Clinical trial NCT03329885
Conditions: Rheumatoid Arthritis Psoriasis Ankylosing Spondylitis Inflammatory Bowel Diseases Nonalcoholic Steatohepatitis
Sponsor: Bristol-Myers Squibb
Start date: 2017-11-02; Completion date: 2018-06-26
Enrollment: 38 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to investigate experimental medication BMS-986251 taken by mouth in healthy patients and patients with average to very serious Psoriasis (a condition characterized by itchy, dry skin with a scaly rash).

Detailed description:

Arms: arm 1: Healthy patient will receive single escalating oral doses of BMS-986251 or placebo arm 2: Healthy patients will receive daily escalating oral doses of BMS-986251 or placebo arm 3: Psoriasis patients will receive daily escalating oral doses of BMS-986251 or placebo
Interventions: intervention 1: BMS-986251 intervention 2: Placebo
Intervention descriptions: intervention 1: Escalating oral dose intervention 2: Escalating oral dose

Protocol documents:
Prot_000.pdf: 
21Sep2017
BMS Confidential
1
A Double-Blind Randomized Placebo-Controlled Single and Multiple 
Ascending Doses Study of the Safety and Tolerability, Pharmacokinetics 
(Including Bioavailability Comparison and Food Effect) and 
Pharmacodynamics of Oral BMS-986251 Administration in Healthy Subjects, 
with Efficacy Assessment of Multiple Doses in Patients with Moderate-to-
Severe Psoriasis
Test Drug:
BMS-986251
Protocol Number: IM024 005
Date and Version: 21 September 2017; Final Version 1.0
EudraCT Number: 2017-003408-38
Study Director
Medical Monitor
Mohamed Okily, MD
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS sponsored 
study. Any permitted disclosures will be made only on a confidential “need to know” basis 
within your organization or to your independent ethics committee(s). Any other use, 
copying, disclosure or dissemination of this information is strictly prohibited unless 
expressly authorized in writing by BMS. Any supplemental information (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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1. SCHEDULE OF ACTIVITIES
Schedules of procedures are described in Table 1 for Part A (single ascending dose [SAD]
healthy subjects, including a cohort to evaluate relative bioavailability and food effect), 
Table 2 for Part B (multiple ascending dose [MAD] healthy subjects), Table 3 for Part C -
MAD psoriasis patients, intensive pharmacokinetic (PK) sampling sub-cohort, and Table 4
for Part C - MAD psoriasis patients, sparse PK sub-cohort.
For PK, pre-dose samples (in the multiple dose parts this applies to samples before the first 
dose only) will be obtained between waking up and dosing. For pre-dose (trough) samples 
during multiple dosing, a 5% time window since the last dose is allowed, but the sample must 
be taken before the next dose. Post-dose samples will be obtained with time margins of 
+/- 5% of the time that has passed since (last) dosing. The +/- 5% time window also applies 
to the start and end times of urine collection intervals and in addition to the total duration of 
each consecutive collection interval. 
For PD, pre-dose samples (in the multiple dose parts this applies to samples before the first 
dose only) will be obtained between waking up and dosing. Post-dose samples up to 40 min 
post-dose will be obtained with a time window of +/- 2 minutes. Thereafter, post-dose 
samples will be obtained with time margins of +/- 5% of the time that has passed since (last) 
dosing.
For safety assessments, pre-dose assessments will be performed between waking up and 
dosing. For safety assessments up to 2.5 hours post-dose a time-window of +/- 15 minutes is 
allowed. Thereafter, assessments will be performed with time margins of +/- 10% of the time 
that has passed since (last) dosing.
In the event assessments are planned for the same scheme time, the order of the assessments 
should be arranged in such a way that PK and PD blood sampling will be done after the ECG 
and vital signs recordings have been conducted, with PK and PD blood sampling as close to 
the planned time as possible. Clinical laboratory blood samples may be taken thereafter. 
During the 24-hour periods of Holter monitoring, vital signs may also be recorded after PK 
blood sampling (when necessary for logistical reasons). When multiple procedures are 
scheduled at the same time as medication dosing, medication dosing will be done exactly on 
time and safety assessments and blood sampling for PK and PD will be done before dosing 
(as close to medication dosing as possible). 


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Table 1
Study Procedural Outline Part A – SAD Healthy Subjects (IM024 005)
Period 1
Period 2 (Cohort for Bioavailability and Food Effect Assessment only)
Period 3 (Cohort for Bioavailability and Food Effect Assessment only)
Visit
Screening
Pre-
Treatment
Treatment
Follow-
up1
Study Days
-21 to -1
-1
1
2
3
4
5
6
7
9
11
Time Post-Dosing 
(hrs)
Pre-dose
0
0.5
1
1.5
2
3
4
6
8
12
24
36
48
72
96
120
144
192
240
Confinement
X
Discharge2
X
Ambulant visit
X
X
X
Informed consent and 
medical history
X
Demographics
X
Physical examination
X
X
Genotyping (CYPs, 
transporters)3
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight and height 
(including BMI 
calculation)4
X
X
X
Eligibility check
X
X
X
12-lead ECG 
X
X
X
X
X
X
X
X
X
X
                                                
1 For relative bioavailability/food effect cohort follow-up assessments on Day 11 of Period 3 only. At the Day 11 visit in Period 1 and 2 only blood sampling for PK and PD 
(Period 1 only), vital signs, and drug and alcohol screen will be performed.
2 Discharge from the clinical research unit.
3 Mandatory whole blood collection for analysis of DNA variants in ADME-related genes (http://pharmaadme.org/Appendix 6). For relative bioavailability/food effect cohort
sample will be collected in Period 1 only. Sample may be taken at any time post-dose during Day 1.
4 Height will only be measured at screening. BMI will also only be calculated at screening.


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Period 1
Period 2 (Cohort for Bioavailability and Food Effect Assessment only)
Period 3 (Cohort for Bioavailability and Food Effect Assessment only)
Visit
Screening
Pre-
Treatment
Treatment
Follow-
up1
Study Days
-21 to -1
-1
1
2
3
4
5
6
7
9
11
Time Post-Dosing 
(hrs)
Pre-dose
0
0.5
1
1.5
2
3
4
6
8
12
24
36
48
72
96
120
144
192
240
(triplicate)
Holter monitoring5 6
X7
X
Clinical laboratory,
hematology incl. 
reticulocytes
X
X
X
X
X
X
Drug and alcohol 
screen
X
X
X
X
HBsAg, anti-HCV, and 
anti-HIV 1/2 tests
X
Quantiferon Gold test
X
FSH (females only)
X
Pregnancy test (females 
only)
X
X
X
Overnight fast 
(10 hours)
X
Standardized lunch, 
snacks, dinner8
X
High-fat breakfast9
X
Randomization
X
                                                
5 For bioavailability/food effect cohort in fasted Period 1 only
6 Including a 15 minute supine period prior to every PK sample
7 In triplicate in 3 supine periods
8 In Period 1 with Holter monitoring only.
9 In Period 3 of bioavailability/food effect cohort only


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Period 1
Period 2 (Cohort for Bioavailability and Food Effect Assessment only)
Period 3 (Cohort for Bioavailability and Food Effect Assessment only)
Visit
Screening
Pre-
Treatment
Treatment
Follow-
up1
Study Days
-21 to -1
-1
1
2
3
4
5
6
7
9
11
Time Post-Dosing 
(hrs)
Pre-dose
0
0.5
1
1.5
2
3
4
6
8
12
24
36
48
72
96
120
144
192
240
Study drug 
administration
X
Taste questionnaire
X10
Previous and 
concomitant 
medications
X
X
PK sampling blood11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine collection for 
parent drug and 
metabolites
X
X
X
X
X
X
X
X
X
Sampling for ex-vivo 
IL-17 inhibition in 
whole blood12
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
Serious adverse events
X
BMI = body mass index; CYP = cytochrome P450; ECG = electrocardiogram; FSH = follicle stimulating hormone; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; 
HIV = human immunodeficiency virus; hrs = hours; IL-17 = interleukin 17; PK = pharmacokinetic
                                                
10 To be completed immediately after drug administration (within first 10 seconds) and after approximately 1 minute (before drinking the provided glass of water)
11 Including a 15 minute supine period prior to every PK sample during Holter monitoring
12 Period 1 only


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Table 2
Study Procedural Outline Part B – MAD Healthy Subjects (IM024 005)
Visit
Screening
Pre-
Treatment
Treatment
Follow-
up
Study Days
-21 to -1
-1
1
141
2-13
15
16
18
20
24
Time Post-Daily Dose (hrs)2
Pre-
dose
0
0.5
1
1.5
2
3
4
6
8
12
Pre-
dose
0
4
24
48
96
144
240
Confinement
X
Discharge3
X
Ambulant visit
X
X
X
X
Informed consent and medical 
history
X
Demographics
X
Physical examination
X
X
Genotyping (CYPs, 
transporters)4
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
Body weight and height 
(including BMI calculation)5
X
X
X
Eligibility check
X
X
X6
12-lead ECG (triplicate)
X
X
X
X
X
X7
X
                                                
1 Schedule for Day 1 (first day of dosing) and Day 14 (last day of dosing).
2 Time is given relative to dosing on the relevant study day. In the CRF, time “0” will be the time of first dosing and all other time points will be relative to time “0”.
3 Discharge from the clinical research unit.
4 Mandatory whole blood collection for analysis of DNA variants in ADME-related genes (http://pharmaadme.org/Appendix 6). Sample may be taken at any time post-dose during 
Day 1; no sample to be taken on Day 14.
5 Height will only be measured at screening. BMI will also only be calculated at screening.
6 Not on Day 14.
7 Days 2, 4, 6, 8, 10, and 12 only.


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Visit
Screening
Pre-
Treatment
Treatment
Follow-
up
Study Days
-21 to -1
-1
1
141
2-13
15
16
18
20
24
Time Post-Daily Dose (hrs)2
Pre-
dose
0
0.5
1
1.5
2
3
4
6
8
12
Pre-
dose
0
4
24
48
96
144
240
Clinical laboratory, hematology 
incl. reticulocytes
X
X
X8
X9
X
X
Holter monitoring 10 11
X12
X
Drug and alcohol screen
X
X
X
X
HBsAg, anti-HCV, and 
anti-HIV 1/2 tests
X
Quantiferon Gold test
X
FSH (females only)
X
Pregnancy test (females only)
X
X
X
Randomization
X13
Overnight fast (10 hours)
X
Standardized lunch, snacks, 
dinner
X
Study drug administration
X
X
Taste questionnaire
X14
Previous and concomitant 
medications
X
X
                                                
8 Day 14 only.
9 Days 3, 7, and 10 only.
10 Including a 15 minute supine period prior to every PK sample.
11 If upcoming preclinical safety results indicate the need for a dedicated TQTc study, Holter monitoring for this study will be simplified and not plan for concentration-effect 
modeling.
12 In triplicate in 3 supine periods.
13 On Day 1 only.
14 On Day 1 only. To be completed immediately after drug administration (within first 10 seconds) and after approximately 1 minute (before drinking the provided glass of water).


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Visit
Screening
Pre-
Treatment
Treatment
Follow-
up
Study Days
-21 to -1
-1
1
141
2-13
15
16
18
20
24
Time Post-Daily Dose (hrs)2
Pre-
dose
0
0.5
1
1.5
2
3
4
6
8
12
Pre-
dose
0
4
24
48
96
144
240
PK sampling blood15
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine collection for parent drug 
and metabolites
X
X16
Sampling for ex-vivo IL-17 
inhibition in whole blood
X
X
X
X
X
X
X17
X
X
X
Sampling for IL-17, IL-22, 
-defensin, and erythropoietin
X
X
X
Sampling for T, B, and NK cells 
(TBNK), T cells, T cell 
subsets.
X
X
X
Adverse events
X
Serious adverse events
X
BMI = body mass index; CYP = cytochrome P450; ECG = electrocardiogram; FSH = follicle stimulating hormone; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; 
HIV = human immunodeficiency virus; hrs = hours; IL-17 = interleukin-17; IL-22 = interleukin-22; NK = natural killer; PK = pharmacokinetic; TBNK = T, B, and NK cells
                                                
15 Including a 15 minute supine period prior to every PK sample during Holter monitoring.
16 24-hours urine collection on Day 14 only
17 Pre-dose at Days 2, 4 and 7 only.


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Table 3
Study Procedural Outline Part C – MAD Psoriasis Patients – Intensive PK Sampling Sub-Cohort (IM024 005)
Visit
Screening
Pre-
Treatment
Treatment
Follow-
up
Study Days
-21 to -1
-1
13
1
14
2
7
15
28
Time post daily dose (hrs)1
Pre-
dose
0
0.5
1
1.5
2
3
4
6
8
12
Confinement
X
Discharge2
X
X
Ambulant visit
X
X
X
Informed consent and medical history
X
Demographics
X
Physical examination
X
X
Genotyping (CYPs, transporters)
X
Vital signs
X
X
X
X
X
X
X
X
X
X
Body weight and height (including BMI calculation)3
X
X4
X
Eligibility check
X
X2
X5
12-lead ECG
X
X
X
X
X
Clinical laboratory, hematology incl. reticulocytes
X
X
X
X
X
Drug and alcohol screen
X
X
X
HBsAg, anti-HCV, and anti-HIV 1/2 tests
X
                                                
1 Time is given relative to dosing on the relevant study day. In the CRF, time “0” will be the time of first dosing and all other time points will be relative to time “0”
2 Discharge from the clinical research unit.
3 Height will only be measured at screening. BMI will also only be calculated at screening.
4 Only on Day -1
5 Only on Day 1


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Visit
Screening
Pre-
Treatment
Treatment
Follow-
up
Study Days
-21 to -1
-1
13
1
14
2
7
15
28
Time post daily dose (hrs)1
Pre-
dose
0
0.5
1
1.5
2
3
4
6
8
12
Quantiferon Gold test
X
FSH (females only)
X
Pregnancy test (females only)
X
X
X
Randomization
X
Overnight fast (10 hours)
X
Study drug administration6
X7
X
X
Previous and concomitant medications
X
X
PK sampling blood
X
X
X
X
X
X
X
X
X
X
X8
X8
X
X
Sampling for ex-vivo IL-17 inhibition
in whole blood
X
X
X
X
X
X
X
X
X
Sampling for IL-17, IL-22,-defensin, and 
erythropoietin
X
X
X
Sampling for T, B, and NK cells (TBNK), T cells, 
T cell subsets.
X
X
X
Plaque biopsy for immunochemistry and RNA 
analysis
X9
X10
Psoriasis affected body area
X
X
Psoriasis Area and Severity Index (PASI) score
X
X
X
                                                
6 Study drug will be administered in the clinical research unit on Days 1, 2, 7, and 14. On Days 3-6 and 8-13, subjects will take the study drug at home.
7 Day 13 only
8 Pre-dose
9 Day -1 only
10 Day 14 only


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Visit
Screening
Pre-
Treatment
Treatment
Follow-
up
Study Days
-21 to -1
-1
13
1
14
2
7
15
28
Time post daily dose (hrs)1
Pre-
dose
0
0.5
1
1.5
2
3
4
6
8
12
Physician Global Assessment (PGA) score
X
X
X
Dermatology Life Quality Index (DLQI)
X
X
X
Adverse events
X
X
Serious adverse events
X
BMI = body mass index; CYP = cytochrome P450; DLQI = Dermatology Life Quality Index; ECG = electrocardiogram; FSH = follicle stimulating hormone; HBsAg = hepatitis B 
surface antigen; HCV = hepatitis C virus; HIV = human immunodeficiency virus; hrs = hours; IL-17 = interleukin-17; IL-22 = interleukin-22; NK = natural killer; PASI = 
Psoriasis Area and Severity Index; PGA = Physician Global Assessment; PK = pharmacokinetic; TBNK = T, B, and NK cells


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Table 4
Study Procedural Outline Part C – MAD Psoriasis Patients – Sparse PK 
Sampling Sub-Cohort (IM024 005)
Visit
Screening
Pre-
Treatment
Treatment
Follow-up
Study Days
-21 to -1
1
1
7
14
28
Ambulant visit
X
X
X
X
X
X
Informed consent and medical history
X
Demographics
X
Physical examination
X
X
Genotyping (CYPs, transporters)
X
Vital signs
X
X
X
X
X
Body weight and height (including BMI 
calculation)1
X
X
X
Eligibility check
X
X
12-lead ECG
X
X
X
X
Clinical laboratory, hematology incl. 
reticulocytes
X
X
X
X
Drug and alcohol screen
X
X
X
X
HBsAg, anti-HCV, and anti-HIV 1/2 tests
X
Quantiferon Gold test
X
FSH (females only)
X
Pregnancy test (females only)
X
X
X
Randomization
X
Study drug administration2
X
Previous and concomitant medications
X
X
PK sampling blood3
X
X
X
Sampling for ex-vivo IL-17 inhibition in 
whole blood
X
X
X
X
Sampling for IL-17, IL-22, -defensin, 
and erythropoietin
X
X
X
X
Sampling for T, B, and NK cell (TBNK), 
T cells, T cell subsets.
X
X
X
X
Plaque biopsy for immunochemistry and 
RNA analysis
X
X
Psoriasis affected body area
X
X
Psoriasis Area and Severity Index (PASI) 
score
X
X
X
X
                                                
1 Height will only be measured at screening. BMI will also only be calculated at screening.
2 Study drug will be administered in the clinical research unit on Days 1, 7, and 14. On Days 2-6 and 8-13, subjects will take 
the study drug at home.
3 Pre-dose PK blood sampling on Days 1, 7 and 14


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Visit
Screening
Pre-
Treatment
Treatment
Follow-up
Study Days
-21 to -1
1
1
7
14
28
Physician Global Assessment (PGA) 
score
X
X
X
X
Dermatology Life Quality Index (DLQI)
X
X
X
X
Adverse events
X
Serious adverse events
X
BMI = body mass index; CYP = cytochrome P450; DLQI = Dermatology Life Quality Index; ECG = electrocardiogram; 
FSH = follicle stimulating hormone; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; hrs = hours; IL-17 = interleukin-17; IL-22 = interleukin-22; NK = natural killer; PASI = Psoriasis 
Area and Severity Index; PGA = Physician Global Assessment; PK = pharmacokinetic; TBNK = T, B, and NK cells


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2. TABLE OF CONTENTS
1.
SCHEDULE OF ACTIVITIES ......................................................................................4
2.
TABLE OF CONTENTS ..............................................................................................16
3.
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS...............................21
4.
ETHICS..........................................................................................................................24
4.1
Ethics Committee ............................................................................................................24
4.2
Ethical Conduct of the Study...........................................................................................24
4.3
Subject Information and Consent ....................................................................................24
6.
26
34
7.
STUDY OBJECTIVES .................................................................................................37
7.1
Study Objectives..............................................................................................................37
7.1.1
Primary Study Objective .................................................................................................37
7.1.2
Secondary Study Objectives............................................................................................37
8.
INVESTIGATIONAL PLAN .......................................................................................38
8.1
Overall Study Design.......................................................................................................38
8.1.1
Part A SAD, Healthy Volunteers.....................................................................................40
8.1.2
Part B MAD, Healthy Volunteers....................................................................................41
8.1.3
Part C, Multiple Dose in Psoriasis Patients .....................................................................42
8.2
End of Study Definition...................................................................................................43
8.3
Study Population..............................................................................................................43
8.3.1
Inclusion Criteria.............................................................................................................44
8.3.1.1
Healthy Subjects (Part A and B)......................................................................................44


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8.3.1.2
Psoriasis Patients (Part C)................................................................................................44
8.3.2
Exclusion Criteria............................................................................................................45
8.3.2.1
Healthy Subjects (Part A and B)......................................................................................45
8.3.2.2
Psoriasis Patients (Part C)................................................................................................47
8.3.3
Lifestyle Restrictions.......................................................................................................50
8.3.4
Screen Failures and Rescreening.....................................................................................50
8.3.5
Withdrawal and Replacement of Subjects.......................................................................51
8.3.5.1
Discontinuation of Treatment..........................................................................................51
8.3.5.2
Discontinuation from the Study.......................................................................................52
8.3.5.3
Lost to Follow-up ............................................................................................................52
8.3.5.4
Replacement of Subjects .................................................................................................53
8.3.5.5
Stopping Rules for Part A and Part B..............................................................................53
8.4
Treatment.........................................................................................................................54
8.4.1
Treatments Administered ................................................................................................57
8.4.1.1
Part A – SAD in Healthy Volunteers...............................................................................57
8.4.1.2
Part B – MAD in Healthy Volunteers..............................................................................57
8.4.1.3
Part C – Multiple Dosing in Psoriasis Patients................................................................58
8.4.2
Method of Treatment Assignment...................................................................................58
8.4.3
Blinding of Study Medication .........................................................................................59
8.4.3.1
Maintaining the Blind......................................................................................................59
8.4.3.2
Circumstances for Unblinding.........................................................................................59
8.4.4
Study Treatment Preparation, Handling, Storage, and Accountability............................61
8.4.4.1
Retained Samples for Bioavailability / Bioequivalence ..................................................61
8.4.5
Dose Modification...........................................................................................................61
8.4.6
Treatment Compliance ....................................................................................................61
8.4.6.1
Part A and B ....................................................................................................................61
8.4.6.2
Part C...............................................................................................................................62
8.4.7
8.4.7.1
Prohibited and/or Restricted Treatments – Part A and B Healthy Volunteers ................62
8.4.7.2
Prohibited and/or Restricted Treatments – Part C Psoriasis Patients ..............................63
8.4.7.3
Permitted Treatments.......................................................................................................64
8.4.7.3.1
Permitted Treatments for Psoriasis (Part C, Psoriasis Patients)....................................64
8.4.8
Treatment After the End of the Study..............................................................................64
8.5
Efficacy and Safety Assessments ....................................................................................65
8.5.1
Efficacy Assessments ......................................................................................................65
8.5.1.1
Psoriasis Area and Severity Index Scoring (PASI) .........................................................65
8.5.1.2
Physician Global Assessment (PGA) ..............................................................................65
8.5.1.3
Dermatology Life Quality Index (DLQI) ........................................................................65
8.5.2
Safety Assessments..........................................................................................................65


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8.5.2.1
Adverse Events................................................................................................................66
8.5.2.1.1
Time Period and Frequency for Collecting Adverse Events and Serious Adverse Events 
Information......................................................................................................................66
8.5.2.1.2
Method of Detecting Adverse Events and Serious Adverse Events..................................67
8.5.2.1.3
Follow-up of Adverse Events and Serious Adverse Events..............................................67
8.5.2.1.4
Regulatory Reporting Requirements for Serious Adverse Events ...................................67
8.5.2.1.5
Pregnancy........................................................................................................................67
8.5.2.1.6
Laboratory Test Result Abnormalities.............................................................................68
8.5.2.1.7
Potential Drug-Induced Liver Injury...............................................................................68
8.5.2.1.8
Other Safety Considerations............................................................................................69
8.5.2.2
Overdose..........................................................................................................................69
8.5.2.3
Physical Examinations.....................................................................................................69
8.5.2.4
Clinical Safety Laboratory Assessments .........................................................................70
8.5.2.5
Vital Signs .......................................................................................................................72
8.5.2.6
12-Lead Electrocardiogram.............................................................................................72
8.5.2.7
Continuous Cardiac Monitoring (Holter Monitoring) .....................................................72
8.5.3
Pharmacokinetics.............................................................................................................72
8.5.4
Pharmacodynamics..........................................................................................................77
8.5.6
Total Blood Volume to be Collected (Part A and Part B) ...............................................83
9.
STATISTICAL CONSIDERATIONS.........................................................................85
9.1
Sample Size Determination .............................................................................................85
9.2
Populations for Analyses.................................................................................................85
9.3
Endpoints.........................................................................................................................86
9.3.1
Primary Endpoints...........................................................................................................86
9.3.2
Secondary Endpoints.......................................................................................................87
9.4
Statistical Analyses..........................................................................................................88
9.4.1
Efficacy Analyses............................................................................................................88
9.4.2
Safety Assessments..........................................................................................................88
9.4.2.1
Adverse Events................................................................................................................88
9.4.2.2
Vitals Signs and ECGs ....................................................................................................89
9.4.2.3
Clinical Laboratory Data .................................................................................................89
9.4.2.4
Physical Examination ......................................................................................................89
9.4.3
Pharmacokinetics.............................................................................................................89


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9.4.4
Pharmacodynamics..........................................................................................................90
9.4.5
Interim Analysis ..............................................................................................................91
11.
APPENDICES................................................................................................................93


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LIST OF TABLES
Table 1
Study Procedural Outline Part A – SAD Healthy Subjects (IM024 005) .................... 5
Table 2
Study Procedural Outline Part B – MAD Healthy Subjects (IM024 005) ................... 8
Table 3
Study Procedural Outline Part C – MAD Psoriasis Patients – Intensive PK 
Sampling Sub-Cohort (IM024 005) ........................................................................... 11
Table 4 
Study Procedural Outline Part C – MAD Psoriasis Patients – Sparse PK Sampling 
Sub-Cohort (IM024 005)............................................................................................ 14
Table 5
Projected Safety Margins – Multiples Based on Monkey Study 2-weeks NOAEL 
(8 mg/kg).................................................................................................................... 33
Table 6
IM024 005; Part A Dose Cohorts............................................................................... 41
Table 7
IM024 005; Part B Dose Cohorts............................................................................... 42
Table 8
IM024 005; Part C Dose Cohort................................................................................. 43
Table 9
Study Treatments for IM024 005 ............................................................................... 56
Table 10
Clinical Laboratory Assessments ............................................................................... 71
Table 11
Pharmacokinetic Sampling Schedule; Part A............................................................. 74
Table 12
Pharmacokinetic Sampling Schedule; Part B............................................................. 75
Table 13
Pharmacokinetic Sampling Schedule; Part C (Sub-Cohort with Intensive PK 
Sampling) ................................................................................................................... 76
Table 14
Pharmacokinetic Sampling Schedule; Part C (Sub-Cohort with Sparse PK 
Sampling) ................................................................................................................... 77
Table 15
Pharmacodynamic Sampling Schedule; Part A.......................................................... 78
Table 16
Pharmacodynamic Sampling Schedule; Part B.......................................................... 79
Table 17
Pharmacodynamic Sampling Schedule; Part C (Sub-Cohort with Intensive PK 
Sampling) ................................................................................................................... 80
Table 18
Pharmacodynamic Sampling Schedule; Part C (Sub-Cohort with Sparse PK 
Sampling) ................................................................................................................... 81
Table 19
Residual Sample Retention for Additional Research Schedule.................................. 82
Table 20
Number and Volume of Blood Samples and Total Blood Volume Collected per 
Subject (Part A, Cohorts A1-A6) ............................................................................... 83
Table 21
Number and Volume of Blood Samples and Total Blood Volume Collected per 
Subject (Part A, Cohorts A7) ..................................................................................... 84
Table 22
Number and Volume of Blood Samples and Total Blood Volume Collected per 
Subject (Part B) .......................................................................................................... 84
LIST OF FIGURES
Figure 1
Study Design Schematic............................................................................................. 39


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3. LIST OF ABBREVIATIONS AND DEFINITION OF TERMS
Term
Definition
A
active
ADME
absorption, distribution, metabolism, and excretion
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BA
bioavailability 
BCRP
Breast Cancer Resistance Protein
BMI
body mass index
BMS
Bristol-Myers Squibb
BSEP
bile salt export pump 
CFR
Code of Federal Regulations
CLCR
creatinine clearance
CLTp
total plasma clearance
CONSORT
Consolidated Standards of Reporting Trials 
CRO
contract research organization
CRU 
clinical research unit 
CTD
Clinical Trial Directive
CV
coefficient of variation
CYP
cytochrome P450
DILI
drug-induced liver injury
DLQI
Dermatology Life Quality Index
EC50
concentration at which 50% effect is observed
ECG
electrocardiogram
eCRF
electronic case report form
EDS
Early Development Services
EU
European Union
FDA
Food and Drug Administration
FE
food effect
FIH
first in human
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GI
gastrointestinal
HBsAg
hepatitis B surface antigen
HDL
high-density lipoprotein
HIV
human immunodeficiency virus
hPBMCs
human peripheral blood mononuclear cells
hsCRP
high sensitivity C-reactive protein


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HRT
hormone replacement therapy 
HV
healthy volunteers
IB
Investigator’s Brochure
IC50
concentration at which 50% inhibition is observed
IC90
concentration at which 90% inhibition is observed
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IL
interleukin
IMP
investigational medicinal product
IP
investigational product
LC-MS/MS
liquid chromatography tandem mass spectometry
LDL
low-density lipoprotein
LDH
lactate dehydrogenase
MAD
multiple ascending dose
MedDRA
Medical Dictionary for Regulatory Activities
MRP
multi drug-resistance protein
MRSD
maximum recommended starting dose 
N
number
NK
natural killer cells
NOAEL
no observed adverse effect level 
NTCP
sodium-taurocholate cotransporting polypeptide 
OATP
organic-anion transporting polypeptide
OCT
organic cation transporter
OTC
over-the-counter 
P
placebo
PASI
Psoriasis Area and Severity Index
PGA
Physician Global Assessment
P-gp
P-glycoprotein
PD
pharmacodynamics(s)
PK
pharmacokinetic(s)
PO
per os (oral)
QD
once daily
SAD
single ascending dose 
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard of deviation 
SOP
standard operating procedure
SUSAR
Suspected Unexpected Serious Adverse Reaction
TB
tuberculosis


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TBNK
T, B, and NK cells
TNF
tumor necrosis factor
UGT
uridine diphosphate-glucuronyltransferase
ULN
upper limit of normal
US(A)
United States (of America)
Vss
volume of distribution at steady state
WOCBP
women of childbearing potential
Definitions of PK parameters to be calculated in this study are provided in Section 8.5.3.
Definitions of PD parameters to be calculated in this study are provided in Section 8.5.4.


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4. ETHICS
4.1 Ethics Committee
This study will be conducted in compliance with Independent Ethics Committee (IEC) and 
International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and 
in accordance with applicable regulations regarding clinical safety data management (E2A, 
E2B[R3]) and scientific integrity (E4, E8, E9, and E10). In addition, this study will adhere to 
all local regulatory requirements, and requirements for data protection.
Before initiating a study, the Investigator must obtain written and dated approval from the 
IEC for the study protocol, written informed consent form (ICF), participant recruitment 
procedures (eg, advertisements), written information to be provided to participants, and a 
statement from the IEC that these comply with GCP requirements. The approval must 
identify the protocol version as well as the documents reviewed.
4.2 Ethical Conduct of the Study
This study will be conducted in accordance with the European Union (EU) Clinical Trial
Directive (CTD) (Directive 2001/20/EC), the Note for Guidance on GCP (ICH Harmonised 
Tripartite Guideline E6 [R1]; United States (US) Food and Drug Administration [FDA] Code 
of Federal Regulations [CFR] [21 CFR Parts 50, 56, and 312]), Declaration of Helsinki 
(Seoul 2008), and all applicable regulatory requirements.
4.3 Subject Information and Consent
The Investigator will explain the benefits and risks of participation in the study to each 
subject in language readily understood by the subject. Written informed consent must be 
obtained before the subject enters the study and before any study-specific procedures are 
performed. If important new information becomes available requiring revisions to the ICF, 
the IEC-approved revised form will be used for re-consent of all subjects.


























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7. STUDY OBJECTIVES
7.1 Study Objectives
7.1.1
Primary Study Objective

To evaluate the safety, tolerability and PK of escalating single and multiple ascending 
doses of BMS-986251 in healthy subjects, and of multiple doses of BMS-986251 in 
patients with moderate-to-severe psoriasis.
7.1.2
Secondary Study Objectives

To evaluate the PD of escalating single and multiple ascending doses of BMS-986251 
in healthy subjects, and of multiple doses of BMS-986251 in patients with moderate-
to-severe psoriasis.

To evaluate the oral BA of an oral suspension of BMS-986251 relative to a liquid 
dosage form at a single dose level in healthy subjects.

To evaluate the effect of a high-fat meal on the PK of an oral suspension of 
BMS-986251 at a single dose level in healthy subjects.

To explore clinical effects of multiple doses of BMS-986251 in patients with 
moderate-to-severe psoriasis.


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8. INVESTIGATIONAL PLAN
8.1 Overall Study Design
This is a double-blind, placebo-controlled, randomized SAD and MAD study in 3 parts in 
approximately 103 participants: 88 healthy subjects and 15 patients with psoriasis. The 
present study is designed to evaluate the safety and tolerability, PK, PD and efficacy of 
BMS-986251. Part A and B will enroll healthy subjects and will be conducted at a single site. 
Part C will enroll patients with psoriasis and will be conducted as a multi-center study in 
multiple countries.
Part A will be an SAD study in a planned number of 6 sequential cohorts of 8 healthy 
subjects (6 active + 2 placebo) each, receiving single escalating oral doses of BMS-986251. 
In the 1st cohort, sentinel dosing will be employed (1 active + 1 placebo, followed after 
72 hours by the remaining subjects of the 1st cohort [5 active + 1 placebo]). In addition to the 
6 ascending dose cohorts, a cohort of 8 healthy subjects (8 active) will be included to assess 
the relative BA of an oral suspension (under development; representative for the solid dosage 
form to be used in Part C) compared to the solution formulation, and to evaluate the effect of 
food on the BA of the oral suspension in a 3-period sequential design (BA/FE cohort).
Part B will be a MAD study in a planned number of 4 sequential cohorts of 8 healthy subjects 
(6 active + 2 placebo) each, receiving daily oral doses of escalating BMS-986251 for 
2 weeks.
Part C will be a multiple dose part in one cohort of 15 patients with moderate-to-severe 
psoriasis (12 active + 3 placebo), treated for 2 weeks, with a potential extension to 12 weeks 
by protocol amendment. Per protocol amendment, this study part may be extended with 
further cohorts, receiving lower repeated BMS-986251 doses than Cohort C1. A decision to 
extend the study with (a) lower-dosed cohort(s) will be based on the efficacy/safety balance 
of the 1st patient cohort. A high therapeutic response or, alternatively, poor safety or 
tolerability observed in the 1st patient cohort may be the basis to amend the study protocol for 
extension to a lower dosed cohort.
An overview of the study is provided in Figure 1.
Any study part may be extended with further cohorts of healthy subjects or patients by 
protocol amendment, when justified by data generated in the study.
This study may be extended by protocol amendment with a study part bridging safety, 
tolerability and PK of BMS-986251 from the current study population to Japanese subjects.


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Figure 1
Study Design Schematic
A = active; BA = bioavailability; FE = food effect; MAD = multiple ascending dose; NHV = healthy volunteers; P = placebo; PD = 
pharmacodynamics; PK = pharmacokinetics; Pso = psoriasis; SAD = single ascending dose; wk = week
Note: SAD Cohort A1 will have a sentinel dosing design with 2 subjects (1 active and 1 placebo) dosed 72 hours prior to the remaining subjects in 
the cohort.


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Subjects will undergo screening evaluations to determine eligibility within 21 days prior to 
(first) administration of study drug.
In all study parts, physical examinations, vital sign measurements, 12-lead 
electrocardiograms (ECGs), and clinical laboratory evaluations will be performed at selected 
times throughout the study (see Section 1). In addition, Holter monitoring will be performed 
for the first 24 hours post-dose in Parts A (Day 1) and B (Day 1 and Day 14). Subjects will 
be closely monitored for AEs throughout the study. In all study parts, blood and urine
samples (urine in Part A and B only) will be collected for PK analysis and blood samples will 
be collected for PD analyses. In Part C, plaque biopsies will be taken at selected times for 
exploratory PD analysis. Preliminary efficacy assessments will be performed in Part C as 
well.
8.1.1
Part A SAD, Healthy Volunteers
Subjects will be admitted to the clinical research unit (CRU) on the day prior to (first) drug 
administration (Day -1). Following drug administration of a single dose of BMS-986251 on 
Day 1, they will remain in the CRU for close observation until discharge from the CRU on 
Day 7 (144 hours post-dose). Subjects will return for ambulatory assessments on Days 9 
and 11, including follow-up assessments on Day 11. 
Subjects enrolled in the BA/FE cohort will return to the CRU for a 2nd and 3rd study period. 
Washout between single dose administrations will be at least 2 weeks, based on an 
anticipated terminal half-life of BMS-986251 of approximately 40 hours. The design of the 
2nd and 3rd study period is the same as the first period, with a mandatory in-clinic stay from 
Day -1 to Day 7 and ambulatory visits on Days 9 and 11. Subjects will be dosed on Day 1 of 
each period. Follow-up assessments will be performed on Day 11 of Period 3 only; on 
Day 11 of Period 1 and 2 limited assessments including blood sampling for PK and PD (PD 
only in Period 1) will be performed. Please refer to the procedural outline in Table 1 to see 
which assessments are to be performed at each visit.
The planned single dose treatments are provided in Table 6. Eight healthy subjects will be 
assigned to each of 6 planned SAD cohorts and the BA/FE cohort. Subjects will be 
randomized within each of the SAD cohorts to receive a single oral dose of BMS-986251 or 
a matched placebo in a ratio of 3:1. All subjects in the BA/FE cohort will receive 
BMS-986251. In the first SAD cohort, sentinel dosing will be employed (see Section 8.1).
Within each cohort, safety, tolerability, PK, and PD assessments will be performed at 
predefined time points. Following completion of each dose cohort there will be a review of 
blinded study data prior to dose escalation by the Sponsor’s dose escalation review group. 
This group will include the Investigator, PRA Medical Monitor, the BMS Study Director, 
and additional personnel as deemed necessary by the Sponsor (such as a pharmacokineticist). 
SAD dose escalation decisions will be based on the safety, tolerability and PK results of the 
ongoing cohort up to and including Day 7, and on the PD results up to and including Day 5. 
Medication administration in the next dose cohort will not start until at least 6 subjects have 
been dosed in the previous dose cohort and the data have been reviewed. The dose escalation 


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review group will determine whether escalation to the next dose level will occur or whether 
dose-stopping criteria (presented in Section 8.3.5.5) have been met.
As new safety and/or PK data become available, the dose-escalation scheme may change. 
Subjects in subsequent dose cohorts may not receive a subsequent higher dose as outlined, 
but may instead be administered a lower dose than originally planned, repeat a lower dose 
level, or repeat the same dose of the study drug.
Table 6
IM024 005; Part A Dose Cohorts
Cohort
Number of Subjects 
(Active / Placebo)
Period
Dose of 
BMS-986251
Fasted / Fed
Formulation
A1
1 / 1 (sentinel group)
1
2 mg
Fasted 
Oral solution
5 / 1
1
2 mg
Fasted 
Oral solution
A2
6 / 2
1
6 mg
Fasted
Oral solution
A3
6 / 2
1
15 mg
Fasted 
Oral solution
A4
6 / 2
1
30 mg
Fasted 
Oral solution
A5
6 / 2
1
60 mg
Fasted 
Oral solution
A6
6 / 2
1
120 mg
Fasted
Oral solution
A7 (BA/FE)
8
1
tbd
Fasted
Oral solution
2
tbd
Fasted
Oral suspension
(under development)
3
tbd
Fed
Oral suspension 
(under development)
BA = bioavailability; FE = food effect; tbd = to be determined
Doses may be adjusted based on data obtained in previous cohorts.
8.1.2
Part B MAD, Healthy Volunteers
Part B will be initiated after thorough review of safety, tolerability, PK and PD data from at 
least the SAD Cohorts A1 up to A4 from Part A.
Subjects enrolled in Part B of the study will be admitted to the CRU on the day prior to first 
drug administration (Day -1). Subjects will be dosed with BMS-986251 on Days 1-14. 
During treatment they will remain in the CRU for close observation. Subjects will be 
discharged on Day 16 (48 hours after the last dose). Subjects will return for ambulatory 
assessments on Days 18, 20, and 24, including follow-up assessments on Day 24.
The planned multiple dose treatments are provided in Table 7. Eight healthy subjects will be 
assigned to each of 4 planned dose cohorts. Subjects will be randomized within each dose 
cohort to receive multiple oral doses of BMS-986251 or a matched placebo in a ratio of 3:1.
Within each cohort, safety, tolerability, PK, and PD assessments will be performed at 
predefined time points. Following completion of dosing for each MAD dose cohort there will 
be a short period to review the data and inform dose escalation by the Sponsor’s dose 
escalation review group. MAD dose escalation decisions will be based on the blinded safety, 
tolerability, PK and PD of the ongoing cohort up to and including Day 14. Ongoing review of 
SAD safety, tolerability, PK and PD data will also be considered for dose-escalation in 


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Part B. The dose escalation review group will determine whether escalation to the next dose 
level will occur or whether dose-stopping criteria (presented in Section 8.3.5.5) have been 
met.
As new safety and/or PK data become available, the dose-escalation scheme may change. 
Subjects in subsequent dose cohorts may not receive a subsequent higher dose as outlined, 
but may instead be administered a lower dose than originally planned, repeat a lower dose 
level, or repeat the same dose of the study drug.
Table 7
IM024 005; Part B Dose Cohorts
Cohort
Subjects 
(Active / Placebo)
Dose of 
BMS-986251 
Duration
Fasted/Fed
Formulation
B1
6 / 2
6 mg QD
14 days
Fasted 
Oral solution
B2
6 / 2
tbd QD
14 days
Fasted 
Oral solution
B3
6 / 2
tbd QD
14 days
Fasted 
Oral solution
B4
6 / 2
60 mg QD
14 days
Fasted 
Oral solution
QD = once daily; tbd = to be determined upon reviewed data
Doses may be adjusted based on data obtained in previous cohorts.
8.1.3
Part C, Multiple Dose in Psoriasis Patients
Part C will be initiated after thorough review of safety, tolerability, PK and PD data (as 
available) from Part A and Part B, and after verification that administration of BMS-986251 
is safe and tolerable enough to administer in psoriasis patients.
In Part C, a total of 15 patients with moderate-to-severe psoriasis will be enrolled in 
2 sub-cohorts: 1 sub-cohort with intensive PK sampling and 1 sub-cohort with sparse PK 
sampling.
At least 6 patients will be enrolled in the sub-cohort with intensive PK sampling. The patients 
enrolled in this cohort will be admitted to the CRU on the day prior to first drug 
administration (Day -1). Patients will be dosed with the first dose of BMS-986251 on Day 1
and will be discharged on Day 2 after intake of the 2nd dose. Between Day 3 and Day 12, the 
patients will take the medication once daily (QD) at home, except on Day 7. Treatment 
compliance information will be collected while subject is dosing at-home via dosing diaries. 
Patients will return to the CRU for an ambulatory visit on Day 7 and will be instructed not to 
take their morning dose at home, but instead bring their study drug and dosing diaries to the 
CRU for administration following pre-dose procedures. Should compliance be lower than 
expected, subjects will be counselled on dose administration. Patients will be re-admitted to 
the CRU for a second stay on Day 13. Subjects will receive their final dose on Day 14. They 
will be discharged on Day 15 (24 hours after intake of the last dose). Follow-up assessments
will be on Day 28.
Patients who are not available for 2 in-clinic periods will be enrolled in the sub-cohort with 
sparse PK sampling. These patients will visit the CRU for ambulatory assessments on Day 1 
in the morning (first dose) and on Days 7, 14, and 28, with follow-up assessments on Day 28. 
On Day 1 they will receive the first dose in the CRU. In addition, on Days 7 and 14 the 
patients will also receive their doses in the CRU. The remaining doses between Days 2-6 and 


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8-13 will be taken at home. Treatment compliance information will be collected while 
subject is dosing at-home via dosing diaries.
The planned multiple dose treatment in patients with moderate-to-severe psoriasis is
provided in Table 8. A total of 15 patients will be enrolled in one planned dose cohort. 
Subjects will be randomized to receive multiple oral doses of BMS-986251 or a matched 
placebo in a ratio of 4:1. The intended dosage form for patients is a tablet formulation, which 
is currently under development. The final selection of the dose will be made by the Sponsor’s 
dose escalation review group and will be based on the safety, tolerability, PK and PD results
of Part A and Part B.
Per protocol amendment the treatment duration may be extended to 12 weeks. Also per 
protocol amendment, Part C of this study may be extended with further cohorts, receiving 
lower repeated BMS-986251 dosed than the first cohort. A decision to extend the study with 
(a) lower-dosed cohort(s) will be based on the preliminary efficacy/safety balance of the 1st
patient cohort. A high therapeutic response or, alternatively, poor safety or tolerability 
observed in the 1st patient cohort may be the basis to amend the study protocol for extension 
to a lower dosed cohort.
Table 8
IM024 005; Part C Dose Cohort
Cohort
Subjects 
(Active / Placebo)
Dose of 
BMS-986251 
Duration
Fasted/Fed
Formulation
C1
12 / 3
60 mg QD
14 days
tbd
Oral tablet
QD = once daily; tbd = to be determined upon reviewed data
Dose may be adjusted based on data obtained in previous study parts.
8.2 End of Study Definition
The start of the study is defined as the first visit for first subject screening. The end of the 
study is defined as the last visit or scheduled procedure shown in the Schedule of Activities 
(Section 1) for the last subject. Subjects who withdraw early from the study will be requested 
to complete the study discharge evaluations.
8.3 Study Population
Eligibility criteria for this study have been carefully considered to ensure the safety of the 
study subjects. It is imperative that subjects fully meet all eligibility criteria as all arms of the 
study will be conducted under a "no-waiver" policy.
All screening 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.
To be eligible for the study, subjects must meet the criteria in Sections 8.3.1 and 8.3.2.


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8.3.1
Inclusion Criteria
8.3.1.1
Healthy Subjects (Part A and B)
1.
Subjects must be willing and able to participate in the study, sign the ICF, and complete 
all study-specific procedures and visits.
2.
Males and females, ages 18 to 55 years, inclusive, at screening.
3.
Healthy subjects, as determined by no clinically significant deviations from normal in 
medical history, physical examination, 12-lead ECGs, vital signs, and clinical laboratory 
results.
4.
Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive, at screening. 
BMI = weight (kg)/height (m)2.
5.
Body weight between 55 and 105 kg, inclusive, at screening.
6.
Females that meet one of the following:
a.
Women of childbearing potential (WOCBP) must have a negative serum or 
urine pregnancy test at screening and prior to the start of investigational 
product (IP) and must agree to follow instructions for method(s) of 
contraception (Appendix 3) for the duration of the study and a minimum of 
3 months after dosing has been completed.
b. Premenopausal female with 1 of the following:
i. Documented hysterectomy
ii. Documented bilateral salpingectomy
iii. Documented bilateral oophorectomy
iv. Sexual abstinence as preferred or usual lifestyle of the subject.
c.
Postmenopausal women (12 months or more amenorrhea and over 45 years of 
age in the absence of other biological or physiological causes). Females under 
55 years of age require follicle stimulating hormone (FSH) >40 mIU/mL at 
screening
7.
Women must not be breastfeeding.
8.
Males that meet one of the following:
a.
Males who are sexually active with WOCBP must agree to follow instructions 
for method(s) of contraception (Appendix 3) for the duration of the study and 
a minimum of 3 months after dosing has been completed. In addition, male 
subjects must be willing to refrain from sperm donation during this time.
b. Vasectomized males are exempt from contraceptive requirements.
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.
8.3.1.2 Psoriasis Patients (Part C)
1.
Subjects must be willing and able to participate in the study and sign the ICF, and be 
willing and able to complete all study-specific procedures and visits.
2.
Males and females, ages 18 to 70 years, inclusive, at screening.
3.
BMI of 18.0 to 35.0 kg/m2, inclusive, at screening. BMI = weight (kg)/height m2.
4.
Body weight between 55 and 120 kg, inclusive, at screening.


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5.
Diagnosed with stable chronic plaque psoriasis, for at least 6 months prior to screening
and be candidates for either photo-therapy or systemic treatment.
6.
Moderate-to-severe intensity of psoriasis as defined by:
a.
Affected body surface area (BSA) of ≥10%.
b. Psoriasis Area and Severity Index (PASI) ≥12.
c.
Physician Global Assessment (PGA; 6-point scale) ≥3.
7.
No clinically significant deviations from normal in medical history, physical 
examination, 12-lead ECGs, vital signs, and clinical laboratory results, other than 
abnormalities expected for this patient population, as judged by the Investigator.
8.
Females that meet one of the following:
a.
WOCBP must have a negative serum or urine pregnancy test at screening and 
prior to the start of IP and must agree to follow instructions for method(s) of 
contraception (Appendix 3) for the duration of the study and a minimum of 
3 months after dosing has been completed.
b. Premenopausal female with 1 of the following:
i. Documented hysterectomy.
ii. Documented bilateral salpingectomy.
iii. Documented bilateral oophorectomy.
iv. Sexual abstinence as preferred or usual lifestyle of the subject.
c.
Postmenopausal women (12 months or more amenorrhea and over 45 years of 
age in the absence of other biological or physiological causes). Females under 
55 years of age require FSH >40 mIU/mL at screening
9.
Women must not be breastfeeding.
10. Males that meet one of the following:
a.
Males who are sexually active with WOCBP must agree to follow instructions 
for method(s) of contraception (Appendix 3) for the duration of the study and 
a minimum of 3 months after dosing has been completed. In addition, male 
subjects must be willing to refrain from sperm donation during this time.
b. Vasectomized males are exempt from contraceptive requirements.
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.
8.3.2
Exclusion Criteria
8.3.2.1 Healthy Subjects (Part A and B)
1.
Previous participation in the current study.
2.
Participation in a drug study or exposure to any investigational drug or placebo within 
2 months prior to (the first) drug administration in the current study. Participation in 
more than 4 other drug studies in the 12 months prior to (the first) drug administration in 
the current study.
3.
Employees of PRA or the Sponsor and their relatives.
4.
Any significant acute or chronic medical condition that presents a potential risk to the 
subject and/or that may compromise the objectives of the study, including active, or 
history of, liver disease, or intestinal disorder including irritable bowel syndrome.


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5.
Current or recent (within 3 months of study treatment administration) gastrointestinal 
disease that could affect pharmacokinetics; history of cholecystectomy is not allowed.
6.
Major surgery within 4 weeks of (first) study treatment administration.
7.
History or presence of malignancy including hematological malignancies; subjects with 
a history of basal cell or squamous cell carcinoma that has been treated with no evidence 
of recurrence will be allowed for inclusion, as judged by the Investigator.
8.
Documented congenital QT syndrome, and/or corrected QT interval (Fridericia 
correction) at screening or first admission >450 ms.
9.
Donation or loss of more than 100 mL of blood within 2 months prior to (the first) drug 
administration. Donation or loss of more than 1.5 L of blood (for male subjects)/more 
than 1.0 L of blood (for female subjects) in the 10 months prior to (the first) drug 
administration in the current study.
10. Inability to be venipunctured and/or tolerate venous access.
11. Subjects who have smoked or used smoking cessation or nicotine containing products 
(including, but not limited, to e-cigarettes, pipes, cigars, chewing tobacco, nicotine 
patches, nicotine lozenges, or nicotine gum, varenicline, bupropion) within 6 months of 
the first dose of study drug.
12. Abuse or drug addiction (including cannabis products) within one year before screening
(Appendix 4).
13. Average intake of more than 24 units of alcohol per week (1 unit of alcohol equals 
approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits).
14. Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines [including 
ecstasy], cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and 
alcohol) at screening or admission to the CRU.
15. Consumption of caffeine or xanthine-containing food or beverages from at least 
72 hours prior to admission to the CRU until at least 24 hours after last drug
administration.
16. Consumption of any nutrients known to modulate CYP enzymes activity (eg, grapefruit 
or grapefruit juice, pomelo juice, star fruit, or Seville [blood] orange products) within 
14 days prior to first administration of study drug until after discharge in the last 
treatment period.
17. Positive blood screen for hepatitis C antibody, hepatitis B surface antigen (HBsAg), or 
HIV-1 or -2 antibodies.
18. History of any significant drug and/or food allergies (such as anaphylaxis or 
hepatotoxicity).
19. Use of any prescription drugs within 4 weeks prior to study drug administration except 
those medications cleared by the Investigator and PRA Medical Monitor.
20. Use of over-counter (OTC) medications and herbal preparations within 2 weeks prior to 
study drug administration, except those medications cleared by the Investigator and PRA 
Medical Monitor.
21. Any history or risk for tuberculosis (TB), specifically subjects with: 1) current clinical,
radiographic or laboratory evidence of active TB; 2) history of active TB; 3) positive 
Quantiferon® test result and history of latent TB, unless subject has documentation of 
completion of anti-TB treatment. 


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22. Known or suspected autoimmune disorder, or any history of known or suspected 
congenital or acquired immunodeficiency state or condition that would compromise the 
subject’s immune status (eg, history of splenectomy).
23. Presence of any factors that would predispose the subject to develop infection eg, 
bronchial asthma, rectal fissures, poor dentition, open skin lesions, and presence of pre-
existing skin conditions eg, Behcet’s Disease, psoriasis, pustular dermatoses.
24. Any serious (eg, requiring intramuscular or IV antibiotics and/or hospitalization) acute 
or chronic bacterial, viral or fungal infection (eg, pneumonia, septicemia) within the 
3 months prior to screening.
25. Active herpes infection, including herpes simplex 1 and 2 and herpes zoster within 
2 months of administration of study medication.
26. History of malaria.
27. History or any evidence of active infection or febrile illness within 7 days of dosing (eg, 
bronchopulmonary, urinary, or gastrointestinal).
28. History of recurrent or chronic sinusitis, bronchitis, pneumonia, urinary tract infection 
(recurrent or chronic urinary tract infection is 2 episodes within 6 months).
29. Immunization with live vaccines or live-attenuated within 2 months prior to Day 1.
30. Inability to comply with protocol procedures, assessments, restrictions, and prohibited 
treatments.
31. Legal incapacity or limited legal capacity.
8.3.2.2 Psoriasis Patients (Part C)
1.
Previous participation in the current study.
2.
Participation in a drug study or exposure to any investigational drug or placebo within 
2 months prior to (the first) drug administration in the current study.
3.
Employees of PRA or the Sponsor and their relatives.
4.
Any significant acute or chronic medical condition that presents a potential risk to the 
subject and/or that may compromise the objectives of the study, including active, or 
history of, liver disease, or intestinal disorder including irritable bowel syndrome.
5.
Current or recent (within 3 months of study treatment administration) gastrointestinal 
disease that could affect pharmacokinetics; history of cholecystectomy is not allowed.
6.
Major surgery within 4 weeks of (first) study treatment administration.
7.
History or presence of malignancy including hematological malignancies; subjects with 
a history of basal cell or squamous cell carcinoma that has been treated with no evidence 
of recurrence will be allowed for inclusion, as judged by the Investigator.
8.
Documented congenital QT syndrome, and/or corrected QT interval (Fridericia 
correction) at screening or first admission >450 ms.
9.
Uncontrolled treated/untreated hypertension (defined as a mean of 3 repeated 
measurements for systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure 
≥105 mmHg); current or documented history of repeated clinically significant 
hypotension or severe episodes of orthostatic hypotension (systolic blood pressure 
< 90 mmHg and/or diastolic blood pressure < 50 mmHg).
10. Evidence of organ dysfunction or any clinically significant deviation from normal in 
physical examination, vital signs, ECG, or clinical laboratory results beyond what is 
consistent with the target population, including any of the following laboratory 
exclusion criteria:


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a. Leukopenia defined as absolute WBC count < 3000/mm3 within 28 days of dosing
with study drug on Day 1
b. Lymphopenia defined as absolute lymphocyte count < 500/mm3 within 28 days of 
dosing with study drug on Day 1
c. Neutropenia defined as absolute neutrophil count < 1000/mm3 within 28 days of
dosing with study drug on Day 1
d. Moderate to severe thrombocytopenia defined as platelet count < 100,000/mm3
within 28 days of dosing with study drug on Day 1
e. Moderate to severe anemia defined as hemoglobin < 9 g/dL within 28 days of
dosing with study drug on Day 1
f. ALT and/or AST > 3X ULN within 28 days of dosing with study drug on Day 1
g. Total, unconjugated, and/or conjugated bilirubin > 2X ULN within 28 days of 
dosing with study drug on Day 1
11. Donation or loss of more than 100 mL of blood within 2 months prior to (the first) drug 
administration. Donation or loss of more than 1.5 L of blood (for male subjects)/more 
than 1.0 L of blood (for female subjects) in the 10 months prior to (the first) drug 
administration in the current study.
12. Inability to be venipunctured and/or tolerate venous access.
13. Subjects who have smoked or used smoking cessation or nicotine containing products 
(including, but not limited, to e-cigarettes, pipes, cigars, chewing tobacco, nicotine 
patches, nicotine lozenges, or nicotine gum, varenicline, bupropion) within 6 months of 
the first dose of study drug.
14. Abuse or drug addiction (including cannabis products) within one year before screening 
(Appendix 4).
15. Average intake of more than 24 units of alcohol per week (1 unit of alcohol equals 
approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits).
16. Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines [including 
ecstasy], cannabinoids, barbiturates, benzodiazepines [if not prescribed or otherwise 
medically indicated, eg for anxiety, insomnia etc., and properly documented in 
concomitant medication], and alcohol) at screening or admission to the CRU.
17. Consumption of caffeine or xanthine-containing food or beverages from at least 
72 hours prior to admission to the CRU and during the stays at the CRU.
18. Consumption of any nutrients known to modulate CYP enzymes activity (eg, grapefruit 
or grapefruit juice, pomelo juice, star fruit, or Seville [blood] orange products) within 
14 days prior to first administration of study drug until after discharge in the last 
treatment period.
19. Subjects diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, 
medication-induced psoriasis, or other skin conditions at the time of the screening visit 
(eg, eczema) that would interfere with evaluations of the effect of IP on psoriasis.
20. Treatment with experimental or commercially available biological agents such as, but 
not limited to, etanercept, adalimumab, infliximab, certolizumab pegol within 3 months 
prior to Day 1.
21. Systemic immunosuppressants (such as, but not limited to, methotrexate, 
cyclosporine A, mycophenolate, tacrolimus, azathioprine, 6-thiguanine, mercaptopurine 


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and hydroxyurea), corticosteroids, or phototherapy (UV A light therapy [with or without 
psoralen], UV B light therapy, or excimer laser) within 1 month prior to Day 1.
22. Topical corticosteroid treatment other than low-strength or lower-mid strength 
corticosteroids on the face, scalp, axillae, and/or groin within 2 weeks prior to Day 1.
23. Concomitant medications (prescription, OTC, or herbal) outside the stable standard of 
care regimens for psoriasis administered during the study unless prescribed by the 
Investigator for treatment of specific clinical events.
24. Positive blood screen for hepatitis C antibody, HBsAg, or HIV-1 or -2 antibodies.
25. History of any significant drug and/or food allergies (such as anaphylaxis or 
hepatotoxicity).
26. Use of any prescription drugs within 4 weeks prior to study drug administration except 
those medications cleared by the Investigator and PRA Medical Monitor.
27. Use of OTC medications and herbal preparations within 2 weeks prior to study drug 
administration, except those medications cleared by the Investigator and PRA Medical 
Monitor.
28. Concomitant medications that are strong inhibitors or inducers of CYP3A4 or 
transporters administered within 2 weeks or 5 half-lives, whichever is longer, prior to the 
start of the study and throughout the study. Patients on stable standard of care 
medications that are moderate inhibitors or inducers of CYP3A4 or transporters will be 
cleared for use by the Investigator and PRA Medical Monitor. For guidance, please refer 
to http://medicine.iupui.edu/clinpharm/ddis/clinical-table or 
https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginte
ractionslabeling/ucm093664.htm
29. Any history or risk for TB, specifically subjects with: 1) current clinical, radiographic or 
laboratory evidence of active TB; 2) history of active TB; 3) positive Quantiferon® test 
result and history of latent TB, unless subject has documentation of completion of 
anti-TB treatment.
30. Known or suspected autoimmune disorder, except psoriasis, or any history of known or 
suspected congenital or acquired immunodeficiency state or condition that would 
compromise the subject’s immune status (eg, history of splenectomy or diabetes).
31. Presence of any factors that would predispose the subject to develop infection eg, 
bronchial asthma, rectal fissures, poor dentition.
32. Any serious (eg, requiring intramuscular or IV antibiotics and/or hospitalization) acute 
or chronic bacterial, viral, or fungal infection (eg, pneumonia, septicemia) within the 
3 months prior to screening.
33. Active herpes infection, including herpes simplex 1 and 2 and herpes zoster within 
2 months of administration of study medication.
34. History of malaria.
35. History or any evidence of active infection or febrile illness within 14 days of dosing 
(eg, bronchopulmonary, urinary, or gastrointestinal).
36. History of recurrent or chronic sinusitis, bronchitis, pneumonia, urinary tract infection 
(recurrent or chronic urinary tract infection is 2 episodes within 6 months).
37. Immunization with live vaccines or live-attenuated within 2 months prior to Day 1.
38. Inability to comply with protocol procedures, assessments, restrictions, and prohibited 
treatments.
39. Legal incapacity or limited legal capacity.


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8.3.3
Lifestyle Restrictions
1.
Subjects are to refrain from strenuous exercise and contact sports from 96 hours prior to 
screening, admission, and for the duration of the study as this could result in abnormal 
clinical laboratory values.
2.
Subjects are not permitted to consume alcohol-containing beverages from 72 hours prior 
to (first) admission to the CRU until completion of all follow-up visits at study discharge
(Part A and B) and from 72 hours prior to each visit to the CRU and during the stays in 
the CRU (Part C).
3.
Subjects are not permitted to consume caffeine-containing food or beverages from 
72 hours prior to admission to the CRU until 24 hours after the last dose (Part A and B), 
and from 72 hours prior to admission to the CRU and during the stays in the CRU 
(Part C).
4.
Subjects are not permitted to consume any nutrients known to modulate CYP enzymes 
activity (eg, grapefruit or grapefruit juice, pomelo juice, star fruit, or Seville [blood] 
orange products) within 14 days prior to first administration of study drug until after 
discharge in the last treatment period.
5.
Subjects are not allowed to smoke or use smoking cessation or nicotine containing 
products (including, but not limited to, e-cigarettes, pipes, cigars, chewing tobacco, 
nicotine patches, nicotine lozenges, or nicotine gum, varenicline, bupropion) within 
6 months of the first dose of study until after discharge in the last treatment period.
6.
Subjects are required to fast overnight with an additional 4 hours of fasting post-dose on 
the following study days: Day 1 (Part A), Day 1 and Day 14 (Part B and Part C 
[intensive PK sampling sub-cohort only]).
7.
Subjects should refrain from consumption of any foods containing poppy seeds within 
48 hours (2 days) prior to screening and admission to the clinical research center to 
avoid false positive drug screen results.
8.3.4
Screen Failures and Rescreening
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 information includes date of 
consent, demography, screen failure details, eligibility criteria, and any serious adverse 
events (SAEs).
The study permits the rescreening (after the end of the initial 3-week screening period) of a 
subject who discontinues the study as a pretreatment failure (ie, the subject failed screening 
and has not been treated). The subject must be re-consented and will be assigned a new 
identification number, and a full screening visit must be performed again.
Screening assessments and/or laboratory parameters (Section 1) may be repeated at the 
Investigator’s discretion, in an effort to find all possible well-qualified subjects. Consultation 


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with the PRA Medical Monitor may be needed to identify whether repeat testing of any 
particular parameter is clinically relevant.
8.3.5
Withdrawal and Replacement of Subjects
8.3.5.1
Discontinuation of Treatment
Subjects MUST discontinue IP or study procedures (in case of single dose treatments) for 
any of the following reasons:

Subject’s request 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 clinical 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.

Termination of the study or program by BMS.

Loss of ability to freely provide consent through imprisonment or involuntarily 
incarceration for treatment of either a psychiatric or physical (eg, infectious disease) 
illness.

Abnormal liver tests suggestive of drug-induced liver injury (DILI) as defined in 
Section 8.5.2.1.7.

Inability to comply with protocol.

Stopping rules as defined in Section 8.3.5.5 are met.

Discretion of the Investigator.
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 electronic case report form (eCRF) page. As indicated, appropriate follow-up 
and/or alternate medical care must be arranged for the subject.
Refer to the Schedule of Activities (Section 1) 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 study treatment should comply with protocol specified 
follow-up procedures as outlined in Section 1. The only exception to this requirement is 
when a subject withdraws consent for all study procedures including post-treatment study 
follow-up or loses the ability to consent freely (ie, is imprisoned or involuntarily incarcerated 
for the treatment of either a psychiatric or physical illness). Replacement of subjects is 
described in Section 8.3.5.4.
To the greatest extent possible, subjects who discontinue study treatment will remain in the 
study for continued follow-up.


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In the case of pregnancy (Section 8.5.2.1.5), the Investigator must immediately notify the 
BMS Study Director and PRA Medical Monitor or designee of this event. In the event a 
normal healthy female subject becomes pregnant during a clinical trial, the study treatment 
must be discontinued immediately. In most cases, the study treatment will be permanently 
discontinued in an appropriate manner (eg, dose tapering if necessary for subject safety). 
Please call the BMS Study Director and PRA Medical Monitor within 24 hours of awareness 
of the pregnancy.
8.3.5.2 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. 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. Expectations are as 
follows:

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, as to whether the withdrawal is from further treatment with study 
treatment only or also from study procedures and/or post-treatment study follow-up, 
and entered on the appropriate eCRF 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.
The following procedures must be performed upon subject withdrawal:

Assessments for the end of treatment visit must be performed, provided that the 
subject has not withdrawn consent for these activities.

All required eCRF pages must be completed, including the date of and explanation 
for the withdrawal.
8.3.5.3
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 as noted above. Lost to 
follow-up is defined by the inability to reach the subject after a minimum of 3 documented 
phone calls, faxes, or emails as well as lack of response by subject to 1 registered mail letter. 
All attempts should be documented in the subject’s medical records. If it is determined that 
the subject has died, the site will use permissible local methods to obtain the date and cause 
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The site staff 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.
8.3.5.4
Replacement of Subjects
Rescreening is discussed in Section 8.3.4.
Subjects will not be replaced if they are discontinued from the study secondary to an AE 
unless the AE can be determined to be unrelated to treatment. Subjects who are discontinued 
from the study for reasons not related to an adverse or other safety observation may be 
replaced. The replacement subject will receive the same treatment as the subject being 
replaced.
8.3.5.5
Stopping Rules for Part A and Part B
In the assessment whether AE related criteria for halting or stopping are met, special 
attention will be paid to any AE that is classed by the investigator as:

A sign or symptom of bacterial, fungal or viral infection.

An intestinal disorder.

A hematological abnormality.
Dosing within a dose cohort will be stopped and further dosing will be halted until 
unblinded safety information (of the subject with the event) can be reviewed in case of one or 
more of the following occurring at any time during the observation period in the ongoing 
cohort:
1. A clinically significant AE that in the opinion of the Investigator, BMS Study 
Director and PRA Medical Monitor, indicates that the limits of safety and tolerability 
have been met, and precludes further safe dosing of subjects.
2. Two or more subjects with a severe or serious AE considered to be related to the 
study drug.
3. Two or more subjects with a serious infection event or 1 subject with opportunistic 
infection requiring systemic therapy (assessed as related to study drug).
4. Two or more subjects with liver function test elevations (confirmed by repeat) in the 
absence of an alternative explanation, including:

aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 x 
upper limit of normal (ULN)

AST or ALT > 3 x ULN with symptoms consistent with hepatic inflammation
5. One or more subjects with liver function test elevations (confirmed by repeat) 
consistent with drug-induced liver injury, in the absence of an alternative explanation, 
including:

AST or ALT > 3 x ULN and total bilirubin > 2 x ULN
6. Two or more subjects have a greater than 60 msec increase in QTcF from the baseline 
value or a QTcF of > 500 msec (confirmed by repeat ECG).


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Pending review of all pertinent information collected to date, one of the following decisions 
may be made:

To continue dosing the remaining subjects of the cohort as planned, or

To reduce the dose and continue dosing the remaining subjects of the cohort at the 
modified dose level (or placebo), or

To terminate further dosing in the ongoing cohort.
In case of one or more occurrences as listed above, dose escalation will be halted until 
unblinded safety information for the subject(s) in the last completed cohort and with the 
event(s) can be reviewed. Pending review of all pertinent information collected to date, one 
of the following decisions may be made:

To escalate to the next dose level as planned, or

To escalate to a lower dose level than planned, or

To extend the last cohort with more subjects exposed to the same dose level (or 
placebo), or

To de-escalate, and to dose the next cohort to a lower dose than evaluated in the last 
cohort (or placebo), or

To terminate further dose escalations in the relevant study part; subsequent study 
parts may be continued with amended dose level(s).
In addition, the Sponsor and Investigator may decide to halt dosing within a panel or 
dose-escalation for reasons not defined above, including but not limited to observing trends 
in a given dose panel and/or across dose panels.
If any of the above criteria are met within a dose level, dosing will be put on hold and all 
safety data available across the study will be evaluated to estimate the risk of continuing 
dosing at the current level and/or proceeding to the higher dose level. The review may 
include unblinding of the subject(s) that experienced AEs listed above. In addition, the 
unblinded data set may include subjects from a dose panel, or if appropriate, all treated 
subjects to date. Unblinding recommendation must be approved by the Sponsor’s safety 
physician.
The maximum acceptable dose will be the dose level below the dose level at which the 
stopping criteria are met, unless it is determined that a lower dose should be designated as the 
maximum acceptable dose.
8.4 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 may include both IP and non-IP and is described in Table 9. In this protocol 
only administration of IP is planned.


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An IP, also known as Investigational Medicinal Product (IMP) in some regions, is defined as 
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, will be 
considered as non-IPs.


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Table 9
Study Treatments for IM024 005
Product Description 
/ Class and Dosage 
Form
Study 
Part/Cohort
Potency
IP/Non-IP
Blinded or Open 
Label
Packaging / 
Appearance
Storage Conditions
(per label)
BMS-986251 / 
oral solution
Part A and Part B
1 mg/mL and 
20 mg/mL
IP
Blinded
On-site compounded 
solution#
Refer to the label on 
container and/or 
pharmacy manual
Placebo for 
BMS-986251 / 
oral solution
Part A and Part B
N/A
IP
Blinded
On-site compounded 
solution#
Refer to the label on 
container and/or 
pharmacy manual
BMS-986251 / 
oral suspension
(under development)
Part A – BA/FE 
cohort only
Depending on final 
formulation
IP
Open label
Depending on 
formulation*
Refer to the label on 
container and/or 
pharmacy manual
BMS-986251 /
tablet
(under development)
Part C
Depending on final 
formulation
IP
Blinded
Formulated tablet in 
a bottle
Refer to label on 
container and/or 
pharmacy manual
Placebo for 
BMS-986251 /
tablet
(under development)
Part C
N/A
IP
Blinded
Formulated tablet in 
a bottle
Refer to label on 
container and/or 
pharmacy manual
IP = investigational product; N/A = not applicable.
#
The composition of the oral solution vehicle and placebo is 50/15/35 %w/w PEG-400 (polyethylene glycol-400)/TPGS (Tocopherol Polyethylene Glycol 
Succinate)/200mM Tris (trisaminomethane) buffer pH 9. 
*
The suspension formulation is under development. All excipients will be of compendial grade.
.


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8.4.1
Treatments Administered
The Investigator must ensure that the IP will be used only in accordance with the protocol.
8.4.1.1
Part A – SAD in Healthy Volunteers
In the morning of Day 1, after fasting for at least 10 hours, each subject will receive a single 
oral dose of BMS-986251 or placebo at approximately 9:00 AM as an oral solution of up to a 
planned volume of 6 mL, depending on the dose level. The medication time is provided as an 
indication only (for scheduling purposes).
Subjects enrolled in the BA/FE cohort will receive a second single oral dose of BMS-986251
at approximately 9:00 AM on the morning of Day 1 of Period 2, as an oral suspension (under 
development; representative for the solid dosage form to be used in Part C), after a 10-hour 
overnight fast. These subjects will receive a third single oral dose of BMS-986251 at 
approximately 9:00 AM on the morning of Day 1 of Period 3, as an oral suspension, 
30 minutes after start of consumption of a high-fat breakfast. The high-fat breakfast (see 
Appendix 5) has to be consumed completely in 20 minutes. The exact time of start and end of 
breakfast and the exact time of dosing will be recorded in the eCRF. Washout between single 
dose administrations will be at least 2 weeks, based on an anticipated terminal half-life of 
BMS-986251 of approximately 40 hours.
In all study periods, at the time of dosing, a total of 240 mL of water will be administered to 
the subjects in all cohorts along with his/her dose of study drug. The time of 
BMS-986251/placebo administration will be called “0” hour. The exact time of dosing will 
be recorded in the eCRF. Subjects will remain fasted until at least 4 hours after 
administration. Water is allowed during fasting, except for 2 hours before and 1 hour after 
administration.
8.4.1.2
Part B – MAD in Healthy Volunteers
In the morning of Days 1-14, each subject will receive a single oral dose of BMS-986251 or 
placebo at approximately 9:00 AM as an oral solution of up to a planned volume of 6 mL, 
depending on the dose level. The medication time is provided as an indication only (for 
scheduling purposes). On Days 1 and 14, subjects will fast for at least 10 hours prior to 
dosing. At the time of dosing, 240 mL of water will be administered to the subject along with 
his/her dose of study drug. The time of first dose administration will be called “0” hour; all 
other time points will be relative to time “0”. The exact time of dosing will be recorded in the 
eCRF. On Days 1 and 14, subjects will remain fasted until at least 4 hours after 
administration. Water is allowed during fasting, except for 2 hours before and 1 hour after 
administration.
On Days 2 to 13, BMS-986251 or placebo will be administered in the fasted state. After 
dosing, subjects will continue their fast until breakfast. The breakfast will be provided 
approximately 2 hours after dosing. Water is allowed during fasting, except for 2 hours 
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8.4.1.3
Part C – Multiple Dosing in Psoriasis Patients
Sub-cohort with intensive PK sampling
On Days 1 and 14, subjects will be dosed in the CRU following an overnight stay. They will 
receive a single oral tablet dose of BMS-986251 or placebo at approximately 9:00 AM in the 
morning, after an overnight fast of at least 10 hours prior to dosing. The medication time is 
provided as an indication only (for scheduling purposes). At the time of dosing, 240 mL of 
water will be administered to the subject along with his/her dose of study drug. The time of 
first dose administration will be called “0” hour; all other time points will be relative to time 
“0”. The exact time of dosing will be recorded in the eCRF. On Days 1 and 14, subjects will 
remain fasted until at least 4 hours after administration. Water is allowed during fasting, 
except for 2 hours before and 1 hour after administration.
On Day 2 subjects will be dosed in the CRU, after an overnight fast. Breakfast will be given 
after dosing. The minimum time between dosing and breakfast will be determined based on 
the results of the FE investigation in Part A. Prior to discharge, subjects will be given a 
dosing diary and study drug will be dispensed for at-home administration in the mornings on 
Days 3-6 and 8-13. Study treatment will be supplied as tablets in a bottle. Subjects will be 
instructed to take study drug at approximately the same time every morning on an empty 
stomach and are instructed to record the time of their taken dose in their dosing diary. Results 
from the FE investigation in Part A may lead to different dosing instructions. If a subject 
forgets a dose, but remembers within approximately 12 hours of the expected dose, the dose 
should be taken. If it is past 12 hours, that dose should be missed and the next expected dose 
should be taken at the usual time.
On Day 7, subjects will not take their morning dose at home, but instead bring their study 
drug and dosing diaries to the CRU for administration of the dose after completion of
pre-dose procedures.
Sub-cohort with sparse PK sampling
Patients enrolled in the sub-cohort with sparse PK sampling will receive the first dose of 
study drug in the CRU. The study drug will be taken with 240 mL of water. In addition, on 
Days 7 and 14 the patients will also receive their doses in the CRU. The remaining doses 
between Days 2-6 and 8-13 will be taken at home. On Day 1, subjects will be given a dosing 
diary and study drug will be dispensed for at-home administration in the mornings on 
Days 3-12. Study treatment will be supplied as tablets in a bottle. Subjects will receive the 
same dosing instructions for dosing at home as above.
8.4.2
Method of Treatment Assignment
Within each cohort (excluding the BA/FE cohort of Part A), subjects will be randomized to 
receive either BMS-986251 or placebo. All subjects who sign informed consent and are 
enrolled (including those not subsequently randomized or treated) will be assigned sequential 
subject numbers. Eligible subjects will be randomized according to a computer-generated 
randomization scheme. Subjects in Cohort A7 in Part A will be assigned sequential subject 


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numbers in the order of enrollment. Eligible subjects will be treated in accordance with the 
study design.
Sealed code break envelopes will be provided prior to the start of the study.
Part A, SAD in Healthy Volunteers:
Approximately 48 subjects (8 in each cohort) enrolling in Cohorts A1 to A6 will be 
randomized to BMS-986251 or matching placebo in a 3:1 randomization ratio. All subjects in 
BA/FE Cohort A7 will receive BMS-986251.
Part B, MAD in Healthy Volunteers:
Approximately 32 subjects will be enrolled in 4 dose cohorts during the MAD study. Each 
dose cohort will randomize 8 subjects in a 3:1 ratio to receive BMS-986251 or matching 
placebo.
Part C, Multiple Dosing in Psoriasis Patients:
Approximately 15 subjects in one planned dose cohort will be randomized in a 
randomization ratio of 4:1 to receive BMS-986251 or matching placebo.
Enrolled subjects meeting all of the inclusion and none of the exclusion criteria will be 
eligible to be dosed.
Subjects may be replaced under some circumstances (Section 8.3.5.4).
8.4.3
Blinding of Study Medication
8.4.3.1
Maintaining the Blind
As all parts of this Phase 1 FIH study are double blind (with the exception of the BA/FE 
cohort), the CRU staff, clinical research associates, Sponsor and designated personnel, study 
subjects, and their families will remain blinded to treatment assignments.
An unblinded PRA statistician will generate the treatment randomization schedule for each 
part of the study separately and the randomization schedules will be stored with restricted 
access.
An unblinded PRA pharmacist will prepare all study doses, however the CRU staff 
administering study medication will remain blinded. An unblinded CRA may be assigned if 
needed for drug accountability checks.
8.4.3.2
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 


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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 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 PRA Medical Monitor, but the Investigator always has 
ultimate authority for the decision to unblind. The 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 may open the emergency unblinding envelope to 
reveal the identity of the medication for that subject. If such unblinding occurs, the 
Investigator shall notify the BMS Study Director and PRA Medical Monitor immediately. 
This information, including the reason for the blind being broken, must be recorded on the 
appropriate study status page of the eCRF. In addition, the information that is requested on 
the emergency unblinding envelope must be completed.
In cases of accidental unblinding, contact the BMS Study Director and PRA Medical Monitor 
and ensure every attempt is made to preserve the blind. Any request to unblind a subject for 
non-emergency purposes should be discussed with the BMS Study Director and PRA 
Medical Monitor.
Within each cohort, safety, PK, and PD assessments will be performed. The bioanalytical 
personnel responsible for performing the analyses of the PK samples will be unblinded 
throughout the study to prevent unnecessary analysis of placebo samples. Following 
completion of each dose panel, there will be a review period between panels, during which 
all available safety, tolerability, PK, and PD data (as applicable) will be reviewed by the 
Sponsor’s dose escalation review group. Limited designated staff of BMS and/or PRA can be 
unblinded at this time to prepare preliminary summaries of PK, PD and safety data. These 
summaries will not reveal individual subjects’ treatment assignments and will include 
summaries and figures of mean data (as applicable). The Sponsor’s dose escalation review 
group will review the data and will determine whether escalation to the next dose level will 
occur, or whether dose-stopping criteria have been met. The pharmacist at the site and/or 
designate will be unblinded to the randomized treatment assignments in order to dispense 
treatment from bulk supplies, as needed. Except as noted above, other members of BMS 
Research and Development and PRA will remain blinded.
Randomization schedules will be shipped directly to a pharmacist or other individual(s) who 
will be responsible for the dispensing of blinded study drug. This (these) individual(s) will be 
unblinded to study drug identification but will not be involved in any other aspect of study 
conduct. The randomization schedules will be maintained in a secure location with access 
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8.4.4
Study Treatment Preparation, Handling, Storage, and Accountability
The IP should be stored in a secure area according to local regulations and site SOPs. It is the 
responsibility of the Investigator to ensure that 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 pharmacy 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 contacted immediately.
Study treatment not supplied by BMS will be stored in accordance with the package insert.
The IP documentation (whether supplied by BMS or not) must be maintained that includes 
all processes required to ensure drug is accurately administered, must be maintained. This 
includes documentation of drug storage, administration, and, as applicable, storage 
temperatures, reconstitution, and use of required processes (eg, required diluents, 
administration sets).
Compounding instructions will be provided separately to sites.
Storage facilities for controlled substances must be securely locked and substantially 
constructed, with restricted access to prevent theft or diversion, as applicable by local 
regulations.
Further guidance and information for final disposition of unused study treatment are provided 
in Appendix 1.
8.4.4.1 Retained Samples for Bioavailability / Bioequivalence
Not applicable.
8.4.5
Dose Modification
No dose reductions or modifications are allowed for a subject.
8.4.6
Treatment Compliance
8.4.6.1
Part A and B
Study drug will be administered in the CRU. After administration, an examination of the oral 
cavity is required to verify that a subject has swallowed the BMS-986251 or matching 
placebo. The subjects should drink the entire aliquot of water given with the oral solution.
Date and time of dosing will be recorded in the eCRF.


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8.4.6.2
Part C
During confinement and ambulatory visits, administration of the study drug will be
supervised by the Investigator or authorized designee to ensure treatment compliance as 
described in Section 8.4.6.1. Date and time of dosing will be recorded in the eCRF.
In the sub-cohort with intensive PK sampling, subjects will be dispensed blinded study drug 
for daily at-home administration on Day 2, prior to discharge from the CRU. Compliance to 
study drug during at-home administration will be monitored through the use of a subject 
dosing diary. Date and time of drug intake will be recorded daily, starting on Day 3 and up to 
and including Day 13 (with the exception of Day 7).
In the sub-cohort with sparse PK sampling, subjects will be dispensed blinded study drug for 
daily at-home administration on Day 1, after administration of the first dose in the CRU 
during an ambulant visit. Compliance to study drug during at-home administration will be 
monitored through the use of a subject dosing diary. Date and time of drug intake will be 
recorded daily starting on Day 2 and up to and including Day 13 (with the exception of 
Day 7).
Subjects will be asked to bring all unused study drug to the CRU at each ambulatory study 
visits. Study site personnel will review subjects’ dosing diaries and if non-compliance is 
noted, site personnel will re-train subjects on protocol of at-home dosing. Study site 
personnel must make reasonable efforts to obtain unused study drugs from subjects who do 
not routinely return them at study site visits. Unreturned drug will be considered to have been 
taken.
Compliance will further be confirmed by bioanalytical assessment of BMS-986251 in plasma 
samples taken during confinement and ambulatory visits.
 
 
 
 
 
 


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8.4.8
Treatment After the End of the Study
At the end of the study for Part C, the Investigator should ensure that subjects continue to 
receive appropriate standard of care to treat the condition under study.
Sponsor/PRA 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 or other reasons; b) 
the development of BMS-986251 for treatment of psoriasis is terminated for other reasons, 
including but not limited to lack of efficacy and/or not meeting the study objectives. In all 
cases Sponsor/PRA will follow local regulations.


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8.5 Efficacy and Safety Assessments
Study procedures and timing are summarized in the Schedule of Activities (Section 1). 
Waivers or exemptions from protocol-required evaluations are not allowed.
8.5.1
Efficacy Assessments
Preliminary efficacy assessments will be performed in Part C only and will consist of 
evaluation of PASI scores, PGA scores, and Dermatology Life Quality Index (DLQI) scores. 
Planned time points for all preliminary efficacy assessments are listed in the Schedule of 
Activities (Section 1).
8.5.1.1
Psoriasis Area and Severity Index Scoring (PASI)
The PASI is a physician assessed index that measures psoriasis severity and evaluates 
erythema, infiltration, and desquamation (scaling) on different body areas including the head, 
upper extremities, the trunk, and lower extremities. The area affected is included in this index 
as well. The PASI provides a clinical summary of psoriasis disease activity, as well as a 
means to assess treatment efficacy in psoriasis and is considered a reliable measure for 
disease severity. Further details are provided in Appendix 7.
8.5.1.2
Physician Global Assessment (PGA)
The Physician’s Global Assessment evaluates the overall severity of disease on a 6-point 
scale based on plaque elevation, scaling and erythema. The same observer should evaluate 
the score throughout the study for a particular subject. Further details are provided in 
Appendix 8.
8.5.1.3 Dermatology Life Quality Index (DLQI)
The DLQI4 has been the most widely used measure for assessing quality of life related to 
skin disease in psoriasis trials. This instrument consists of 10 questions covering six domains 
(symptoms and feelings, daily activities, leisure, work and school, personal relationships, and 
bother with psoriasis treatment). The DLQI can be found in Appendix 9.
8.5.2
Safety Assessments
Planned time points for all safety assessments are listed in the Schedule of Activities 
(Section 1). All urgent safety concerns must be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue treatment.
Safety evaluations that will be performed in addition to AE monitoring are physical 
examinations, vital signs, 12-lead ECGs, concomitant medication use, clinical laboratory 
tests, and continuous cardiac monitoring (Holter monitoring; Part A and B only).


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8.5.2.1
Adverse Events
The definitions of an AE or SAE can be found in Appendix 2.
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 2.
8.5.2.1.1 Time Period and Frequency for Collecting Adverse Events and Serious Adverse 
Events Information
The collection of non-serious AE information should begin at initiation of study treatment 
until the follow-up visit, at the time points specified in the Schedules of Activities 
(Section 1). Non-serious AE information should also be collected from the start of a placebo 
lead-in period or other observational period intended to establish a baseline status for the 
subjects.
After the subject’s written consent to participate in the study is obtained, all SAEs, whether 
related or not related to study drug, must be collected, including those thought to be 
associated with protocol specified procedures. All SAEs must be collected that occur during 
the screening period and within 30 days of discontinuation of dosing. If applicable, SAEs 
must be collected that relate to any later protocol specified procedure. The Investigator must 
report any SAE that occurs after this time period and that is believed to be related to study 
drug or protocol-specified procedure.
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 intensity and assessing causality of AEs and SAEs and the 
procedures for completing and reporting/transmitting SAE reports are provided in 
Appendix 2.

Medical occurrences that begin before the start of study treatment but after obtaining 
informed consent will be recorded on the appropriate section of the eCRF.

All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as 
indicated in Appendix 2.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
this being available.


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8.5.2.1.2 Method of Detecting Adverse Events and Serious Adverse Events
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.
8.5.2.1.3 Follow-up of Adverse Events and Serious Adverse Events

Non-serious AEs should be followed to resolution or stabilization, or reported as 
SAEs if they become serious (see Appendix 2).

Follow-up is also required for non-serious AEs that cause interruption or 
discontinuation of study treatment and for those present at the end of study treatment 
as appropriate.

All identified non-serious AEs must be recorded and described on the non-serious AE 
page of the eCRF. Completion of supplemental eCRFs 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 8.3.5.3).
Further information on follow-up procedures is given in Appendix 2.
8.5.2.1.4 Regulatory Reporting Requirements for Serious Adverse Events

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 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 and FDA Code 
of Federal Regulations 21 CFR Parts 312 and 320. A Suspected Unexpected Serious Adverse 
Reaction (SUSAR) is a subset of SAEs and will be reported to the appropriate regulatory 
authorities and Investigators following local and global guidelines and requirements.
8.5.2.1.5 Pregnancy
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 


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pregnancy. Investigators shall advise on the use of highly effective methods of contraception 
(ie, those that have a failure rate of < 1% when used consistently and correctly; Appendix 3).
If, following initiation of the study treatment, it is subsequently discovered that a subject is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half-lives after product administration, the Investigator must immediately notify the BMS 
Study Director, PRA Medical Monitor or designee of this event and complete and forward a 
Pregnancy Surveillance Form to BMS designee within 24 hours of awareness of the event 
and in accordance with SAE reporting procedures described in Appendix 2.
In most cases, the study treatment will be permanently discontinued in an appropriate manner 
(eg, dose tapering if necessary for subject safety). Please call the BMS Study Director within 
24 hours of awareness of the pregnancy.
Follow-up information regarding the course of the pregnancy, including perinatal and 
neonatal outcome and, where applicable, offspring information must be reported on the 
Pregnancy Surveillance Form.
Any pregnancy that occurs in a female partner of a male study subject should be reported to 
Sponsor or designee. In order for Sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner must sign an ICF form for disclosure 
of this information. Information on this pregnancy will be collected on the Pregnancy 
Surveillance Form.
8.5.2.1.6 Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the non-serious AE 
eCRF page or electronic SAE Report Form, 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).
8.5.2.1.7 Potential Drug-Induced Liver Injury
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities 
should occur prior to the reporting of a potential DILI event. All occurrences of potential 
DILIs, meeting the defined criteria, must be reported as SAEs (see Appendix 2 for reporting 
details).


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Potential DILI is defined by presence of all of the following characteristics:

ALT or AST elevation > 3 × ULN.

Total bilirubin > 2 × ULN, without initial findings of cholestasis (elevated serum 
alkaline phosphatase).

No other immediately apparent possible causes of aminotransferase 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.
8.5.2.1.8 Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, ECG, or any 
other potential safety assessment required or not required by protocol should also be recorded 
as a non-serious or serious AE, as appropriate, and reported accordingly.
8.5.2.2
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a 
product that is considered both excessive and medically important. All occurrences of 
overdose must be reported as SAEs (see Appendix 2).
In the event of an overdose, the Investigator should do the following:
1. Contact the medical monitor immediately.
2. Closely monitor the subject for AEs/SAEs and laboratory abnormalities until 
BMS-986251 can no longer be detected systemically (at least 3 days).
3. Obtain an additional plasma sample for PK analysis if requested by the medical 
monitor (determined on a case-by-case basis).
4. Document the quantity of the excess dose as well as the duration of the overdosing in 
the eCRF.
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.
8.5.2.3
Physical Examinations
Schedules for physical examinations are provided in Section 1. Complete and/or targeted 
physical examinations will be performed according to the CRO’s standard operating 
procedures (SOPs). In addition, body weight and height will be measured according to CRO 
SOPs.
Symptom-directed, targeted physical examinations are not listed in the schedules in 
Section 1, but will be conducted as needed/appropriate, at the Investigator’s discretion. 
Documentation of who performed the examination is to be recorded in source notes. A 
targeted physical examination may note any changes in the subject’s condition (body 
systems) since the last assessment and does not preclude examination of any of the other 


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body systems as clinically indicated. Every effort should be made to ensure the same 
evaluator will complete the examination for each subject at all visits throughout the study.
8.5.2.4
Clinical Safety Laboratory Assessments
Investigators must document their review of each laboratory safety report. A local laboratory 
will perform the analyses and will provide reference ranges for these tests. Results of clinical 
laboratory tests performed on Day -1 must be available prior to first dosing.
Results of all laboratory tests required by this protocol must be provided to BMS, either 
recorded on the laboratory pages of the eCRF or by another mechanism as agreed upon 
between the Investigator and BMS (eg, provided electronically). In case of unexplained or 
unexpected clinical laboratory test values, the tests will be repeated as soon as possible and 
followed up until the results have returned to the normal range and/or an adequate 
explanation for the abnormality is found. The clinical laboratory will clearly mark all 
laboratory test values that are outside the normal range and the Investigator will indicate 
which of these deviations are clinically significant. Any abnormal laboratory test result
considered clinically significant by the Investigator must be recorded on the appropriate AE 
page of the eCRF (Section 8.5.2.1.6).
Samples for clinical laboratory will be taken in the fasted state (at least 4 hours).


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Table 10
Clinical Laboratory Assessments
Hematology
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
Red blood cell count
Reticulocyte count
Chemistry
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Total bilirubin
Direct bilirubin
Alkaline phosphatase
Lactate dehydrogenase (LDH)
Creatinine
Urea
Uric acid
Fasting glucose
High sensitivity C-reactive protein (hs-CRP)
Total protein
Albumin
Sodium
Potassium
Chloride
Calcium
Inorganic phosphate
Magnesium
Creatine kinase
Creatinine clearance (CLcr)- screening only
Cholesterol
Triglycerides
High-density lipoprotein (HDL)
Low-density lipoprotein (LDL)
Urinalysis
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, protein or leukocytes esterase are positive on the dipstick
Serology 
Serum for hepatitis C antibody, HBsAg, and HIV-1 and -2 antibody (at screening only)
Quantiferon Gold test® for tuberculosis (TB) (at screening only)
Other Analyses 
Urine test for alcohol (see Table 1 through Table 4)
Urine test for drugs of abuse (see Table 1 through Table 4)
Pregnancy test (females only; see Table 1 through Table 4)
FSH (screening only; test will be performed in all females for logistical purposes)


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8.5.2.5
Vital Signs
Systolic and diastolic blood pressure and pulse will be recorded after the subject has been 
resting for at least 5 minutes in the supine position. These assessments will be made using an 
automated device. Body temperature and respiratory rate will be measured subsequently.
8.5.2.6
12-Lead Electrocardiogram
Standard 12-lead ECG will be recorded in triplicate (3 measurements within 5 minutes) after 
the subject has been resting for at least 5 minutes in the supine position. All ECG recordings 
will be performed using a standard high-quality, high-fidelity machine equipped with 
computer-based interval measurements and automated interpretation. The following ECG 
parameters will be recorded: heart rate, PR-interval, QRS-duration, QT-interval, QTc-
interval (Fridericia's) and the interpretation of the ECG profile by the Investigator. Changes 
of the T-wave and U wave morphology will be documented. Source documentation for ECG 
recordings will be kept.
8.5.2.7
Continuous Cardiac Monitoring (Holter Monitoring)
Continuous ECG monitoring will be performed to help monitor patient safety; primarily to 
detect ventricular and atrial arrhythmias. The site will follow their normal operating 
procedures established for ECG monitoring. Clinically significant findings from the 
monitoring will be recorded as AEs and SAEs per the Investigator’s decision, and at the 
Investigator’s discretion the study drug may be discontinued for clinically significant 
arrhythmias.
The ECGs collected by continuous monitoring will be stored for potential later use. These 
ECGs may or may not be analyzed for the purpose of Concentration Effect Modelling, based 
on future development decisions for BMS-986251. If analyzed, results of the modeling will 
not be included in the clinical study report, but will be included in a separate report.
8.5.3
Pharmacokinetics
Pharmacokinetic variables will be the plasma concentrations and urine concentrations (Part A 
and B only) of BMS-986251 and derived PK parameters. The PK parameters to be assessed 
for BMS-986251 include but are not limited to the parameters given below. Some of the 
listed parameters may only be calculated for specific parts of the study; this includes the 
assessment of urinary excretion of parent compound and metabolites in urine, which may be 
limited to the higher dosed cohorts in Part A and B. The relevant PK parameters to be 
calculated for each study part and study day are listed in Section 9.3.1.


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Cpre
Pre-dose plasma concentration
Cmax
Maximum observed plasma concentration
tmax
Time of maximum observed plasma concentration
AUC0-t
Area under the plasma concentration-time curve from time zero to 
time of last quantifiable concentration
AUC0-inf
Area under the plasma concentration-time curve from time zero 
extrapolated to infinite time 
AUC0-24
Area under the concentration-time curve over 24 hours (one dosing 
interval)
ARCmax
Accumulation ratio: ratio of Cmax following last dose (Day 14) to Cmax
following first dose (Day 1)
ARAUC0-24
Accumulation ratio: ratio of AUC0-24 following last dose (Day 14) to 
AUC0-24 following first dose (Day 1)
kel
Terminal elimination rate constant
t1/2
Terminal elimination half-life, calculated as 0.693/kel
CL/F
Apparent (oral) clearance, calculated as dose/AUC0-inf for single dose 
(Part A, Day 1) or dose/AUC0-24 for multiple dose (Part B and C, 
Day 14)
Vz/F
Apparent volume of distribution at terminal phase 
Aet
Cumulative urinary excretion (of the unchanged drug) (Part A and B 
only)
Feurine%
Amount excreted unchanged in urine (% of dose) (Part A and B only)
CLR
Renal clearance (Part A and B only)
Individual subject PK parameter values will be derived by non-compartmental methods by a 
validated PK analysis program. Actual times of sample collection will be used for the 
analyses. Table 11 (Part A), Table 12 (Part B), Table 13 (Part C, sub-cohort with intensive 
PK sampling), and Table 14 (Part C, sub-cohort with sparse PK sampling) list the sampling 
schedule to be followed for the assessment of PK in plasma (all study parts) and in urine 
(Part A and B only). In addition, exploratory metabolite profiling may be evaluated in select 
dose cohorts in blood and urine. No separate blood samples are planned for this, but residual 
plasma samples may be used for this purpose. An additional urine sample from each 
collection interval will be aliquoted for this purpose.
If deemed necessary by the Investigator or the Sponsor, the number and/or volume of blood 
samples per assessment may be increased as long as the total volume of blood drawn for a 
subject does not surpass 500 mL (except when extra blood samples need to be taken for 
safety reasons).
Blood and urine collection, processing, and shipping details will be outlined in the 
Laboratory Manual.
The plasma will be analyzed for BMS-986251 by a validated liquid chromatography-tandem 
mass spectrometry (LC-MS/MS) assay by PRA. The urine (Part A and B only) will be 
analyzed for BMS-986251 by a validated LC-MS/MS assay by PRA.


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Residual plasma and urine samples for exploratory metabolite profiling will be analyzed by 
an exploratory LC-MS/MS assay by BMS or BMS contracted laboratories.
Table 11
Pharmacokinetic Sampling Schedule; Part A
Sample Collection 
Time
Time
(relative to dosing)
hour:min
Blood Sample
Urine Sample
Study 
Day
Time 
(event)
PK Blood Sample
Collection Interval
-1
NA
NA
X
1
0 h
(pre-dose)
00:00
X
1
0.5 h
00:30
X
X (0-12 h)
1
1 h
01:00
X
1
1.5 h
01:30
X
1
2 h
02:00
X
1
3 h
03:00
X
1
4 h
04:00
X
1
6 h
06:00
X
1
8 h
08:00
X
1
12 h
12:00
X
X (12-24 h)
2
24 h
24:00
X
2
36 h
36:00
X
X (24-48 h)
3
48 h
48:00
X
4
72 h
72:00
X
X (48-72 h)
5
96 h
96:00
X
X (72-96 h)
6
120 h
120:00
X
X (96-120 h)
7
144 h
144:00
X
X (120-144 h)
9
192 h
192:00
X
11
240 h
240:00
X
h = hour; min = minute; PK = pharmacokinetic.


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Table 12
Pharmacokinetic Sampling Schedule; Part B
Sample Collection Time
Time
(relative to dosing)
hour:min
Blood Sample
Urine Sample
Study Day
Time 
(event)
PK Blood Sample
Collection Interval
-1
NA
NA
X
1
0 h 
(pre-dose)
00:00
X
1
0.5 h
00:30
X
1
1 h
01:00
X
1
1.5 h
01:30
X
1
2 h
02:00
X
1
3 h
03:00
X
1
4 h
04:00
X
1
6 h
06:00
X
1
8 h
08:00
X
1
12 h
12:00
X
2-13
0 h 
(pre-dose)
0:00
X
2-13
4 h
4:00
X
14
0 h 
(pre-dose)
0:00
X
X (0-24 h on Day 14)
14
0.5 h
00:30
X
14
1 h
01:00
X
14
1.5 h
01:30
X
14
2 h
02:00
X
14
3 h
03:00
X
14
4 h
04:00
X
14
6 h
06:00
X
14
8 h
08:00
X
14
12 h
12:00
X
15
24 h
24:00
X
16
48 h
48:00
X
18
96 h
96:00
X
20
144 h
144:00
X
24
240 h
240:00
X
h = hour; min = minute; NA = not applicable; PK = pharmacokinetic.


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Table 13
Pharmacokinetic Sampling Schedule; Part C (Sub-Cohort with Intensive 
PK Sampling)
Sample Collection Time
Time
(relative to dosing)
hour:min
Blood Sample
Study Day
Time (event)
PK Blood Sample
1
0 h 
(pre-dose)
00:00
X
1
0.5 h
00:30
X
1
1 h
01:00
X
1
1.5 h
01:30
X
1
2 h
02:00
X
1
3 h
03:00
X
1
4 h
04:00
X
1
6 h
06:00
X
1
8 h
08:00
X
1
12 h
12:00
X
2
0 h 
(pre-dose)
0:00
X
7
0 h 
(pre-dose)
0:00
X
14
0 h 
(pre-dose)
0:00
X
14
0.5 h
00:30
X
14
1 h
01:00
X
14
1.5 h
01:30
X
14
2 h
02:00
X
14
3 h
03:00
X
14
4 h
04:00
X
14
6 h
06:00
X
14
8 h
08:00
X
14
12 h
12:00
X
15
24 h
24:00
X
28
NA
NA
X
h = hour; min = minute; NA = not applicable; PK = pharmacokinetic.


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Table 14
Pharmacokinetic Sampling Schedule; Part C (Sub-Cohort with Sparse 
PK Sampling)
Sample Collection Time
Time
(relative to dosing)
hour:min
Blood Sample
Study Day
Time (event)
PK Blood Sample
1
0 h 
(pre-dose)
00:00
X
7
0 h 
(pre-dose)
00:00
X
14
0 h 
(pre-dose)
00:00
X
h = hour; min = minute; NA = not applicable; PK = pharmacokinetic
8.5.4
Pharmacodynamics
Planned time points for all PD assessments are listed in the Schedule of Activities 
(Section 1).
The following PD assessment is planned in this study:

Blood sampling for ex-vivo inhibition (I) of IL-17 secretion in whole blood (all study 
parts)
In addition, the following exploratory PD assessments are planned in this study:

Blood sampling for IL-17, IL-22, -defensin, and erythropoietin concentrations in 
serum or plasma (Part B and Part C).

Blood sampling for TBNK cells, T cells, T cell subsets (Part B and Part C).

Plaque biopsy for immunochemistry and RNA analysis (Part C).
Table 15 (Part A), Table 16 (Part B), Table 17 (Part C, sub-cohort with intensive PK 
sampling), and Table 18 (Part C, sub-cohort with sparse PK sampling) list the sampling 
schedule to be followed for the (exploratory) PD assessments. Further details of whole blood, 
plasma, and plaque biopsy collection and processing will be provided in a separate 
Laboratory Manual.
For the ex-vivo inhibition of IL-17 secretion in whole blood, PD parameters will be 
calculated as listed below. Some of the listed parameters may only be calculated for specific 
parts of the study. The relevant PD parameters calculated for each study part and study day 
are listed in Section 9.3.2.


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Ipre
Pre-dose inhibition
It
Inhibition at time t
Imax
Maximum observed inhibition
tImax
Time of maximum observed inhibition
tI>50%
Time of inhibition above 50%
tI>90%
Time of inhibition above 90%
Table 15
Pharmacodynamic Sampling Schedule; Part A
Sample Collection Time
Time
(relative to 
dosing)
hour:min
Blood Samples
Study Day
Time (event)
Ex-vivo IL-17 Inhibition in Whole Blood
-1
Admission
NA
X
1
0 h 
(pre-dose)
00:00
X
1
1 h
01:00
X
1
2 h
02:00
X
1
4 h
04:00
X
1
12 h
12:00
X
2
24 h
24:00
X
3
48 h
48:00
X
5
96 h
96:00
X
7
144 h
144:00
X
11
240 h
240:00
X
h = hour; IL-17 = interleukin-17; min = minute; NA = not applicable.


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Table 16
Pharmacodynamic Sampling Schedule; Part B
Sample Collection 
Time
Time
(relative to 
dosing)
hour:min
Blood Sample
Study 
Day
Time 
(event)
Ex-vivo IL-17 
inhibition in whole 
blood 
IL-17, IL-22, 
β-defensin, and 
erythropoietin 
concentrations
T, B, and NK cells
(TBNK), T cells, 
T cell subsets
-1
Admission
NA
X
1
0 h 
(pre-dose)
00:00
X
X
X
1
1 h
01:00
X
1
2 h
02:00
X
1
4 h
04:00
X
1
12 h
12:00
X
2
0 h 
(pre-dose)
0:00
X
4
0 h 
(pre-dose)
0:00
X
7
0 h 
(pre-dose)
0:00
X
14
0 h 
(pre-dose)
0:00
X
14
1 h
01:00
X
14
2 h
02:00
X
14
4 h
04:00
X
14
12 h
12:00
X
15
24 h
24:00
X
X
16
48 h
48:00
X
20
144 h
144:00
X
24
240 h
240:00
X
X
X
h = hour; IL-17 = interleukin-17; IL-22 = interleukin-22; min = minute; NA = not applicable; NK = natural 
killer.


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Table 17
Pharmacodynamic Sampling Schedule; Part C (Sub-Cohort with 
Intensive PK Sampling)
Sample Collection 
Time
Time
(relative to 
dosing)
hour:min
Blood Sample
Plaque Biopsy
Study 
Day
Time 
(event)
Ex-vivo 
IL-17 
inhibition 
in whole 
blood 
IL-17, IL-22, 
β-defensin, and 
erythropoietin 
concentrations
T, B, and NK 
cells (TBNK), 
T cells, T cell 
subsets
Immuno-
chemistry and 
RNA analysis
-1a
Admission
NA
X
X
1
0 h 
(pre-dose)
00:00
X
X
X
1
1 h
01:00
X
1
2 h
02:00
X
1
4 h
04:00
X
1
12 h
12:00
X
2
0 h 
(pre-dose)
0:00
X
7
0 h 
(pre-dose)
0:00
X
X
14
0 h 
(pre-dose)
0:00
X
X
X
14
1 h
01:00
X
14
2 h
02:00
X
14
4 h
04:00
X
X
14
12 h
12:00
X
15
24 h
24:00
X
28
NA
NA
X
X
X
h = hour; IL-17 = interleukin-17; IL-22 = interleukin-22; min = minute; NA = not applicable; NK = natural 
killer.


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Table 18
Pharmacodynamic Sampling Schedule; Part C (Sub-Cohort with Sparse 
PK Sampling)
Sample Collection 
Time
Time
(relative to 
dosing)
hour:min
Blood Samplea
Plaque Biopsy
Study 
Day
Time 
(event)
Ex-vivo 
IL-17 
inhibition 
in whole 
blood 
IL-17, IL-22, 
β-defensin, and 
erythropoietin 
concentrations
T, B, and NK 
cells (TBNK), 
T cells, T 
cell subsets
Immuno-
chemistry and 
RNA analysis
1
0 h 
(pre-dose)
00:00
X
X
X
X
7
0 h 
(pre-dose)
00:00
X
X
X
14
0 h 
(pre-dose)
00:00
X
X
X
X
28
NA
NA
X
X
X
 
 
 
 
 
 
 


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8.5.6
Total Blood Volume to be Collected (Part A and Part B)
The number and volume of blood samples and the total volume of blood that will be 
collected throughout the study per subject is given in Table 20 (Cohorts A1 to A6) and 
Table 21 (Cohort A7) for Part A, and in Table 22 for Part B.
If deemed necessary by the Investigator or the Sponsor, the number and/or volume of blood 
samples per assessment may be increased as long as the total volume of blood drawn for a 
subject does not surpass 500 mL (except when extra blood samples need to be taken for 
safety reasons).
Table 20
Number and Volume of Blood Samples and Total Blood Volume 
Collected per Subject (Part A, Cohorts A1-A6)
Assessment
Maximum # 
samples
Volume of blood per 
sample (mL)
Total volume of 
blood (mL)
Pharmacokinetics
- BMS-986251 in plasma
19
5
95
Pharmacodynamics
- Ex vivo inhibition of IL-17 
secretion in whole blood
11
1
11
Whole blood for potential 
analysis of DNA variants in 
ADME-related genes 
1
6
6
Clinical chemistry
6
3.5
21
Hematology 
6
3
18
Serology
1
5
5
QuantiFERON® test
1
4
4
Total volume of blood drawn
160


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Table 21
Number and Volume of Blood Samples and Total Blood Volume 
Collected per Subject (Part A, Cohorts A7)
Assessment
Maximum # 
samples
Volume of blood per 
sample (mL)
Total volume of 
blood (mL)
Pharmacokinetics
- BMS-986251 in plasma
57
5
285
Pharmacodynamics
- Ex vivo inhibition of IL-17 
secretion in whole blood
11
1
11
Whole blood for potential 
analysis of DNA variants in 
ADME-related genes 
1
6
6
Clinical chemistry
14
3.5
49
Hematology 
14
3
42
Serology
1
5
5
QuantiFERON® test
1
4
4
Total volume of blood drawn
402
Table 22
Number and Volume of Blood Samples and Total Blood Volume 
Collected per Subject (Part B)
Assessment
Maximum # 
samples
Volume of blood per 
sample (mL)
Total volume of 
blood (mL)
Pharmacokinetics
- BMS-986251 in plasma
49
5
245
Pharmacodynamics
- Ex vivo inhibition of IL-17 
secretion in whole blood
- IL-17, IL-22, β-defensin, 
erythropoietin
  
17
4
4
1
2.5
5
17
10
20
Whole blood for potential 
analysis of DNA variants in 
ADME-related genes 
1
6
6
Clinical chemistry
8
3.5
28
Hematology 
8
3
24
Serology
1
5
5
QuantiFERON® test
1
4
4
Total volume of blood drawn
359


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9. STATISTICAL CONSIDERATIONS
9.1 Sample Size Determination
Part A and B – SAD and MAD cohorts
The current design of 8 subjects per cohort with 6 subjects assigned to active treatment is a 
commonly used design for SAD and MAD studies and is considered sufficient to achieve the 
study objectives. Although this number of is not based on statistical power considerations, 
administration of BMS-986251 to 6 subjects in each dose cohort provides approximately 
80% probability of observing at least one occurrence of any AE which would occur with 
approximately 24% incidence in the population from which the sample is drawn.
Part A – BA/FE cohort
The planned number of 8 subjects on active treatment to be enrolled in the BA/FE cohort (in 
which BA and FE of an oral suspension will be evaluated in a 3-period sequential design), 
has not been based on formal statistical sample size calculations. This number of subjects is a 
commonly accepted number of subjects for this type of exploratory study and is considered 
sufficient to achieve the study objectives.
Part C – Psoriasis patients
Like Parts A and B, Part C is also an exploratory study. Therefore, no formal statistical 
sample size calculation has been performed and the sample size is not based on a power 
calculation. The planned number of 15 subjects with 12 subjects on active treatment is a 
commonly accepted number of subjects for this type of exploratory study. Formal statistical 
hypotheses were not set up. Any statistical test performed will be exploratory.
9.2 Populations for Analyses
The following populations are defined for each part of the study and will be used for analysis 
purposes:
Population
Description
Enrolled 
All subjects who sign informed consent.
Randomized
All subjects who are randomized to a treatment, analyzed 
as per randomized treatment. 
Safety
All subjects who had received at least one dose of 
BMS-986251 or placebo. 
Pharmacokinetic (PK)
All subjects who receive at least 1 dose of BMS-986251
and 
have 
any 
available 
concentration-time 
data. 
Additionally, the evaluable PK population is defined as 
subjects who have adequate PK profiles.


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Population
Description
Pharmacodynamic (PD)
All subjects who receive at least 1 dose of BMS-986251 
or placebo and have any available concentration-time 
data for the PD assessments. Additionally, the evaluable 
PD population is defined as subjects who have adequate 
PD profiles.
Efficacy
All subjects who receive at least 1 dose of BMS-986251 
or placebo and have available data for the efficacy 
assessments at baseline and the last visit at a minimum.
9.3 Endpoints
9.3.1
Primary Endpoints
The primary objective to assess the safety, tolerability and PK of single and multiple oral 
doses of BMS-986251 in healthy subjects and in patients with moderate-to-severe psoriasis
will be measured by the following primary endpoints:
Safety and tolerability

Number and percent of subjects that experience the following: SAE, death or an AE 
leading to study discontinuation, during the study participation or up to 1 month post 
discontinuation of dosing or last participation in the study for SAE.

Number and percent of subjects with potentially clinically significant changes in ECG 
parameters, vital signs, or clinical laboratory parameters from Day 1 through the final 
follow visit.
Other safety measures collected during the study are not considered among the primary 
endpoint and will be summarized as safety endpoints. Stopping rules for safety are discussed 
in Section 8.3.5.5.
Pharmacokinetics
PK parameters will be derived from BMS-986251 concentration versus time data measured 
at the time points specified in the schedule of assessments for each part of the study. The PK 
parameters to be assessed are listed in Section 8.5.3. The PK parameters to be evaluated in 
each part include but are not limited to the following:

Part A: Cmax, tmax, AUC0-t, AUC0-inf, t1/2, CL/F, Vz/F, Aet, Feurine%, CLR

Part B: 
Day 1: Cmax, tmax, AUC0-t, AUC0-24
Days 2-14: Cpre
Day 14: Cmax, tmax, AUC0-t, AUC0-24, CL/F, Vz/F, t1/2, ARAUC0-24, ARCmax, Aet, 
Feurine%, CLR

Part C (intensive PK sampling sub-cohort): 
Day 1: Cmax, tmax, AUC0-t, AUC0-24


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Days 2-14: Cpre
Day 14: Cmax, tmax, AUC0-t, AUC0-24, CL/F, Vz/F, t1/2, ARAUC0-24, ARCmax

Part C (sparse PK sampling sub-cohort): 
Days 7 and 14: Cpre
9.3.2
Secondary Endpoints
The secondary objective to assess PD of single and multiple oral doses of BMS-986251 in 
healthy subjects and in patients with moderate-to-severe psoriasis will be measured by 
evaluating the percentage ex-vivo inhibition (I) of IL-17 secretion in whole blood. PD 
parameters will be derived from inhibition versus time data measured at the time points 
specified in the schedule of assessments for each part of the study. The PD parameters to be 
assessed are listed in Section 8.5.4. The PD parameters to be evaluated in each part include:

Part A: Imax, tImax, tI>50%, tI>90%

Part B: Imax, tImax, tI>50%, tI>90% (Day 1 and Day 14); Ipre (Days 2, 4, 7, and 14); It (Days 
16, 20, and 24)

Part C (intensive PK sampling sub-cohort): Imax, tImax, tI>50%, tI>90% (Day 1 and Day 
14); Ipre (Days 1, 2, and 14); It (Days 15 and 28)

Part C (sparse PK sampling sub-cohort): Ipre (Days 1, 7 and 14); It (Day 28)
The secondary objectives to evaluate the oral BA of an oral suspension of BMS-986251 
relative to a liquid dosage form at a single dose level in healthy subjects, and to evaluate the 
effect of a high-fat meal on the PK of an oral suspension of BMS-986251 at a single dose 
level in healthy subjects will be evaluated by comparing the PK parameters listed for the 
SAD part in Section 9.3.1.
The secondary objective to evaluate the efficacy of multiple doses of BMS-986251 in 
patients with moderate-to-severe psoriasis will be evaluated by evaluating the following 
endpoints:

PASI score at baseline, and Days 7, 14, and 28

PGA score at baseline, and Days 7, 14, and 28

DLQI at baseline, and Days 7, 14, and 28
 
 
 


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9.4 Statistical Analyses
A statistical analysis plan (SAP) will be developed and finalized prior to database lock and 
will provide detailed specifications of the analysis of all study endpoints.
Descriptive summaries will be presented for continuous variables using number of subjects 
(N), mean, standard deviation (SD), median, minimum, and maximum. In addition geometric 
mean and coefficient of variation (CV) will be reported for selected variables as appropriate. 
Descriptive summaries for categorical variables will utilize counts (N) and percentages (%).
Each part of the study will be summarized separately. Subjects receiving placebo in any 
cohort will be pooled into a single placebo group.
9.4.1
Efficacy Analyses
Efficacy analyses will be performed using the efficacy population. Efficacy assessments will 
be summarized descriptively. Descriptive statistics of PASI, PGA, and DLQI scores will be 
provided for each time point. In addition, exposure-response analysis (if sufficient data are 
available) or dose–response analysis (in case more dose cohorts are included in Part C) may
be performed of the percent change from baseline in PASI score on Days 7, 14, and 28 and 
for the percentage of active-treated patients per cohort with 75% reduction in PASI score 
(PASI75) on Day 28 versus baseline. Exposure-response analysis (if sufficient data are 
available) or dose–response analysis (in case more dose cohorts are included in Part C) of 
change in PGA and DLQI on Days 7, 14 and 28 may be performed as well. Further details of 
the exploratory efficacy analyses may be added to the protocol via protocol amendment prior 
to start of Part C and will also be provided in the SAP.
9.4.2
Safety Assessments
Safety analyses will be performed using the safety population.
9.4.2.1
Adverse Events
All recorded AEs will be listed and tabulated by system organ class, preferred term, and 
treatment for each part of the study. Coding will be performed according to the current 
version of the Medical Dictionary for Regulatory Activities (MedDRA) dictionary. Adverse 
events which occur on or after the first dose of study treatment through study participation 
will be considered treatment emergent and will be summarized. Serious AEs will be recorded 
from signing of the ICF up to 1 month after the last dose of study treatment or last 


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participation in the study (whichever is longer) and will be included in summary statistics. 
Adverse events leading to discontinuation or death will be listed.
9.4.2.2
Vitals Signs and ECGs
Vital sign measurements and 12-lead ECG test results will be listed and summarized.
Vital sign parameters (temperature, SBP, DBP respiratory rate and heart rate) at each 
collected time point during the study period will be summarized for each treatment by study 
part. Change from baseline will be derived for each time point and will be summarized. If 
considered informative, plots of the mean change from baseline for each parameter versus 
time since dosing may be presented by treatment.
ECG parameters (heart rate, QTcF, PR, QRS) will be summarized using descriptive statistics. 
Each parameter and the corresponding change from baseline will be summarized by 
treatment and time point in each part of the study. Electrocardiogram readings will be 
evaluated by the Investigator and abnormalities, if present, will be listed.
The baseline value is defined as the Day 1 (pre-dose) value, or the last assessment obtained 
prior to study drug administration.
9.4.2.3
Clinical Laboratory Data
Clinical laboratory data will be listed and summarized by treatment and time point. Change 
from baseline will also be displayed. Shift tables and graphical presentation of laboratory 
values over time may be provided (absolute values and/or change from baseline). Baseline 
value is defined as the last result obtained prior to study drug administration (Day -1 or 
Day 1 [pre-dose], whichever is the last result obtained).
Abnormal test results will be listed.
9.4.2.4
Physical Examination
Abnormal physical examination findings will be collected and listed by treatment and dosing 
cohort.
9.4.3
Pharmacokinetics
All available concentration-time data from subjects who receive BMS-986251 will be 
reported.
All available derived PK parameters will be included in the PK data set and reported, but 
only subjects with adequate PK profiles will be included in the summary statistics and 
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BMS-986251 plasma concentrations and derived PK parameters (see Section 8.5.3) will be 
listed and summarized descriptively by study part, treatment, and study day/time point 
(where appropriate) in tabular and/or graphical form using appropriate descriptive statistics. 
Details will be provided in the SAP.
Dose-linearity analysis will be performed of Cmax, AUC0-t, and AUC0-inf (Part A), and Cmax
and AUC0-24 (Days 1 and 14) (Part B). Scatter plots of the appropriate PK parameters versus 
dose will be presented. Dose proportionality will be assessed by estimating the slope of the 
linear regressions of log[AUC0-t], log[AUC0-inf], and log(Cmax) on log(dose). The power 
model described by Gough et al5 will be used to assess the dose proportionality of 
BMS-986251. Details on the analysis will be provided in the SAP.
To assess the relative BA (Cmax, AUC0-t, and AUC0-inf) and change in tmax comparing an oral 
suspension (under development; representative for a solid dosage form to be used in Part C; 
Cohort A7, Period 2) and a liquid dosage form (Cohort A7, Period 1), linear mixed model 
analyses will be performed. Point estimates and 90% confidence intervals will be constructed 
for the ratios of oral suspension to liquid dosage form geometric means. Treatment 
differences on the log-scale will be exponentiated to obtain estimates for ratios of geometric 
means on the original scale. Details on these statistical analyses will be provided in the SAP.
To evaluate the effect of food on the PK of BMS-986251 given as an oral suspension 
(Cohort A7, Periods 2 and 3), linear mixed model analyses will be performed. Point 
estimates and 90% confidence intervals will be constructed for the ratios of fed (Period 3) to 
fasted (Period 2) geometric means. Treatment differences on the log-scale will be 
exponentiated to obtain estimates for ratios of geometric means on the original scale. Details 
on these statistical analyses will be provided in the SAP.
Individual PK parameters from the 3 periods will be plotted versus treatment (liquid dosage 
form fasted, oral suspension fasted, or oral suspension fed).
If warranted, analysis of PK and exposure-response relationships of BMS-986251 will be 
conducted using a population approach as appropriate and reported separately from the 
clinical study report.
9.4.4
Pharmacodynamics
Percentage of inhibition of ex-vivo IL-17 secretion in whole blood and derived PD 
parameters (see Section 8.5.4) will be listed and summarized by treatment and time point 
collected in tabular and/or graphical form using appropriate descriptive statistics. Results of 
exploratory PD assessments will be listed and summarized descriptively as well. Details will 
be provided in the SAP.


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Dose-response analysis will be performed of Imax, tI>50%, and tI>90% for inhibition of ex-vivo 
stimulated IL-17 secretion in whole blood. Concentration-effect modeling will be performed 
for BMS986251 plasma concentrations versus PD, including exploratory PD assessments.
PK and exploratory PD profiles will be compared on Days 1 and 14 (Parts B and C). Time-
dependent changes will be evaluated. Details on these analyses will be provided in the SAP.
9.4.5
Interim Analysis
Dose escalation reports will be prepared after each cohort in Parts A and B after completion 
of each cohort. Safety and preliminary PK and/or PD data from Parts A and B will be 
summarized as an interim report prior to initiation of Part C. The report will be submitted to 
the relevant health authorities.




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11. APPENDICES
Appendix 1
Study Governance Considerations..............................................................................94
Appendix 2
Adverse Events and Serious Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting....................................................101
Appendix 3
Women of Childbearing Potential Definitions and Methods of Contraception........104
Appendix 4
Diagnostic Criteria for Drug and Alcohol Abuse .....................................................108
Appendix 5
Representative Standard High Fat and High Calorie Meal.......................................110


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APPENDIX 1
STUDY GOVERNANCE CONSIDERATIONS
The term ‘Subject’ used in the eCRF is intended to refer to a person who has consented to 
participate in the clinical research study.
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);

the ethical principles underlying European Union-Clinical Trial Directive (EU-CTD) 
2001/20/EC;

United States Code of Federal Regulations, Title 21, Part 50 (21CFR50); and

applicable local requirements.
The study will be conducted in compliance with the protocol. The protocol and any 
amendments and the subject informed consent form (ICF) will receive approval/favorable 
opinion by the Independent Ethics Committee (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).
INDEPENDENT ETHICS COMMITTEE
Before study initiation, the Investigator must have written and dated approval/favorable 
opinion from the IEC for the protocol, ICF, subject recruitment materials (eg, 
advertisements), and any other written information to be provided to subjects. The 
investigator or BMS should also provide the 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 IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according 
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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 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:

IEC

Regulatory Authority(ies), if applicable by local regulations (per national 
requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IEC 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 ICF must be revised and submitted to the IEC 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 IEC.
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.
Sponsor or designee will provide the Investigator with an appropriate (ie, Global or Local) 
sample ICF which will include all elements required by ICH, GCP, and applicable regulatory 
requirements. The sample ICF will adhere to the ethical principles that have their origin in 
the Declaration of Helsinki.


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Investigators must:

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 to inquire about the details of the study.

Obtain an ICF 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 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.

Revise the ICF 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 Health Insurance Portability Act Authorization.
The ICF must also include a statement that BMS and regulatory authorities have direct access 
to subject records.
The rights, safety, and well-being of the study subjects are the most important considerations 
and should prevail over interests of science and society.
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, adverse event tracking/reporting, protocol required assessments, 
and/or drug accountability records).
When paper records from such systems are used in place of electronic format to perform 
regulated activities, 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.


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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 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 drug integrity in accordance with 
requirements applicable under law and the 
SOPs/standards of the sourcing pharmacy.
These records should include:

label identification number or batch 
number

amount dispensed to and returned by 
each subject, including unique subject 
identifiers


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If
Then

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 eCRF 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 Pregnancy Surveillance form, respectively. 
If electronic SAE form is not available, a paper SAE form can be used. Spaces may be left 
blank only in those circumstances permitted by study-specific CRF completion guidelines 
provided by sponsor or designee.
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 Sub-Investigator and who is delegated this 
task on the Delegation of Authority Form. Sub-Investigators in Japan may not be delegated 
the CRF approval task. 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.
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.


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MONITORING
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.
In addition, the study may be evaluated by sponsor or designee internal auditors and 
government inspectors who must be allowed access to eCRFs, 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). 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).
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) (eg,study 
treatments sourced from the sites’ stock or 
It is the Investigator’s or designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 


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commercial supply, or a specialty pharmacy)
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 single site protocol, the Principal Investigator for the site will sign the clinical study 
report.
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 governing study site 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 2
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.
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/incapacity
Is a congenital anomaly/birth defect


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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 8.5.2.1.7) for the definition of potential DILI). 
Suspected transmission of an infectious agent (eg, pathogenic or nonpathogenic) via the 
study treatment is an SAE.
Although pregnancy, overdose, cancer, and potential DILI are not always serious by 
regulatory definition, these events must be handled as SAEs (see Section 8.5.2.1.5 for 
reporting pregnancies).
EVALUATING AES AND SAES
Assessment of Intensity
The intensity of AEs is determined by a physician and will use the following levels:

Mild

Moderate

Severe
Assessment of Causality
The causal relationship to study drug is determined by a physician and should be used to 
assess all AEs. The causal relationship can be one of the following:

Related: There is a reasonable causal relationship between study drug 
administration and the AE.

Not related: There is not a reasonable causal relationship between study drug 
administration and the AE.
The term “reasonable causal relationship” means there is evidence to suggest a causal 
relationship. 
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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REPORTING OF SAES TO SPONSOR OR DESIGNEE

SAEs, whether related or not related to study drug, and pregnancies must be 
reported to PRA Drug Safety within 24 hours of awareness of the event.

SAEs must be recorded on the Safety Report Form; pregnancies on the Pregnancy 
Surveillance Form (paper forms) and entered on the eCRF.

The preferred method for SAE/pregnancy data reporting collection is through the 
paper SAE/pregnancy surveillance forms. The paper forms are to be transmitted 
via email or confirmed facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list.
When paper forms are used, the original paper forms are to remain on site.


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APPENDIX 3
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
DEFINITIONS
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal 
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:
o
Documented hysterectomy
o
Documented bilateral salpingectomy
o
Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.
Postmenopausal female
A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 45 years 
in the absence of other biological or physiological causes. In addition, females under the age 
of 55 years must have a serum 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 periods below are suggested guidelines and the investigators should 
use their judgment in checking serum FSH levels.

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months. If the serum 
FSH level is > 40 mIU/mL at any time during the washout period, the woman can be 
considered postmenopausal.


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CONTRACEPTION GUIDANCE FOR FEMALE PARTICIPANTS OF CHILD 
BEARING POTENTIAL
One of the methods of contraception listed below is required for the duration of treatment 
with BMS-986251 until at least 3 months post treatment completion.

Non-hormonal intrauterine device

Intrauterine hormone-releasing system

Bilateral tubal occlusion

Complete abstinence as defined below

Vasectomized partner with documented azoospermia 3 months after procedure
Local laws and regulations may require use of alternative and/or additional contraception 
methods.
“Highly effective” denotes methods with a failure rate of < 1% per year when used 
consistently and correctly. Typical use failure rates may differ from those when used 
consistently and correctly. Use should be consistent with local regulations regarding the use 
of contraceptive methods for participants participating in clinical studies.
“Less than highly effective” denotes methods with a failure rate of > 1% per year when used 
consistently and correctly.
Highly Effective Contraceptive Methods That Are User Dependent 

Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation: oral, intravaginal, or transdermal

Progestogen-only hormonal contraception associated with inhibition of ovulation: oral 
or injectable
Note: Hormonal contraception may be susceptible to interaction with the study drug, which 
may reduce the efficacy of the contraceptive method. Hormonal contraception is permissible 
only when there is sufficient evidence that the study drug 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.
Highly Effective Methods That Are User Independent

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation (see above note about potential for interaction of study drug and hormonal 
methods)

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)

Bilateral tubal occlusion
Note: IUDs and IUSs are acceptable methods of contraception in the absence of definitive 
drug interaction studies when hormone exposures from IUDs do not alter contraception 
effectiveness.


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
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.

Sexual abstinence: Sexual abstinence is considered a highly effective method only if 
defined as refraining from heterosexual intercourse during the entire period of risk 
associated with the study drug. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the participant.
o
It is not necessary to use any other method of contraception when complete 
abstinence is elected.
o
WOCBP participants who choose complete abstinence must continue to have 
pregnancy tests, as specified in Section 1.
o
Acceptable alternate methods of highly effective contraception must be 
discussed in the event that the WOCBP participants chooses to forego 
complete abstinence
o
The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the subject
Less Than Highly Effective Contraceptive Methods That Are User Dependent

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, postovulation methods)

Withdrawal (coitus interruptus).

Spermicide only

Lactation amenorrhea method 
CONTRACEPTION GUIDANCE FOR MALE PARTICIPANTS WITH PARTNER(S)
OF CHILD BEARING POTENTIAL
Male participants with female partners of childbearing potential are eligible to participate if 
they agree to the following during the treatment and until the end of relevant systemic 
exposure.

Inform any and all partner(s) of their participation in a clinical drug study and the 
need to comply with contraception instructions as directed by the investigator.

Male participants are required to use a condom for study duration and a minimum of 
3 months after dosing has been completed.


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
Female partners of males participating in the study to consider use of effective 
methods of contraception for the duration of the study and a minimum of 3 months 
after dosing has been completed.

Male participants with a pregnant or breastfeeding partner must agree to remain 
abstinent from penile vaginal intercourse or use a male condom during each episode 
of penile penetration during the treatment and a minimum of 3 months after dosing 
has been completed.

Male participants must refrain from donating sperm for the duration of the study and 
a minimum of 3 months after dosing has been completed.
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the 
Pregnancy Surveillance Form is provided in Section 8.5.2.1.5 and the Appendix for Adverse 
Events and Serious Adverse Events Definitions and Procedures for Evaluating, Follow-up, 
and Reporting (Appendix 2).


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APPENDIX 4
DIAGNOSTIC CRITERIA FOR DRUG AND ALCOHOL ABUSE
The following is taken from the Diagnostic and Statistical Manual of Mental Disorders, 
4th edition:
DIAGNOSTIC CRITERIA FOR PSYCHOACTIVE SUBSTANCE DEPENDENCE
A maladaptive pattern of substance use, leading to clinically significant impairment or 
distress as manifested by 3 (or more) of the following, occurring at any time in the same 12-
month period:
1) Tolerance, as defined by either of the following:
a) A need for markedly increased amounts of the substance to achieve intoxication or 
desired effect
b) Markedly diminished effect with continued use of the same amount of the substance
2) Withdrawal, as manifested by either of the following:
a) The characteristic withdrawal syndrome for the substance
b) The same (or closely related) substance is taken to relieve or avoid withdrawal 
symptoms
3) The substance is often taken in larger amounts or over a longer period than was intended
4) There is a persistent desire or unsuccessful efforts to cut down or control substance use
5) A great deal of time is spent in activities necessary to obtain the substance (eg, visiting 
multiple doctors or driving long distances), use the substance (eg, chain-smoking), or 
recover from its effects
6) Important social, occupational, or recreational activities are given up or reduced because 
of substance use
7) The substance use is continued despite knowledge of having a persistent or recurring 
physical or psychological problem that is likely to have been caused or exacerbated by 
the substance (eg, current cocaine use despite recognition of cocaine-induced depression, 
or continued drinking despite recognition that an ulcer was made worse by alcohol 
consumption.)
CRITERIA FOR SEVERITY OF PSYCHOACTIVE SUBSTANCE DEPENDENCE
Mild: Few, if any, symptoms in excess of those required to make the diagnosis, and the 
symptoms result in no more than mild impairment in occupational functioning or in usual 
social activities or relationships with others.
Moderate: Symptoms or functional impairment between “mild” and “severe.”
Severe: Many symptoms in excess of those required to make the diagnosis, and the 
symptoms markedly interfere with occupational functioning or with usual social activities or 
relationships with others.
In Partial Remission: During the past 6 months, some use of the substance and some 
symptoms of dependence.
In Full Remission: During the past 6 months, either no use of the substance, or use of the 
substance and no symptoms of dependence.


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DIAGNOSTIC CRITERIA FOR PSYCHOACTIVE SUBSTANCE ABUSE
A. A maladaptive pattern of psychoactive substance use, leading to clinically significant 
impairment or distress as manifested by 1 (or more) of the following, occurring at any 
time in the same 12-month period:
1) Recurrent substance use resulting in a failure to fulfill major role obligations at work, 
school, or home (eg, repeated absences or poor work performance related to 
substance use; substance-related absences, suspensions, or expulsions from school, 
neglect of children or household)
2) Recurrent substance use in situations in which it is physically hazardous (eg, driving 
an automobile or operating a machine when impaired by substance use)
3) Recurrent substance-related legal problems (eg, arrests for substance-related 
disorderly conduct)
4) Continued substance use despite having persistent or recurrent social or interpersonal 
problems caused or exacerbated by the effects of the substance (eg, arguments with 
spouse about consequences of intoxication, physical fights)
B. The symptoms have never met the criteria for substance dependence for this class of 
substance


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APPENDIX 5
REPRESENTATIVE STANDARD HIGH FAT AND HIGH 
CALORIE MEAL
STANDARD HIGH-FAT AND HIGH-CALORIE MEAL
The standard FDA high-fat breakfast of 918 kcal consists of:

2 fried eggs (in 15 g butter/margarine) (approximately 100 g)

1 portion of bacon (40 g)*

1 portion of fried potatoes (115 g)

2 slices of (toasted) (wheat) bread with 15 g margarine

1 glass of high fat milk (240 mL)
* For vegetarians bacon may be replaced by brie 60+
The total of 918 kcal (vegetarian version 915 kcal) can be broken down as follows:

39 g protein
=
156 kcal

59 g fat
=
527 kcal

59 g carbohydrates
=
235 kcal



































SAP_001.pdf: 
Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 1 of 36 
 
 
 
Statistical Analysis Plan 
 
 
 
Sponsor: 
Bristol-Myers Squibb Research  and Development 
Protocol No: 
IM024 005 
Protocol  Title: 
A Double-Blind  Randomized Placebo-Controlled  Single and Multiple 
Ascending Doses Study of the Safety and Tolerability, 
pharmacokinetics  (Including  Bioavailability  Comparison  and Food 
Effect) and Pharmacodynamics  of Oral BMS-986251 Administration in 
Healthy Subjects, with Efficacy Assessment of Multiple Doses in 
Patients with Moderate-to-Severe   Psoriasis 
PRA Project ID: 
BMS616EC-176161 
Version Date: 
23-Aug-2018 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 2 of 36 
 
 
2.0 Table of Contents 
1.0 
 
2.0 Tabl e of Contents ........................................................................................................................................... 2 
3.0 Int roduction ..................................................................................................................................................... 4 
4.0 Changes from Previ ous Version of Approved SAP........................................................................................ 4 
5.1 Study Objecti ves ................................................................................................................................................................... 4 
5.2 Primary ..................................................................................................................................................... 4 
5.2.1 Primary Endpoint ................................................................................................................................. 4 
5.3 Secondary ................................................................................................................................................ 5 
5.3.1 Secondary Endpoi nt ........................................................................................................................................ 5 
 
6.1 Planned Study Design .................................................................................................................................... 5 
6.2 Sample Size Considerations ...................................................................................................................... 7 
6.3 Randomization ......................................................................................................................................... 7 
7.1 Overview of Planned Analysis .................................................................................................................. 8 
7.2 Changes from Prot ocol .................................................................................................................................. 8 
7.3 Planned Analyses .................................................................................................................................... 8 
7.3.1 Prelimi nary Analysis ...................................................................................................................... 8 
7.3.2 Final Analysis ................................................................................................................................ 8 
8.1 Definitions and General Analysis Methods .......................................................................................................... 9 
8.2 Analysis Data Presentation ........................................................................................................................ 9 
8.2.1 Rounding ............................................................................................................................................. 9 
8.2.2 Im putation ............................................................................................................................................ 9 
8.2.3 Descri pti ve Statistics ..................................................................................................................... 9 
8.2.4 Pooling ................................................................................................................................................. 9 
8.2.5 Unschedul ed Measurements .............................................................................................................. 9 
8.3 Analysis Data Defi nitions .................................................................................................................................. 9 
8.3.1 Baseline Definition............................................................................................................................... 9 
8.3.2 Treatment/Subject Groupi ng..................................................................................................................... 10 
8.3.3 Common V ariable Deri vations ....................................................................................................... 10 
8.2.4 QC ...................................................................................................................................................... 10 
8.2.5 ADaM Datasets and Metadata .......................................................................................................... 10 
8.4 Soft ware ................................................................................................................................................... 10 
8.5 Statistical Methods ......................................................................................................................................... 10 
8.5.1 Statistical Outlier Determination ..................................................................................................... 10 
8.5.2 Predetermined Covari ates and Prognostic Factors ....................................................................... 11 
8.5.3 Hypothesis Testing ......................................................................................................................... 11 
9.1 Analysis Sets ................................................................................................................................................ 11 
9.2 Enroll ed.................................................................................................................................................................... 11 
9.3 Safety ........................................................................................................................................................ 11 
9.4 Pharmacokinetic ....................................................................................................................................... 11 
9.5 Pharmacody namic .................................................................................................................................... 11 
10.0 Subj ect Disposition ..................................................................................................................................... 11 
11.0 Prot ocol Deviati ons .................................................................................................................................................. 11 
12.1 Demographic and Baseline Characteristics ............................................................................................... 12 
12.2 Demographics ......................................................................................................................................... 12 
12.3 Medical History ....................................................................................................................................... 12 
12.4 Other Baseline Characteristics............................................................................................................... 12 
13.0 Prior and Concomitant Medications ............................................................................................................ 12 
14.0 Treatment Com pliance and Exposure ........................................................................................................ 12 
15.1 Pharmacoki netic Analyses ......................................................................................................................... 12 
15.2 Pharmacoki netic Variables ..................................................................................................................... 12 
15.2.1 Plasma Variables .......................................................................................................................... 12 
15.2.2 Urine Vari ables .................................................................................................................................. 14 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 3 of 36 
 
 
15.3 Pharmacoki netic Summari es ............................................................................................................................. 15 
15.3.1 Pharm acokinetic Concentrations .................................................................................................... 15 
15.3.2 Pharm acokinetic Param eters .............................................................................................................. 15 
15.3.3 Statistical Analyses ......................................................................................................................... 15 
15.3.4 Urine Pharmacokinetics .................................................................................................................. 16 
16.1 Pharmacodynamic Analysis ....................................................................................................................... 16 
16.2 Pharmacodynamic Variabl es ............................................................................................................................. 16 
16.2.1 IL-17 Inhi bition in Whole Blood Vari ables ........................................................................................... 16 
16.2.2 IL-17 Inhi bition PD Parameters ....................................................................................................... 16 
16.3 Pharmacodynamic Summari es ......................................................................................................................... 17 
16.3.1 IL-17 Inhi bition in Whole Blood ....................................................................................................... 17 
16.3.2 Pharm acodynamic Param eters ........................................................................................................... 17 
16.3.3 Evaluation of PK/PD correlation ...................................................................................................... 17 
17.1 Safety Analyses .......................................................................................................................................... 17 
17.2 Safety Variables ..................................................................................................................................... 17 
17.2.1 Adverse E vents ..................................................................................................................................... 18 
17.2.2 Deaths and Seri ous Adverse E vents .................................................................................................. 18 
17.2.3 Laboratory Data .................................................................................................................................... 18 
17.2.4 Vital Signs .............................................................................................................................................. 19 
17.2.5 Electrocardi ograms ......................................................................................................................... 19 
 
 
Appendix 1: Glossary of Abbreviations .............................................................................................................. 20 
Appendix 2: Schedul e of Assessments from Protocol ....................................................................................... 22 
Appendix 3: Pharm acokinetic Sampli ng Schedule from Protocol ...................................................................... 28 
Appendix 4: List of Tabl es, Figures, and Listings ............................................................................................... 32 
Appendix 5: Shells for Tabl es, Figures and Listings .......................................................................................... 35 
19.0 Document History ....................................................................................................................................... 36 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 4 of 36 
3.0 Introduction 
This Statistical Analysis Plan (SAP) describes the statistical methods that will be used during the analysis 
and reporting of data collected under Bristol-Myers Squibb Research and Development  (BMS) Protocol 
IM024 005. 
This SAP should be read in conjunction with the study protocol and electronic case report  form  (eCRF). 
This version of the plan has been developed using the final  protocol  version  1.0  dated  21-Sep-2017 
(including all amendments up to this protocol date) and the final eCRF(s) dated 12-Feb-2018  (single 
ascending dose [SAD]) and 01-Jun-2018   (multiple ascending dose [MAD]). 
An approved and signed SAP is a requirement for database lock. An approved SAP is also required for 
unblinding  of the study treatments. 
This SAP only covers the results that will be processed by the PRA Early Development Services (EDS) 
Biostatistics  Department. 
PRA EDS will perform  the pharmacokinetic  (PK), pharmacodynamic  (PD), and safety and tolerability 
evaluation. 
This SAP was written after the clinical study was terminated due to non-clinical findings. The study was 
stopped after completion of Part A, Cohorts A1 – A4 and during dosing of the cohort A5 and the first cohort 
of Part B, B1. Cohort A6 and bioavailability (BA) / food effect  (FE) cohort in Part A, cohorts B2-B4 in Part B 
and Part C were not conducted. In this SAP, only analyses applicable for the data collected are included. 
This SAP supersedes the statistical considerations identified in the protocol; where considerations are 
substantially different, they will be so identified. Any post-hoc or unplanned analyses, or significant changes 
from the planned analysis in this SAP, will be clearly identified in Section 9.8.2 of the clinical study report 
(CSR). Changes to planned analyses do not require an updated SAP but will be included in the CSR if 
significant. 
4.0 Changes from Previous Version of Approved SAP 
This is the first version of the SAP. 
5.0 Study Objectives 
5.1 Primary 
To evaluate the safety, tolerability and PK of escalating single and multiple ascending doses of BMS-
986251 in healthy subjects, and of multiple doses of BMS-986251 in patients with moderate-to-seve re 
psoriasis. 
5.1.1 Primary Endpoint 
Safety and tolerability 
x 
Number and percent of subjects that experience the following: SAE, death or an AE leading  to 
study discontinuation, during the study participation or up to 1 month post discontinuation of dosing 
or last participation in the study for SAE. 
x 
Number and percent of subjects with potentially clinically significant changes in ECG parameters , 
vital signs, or clinical laboratory parameters  from Day 1 through the final follow visit. 
Other safety measures collected during the study are not considered  among the primary endpoint 
and will be summarized as safety endpoints. 
Pharmac ok inetics 
x 
Plasma concentrations  of BMS-986251  and derived  PK parameters  as applicable 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 5 of 36 
 
 
5.2 Secondary 
x 
To evaluate  the PD of escalating single and multiple ascending doses of BMS-986251  in healthy 
subjects, and of multiple doses of BMS-986251  in patients with moderate-to-severe  psoriasis. 
x 
To evaluate  the oral bioavailability  (BA) of an oral suspension of BMS-986251  relative  to a liquid 
dosage form at a single dose level in healthy subjects. 
x 
To evaluate the effect of a high-fat  meal on the PK of an oral suspension of BMS-986251 at a single 
dose level  in healthy subjects. 
x 
To explore  clinical effects  of multiple doses  of BMS-986251  in patients with moderate-to-seve re 
psoriasis. 
5.2.1 Secondary Endpoint
x 
The percentage  ex-vivo  inhibition (I) of interleukin (IL)-17   secretion in whole blood and derived  PD 
parameters 
x 
Plasma concentrations  of BMS-986251  following  oral suspension and derived  PK parameters  as 
applicable 
x 
Plasma concentrations  of BMS-986251  following  high-fat  meal and derived  PK parameters  as 
applicable 
6.0  Planned Study Design 
This is a double-blind,  placebo-controlled,  randomized SAD and MAD study in 3 parts in a planned number 
of approximately 103 participants: 88 healthy subjects and 15 patients with psoriasis. The present study is 
designed to evaluate the safety and tolerability,  PK, PD and efficacy of BMS-986251. Part A and B are 
planned to enroll healthy subjects and is conducted at a single site. Part C was planned to enroll patients 
with psoriasis and to be conducted as a multi-center study in multiple countries. Part C was not executed 
due to study termination. 
Part A is a  SAD study  in a planned  number  of 6 sequential  cohorts  of 8  healthy  subjects  (6  active  + 
2 placebo) each, receiving single escalating oral doses of BMS-986251.  In the 1st cohort, sentinel dosing 
will be employed (1 active + 1 placebo, followed  after 72 hours by the remaining  subjects of the 1st cohort 
[5 active + 1 placebo]). In addition to the 6 ascending dose cohorts, a cohort of 8 healthy subjects (8 active) 
will be included to assess the relative BA of an oral suspension (under development; representative for the 
solid dosage form to be used in Part C) compared to the solution formulation, and to evaluate the effect of 
food on the BA of the oral suspension in a 3-period  sequential  design (BA/food effect  [FE] cohort). 
Part B is a MAD study in a planned number of 4 sequential cohorts of 8 healthy subjects (6 active + 2 
placebo) each, receiving  daily oral doses of escalating BMS-986251  for 2 weeks. 
Part C is a multiple dose part in one cohort of 15 patients with moderate-to-severe psoriasis (12 active + 3 
placebo), treated for 2 weeks, with a potential extension to 12 weeks by protocol amendment. Per protocol 
amendment, this study part may be extended with further cohorts, receiving lower repeated BMS-986251 
doses than Cohort C1. A decision to extend the study with (a) lower-dosed cohort(s) will be based on the 
efficacy/safety  balance of the 1st patient cohort. A high therapeutic  response or, alternatively,  poor safety 
or tolerability observed  in the 1st patient cohort may be the basis to amend the study protocol for extension 
to a lower dosed cohort. 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 6 of 36 
 
 
An overview  of the study is provided  in Figure 1, Table 1, Table 2 and Table 3. 
Figure 1 
Study Design Schematic 
 
A = active; BA = bioavailability; FE = food effect; MAD = multiple ascending dose; NHV = healthy volunteers; P = 
placebo; PD = pharmacodynamics; PK = pharmacokinetics; Pso = psoriasis; SAD = single ascending dose; wk = 
week 
 
Note: SAD Cohort A1 will have a sentinel dosing design with 2 subjects (1 active and 1 placebo) dosed 72 hours prior 
to the remaining subjects in the cohort. 
 
 
Table 1 
Part A Dose Cohorts 
 
Cohort 
Number of 
Subjects 
(Active  / Placebo) 
Period 
Dose of 
BMS-986251 
Fasted / Fed 
Formulation 
A1 
1 / 1 (sentinel 
group) 
1 
2 mg 
Fasted 
Oral solution 
 
5 / 1 
1 
2 mg 
Fasted 
Oral solution 
A2 
6 / 2 
1 
6 mg 
Fasted 
Oral solution 
A3 
6 / 2 
1 
15 mg 
Fasted 
Oral solution 
A4 
6 / 2 
1 
30 mg 
Fasted 
Oral solution 
A5 
6 / 2 
1 
60 mg 
Fasted 
Oral solution 
A6 
6 / 2 
1 
120 mg 
Fasted 
Oral solution 
A7 (BA/FE) 
8 
1 
tbd 
Fasted 
Oral solution 
 
 
2 
tbd 
Fasted 
Oral suspension
(under  development) 
 
 
3
tbd
Fed
Oral suspension
(under development)
BA = bioavailability; FE = food effect; tbd = to be determined 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 7 of 36 
 
 
Doses maybe adjusted based on data obtained in previous cohorts. 
 
 
Table 2 
Part B Dose Cohorts 
 
Cohort 
Subjects 
(Active / Placebo) 
Dose of 
BMS-986251 
Duration
Fasted/Fed 
Formulation 
B1 
6 / 2 
6 mg QD 
14 days 
Fasted 
Oral solution 
B2 
6 / 2 
tbd QD 
14 days 
Fasted 
Oral solution 
B3 
6 / 2 
tbd QD 
14 days 
Fasted 
Oral solution 
B4 
6 / 2 
60 mg QD 
14 days 
Fasted 
Oral solution 
QD = once daily; tbd = to be determined upon reviewed data 
Doses maybe adjusted based on data obtained in previous cohorts. 
 
 
Table 3 
Part C Dose Cohort 
 
Cohort 
Subjects 
(Active / Placebo) 
Dose of 
BMS-986251 
Duration
Fasted/Fed 
Formulation 
C1 
12 / 3 
60 mg QD 
14 days 
tbd 
Oral tablet 
QD = once daily; tbd = to be determined upon reviewed data
Dose may be adjusted based on data obtained in previous study parts. 
 
 
6.1 Sample  Size Considerations 
Part A and B – SAD and MAD cohorts 
The current design of 8 subjects per cohort with 6 subjects assigned to active treatment is a commonly 
used design for SAD and MAD studies and is considered sufficient to achieve the study objectives. Although 
this number of is not based on statistical power considerations, administration of BMS-986251  to 6 subjects 
in each dose cohort provides approximately  80%  probability  of observing  at least one occurrence  of any 
AE which would occur with approximately 24% incidence in the population from which the sample is drawn. 
Part A – BA/FE cohort 
The planned number of 8 subjects on active treatment to be enrolled in the BA/FE cohort (in which BA and 
FE of an oral suspension will be evaluated in a 3-period sequential design), has not been based on formal 
statistical sample size calculations. This number  of subjects is a commonly accepted number  of subjects 
for this type of exploratory  study and is considered sufficient to achieve  the study objectives. 
Part C – Psorias is patients 
Like Parts  A and B, Part C is  also an exploratory study. Therefore, no formal statistical sample size 
calculation has been performed and the sample size is not  based on a power calculation. The planned 
number of 15 subjects with 12 subjects on active treatment is a commonly accepted number of subjects for 
this type of exploratory study. Formal statistical hypotheses were not set up. Any statistical test perform ed 
will be exploratory. 
 
6.2 Randomization 
Within each cohort (excluding the BA/FE cohort of Part A), subjects will be randomized to receive either 
BMS-986251 or placebo. All subjects who sign informed consent and are enrolled (including those not 
subsequently randomized or treated) will be assigned sequential subject numbers. Eligible subjects will be 
randomized according  to a computer-generated  randomization  scheme. Subjects in Cohort  A7 in Part A 
will be assigned sequential subject numbers in the order of enrollment. Eligible subjects will be treated in 
accordance with the study design. 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 8 of 36 
 
 
Part A, SAD in Healthy Volunteers: 
Approximately 48 subjects (8 in each cohort) enrolling in Cohorts A1 to A6 will be randomized  to BMS-
986251 or matching placebo in a 3:1 randomization ratio. All subjects in BA/FE Cohort A7 will recei ve BMS-
986251. 
Part B, MAD in Healthy Volunteers: 
Approximately  32 subjects will be enrolled in 4 dose cohorts during the MAD study. Each dose cohort will 
randomize 8 subjects in a 3:1 ratio to receive BMS-986251  or matching placebo. 
Part C, Multiple Dos ing in Psorias is Patients: 
Approximately 15 subjects in one planned dose cohort will be randomized in a randomization ratio of 4:1 to 
receive  BMS-986251 or matching placebo. 
 
7.0 Overviewof Planned Analysis 
7.1 Changes  from Protocol 
This  study  was terminated  on  June  25,  2018  prior  to completion  of dosing  in all planned  cohorts and 
subjects within cohort.   Following cohorts have  been dosed before  the termination: 
Part A 
Cohort  A1 (2mg): n=8 
Cohort  A2 (6 mg): n=8 
Cohort  A3 (15 mg): n=8 
Cohort  A4 (30 mg): n=8 
Cohort  A5 (60 mg):  n=4 
Part B 
Cohort  B1 (3 mg QD): n=2 (dosing till Day 10) 
Summary tables of disposition, demographics  and adverse  events  will be provide  for Part B, but data from 
Part B subjects will be presented in all listings with data for Part B. 
Cohort  A6 and BA/FE cohort in Part A, cohorts B2-B4 in Part B and Part C were not conducted. 
 
7.2 Planned  Analyses 
7.2.1 Preliminary Analysis 
Interim  PK blinded results were provided  after each cohort to the study team. A non-project  team member 
PK Scientist will be the only team member to have access to the unblinded results. 
 
7.2.2 Final Analysis 
The full set of draft table, figures  and listings (TFLs) will be provided  after database lock. After comments 
have  been incorporated  on the draft TFLs, the TFLs will be finalized and incorporated in the CSR. 


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8.0 Definitions and General Analysis Methods 
8.1 Analysis  Data  Presentation 
8.1.1 Rounding 
In listings, data will be presented with the same precision as the original data. Derived  data will be rounded 
for presentation  purposes. 
For all summaries (with the exception of PK), the mean will be presented to 1 decimal greater than the 
original data, the standard deviation (SD) to 2 decimals greater than the original data, and the median, 
minimum (min) and maximum (max) values will be presented to the same number of decimal places as the 
original  data. 
For PK summaries, mean, SD, median, min, and max values   100 will be presented as integers and values 
< 100  10 will be presented with 1 decimal, Values < 10 but  1 will be presented with 2 decimals, and 
Values < 1 will be presented with 3 decimals. Ratios will be presented with 2 decimals. Coefficient of 
variation  (%CV) will be presented with 1 decimal. 
For listing presentation purposes, PK parameters will be rounded in the same manner as noted above for 
summaries. The Tmax will be reported  with 2 decimals. 
P-values will be reported to 4 decimal places; p-values less than 0.0001 will be reported as p <0.0001. 
Percentages will be rounded to 1 decimal, except 100% which will be displayed without any decimal places. 
8.1.2 Imputation 
Unless otherwise noted (section 15.2.1 and 17.1.1), data will not be imputed. 
 
8.1.3 Descriptive Statistics 
Unless otherwise indicated in specific data type sections, continuous variables will be summarized with the 
following  descriptive statistics: n (number of observations),  (arithmetic) mean, SD, median, min, and max. 
Categorical data will be summarized with frequencies and percentages. Percentages by categories will be 
based on the number of subjects within a treatment group. Percentages will be rounded to 1 decimal, except 
100% which will be displayed without any decimal places. Percentages will not be displayed for zero counts. 
Categories  will be presented in the tables exactly as they appear in the eCRF / Database. 
 
8.1.4 Pooling 
Summary statistics will be calculated by study part, treatment (and time point, if applicable). Placebo data 
will be pooled across cohorts in Part A for descriptive  statistics. 
8.1.5 Unscheduled Measurements 
Unscheduled measurements will be  included in  the  listings. With the  exception  of unscheduled 
measurements used for baseline, unscheduled measurements will be excluded from the  descriptive 
statistics and statistical analysis. 
 
8.2 Analysis Data Definitions 
8.2.1 Baseline Definition 
Unless otherwise stated, baseline for post-dose evaluations within each period is defined as the last 
observation  recorded before the first study drug administration in each period.  The last observation  can be 
an unscheduled / repeated measurement. 


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8.2.2 Treatment/Subje ct Grouping 
Label 
Grouping 
Study Drug 
BMS-986251,  Placebo 
Treatment 
Part A SAD cohorts: oral BMS-986251 
Part B MAD cohorts: oral BMS-986251 
Dose  Level 
Part A SAD cohorts: 2 mg, 6 mg, 15 mg, 30 mg, 60 mg 
Part B MAD cohorts: 3 mg QD 
8.2.3 Common Variable Derivations 
 
Variable 
Dataset 
Definition/Calculation 
Change from  Baseline 
All 
Post-dose Observation  minus Baseline Observation 
Percent Change from Baseline 
All 
Post-dose Observation  minus Baseline Observation 
then divided  by Baseline Observation 
Analysis Period 
All 
Interval  of time during which treatment is constant. 
Duration 
AE 
Stop date/time minus start date/time plus 1, presented in 
dd:hh:mm. 
 
8.2.4 QC 
The analysis datasets and the TFLs will be quality control (QC)’d according to the PRA EDS QC plan that 
is developed  according to the EDSREP 009 SOP. 
 
8.2.4.1 Critical Data 
The QC plan requires datasets be classified as critical or non-critical. As key objectives of this study are to 
characterize the pharmacokinetics and assess safety and tolerability, the datasets considered critical are 
subject level, pharmacokinetic, and adverse events (ADSL, ADPC, ADPP, and ADAE). As these are related 
to the primary objectives  these datasets will be double programmed  per the QC Plan. 
8.2.5 ADaM Datasets and Metadata 
The analysis datasets will be generated  in accordance with Clinical Data Interchange  Standard Consortium 
(CDISC)  Analysis Data Model (ADaM) Version 2.1. 
ADaM compliant datasets will be delivered  to the sponsor. A define.xml file version 2 with the correspondi ng 
metadata will be included. Analysis results metadata are excluded. 
 
8.3 Software 
The statistical analysis and reporting  will be done using SAS® for WindowsTM  Version 9.4 or higher (SAS 
Institute, Inc.). 
PK parameter  calculations will primarily  be done using Phoenix®  WinNonlin®   (WNL) Version 6.3 or higher 
(Pharsight, Inc.). Additional PK computations may be performed  in SAS®. 
 
8.4 Statistical  Methods 
8.4.1 Statistical Outlier Determination 
No statistical outlier analysis is planned. 


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8.4.2 Predetermined Covariates and Prognostic Factors 
There  are no predetermined  covariates  or prognostic factors. 
 
8.4.3 Hypothesis Testing 
No formal  hypothesis testing will be done. 
 
9.0 Analysis Sets 
 
Analyses 
Enrolled 
Safety 
PK 
PD 
Disposition 
3
 
Demographics and 
Baseline 
Characteristics 
3
 
Safety 
Assessments 
3
PK Concentrations 
3
 
PK Parameters 
3
 
PD Concentrations 
3
 
9.1 Enrolled 
The Enrolled analysis set will consist of all subjects who signed informed  consent. This analysis set will be 
used for disposition summaries. 
 
9.2 Safety 
The Safety analysis set will consist of subjects who receive at least one dose of study drug. This set will be 
used for disposition summaries, baseline characteristic summaries, and safety summaries. 
 
9.3 Pharmacokinetic 
The  PK analysis  set will consist of  all subjects  who  receive  at  least  1 dose of BMS-986251  and have 
sufficient concentration-time  data to calculate a valid Cmax and AUC(0-T). 
 
9.4 Pharmacodynamic 
All subjects who receive  at least 1 dose of BMS-986251  or placebo and have  any available  data for the 
PD assessments. 
 
10.0 Subject Disposition 
The number of subjects in each analysis set will be presented. The  number  and percentage  of subjects 
who withdrew from the study prematurely  and a breakdown  of the corresponding  reasons  for withdrawal 
will also be presented.  Percentages will be based on the total number of subjects in the analysis set. 
 
11.0 Protocol Deviations 
Protocol deviations will be collected and entered into the Clinical Trial Management System (CTMS) per 
clinical monitoring Standard Operating Procedures. From CTMS, protocol deviations will be  pulled  into 
SDTM. All protocol deviation  data will be listed by subject. 


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12.0 Demographic and Baseline Characteristics 
12.1 Demographics 
Subject demographics will be summarized descriptively for all subjects by analysis set and treatment group. 
The summary will include the subjects’ age (in years), sex, race, ethnicity, weight (in kg), height  (in cm), 
and body mass index (BMI) (in kg/m2). Any measurements will be included from assessments perform ed 
during the Screening Visit. Demographics will be summarized for the Safety, PK and PD analysis sets. 
All demographic  data, as collected during the screening visit and Day -1, will be listed by subject. 
 
12.2 Medical  History 
Medical history will be listed by subject. Medical history data will be coded according to the latest Medical 
Dictionary for Regulatory  Activities (MedDRA)  version 21.0. 
 
12.3 Other  Baseline  Characteristics 
Substance use (tobacco and alcohol) will be listed. 
The results of drug and alcohol screen at screening and at pre-treatment  will be listed. 
The  results  of pregnancy  tests at screening  and  at pre-treatment  will  be  listed, the  results for  follicle 
stimulating hormone  (FSH) tests at screening will be listed. 
The  results  of  serology,  including  hepatitis  B  surface  antigen  (HBsAg),  anti-hepatitis  C  virus  (HCV) 
antibodies  or anti-human  immunodeficiency  virus  (HIV) 1 and 2 antibodies will be listed. 
The results of Quantiferon  Gold test®  for tuberculosis (TB) at screening will be listed. 
Non-compliance  to in- or exclusion criteria (if any) will be listed. 
13.0 Prior and Concomitant Medications 
Prior and concomitant medications, categorized by medication group and subgroup according to the World 
Health Organization (WHO) Drug Dictionary Version 2018MAR01+HD  (Enhanced+Herbal)  B3, will be listed 
by subject. Medications with an end date prior to the first dose of study drug will be considered prior 
medications and will be identified in the listing. If a partial date allows a medication to be considered 
concomitant it will be categorized as such. 
 
14.0 Treatment Compliance and Exposure 
The number of subjects receiving  each dose of study drug will be summarized. 
All study drug administration  data will be listed by subject. If applicable,  date and time and food and fluid 
intake and comments will be listed. 
 
15.0 Pharmacokinetic Analyses 
The PK summaries described in this section will be created using the PK analysis set. 
 
15.1 Pharmacokinetic  Variables 
15.1.1 Plasma Variables 
15.1.1.1 Concentrations 
x 
Plasma concentration  of BMS-986251 


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15.1.1.2 Parameters 
PK Parameters for BMS-986251  as defined Table 4. 
 
Table 4 
Plasma BMS-986251  PK Parameters- Part A (SAD Part) 
 
Parameter 
SAD 
Part 
MAD 
Part
Day 1* 
Description 
SAS  Programming 
Notes 
Cmax 
X 
X 
Maximum  plasma concentration. 
Observed  peak analyte concentration 
obtained directly from the experimental 
data without interpolation,  expressed in 
concentration  units 
Cmax from WNL 
Tmax 
X 
X 
Time to maximum plasma concentration. 
First observed  time to reach peak 
analyte concentration  obtained directly 
from the experimental  data without 
interpolation,  expressed in time units. 
Tmax from WNL 
AUC(0-T) 
X 
X 
Area under the concentration-time curve 
(time 0 to time of last quantifiable 
concentration). 
AUClast from WNL 
AUC(INF) 
X 
X 
Area under the plasma concentration- 
time curve (time 0 to infinity). 
A valid half-life is required to retain this 
parameter. 
AUCINF_obs  from 
WNL 
If T-HALF  is present. 
AUC%Extrap 
X 
X 
Percentage of the AUC(INF)  that is 
extrapolated. 
AUC_%Extrap_obs 
from WNL– Listed 
only 
T-HALF 
X 
X 
Terminal  phase half-life expressed in 
time units. 
A valid Lz is required  to retain. 
HL_Lambda_z  from 
WNL 
Lz 
X 
X 
Terminal  phase rate constant calculated 
by the WinNonlin generated best fit 
linear regression of the terminal  log- 
linear portion of the concentration vs. 
time curve. 
Linear regression of at least 3 points and 
an adjusted R2 > 0.80 are required to 
retain. 
Lambda_z  from WNL. 
CL/F 
X 
X 
Apparent  clearance 
CL_F_obs  from  WNL 
Vd/F 
X 
X 
Apparent  volume  of distribution at 
terminal phase 
Vz_F_obs from WNL 
Adj R2 
X 
X 
Adjusted R2 value of terminal elimination 
phase 
Rsq_adjusted  from 
WNL – Listed only 


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Parameter 
SAD 
Part 
MAD 
Part 
Day 1* 
Description 
SAS  Programming 
Notes 
Lz_Start 
X 
X 
The time point starting the log-linear 
elimination phase defining their terminal 
half-life 
Lambda_z_lower  from 
WNL – Listed only 
Lz_End 
X 
X 
The time point ending the log-linear 
elimination phase defining the terminal 
half-life 
Lambda_z_upper 
from WNL – Listed 
only 
Lz_N 
X 
X 
Number of time points in the log-linear 
elimination phase defining the terminal 
half-life 
No_points_lambda_z 
from WNL – Listed 
only 
Note: AUCs will be calculated using linear up / log down, expressed in units of concentration x time. 
* There are only 2 subjects in cohort B1 who have  been dosed till Day 10. PK parameters  will be 
calculated for Part B (MAD part) Day 1 if feasible. 
15.1.2 Urine Variables 
 
15.1.2.1 Amounts Excreted 
x 
Amount of BMS-986251 excreted in urine (Ae) 
o Calculated as the urine volume  times the urine concentration for each interval. 
 
15.1.2.2 Parameters 
x 
PK Parameters for BMS-986251  as defined in Table 5. 
Table 5 
Urine Parameter –SAD Part 
 
Parameter 
Description 
SAS  Programming 
Notes 
Ae(0-T) 
Total amount  of drug excreted unchanged into urine to 
time t obtained by adding the amounts excreted over 
each collection interval. 
Summation i = 1 to n of 
(Concentration (ng/mL) 
ti-1-ti*volume(mL)ti-1-ti) 
Parameter will be 
missing if data is 
missing for any prior 
individual  time interval. 
Ae 
Total amount  of drug excreted unchanged into urine to 
last time obtained by adding the amounts excreted over 
each collection interval. 
Summation i= 1 to n of 
(Concentration (ng/mL) 
ti-1-ti*volume(mL)ti-1-ti) 
Parameter will be 
missing if data is 
missing for any 
individual  time interval. 
Fe 
Fraction (%) of the administered  dose excreted 
unchanged  into urine 
Ae/XXmg  (dose)*100 
CLr
Renal clearance
Ae(0-T)/AUC(0-T)


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15.2 Pharmacokinetic  Summaries 
15.2.1 Pharmacokinetic Concentrations 
Plasma concentrations for BMS-986251 below the limit of quantification (BLQ) will be set to zero in the 
computation of mean concentration values. Descriptive statistics (n, mean, SD, geometric mean, %CV, 
median, min, and max) will be used to summarize the plasma concentrations by treatment  at  each 
scheduled time point. If over 50% of the subjects in a given cell have values BLQ, then the descriptive 
statistics will not be presented and will instead display as BLQ for the mean and minimum. With the 
exceptions of n and maximum, all other statistics will be missing. 
Linear and semi-logarithmic plots of the arithmetic mean plasma concentrations  + SD by  scheduled 
sampling times will be provided for Part A, the treatments will be presented in one plot. These plots will 
show time in hours. The plots will match the summary table results and will not have an observation at a 
given time point if more than half of the subjects have values BLQ. Linear plots will be presented to 24 hours 
and to the last scheduled time point. Semi-log plots will be presented to the last scheduled time point. The 
linear and semi-logarithmic  plots will be presented side-by-side on a single page. 
Linear and semi-logarithmic plots of the individual plasma concentrations by actual sampling times will be 
provided by subject. These plots will show time in hours. Individual plots will use  the  BLQ  handling 
procedure described below for “Pharmacokinetic Parameters”.  Linear  plots will be presented  to 24 hours 
and semi-log plots will be presented to the last scheduled time point. 
Linear and semi-logarithmic spaghetti plots of  the individual  plasma  concentrations  by  actual sampling 
times will be provided by treatment. These plots will show time in hours. Spaghetti plots will use the BLQ 
handling  procedure  described below  for “Pharmacokinetic  Parameters”.  Linear  plots will be presented  to 
24 hours and semi-log plots will be presented to the last scheduled time point. 
All individual  subject plasma concentration data will be listed, including time deviations  and comments. 
 
15.2.2 Pharmacokinetic Parameters 
PK parameters for BMS-986251 will be estimated using non-compartmental methods with WinNonlin®.The 
plasma PK parameters will be estimated from the concentration-time profiles. In estimating the PK 
parameters, BLQ values at the beginning of the profile will be set to zero. BLQ values that occur after the 
first quantifiable point will be considered missing. Values that are embedded between BLQs, or quantifiabl e 
values occurring after two or more BLQs, will be set to missing at the discretion of the pharmacokineticist. 
Actual sampling times, rather than scheduled sampling times, will be used in all computations invol ving 
sampling times. If the actual time or dose time is missing, the scheduled time may be substituted in order 
to calculate the PK parameter. 
Descriptive statistics (n, mean, SD, geometric mean, %CV, median, min, and max) will be used to 
summarize the calculated PK parameters by treatment. For Tmax,  only n, median,  min and max will be 
presented. 
The points to be included in the Lz range will be from the WinNonlin best fit generated profiles.  At least 3 
points will be required  to be used. The Cmax data point will not be included. 
15.2.3 Statistical Analyses 
 
15.2.3.1 Dose-proportionality 
The pharmacokinetic parameters  Cmax, AUC(0-T),  and AUC(INF)  for BMS-986251 from the Part A groups 
will be compared across each dose level to assess dose proportionality. Dose  proportionality  will be 
assessed by estimating the slope of the linear regressions of natural logarithmic transformed AUC(0-T), 
AUC(INF),  and Cmax on log(dose). 
Statistical analyses will be done using a power model (Gough et al, 1995) with mixed effects of the followi ng 
general  form, 


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ln(PK) = OQȕ + ȕāOQ'RVH  + İ 
where 
PK is the pharmacokinetic parameter tested (e.g., Cmax or AUC) 
OQȕ is the y-intercept, 
ȕ is the slope (a value of ȕ 1 indicates linearity), and 
İ is an error term 
The estimate of ȕ and 90% CI will be reported  along with the associated p-value  and the dose range for 
proportionality.  A significant difference  from unity (1) and lack of proportionality  will be defined as p < 0.05. 
Plots of AUC(0-T),  AUC(INF)  and  Cmax  versus  dose on the linear   scale and the equation  line will be 
provided  to assess dose proportionality. 
15.2.4 Urine Pharmacokinetics 
If applicable, descriptive statistics (n, mean, SD, geometric mean,  %CV, median,  min, and max) will be 
used to summarize the urine concentrations, amounts excreted and derived PK parameters for BMS-
986251  in SAD part and treatment  at each scheduled time interval  and cumulative. 
All available  derived  urine PK parameters will be included in the PK data set and reported,  but only subjects 
with adequate  PK profiles will be included in the summary statistics and statistical analysis. 
All available  individual  subject urine  BMS-986251 concentrations, amount excreted data, urine parameters 
will be listed. 
 
16.1 Pharmacodynamic Analysis 
The following PD assessment is planned in this study: 
x 
ex-vivo  inhibition (I) of IL-17  secretion in in stimulated and unstimulated whole blood 
16.1 Pharmacodynamic  Variables 
16.1.1 IL-17 Inhibition in Whole Blood Variables 
x 
The IL-17 concentrations in stimulated whole blood 
x 
The IL-17 concentrations in unstimulated whole blood 
x 
Percentage of IL-17 inhibition in stimulated whole blood 
 
16.1.2 IL-17 Inhibition PD Parameters 
Table 6 
IL-17 PD Parameters (in whole blood) 
 
Parameter 
Description 
SAS  Programming 
Notes 
Imax 
Maximum observed  inhibition 
In SAS 
tImax 
Time of maximum observed  inhibition 
In SAS 
tI>50%* 
Time of inhibition above  50% 
 
tI>90%* 
Time of inhibition above  90% 
 
*if feasible 


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16.2 Pharmacodynamic   Summaries 
16.2.1 IL-17 Inhibition in Whole Blood 
Individual data of IL-17 concentration in stimulated and unstimulated whole blood will be listed. Descripti ve 
statistics (n, mean, SD, geometric mean, %CV, median, min, and max) of the IL-17 whole  blood 
concentration will be summarize by treatment and time point. Levels  of BLQ will be set to 0. 
Percentage of IL-17 inhibition is calculated as: 
[(stimulated concentration  at baseline – unstimulated concentration at baseline) - (stimulated concentration 
at Rx time point – unstimulated concentration at Rx time point)] / (stimulated concentration at baseline – 
unstimulated concentration  at baseline)  *100%. 
Baseline is defined as the average concentration of pre-dose (T=-18.00 hr and T=0.00 hr). Percentage of IL-
17 inhibition will be listed and summarized by treatment and time point. Linear  plots of the arithmetic mean 
of percentage of IL-17 inhibition + SD in the whole blood by scheduled sampling times will be provi ded for 
SAD part. Linear plots of the combined individual percentage of IL-17 inhibition in the whole blood by 
scheduled sampling times will be provided  by dose of BMS-986251  and placebo. 
Mean plots of percentage of IL-17 inhibition versus mean BMS-986251  plasma  concentration  will be 
provided  by treatment. 
16.2.2 Pharmacodynamic Parameters 
Descriptive statistics (n, mean, SD, geometric mean, %CV, median, min, and max) will be used to 
summarize the calculated PD parameters by treatment. For tImax, tI>50%, and tI>90%,  only n, median, 
min and max will be presented. 
 
16.2.3 Evaluation of PK/PD correlation 
PK/PD correlation will be evaluated by scatter Plot of IL-17 Inhibition versus BMS-986251 plasma 
concentration. 
 
17.0 Safety Analyses 
The safety summaries described in this section will be created using the Safety analysis set. Changes will 
not be provided  if collections are not made during treatment periods. 
 
17.1 Safety  Variables 
The following safety variables  will be summarized: 
x 
Treatment-Emergent   Adverse  Events  (TEAE) 
x 
Clinical Laboratory  Evaluations 
o 
Clinical  Chemistry 
o 
Hematology 
o 
Urinalysis 
o 
Coagulation 
x 
Vital Signs 
o 
Systolic Blood Pressure (SBP) 
o Diastolic Blood Pressure (DBP) 
o Heart rate 
o 
Oral body temperature 
o 
Respiratory  rate 
x 
Electrocardiograms  (ECG) 
o 
Heart Rate 
o 
PR Interval 
o 
QRS-Duration 


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o 
QT Interval 
o 
QTc (Frederica)  Interval 
o 
T-Wave  Assessment 
o 
U-Wave  Assessment 
x 
Physical Examination 
x 
Taste questionnaire 
 
17.1.1 Adverse Events 
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition 
in a clinical investigation participant that does not necessarily have a causal relationship with treatment. AE 
summaries will include only TEAEs. TEAEs are those which occur after the first dose of study drug. All 
TEAE summaries will be presented alphabetically by system organ class, with preferred terms sorted in 
decreasing order of frequency  within each system organ class based on MedDRA  version 21.0. 
TEAEs occurring following dosing in a specific period but before dosing in the following period will be 
attributed to that specific period. If the time is missing for an AE on a dosing day then the AE will be attributed 
to the treatment given  on that day. 
The following missing data will be imputed (for calculations only) as defined: 
x 
Missing AE start and / or end times for the calculation of onset and duration will be assumed to be 
at 00:01 for a start time and 23:59 for end times 
x 
Missing AE severity or relationship will be left as missing 
x 
Missing AE start times for the determination of treatment emergence will be assumed to occur after 
treatment unless partial date documents the AE as happening  prior to treatment 
x 
Missing AE start times for the determination of treatment assignment will be assumed to occur after 
treatment on the recorded date one minute after dosing 
x 
Missing AE start date will be assumed to be after treatment for the determination of TEAE, but will 
not be attributed to a specific treatment in studies with multiple treatments. 
A summary of the number and percentage of subjects reporting TEAEs, serious AEs (SAEs), who 
discontinue study drug due to a TEAE, and will be presented by treatment and overall. 
A summary of the number and percentage of subjects reporting each TEAE will be presented by treatment 
and overall. Counting will be done by subject only, not by event; subjects will only be counted once within 
each body system or preferred  term. 
A summary of the number and percentage of subjects reporting each TEAE will be presented by relationshi p 
to study drug (as recorded on the eCRF) and by treatment and overall.  Subjects with multiple events  within 
a particular system organ class (SOC) or preferred term will be counted as related unless no events were 
related in that SOC/preferred  term. 
A summary of the number and percentage  of subjects reporting  each TEAE will be presented  by severit y 
(as recorded on eCRF) and by treatment and overall. Subjects with multiple events  within a particular 
system organ class or preferred term will be counted under the category of their most severe event within 
that system organ class or preferred  term. 
All AEs (including non-treatment-emergent  events)  recorded on the eCRF will be listed by subject. 
A separate listing of AEs leading to study drug discontinuation will be provided. 
17.1.2 Deaths and Serious Adverse Events 
A listing of deaths and other SAEs will be provided  for all subjects. 
 
17.1.3 Laboratory Data 
Clinical laboratory data will be presented  using units from the study data tabulation  model  (SDTM) 
Controlled  Terminology. 


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A descriptive statistics summary of continuous laboratory results for clinical chemistry, hematology and 
derived  changes  from baseline will be provided  by treatment and scheduled time point. 
Shift tables describing the change in clinical laboratory values from  baseline to each post-dose scheduled 
time point (number and percentage of subjects) will also be provided by treatment. The following categories 
will be used: low, normal, and high. 
All laboratory  data will be listed by subject, including laboratory  variables  not listed in the protocol. 
A separate listing of out-of-range values will also be provided. Normal ranges will be used directly from the 
clinical laboratory  and will be included in the listings for reference. 
17.1.4 Vital Signs 
A descriptive statistics summary of vital signs and derived changes from baseline will be provided  by 
treatment and scheduled time point. 
If considered informative by the data obtained,  plots of the mean change from baseline for the vital signs 
parameters  versus  time since dosing will be presented by part and treatment. 
All vital signs data will be listed by subject. 
 
17.1.5 Electrocardiograms 
The observed  measurements for all ECG parameters and the corresponding  abnormalities  will be listed for 
all time points.  The means of triplicate measurements for continuous parameters and the change from 
baseline of the mean triplicate measurements  at each scheduled time point will be listed by subject. 
Descriptive statistics will be provided to summarize mean ECG parameters (observed and changes from 
baseline) by treatment and scheduled time. 
QTC prolongation potential will be by scatter Plot of change from baseline of QTcF versus BMS-986251 
plasma  concentration. 


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Appendix 1: Glossary of Abbreviations 
 
Glossary  of Abbreviations: 
AE 
Adverse  event 
ADaM 
Analysis data model 
BA 
Bioavailability 
BMI 
Body mass index 
BMS 
Bristol-Myers Squibb Research  and Development 
BLQ 
Below the limit of quantification 
CDISC 
Clinical Data Interchange  Standard  Consortium 
CSR 
Clinical study report 
CTMS 
Clinical Trial Management  System 
CV 
Coefficient  of variation 
DBP 
Diastolic blood pressure 
ECG 
Electrocardiogram 
eCRF 
Electronic case report  form 
EDS 
Early Development  Services 
FE 
Food effect 
FSH
Follicle stimulating hormone 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hhepatitis C virus 
HIV 
Human  immunodeficiency  virus 
I 
Inhibition 
ICH 
The International  Conference  on Harmonization  of Technical Requirements 
for Registration of Pharmaceuticals for Human Use 
IL 
Interleukin 
LLOQ 
Lower limit of quantification 
MAD 
Multiple ascending dose 
Max 
Maximum 
MedDRA 
Medical Dictionary for Regulatory  Activities 
Min 
Minimum 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
Pso 
Psoriasis 
QC(’d) 
Quality control(led) 
QD 
Once daily 


EDSREP 009 T 01 G 
Page 21 of 36 
Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
 
 
SAD 
Single ascending dose 
SAP 
Statistical analysis plan 
SAE 
Serious adverse  event 
SBP 
Systolic blood pressure 
SD 
Standard  deviation 
SDTM 
Study data tabulation model 
SOC 
System organ  class 
tbd 
To be determined 
TB 
Tuberculosis 
TBNK 
T, B, and natural killer cells 
TEAE 
Treatment-emergent  adverse  event 
TFL(s) 
Tables, figures  and listings 
WHO 
World Health Organization 
WNL 
WinNonlin 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 22 of 36 
 
 
 
 
Appendix 2: Schedule of Assessments from Protocol 
Table 7 
Study Procedural Outline Part A – SAD Healthy Subjects (IM024 005) 
 
 
 
Period 1
Period 2 (Cohort for Bioavailability and Food Effect Assessment only) 
Period 3 (Cohort for Bioavailability and Food Effect Assessment only) 
Visit 
S creening 
Pre- 
Treatment
Treatment 
Follow- 
up1
Study Days 
-21 to -1 
-1 
1 
2 
3 
4 
5 
6 
7 
9 
11 
Time Post-Dosing 
(hrs) 
 
Pre-dose 
0 
0.5 
1 
1.5 
2 
3 
4 
6 
8 
12 
24 
36 
48 
72 
96 
120 
144 
192 
240 
Confinement 
 
X 
 
Discharge2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
Ambulant visit 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Informed consent 
and medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Genotyping(CYPs, 
transporters)3 
 
X 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Body weight and 
height (including 
BMI calculation)4 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Eligibility check 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
(triplicate) 
X 
X 
X  
X  
 
X  
X  
X  
X  
X  
X 
 
 
1 For relative bioavailability/food effect cohort follow-up assessments on Day 11 of Period 3 only. At the Day 11 visit in Period 1 and 2 only blood sampling for PK and PD 
(Period 1 only), vital signs, and drug and alcohol screen will be performed. 
2 Discharge from the clinical research unit. 
3 Mandatory whole blood collection for analysis of DNA variants in ADME-related genes (http://pharmaadme.org/Appendix 6). For relative bioavailability/food effect cohort sample will be collected in
Period 1 only. Sample may be taken at any time post-dose during Day 1. 
4 Height will only be measured at screening. BMI will also only be calculated at screening. 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 23 of 36 
 
 
 
 
Period 1 
Period 2 (Cohort for Bioavailability and Food Effect Assessment only) 
Period 3 (Cohort for Bioavailability and Food Effect Assessment only) 
 
Visit 
S creening 
Pre- 
Treatment 
Treatment 
Follow- 
up1 
Study Days 
-21 to -1 
-1
1
2
3
4 
5 
6 
7 
9 
11 
Time Post-Dosing 
(hrs) 
Pre-dose 
0 
0.5 
1 
1.5 
2 
3 
4 
6 
8 
12 
24 
36 
48 
72 
96 
120 
144 
192 
240 
Holter monitoring5  6 
X 7 
X 
Clinical laboratory, 
hematology incl. 
reticulocytes 
X 
X 
X 
X 
X 
X 
Drug and alcohol 
screen 
X 
X 
X 
X 
HBsAg, anti-HCV, 
and anti-HIV 1/2 
tests 
X 
 
Quantiferon Gold 
test 
X 
 
FSH (females only) 
X 
 
Pregnancy test 
(females only) 
X 
X 
 
X 
Overnight fast 
(10 hours) 
X 
Standardized lunch, 
snacks, dinner8 
X 
High-fat breakfast 9 
X 
Randomization 
X 
Study drug 
administration 
X 
Taste questionnaire 
X10 
5 For bioavailability/food effect cohort in fasted Period 1 only 
6 Including a 15 minute supine period prior to every PK sample 
7 In triplicate in 3 supine periods 
8 In Period 1 with Holter monitoring only. 
9 In Period 3 of bioavailability/food effect cohort only 
10 To be completed immediately after drug administration (within first 10 seconds) and after approximately 1 minute (before drinking the provided glass of water) 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 24 of 36 
 
 
 
 
 
Period 1 
Period 2 (Cohort for Bioavailability and Food Effect Assessment only) 
Period 3 (Cohort for Bioavailability and Food Effect Assessment only) 
 
Visit 
S creening 
Pre- 
Treatment 
Treatment 
Follow- 
up1 
Study Days 
-21 to -1 
-1 
1 
2 
3 
4 
5 
6 
7 
9 
11 
Time Post-Dosing
(hrs)
 
Pre-dose 
0 
0.5 
1 
1.5 
2 
3 
4 
6 
8 
12 
24 
36 
48 
72 
96 
120 
144 
192 
240 
Previous and 
concomitant 
medications 
 
X 
X 
 
PK sampling blood11  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine collection for 
parent drug and 
metabolites 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X  
Sampling for ex- 
vivo IL-17 inhibition 
in whole blood12 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse events 
 
X 
 
Serious adverse 
events 
 
X 
 
BMI = body mass index; CYP = cytochrome P450; ECG = electrocardiogram;  FSH = follicle stimulating hormone; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; 
HIV = human immunodeficiency  virus; hrs = hours; IL-17 = interleukin 17; PK = pharmacokinetic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11 Including a 15 minute supine period prior to every PK sample during Holter monitoring 
12 Period 1 only 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 25 of 36 
 
 
 
 
Table 7 
Study Procedural Outline Part B – MAD Healthy Subjects (IM024 005) 
 
Visit 
S creening 
Pre- 
Treatment 
Treatment 
Follow- 
up 
Study Days 
-21 to -1 
-1 
1
1413 
2-13 
15 
16 
18 
20 
24 
Time Post-Daily Dose 
(hrs)14 
 
 
Pre- 
dose 
0 
0.5 
1 
1.5 
2 
3 
4 
6 
8 
12 
Pre- 
dose 
0 
4 
24 
48 
96 
144 
240 
Confinement 
 
X 
 
 
Discharge15 
 
 
 
 
 
 
 
 
 
 
 
X  
 
Ambulant visit 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Informed consent and 
medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Genotyping(CYPs, 
transporters)16 
 
 
 
X 
 
 
 
 
 
Vital signs 
X 
 
X 
 
X 
X  
X  
X  
X 
 
X 
X 
X 
X 
X 
X 
Body weight and height 
(including BMI 
calculation)17 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Eligibility check 
X 
X 
X 18 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG (triplicate) 
X 
 
X 
 
X 
X  
 
X  
 
X19 
 
 
X 
 
 
 
 
 
 
13 Schedule for Day 1 (first day of dosing) and Day 14 (last day of dosing). 
14 Time is given relative to dosing on the relevant study day. In the CRF, time “0” will be the time of first dosing and all other time points will be relative to time “0”. 
15 Discharge from the clinical research unit. 
16 Mandatory whole blood collection for analysis of DNA variants in ADME-related genes (http://pharmaadme.org/Appendix 6). Sample may be taken at any time post-dose 
during Day 1; no sample to be taken on Day 14. 
17 Height will only be measured at screening. BMI will also only be calculated at screening. 
18 Not on Day 14. 
19 Days 2, 4, 6, 8, 10, and 12 only. 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 26 of 36 
 
 
 
Visit 
S creening 
Pre- 
Treatment 
Treatment 
Follow- 
up 
Study Days 
-21 to -1 
-1 
1 
1413 
2-13 
15 
16 
18 
20 
24 
Time Post-Daily Dose 
(hrs)14 
 
 
Pre- 
dose 
0 
0.5 
1 
1.5 
2 
3 
4 
6 
8 
12 
Pre- 
dose 
0 
4 
24 
48 
96 
144 
240 
Clinical laboratory, 
hematology incl. 
reticulocytes 
 
X 
 
X 
X 20 
 
 
 
 
 
 
X 21  
 
 
X  
 
X 
Holter monitoring 22 23 
 
 
X 24 
X 
 
 
 
 
 
Drug and alcohol screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
HBsAg, anti-HCV, and 
anti-HIV 1/2 tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Quantiferon Gold test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (females only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test (females 
only) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Randomization 
 
 
X 25 
 
 
 
 
 
 
 
 
 
 
 
Overnight fast (10 hours) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Standardized lunch, snacks, 
dinner 
 
 
 
X 
 
 
 
 
 
Study drug administration 
 
 
 
X  
 
 
 
 
 
X  
 
 
 
Taste questionnaire 
 
 
 
X26  
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
X 
X 
 
 
 
 
20 Day 14 only.
21 Days 3, 7, and 10 only. 
22 Including a 15 minute supine period prior to every PK sample. 
23 If upcoming preclinical safety results indicate the need for a dedicated TQTc study, Holter monitoring for this study willbe simplified and not plan for concentration-effect
modeling. 
24 In triplicate in 3 supine periods. 
25 On Day 1 only. 
26 On Day 1 only. To be completed immediately after drug administration (within first 10 seconds) and after approximately 1 minute (before drinking the provided glass of water). 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 27 of 36 
 
 
 
Visit 
S creening 
Pre- 
Treatment 
Treatment 
Follow- 
up 
Study Days 
-21 to -1 
-1 
1 
1413 
2-13 
15 
16 
18 
20 
24 
Time Post-Daily Dose 
(hrs)14 
 
 
Pre- 
dose 
0 
0.5 
1 
1.5 
2 
3 
4 
6 
8 
12 
Pre- 
dose 
0 
4 
24 
48 
96 
144 
240 
PK sampling blood27 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Urine collection for parent 
drug and metabolites 
 
X 
 
X 28 
 
 
 
 
 
Sampling for ex-vivo IL-17 
inhibition in whole blood 
 
X 
X 
 
X 
X  
X  
X 
X 29  
 
X  
X 
X 
Sampling for IL-17, IL-22, 
E-defensin, and 
erythropoietin 
 
 
X 
 
 
 
 
 
 
 
 
X  
 
X 
Sampling for T, B, and NK 
cells (TBNK), JGT cells, T 
cell subsets. 
 
 
 
X 
 
 
 
 
 
 
 
 
X  
 
 
X 
Adverse events 
 
 
 
X 
Serious adverse events 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
27 Including a 15 minute supine period prior to every PK sample during Holter monitoring. 
28 24-hours urine collection on Day 14 only 
29 Pre-dose at Days 2, 4 and 7 only. 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 28 of 36 
 
 
 
Appendix 3: Pharmacokinetic Sampling Schedule from Protocol 
Table 8 
Pharmacokinetic Sampling Schedule; Part A 
 
Sample  Collection 
Time 
 
Time 
(relative  to dosing) 
hour:min 
Blood Sample 
Urine  Sample 
Study 
Day 
Time 
(event) 
PK Blood Sample 
Collection  Interval 
-1 
NA 
NA 
 
X 
1 
0 h 
(pre-dose) 
 
00:00 
 
X 
 
1 
0.5 h 
00:30 
X 
 
 
 
 
 
 
X (0-12 h) 
1 
1 h 
01:00 
X 
1 
1.5 h 
01:30 
X 
1 
2 h 
02:00 
X 
1 
3 h 
03:00 
X 
1 
4 h 
04:00 
X 
1 
6 h 
06:00 
X 
1 
8 h 
08:00 
X 
1 
12 h 
12:00 
X 
 
X (12-24  h) 
2 
24 h 
24:00 
X 
2 
36 h 
36:00 
X 
 
X (24-48  h) 
3 
48 h 
48:00 
X 
4 
72 h 
72:00 
X 
X (48-72  h) 
5 
96 h 
96:00 
X 
X (72-96  h) 
6 
120 h 
120:00 
X 
X (96-120  h) 
7 
144 h 
144:00 
X 
X (120-144  h) 
9 
192 h 
192:00 
X 
 
11 
240 h 
240:00 
X 
 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 29 of 36 
 
 
 
Table 9 
Pharmacokinetic Sampling Schedule; Part B 
 
Sample  Collection Time 
Time 
(relative  to dosing) 
hour:min 
Blood Sample 
Urine  Sample 
Study  Day 
Time  (event) 
PK Blood Sample 
Collection  Interval 
-1 
NA 
NA 
 
X 
1 
0 h 
(pre-dose) 
00:00 
X 
1 
0.5 h 
00:30 
X 
1 
1 h 
01:00 
X 
1 
1.5 h 
01:30 
X 
1 
2 h 
02:00 
X 
1 
3 h 
03:00 
X 
1 
4 h 
04:00 
X 
1 
6 h 
06:00 
X 
1 
8 h 
08:00 
X 
1 
12 h 
12:00 
X 
2-13 
0 h 
(pre-dose) 
0:00 
X 
2-13 
4 h 
4:00 
X 
14 
0 h 
(pre-dose) 
0:00 
X 
X (0-24 h on Day 14) 
14 
0.5 h 
00:30 
X 
14 
1 h 
01:00 
X 
14 
1.5 h 
01:30 
X 
14 
2 h 
02:00 
X 
14 
3 h 
03:00 
X 
14 
4 h 
04:00 
X 
14 
6 h 
06:00 
X 
14 
8 h 
08:00 
X 
14 
12 h 
12:00 
X 
15 
24 h 
24:00 
X 
16 
48 h 
48:00 
X 
18 
96 h 
96:00 
X 
20 
144 h 
144:00 
X 
24 
240 h 
240:00 
X 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 30 of 36 
 
 
Table 10 
Pharmacodynamic Sampling Schedule; Part A 
 
 
 
 
n Whole Blood 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
h = hour; IL-17  = interleukin-17;  min = minute; NA = not applicable. 
 
 
Table 11 
Pharmacodynamic Sampling Schedule; Part B 
 
Sample  Collection 
Time 
 
Time 
(relative  to 
dosing) 
hour:min 
 
Blood Sample 
Study 
Day 
 
Time 
(event) 
 
Ex-vi vo  IL-17 
inhibition  in whole 
blood 
IL-17,  IL-22, 
ȕ-defensin,  and 
erythropoietin 
concentrations 
T, B, and NK cells 
(TBNK),  JGT cells, 
T cell subsets 
-1 
Admission 
NA 
X 
 
1 
0 h 
(pre-dose) 
 
00:00 
 
X 
 
X 
X 
1 
1 h 
01:00 
X 
 
1 
2 h 
02:00 
X 
 
1 
4 h 
04:00 
X 
 
1 
12 h 
12:00 
X 
 
2 
0 h 
(pre-dose) 
0:00 
X 
 
4 
0 h 
(pre-dose) 
0:00 
X 
 
Sample  Collection Time 
Time 
Blood Samples
(relative  to 
Study  Day 
Time  (event) 
dosing) 
hour:min 
Ex-vi vo  IL-17 Inhibition  i 
-1 
Admission 
NA 
X 
1 
0 h 
(pre-dose) 
00:00 
X 
1 
1 h 
01:00 
X 
1 
2 h 
02:00
X 
1 
4 h 
04:00
X 
1 
12 h 
12:00
X 
2 
24 h 
24:00 
X 
3 
48 h 
48:00 
X 
5 
96 h 
96:00 
X 
7 
144 h 
144:00 
X 
11 
240 h 
240:00 
X 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 31 of 36 
 
 
 
Sample 
T
Collection 
ime 
 
Time 
 
 
Blood Sample 
 
Study 
Day 
 
Time 
(event) 
(relative  to 
dosing) 
hour:min 
Ex-vi vo  IL-17 
inhibition  in whole 
blood 
IL-17,  IL-22, 
ȕ-defensin,  and 
erythropoietin 
concentrations 
T, B, and NK cells 
(TBNK),  JGT cells, 
T cell subsets 
7 
0 h 
(pre-dose) 
0:00 
X 
14 
0 h 
(pre-dose) 
0:00 
X 
14
1 h 
01:00
X 
14 
2 h 
02:00 
X 
14 
4 h 
04:00 
X 
14 
12 h 
12:00 
X 
15 
24 h 
24:00 
 
X 
X 
16 
48 h 
48:00 
X 
20 
144 h 
144:00 
X 
24 
240 h 
240:00 
X 
X 
X 
h = hour; IL-17  = interleukin-17;  IL-22 = interleukin-22;  min = minute; NA = not applicable; NK = natural killer. 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 32 of 36 
 
 
 
 
 
Appendix 4: List of Tables, Figures, and Listings 
 
List of Tables and Figures: 
Output 
Title 
Analysis  Set 
Section 14.1 – Disposition and Demographic  Data 
Table  14.1.1 
Summary of Analysis Sets 
All sets 
Table  14.1.2 
Summary of Subject Disposition 
All sets 
Table  14.1.3 
Summary  of Demographics 
All sets 
Table  14.1.4 
Summary of Dosing 
Safety 
Section 14.2 – Pharmacok inetic Data 
Table  14.2.1.1 
Summary  of BMS-986251  Plasma Concentration 
PK 
Table  14.2.1.2 
Summary  of Plasma Pharmacokinetic  Parameters 
PK 
Table  14.2.1.3 
Summary Analysis of Dose Proportionality 
PK 
 
Figure  14.2.1.4 
Plot of Arithmetic Mean (+SD) BMS-986251 Plasma 
Concentrations  versus  Time on Linear and Semi-logarithmic 
Scales - SAD Part 
PK 
Figure  14.2.1.5 
Plot of Individual  BMS-986251 Plasma Concentrations  Versus 
Time on Linear and Semi-logarithmic  Scales by Subject 
PK 
 
Figure  14.2.1.6 
Spaghetti Plot of Individual  BMS-986251  Plasma Concentrations 
Versus Time on Linear and Semi-logarithmic  Scales by 
Treatment 
 
PK 
Figure  14.2.1.7 
Plot of Dose Proportionality:  AUC(0-T),  AUC(INF)  and Cmax 
versus  Dose (Log scale) 
PK 
Table  14.2.2.1 
Individual  Values and Descriptive  Statistics of BMS-986251 
Excretion Parameters  in Urine 
PK 
Section 14.3 – Pharmacodynamic  Data 
 
Table  14.3.1 
Individual  Values and Descriptive Statistics of IL-17 
Concentrations  in Whole Blood 
 
PD 
Table  14.3.2 
Individual  Values and Descriptive Statistics of IL-17 Inhibition 
PD 
Table  14.3.3 
Individual  Values and Descriptive Statistics of IL-17 Inhibition 
Pharmacodynamic  Parameters 
PD 
Figure  14.3.4 
Arithmetic Mean +/- SD IL-17 Inhibition Versus Time (Linear 
Scale) –SAD Part 
PD 
Figure  14.3.5 
Combined  Individual  IL-17 Inhibition Versus Time (Linear  Scale) 
PD 
 
Figure  14.3.6 
Scatter Plot of IL-17  Inhibition Versus BMS-986251  Plasma 
Concentration 
 
PD 
Section 14.4 – Safety Data 
Table  14.4.1.1 
Summary of Adverse Events 
Safety 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 33 of 36 
 
 
 
Table  14.4.1.2 
Summary of Treatment  Emergent  Adverse Events  by System 
Organ Class and Preferred  Term 
Safety 
Table  14.4.1.3 
Summary of Treatment  Emergent  Adverse Events  by System 
Organ Class, Preferred  Term  and Relationship to Study Drug 
Safety 
 
Table  14.4.1.4 
Summary of Treatment  Emergent  Adverse Events  System Organ 
Class, Preferred  Term  and Severity 
 
Safety 
Table  14.4.2.1 
Listing of Deaths and Other Serious Adverse  Events 
All Subjects 
Table  14.4.3 
Not part of TFL – Reserved  for Narratives  in CSR 
 
Table  14.4.4.1 
Listing of Abnormal  Laboratory  Values 
All Subjects 
Table  14.4.4.2 
Summary of Safety Laboratory  Results 
Safety 
Table  14.4.4.3 
Shift Summary of Laboratory  Results by Reference  Range and 
Time Point 
Safety 
Table  14.4.4.4 
Summary of Vital Signs 
Safety 
Figure  14.4.4.5 
Plots of mean change from baseline of Vital Signs 
Safety 
Table  14.4.4.6 
Summary of 12-Lead  Electrocardiograms 
Safety 
 
List of End of Text Listings: 
Output 
Title 
Section 16.2.1 – Disposition 
Listing 16.2.1.1 
Subject Disposition 
Listing 16.2.1.2 
Tuberculosis  Screening 
Section 16.2.2 – Protocol Deviations 
Listing 16.2.2 
Important  Protocol Deviations 
Section 16.2.3 – Excluded  Subjects 
Listing 16.2.3 
Analysis Sets 
Section 16.2.4 – Demographics  and Baseline Characteristics 
Listing 16.2.4.1 
Subject Demographics 
Listing 16.2.4.2 
Medical History 
Listing 16.2.4.3 
Prior and Concomitant Medications 
Listing 16.2.4.4 
Tobacco and Alcohol Use 
Section 16.2.5 - Compliance 
Listing 16.2.5.1 
Study Drug Administration 
Section 16.2.6 – Response Data 
Listing 16.2.6.1 
Plasma BMS-986251  Concentrations 
Listing 16.2.6.2 
Plasma Pharmacokinetic  Parameters 
Listing 16.2.6.3 
Urine BMS-986251 Concentrations  and Amounts Excreted 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 34 of 36 
 
 
 
Listing 16.2.6.4 
Urine  Pharmacokinetic  Parameters 
Listing 16.2.6.5 
IL-17 Concentrations  in Stimulated and Unstimulated Whole Blood 
Listing 16.2.6.6 
IL-17 Inhibition in Whole Blood 
Listing 16.2.6.7 
IL-17 Inhibition in Whole Blood Pharmacokinetic Parameters 
Section 16.2.7 – Adverse Events Data 
Listing 16.2.7.1 
Adverse  Events 
Listing 16.2.7.2 
Adverse  Events Leading to Study Drug Discontinuation 
Section 16.2.8 – Laboratory  Data 
Listing 16.2.8.1 
Clinical Laboratory  Results – Chemistry 
Listing 16.2.8.2 
Clinical Laboratory  Results – Hematology 
Listing 16.2.8.3 
Clinical Laboratory  Results – Urinalysis 
Listing 16.2.8.4 
Clinical Laboratory  Results – Serology 
Listing 16.2.8.5 
Clinical Laboratory  Results – Pregnancy 
Listing 16.2.8.6 
Clinical Laboratory  Results – Drug and Alcohol Screen 
Listing 16.2.8.7 
Clinical Laboratory  Results – Comments 
Section 16.2.9– Other Safety Data 
Listing 16.2.9.1 
Vital Signs 
Listing 16.2.9.2 
12-Lead  Electrocardiograms 
Figure  16.2.9.3 
Scatter Plots of ǻ47F) Versus BMS-986251  Plasma Concentration 
Listing 16.2.9.4 
Physical Examinations 
Listing 16.2.9.5 
Taste Questionnaire 
 
 
Other Appendix Outputs: 
Output 
Title 
Appendix  16.1.7 
Randomization 
Appendix  16.1.9.2 
Statistical Appendices 


Statistical Analysis Plan 
BMS616EC-176161 
Protocol: IM024 005 
Version Date: 23-Aug-2018 
EDSREP 009 T 01 G 
Page 35 of 36 
 
 
 
 
Appendix 5: Shells for Tables, Figures and Listings 
Shells are provided  in a separate document.