® version 9.4 will be used for statistical analyses, tabulations and graphical presentations. 
7.2 
Study Conduct 
7.2.1 
Relevant Protocol Deviations 
Relevant protocol deviations, which could have an impact on the primary efficacy endpoint, will 
be identified for all subjects who are randomized and receive study medication during the treatment 
period. Details of relevant protocol deviations are provided in Appendix 1. 
All subjects with relevant protocol deviations will be identified prior to database lock and 
unblinding of treatment assignment. All relevant protocol deviations will be listed and summarized 
by treatment group based on All Randomized and Treated Subjects.  
If there are more than 10% of the study subjects with relevant protocol deviations, a Per-Protocol 
analysis excluding these subjects will be performed for the primary efficacy endpoint. 
7.3 
Study Population 
Unless otherwise specified, the study population data will be presented on All Randomized and 
Treated Subjects by treatment group, all active treatment groups combined, and all treated subjects 
combined. 
7.3.1 
Subject Disposition 
The following summary tables will be provided: 
• Pre-Randomized Subject Status: subjects enrolled, randomized, not randomized, reason for 
being not randomized. 
• Treatment Phase Subject Status: subjects completing the treatment period, not completing 
the treatment period, reason for not completing the treatment period, not reported (if any). 
• End of Study Subject Status: subjects completing the study, not completing the study, 
reason for not completing the study, not reported (if any). 
• The following by-subject listings will be provided: 
o Pre-randomized subject status  
o Treatment phase subject status 
o End of study subject status  
7.3.2 
Demographic Characteristics 
The following summary table will be provided by treatment group:  
• Demographic Characteristics Summary: age, gender, race, ethnicity, region, country.  
The following by-subject listing will be provided: 
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• Demographic Characteristics: region, country, treatment group, informed consent date, 
birth date, age, gender, ethnicity, race.   
7.3.3 
Physical Measurement Summary 
The following summary table will be provided by treatment group:  
• Physical Measurement Summary: height (cm), weight (kg), body mass index (kg/m2).  
The following by-subject listing will be provided: 
• Physical Measurements: visit, date, study day, height (cm), weight (kg), BMI (kg/m2).      
7.3.4 
Medical History 
The following summary table will be provided by treatment group:  
• Medical History: history system. 
The following by-subject listing will be provided: 
• Medical History: history system, history details. 
7.3.5 
Prior and Concomitant Therapy 
Prior medication is defined as any medication that is stopped prior to the first dose of study 
treatment; and concomitant medication is defined as any medication that is on-going at the time of 
the first dose or started after the first dose of study treatment. Medications will be coded using the 
WHO DRUG Dictionary Coding Guidelines (WHODrug Enhanced). 
The following summary tables will be provided by treatment group:  
• Concomitant Medication Summary: total subjects using medication, subjects by 
anatomic class/therapeutic class/generic name. 
• Prior Medication Summary: total subjects using medication, subjects by anatomic 
class/therapeutic class/generic name. 
The following by-subject listing will be provided: 
• Prior and Concomitant Medications: start date, stop date, study day, anatomic 
class/therapeutic class/generic name/reported medication, total daily use, prior or 
concomitant. 
7.4 
Extent of Exposure 
The exposure data will be presented on the As-Treated Analysis Population by treatment group. 
7.4.1 
Administration of Study Therapy 
Table 7.4-1 provides the definition of parameters for administration of study therapy. 
 
 
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The following parameters will be summarized (descriptive statistics): 
• Number of doses received 
• Total dose  
• Duration of treatment 
The following by-subject listing will be provided: 
• Study Drug Administration: visit, date/day of dose, blister card number (flag if drug 
assigned but not taken), number of capsules per day.  
7.4.2 
Treatment Compliance 
The CRF for this study will capture information on doses of the study medication. All subjects 
who skip any study drug dose will be listed. The number of subjects with missed doses (excluding 
missed doses due to premature discontinuation from the study) by number of missed doses will be 
summarized by treatment groups.   
7.5 
Efficacy 
Unless otherwise specified, the efficacy data will be presented using the Efficacy Analysis 
population. 
7.5.1 
Primary Efficacy Analysis 
The algorithm for PASI scoring is provided in Section 8.1.1. The percentage change from baseline 
in PASI will be calculated using the following formula: 
[(PASI Score at Day 85 – Baseline)/Baseline]*100 
For a subject, PASI-75 is 1 if the percentage change from baseline is less than or equal to -75%, 
i.e., the subject has greater than or equal to 75% improvement in PASI score comparing to baseline. 
Otherwise, PASI-75 is 0. Missing value for PASI-75 will be imputed and the imputation method 
is described in Section 8.3.1. 
The following analyses will be provided:  
• To compare the response rates between each treatment group and placebo, the PASI-75 at 
Day 85 will be analyzed by two-sample Fisher’s exact test or Chi-square test based on the 
observed counts. The odds ratio (odds in treatment group/odds in placebo) and the 
Table 7.4-1: 
Administration of Study Therapy: Definition of Parameters 
 
BMS-986165 
Dosing schedule per 
protocol 
3mg Q2D, 3mg QD, 3mg BID, 6mg BID, and 12mg QD  
Total Dose 
Total dose (mg) is sum of all doses administered during the study 
Duration of treatment  
Last dose date - Start dose date +1 
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difference in the response rates and their corresponding two-sided 95% confidence 
intervals (CIs) will be provided.    
There will be no adjustment for multiplicity. All comparisons will be performed in a pre-
specified hierarchical procedure starting from the highest dose arm to the lowest dose arm. 
If a comparison is not significant at level 0.05, all p-values in subsequent comparisons will 
be considered nominal. 
• For the primary efficacy endpoint, the proportion of subjects with moderate to severe 
psoriasis experiencing a 75% improvement in PASI score at Day 85 (PASI-75), the count 
and percentage of subjects with PASI-75, along with the 95% asymptotic and Clopper-
Pearson exact two-sided CIs, will be provided in each treatment group.   
• A logistic regression model analysis will be performed to evaluate the impact of treatments 
on PASI-75 at Day 85, with treatment group, age, gender, weight, BMI, baseline PASI 
score, use of previous biologic treatment, study region, and use of previous biologic 
treatment-by-study region interaction as covariates, if applicable. 
• A bar chart of PASI-75 response rate at Day 85 by treatment group will be provided. 
7.5.2 
Secondary Efficacy Analyses 
7.5.2.1 
PASI-75 
The following analyses will be provided for PASI-75: 
• The Cochran-Armitage trend test will be performed to assess a positive trend between 
treatment groups of BMS-986165 and proportion of subjects experiencing a 75% reduction 
in PASI score at Day 85. 
• A repeated measures logistic regression model analysis will be performed using a 
generalized estimating equations (GEE) model. The model will be fitted with treatment, 
visit, and treatment-by-visit interaction as the fixed effects and measurements within each 
subject as the repeated measurements. The use of previous biologic treatment, study region, 
and use of previous biologic treatment-by-study region interaction will be added into the 
model as covariates. 
• A longitudinal line plot of the response rate in PASI-75 grouped by treatment will be 
provided. 
7.5.2.2 
PASI Score 
The following analyses will be provided for PASI score: 
• PASI score will be presented using the descriptive statistics (n, mean, median, min, max, 
standard deviation, Q1, Q3) at Day 1 (baseline), Day 8, Day 15, Day 29, Day 57, Day 85, 
and Day 115 for each group. Point estimates at each visit and two-sided 95% CIs for mean 
change from baseline within each treatment group will be provided.  
• A longitudinal line plot of mean change (with standard error) in PASI score from baseline 
grouped by treatment will be provided. 
• A mixed effect model analysis with repeated measures will be performed to evaluate the 
impact of treatments on PASI score over time. The mixed effect model will be fitted with 
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treatment, visit, and treatment-by-visit interaction as the fixed effects and change from 
baseline measurements within each subject as the repeated measurements. The baseline 
value, use of previous biologic treatment, study region, and use of previous biologic 
treatment-by-study region interaction will be added into the model as covariates. Based on 
the mixed effect model, the estimate and 95% confidence interval will be calculated for the 
difference between each active treatment and the placebo at each specified visit. 
The following by-subject listing will be provided:  
• PASI: date of assessment, visit, body location, area of involvement score, induration 
(thickness) score, erythema (redness) score, scaling (desquamation) score, derived PASI 
score, change from baseline, percentage change from baseline, PASI-50, PASI-75, PASI-
90, and PASI-100.   
7.5.2.3 
PASI-50, PASI-90, and PASI-100 
Similar analyses as in primary efficacy analyses will be performed for PASI-50, PASI-90, and 
PASI-100. 
• The proportion of subjects with moderate to severe psoriasis experiencing a 50%, 95%, 
and 100% improvement  in PASI score at Day 85, along with the 95% asymptotic and 
Clopper-Pearson exact two-sided CIs will be provided in each group, respectively.   
• To compare the response rates between each treatment group and placebo, the PASI-50, 
PASI-90, and PASI-100 will be analyzed by two-sample Fisher’s exact test or Chi-square 
test based on the observed counts. The odds ratio (odds in treatment group/odds in placebo) 
and the difference in the response rates and their corresponding two-sided 95% CIs will be 
provided. 
• A logistic regression model analysis will be performed to evaluate the impact of treatments 
on PASI-50, PASI-90, or PASI-100 at Day 85, with treatment group, age, gender, weight, 
BMI, baseline PASI score, use of previous biologic treatment, study region and use of 
previous biologic treatment-by-study region interaction as covariates. 
• A repeated measures logistic regression model analysis will be performed using a GEE 
model. The model will be fitted with treatment, visit, and treatment-by-visit interaction as 
the fixed effects and measurements within each subject as the repeated measurements. The 
use of previous biologic treatment, study region, and use of previous biologic treatment-
by-study region interaction will be added into the model as covariates. 
7.5.2.4 
sPGA 
The algorithm for sPGA scoring is provided in Section 8.1.2. 
The following analyses will be provided: 
• The sPGA score of 0/1 (0/cleared, 1/minimal)  versus > 1 will be presented using 
descriptive statistics (count and percentage) at Day 1, Day 8, Day 15, Day 29, Day 57, Day 
85, and Day 115 for each group. 
• To compare the response rates between each treatment group and placebo, the sPGA 
distribution of 0/1 vs. >1 at Day 85 will be analyzed by a two-sample Fisher’s exact test or 
a Chi-square test. The odds ratio and the difference in the response rates and their 
corresponding two-sided 95% CIs will be provided. 
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• A logistic regression model analysis will be performed to evaluate the impact of treatments 
on sPGA (0/1 vs. >1) at Day 85, with treatment group, age, gender, weight, BMI, baseline 
PASI score, use of previous biologic treatment, study region, and use of previous biologic 
treatment-by-study region interaction as covariates. 
The following by-subject listing will be provided:  
• sPGA: date of completion, visit, language code, BMS scale identifier, scale question 
identifier, sub-scale score (I/E/S), and sPGA score.   
7.5.2.5 
DLQI 
The following analyses will be provided: 
• The DLQI score will be presented using the descriptive statistics (n, mean, median, min, 
max, standard deviation, Q1, Q3) for each group at Day 1 (baseline), Day 29, Day 57, Day 
85, and Day 115. Point estimates for each visit and two-sided 95% CIs for mean change 
from baseline within each treatment group will be provided. 
• A mixed effect model analysis with repeated measures will be performed to evaluate the 
impact of treatments on DLQI score over time. The model will be fit with treatment, visit, 
and treatment-by-visit interaction as the fixed effects and measurements (changes from 
baseline) within each subject as the repeated measurements. The baseline value, use of 
previous biologic treatment, study region, and use of previous biologic treatment-by-study 
region interaction will be added into the model as covariates. Based on the mixed effect 
model, the estimate and 95% confidence interval will be calculated for the difference 
between each active treatment and the placebo at each specified visit.  
The following by-subject listing will be provided:  
• DLQI: date of completion, visit, language code, BMS scale identifier, question 1-10, score 
total, and change from baseline. 
7.5.2.6 
BSA 
The following analyses will be provided: 
• BSA will be presented using the descriptive statistics (n, mean, median, min, max, standard 
deviation, Q1, Q3) for each group at Day 1, Day 8, Day 15, Day 29, Day 57, Day 85 and 
Day 115 for each group. Point estimates for each visit and two-sided 95% CIs for mean 
change from baseline within each treatment group will be provided. 
• A mixed effect model analysis with repeated measures will be performed to evaluate the 
impact of treatments on BSA over time.  The model will be fitted with treatment, visit, and 
treatment-by-visit interaction as the fixed effects and measurements (changes from 
baseline) within each subject as the repeated measurements. The baseline value, use of 
previous biologic treatment, study region, and use of previous biologic treatment-by-study 
region interaction will be added into the model as covariates. Based on the mixed effect 
model, the estimate and 95% confidence interval will be calculated for the difference 
between each active treatment and the placebo at each specified visit. 
The following by-subject listing will be provided:  
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• BSA: date of assessment, visit, BSA result (%), and change from baseline. 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
7.5.4 
Subgroup Analyses 
To investigate the impact of study region (Japan vs rest of world) and the use of previous biologic 
treatment on the primary efficacy endpoint, subgroup analyses will be performed. The Cochran–
Mantel–Haenszel Chi-square test on the response rates in PASI-75 at Day 85 will be conducted 
and the odds ratio (odd in a treatment group/odd in placebo) in the response rates and its 
corresponding two-sided 95% CI will be provided.   
7.5.5 
Sensitivity Analyses 
If more than 10% of total subjects in the efficacy analysis population discontinued due to any 
reasons other than lack of efficacy, AE or unknown reason, a sensitivity analysis may be performed 
for the primary efficacy endpoint. 
7.5.6 
Per-Protocol Analyses 
If at least 10% of total subjects in efficacy analysis population demonstrate relevant protocol 
deviations, a per-protocol analysis may be performed. A Per-protocol (PP) analysis population will 
exclude all subjects with at least one relevant protocol deviation (defined in Appendix 1) from the 
efficacy analysis population. A per-protocol analysis will be carried out for the primary efficacy 
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endpoint based on the PP analysis population. The grouping scheme will be the same as in the 
primary efficacy analysis. 
7.6 
Safety 
Unless otherwise specified, the safety data will be presented using the As-Treated Analysis 
Population by treatment group, BMS combined treatment group, and all treated subjects combined. 
All AEs will be coded using version 19.1 of the Medical Dictionary for Regulatory activities 
(MedDRA) to a standard system-organ class (SOC) and preferred term (PT). 
AEs are classified as treatment emergent (TEAEs) if they begin after the administration of study 
drug and within 30 days after the last dose. 
7.6.1 
Deaths 
A by-subject listing of deaths will be provided for the All Enrolled Subjects population. 
7.6.2 
Serious Adverse Events 
The following summary tables (counts and percentages) will be provided: 
• Serious TEAEs summary by SOC/PT 
• Serious drug-related TEAEs by SOC/PT 
A by-subject SAE listing will be provided. 
7.6.3 
Adverse Events Leading to Discontinuation of Study Therapy 
The following summary tables (counts and percentages) will be provided: 
• AEs leading to discontinuation by SOC/PT 
A by-subject listing of AEs leading to discontinuation of study therapy will be provided. 
7.6.4 
Adverse Events Leading to Dose Modification 
The following summary tables (counts and percentages) will be provided: 
• Summary of AEs leading to reduction and/or interruption by SOC/PT 
A by-subject listing of AEs leading to dose reduction and/or interruption will be provided. 
7.6.5 
Adverse Events 
The following summary tables (counts and percentages) will be provided: 
• TEAEs summary of by SOC/PT 
• Study drug-related TEAEs by SOC/PT 
A by-subject AE listing will be provided.   
7.6.6 
Clinical Laboratory Evaluations 
The following summary tables will be provided: 
• Laboratory Test Results Summary of Marked Laboratory Abnormalities: hematology, liver 
and kidney function, and chemistry panel. 
The following by-subject listings will be provided: 
• Marked Laboratory Abnormality Criteria. 
• Laboratory Listing by Lab Test.   
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• Subjects meeting marked laboratory abnormality criteria. 
• Subjects with aspartate transaminase (AST)/alanine transaminase (ALT)>3x upper limit of 
normal (ULN) and total bilirubin>2xULN on the same date.  
7.6.7 
Electrocardiogram 
Summary statistics (n, mean, standard deviation, median, minimum, and maximum) will be 
presented for each ECG parameters and the corresponding changes from baseline by treatment and 
visit. The baseline value is defined as the last measurement before the first dose. ECG readings 
will be evaluated by the Investigator and abnormalities, if present, will be listed. 
The frequency distribution of subjects’ maximum recorded post-dose QTcF, PR, QRS and 
∆QTcF will be summarized by treatment group for the following ranges: 
• QTcF: QTcF ≤ 450 msec, 450 msec < QTcF ≤ 480 msec, 480 msec < QTcF ≤ 500 msec, 
QTcF > 500 msec 
• PR: PR ≤ 200 msec, PR > 200 msec 
• QRS: QRS ≤ 120 msec, QRS > 120 msec 
• 
∆QTcF: ∆QTcF ≤ 30 msec, 30 msec < ∆QTcF ≤ 60 msec, ∆QTcF > 60 msec 
 
Individual QTcF, PR, QRS or ∆QTcF values meeting the above criteria will be flagged in the data 
listing.  
 
The following summary tables will be provided: 
• Electrocardiogram Summary: Summary Statistics for ECG Values and changes from 
baseline 
• Frequency Distribution of Maximum Post-Dose ECG Interval 
The following by-subject listings will be provided: 
• Electrocardiogram (ECG) Results: visit, date, study day, heart rate (bpm), interval (PR, 
QRS, QT, QTC), interpretation of findings. 
• Investigator Identified Abnormal ECG Results: visit, date, study day, heart rate (bpm), 
interval (PR, QRS, QT, QTC), interpretation of findings 
• Subjects with Heart Rates and Out-Of-Range ECG Intervals: visit, date, study day, time, 
heart rate (bpm), interval (PR, QRS, QT, QTcB, QTcF), change from baseline (HR, PR,    
QRS, QT, QTcB, QTcF). 
7.6.8 
Vital Signs and Physical Findings 
Vital signs parameters (systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate 
and body temperature) will be listed. Summaries of vital sign parameters and respective changes 
from baseline will be provided at corresponding visits by treatment group. Subjects with vital signs 
outside of a pre-specified range will also be listed. 
 
The following criteria will be used to determine vital sign results that are outside of a pre-specified 
range, where changes from baseline are based on matched postural positions and are calculated as 
parameter value - baseline parameter value: 
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The following summary tables will be provided: 
• Vital Signs Summary: Summary Statistics for Vital Signs and Changes from Baseline 
The following by-subject listings will be provided: 
• Vital Signs by Subject: visit, date, study day, position, blood pressure (mmHg), heart rate 
(bpm), respiration rate (breaths/min), temperature (○C). 
• Subjects with Out-Of-Range Vital Signs: visit, date, study day, position, blood pressure 
(mmHg) (systolic, diastolic), pulse rate (bpm), respiration rate (breaths/min), temperature 
(○C), criteria. 
• Physical Examination with Abnormal Finding: examine criteria, abnormality. 
7.6.9 
Other Observations Related to Safety 
The following by-subject listings will be provided:  
• Medical Treatment Procedures: procedure, start and stop date, reason for procedure. 
• Diagnostic Procedures: procedure, date of procedure, reason for procedure, findings. 
7.7 
Pharmacokinetic Results 
The PK analysis will be performed for the Pharmacokinetic Population. Samples for PK 
assessment will be collected per the Pharmacokinetics Sampling Schedule as described in Table 
5.5.1-1 of the study protocol. The summary statistics of BMS-986165 concentrations will be 
provided by treatment group and nominal visit.   
The following summary table will be provided: 
• Summary Statistics of Ctrough (mean, SD, geometric mean, % CV, median, min, and max). 
The following by-subject listing will be provided: 
• Concentration of BMS-986165, including treatment, study day, actual time of sampling, 
and nominal time. Actual time since previous dose and actual time since Day 1 will be 
calculated and included in the listing for samples other than Ctrough. 
The following graph will be provided: 
Table 7.6.8-1: 
Vital Sign Parameter Cut-Off Values 
Heart Rate(bpm) 
Value > 100 and change from baseline > 30, or 
Value < 55 and change from baseline < -15 
Systolic BP(mmHg) 
Value > 140 and change from baseline > 20, or 
Value < 90 and change from baseline < -20 
 
Diastolic BP(mmHg) 
Value > 90 and change from baseline > 10, or 
Value < 55 and change from baseline < -10 
 
Respiration(breaths/min) 
Value > 16 or change from baseline > 10 
 
Temperature (°C) 
Value > 38.3°C or change from baseline > 1.6°C 
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• Plot of Ctrough over time (Mean +/-SD) by treatment arm. 
• Plot of individual Ctrough over time. 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8 
CONVENTIONS 
8.1 
Calculations of Key Measures 
8.1.1 
Evaluation of PASI 
The PASI is a grading system used for the evaluation of the severity of psoriatic lesions and their 
response to treatment. The PASI produces a numeric score that can range from 0 to 72. The severity 
of a subject’s disease is calculated as described below: 
In the PASI system, the body is divided into 4 regions: the head (h), trunk (t), upper extremities 
(ux) and lower extremities (lx), which account for 10%, 30%, 20%, and 40% respectively of the 
total body surface area (BSA). Each of these areas are evaluated for erythema, induration and 
scaling, which are rated on a scale from 0 to 4. 
The scoring system for the signs of disease (erythema, in duration and scaling) is below: 
0 = none 
1 = slight 
2 = moderate 
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3 = severe 
4 = very severe 
The scoring system for estimating the area of involvement for psoriatic lesions is outlined below: 
0 = no involvement 
1 = 1% to 9% involvement 
2 = 10% to 29% involvement 
3 = 30% to 49% involvement 
4 = 50% to 69% involvement 
5 = 70% to 89% involvement 
6 = 90% to 100% involvement 
To aid in the area assessments, the following conventions are followed: 
a. 
the neck is considered part of the head 
b. 
the axilla and groin are considered part of the trunk 
c. 
the buttocks are considered part of the lower extremities 
The PASI formula is: 
PASI = 0.1(Eh + Sh + Ih)Ah + 0.3(Et + St + It)At + 0.2(Eux + Sux + Iux)Aux + 0.4(Elx + Slx+ Ilx)Alx 
8.1.2 
Evaluation of sPGA 
The sPGA is used to determine the subject’s psoriasis lesions overall at a given time point. Overall 
lesions will be graded for induration, erythema, and scaling based on the scales below. The sum 
of the 3 scales will be divided by 3 to obtain a final PGA score. 
Induration (I) (averaged over all lesions; use the National Psoriasis Foundation Reference card for 
measurement) 
0 = no evidence of plaque elevation 
1 = minimal plaque elevation, = 0.25 mm 
2 = mild plaque elevation, = 0.5 mm 
3 = moderate plaque elevation, = 0.75 mm 
4 = marked plaque elevation, = 1 mm 
5 = severe plaque elevation, = 1.25 mm or more 
Erythema (E) (averaged over all lesions) 
0 = no evidence of erythema, hyperpigmentation may be present 
1 = faint erythema 
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2 = light red coloration 
3 = moderate red coloration 
4 = bright red coloration 
5 = dusky to deep red coloration 
Scaling (S) (averaged over all lesions) 
0 = no evidence of scaling 
1 = minimal; occasional fine scale over less than 5% of the lesion 
2 = mild; fine scale dominates 
3 = moderate; coarse scale predominates 
4 = marked; thick, nontenacious scale dominates 
5 = severe; very thick tenacious scale predominates 
Add I + E + S = / 3 = (Total Average) 
Physician’s Static Global Assessment based upon above Total Average 
0 = Cleared, except for residual discoloration 
1 = Minimal - majority of lesions have individual scores for I + E + S / 3 that averages 1 
2 = Mild - majority of lesions have individual scores for I + E + S / 3 that averages 2 
3 = Moderate - majority of lesions have individual scores for I + E + S / 3 that averages 3 
4 = Marked - majority of lesions have individual scores for I + E + S / 3 that averages 4 
5 = Severe - majority of lesions have individual scores for I + E + S / 3 that averages 5 
Note: Scores should be rounded to the nearest whole number. If total ≤ 1.49, score = 1; if total ≥ 
1.50, score = 2. 
8.2 
Baseline Measures 
The baseline value is the last assessment taken prior to the first dose of study medication. In 
general, baseline value is the assessment taken on study Day 1 before the administration of study 
medication. If a measurement on Day 1 is missing, the last assessment taken at the screening period 
prior to the first dose of study medication will be used. 
8.3 
Missing Measurements 
8.3.1 
Imputation of Missing Data for Binary Variables 
This imputation is applicable for all binary variables (PASI-50, PASI-75, PASI-90, PASI-100, 
sPGA score of 0/1). 
If the response cannot be assessed due to missing data or a subject’s early discontinuation, the 
following conventions will be implemented in a sequence: 
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• Any subject who prematurely discontinues the trial during the treatment period after receiving 
study medication will have data imputed as non-responder at all scheduled protocol visits 
subsequent to the point of discontinuation up to the end of the treatment period. 
• If for some reason the binary variable still cannot be determined, including the case where 
baseline data is missing, then the value will be set to non-responder. 
Efficacy data (PASI-50, PASI-75, PASI-90, PASI-100, sPGA score of 0/1) will be presented after 
imputation; and the number of the subjects with missing efficacy measures in each treatment group 
will be provided.   
For listings, missing responses will be presented as missing. 
8.3.2 
Imputation of Missing Data for Continuous Variables 
For analyses of change from baseline in efficacy measures, missing values will be dealt with via 
the longitudinal repeated measures analysis assuming MAR (missingness at random). 
For all safety (including laboratory measurements) and PK measures, missing values will not be 
imputed. 
8.4 
Missing, Unknown or Partial Dates 
The BMS safety guidelines for conventions relating to the handling of missing or partial dates and 
the determination of appropriate default values in such cases (in particular, for concomitant 
medication dose start-dates and end-dates and AE onset dates) will be utilized. 
The following conventions may be used for imputing partial dates for analyses requiring dates: 
For missing and partial adverse event onset dates, imputation will be performed using the Adverse 
Event Domain Requirements Specification1. 
For missing and partial adverse event resolution dates, imputation will be performed as follows 
(these conventions may change): 
• If only the day of the month is missing, the last day of the month will be used to replace the 
missing day. 
• If the day and month are missing or a date is completely missing, it will be considered as 
missing. 
Missing and partial non-study medication domain dates will be imputed using the derivation 
algorithm described in 4.3.3 of BMS Non-Study Medication Domain Requirements 
Specification2. 
For other partial/missing dates, the following conventions may be used: 
• If only the day of the month is missing, the 15th of the month will be used to replace the 
missing day. 
• If both the day and the month are missing, “July 1” will be used to replace the missing 
information. 
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• If a date is completely missing, it will be considered as missing. 
The following conversion factors will be used to convert days to months or years: 1 month = 
30.4375 days and 1 year = 365.25 days. 
All statistical analyses will be carried out using SAS (Statistical Analysis System software, SAS 
Institute, North Carolina, USA) unless otherwise noted. 
8.5 
Day Ranges for Analysis of Time Points 
Subjects who do not always adhere strictly to the visit schedule timing in the protocol. Therefore, 
the designation of visits during the treatment period of the study will be based on the day of 
evaluation relative to the trial (day of first study medication = study Day 1) rather than the nominal 
visit recorded in the eCRF. Mutually exclusive relative day windows are defined below to provide 
derived visits that correspond to the post-baseline time points. If a visit falls outside of the pre-
specified visit windows, then the data collected at that visit will not be assigned a derived visit but 
will remain in the derived data sets. Determination of baseline values is addressed in Section 8.2. 
If a subject has more than 1 visit where a measurement is recorded within a window, the 
measurement closest to the target day will be used. In case of 2 visits being equidistant from the 
target, the earlier measurement will be used in analyses. For these safety indicators, the least 
favorable value (toward a positive response) in the window will be used. 
Designation of visits for efficacy assessments during the treatment period is tabulated below. 
 
 
 
 
 
 
 
 
* DLQI is not assessed on Day 8 and Day 16. Days range for DLQI of Day 29 is 2-43. 
 
9 
CONTENT OF REPORTS 
All analyses described in this SAP will be included in the Clinical Study Report except where 
otherwise noted. Other analyses may be performed upon the request of the study team. Refer to 
the Data Presentation Plan for mock-ups of all tables and listings. 
 
 
    
 
Table 8.5-1: 
Day Ranges for Efficacy Assessments  
Visit 
Target Day 
Days Range 
 
Baseline/Day 1 
Day 8 
Day 15 
Day 29 
Day 57 
Day 85 
1 
8 
15 
29 
57 
85 
1 
2-11 
12-22 
23-43 * 
44-71 
72-100 
 
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DOCUMENT HISTORY 
Table 10-1: 
Document History 
Version 
Author 
Summary of Changes 
1.0 
Mei Jiang 
Original version 
2.0 
Mei Jiang 
• 
Revised the definitions of some endpoints  
- Changed “after 12 week” to “at Day 85” 
- Revised wording for secondary endpoints in Section 4.2   
• 
Further clarified the analysis: 
- Rearranged the analyses Sections 
- Added how to calculation PASI-75 from the PASI scores 
- Added sub-sections for subgroup analysis, sensitivity analysis, 
and per-protocol analysis under section 7.5  
- Added “change from baseline” or “percentage change from 
baseline” for continuous efficacy endpoints and key endpoints 
(PASI-75, etc.) in the listing 
- Added a treatment compliance section under section 7.4 
- Modified listing for study medication administration 
- Changed confidence level from 90% to 95% 
• 
Fixed several typos in the text 
• 
Fixed format for some bullets 
 
 
 
 
APPENDIX 1 
RELEVANT RROTOCOL DEVIATIONS 
 
Eligibility Deviations: 
• Subjects with a diagnosis of plaque psoriasis for < 6 months  
• Body mass index (BMI) not within 18-40 kg/m2 or total body weight ≤ 50 kg (110 lb.) 
• Subject with psoriatic plaques cover <  10% of body surface area (BSA)  
• Subject with PASI score < 12 or sPGA < 3 
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• Diagnosis of non-plaque psoriasis  
 
Incorrect dosing: 
• Subjects who receive treatment different than randomized group 
• Subjects taking less than 80% or more than 120% of the planned medication during the entire 
treatment period 
• Randomized subjects who do not take any blinded study medication for ≥ two consecutive 
weeks 
• Restricted and Prohibited medications (refer to Protocol Section 3.4.1): 
• Subjects receiving prohibited concomitant treatments while on study therapy. The prohibited 
and/or restricted treatments are described in Table 3.4.1-1 of the study protocol. 
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