A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of BMS-986165 in Subjects With Moderate-to-Severe Plaque Psoriasis
Phase: PHASE3
Conditions: Psoriasis
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
An Investigational Study to Evaluate Experimental Medication BMS-986165 Compared to Placebo in 
Participants With Plaque Psoriasis (POETYK-PSO-3) in Mainland China, Taiwan, and South Korea 
(POETYK-PSO-3) 
 
NCT Number: NCT04167462 
Document Date (Date in which document was last revised): 11-Nov-2020 

Page:
1
Protocol Number:
IM011065
IND Number:
131,993
EX-US
Non-IND
EUDRACT Number:
N/A
Date:
11-Nov-2020
Revised Protocol 05, Final Approved
Clinical Protocol IM011065:
A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate 
the Efficacy and Safety of BMS-986165 in Subjects With Moderate-to-Severe Plaque 
Psoriasis
Short Title: Efficacy and Safety of BMS-986165 versus Placebo in Subjects with Plaque 
Psoriasis
Revised Protocol 05
Site Number: All sites in Mainland China, Taiwan, and South Korea
Study Director
Medical Monitor
24-hr Emergency Telephone Number
North America: 
Asia Pacific: 
Bristol-Myers Squibb Research and Development
3401 Princeton Pike
Lawrenceville, NJ 08648
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
6-5-1 Nishi-Shinjuku, Shinjuku-ku,
Tokyo, 163-1328, Japan
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 
Approved
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Clinical Protocol 
IM011065 
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
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 (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must 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, eg, a Contract Research Organization 
(CRO).
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
DOCUMENT HISTORY
Document
Date of Issue
Approver(s)
Summary of Change
Revised 
Protocol 05
(im011065-
revprot05)
11-Nov-2020
-Added a Week 16 database
lock so the analysis of the
efficacy and safety data
collected up to Week 16
could be performed after the
double-blind portion of the
study is complete
-Clarified the unblinding
procedures for personnel
performing the Week 16
primary endpoint analysis
Revised 
Protocol 03b 
South Korea–
specific
(Revised 
Protocol 05a)
(im011065-
revprot03b-sk-
specific)
18-Sept-2020
Korea-Specific Revised 
Protocol - Included changes 
listed above for the Global 
Revised Protocol 04
Revised 
Protocol 04
(im011065-
revprot04)
19-Jun-2020
-Provided clarifications in
the protocol to aid sites and
subjects in the conduct of
the study
-Updated sample size from
180 subjects to
approximately 219 subjects
-Added and updated
relevant protocol deviation
criteria for the Per Protocol
Set
-Corrected typographical
errors
-In the set of subgroup
analyses for the coprimary
efficacy endpoints, added a
new analysis for systemic
treatment-naïve subjects.
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Document
Date of Issue
Approver(s)
Summary of Change
Revised 
Protocol 03a 
South Korea–
specific 
(Revised 
Protocol 04a)
(im011065-
revprot03a-sk-
specific)
05-Jul-2019
South Korea–specific 
Revised Protocol to include 
HBV DNA monitoring 
plans for subjects who are 
HBsAg-, and HBsAb+
and/or HBcAb+.
Revised 
Protocol 03 
(Amendment 
03a)
(im011065-
revprot03)
24 June 2019
-Updated the Sponsor’s 
contact information, made 
typographic corrections to 
the protocol, and revised 
certain exclusion criteria to 
be consistent with certain 
elements of the Phase 2 
study of BMS-986165 in 
psoriasis as well as other 
Phase 3 studies in psoriasis.
-Updated text in the 
definition of sPGA in 
Section 8.1.1.1 to be 
consistent with the 
description in Appendix 5. 
 
 
 
 
 
 
 
 
-Removed ‘change from 
baseline in DLQI score.’ 
The reason for this change 
is that DLQI endpoint 
‘DLQI 0/1 among subjects 
with baseline DLQI score 
≥2’ is clinically meaningful 
and is already in the 
hierarchy.
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Document
Date of Issue
Approver(s)
Summary of Change
Revised 
Protocol 02 
(Amendment 
02a)
(im011065-
revprot02)
09 April 2019
Includes modifications to 
protocol sections affected 
by removal of sites in 
Singapore, where the -065 
study will no longer be 
conducted. Overall, the 
subject population will 
remain at 180 subjects and 
enrollment will be 
competitive.
Revised 
Protocol 01 
(Amendment 
01a)
(im011065-
revprot01)
03 December 
2018
Includes modifications to 
protocol sections affected 
by the addition to this 
mainland China-specific 
study of one region 
(Taiwan) and two countries 
where the -065 study will 
also be conducted 
(Singapore and South 
Korea). Overall, the subject 
population will remain at 
180 subjects and enrollment 
will be competitive.
Original 
Protocol
(im011065-
prot)
22 June 2018
N/A
a Document naming conventions have been updated. Legacy
numbering is provided for consistency.
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
OVERALL RATIONALE FOR REVISED PROTOCOL 05:
Rationale:
The primary purpose of this global revised protocol is to provide clarifications in the protocol to 
aid sites and subjects in the conduct of the study.
Key modifications and clarifications are summarized as follows: 
•
Added a Week 16 database lock so the analysis of the efficacy and safety data collected up
to Week 16 could be performed after the double-blind portion of the study is complete
•
Clarified the unblinding procedures for personnel performing the Week 16 primary
endpoint analysis
Substantive changes made to the previous version of the global protocol and the rationale for these 
changes are noted below in the summary of key changes table. All changes applied to the protocol 
body were applied to the synopsis, as necessary; synopsis changes are not included in the summary 
of key changes table. Only major additions and deletions are provided in this summary document; 
all minor grammatical, formatting, stylistic changes, or clarifications as well as organizational 
changes are not included.
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL05:
Protocol Section
Revised Protocol Text
Rationale for Change
Study 
Acknowledgment
/Disclosure
This page was removed.
To conform to the BMS 
protocol model document,
this page is now provided as a 
standalone document.
1.3 Schedule of 
Activities
Updated row in Table 1 (Screening Procedures):
Fasting Lipid Panel
Added text in the Notes column for this row:
Subjects are required to fast for at least 10 hours prior to 
collection.
Clarified that the lipid panel 
in the Screening Procedures 
should be performed after the 
subject has fasted for 
10 hours, like other lipid 
panels in the study
 
9.4 Efficacy 
Analyses
9.4.1.2 
Sensitivity 
Analyses for the 
Coprimary 
Endpoints
9.6.3 Relevant 
Protocol 
Deviations
Updated text in Section 9.4:
Details of the planned analyses of endpoints during 
the 16-week double-blind placebo-controlled period
will be documented in the statistical analysis plan 
(SAP) and finalized before the Week 16 database 
lock.
Updated text in Section 9.4.1.2:
Clarified that the database 
lock mentioned in each 
section refers to the newly
added Week 16 database lock
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL05:
Protocol Section
Revised Protocol Text
Rationale for Change
Sensitivity analyses to be performed for the coprimary 
endpoints will be described in the SAP prior to the 
Week 16 database lock.
Updated text in Section 9.6.3:
All subjects with relevant protocol deviations will be 
identified prior to the Week 16 database lock.
6.3.3 Unblinding
for Week 16 
Primary Endpoint 
Analysis
Added section:
An unblinded analysis of data through Week 16 will 
be performed after all subjects complete their 
Week 16 visit or have discontinued prior to Week 16. 
A select group of personnel who are not involved in 
the conduct of the study will review the results to 
write a clinical study report. Following the Week 16 
analysis until the end of the study, the investigators, 
subjects, and clinical trial team members who directly 
cooperate with the site staff will continue to remain 
blinded to the initial treatment assignment. Details of 
maintaining the blind following the unblinded 
analysis will be finalized prior to the Week 16 
database lock. A final analysis will be performed after 
all subjects complete the Week 52 visit or discontinue 
prior to the Week 52 visit, and a clinical study report 
will be written.
Clarified the unblinding 
procedures for the personnel 
performing the Week 16 
primary endpoint analysis
9.8 Analysis and 
Reporting
Added section:
An unblinded analysis of the data collected up to 
Week 16 will be conducted once all randomized 
subjects have either completed the placebo-controlled
treatment period (ie, through Week 16) or have 
discontinued prior to Week 16. Details of these 
analyses will be provided in an SAP that will be 
finalized before the Week 16 database lock. A final
database lock and analysis will occur after all subjects 
complete Week 52 or discontinue prior to Week 52.
Added a Week 16 database 
lock so the analysis of the 
efficacy and safety data 
collected up to Week 16 
could be performed after the 
double-blind portion of the 
study is complete
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
TABLE OF CONTENTS .............................................................................................. 
11 APPENDICES ......................................................................................................... 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW-UP, AND REPORTING ....................................................................... 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINTIONS AND 
METHODS OF CONTRACEPTION ..................................................................... 
APPENDIX 5 STATIC PHYSICIAN’S GLOBAL ASSESSMENT OF PSORIASIS 
(SPGA) .................................................................................................................... 
APPENDIX 6 PSORIASIS AREA AND SEVERITY INDEX (PASI) ....................... 
APPENDIX 7 SCALP-SPECIFIC PHYSICIAN’S GLOBAL ASSESSMENT 
(SSPGA) ................................................................................................................. 
APPENDIX 9 PHYSICIAN’S GLOBAL ASSESSMENT-FINGERNAILS (PGA-F)
................................................................................................................................. 
APPENDIX 11 PALMOPLANTAR PSORIASIS PHYSICIAN’S GLOBAL 
ASSESSMENT (PP-PGA)...................................................................................... 
APPENDIX 13 PSORIASIS SYMPTOMS AND SIGNS DIARY (PSSD) ................. 
APPENDIX 14 DERMATOLOGY LIFE QUALITY INDEX (DLQI) ....................... 
APPENDIX 20 PSORIATIC ARTHRITIS SCREENING AND EVALUATION 
(PASE) QUESTIONNAIRE ................................................................................... 
APPENDIX 21 EIGHT-ITEM PATIENT HEALTH QUESTIONNAIRE (PHQ-8) ... 
APPENDIX 22 SUICIDAL IDEATION AND BEHAVIOR CATEGORIES AND 
DEFINITIONS ........................................................................................................ 
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study 
to Evaluate the Efficacy and Safety of BMS-986165 in Subjects with Moderate-to-Severe Plaque 
Psoriasis
Short Title: Efficacy and Safety of BMS-986165 versus Placebo in Subjects with Plaque Psoriasis
Study Phase: 3
Rationale:
BMS-986165 is being evaluated as a therapeutic option for the treatment of subjects with 
moderate-to-severe plaque psoriasis based on results of a recently completed 12-week,
randomized, Phase 2, placebo-controlled, parallel-group study (Study IM011011). The Phase 2 
study was conducted with the following 5 different BMS-986165 treatment arms: 3 mg every other 
day (QOD); 3 mg once daily (QD); 3 mg twice daily (BID); 6 mg BID; and 12 mg QD. Overall, 
267 subjects were randomized (44 to 45 subjects per treatment arm) in the Phase 2 study. All 
BMS-986165 treatment groups, except 3 mg QOD, achieved the primary endpoint of superiority 
compared to placebo in the proportion of subjects experiencing at least a 75% improvement in the 
Psoriasis Area and Severity Index (PASI 75) after 12 weeks of treatment. Compared with the 
placebo treatment group (6.7%), 38.6% (p = 0.0003), 68.9% (p < 0.0001), 66.7% (p < 0.0001) and 
75% (p < 0.0001) of the subjects treated with BMS-986165 at 3 mg QD, 3 mg BID, 6 mg BID and 
12 mg QD doses achieved a PASI 75 response respectively. The PASI 75 responses appear to 
plateau at the dose of 3 mg BID. The Phase 3 IM011065 study is designed to confirm the efficacy 
and safety of BMS-986165 6 mg QD, which is expected to have equivalent efficacy as the 3 mg 
BID dose in Phase 2, in a population of subjects with stable moderate-to-severe plaque psoriasis.
Study Population:
Study IM011065 will enroll subjects in mainland China, Taiwan, and South Korea. Men and 
women ≥18 years of age diagnosed with stable (defined as no morphology changes or significant 
flares of disease activity in the opinion of the investigator) plaque psoriasis for ≥6 months and with
moderate-to-severe disease characterized by involvement of ≥10% of body surface area (BSA),
static Physician’s Global Assessment (sPGA) ≥3, and a PASI score ≥12, and who are candidates
for phototherapy or systemic therapy (Section 5.1) will be eligible to participate in the study.
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Objectives and Endpoints:
Objective
Endpoint
Primary
•
Assess whether BMS-986165 is superior to
placebo at Week 16 in the treatment of subjects
with moderate-to-severe plaque psoriasis
•
sPGA 0/1
•
PASI 75
Selected Secondary Endpoints
•
Assess whether BMS-986165 is superior to
placebo over the first 16 weeks of treatment
•
sPGA 0/1
•
PASI 90
•
sPGA 0
•
PASI 100
•
Evaluate improvement in patient reported
outcomes for BMS-986165 compared with
placebo through Week 16
•
Change from baseline in Psoriasis Symptoms and
Signs Diary (PSSD) symptom score
•
PSSD symptom score of 0 (among subjects with a
baseline PSSD symptom score ≥1)
Overall Design:
This will be a 52 week, multicenter, randomized, double-blind, placebo-controlled study in 
subjects with stable moderate-to-severe plaque psoriasis. Subjects will undergo screening 
evaluations within 28 days prior to administration of study treatment to determine eligibility. 
Following the screening process, approximately 219 subjects will be randomized in a 2:1 ratio to 
either BMS-986165 6 mg QD or placebo, respectively.
Randomization should not occur until at least 8 days after the screening visit to allow collection 
of PSSD data during screening in order to calculate a baseline PSSD score. Randomization will be 
stratified by country (mainland China vs. non-mainland China) and previous biologic use (for 
psoriasis, psoriatic arthritis or other inflammatory diseases only; yes/no).
At Week 16, subjects randomized to placebo from screening through the Week 16 visit will be 
switched to BMS-986165 6 mg QD through Week 52 in a blinded manner, so that subjects who 
had been randomized to placebo will not know if they had been randomized to BMS-986165 or to 
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
placebo post-screening. Subjects randomized to BMS-986165 6 mg QD will continue their current 
dose through Week 52.
At Week 24, a subject with sPGA ≥3 may be treated with restricted topical medications, such as 
topical high potency corticosteroids (WHO Classes I-V) but only at this time point and at the 
discretion of the investigator. This treatment may be continued through end of study.
Subjects who discontinue study treatment early are expected to remain in the study for continued 
follow-up until Week 52.
Subjects completing 52 weeks of treatment may be eligible to roll over to a separate long-term 
extension study and be treated with open-label BMS-986165 6 mg QD.
Subjects who choose not to roll over to the long-term extension study at Week 52 will be followed 
up for safety for 4 additional weeks, from Week 52 through Week 56.
Treatment Arms and Duration:
Study treatment: Subjects in both treatment groups will take oral doses of one of the 
investigational product (IP), either BMS-986165 or placebo QD, for 16 weeks. After Week 16, all 
subjects will receive BMS-986165.
Study Drug for Study IM011065
Medication 
Potency 
IP/Non-IP 
BMS-986165 tablet
6 mg
IP
placebo tablet
n/a
IP
•
IP = Investigational Product; n/a = not applicable.
Statistical Methods:
General Methodology
The primary efficacy analysis population will be the Full Analysis Set (FAS). The FAS will 
include all subjects who were randomized to receive assigned study treatment. 
The analysis model for the coprimary efficacy endpoints and secondary binary endpoints will use 
stratified Cochran-Mantel-Haenszel (CMH) tests stratified by country (mainland China vs. 
non-mainland China) and previous biologic treatment use for psoriasis, psoriatic arthritis or other 
inflammatory disease (yes/no) to compare the response rates of BMS-986165 6 mg QD to placebo
(see also Section 4.1.2). Nonresponder imputation will be used for binary endpoints for subjects 
who discontinue early, start a protocol prohibited medication/therapy that could improve psoriasis, 
or who have otherwise missing endpoint data prior to the specified timepoint.
The analysis model for continuous secondary endpoints will use analysis of covariance 
(ANCOVA) with treatment and previous biologic treatment use for psoriasis, psoriatic arthritis or 
other inflammatory disease (yes/no) as fixed effects. The baseline value will be added to the model 
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
as a covariate. Treatment differences based on least-squares (LS) means and the corresponding 
2-sided 95% confidence intervals (CIs) will be provided for the difference between BMS-986165
6 mg QD and placebo for each endpoint being assessed.
Testing Strategy for Efficacy Endpoints
The primary family of coprimary endpoints will each be tested at a probability of making a Type 
I error of 0.05 first, and if significant for both endpoints, testing will proceed for the secondary 
family of key secondary endpoints. The primary family of coprimary endpoints will be the serial 
gatekeeper for proceeding with testing of the secondary family of key secondary efficacy
endpoints.
Primary Family – Coprimary endpoints compared with placebo; both must be significant at the
probability of making a Type I error of 0.05 in order to proceed with the secondary family tests 
for the key secondary endpoints: 
•
Primary 1: Proportion of subjects who achieve sPGA 0/1 at Week 16
•
Primary 2: Proportion of subjects who achieve PASI 75 at Week 16
In order to control for Type I error rate inflation within the secondary family of key secondary 
endpoints, a hierarchical testing method will be implemented for the key secondary endpoints. A 
hierarchical test may only proceed to the next key secondary endpoint if the null hypothesis is 
rejected at a probability of making a Type I error of 0.05. If an endpoint fails at any step, then all 
subsequent p-values will be considered descriptive.
Safety Analysis
Safety data will be summarized using descriptive statistics (n, mean, standard deviation, median, 
minimum, and maximum) for continuous variables and frequency distributions (counts and 
percentages) for categorical variables.
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
1.2
Schema
QD = once daily
The coprimary endpoints will be evaluated at Week 16. The duration of the study for each 
participant will be up to 52 weeks on treatment and 4 additional weeks for safety follow-up.
1.3
Schedule of Activities (SOA)
The schedules of assessments and procedures are documented in Table 1 for screening, Table 2
for baseline through Week 20, and Table 3 for Week 24 through Week 52.
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 1:
Screening Procedural Outline (IM011065)
Procedure
Screening
V1
Notes
Eligibility Assessments
Informed Consent
X
A subject is considered enrolled only when a protocol-specific informed consent is 
signed.
Enroll Subject
X
Obtain number from IRT
Inclusion/Exclusion Criteria
X
Includes duration of plaque psoriasis and documentation of presence of plaque 
psoriasis by the investigator
Medical History
X
See Section 5.2 for complete eligibility criteria associated with medical history. Of 
note, subjects need to be screened for any current uncontrolled neuropsychiatric 
illness or history of suicidality; any history of TB; any congenital or acquired 
immunodeficiency; any significant drug allergy such as anaphylaxis; any cancer 
currently or in the previous 5 years. Investigators are encouraged to check whether 
subjects have had preventive health measures such as cancer screening (e.g. Pap 
smear, colonoscopy, mammograms) that is up to date according to local guidelines
History of Tobacco Use
X
Include description of current tobacco use.
Psoriasis-related History
X
Includes scalp symptoms, PsA/joint pain, nail involvement, palmoplantar 
involvement, genital involvement, history of other forms of psoriasis.
Psoriasis-related Systemic Treatment
X
History of: conventional systemic (eg, methotrexate), biologic, and/or 
phototherapy. For each therapy, include length of time on treatment and reason(s) 
for discontinuation (eg, lack of efficacy, intolerance, side effects, loss of access to 
treatment), if applicable. 
Other Prior and Concomitant Treatment
X
Includes topical treatments and shampoos for psoriasis and all medications for other 
conditions such as cardiovascular and mood disorders.
Safety Assessments
Physical Examination
X
Complete PE
Physical Measurements
X
Includes height and weight.
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.
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 1:
Screening Procedural Outline (IM011065)
Procedure
Screening
V1
Notes
Electrocardiogram
X
ECGs should be recorded after the subject has been supine for at least 5 minutes. 
Chest Imaging (eg, Chest x-ray)
X
Chest imaging is required if not performed within 6 months of screening visit, copy 
of radiology report must be on file and reviewed by the investigator. Section 8.4.4.
Neuropsychiatric Illness Assessment
X
Based on subject/family response, medical history/medical records, investigator 
judgment
PHQ-8
X
For establishing baseline depression severity
Suicidal Ideation and Behavior Assessment
X
Based on subject/family response, medical history/medical records, investigator 
judgment
eC-SSRS
X
eC-SSRS Assessment: Response of “Actual Suicide Attempt-Lifetime” or suicidal 
ideation (Severity of 4 or 5) or suicidal behavior will be exclusionary. Rescreening
will not be allowed. Section 8.4.7
Monitor for SAEs
X
All SAEs must be collected from the date of subject’s written consent until 30 days 
post discontinuation of dosing or subject’s participation in the study.
Laboratory Tests
Hematology
X
Complete Blood Count (CBC) with differential
Chemistry Panel
X
Fasting Lipid Panel
X
Subjects are required to fast for at least 10 hours prior to collection.
Urinalysis
X
Hemoglobin A1C
X
TSH
X
If TSH above normal reference range, test free T4; if TSH below normal range, test 
free T4 & T3..
hs-CRP
X
Serology
X
Includes HCV antibody, HBsAg, HBsAb, HBcAb, HBV DNA, and HIV 
antibodies.
TB Test
X
In accordance with QuantiFERON-TB (details described in Section 8.4.4).
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 1:
Screening Procedural Outline (IM011065)
Procedure
Screening
V1
Notes
Pregnancy Test (serum)
X
For WOCBP only
FSH
X
To confirm menopausal status (see APPENDIX 4)
Clinical Efficacy/Health Outcomes
sPGA
X
PASI
X
BSA
X
PASE Questionnaire
X
For subjects with peripheral joint complaints to screen for presence of psoriatic 
arthritis
PSSD
X
All consented subjects will be given a diary device at the Screening Visit and will 
begin recording psoriasis signs and symptoms on a daily basis in the diary device. 
Subjects who are not randomized will stop recording and return their diary device 
to the site. Subjects who are randomized will continue recording their psoriasis 
signs and symptoms on a daily basis in the diary device through Week 52.
BSA = body surface area; CBC = complete blood count; DNA = deoxyribonucleic acid; ECG = electrocardiogram; eC-SSRS = electronic Columbia Suicide 
Severity Rating Scale; FSH = follicle stimulating hormone; HBV = hepatitis B virus; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; 
HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human immunodeficiency virus; hs-CRP = high-sensitivity C-reactive protein; IRT = 
interactive response technology; PASE = psoriatic arthritis screening and evaluation; PASI = Psoriasis Area and Severity Index; PE = physical examination; PHQ-
8 = eight-item Patient Health Questionnaire; PsA = psoriatic arthritis; PSSD = Psoriasis Symptoms and Signs Diary; SAE = serious adverse vent; sPGA = static 
Physician Global Assessment; T3 = triiodothyronine; T4 = thyroxine; TB = tuberculosis; TSH = thyroid stimulating hormone; V = visit; WOCP = women of 
childbearing potential.
16
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3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 2:
On-Treatment Procedural Outline (IM011065): Week 0 through Week 20
Procedure
Week 0
Baseline / D1
V2
Week 1
D8
(±3 d)
V3
Week 2
D15
(±3 d)
V4
Week 4
D29
(±3 d)
V5
Week 8
D57
(±3 d)
V6
Week 12
D85
(±3 d)
V7
Week 16
D113
(±3 d)
V8
Week 20
D141
(±3 d)
V9
Notes
Clinical Efficacy/Health 
Outcomes
DLQI
X
X
X
X
X
X
X
sPGA
X
X
X
X
X
X
X
PASI 
X
X
X
X
X
X
X
ss-PGAa
X
X
X
X
X
X
PGA-Fb
X
X
X
X
Palmoplantar PGAc
X
X
X
X
X
X
17
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1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 2:
On-Treatment Procedural Outline (IM011065): Week 0 through Week 20
Procedure
Week 0
Baseline / D1
V2
Week 1
D8
(±3 d)
V3
Week 2
D15
(±3 d)
V4
Week 4
D29
(±3 d)
V5
Week 8
D57
(±3 d)
V6
Week 12
D85
(±3 d)
V7
Week 16
D113
(±3 d)
V8
Week 20
D141
(±3 d)
V9
Notes
PSSD
Safety Assessments
Complete PE
X
X
Targeted PE
X
X
X
X
X
X
See Section 8.4.1
Body Weight
X
X
Vital Signs
X
X
X
X
X
X
X
X
ECG
X
X
PHQ-8
X
X
X
See Section 8.4.6.1
eC-SSRS Assessment
X
X
X
Suicidal Ideation and 
Behavior since last 
visit
Adverse Event Assessment
X
X
X
X
X
X
X
X
Concomitant Medication Use
X
X
X
X
X
X
X
X
Laboratory Tests
Hematology
X
X
X
X
X
X
X
X
Lymphocytes Subsets (TBNK)
X
X
X
Chemistry Panel
X
X
X
X
X
X
X
X
If CK >2.5 × ULN, 
reflex testing is 
required (see 
Section 8.4.5)
Hemoglobin A1C
X
X
hs-CRP
X
X
X
X
X
X
X
18
Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 2:
On-Treatment Procedural Outline (IM011065): Week 0 through Week 20
Procedure
Week 0
Baseline / D1
V2
Week 1
D8
(±3 d)
V3
Week 2
D15
(±3 d)
V4
Week 4
D29
(±3 d)
V5
Week 8
D57
(±3 d)
V6
Week 12
D85
(±3 d)
V7
Week 16
D113
(±3 d)
V8
Week 20
D141
(±3 d)
V9
Notes
Fasting Lipid Panel
X
X
X
Subjects are required 
to fast for at least 10 
hours prior to 
collection
Fasting Plasma Glucose
X
X
X
Urinalysis
X
X
Serum Immunoglobulin Levels 
(IgM, IgG, IgA, IgE)
X
X
X
Pregnancy Test (Urine)
X
X
X
X
X
X
WOCBP Only
Study Treatment
Randomize
X
Dispense Study Treatment
X
X
X
X
X
X
X
Study Treatment Compliance
X
X
X
X
X
X
X
See Section 6.6
 CK = creatine kinase; D = Day; d = days; DLQI = Dermatology Life Quality Index; ECG = electrocardiogram; eC-SSRS = electronic Columbia Suicide 
Severity Rating Scale; 
 hs-CRP = high-sensitivity 
C-reactive protein; Ig = immunoglobulin; 
 PASI = Psoriasis Area and Severity Index; PE = physical examination; PGA = 
Physician’s Global Assessment; PGA-F = Physician Global Assessment-Fingernails; PHQ-8 = eight-item Patient Health Questionnaire; 
 PSSD = Psoriasis 
Symptoms and Signs Diary; 
 sPGA = static Physician Global Assessment; ss-PGA = scalp-
specific Physician’s Global Assessment; TBNK = T, B, and natural killer cells;
 Wk = Week; WOCP = women of childbearing potential.
Note: All visits ±3 Days
a In subjects with scalp psoriasis at baseline
b In subjects with nail psoriasis at baseline
19
Approved
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Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
c
In subjects with palmoplantar psoriasis at baseline
When multiple assessments are conducted at a single visit, the following is the order in which they should be done:
1)
Health outcomes assessments
2)
Safety assessments
3)
Clinical efficacy assessments
4)
Laboratory tests (eg, safety laboratory tests, 
On fasting days, safety assessments can be done first followed by blood draws, and then health outcomes and, finally, efficacy assessments. The dose of the drug
on a visit day is to be taken after blood draws.
20
Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 3:
On-Treatment Procedural Outline (IM011065): Week 24 through Week 52
Procedure
Week 24
D169
(±3 d)
V10
Week 28
D197
(±3 d)
V11
Week 32
D225
(±3 d)
V12
Week 36
D253
(±3 d)
V13
Week 40
D281
(±3 d)
V14
Week 44
D309
(±3 d)
V15
Week 48
D337
(±3 d)
V16
Week 52a
(or early 
DC)
D365
(±3 d)
V17
Safety 
Follow-upb
(Week 56)
D393
(±3 d)
V18
Notes
21
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v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 3:
On-Treatment Procedural Outline (IM011065): Week 24 through Week 52
Procedure
Week 24
D169
(±3 d)
V10
Week 28
D197
(±3 d)
V11
Week 32
D225
(±3 d)
V12
Week 36
D253
(±3 d)
V13
Week 40
D281
(±3 d)
V14
Week 44
D309
(±3 d)
V15
Week 48
D337
(±3 d)
V16
Week 52a
(or early 
DC)
D365
(±3 d)
V17
Safety 
Follow-upb
(Week 56)
D393
(±3 d)
V18
Notes
Safety Assessments
Full PE
X
X
X
Targeted Physical 
Examination
X
X
X
X
X
X
Body Weight
X
X
Vital Signs
X
X
X
X
X
X
X
X
X
ECG
X
X
PHQ-8
X
X
X
See 
Section 8.4.6.1
eC-SSRS
X
X
X
Suicidal Ideation 
and Behavior 
since last visit
Adverse Event 
Assessment
X
X
X
X
X
X
X
X
X
22
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3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 3:
On-Treatment Procedural Outline (IM011065): Week 24 through Week 52
Procedure
Week 24
D169
(±3 d)
V10
Week 28
D197
(±3 d)
V11
Week 32
D225
(±3 d)
V12
Week 36
D253
(±3 d)
V13
Week 40
D281
(±3 d)
V14
Week 44
D309
(±3 d)
V15
Week 48
D337
(±3 d)
V16
Week 52a
(or early 
DC)
D365
(±3 d)
V17
Safety 
Follow-upb
(Week 56)
D393
(±3 d)
V18
Notes
Concomitant 
Medication Use
X
X
X
X
X
X
X
X
X
Laboratory Tests
Hematology 
X
X
X
X
X
X
X
X
X
Lymphocytes Subsets 
(TBNK)
X
X
Chemistry Panel
X
X
X
X
X
X
X
X
X
If CPK >2.5 × 
ULN, reflex 
testing is 
required (see 
Section 8.4.5)
Fasting Lipid Panel
X
X
Subjects are 
required to fast 
for at least 10 
hours prior to 
collection
Fasting Plasma 
Glucose
X
X
hs-CRP
X
X
X
Hemoglobin A1C
X
X
Urinalysis
X
X
X
Serum 
Immunoglobulin 
Levels (IgM, IgG, IgA, 
IgE)
X
X
23
Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 3:
On-Treatment Procedural Outline (IM011065): Week 24 through Week 52
Procedure
Week 24
D169
(±3 d)
V10
Week 28
D197
(±3 d)
V11
Week 32
D225
(±3 d)
V12
Week 36
D253
(±3 d)
V13
Week 40
D281
(±3 d)
V14
Week 44
D309
(±3 d)
V15
Week 48
D337
(±3 d)
V16
Week 52a
(or early 
DC)
D365
(±3 d)
V17
Safety 
Follow-upb
(Week 56)
D393
(±3 d)
V18
Notes
Pregnancy Test (Urine)
X
X
X
X
X
X
X
X
X
WOCBP Only
Study Treatment
Dispense Study 
Treatment
X
X
X
X
X
X
X
Study Treatment 
Compliance
X
X
X
X
X
X
X
X
BMI = body mass index; 
 eC-SSRS = electronic Columbia-Suicide Severity Rating Scale; CK = creatine kinase; 
 
 ECG = electrocardiogram; 
 
 hs-CRP = high-sensitivity C-reactive protein; Ig = immunoglobulin; 
 
 PE = physical examination; 
 PHQ-8 = eight-item Patient Health Questionnaire; 
 
 
ULN = upper limit of normal; TBNK = T, B, and natural killer cells;
 
 Wk = Week; WOCP = women of childbearing potential
a For subjects who discontinue from the study prior to Week 52, all Week 52 Visit assessments are to be performed.
b
For subjects who do not continue in a long-term extension study
When multiple assessments are conducted at a single visit, the following is the order in which they should be done:
1)
Health outcomes assessments
2)
Safety assessments
3)
Clinical efficacy assessments
24
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v
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1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
4)
Laboratory tests (eg, safety laboratory tests, 
)
On fasting days, safety assessments can be done first followed by blood draws, and then health outcomes and, finally, efficacy assessments. 
The dose of a drug on a visit day is to be taken after blood draws.
25
Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
2
INTRODUCTION
Psoriasis is a chronic inflammatory skin disorder, characterized primarily by erythematous scaly 
plaques, that affects up to 3% of the general population. Men and women are equally affected and 
it can present at any age.1,2 Several studies have observed a bimodal distribution of psoriasis onset 
with the first peak ranging from 15 to 22 years of age, and the second peak ranging from 55 to 
60 years of age.3, 4, 5 The most common form of psoriasis (58% to 97% of cases) is plaque psoriasis 
(psoriasis vulgaris), with less common forms being guttate, pustular, inverse (flexural), and 
erythrodermic psoriasis. The disease can have a fluctuating relapsing course, with flares that may 
be induced by factors such as infections, trauma, smoking, and stress.3 Psoriasis can involve skin 
in any part of the body; particularly disabling is the involvement of specific anatomic regions, such 
as hands and feet (palmoplantar), face, scalp and nails. Disease severity can be graded by body 
surface area (BSA) involvement with mild defined as ≤10% BSA, and moderate-to-severe as 
>10% BSA.6 Psoriasis has a profound impact on quality of life and can lead to psychological,
social and economic consequences, especially in moderate-to-severe disease. This condition is also
associated with an increased risk of depression, occurrence of sleep disturbances, social stigma
and decreased work productivity.7,8 Commonly associated comorbidities found in psoriasis
patients include diabetes mellitus and metabolic syndrome. In patients with more severe forms of
the disease, life expectancy is decreased due to an increase of cardiovascular risk.9
Treatments include topical preparations, eg, corticosteroids, vitamin D analogues, calcineurin 
inhibitors, and salicylic acid; phototherapy modalities, including PUVA (psoralens with UVA) and 
narrow band UVB; and systemic therapies. In moderate-to-severe disease, systemic treatments are 
usually needed and may include oral agents (retinoids, methotrexate, cyclosporine, and apremilast) 
or injectables (eg, biologics such as tumor necrosis factor (TNF) inhibitors etanercept, infliximab, 
and adalimumab) anti-IL-12/23p40 antibody (ustekinumab), IL-17 antagonists (secukinumab, 
ixekizumab, and brodalumab), and anti–IL-23p19 antibody (guselkumab). Many of these 
treatments are associated with increased risk of adverse events (AEs) such as hepatotoxicity and 
neutropenia (methotrexate);10 nephrotoxicity (cyclosporine);11 depression and weight loss 
(apremilast);12 serious infections (cytokine inhibitors);13,14,15,16 candidiasis and Crohn’s disease 
(IL-17 antagonists).16, 17, 18
Although effective therapeutic options are available, under-treatment or nontreatment of psoriasis 
has been reported in up to half of surveyed patients (based on absence of treatment and/or 
dissatisfaction with treatment).19 Many patients with severe disease are still being managed with 
only topicals,4,8 and many patients consider their psoriasis treatment to be inadequate.
Accordingly, there remains a need for more effective oral options, when compared with currently 
available agents, that would increase adherence to treatment.
2.1
Study Rationale
BMS-986165 could be a therapeutic option for the treatment of subjects with moderate-to-severe 
plaque psoriasis based on results of a recently completed 12-week, randomized, Phase 2, 
placebo-controlled, parallel-group study with 5 different BMS-986165 treatment arms: 3 mg every 
26
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v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
other day (QOD); 3 mg once daily (QD); 3 mg twice daily (BID); 6 mg BID; and 12 mg QD (Study 
IM011011). Overall, 267 subjects were randomized (44 to 45 subjects per treatment arm) in the 
Phase 2 study. All BMS-986165 treatment groups, except 3 mg QOD, achieved the primary 
endpoint of superiority compared with placebo in the proportion of subjects achieving PASI 75 
after 12 weeks of treatment. Compared with placebo treatment group, in which 6.7% of the subjects 
achieved PASI 75 response, 38.6% (P = 0.0003), 68.9% (P < 0.0001), 66.7% (P < 0.0001) and 
75% (P < 0.0001) of subjects treated with 3 mg QD, 3 mg BID, 6 mg BID, and 12 mg QD achieved 
PASI 75, respectively. The PASI 75 responses plateaued at a dose of 3 mg BID. Also, there was a 
clinically significant proportion of subjects treated with BMS-986165 achieving an sPGA score of 
0 or 1 compared with placebo at Week 12. Compared with the placebo treatment group in which 
6.7% of the subjects achieved an sPGA score of 0 or 1, 41.5%, 75.6%, 65.9%, and 75% of the 
subjects treated with 3 mg QD, 3 mg BID, 6 mg BID, and 12 mg QD achieved an sPGA score of 
0 or 1, respectively with responses again plateauing at dose of 3 mg BID. The Phase 3 dose selected 
(6 mg QD) is expected to demonstrate equivalent efficacy to the 3 mg BID dose. 
 
This Phase 3 study is designed to confirm the efficacy and safety of BMS-986165 6 mg QD in a 
population of subjects with moderate-to-severe plaque psoriasis. 
2.2
Background
Tyrosine kinase 2 (TYK2) is a nonreceptor tyrosine kinase associated with receptors for the 
p40-containing cytokines IL-12 and IL 23, as well as the Type I interferon (IFN) receptor, and is 
required for the activation of their downstream signaling pathways. TYK2 catalyzes the 
phosphorylation of the intracellular receptor domains and signal transducer and activator of 
transcription (STAT) proteins resulting in the activation of STAT-dependent transcription and 
functional responses specific for these cytokines.20,21,22 Because TYK2-dependent cytokines (eg,
Type I IFNs, IL-12, IL-23) are distinct from those dependent on closely related Janus kinase (JAK) 
family members JAK1/JAK3 (eg, IL-2, IL-15, IL-7) or JAK2 (eg, erythropoietin, thrombopoietin, 
GM-CSF), a TYK2 inhibitor would be expected to have a highly differentiated profile from 
inhibitors of other JAK family kinases. TYK2 dependent pathways and the cytokine networks they 
modulate (eg, IL-23/IL-17, IFNα) have been implicated in the pathophysiology of multiple 
immune-mediated diseases, including psoriasis, lupus, spondyloarthritides, and Crohn’s disease.
BMS-986165 is a potent, highly selective, oral small molecule inhibitor of TYK2. A 
comprehensive in vitro and in vivo characterization of BMS-986165 has been established and 
supports the development of this compound in humans. Inhibition of TYK2 is expected to provide 
therapeutic benefit for subjects with psoriasis for multiple reasons: 1) Many of the pathways in the 
TYK2 signaling cascade (IL-23 and the downstream mediators IL-17 and IL-22; IFNα) have been 
implicated in pathogenesis of psoriasis.7 2) Biologic agents targeting the IL-17, IL-23p19, and 
IL-12/23 p40 pathways have been approved for and are highly efficacious in the treatment of 
psoriasis.
 
 
27
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v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
 
2.2.1
Early Clinical Development
The clinical data available to date supporting the safety, pharmacokinetics (PK) and 
pharmacodynamics (PD) of BMS-986165 are from 5 completed Phase 1 studies in healthy subjects
(IM011002, IM011015, IM011016, IM011031, and IM011039) and 1 completed Phase 2 study in 
adult subjects with moderate-to-severe plaque psoriasis (IM011011). 
Overall, BMS-986165 has been generally well tolerated across all studies, and no safety issues
have been identified to limit the investigation of the dose of BMS-986165 up to 12 mg QD in 
further clinical studies. A detailed description of the chemistry, pharmacology, efficacy, and safety 
of BMS-986165 is provided in the Investigator Brochure (IB).
28
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v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
3
OBJECTIVES AND ENDPOINTS
Table 4:
Objectives and Endpoints
Objectives
Endpoints
Primary
•
Assess whether BMS-986165 is superior to placebo at
Week 16 in the treatment of subjects with moderate-to-
severe plaque psoriasis
•
static Physician Global Assessment (sPGA)
0/1 response
•
Psoriasis 
Area 
and 
Severity 
Index
(PASI) 75 response (defined as a 75%
improvement in PASI score from baseline)
Secondary
•
Assess whether BMS-986165 is superior to placebo over
the first 16 weeks of treatment
•
sPGA 0/1 response
•
PASI 90 response
•
sPGA 0 response
•
PASI 100 response
•
Assess whether BMS-986165 is superior to placebo in nail
psoriasis through Week 16 in those subjects who have
baseline Physician’s Global Assessment of Fingernail
Psoriasis (PGA-F) score ≥3
•
PGA-F 0/1
•
Assess whether BMS-986165 is superior to placebo in
palmoplantar psoriasis through Week 16 in those subjects
who have baseline palmoplantar Physician’s Global
Assessment (pp-PGA) score ≥3
•
pp-PGA 0/1 response
29
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v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 4:
Objectives and Endpoints
Objectives
Endpoints
•
Evaluate improvement in patient reported outcomes for 
BMS-986165 compared with placebo through Week 16
•
Change 
from 
baseline 
in 
Psoriasis 
Symptoms and Signs Diary (PSSD) 
symptom score
•
PSSD symptom score of 0 (among subjects 
with a baseline PSSD symptom score ≥1)
•
DLQI 0/1 (among subjects with a baseline 
DLQI score ≥2)
4
STUDY DESIGN
4.1
Overall Design
Study IM011065 will be a 52-week, multi-center, randomized double-blind, placebo-controlled
study to evaluate the safety and efficacy of BMS-986165 vs placebo. A total of approximately 
219 qualified subjects with moderate-to-severe plaque psoriasis in mainland China, Taiwan, and 
30
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v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
South Korea will be enrolled (see additional details in Section 4.2
 
). 
The duration of study participation is approximately 60 weeks, and will be divided into the 
following periods: screening (up to 4 weeks), treatment (52 weeks), and follow-up ( 4 weeks).
Physical exams, 12-lead ECGs, and clinical laboratory evaluations will be done at select visits 
during the study. Subjects in this study will be monitored for AEs. 
 
4.1.1
Screening Period
Subjects will be evaluated during the screening period to ensure that they meet eligibility criteria.
A detailed medical history will be done at this time, as well as a complete physical exam. 
Psoriasis-related history, which will include length of diagnosis, body involvement, and history of 
systemic treatment, will be assessed here. Depression and suicidality assessments will also be 
performed. An evaluation for tuberculosis will be done based on medical history, recent chest 
imaging, and a QuantiFERON-TB test.
4.1.2
Treatment Period
Qualified subjects who have completed the screening procedures and have met the 
inclusion/exclusion criteria will be randomized on Day 1 in a 2:1 ratio to either BMS-986165 6 mg 
QD or placebo, respectively.
Dummy tablets (placebo to BMS-986165 6 mg tablets) will be administered to subjects to maintain 
blinding. Additional details are provided in Section 6.1.
Randomization should not occur until at least 8 days after the screening visit to allow collection 
of PSSD data during screening in order to calculate a baseline PSSD score. Randomization will be 
stratified by country (mainland China vs. non-mainland China) and previous biologic use (for 
psoriasis, psoriatic arthritis or other inflammatory diseases only; yes/no).
31
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
4.1.3
Week 16
The coprimary endpoints (sPGA 0/1 and PASI 75) will be assessed at Week 16. Subjects receiving 
placebo will be switched in a blinded manner to BMS-986165 6 mg QD at Week 16. Subjects who 
are randomized to BMS-986165 6 mg QD will continue their treatment regimen through Week 52.
4.1.4
Week 24
At Week 24, a subject who has 
 may be treated with restricted 
topicals/shampoos as described in Section 6.7.1 at the investigator’s discretion. These treatments 
may be initiated only at Week 24 and not at subsequent time points. A subject who is started on 
these treatments at Week 24 may use them as needed per the investigator’s judgement through 
Week 52.
4.1.5
Week 52 and Follow-up Period
The follow-up period is a 4-week window after the Week 52 visit, unless the subject rolls over into 
the long-term extension. The subject will be encouraged to report any SAEs or AEs experienced 
during this time.
Subjects who discontinue study treatment early should remain in the study for protocol-specified 
procedures (please refer to Section 7.1 for more details).
Subjects completing 52 weeks of treatment will be offered the opportunity to roll over to a separate 
long-term extension study (≥2 years) where they will be treated with BMS-986165 6 mg QD.
The study design schematic is presented in Figure 1.
Figure 1:
Study Design Schematic
QD = once daily.
The coprimary endpoints will be evaluated at Week 16.
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
4.1.6
Data Monitoring Committee and Other External Committees
4.1.6.1
Data Monitoring Committee
An external data monitoring committee (DMC) with multi-disciplinary representation will be 
established to evaluate on a periodic basis; AEs, laboratory measurements, and safety assessments 
to ensure the ongoing safety of study subjects. An independent reporting statistician not involved 
in the conduct of the study will be designated by 
 to provide the DMC with essential safety 
data during the study.
The DMC responsibilities, authorities, and procedures will be documented and followed according 
to the DMC charter.
4.1.6.2
Infection Adjudication Committee
An independent Infection Adjudication Committee, composed of individuals with relevant 
expertise, will review in a blinded manner and adjudicate infection AEs, such as opportunistic 
infections, influenza, herpes zoster, and TB, reported in the study per criteria specified in a separate 
charter. Additional information about these infections may be collected on the case report form in 
order to characterize and understand them. The Adjudication Committee members will be blinded 
to the treatment assignment of subjects. The structure, responsibilities, and procedures of the 
Adjudication Committee will be outlined in a charter. The Adjudication Committee is distinct from 
the DMC and Adjudication Committee members will not be investigators on the study.
4.1.6.3
CV Adjudication Committee
An independent cardiovascular (CV) Adjudication Committee, composed of individuals with 
relevant expertise, will review in a blinded manner and adjudicate cardiovascular and 
cerebrovascular AEs such as, but not limited to, Major Adverse Cardiovascular Events (MACE) 
that include death, non-fatal myocardial infarction, non-fatal stroke; revascularization procedures; 
heart failure; dysrhythmias; heart blocks; and thrombotic events reported in the study per criteria 
specified in a separate charter. Additional information about cardiovascular and cerebrovascular 
AEs may be collected on the case report form in order to characterize and understand them. The 
Adjudication Committee members will be blinded to the treatment assignment of subjects. The 
structure, responsibilities, and procedures of the Adjudication Committee will be outlined in a 
charter. The Adjudication Committee is distinct from the DMC and Adjudication Committee 
members will not be investigators on the study.
4.1.6.4
Suicidal Ideation and Behavior Adjudication Committee
An independent Suicidal Ideation and Behavior Adjudication Committee, composed of individuals 
with relevant expertise, will review in a blinded manner and adjudicate suicidal ideation/behavior 
reported in the study per criteria specified in a separate charter. Additional information about 
suicidal ideation/behavior may be collected on the case report form. The Adjudication Committee 
members will be blinded to the treatment assignment of subjects. The structure, responsibilities, 
and procedures of the Adjudication Committee will be outlined in a charter. The Adjudication 
Committee is distinct from the DMC and Adjudication Committee members will not be 
investigators on the study.
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IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
4.2
Number of Subjects
Approximately 219 qualified subjects will be randomized in a 2:1 ratio to BMS-986165 6 mg QD 
or placebo, respectively. 
4.3
End of Study Definition
The duration of study participation for individual subjects is expected to be up to 60 weeks 
(420 days), which includes screening (up to 4 weeks), treatment (52 weeks) and follow-up (up to 
4 weeks) periods.
The start of the study is defined as first visit for first subject screened. The end of the study is 
defined as the last visit or scheduled procedure shown in the Schedule of Activities (Section 1.3) 
for the last subject. Study completion is defined as the final date on which data was or is expected 
to be collected (Week 56 for collection of potential SAEs).
4.4
Scientific Rationale for Study Design
This Phase 3 study will be conducted in a population of subjects with stable moderate-to-severe 
plaque psoriasis who are candidates for systemic psoriasis therapy. The study is designed to 
confirm the efficacy and safety of BMS-986165 compared with placebo in achieving sPGA of 0/1 
and PASI 75 at Week 16. The sPGA and PASI 75 are standard measures in clinical trials of 
demonstrating efficacy of systemic psoriasis treatments. The placebo arm is included in this study 
for a duration of 16 weeks to provide a control for the natural fluctuation of psoriasis activity that 
may occur and to provide a safety standard for comparison. Subjects in the placebo arm will be 
switched to BMS-986165 at Week 16 to provide them psoriasis treatment after the coprimary 
endpoints are collected.
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IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
5
STUDY POPULATION
Eligibility criteria for this study have been carefully considered to ensure 1) selection of 
appropriate subjects with psoriasis, 2) safety of the study subjects and 3) the results of the study 
can be used for regulatory filing and other purposes. It is imperative that subjects fully meet all 
eligibility criteria.
All screening and randomization evaluations must be completed and reviewed to confirm that 
potential subjects meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for screening 
failure, as applicable.
5.1
Inclusion Criteria
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria:
1) Signed Written Informed Consent
a) Subjects must be willing to participate in the study and sign the informed consent form 
(ICF)
2) Type of Subject and Target Disease Characteristics
a) N/A
b) Deemed by the investigator to be eligible for phototherapy or systemic therapy
c) ≥10% of BSA involvement at screening visit and Day 1
d) Psoriasis Area and Severity Index (PASI) score ≥12 and static Physician’s Global 
Assessment (sPGA) ≥3 at screening visit and Day 1
e) Men and women in mainland China, Taiwan, and South Korea diagnosed with stable 
plaque psoriasis for 6 months or more. Stable psoriasis is defined as no morphology 
changes or significant flares of disease activity in the opinion of the investigator
3) Age and Reproductive Status
a) Men and women aged ≥18 years or legal age at the time of screening visit
b) Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at 
screening visit, and a negative urine pregnancy test (minimum sensitivity 25 IU/L or 
equivalent units of human chorionic gonadotropin [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 must agree to use correctly a highly effective method(s) 
of contraception for the duration of treatment (52 weeks) with study drug(s) BMS-986165 
plus 5 half-lives of study drug (3 days) plus 30 days (duration of ovulatory cycle) for a total 
of 33 days post-treatment completion (total of 33 days after last dose of study drug). 
WOCBP who are continuously not heterosexually active are exempt from contraceptive 
requirements, but must still undergo pregnancy testing as described in this protocol
e) Male subjects who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception (APPENDIX 4 for the duration of treatment with study 
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IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
treatment(s) plus 5 half-lives of the study treatment (3 days) for a total of 3 days 
post-treatment completion. In addition, male subjects must be willing to refrain from sperm 
donation during this time
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 4) 
which have a failure rate of < 1% when used consistently and correctly.
5.2
Exclusion Criteria
An individual who meets any of the following criteria will be excluded from participation in this 
study:
1) Target Disease Exceptions
a) Has nonplaque psoriasis (ie, guttate, inverse, pustular, erythrodermic or drug-induced 
psoriasis) at screening or Day 1
2) Infectious/Immune-related Exclusions
a) History or evidence of outpatient active infection and/or febrile illness within 7 days prior 
to Day 1 
b) History of serious bacterial, fungal, or viral infection requiring hospitalization and/or
intravenous (IV) antimicrobial treatment within 60 days prior to Day 1
c) Any untreated bacterial infection within 60 days prior to Day 1
d) Any ongoing evidence of chronic, bacterial infection (eg, chronic pyelonephritis, chronic 
osteomyelitis, chronic bronchiectasis)
e) Any history of proven infection of a joint prosthesis in which the prosthesis was not 
removed or replaced, or received antibiotics for suspected infection of a joint prosthesis in 
which the prosthesis was not removed or replaced
f)
Received live vaccines within 60 days prior to Day 1, or plans to receive a live vaccine 
during the study, or within 60 days after completing study treatment
g) Presence of herpes zoster lesions at screening or Day 1
h) History of serious herpes zoster or serious herpes simplex infection which includes, but is 
not limited to, any episode of disseminated herpes simplex, multidermatomal herpes zoster, 
herpes encephalitis, ophthalmic herpes, or recurrent herpes zoster (recurrent is defined as 
2 episodes within 2 years)
i)
Evidence of, or test positive for, hepatitis B virus (HBV) at Screening. Positive hepatitis B 
lab testing is defined as: 1) Positive hepatitis B surface antigen (HBsAg+) OR 2) Presence 
of hepatitis B virus deoxyribonucleic acid (DNA) OR 3) Positive anti-hepatitis B core 
antibody without concurrent positive hepatitis B surface antibody (HBcAb+ and HBsAb-)
j)
Evidence of, or test positive for, hepatitis C virus (HCV) at screening. A positive test for 
HCV is defined as: 1) positive for hepatitis C antibody (anti-HCVAb) AND 2) positive via 
a confirmatory test for HCV (eg, HCV polymerase chain reaction)
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
k) Positive for human immunodeficiency virus by antibody testing (HIV-1 and -2 Ab) at 
screening
l)
Any history of known or suspected congenital or acquired immunodeficiency state or 
condition that would compromise the subject’s immune status (eg, history of opportunistic 
infections [eg, Pneumocystis jirovecii pneumonia, histoplasmosis, or coccidioidomycosis], 
history of splenectomy, primary immunodeficiency)
3) Any of the following tuberculosis (TB) criteria:
a) History of active TB prior to screening visit, regardless of completion of adequate 
treatment
b) Signs or symptoms of active TB (eg, fever, cough, night sweats, and weight loss) during 
screening as judged by the investigator
c) Any imaging of the chest (eg, chest x-ray, chest computed tomography [CT] scan) obtained 
during the screening period or anytime within 6 months prior to screening with 
documentation, showing evidence of current active or history of active pulmonary TB
d) Latent TB infection (LTBI) defined as positive IFN gamma release assay (IGRA), by 
QuantiFERON-TB testing at screening, in the absence of clinical manifestations
Note: Subject is eligible if (i) there are no current signs or symptoms of active TB AND
(ii) subject has received adequate documented treatment for LTBI within 5 years of 
screening OR has initiated prophylactic treatment for LTBI per local guidelines and is 
rescreened after 1 month of treatment. To continue in the study, subject must agree to 
complete a locally-recommended course of treatment for LTBI. 
Note: An IGRA test that is indeterminate with no signs or symptoms of active TB must be 
re-tested for confirmation. If the second test is again indeterminate the subject will be 
excluded from the study. If the re-test is positive, the subject should be treated as having 
LTBI. If the re-test is negative, subject may be eligible provided no other exclusion criteria 
for TB are met.
4) Medical History and Concurrent Diseases
a) Any major surgery within 8 weeks prior to Day 1, or any planned surgery for the first 
52 weeks of the study
b) Has donated blood >500 mL within 4 weeks prior to Day 1, or plans to donate blood during 
the course of the study
c) Drug or alcohol abuse, as determined by the investigator, within 6 months prior to Day 1
d) Medical marijuana or prescription marijuana taken for medicinal reasons
e) Any major illness/condition or evidence of an unstable clinical condition (eg, renal, 
hepatic, hematologic, gastrointestinal, endocrine, pulmonary, psychiatric, neurologic, 
immunologic, or local active infection/infectious illness) that, in the investigator’s 
judgment or after consultation with the Medical Monitor, will substantially increase the 
risk to the subject if he or she participates in the study
f)
Unstable cardiovascular disease, defined as a recent clinical cardiovascular event (eg,
unstable angina, myocardial infarction, stroke, rapid atrial fibrillation) in the last 3 months 
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IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
prior to screening, or a cardiac hospitalization (e.g. revascularization procedure, pacemaker 
implantation) within 3 months prior to screening
g) Has uncontrolled arterial hypertension characterized by a systolic blood pressure (BP) 
>160 mm Hg or diastolic BP >100 mm Hg
Note: Determined by 2 consecutive elevated readings. If an initial BP reading exceeds this 
limit, the BP may be repeated once after the subject has rested sitting for ≥10 minutes. If 
the repeat value is less than the criterion limits, the second value may be accepted
h) Class III or IV congestive heart failure by New York Heart Association Criteria
i)
Has cancer or 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, or carcinoma of cervix in situ that has 
been treated with no evidence of recurrence)
j)
Any significant/uncontrolled neuropsychiatric illness as clinically judged by the 
investigator during screening or at Day 1
OR
Any lifetime history of suicidal ideation, suicidal behavior, or suicidal attempts by medical 
history or by electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) 
documentation, or by answering “yes” to Question 4 or 5 which indicates a suicidal ideation 
severity level of 4 or 5 on the eC-SSRS at Screening or at Day 1, or is clinically deemed to 
have a suicide risk by the investigator
k) Prior exposure to investigational product (ie, BMS-986165)
l)
If the subject has received biologics previously, the following exclusion criteria for 
washout will apply: 
i)
Antibodies to IL-12, IL-17 or IL-23 (eg, ustekinumab, secukinumab, tildrakizumab, 
ixekizumab, or guselkumab) within 6 months of Day 1
ii) TNF inhibitor(s) (e.g. etanercept, adalimumab, infliximab, certolizumab) within 
2 months of Day 1
iii) Agents that modulate integrin pathways to impact lymphocyte trafficking (eg,
natalizumab), or agents that modulate B cells or T cells (eg, alemtuzumab, abatacept, 
or visilizumab) within 3 months of Day 1
iv) Rituximab within 6 months of Day 1
m) Has received systemic non-biologic psoriasis medications and/or any systemic 
immunosuppressants (including, but not limited to, methotrexate, azathioprine, 
cyclosporine, JAK inhibitors, 6-thioguanine, mercaptopurine, mycophenolate mofetil, 
hydroxyurea, tacrolimus, oral or injectable corticosteroids, retinoids, 1,25-dihydroxy 
vitamin D3 and analogues, psoralens, sulfasalazine, or fumaric acid derivatives) within 
4 weeks prior to Day 1
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IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
n) Has used leflunomide within 6 months prior to Day 1
o) Has used opioid analgesics within 4 weeks prior to Day 1
p) Has received lithium, antimalarials, or intramuscular (IM) gold within 4 weeks of the first 
administration of any study medication
q) Has received phototherapy (including either oral and topical PUVA light therapy, 
ultraviolet B [UVB] or self-treatment with tanning beds or therapeutic sunbathing) within 
4 weeks prior to Day 1
r)
Has used topical medications/treatments that could affect psoriasis evaluation (including, 
but not limited to, high potency corticosteroids (WHO Classes I-V), >3% salicylic acid, 
urea, alpha- or beta-hydroxyl acids, anthralin, calcipotriene, topical vitamin D derivatives, 
retinoids, tazarotene, methoxsalen, trimethylpsoralens, pimecrolimus, and tacrolimus) 
within 2 weeks prior to Day 1
Note: Low potency topical steroids (WHO Class VI and VII) are permitted on the palms, 
soles, face, and intertriginous areas but should not be used within 24 hours prior to any 
study visit. Bland emollients (defined as emollients without urea or alpha- or beta-hydroxy 
acids or other ingredients which are pharmacologically active) are allowed on all body 
regions but should not be used within 24 hours prior to any study visit.
s) Use of shampoos that contain corticosteroids, coal tar, >3% salicylic acid, or vitamin D3 
analogues within 2 weeks prior to Day 1
t)
Has received an experimental antibody or experimental 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) prior to Day 1 OR is currently 
enrolled in an investigational study
u) Any botanical preparations (eg, herbal supplements or traditional Chinese medicines 
derived from plants, minerals, or animals) intended to treat psoriasis or other 
immunological diseases within 4 weeks prior to Study Day 1
v) Any other sound medical, psychiatric and/or social reasons as determined by the 
investigator
5) Physical and Laboratory Evaluations
a) At screening
i)
Absolute WBC count <3000/mm3
ii)
Absolute lymphocyte count <500/mm3
iii)
Absolute neutrophil count <1000/mm3
iv)
Platelet count <100,000/mm3
v)
Hemoglobin <9 g/dL 
vi)
ALT and/or AST >3X upper limit of normal (ULN)
vii)
Total, unconjugated, and/or conjugated bilirubin >2 × ULN
viii)
Thyroid stimulating hormone (TSH) outside the normal range 
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
AND
Free T4 (thyroxine) or T3 (triiodothyronine) outside the normal reference range
b) ECG abnormalities that are considered clinically significant and would pose an 
unacceptable risk to the subject if participating in the study
c) Renal impairment based on an estimated glomerular filtration rate (eGFR) <45 mL/min
d) Inability to be venipunctured and/or tolerate venous access
e) Any other significant laboratory abnormalities that, in the opinion of the investigator, might 
place the subject at unacceptable risk for participation in this study
6) Allergies and Adverse Drug Reactions
a) History of any significant drug allergy (such as anaphylaxis)
7) 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 BMS approval is required).
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
c) Inability to comply with restrictions and prohibited activities/treatments as listed in the 
study protocol
d) Site personnel or their immediate family
5.3
Lifestyle Restrictions
General skin care measures (with above restrictions for topical treatments) that are standard for 
patients with plaque psoriasis are permitted. Subjects should avoid excessive sun exposure and 
avoid risks that are known to provoke flare of psoriasis.
5.3.1
Meals and Dietary Restrictions
Study treatment may be taken without regard to meals; however, subjects are required to fast for a 
minimum of 10 hours before visits on which fasting lipid, fasting glucose
 
samples will be drawn. 
5.3.2
Caffeine, Alcohol, and Tobacco
No restrictions are required; however, extensive use of caffeine, alcohol and tobacco should be 
avoided.
5.3.3
Activity
No restrictions are required; however, unusual physical exertion should be avoided during the 
study.
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IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
5.4
Screen Failures
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently randomized in the study for any reason. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure subjects, to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements, and to respond to queries 
from regulatory authorities. Minimal set of screen failure information includes date of consent, 
demography, screen failure details (ie, eligibility criteria that the subject did not meet), and any 
serious AEs during the screening period.
5.4.1
Retesting During Screening or Rescreening
For laboratory parameters that initially do not meet eligibility requirements, a single retest within 
the 28-day screening period is permitted before subject is declared a screen failure. This is 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 would be clinically relevant.
The study permits the rescreening (after the end of the initial 28-day screening period) of a subject 
who discontinues the study as a pretreatment failure (ie, the subject fails to meet eligibility criteria 
and has not been treated). The subject must be reconsented, will be assigned a new identification 
number, and a full screening visit must be performed again. A subject can only be rescreened
1 time (ie, if the subject fails 1 rescreening attempt, no additional rescreening is allowed). 
Depending on the timing of rescreening, repeat chest imaging may not be required. Duration of 
existing treatments and required discontinuation periods shall be considered relative to the new 
screening visit and/or randomization.
The most current result prior to randomization is the value by which study inclusion will be 
assessed, as it represents the subject’s most current clinical state.
6
TREATMENT
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device intended to be administered to a study subject according to the study randomization 
or treatment allocation.
Study 
treatment 
includes 
both 
Investigational 
[Medicinal] 
Product 
(IP/IMP) 
and 
Non-investigational [Medicinal] Product (Non-IP/Non-IMP) and can consist of the following: 
BMS-986165 and placebo.
An IP, also known as IMP in some regions, is defined a 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 or assembled (formulated or packaged) differently than the 
authorized form, or used for an unauthorized indication, or when used to gain further information 
about the authorized form.
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-IP. 
Table 5 shows the study treatments for Protocol IM011065.
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IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
Table 5:
Study Treatments for IM011065
Product 
Description / 
Class and 
Dosage Form
Potency
IP/Non-IP
Blinded or 
Open Label
Packaging / 
Appearance
Storage 
Conditions
(per label)
BMS-986165 
tablet
6 mg
IP
Blinded
Bottle
Store 15°C to 
25°C; Store in a 
tightly closed 
container; 
Protect from 
light
Placebo tablet 
to match 
BMS-986165 
6 mg
n/a
IP
Blinded
Bottle
Store 15°C to 
25°C; Store in a 
tightly closed 
container; 
Protect from 
light
IP = investigational product; n/a = not applicable
6.1
Treatments Administered
Study treatment will be administered as described in Section 4.1.2. The selection and timing of 
dose for each subject is as follows:
Table 6:
Selection and Timing of Dose
Study Treatment
Unit dose 
strength(s)/Dosage 
level(s)
Dosage formulation
Frequency of Administration
Route of 
Administration
BMS-986165
6 mg
1 active tablet QD in the morning
oral
Placebo QD
n/a
1 BMS-986165 placebo QD in the 
morning
oral
QD = once daily, n/a = not applicable
6.2
Method of Treatment Assignment
Before the study is initiated, each user (at investigative sites) will receive log-in information and 
directions on how to access the interactive response technology (IRT) system. At the time of the 
screening visit, immediately after informed consent is obtained and before any study-related 
procedures are performed, the investigative site will access the enrollment option of the IRT 
system for assignment of a subject number for all subjects, including subjects not subsequently 
randomized or treated. The subject number is assigned sequentially by the system and will be 
unique across all sites. All enrolled subjects will be assigned sequential subject numbers. The 
subject number will not be used for any other subject. If a subject is rescreened, they will be given 
a new identification number.
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IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
At Week 0 (Day 1), subjects who meet all criteria for enrollment at Screening and Day 1 will be 
centrally randomized in a 2:1 ratio to BMS-986165 6 mg QD or placebo as determined by a 
computer-generated randomization schedule using IRT. The randomization lists will be generated 
by the IRT vendor using a permuted block design within each stratum level. The randomization in 
this study will be stratified by country (mainland China vs. non-mainland China) and previous 
biologic use for psoriasis, psoriatic arthritis or other inflammatory diseases only (yes/no). After all 
inclusion/exclusion criteria have been met for a subject, the investigative site will access the IRT 
on Day 1 for the purpose of randomizing a subject. A treatment group will be assigned by IRT 
based on the above-described randomization schedule and each subject will be assigned a unique 
randomization number. In addition, a unique kit number will be assigned to the subject 
corresponding to the treatment assignment.
A kit will contain adequate study treatment for a 4-week supply. At subsequent visits, when new 
treatment kits need to be provided, the investigative site will access the IRT to obtain the kit 
number to assign to the subject. Study treatment will be dispensed at study visits as shown in the 
Schedule of Activities (Section 1.3).
At Week 16, subjects receiving placebo will be switched in a blinded manner to BMS-986165 
6 mg QD.
6.3
Blinding
6.3.1
Maintaining the Blind
Blinded treatment assignments will be managed using IRT. IP supply will be controlled by IRT at 
each visit.
All tablets are identical in appearance and will be supplied in bottles with each daily dose made 
up of the appropriate combination of active and/or placebo tablets to provide the correct treatment, 
as shown in Table 5. Investigative site staff, Sponsor and designee personnel, and subjects and 
their families will remain blinded to treatment assignments.
6.3.2
Circumstances for 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 IP
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, ie, that it will alter the subject's immediate 
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IM011065
BMS-986165
TYK2 Inhibitor
Revised Protocol No.: 05
Date: 11-Nov-2020
management. In many cases, particularly when the emergency is clearly not related to the IP, 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 case of an emergency, the investigator has unrestricted access to randomization information via 
IRT and is capable of breaking the blind through the IRT system without prior approval from the 
sponsor. After the unblinding, the investigator shall notify the medical monitor and/or study 
director. The method of unblinding for emergency purposes is described in the IRT manual. 
Subject and unblinded treatment information and the reason for the blind being broken must be 
recorded on the appropriate study status page of the electronic case report form (eCRF). After 
unblinding via IRT, the investigator shall notify the Medical Monitor.
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 must be 
discussed with the Medical Monitor prior to unblinding.
If a subject is unblinded for any reason, the subject will be discontinued from treatment.
6.3.3
Unblinding for Week 16 Primary Endpoint Analysis
An unblinded analysis of data through Week 16 will be performed after all subjects complete their 
Week 16 visit or have discontinued prior to Week 16. A select group of personnel who are not 
involved in the conduct of the study will review the results to write a clinical study report. 
Following the Week 16 analysis until the end of the study, the investigators, subjects, and clinical 
trial team members who directly cooperate with the site staff will continue to remain blinded to 
the initial treatment assignment. Details of maintaining the blind following the unblinded analysis 
will be finalized prior to the Week 16 database lock. A final analysis will be performed after all 
subjects complete the Week 52 visit or discontinue prior to the Week 52 visit, and a clinical study 
report will be written.
6.4
Dosage Modification
There is no provision for dose modification of study treatment. If a subject interrupts treatment 
due to an AE, study treatment can be restarted in consultation with the Medical Monitor.
6.5
Preparation/Handling/Storage/Accountability
The IP should be stored in a secure area according to local regulations. It is the responsibility of 
the investigator to ensure that the IP is only dispensed to study subjects. The IP must be dispensed 
only from official study sites by authorized personnel according to local regulations.
The product storage manager should ensure that the study treatment is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. If 
concerns regarding the quality or appearance of the study treatment arise, the study treatment 
should not be dispensed and BMS should be contacted immediately.
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Investigational product documentation (whether supplied by BMS or not) must be maintained that 
includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
•
Guidance and information for final disposition of unused study treatment are provided in 
APPENDIX 2.
6.5.1
Retained Samples for Bioavailability/Bioequivalence
Not applicable.
6.6
Treatment Compliance
Study treatment compliance will be periodically monitored using standard drug accountability 
procedures (comparing the number of tablets returned to number dispensed, considering the 
expected regimen and any reported missed doses). Drug accountability will be reviewed by the 
investigative site staff at each visit to confirm treatment compliance. Site staff will discuss any 
discrepancies with the subject and remind the subject of the importance of compliance with the 
assigned regimen. A real-time monitoring platform may be used.
6.7
Concomitant Therapy
6.7.1
Prohibited and/or Restricted Treatments
Prohibited and/or restricted medications in the study are described below. Medications taken 
within 4 weeks prior to study drug administration must be recorded on the CRF.
1) Exposure to any investigational drug or placebo outside of the current study
2) Use of any medications/therapy that would aggravate psoriasis. These include agents such as 
lithium, antimalarials (quinacrine, chloroquine, and hydroxychloroquine), propranolol, 
indomethacin, and quinidine unless it is considered necessary for the subject’s welfare and/or 
treatment of an AE/SAE
3) Use of opioid analgesics unless it is considered necessary for the subject’s welfare and / or 
treatment of an AE/SAE
4) Phototherapy; use of tanning booths or therapeutic sunbathing 
5) Any use of biologic medications (eg, adalimumab, etanercept, infliximab, ustekinumab)
6) Any use of oral psoriasis medications (eg, methotrexate, cyclosporine, retinoids, fumaric acid 
derivatives) for any indication
7) Any use of oral or injectable corticosteroids (prednisone, methylprednisolone, etc.), unless it 
is considered necessary for the subject’s welfare and/or treatment of an AE/SAE
8) Note: otic, ophthalmic, nasal, or inhaled corticosteroids within recommended doses and with 
no systemic effects are permitted.
9) Any topical medications/treatments, which are used for any indication, that could affect 
psoriasis evaluation (including, but not limited to, high potency corticosteroids [WHO Classes 
I-V], >3% salicylic acid, urea, alpha- or beta-hydroxyl acids, anthralin, calcipotriene, 
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vitamin D derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens, pimecrolimus, 
and tacrolimus)
Exception: The following topical treatments may be initiated only at Week 24 per 
investigator’s discretion in subjects who have 
 (see Section 4.1.4)
•
High potency corticosteroids (WHO Classes I-V), >3% salicylic acid, urea, alpha- or 
beta-hydroxyl acids , anthralin, calcipotriene, vitamin D derivatives, retinoids, tazarotene
Note: Low potency topical steroids (WHO Class VI and VII) are permitted on the palms, soles, 
face, and intertriginous areas but should not be used within 24 hours prior to any study visit. 
Bland emollients (defined as emollients without urea or alpha- or beta-hydroxy acids or other 
ingredients which are pharmacologically active) are allowed on all body regions but should 
not be used within 24 hours prior to any study visit.
10) Any medicated shampoos that contain corticosteroids, coal tar, >3% salicylic acid, or vitamin 
D3 analogues
Exception: The above shampoos may be initiated only at Week 24 per investigator’s discretion 
in subjects who have 
 (see Section 4.1.4)
11) Live vaccination
12) Any botanical preparation (eg, herbal supplements or traditional Chinese medicines derived 
from plants, minerals, or animals) intended to treat psoriasis or other immunological diseases.
No concomitant medications (prescription, over-the-counter or herbal) are to be administered 
during the study unless prescribed for treatment of specific clinical events. Any concomitant 
therapies must be recorded on the CRF.
The investigator should contact and confirm agreement with the Medical Monitor prior to the 
administration of any concomitant medications.
6.7.2
Permitted Concomitant Medications
Stable doses of concomitant medication for chronic medical conditions are permitted as long as 
neither the medication nor the medical condition meet exclusion criteria as detailed in Section 5.2. 
Dose adjustments of these medications should be avoided during the study unless clinically 
indicated. If a dose adjustment of these medications should occur, they must be recorded on the 
Concomitant medications eCRF or the Procedures and Significant non-drug therapies eCRF. The 
investigator should instruct the subject to notify the study site about any new treatments he/she 
takes after the start of the study treatment. All medications and significant non-drug therapies 
(including physical therapy and blood transfusions) administered after the subject starts study 
treatment must be listed on the Concomitant medications eCRF or the Procedures and Significant 
non-drug therapies eCRF.
Note: Low potency topical steroids (WHO Class VI and VII) are permitted on the palms, soles, 
face, and intertriginous areas but should not be used within 24 hours prior to any study visit. Bland 
emollients (defined as emollients without urea or alpha- or beta-hydroxy acids or other ingredients
which are pharmacologically active) are allowed on all body regions but should not be used within 
24 hours prior to any study visit.
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6.7.3
Rescue Medications
At Week 24, a subject who has 
may be treated with restricted 
topicals or shampoos, respectively, as described in Section 6.7.1 at the investigator’s discretion. 
These treatments may be initiated only at Week 24 and not at subsequent time points. A subject 
who is started on these treatments at Week 24 may use them as needed per the investigator’s 
judgement through Week 52.
6.8
Treatment After the End of the Study
At the end of the study, the investigator should ensure that subjects continue to receive appropriate 
standard of care to treat the condition under study.
In addition, for subjects who continue to demonstrate clinical benefit, BMS may continue to 
provide study treatment via a rollover extension study requiring approval by responsible health 
authority and ethics committee, or through another mechanism at the discretion of BMS. 
BMS reserves the right to terminate access to BMS supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns; b) the development of BMS-986165 is 
terminated for other reasons, including but not limited to lack of efficacy and/or not meeting the 
study objectives; c) the subject can obtain medication from a government sponsored or private 
health program. In all cases BMS will follow local regulations.
7
DISCONTINUATION CRITERIA
7.1
Discontinuation from Study Treatment
Subjects MUST discontinue IP (and non-IP at the discretion of the investigator) for any of the 
following reasons:
•
Subject requests to stop study treatment. Subjects who request to discontinue study treatment
will 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 subject to provide this
information.
•
Any clinically significant AE, laboratory abnormality, or 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. If treatment is discontinued due to an AE, the AE eCRF must be
completed to show that the AE caused discontinuation
•
eGFR <45 mL/min on repeat assessment within 7 days
•
Abnormal liver tests suggestive of drug-induced liver injury (DILI), as defined in Section 8.2.8
or if the investigator believes that it is in the best interest of the subject
•
Subject reports suicidal ideation, suicidal behavior, or suicide attempts at any time after 
randomization, or documents suicidal ideation by answering “Yes” to Question 4 or 5 on the 
eC-SSRS, or documents suicidal behavior on the eC-SSRS at any time during the study. The 
subject should then be immediately referred to a mental health professional for evaluation of 
suicide risk.
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•
The subject develops a malignancy with the exception of a subject who develops nonmelanoma 
skin cancer who may continue in the study at the discretion of the investigator.
•
Pregnancy, positive pregnancy test or subject expresses an interest in becoming pregnant (refer 
to Section 8.2.6)
•
Subject develops active TB during the study or prematurely discontinues treatment for LTBI, 
or subject is noncompliant with LTBI therapy (refer to Section 8.4.4)
•
Termination of the study or program by BMS
•
Unblinding of a subject’s treatment assignment for any reason (emergency or nonemergency)
•
Inability or failure to comply with protocol requirements in the opinion of the investigator
•
Loss of ability to freely provide consent through imprisonment or involuntary incarceration for 
treatment of either a psychiatric or physical (eg, infectious disease) illness
Refer to the Schedule of Activities (Section 1.3) for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that can be completed.
All subjects who discontinue BMS-986165 should comply with protocol-specified follow-up 
procedures as outlined in Section 1.3. The only exception to this requirement is when a subject 
withdraws consent for all study procedures including posttreatment study follow-up or loses the 
ability to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either 
a psychiatric or physical illness). Replacement of subjects is not permitted.
If study treatment is 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 eCRF page.
7.1.1
Temporary Discontinuation of Study Medication
Temporary study treatment discontinuation is allowed only if the subject develops an AE which, 
in the opinion of the investigator, indicates that it is in the subject’s best interest that the study 
treatment be placed on hold. Study treatment in this situation should be stopped until the AE is 
medically treated and/or has resolved per PI judgement.
Any temporary study treatment discontinuation as well as restart must be documented on the 
corresponding eCRF.
7.1.2
Post-Study Treatment Follow-up
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 treatment must continue to be followed for 
collection of outcomes and/or survival follow-up data as required and in line with Section 4 until 
death or the conclusion of the study.
Subjects who discontinue study treatment should be encouraged to undergo the Week 52/Early 
Termination visit and the safety follow-up visit (Section 1.3) in order to support the final efficacy 
and safety analysis.
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7.2
Discontinuation from the Study
Subjects who request to discontinue study treatment will remain in the study and must continue to 
be followed for protocol specified follow-up procedures as specified in Section 1.3. The only 
exception to this is when a subject specifically withdraws consent for any further contact with 
him/her or persons previously authorized by subject to provide this information. 
•
Subjects should notify the investigator of the decision to withdraw consent from future
follow-up in writing, whenever possible.
•
The withdrawal of consent should be explained in detail in the medical records by the 
investigator 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.
•
If the subject withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent.
7.3
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.
•
Lost to follow-up is defined by the inability to reach the subject after a minimum of three
documented phone calls, faxes, 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 
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 assist site 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.
8
STUDY ASSESSMENTS AND PROCEDURES
•
Study procedures and timing are summarized in the Schedule of Activities (Section 1.3) and 
described in Section 4.1. 
•
Protocol waivers or exemptions are not allowed.
•
All significant safety concerns must be discussed with the Medical Monitor immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue treatment.
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•
Adherence to the study design requirements, including those specified in the Schedule of 
Activities (Section 1.3), is essential and required for study conduct.
•
All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria before randomization. Randomization should not occur until at least 
8 days after the screening visit to allow collection of PSSD data during screening in order to 
calculate a baseline PSSD score. The investigator will maintain a screening log to record details 
of all subjects screened and to confirm eligibility or record reasons for screening failure, as 
applicable.
•
Procedures conducted as part of the subject’s routine clinical management (eg, blood count) 
and obtained before signing of informed consent may be utilized for screening or baseline 
purposes provided the procedure meets the protocol-defined criteria and has been performed 
within the timeframe defined in the Schedule of Activities (Section 1.3).
•
For several assessments, appropriate training will be provided to investigators and designated 
personnel at sites. Only those individuals trained and certified to perform these assessments 
will be performing these assessments during the study
8.1
Efficacy Assessments
Every effort must be made to ensure that the same evaluator(s) complete the assessment for each 
subject. If the evaluator(s) is unable to complete the evaluation, then a qualified individual with 
overlapping experience may perform the evaluation. Documentation of who performed the 
evaluation is to be recorded in source documents. Assessments are to be performed at 
approximately the same time of day throughout the duration of the study. 
Baseline assessments must be performed per protocol. Procedures not specified in the protocol that 
are part of standard care may be performed if they do not interfere with study procedures; any data 
arising from such procedures are not to be reported in the eCRF.
8.1.1
Investigator-administered Assessments
8.1.1.1
Static Physician Global Assessment (sPGA)
The sPGA is 5-point scale of an average assessment of all psoriatic lesions based on erythema, 
scale, and induration.24 The sPGA measure determines psoriasis severity at a single point in time 
(without taking into account the baseline disease condition) as clear (0), almost clear (1), mild (2), 
moderate (3), or severe (4). All sPGA assessments should be performed by a trained physician (eg,
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 5).
8.1.1.2
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 the area of involvement (head, arms, trunk to groin, and 
legs to top of buttocks).25 The PASI produces a numeric score that can range from 0 to 72, with 
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higher PASI scores denoting more severe disease activity. The 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. All PASI assessments should be performed by a trained 
physician (dermatologist) or appropriately trained investigator who is experienced in the 
assessment of psoriasis patients (see APPENDIX 6).
8.1.1.3
Body Surface Area (BSA)
Measurement of psoriasis BSA involvement is estimated using the handprint method with the size 
of a subject’s handprint (including fingers and thumb) representing 1% of BSA involved.26,27,28
The 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% (40 handprints). BSA assessments 
should be performed by a dermatologist or appropriately trained investigator who is experienced 
in the assessment of psoriasis patients.
8.1.1.4
Scalp-Specific Physician’s Global Assessment (ss-PGA)
For this assessment in subjects with scalp involvement,29 scalp lesions are evaluated in terms of 
clinical signs of redness, thickness, and scaliness and scored on the following 5-point ss-PGA 
scale:
0 = absence of disease, 1 = very mild disease, 2 = mild disease, 3 = moderate disease, 
4 = severe disease.
The ss-PGA should be performed by a dermatologist or appropriately trained investigator who is 
experienced in the assessment of psoriasis patients. An example of the ss-PGA is provided in 
APPENDIX 7.
8.1.1.6
Physician Global Assessment-Fingernails (PGA-F)
In this assessment,31 the overall condition of the fingernails is rated on a 5-point scale:
0 = clear, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe
The PGA-F will be performed only in subjects with psoriatic fingernail involvement to assess 
severity and subsequent improvement. An example is provided in APPENDIX 9. The PGA-F 
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should be performed by a dermatologist or appropriately training investigator who is experienced 
in the assessment of psoriasis patients.
8.1.1.8
Palmoplantar PGA (pp-PGA)
This measure will be used for subjects with palmoplantar involvement at baseline.33 The pp-PGA 
uses a 5-point (0-4) scale:
0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; and 4 = severe (see APPENDIX 11).
The pp-PGA should be performed by a dermatologist or appropriately trained investigator who is 
experienced in the assessment of psoriasis patients.
8.1.2
Subject-reported Assessments
8.1.2.1
Psoriasis Symptoms and Signs Diary (PSSD)
The PSSD is an 11-item subject-reported instrument that assesses severity of symptoms and 
subject-observed signs commonly associated in plaque psoriasis.35,36 It has been shown to be 
reliable and valid in measuring symptoms and signs of subjects with moderate-to-severe plaque 
psoriasis in the clinic and has strong psychometric properties in assessing treatment effects in 
clinical trials.37 The PSSD assesses severity of 5 symptoms (itch, pain, stinging, burning, skin 
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tightness) and 6 subject-observed signs (skin dryness, cracking, scaling, shedding or flaking, 
redness, bleeding) using 0–10 numerical ratings. The severity of each item is rated on an 11-point 
numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). Two versions of the PSSD 
were developed, one with a 24-hour recall period (PSSD-24h) and one with a 7-day recall period. 
The PSSD-24h will be administered daily in this trial to avoid recall bias with a longer recall period 
(see APPENDIX 13).
8.1.2.2
Dermatology Life Quality Index (DLQI)
The DLQI38 is 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: 0 – “not at all”, 1 
– “a little”, 2 – “a lot”, or 3 – “very much”. The scores are summed, giving a range from 0 (no 
impairment of life quality) to 30 (maximum impairment) (see APPENDIX 14).
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8.1.2.8
Psoriatic Arthritis Screening and Evaluation (PASE) Questionnaire
The PASE questionnaire will be administered at screening in subjects with peripheral joint 
complaints. The PASE questionnaire is a self-administered tool that is used to screen for psoriatic 
arthritis among subjects who have psoriasis. The PASE questionnaire consists of 15 questions 
subdivided into 7 questions focusing on symptoms of psoriatic arthritis, and 8 questions focusing 
on the impact of psoriatic arthritis on function. Each question is scored on a 1-5 scale, with a 
maximum score of 75. A score of 47 or above has been shown to distinguish between psoriatic 
arthritis and non-psoriatic arthritis.44 This questionnaire is only intended to be a screening tool for 
psoriatic arthritis and does not replace a comprehensive musculoskeletal exam performed by a 
rheumatologist. The PASE questionnaire should take 6 to 10 minutes to complete and is done only 
at screening (See APPENDIX 20).
8.2
Adverse Events
The definitions of an AE and SAE can be found in APPENDIX 3.
All AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject's legally authorized representative). 
The investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE and remain responsible for following up AEs that 
are serious, considered related to the study treatment or the study, or that caused the subject to 
discontinue before completing the study. 
Contacts for SAE reporting are specified in APPENDIX 3.
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8.2.1
Adverse Events of Interest
Adverse events of interest (AEIs) are AEs for a particular product or class of products that a 
Sponsor may wish to monitor carefully. Adverse events of interest may be serious or non-serious. 
Such events may require further investigation to better characterize and understand them. In the 
BMS-986165 clinical development program, certain skin-related AEs (eg, acne), infection AEs, 
and CK elevation have been identified as potential AEIs; however, there has been no definitive 
assessment on the causal relationship between these events and treatment with BMS-986165. 
Additionally, given a potential association between treatment for autoimmune diseases and 
increased risk for cancer, malignancy has been identified as a potential AEI. Therefore, additional 
information about certain skin-related AEs, infection AEs, CK elevation, and malignancy may be 
collected on the case report form in order to better characterize and understand them.
8.2.2
Time Period and Frequency for Collecting AE and SAE Information
The collection of nonserious AE information should begin at initiation of study treatment until 
discharge from the study (ie, final study visit for a given subject), at the timepoints specified in the 
Schedule of Activities (Section 1.3). 
The Reference Safety Information in Sections 5.6.1 and 5.6.2 of the IB should be used to determine 
expectedness of SAEs 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 from the date of subject’s written consent until 30 days after the final 
dose of the study drug or subject’s participation in the study if the last scheduled visit occurs at a 
later time. Monitoring for SAEs will occur at every study visit. 
•
The investigator must report any SAE that occurs after these time periods and that is believed 
to be related to study drug or protocol-specified procedure. Medical occurrences that begin 
before the start of study treatment but after obtaining informed consent will be recorded on the 
appropriate section of the CRF.
•
All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated 
in APPENDIX 3. 
•
The investigator will submit any updated SAE data to the sponsor within 24 hours of this being 
available.
Investigators are not obligated to actively seek AEs or SAEs in former study subjects; however, if 
the investigator learns of any SAE, including a death, at any time after a subject has been 
discharged from the study, and he/she considers the event reasonably related to the study treatment 
or study participation, the investigator must promptly notify the Sponsor.
The method of evaluating and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in APPENDIX 3.
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8.2.3
Method of Detecting AEs and SAEs
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.)
8.2.4
Follow-up of AEs and SAEs
•
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see APPENDIX 3).
•
Follow-up is also required for nonserious AEs that cause interruption or discontinuation of 
study treatment and for 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. Completion of supplemental CRFs may be requested for AEs and/or laboratory 
abnormalities that are reported/identified during the course of the study.
•
After the initial AE/SAE report, the investigator is required to proactively follow each subject 
at subsequent visits/contacts. All SAEs will be followed until resolution, until the condition 
stabilizes, until the event is otherwise explained, or until the subject is lost to follow-up (as 
defined in Section 7.3).
Further information on follow-up procedures is given in APPENDIX 3.
8.2.5
Regulatory Reporting Requirements for SAEs
•
Prompt notification by the investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a product 
under clinical investigation are met.
•
An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with 
the IB and will notify the IRB/IEC, if appropriate according to local requirements.
Sponsor or designee will be reporting AEs to regulatory authorities and ethics committees 
according to local applicable laws including European Directive 2001/20/EC, FDA Code of 
Federal Regulations 21 CFR Parts 312 and 320, and Standard and Procedure for Expedited 
Reporting of Safety Data during Clinical Trials of Drugs, issued by the CDE. A SUSAR 
(Suspected, Unexpected Serious Adverse Reaction) is a subset of SAEs and will be reported to the 
appropriate regulatory authorities and investigators following local and global guidelines and 
requirements.
8.2.6
Pregnancy
In the event a subject becomes pregnant during the trial, the study treatment must be discontinued 
immediately. If the subject becomes pregnant while on treatment or within 3 days of discontinuing 
study treatment, the investigator must immediately notify 
 Drug Safety of this event and 
complete and forward a Pregnancy Surveillance Form to 
 Drug Safety within 24 hours of 
awareness of the event and in accordance with SAE reporting procedures described in APPENDIX 
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3. The investigator must also notify the Medical Monitor or designee of this event within 24 hours 
of awareness of pregnancy. 
The pregnant subject will need to be followed up until the conclusion of the pregnancy for 
pregnancy outcomes. The safety data of the subject will continue to be collected under the same 
rules as instructed in Section 7.1.
Any pregnancy that occurs in a female partner of a male study subject should be reported to 
 
Drug Safety. In order for Sponsor or designee to collect any pregnancy surveillance information 
from the female partner, the female partner must sign an ICF for disclosure of this information. 
Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
8.2.7
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.
•
Any laboratory test result that is clinically significant or meets the definition of an SAE 
•
Any laboratory test result abnormality that required the subject to have study treatment 
discontinued or interrupted
•
Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia versus low hemoglobin value).
8.2.8
Potential Drug Induced Liver Injury (DILI)
All occurrences of potential DILIs, meeting the defined criteria, must be reported as SAEs (see 
Section 8.2 and APPENDIX 3 for reporting details). Wherever possible, timely confirmation of 
initial liver-related laboratory abnormalities should occur prior to the reporting of a potential DILI 
event.
Potential DILI is defined as: 
1) ALT or AST elevation >3 times 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 liver function test 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.
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8.2.9
Other Safety Considerations
Any significant worsening of a pre-existing medical condition noted during interim or final 
physical examinations, electrocardiogram, x-ray filming, 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.
8.3
Overdose
For this study, taking more than 2 days’ worth of study medication within a 24-hour time period 
will be considered an overdose.
In the event of an overdose the investigator should:
1) Contact the Medical Monitor immediately
2) Closely monitor the subject for AEs/SAEs and laboratory abnormalities
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the subject.
8.4
Safety
Planned time points for all safety assessments are listed in the Schedule of Activities (Section 1.3).
8.4.1
Physical Examinations
A complete physical examination will include general appearance, vital signs, eyes, ears, nose 
mouth, throat, neck, respiratory, cardiovascular, respiratory, GI, lymphatic, musculoskeletal, skin, 
psychiatric and neurologic exams. A targeted physical examination will include vital signs, and 
any organ system associated with an AE or a laboratory abnormality.
8.4.2
Vital Signs
Refer to Schedule of Activities (Section 1.3).
8.4.3
Electrocardiograms
A 12-lead ECG will be performed at the visits indicated in the Schedule of Activities (Section 1.3). 
The patient will remain supine for 5-10 minutes prior to the ECG and must have their lab work 
done after the tracing so that the ECG results remain as accurate as possible. The ECG results will 
be read by the primary study investigator or a designee.
8.4.4
Tuberculosis Screening and Chest Imaging
Chest imaging results and PE are part of the process to assess a subject’s eligibility, as outlined in 
Section 1.3 and as defined in exclusion criterion 3.c (Section 5.2). Chest imaging (eg, chest x-ray, 
chest CT scan) at the screening visit is required if not already performed and documented within 
6 months of obtaining written informed consent. A subject must not have active signs or symptoms 
of TB, as judged by the investigator, to be eligible for the study.
In addition to a complete PE and medical history to evaluate exposure to TB, all subjects will have 
a screening test, an IGRA (eg, QuantiFERON®-TB test) performed centrally. If unable to obtain 
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central laboratory results, an IGRA test could be obtained locally, after consultation with the 
 
Medical Monitor. A subject with an indeterminate IGRA test result must be retested for 
confirmation. If the second result is again indeterminate, the subject will be excluded from the 
study. If the second result is positive, the subject should be treated as having LTBI provided there 
are no signs or symptoms of active TB. If the second result is negative, the subject may be eligible 
provided no other exclusion criterion for TB is met.
8.4.5
Clinical Safety Laboratory Assessments
Investigators must document their review of each laboratory safety report
Hematology
Hemoglobin (Hgb)
Hematocrit (Hct)
White Blood Cell Count, including differential
Platelet Count
Chemistry
AST
ALT
Total Bilirubin
Direct Bilirubin (if total bilirubin >ULN)
Alkaline Phosphatase
Lactate Dehydrogenase (LDH)
Creatinine
Blood Urea Nitrogen (BUN)
Uric Acid 
Glucose (fasting at some visits)
Total Protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Creatine Kinase (CPK)*
Estimated Glomerular Filtration Rate (eGFR)
Urinalysis
Protein
Glucose
Blood
Leukocyte Esterase
Specific Gravity
pH
Microscopic Examination (reflex if abnormal)
Lipid Panel
Cholesterol (total)
High Density Lipoprotein (HDL)
Low Density Lipoprotein (LDL)
Triglycerides 
Infectious Serologies
(HIV RNA as appropriate)
Hepatitis C Antibody with reflex to Hepatitis C RNA if positive
Hepatitis B Surface Antigen (HBsAg)
Hepatitis B Surface Antibody (HBsAb)
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Hepatitis B Core Antibody (HBcAb)
Hepatitis B DNA Viral Load (HBV-DNA)
HIV-1 and -2 antibody 
Other Analyses
Pregnancy test (WOCBP only: serum hCG test at screening, followed by urine hCG test or 
serum hCG test every 4 weeks)
Follicle Stimulating Hormone (FSH) (to confirm menopausal status [see APPENDIX 4], at 
screening) use as applicable
Hemoglobin A1C 
Thyroid Stimulating Hormone (TSH)
•
If TSH above normal reference range, test free T4; if TSH below normal range, test 
free T4 & T3
High Sensitivity C Reactive Protein (hsCRP)
Serum immunoglobulin (IgM, IgG, IgA, IgE)
*If CK >2.5 × ULN, then reflex testing (ie, CK-MB, Troponin I) will be required.
8.4.5.1
Estimated Glomerular Filtration Rate (eGFR)
Glomerular filtration rate will be estimated using the Modification of Diet in Renal Disease 
(MDRD) equation at screening and during the study at selected visits.
The MDRD equation is as follows:45
eGFR = 175 × standardized SCr−1.154 × age−0.203 × 1.212 [if black] or 0.742 [if female]
Note: GFR is expressed as mL/min/1.73 m2 of body surface area and SCr (serum creatinine) is expressed in mg/dL.
Subjects with an eGFR <45 mL/min will be excluded from participation
8.4.6
Depression Monitoring
Depression will be monitored by administration of the eight-item Patient Health Questionnaire 
(PHQ-8) at screening and during visits as outlined in Section 1.3.
8.4.6.1
Eight Item Patient Health Questionnaire (PHQ-8)
The PHQ-8 is established as a valid diagnostic and severity measure for depressive disorders in 
large clinical studies.46 Each of the 8 questions is based on a 2-week recall and scored on a scale 
of 0 to 3 by a tick box as: Not at All, Several Days, More than Half the Days and Nearly Every 
Day. A score of ≥10 is suggestive of moderate depressive symptoms (see APPENDIX 21).47 If a 
subject scores ≥ 15 on the PHQ-8 during the study, the investigator will review the situation and 
refer the subject to a mental health professional if deemed necessary.
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8.4.7
Suicidal Ideation and Behavior (SIB) Monitoring
Subjects in this clinical trial will be monitored for SIB by the eC-SSRS (Section 8.4.7.1) at the 
visits outlined in the Schedule of Activities (Section 1.3). Subjects who answer yes to Questions 4 
or 5 which indicates a suicidal ideation severity level of 4 or 5 or document suicidal behavior or 
suicidal attempts on the eC-SSRS will have their treatments discontinued and be immediately 
referred to a mental health professional for further evaluation. In addition, family members or 
caregivers of the subjects will be instructed to immediately report any suicidal ideation, suicidal 
behavior, or suicide attempt to the investigator.
8.4.7.1
Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a computer-automated, 
patient-reported version of the C-SSRS instrument that defines 11 categories of SIB events.48,49,50
The categories are as follows:
•
Suicidal ideation
1) Passive
2) Active: Nonspecific (no method, intent, or plan)
3) Active: Method, but no intent or plan
4) Active: Method and intent, but no plan
5) Active: Method, intent, and plan
•
Suicidal behavior
1) Completed suicide
2) Suicide attempt
3) Interrupted attempt
4) Aborted attempt
5) Preparatory actions toward imminent suicidal behaviors
•
Self-injurious behavior, no suicidal intent
Definitions of these categories can be found in APPENDIX 2251
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8.6
Health Economics OR Medical Resource Utilization and Health 
Economics
Health Economics/Medical Resource Utilization and Health Economics parameters will not be 
evaluated in this study.
9
STATISTICAL CONSIDERATIONS
9.2
Populations for Analyses
For purposes of analysis, the following analysis sets will be used in this study:
Enrolled Population: All subjects who sign informed consent.
Full Analysis Set (FAS): All subjects who were randomized. Following the intent-to-treat 
principle, subjects will be analyzed according to the treatment group assigned at randomization. 
The FAS will be the primary efficacy analysis population.
Per Protocol Set (PPS): A subset of the FAS who are compliant with study treatment and who do 
not have any relevant protocol deviations that may impact the coprimary efficacy endpoint 
assessments (Section 9.6.3). The PPS will be analyzed for the coprimary endpoint comparisons 
according to the treatment assigned at randomization. 
As-treated Population: All randomized subjects who took at least one dose of study treatment. 
Subjects will be analyzed according to treatment received. The As-treated population will be for 
safety analyses.
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9.3
Endpoints
9.3.1
Primary Endpoints
The coprimary efficacy endpoints for BMS-986165 compared to placebo at Week 16 are defined 
as:
•
sPGA 0/1 response assessed as a proportion of subjects with a sPGA score of 0 or 1
•
PASI 75 response assessed as a proportion of subjects who achieve a 75% improvement from 
baseline in the PASI score
9.3.2
Key Secondary Endpoints
The key secondary endpoints for BMS-986165 compared to placebo at Week 16 are defined as:
•
PASI 90 response assessed as a proportion of subjects who achieve a 90% improvement from 
baseline in the PASI score
•
sPGA 0 response assessed as a proportion of subjects with a sPGA score of 0
•
PASI 100 response assessed as a proportion of subjects who achieve a 100% improvement 
from baseline in the PASI score
•
Change from baseline in PSSD symptom score
•
PSSD symptom score of 0 assessed as a proportion of subjects with a PSSD symptom score of 
0 among subjects with a baseline PSSD symptom score ≥1
•
ss-PGA 0/1 assessed as a proportion of subjects with a ss-PGA score 0 or 1 among subjects 
with a baseline ss-PGA score ≥3
•
DLQI 0/1 assessed as a proportion of subjects with a DLQI score of 0 or 1 among subjects 
with a baseline DLQI score ≥2
•
PGA-F 0/1 assessed as a proportion of subjects with a PGA-F score of 0 or 1 among subjects 
with a baseline PGA-F score ≥3
•
pp-PGA 0/1 assessed as a proportion of subjects with a pp-PGA score of 0 or 1 among subjects 
with a baseline pp-PGA score ≥3
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9.4
Efficacy Analyses
Categorical data will be summarized as frequency counts and percentages. Continuous data will 
be summarized using n, mean, standard deviation, median, minimum, and maximum unless 
otherwise specified. Efficacy values will be summarized for all visits in which the variable is 
assessed. Details of the planned analyses of endpoints during the 16-week double-blind placebo-
controlled period will be documented in the statistical analysis plan (SAP) and finalized before the 
Week 16 database lock.
During the first 16 weeks of treatment, data will be presented for the following treatments:
•
BMS-986165 6 mg QD
•
Placebo
After Week 16, data will be presented for the following treatments:
•
BMS-986165 6 mg QD
•
Placebo      BMS-986165 6 mg QD (starting from Week 16 through Week 52)
•
All BMS-986165 6 mg QD (all subjects exposed to BMS-986165 6 mg QD; includes subjects 
on placebo that switched to BMS-986165 6 mg QD)
9.4.1
Coprimary Endpoint Analyses
The analysis model for the coprimary efficacy endpoints, sPGA 0/1 and PASI 75 
(responder/nonresponder) at Week 16, will use stratified Cochran-Mantel-Haenszel (CMH) tests 
stratified by the stratification factors used for randomization (see Section 4.1.2) to compare the 
response rates of BMS-986165 6 mg QD to placebo using the Week 16 data of the FAS. The odds 
ratio (ratio of odds in BMS-986165 6 mg QD group to the odds in placebo group) and the 
corresponding 2-sided 95% confidence interval (CI) will be provided. Estimates of proportions 
and their 2-sided 95% CIs will be provided.
9.4.1.1
Imputation Methods for Coprimary Endpoints
Non-responder imputation (NRI) will be used for coprimary efficacy endpoints for subjects who 
discontinue treatment or study prior to Week 16, start a protocol prohibited medication/therapy 
that could improve psoriasis during the first 16 weeks of treatment, or who have otherwise missing 
endpoint data at the specified timepoint. NRI will be the primary method of imputation for the 
coprimary efficacy endpoints.
9.4.1.2
Sensitivity Analyses for the Coprimary Endpoints
Sensitivity analyses to be performed for the coprimary endpoints will be described in the SAP 
prior to the Week 16 database lock.
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9.4.1.3
Supportive Analyses for the Coprimary Endpoints
The coprimary efficacy endpoints will be analyzed using the Week 16 data of the PPS using the 
analysis described in Section 9.4.1 and the imputation methods described in Section 9.4.1.1.
Additionally, the coprimary efficacy endpoints for the FAS will be analyzed with a logistic 
regression model with treatment and the stratification factors used for randomization as covariates. 
9.4.1.4
Subgroup Analyses for the Coprimary Endpoints
Subgroup analyses will be conducted for the coprimary efficacy endpoints for the FAS using the 
analysis described in Section 9.4.1 and the imputation methods described in Section 9.4.1.1. 
Subgroups to be evaluated may include the following:
•
Gender
•
Age categories (<65; ≥65)
•
Prior biologic use (yes/no)
•
Prior systemic treatment of psoriasis (yes/no)
•
Country
Additional subgroups may be defined for descriptive summaries in the SAP.
9.4.2
Secondary Endpoint Analyses
The analysis model for the binary secondary endpoints will use stratified CMH tests stratified by 
the stratification factors used for randomization (see Section 4.1.2) to compare the response rates 
of BMS-986165 6 mg QD to placebo for the FAS. The odds ratio (ratio of odds in BMS-986165 
6 mg QD group to the odds in placebo group) and the corresponding 2-sided 95% CI will be 
provided.
The analysis model for continuous secondary endpoints will use analysis of covariance 
(ANCOVA) with treatment and stratification factors used for randomization as fixed effects. The 
baseline value will be added into the model as a covariate. Treatment differences based on 
least-squares (LS) means and the corresponding 2-sided 95% CIs will be provided for the 
difference between BMS-986165 6 mg QD and placebo.
9.4.2.1
Imputation Methods for Secondary Endpoints
The NRI will be applied to the analyses of binary secondary efficacy endpoints for subjects who 
discontinue early, start a protocol prohibited medication/therapy that could improve psoriasis, or 
who have otherwise missing endpoint data prior to the specified timepoint. 
For continuous secondary efficacy endpoints, a modified baseline observation carried forward 
(mBOCF) will be used for missing data. The baseline observation will be carried forward for 
subjects who discontinue study treatment due to:
•
Lack of efficacy
•
AEs
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and for subjects who start a protocol prohibited medication/therapy that could improve psoriasis 
prior to the endpoint. The last valid observation will be carried forward for all other subjects with 
missing data.
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9.5
Safety Analyses
Safety data will be analyzed for AEs, SAEs, laboratory analytes, vital signs, ECGs, and suicidality 
and depression. Safety will be summarized using the As-treated population. Categorical data will 
be summarized as frequency counts and percentages. Continuous data will be summarized using 
n, mean, standard deviation, median, minimum, and maximum unless otherwise specified.
During the first 16 weeks of treatment data will be presented for the following treatments:
•
BMS-986165 6 mg QD
•
Placebo
After Week 16 data will be presented for the following treatments:
•
BMS-986165 6 mg QD
•
Placebo→BMS-986165 6 mg QD (starting from Week 16 through Week 52)
•
All BMS-986165 6 mg QD (all subjects exposed to BMS-986165 6 mg QD; includes subjects 
on placebo that switched to BMS-986165 6 mg QD)
9.5.1
Adverse Events
Treatment-emergent adverse events (TEAEs), SAEs and deaths, and AEs leading to study 
treatment discontinuation, AEs by maximum severity, and AEs by relationship will be summarized 
by the MedDRA system organ class and preferred term. All TEAEs, AEIs, as well each AE 
adjudicated category (ie, infections, cardiovascular, and suicidal ideation and behavior) will also 
be summarized by preferred term sorted by decreasing frequency. 
9.5.2
Vital Signs and ECGs
Vital signs and ECGs will be summarized as raw, change from baseline, and change from 
maximum postbaseline value. Incidence of abnormal ECG will also be summarized.
9.5.3
Clinical Laboratory Tests
Laboratory analytes will be summarized as raw, change from baseline, and change from maximum 
postbaseline value. Incidence of abnormal, high, or low values will be summarized.
9.5.4
Suicidality and Depression Assessments
Suicidality and depression will be assessed using eC-SSRS and PHQ-8. Data will be summarized, 
as applicable.
9.6
Other Analyses 
9.6.1
Demographics and Baseline Data
Demographics and baseline data will be summarized by treatment for each applicable analysis 
population. Categorical data will be summarized as frequency counts and percentages. Continuous 
data will be summarized using n, mean, standard deviation, median, minimum, and maximum 
unless otherwise specified.
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9.6.2
Prior and Concomitant Medications
Prior and concomitant medications, categorized by medication group and subgroup according to 
the World Health Organization (WHO) Drug Dictionary, will be summarized by treatment for the 
As-treated population. Medications with an end date prior to the first dose of study drug will be 
considered prior medications.
9.6.3
Relevant Protocol Deviations
Relevant protocol deviations are deviations that can have an impact on the primary efficacy 
endpoints. The impact of relevant protocol deviations on the primary efficacy results will be 
assessed by excluding subjects from the FAS to define the PPS in supportive analyses of the 
primary efficacy endpoints. Relevant protocol deviations to be considered regarding exclusion of 
subjects from the FAS will include the following:
•
Subject was randomized but did not take any study treatment
•
Subject failed to meet any study inclusion criteria but was randomized to receive study
treatment
•
Subject met a study exclusion criterion which may have an impact on the coprimary efficacy
endpoints but was randomized to receive study treatment
•
Subject was noncompliant with study treatment within the first 16 weeks of treatment; defined
as <80% compliant with study treatment
•
Subject took prohibited concomitant medication prior to Week 16
•
Subject received treatment different than assigned treatment at any visit prior to Week 16
All subjects with relevant protocol deviations will be identified prior to the Week 16 database lock. 
Relevant protocol deviations will be summarized by treatment group and deviation category for 
the FAS population.
9.7
Interim Analyses
No interim analysis is currently planned.
9.8
Analysis and Reporting
An unblinded analysis of the data collected up to Week 16 will be conducted once all randomized 
subjects have either completed the placebo-controlled treatment period (ie, through Week 16) or 
have discontinued prior to Week 16. Details of these analyses will be provided in an SAP that will 
be finalized before the Week 16 database lock. A final database lock and analysis will occur after 
all subjects complete Week 52 or discontinue prior to Week 52.
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10
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(ESTEEM) clinical trials in patients with moderate to severe psoriasis. J Am Acad Dermatol. 
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35 Feldman SR. Development of a patient-reported outcome questionnaire for use in adults with 
moderate-to-severe plaque psoriasis: The Psoriasis Symptoms and Signs Diary. Journal of 
Dermatology & Dermatologic Surgery. 2016;20:19–26.
36 Mathias SD. Measurement properties of a patient-reported outcome measure assessing 
psoriasis severity: The psoriasis symptoms and signs diary. Journal of Dermatological 
Treatment. 2016;27(4):322-327.
37 Armstrong A, Puig L, Langley R, et al. Validation of psychometric properties and development 
of response criteria for the Psoriasis Symptoms and Signs Diary (PSSD): results from a phase 
III 
clinical 
trial. 
Journal 
of 
Dermatological 
Treatment.
2017: 
1-31. 
DOI: 
10.1080/09546634.2017.1364694.
38 Finlay, AY, Khan, GK: Dermatology Life Quality Index (DLQI): A simple practical measure 
for routine clinical use. Clin Exp Dermatol. 1994;19:210–216.
 
 
 
 
44 Husni ME, Meyer KH, Cohen DS, Mody E, Qureshi AA. J Am Acad Dermatol 
2007;57(4):581-7
45 Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, et al. Using standardized 
serum creatinine values in the modification of diet in renal disease study equation for 
estimating glomerular filtration rate. Ann Intern Med 2006;145(4):247–54.
46 Kroenke K, Strine TW, Spitzer RL, et al. The PHQ-8 as a measure of current depression in the 
general population. J Affect Disord. 2009;114(1-3):163-173.
47 Dhingra SS, Kroenke K, Zack MM, Strine TW, Balluz LS. PHQ-8 Days: a measurement option 
for DSM-5 Major Depressive Disorder (MDD) severity. Population Health Metrics. 2011;9:11. 
doi:10.1186/1478-7954-9-11.
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Revised Protocol No.: 05
Date: 11-Nov-2020
48 The Federal Register. Guidance for Industry- Suicidal ideation and behavior: prospective 
assessment 
of 
occurrence 
in 
clinical 
trials.
(06-Aug-2012). 
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidanc
es/UCM225130.pdf. Accessed 22-Mar-2018.
49 Greist JH, Mundt JC, Gwaltney CJ, Jefferson JW, Posner K. Predictive value of baseline
electronic Columbia–Suicide Severity Rating Scale (eC–SSRS) assessments for identifying
risk of prospective reports of suicidal behavior during research participation. Innov Clin 
Neurosci. 2014;11(9–10):23–31.
50 Mundt JC, Greist JH, Jefferson JW, Federico M, Mann JJ, Posner K. Prediction of suicidal 
behavior in clinical research by lifetime suicidal ideation and behavior ascertained by the 
electronic Columbia-Suicide Severity Rating Scale. J Clin Psychiatry. 2013;74(9):887-893.
51 Posner, K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification Algorithm 
of Suicide Assessment (C-CASA): Classification of Suicidal Events in the FDA’s Pediatric 
Suicidal Risk Analysis of Antidepressants. Am J Psychiatry. 2007;164:1035-1043
52 Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: what is moderate 
pain in millimetres? Pain. 1997;72(1-2):95-7.
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11
APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
AE
adverse event
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
ANOVA
analysis of variance
Anti-HCV
hepatitis C virus antibody
AST
aspartate aminotransferase
 
 
 
BID
twice daily
BMS
Bristol-Myers Squibb
BOCF
baseline observation carried forward
BSA
body surface area
BUN
blood urea nitrogen
CFR
Code of Federal Regulations
CI
confidence interval
CMH
Cochran-Mantel-Haenszel 
CK
creatine kinase
 
DILI
drug-induced liver injury
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
ECG
electrocardiogram
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Term
Definition
eCRF
electronic case report form
eC-SSRS
electronic Columbia-Suicide Severity Rating 
Scale
eGFR
Estimated Glomerular Filtration Rate
 
FAS
Full Analysis Set
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus 
HCV
hepatitis C virus
Hgb
hemoglobin
HIV
human immunodeficiency virus
hs-CRP
high-sensitivity C-reactive protein
IB
Investigator Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IFN
interferon
IFNγ 
interferon gamma
IgG
immunoglobulin gamma
IGRA
interferon gamma release assay
IL
interleukin
IMP
investigational medicinal product
IP
investigational product 
IRT
interactive response technology
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Term
Definition
ITT
intent-to-treat
IV
intravenous
JAK
Janus kinase
LOCF
last observation carried forward
LS
least-squares
LTBI
latent tuberculosis infection
MACE
Major Adverse Cardiovascular Event
mBOCF
modified baseline observation carried forward
NRI
non-responder imputation
NSAID
nonsteroidal anti-inflammatory drug
PASE
psoriatic arthritis screening and evaluation
PASI
Psoriasis Area and Severity Index
PD
pharmacodynamics
PE
physical examination
PGA-F
Physician Global Assessment-Fingernails
PHQ-8
Eight Item Patient Health Questionnaire
PK
pharmacokinetics
 
pp-PGA
palmoplantar Physician’s Global Assessment
PPS
Per Protocol Set
PRO
patient reported outcome
PsA
psoriatic arthritis
PSSD
Psoriasis Symptoms and Signs Diary
QD 
once daily
QOD
every other day
RBC
red blood cell
RNA
ribonucleic acid 
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Term
Definition
SAE
serious adverse event
SAP
statistical analysis plan
SIB
Suicidal Ideation and Behavior
SLE
systemic lupus erythematosus
sPGA
static Physician Global Assessment
ss-PGA
scalp-specific Physician’s Global Assessment
STAT
signal transducer and activator of 
transcription
TB
tuberculosis
T4
thyroxine
T3
triiodothyronine
TEAE
treatment-emergent adverse event
TNF
tumor necrosis factor 
TYK2
tyrosine kinase 2
ULN
upper limit of normal
WOCBP
women of childbearing potential
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
REGULATORY AND ETHICAL CONSIDERATIONS
GOOD CLINICAL PRACTICE
This study will be conducted in accordance with:
•
Good Clinical Practice (GCP), 
•
as defined by the International Council on Harmonisation (ICH)
•
in accordance with the ethical principles underlying European Union Directive 2001/20/EC
•
United States Code of Federal Regulations, Title 21, Part 50 (21CFR50) 
•
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 approval/favorable opinion by Institutional Review 
Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study.
All potential serious breaches must be reported to Sponsor or designee immediately. 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 (eg, loss of medical licensure, debarment). 
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 
(eg, advertisements), and any other written information to be provided to subjects. The 
investigator or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure
or product labeling information to be provided to subjects and any updates. 
The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
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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 relevant approval/favorable opinion(s) the deviation or change will be submitted, as 
soon as possible to:
•
IRB/IEC for 
•
Regulatory Authority(ies), if applicable by local regulations (per national requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of 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).
FINANCIAL DISCLOSURE
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate health authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study.
INFORMED CONSENT PROCESS
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. 
In situations where consent cannot be given to subjects, 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. 
Sponsor or designee will provide the investigator with an appropriate (ie, Global or Local) sample 
informed consent form 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:
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•
Provide a copy of the consent form 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 ICF 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 her 
informed consent 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 must also include a statement that BMS and regulatory authorities have direct 
access to subject records.
For minors, according to local legislation, one or both parents or a legally acceptable 
representative must be informed of the study procedures and must sign the informed consent form 
approved for the study prior to clinical study participation. The explicit wish of a minor, who is 
capable of forming an opinion and assessing this information to refuse participation in, or to be 
withdrawn from, the clinical study at any time should be considered by the investigator. 
Minors who are judged to be of an age of reason must also give their written assent.
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to refuse 
participation in, or to be withdrawn from, the clinical study at any time should be considered by 
the investigator.
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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SOURCE DOCUMENTS
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), AE 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, such paper 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. 
STUDY TREATMENT RECORDS
Records for study treatments (whether supplied by BMS, its vendors, or the site) must substantiate 
study treatment integrity and traceability from receipt, preparation, administration, and through 
destruction or return. Records must be made available for review at the request of BMS/designee 
or a Health Authority.
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 (eg, 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 
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If
Then
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 designee accepts 
responsibility for documenting traceability 
and study treatment 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 designee will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
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 designee electronic 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 electronic SAE form and paper Pregnancy Surveillance form, respectively. 
If electronic SAE form is not available, a paper SAE form can be used.
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 signatures and 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 subinvestigator and who is delegated this task on 
the Delegation of Authority Form. For electronic CRFs, review and approval/signature is 
completed electronically through the electronic data capture tool. The investigator must retain a 
copy of the CRFs including records of the changes and corrections.
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Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the electronic data capture tool using the unique user account 
provided by Sponsor or designee. User accounts are not to be shared or reassigned to other 
individuals
MONITORING
Sponsor or designee representatives 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 Sponsor or designee internal 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 Sponsor or designee. 
RECORDS RETENTION
The investigator must retain all study records and source documents for the maximum period 
required by applicable regulations and guidelines, or institution procedures, or for the period 
specified by BMS or designee, whichever is longer. The investigator must contact BMS prior to 
destroying any records associated with the study.
BMS or designee will notify the investigator when the study records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee. 
RETURN OF STUDY TREATMENT
For this study, study treatments (those supplied by BMS, a vendor or sourced by the investigator) 
such as partially used study treatment containers, vials and syringes may be destroyed on site. 
If
Then
Study treatments supplied by BMS (including 
its vendors
Any unused study treatments supplied by 
BMS can only be destroyed after being 
inspected and reconciled by the responsible 
Study Monitor unless study treatments 
containers must be immediately destroyed as 
required for safety, or to meet local 
regulations (eg, cytotoxics or biologics).
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If study treatments will be returned, the return 
will be arranged by the responsible Study 
Monitor.
Study treatments sourced by site, not supplied 
by BMS (or its vendors) (examples include 
study treatments sourced from the sites stock 
or commercial supply, or a specialty 
pharmacy)
It is the investigator’s or designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
It is the investigator’s or designee’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, ie, 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 designee’s responsibility to arrange for disposal of all empty containers.
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of non- study 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee.
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 designee
•
Subject recruitment (eg, among the top quartile of enrollers)
•
Involvement in trial design
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•
Regional representation (eg, 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 Sponsor 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 
Sponsor or designee 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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APPENDIX 3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING
ADVERSE EVENTS
Adverse Event Definition:
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation subject administered study drug and 
that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study drug, whether or not 
considered related to the study drug.
Events Meeting the AE Definition
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis.
•
Exacerbation of a chronic or intermittent preexisting condition including either an increase 
in frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after study intervention administration even though 
it may have been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose, as a verbatim term (as reported by the 
investigator), should not be reported as an AE/SAE unless it is an intentional overdose 
taken with possible suicidal/self-harming intent. Such overdoses should be reported 
regardless of sequelae and should specify “intentional overdose” as the verbatim term.
Events NOT Meeting the AE Definition
•
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.
•
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
DEFINITION OF SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met.
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SERIOUS ADVERSE EVENTS
Serious Adverse Event Definition: Any untoward medical occurrence that, at any dose:
Results in death
Is life-threatening (defined as an event in which the subject was at risk of death 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 note 
below)
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 (eg, 
routine colonoscopy)
•
medical/surgical admission other than to 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 (eg, lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason)
•
admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
Results in persistent or significant disability or permanent damage
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 [eg, 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 8.2.8 for the definition of potential DILI). 
Pregnancy and potential DILI must follow the same transmission timing and processes to BMS 
as used for SAEs (see Section 8.2.6 for reporting pregnancies).
EVALUATING AES AND SAES
Assessment of Intensity
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The intensity of AEs is determined by a physician and will use the following levels:
•
Mild: An event that is easily tolerated by the subject, causing minimal discomfort, and 
not interfering with everyday activities.
•
Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.
•
Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. Severe is a category utilized for rating the 
intensity of an even; and both AEs and SAEs can be assessed as severe.
Assessment of Causality
•
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. A “reasonable possibility of a relationship” conveys 
that there are facts, evidences, and/or arguments to suggest a causal relationship rather 
than a relationship cannot be ruled out.  
•
The investigator will use clinical judgment to determine the relationship.
•
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.
•
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.
•
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.
•
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Sponsor. However, it is very important 
that the investigator always make an assessment of causality for every event before the 
initial transmission of the SAE data to Sponsor.
•
The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment.
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.. 
Follow-up of AEs and SAEs
If only limited information is initially available, follow-up reports are required. Note: 
Follow-up SAE reports must include 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 BMS (or designee) using the same procedure used for transmitting the initial 
SAE report.
All SAEs must be followed to resolution or stabilization.
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Clinical Protocol
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REPORTING OF SAES TO SPONSOR OR DESIGNEE
SAEs, whether related or not related to study drug, and pregnancies must be reported to 
 Drug Safety within 24 hours of awareness of the event.
SAEs must be recorded on the SAE Report Form. For studies capturing SAEs through 
electronic 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.
Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted via 
email or confirmed facsimile (fax) transmission to:
SAE Email Address: 
SAE Fax Number: 
Americas: 
Europe/East Asia Pacific:
 
SAE Telephone Contact - For questions on SAE/pregnancy reporting, please call:
Americas: 
Europe/East Asia Pacific: 
.
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Clinical Protocol
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APPENDIX 4
WOMEN OF CHILDBEARING POTENTIAL DEFINTIONS 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 subject’s medical 
records, medical examination, or medical history interview.
•
Postmenopausal female
o
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 follicle stimulating 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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Clinical Protocol
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CONTRACEPTION GUIDANCE FOR FEMALE SUBJECTS 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 days after 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 
Failure rate of <1% per year when used consistently and correctly.a 
•
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationb
o
oral 
o
intravaginal 
o
transdermal 
•
Progestogen-only hormonal contraception associated with inhibition of ovulationb
o
oral 
o
injectable 
Highly Effective Methods 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
•
Vasectomized partner 
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. 
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•
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 treatment. 
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 subject.
•
It is not necessary to use any other method of contraception when complete abstinence is 
elected. 
•
WOCBP subjects who choose complete abstinence must continue to have pregnancy tests, 
as specified in Section 5.1
•
Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP subjects chooses 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 
subjects participating in clinical studies. 
b
Hormonal contraception may be susceptible to interaction with the study treatment, 
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).
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•
Spermicide only
•
Lactation amenorrhea method (LAM)
CONTRACEPTION GUIDANCE FOR MALE SUBJECTS WITH PARTNER(S) OF 
CHILD BEARING POTENTIAL.
Male subjects 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.
•
Male subjects are required to use a condom for study duration and until the end of relevant 
systemic exposure defined as 3 days after the end of treatment in the male subject.
•
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 days after the end of 
treatment in the male subject.
•
Male subjects 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 days after the end of treatment. 
•
Refrain from donating sperm for the duration of the study treatment and for 3 days after the 
end of treatment.
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 8.2.6 and APPENDIX 3
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Clinical Protocol
IM011065
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APPENDIX 5
STATIC PHYSICIAN’S GLOBAL ASSESSMENT OF PSORIASIS 
(SPGA)
The static PGA is used to determine the subject’s psoriasis lesions overall at a given time point. 
Overall lesions will be graded for erythema, induration, and scaling based on the scales below. 
The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA 
score.
Characteristics
Score
Rating Score
Erythema (E)
(averaged over the whole 
body)
0 = No evidence of erythema, but post 
inflammatory hyper/hypopigmentation 
changes may be present
1 = Faint erythema
2 = Light red coloration
3 = Moderate red 
coloration 
4 = Bright red 
Induration (I)
(averaged over the whole 
body)
0 = No evidence of plaque elevation
1 = Minimal plaque elevation, barely palpable, = 0.25 
mm
2 = Mild plaque elevation, slight but definite elevation, 
indistinct edge, = 0.5 mm
3 = Moderate plaque elevation, elevated with distinct 
edges, = 0.75 mm
4 = Severe plaque elevation, hard/sharp borders, ≥ 1 
mm
Scaling (S)
(averaged over the whole
body)
0 = No evidence of scaling
1 = Minimal; occasional fine scaling
2 = Mild; fine scale dominates
3 = Moderate; coarse scale predominates
4 = Severe; thick scale predominates
E + I + S = / 3 = (Total Average)
Physician’s Static Global Assessment based upon above Total Average 
0 = Clear, except for residual discoloration 
1 = Almost clear -majority of lesions have individual scores for E + I + S / 3 that averages 1 
2 = Mild -majority of lesions have individual scores for E + I + S / 3 that averages 2 
3 = Moderate -majority of lesions have individual scores for E + I + S / 3 that averages 3 
4 = Severe -majority of lesions have individual scores for E + I + S / 3 that averages 4 
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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Clinical Protocol
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TYK2 Inhibitor
APPENDIX 6
PSORIASIS AREA AND SEVERITY INDEX (PASI)
Psoriasis Area and Severity Index (PASI); a quantitative rating scale for measuring the severity 
of psoriatic lesions based on area coverage and plaque appearance. Please complete all sections 
of the table and shade in the affected areas on the body diagrams below.
Plaque Characteristic
Rating score
Body region (and weighting factor)
Head
Upper Extremities
Trunk
Lower Extremities
Erythema (Redness)
0 = None
1 = Slight
2 = Moderate
3 = Severe
4 = Very severe
Infiltration (Thickness)
Desquamation (Scaling)
Add together each of the 3 scores for each of the body regions to give 4 separate sub totals.
Sub Totals A1 =
A2 =
A3 =
A4 =
Multiply each sub total by amount of body surface area represented by that region i.e. A1 x 0.1 for head, A2 x 0.2 for 
upper extremities, A3 x 0.3 for trunk, A4 x 0.4 for lower extremities to give a value B1, B2, B3 and B4 for each body 
A1 x 0.1 = B1
A2 x 0.2 = B2
A3 x 0.3 = B3
A4 x 0.4 = B4
B1 =
B2 =
B3 =
B4 =
Degree of 
involvement as % for 
each body region 
affected; (score each 
region with score 
between 0-6)
0 = None
1 = 1-9 %
2 = 10-29%
3 = 30-49%
4 = 50 -69%
5 = 70-89%
6 = 90-100%
For each body region multiply sub total B1, B2, B3 and B4 by the score (0-6) of the % of body region involved to give 4 
subtotals C1, C2, C3 and C4
B1 x score = C1
B2 x score = C2
B3 x score = C3
B4 x score = C4
C1 =
C2 =
C3 =
C4 =
The patient’s PASI score is the sum of C1 + C2 + C3 + C4
PASI=
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Clinical Protocol
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APPENDIX 7
SCALP-SPECIFIC PHYSICIAN’S GLOBAL ASSESSMENT 
(SSPGA)
Please rate overall scalp psoriasis severity by selecting the overall score based on the following 
rating scale:
Score
Category
Description
0
Absence of 
Disease
No evidence of redness, no evidence of thickness, and no 
evidence of scaliness on the scalp
1
Very Mild Disease
The overall clinical picture consists of flat lesions with barely 
perceptible erythema, with or without a trace of overlying fine 
scale
2
Mild Disease
The overall clinical picture consists of lesions with mild 
erythema, slight, but definite, thickness, and a thin scale layer
3
Moderate Disease
The overall clinical picture consists of lesions with moderate 
erythema, a moderate thickness, and a moderate scaled layer
4
Severe Disease
The overall clinical picture consists of lesions with bright 
erythema, severe thickness, and a severe, coarse thick scale 
layer
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IM011065
BMS-986165
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Clinical Protocol
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APPENDIX 9
PHYSICIAN’S GLOBAL ASSESSMENT-FINGERNAILS (PGA-F)
For this assessment in subjects with psoriasis fingernail involvement, the overall condition of the 
fingernails is rated by the investigator on a 0-4 (5-point) scale. The overall score assigned based 
on the higher of the nail bed/nail matrix score:
Nail Bed Signs
Nail Matrix Signs
Clear
0
Onycholysis- consistent with a normal nail
AND
Hyperkeratosis- none
AND
Splinter Hemorrhages-consistent with non-psoriatic splinter 
hemorrhages
AND
Nail Bed Erythema- none
No nonpsoriatic nail plate 
irregularities including 
pitting, crumbling, Beau’s 
lines, senile onychorrhexis, 
and nonpsoriatic leukonychia
Minimal
1
Onycholysis- < 10% involved on all nails
OR
Hyperkeratosis- present, but barely detectable elevation of 
nail plate
OR
Nail Bed Erythema- faint
AND
Splinter Hemorrhages- consistent with non-psoriatic splinter 
hemorrhages
No more than 5 pits or 
psoriatic leukonychia on any 
nail
AND
No crumbling
Mild
2
Onycholysis- >10% on five or more nails
OR
Hyperkeratosis- present with mild elevation of nail plate
OR
Splinter Hemorrhages- present on four or fewer nails
OR
Nail Bed Erythema- mild
Five or more nails with mild 
pitting (eg, >10 pits/nail) or 
psoriatic leukonychia
AND
No crumbling
Moderate
3
Onycholysis- >30% on at least one nail
OR
Hyperkeratosis- present with moderate elevation of nail plate
OR
Splinter Hemorrhages-  scattered and present on five or more 
nails
OR
Nail Bed Erythema- moderate
Five or more nails with 
moderate pitting (eg, >25 
pits/nail)
AND
≤25% crumbling on any nails
Severe
4
Onycholysis- >50% on at least one nail
OR
Hyperkeratosis- present with severe elevation of nail plate
OR
Splinter Hemorrhages- numerous and present on five or more 
nails
OR
Nail Bed Erythema- severe
Five or more nails with 
severe pitting (>50 pits/nail)
OR
>25% crumbling on any nail
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Clinical Protocol
IM011065
BMS-986165
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IM011065
BMS-986165
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Clinical Protocol
IM011065
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APPENDIX 11
PALMOPLANTAR PSORIASIS PHYSICIAN’S GLOBAL 
ASSESSMENT (pp-PGA)
Palmoplantar (including finger and toe surfaces) psoriasis lesions are evaluated by the 
investigator based on overall severity, then scored on the following 5-point scale:
Score
Category
Description
0
Clear
No signs of plaque psoriasis
1
Almost 
Clear
Just perceptible erythema and just perceptible scaling
2
Mild
Light pink erythema, with minimal scaling with or without pustules
3
Moderate
Dull red, clearly distinguishable erythema with diffuse scaling, some 
thickening of the skin, with or without fissures, with or without pustule 
formation
4
Severe
Deep, dark red erythema with obvious and diffuse scaling and 
thickening as well as numerous fissures with or without pustule 
formation
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Clinical Protocol
IM011065
BMS-986165
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Clinical Protocol
IM011065
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APPENDIX 13
PSORIASIS SYMPTOMS AND SIGNS DIARY (PSSD)
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APPENDIX 14
DERMATOLOGY LIFE QUALITY INDEX (DLQI)
Hospital No:
Date:
Score:
Name:
Diagnosis:
Address:
The aim of this questionnaire is to measure how much your skin problem has affected your 
life OVER THE LAST WEEK. Please tick one box for each question.
1.
Over the last week, how itchy, sore, painful or stinging has your skin 
been?
Very 
much A 
lot
A little 
2.
Over the last week, how embarrassed or self-conscious have you 
been because of your skin?
Very 
much A 
lot
A little 
3.
Over the last week, how much has your skin interfered with you 
going shopping or looking after your home or garden?
Very 
much A 
lot
A little 
Not relevant
4.
Over the last week, how much has your skin influenced the clothes you 
wear?
Very 
much A 
lot
A little 
Not relevant
5.
Over the last week, how much has your skin affected any social or 
leisure activities?
Very 
much A 
lot
A little 
Not relevant
6.
Over the last week, how much has your skin made it difficult for you to do 
any sport?
Very 
much A 
lot
A little 
Not relevant
7.
Over the last week, has your skin prevented you from working or 
studying?
y
e
s 
Not relevant
If “No”, over the last week how much has your skin been a problem at 
work or
studying?
A 
lot 
A
littl
e
8.
Over the last week, how much has your skin created problems with 
your partner or any of your close friends or relatives?
Very 
much A 
lot
A little 
Not relevant
9.
Over the last week, how much has your skin caused any sexual 
difficulties?
Very 
much A 
lot
A little 
Not relevant
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Clinical Protocol
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10. Over the last week, how much of a problem has the treatment for 
your skin been, for example by making your home messy, or by taking 
up time?
Very 
much A 
lot
A little 
Not relevant
Please check you have answered EVERY question. Thank you
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
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Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
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IM011065
BMS-986165
TYK2 Inhibitor
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IM011065
BMS-986165
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3.0
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Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
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Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
5HYLVHG3URWRFRO1R
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Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
5HYLVHG3URWRFRO1R
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Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
5HYLVHG3URWRFRO1R
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Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
5HYLVHG3URWRFRO1R
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Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
5HYLVHG3URWRFRO1R
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Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
APPENDIX 20
PSORIATIC ARTHRITIS SCREENING AND EVALUATION 
(PASE) QUESTIONNAIRE
PSORIATIC ARTHRITIS SCREENING AND EVALUATION (PASE) QUESTIONNAIRE
Please circle or mark ONLY ONE of the five choices on the following 15 questions. The 
answers to these questions will help us better understand your symptoms. This should 
take about 5-6 minutes to complete. Thank you for your time.
Symptoms sub-scale
Strongly 
Disagree
Disagree
Neutral
Agree
Strongly 
Agree
1.
I feel tired for most of the day
1
2
3
4
5
2.
My joints hurt
1
2
3
4
5
3. My back hurts
1
2
3
4
5
4. My joints become swollen
1
2
3
4
5
5. My joints feel ‘hot’
1
2
3
4
5
6. Occasionally, an entire finger or toe 
becomes swollen, making it look like a 
‘sausage’
1
2
3
4
5
7. I have noticed that the pain in my joints 
moves from one joint to another, eg my wrist 
will hurt for a few days then my knee will hurt 
and so on.
1
2
3
4
5
SYMPTOM SCORE (Max 35)
Add scores for questions 1-7 and write in 
box A
A.
Function sub-scale
Strongly 
Disagree
Disagree
Neutral
Agree
Strongly 
Agree
8. I feel that my joint problems have affected 
my ability to work
1
2
3
4
5
9. My joint problems have affected my ability 
to care for myself, eg getting dressed or 
brushing my teeth
1
2
3
4
5
10. I have had trouble wearing rings on my 
fingers or my watch
1
2
3
4
5
11. I have had trouble getting into or out of a 
car
1
2
3
4
5
12. I am unable to be as active as I used to be
1
2
3
4
5
13. I feel stiff for more than 2 hours after 
waking up in the morning
1
2
3
4
5
14. The morning is the worst time of day for 
me
1
2
3
4
5
15. It takes me a few minutes to get moving to 
the best of my ability, any time of the day
1
2
3
4
5
FUNCTION SCORE (Max 40)
Add scores for questions 8-15 and write in 
box B
B.
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Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
TOTAL PASE SCORE (Max 75)
Add scores in boxes A and B and write in 
box C
C.
5HYLVHG3URWRFRO1R
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
Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
APPENDIX 21
EIGHT-ITEM PATIENT HEALTH QUESTIONNAIRE (PHQ-8)
The eight-item Patient Health Questionnaire depression scale is established as a valid 
self-administered diagnostic and severity measure for depressive disorders. It consists of 8 
different questions, with an answer scale from 0-3. The overall score is determined by adding up 
each of the individual answers from each question. 
Scoring interpretation is as follows: 0-4 no significant depressive symptoms, 5-9 mild depressive 
symptoms, 10-14 moderate depressive symptoms, 15-19 moderately severe depressive symptoms, 
and 20-24 severe depressive symptoms
Over the last 2 weeks, how often have you
been bothered by any of the following
problems?
Not at all
Several 
Days
More than 
half the days
Nearly 
every day
1. Little interest or pleasure in doing things
0
1
2
3
2. Feeling down, depressed, or hopeless
0
1
2
3
3. Trouble falling or staying asleep, or 
sleeping too much
0
1
2
3
4. Feeling tired or having little energy
0
1
2
3
5. Poor appetite or over eating
0
1
2
3
6. Feeling bad about yourself, or that you 
are a failure, or have let yourself or your 
family down
0
1
2
3
7. Trouble concentrating on things, such as 
reading the newspaper, or watching 
television
0
1
2
3
8. Moving or speaking so slowly that other 
people could have noticed? Or the 
opposite, being so fidgety or restless that 
you have been moving around a lot more 
than usual
0
1
2
3
Total Score:
5HYLVHG3URWRFRO1R
'DWH1RY
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Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
APPENDIX 22
SUICIDAL IDEATION AND BEHAVIOR CATEGORIES AND 
DEFINITIONS
Suicidal Ideation
Passive suicidal ideation: wish to be dead
Patient has thoughts about a wish to be dead or not alive anymore, or wish to fall asleep 
and not wake up.
Active suicidal ideation: nonspecific (no method, intent, or plan)
General nonspecific thoughts of wanting to end one’s life or commit suicide (eg, “I’ve 
thought about killing myself”) without general thoughts of ways to kill oneself/associated 
methods, intent, or plan during the assessment period.
Active suicidal ideation: method, but no intent or plan
Patient has thoughts of suicide and has thought of at least one method during the assessment 
period. This situation is different than a specific plan with time, place, or method details 
worked out (eg, thought of method to kill self but not a specific plan). Includes person who 
would say, “I thought about taking an overdose but I never made a specific plan as to when, 
where, or how I would actually do it . . . and I would never go through with it.”
Active suicidal ideation: method and intent, but no plan
Active suicidal thoughts of killing oneself, and patient reports having some intent to act on 
such thoughts, as opposed to “I have the thoughts but I definitely will not do anything about 
them.”
Active suicidal ideation:  method, intent, and plan
Thoughts of killing oneself with details of plan fully or partially worked out and patient 
has some intent to carry it out (ie, some degree of intent is implicit in the concept of plan).
Suicidal Behavior
Completed suicide
A self-injurious behavior that resulted in fatality and was associated with at least some 
intent to die as a result of the act. Evidence that the individual intended to kill him- or 
herself, at least to some degree, can be explicit or inferred from the behavior or 
circumstance.
Suicide attempt
A potentially self-injurious behavior, associated with at least some intent to die as a result 
of the act. Evidence that the individual intended to kill him- or herself, at least to some 
degree, can be explicit or inferred from the behavior or circumstance. A suicide attempt 
may or may not result in actual injury.
Interrupted suicide attempt
5HYLVHG3URWRFRO1R
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Approved
3.0
v
Approved
1.0
v

Clinical Protocol
IM011065
BMS-986165
TYK2 Inhibitor
When the person is interrupted (by an outside circumstance) from starting a potentially 
self-injurious act (if not for that, actual attempt would have occurred).
Aborted suicide attempt
When person begins to take steps toward making a suicide attempt, but stops before 
actually engaging in any self-destructive behavior. Examples are similar to interrupted 
attempts, except that the individual stops before being stopped by something else.
Preparatory acts toward imminent suicidal behaviors
This category can include anything beyond a verbalization or thought, but it stops short of 
a suicide attempt, an interrupted suicide attempt, or an aborted suicide attempt. This might 
include behaviors related to assembling a specific method (eg, buying pills, purchasing a 
gun) or preparing for one’s death by suicide (eg, giving things away, writing a suicide 
note).
Self-Injurious Behavior Without Suicidal Intent
Self-injurious behavior associated with no intent to die.  The behavior is intended purely for other 
reasons, either to relieve distress (often referred to as self-mutilation (eg, superficial cuts or 
scratches, hitting or banging, or burns) or to effect change in others or the environment.
5HYLVHG3URWRFRO1R
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Approved
3.0
v
Approved
1.0
v