Clinical trial NCT02843659
Conditions: Sjögren's Syndrome
Sponsor: Bristol-Myers Squibb
Start date: 2016-10-18; Completion date: 2017-07-24
Enrollment: 45 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the efficacy of treatment with either lulizumab or BMS-986142 versus placebo in subjects with moderate to severe primary Sjögren's syndrome as measured by the change from baseline in ESSDAI at Week 12 between active treatment arms (lulizumab or BMS-986142, respectively) and the placebo arm.

Detailed description:

Arms: arm 1: Subcutaneous weekly injection + daily oral placebo tablets arm 2: Daily oral tablets + subcutaneous placebo (weekly) injection arm 3: Weekly subcutaneous placebo injection +daily oral placebo tablets
Interventions: intervention 1: BMS-931699 intervention 2: BMS-986142 intervention 3: Placebo
Intervention descriptions: intervention 1: Specified dose on specified days intervention 2: Specified dose on specified days intervention 3: Specified dose on specified days

Protocol documents:
Prot_000.pdf: 
Page:
1
Protocol Number:
IM128035
IND Number:
122,786
Ex-US
Non-IND
EUDRACT Number
2016-000101-37
Date:
05-May-2016
Revised Date:
13-Feb-2017
Clinical Protocol IM128035
A Phase II, Randomized, Multi-Center, Double-Blind, Placebo Controlled Study to Evaluate the 
Efficacy and Safety of BMS-931699 (lulizumab) or BMS-986142 in Subjects with Moderate to 
Severe Primary Sjögren's Syndrome
Revised Protocol Number: 02
Incorporates Amendment 02 and Administrative Letter 02
Study Director and Medical Monitor
Karen Sims, MD, PhD
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) 
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Revised Protocol No.: 02
Date: 13-Feb-2017
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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).
Replace all previous version(s) of the protocol with this revised protocol and please provide 
a copy of this revised protocol to all study personnel under your supervision, and archive 
the previous versions.
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
SYNOPSIS
Clinical Protocol IM128035
Protocol Title: A Phase II, Randomized, Multi-Center, Double-Blind, Placebo Controlled Study to Evaluate the 
Efficacy and Safety of BMS-931699 (lulizumab) or BMS-986142 in Subjects with Moderate to Severe Primary 
Sjogren's Syndrome
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s):
BMS-931699 (lulizumab) is an anti-human cluster of differentiation (CD)28 receptor antagonist Vk domain 
antibody (dAb), formatted with 40 kDa branched polyethylene glycol (PEG). It will be administered subcutaneously 
(SC) at a dose of 12.5 mg weekly in a double-blind fashion for 12 weeks.
BMS-986142 is a reversible Bruton’s tyrosine kinase (BTK) inhibitor that will be administered orally at a dose of 
350 mg daily in a double-blind fashion for 12 weeks. 
Study Phase: II
Research Hypothesis: Treatment with BMS-931699 (lulizumab) or BMS-986142 for 12 weeks is more effective 
than placebo in decreasing the ESSDAI score in subjects with moderate to severe primary Sjögren’s syndrome
(pSS).
Objectives:
Primary: To evaluate the efficacy of treatment with either lulizumab or BMS-986142 versus placebo in subjects 
with moderate to severe primary Sjögren’s syndrome as measured by the change from baseline in ESSDAI at 
Week 12 between active treatment arms (lulizumab or BMS-986142, respectively) and the placebo arm.
Secondary:
To assess the:

Change from baseline in ESSPRI score at Week 12

Proportion of subjects with a 3 point improvement from baseline in ESSDAI at Week 12

Proportion of subjects with a 1 point improvement from baseline in ESSPRI at Week 12

Proportion of subjects with both 3 point improvement in ESSDAI and 1 point improvement in ESSPRI from 
baseline at Week 12

Change from baseline in ESSDAI scores at Week 4 and Week 8

Change from baseline in ESSPRI scores at Week 4 and Week 8

Change from baseline in ESSPRI components (Dryness, Fatigue, and Pain) at Week 4, 8 and 12

Change from baseline in unstimulated and stimulated salivary flow rate at Weeks 4, 8, and 12

Change from baseline in ocular surface staining, Schirmer’s test, and tear-break up time test at Weeks 4, 8,
and 12

Safety and tolerability of lulizumab or BMS-986142 in subjects with moderate to severe pSS, as measured by 
adverse events, laboratory parameters, vital signs, physical exams, and ECGs 

Change from baseline in patient and physician assessments of disease activity:
-
Numeric rating scale (NRS) scores for mouth, eye and vaginal dryness
-
Subject global assessment of disease activity (SubGDA) and physician global assessment of disease 
activity (phyGDA)
-
PROMIS Fatigue Short Form
-
Short Form-36 acute (SF-36 acute)
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BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
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Female Sexual Function Index (FSFI)
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Work participation and activity impairment questionnaire (WPAI)

Trough concentrations of lulizumab and BMS-986142 in pSS subjects
Study Design:
This is a 12-week randomized, double-blind, placebo-controlled, parallel group study with adaptive design features 
based on an interim analysis (IA). The study will initially have a 28-day Screening Period followed by up to 
12 weeks of double-blind treatment with either lulizumab, BMS-986142, or placebo.
Screening Period: The standard duration of the Screening Period is up to 28 days (4 weeks), with up to two 
Screening Visits allowed for subjects who require adjustment of oral corticosteroids or who are taking 
hydroxychloroquine. Subjects who are on oral corticosteroids at a dose higher than 10 mg/day will require a taper at 
the beginning of the Screening Period to a stable dose of no more than 10 mg/day of prednisone (or equivalent) by at 
least 14 days prior to dosing (Day -14), and will need to be reevaluated at a second screening visit prior to 
randomization (Day 1). Subjects who are taking hydroxychloroquine (HCQ, Plaquenil) at screening who meet the 
study criteria will be required to return for a second visit during the screening period to collect baseline HCQ PK 
samples. Should more time be needed, the duration of the Screening Period may be extended up to another week 
(total of 5 weeks or 35 days) depending on dose stabilization, technical issues, or subject scheduling.
Study Summary: Subjects with moderate to severe primary Sjögren’s syndrome will receive lulizumab, 
BMS-986142, or matching placebos for up to 12 weeks, followed by a 6-week follow-up period. 
Upon meeting the Inclusion/Exclusion criteria, approximately 75 subjects will be equally randomized to 1 of the 
3 treatment arms as shown in Figure 1 below.
An interim analysis will be conducted after at least 30 subjects reach Week 12 (complete 12 weeks of treatment) and 
complete the specified assessments for the Week 12 ESSDAI score. The interim analysis will be conducted in a fully 
blinded manner such that treatment group assignments of study subjects are not known and are not used in any 
manner in the analysis. A blinded examination of the variance of the primary endpoint will be performed and 
compared to the assumption used in planning the study. If this comparison suggests the initial assumption was 
substantially too low, the total study sample size may be increased by up to 45 additional subjects (ie, to a maximum 
of 120 subjects in total) to maintain adequate statistical power. The blinded IA will not interfere or alter any 
subject’s treatment, that is, subjects who were enrolled before the IA is completed will continue the originally 
assigned treatment arm if they have received at least 1 treatment and the dose is considered safe.
Ongoing assessment of safety will be performed by an independent Data Monitoring Committee (DMC). The DMC 
may make recommendations to the Sponsor regarding conduct of the study based on safety observations.
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Figure 1:
Study Design Schematic
Duration of Study:
The approximate duration of the study is up to a 5-week screening period (35 days), a 12-week double-blind 
treatment period (84 days), and 6 weeks of follow-up (42 days), for a total of up to 23 weeks (161 days).
Number of Subjects:
Approximately 75 subjects will be randomized across the three arms of this study. The study will utilize an equal 
randomization scheme (1:1:1) that will result in approximately 25 subjects in each arm. An interim analysis will be 
conducted in a fully blinded manner to examine the variability of the primary outcome measure and compare that to 
the assumption used in planning the study. If this comparison suggests the initial assumption was substantially too 
low, the total study sample size may be increased by up to 45 additional subjects (ie, to a maximum of 120 subjects 
in total) to maintain adequate study power.
Study Population:
Men or women (not nursing or pregnant) ages 18 to 70 years old (inclusive at time of randomization), diagnosed 
with primary Sjögren’s syndrome by the 2016 ACR-EULAR Classification Criteria, for at least 16 weeks prior to 
screening. Women of childbearing potential must use an acceptable method of highly effective contraception to 
avoid pregnancy for the duration of dosing and at least 65 days after the last dose of study medication.
Key Inclusion Criteria:
1. Subjects diagnosed or classified as having moderate to severe primary Sjögren’s syndrome based on the 2016
ACR-EULAR Classification Criteria for Sjögren’s syndrome, with disease duration from time since diagnosis of 
at least 16 weeks prior to the Screening Visit
2. ESSDAI 5; including disease activity (any score > 0) in at least one of the following domains: Glandular, 
Articular, Hematological, Biological, Lymphadenopathy
3. Positive anti-SS-A/Ro or anti-SS-B/La autoantibody
4. Unstimulated whole saliva secretion > 0.01 mL/min
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational 
[Medicinal] Products (Non-IP/Non-IMP) as listed:
Study Drug for IM128-035
Medication
Potency
IP/Non-IP
BMS-931699-01a Injection
12.5 mg/mL
IP
BMS-986142-01 Film Coated Tablet
50 mg
IP
Matching Film-Coated placebo for 50 mg 
BMS-986142-01 tablets
placebo
IP
BMS-986142-01 Film Coated Tablet
150 mg
IP
Matching Film Coated Placebo for 
150 mg BMS-986142-01 tablets
placebo
IP
a The clinical label will reflect the product name as “BMS-931699-01” to be linked with the product description on 
the vial.
Study Assessments:
Efficacy will be assessed using the ESSDAI and ESSPRI scores, as well as various other pharmacodynamic (PD), 
clinical, and patient reported measures of dryness and disease activity as listed under the objectives and endpoints.
Safety (through reporting of adverse events, clinical laboratory results, physical examination, which includes vital 
signs and electrocardiograms [ECGs]), PK, pharmacodynamics, exploratory biomarkers, target engagement, and 
immunogenicity will also be assessed.
Statistical Considerations:
Sample Size:
The sample size calculation is based on the power to compare change from baseline in ESSDAI at Week 12 between 
active treatment arms (lulizumab or BMS-986142) and the placebo arm. With a two-sided, two-sample t-test at 
significance level 0.05, data from 25 treated subjects per arm will provide approximately 90% power to detect a 
placebo-adjusted 3-point decrease from baseline for each active treatment group, assuming common standard 
deviations of 3.2. In addition, the Hochberg’s step-up procedure will be used to adjust the multiplicity due to the 
comparison of two active treatment arms (lulizumab or BMS-986142) to the placebo arm.
The primary efficacy analysis will be conducted on all randomized subjects who received at least one dose of study 
drug.
An interim analysis will be conducted after at least 30 subjects reach Week 12 (complete 12 weeks of treatment) and 
complete the specified assessments for ESSDAI. The interim analysis will be conducted in a fully blinded manner 
such that treatment group assignments of study subjects are not known and are not used in any manner in the 
analysis. A blinded examination of the variance of the primary endpoint will be performed and compared to the 
assumption used in planning the study. If this comparison suggests the initial assumption was substantially too low, 
the total study sample size may be increased by up to 45 additional subjects (ie, to a maximum of 120 subjects in 
total) to maintain the desired study power. Regardless of the outcome from the blinded examination of variability, 
the study sample size will not be decreased. A maximum study sample size of 120 subjects in total, ie, 40 subjects 
per arm, can provide each active treatment arm 79% power to detect a placebo-adjusted 3-point decrease from 
baseline for common standard deviations as large as 4.8, using a two-sided two-sample t-test comparing each active 
treatment arm to placebo at significant level 0.05.
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Endpoints:
The primary endpoint is to compare the change from baseline in ESSDAI score at Week 12 between active 
treatment arms (lulizumab or BMS-986142) and the placebo arm.
Secondary Endpoints:

Change from baseline in ESSPRI score at Week 12

Proportion of subjects with 3 points of improvement from baseline in ESSDAI at Week 12

Proportion of subjects with 1 point of improvement from baseline in ESSPRI at Week 12

Proportion of subjects with both 3 points improvement in ESSDAI and 1 point of improvement in ESSPRI 
from baseline at Week 12

Change from baseline in:
o
ESSDAI scores at Weeks 4 and Week 8
o
ESSPRI scores at Weeks 4 and Week 8
o
ESSPRI individual component (Dryness, Fatigue, and Pain) scores at Weeks 4, 8, and 12
o
Unstimulated and stimulated salivary flow rate at Weeks 4, 8, and 12
o
Ocular surface staining, Schirmer’s test and tear break-up time test at Weeks 4, 8, and 12

Safety and tolerability of lulizumab or BMS-986142 as measured by adverse events, laboratory parameters, 
vital signs, physical exams, and ECGs

Change from baseline in patient and physician assessments of disease activity:
-
Numeric rating scale (NRS) for mouth, eye and vaginal dryness
-
Subject global assessment of disease activity (SubGDA) and physician global assessment of disease 
activity (phyGDA)
-
Short Form-36 (SF-36)
-
Female Sexual Function Index (FSFI)
-
Work participation and activity impairment questionnaire (WPAI)
-
PROMIS Fatigue Short Form
o
Trough concentrations of BMS-931699 and BMS-986142 at protocol-specified time points
Efficacy Analyses:
Primary efficacy analysis:
The mixed effects model with repeated measures (MMRM) will be used to model the change from baseline in 
ESSDAI score over time for all treatment arms. Details of the model will be given in the statistical analysis plan. 
The least square means of the differences of Week 12 change in ESSDAI from baseline between each active 
treatment and the placebo will be estimated and their corresponding two-sided 95% confidence intervals will be 
provided. In addition, as part of the secondary objective, similar outputs will be provided for the changes in ESSDAI 
score at Weeks 4 and 8. 
The Hochberg’s step-up procedure will be used to adjust the multiplicity due to the comparison of two active 
treatments (lulizumab or BMS-986142) to the placebo arm in the primary endpoint (ie, change from baseline in 
ESSDAI at Week 12). The corresponding adjusted p-values for the Hochberg procedure will be provided.
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Secondary efficacy analysis:
For all secondary endpoints, no multiplicity adjustment will be applied, and nominal p-values may be provided if 
applicable. For each of the following categorical secondary endpoints, the estimate and its corresponding two-sided 
95% confidence interval will be calculated for the proportion for each treatment arm. In addition, as exploratory 
analyses, differences of the proportions between each active treatment arm and the placebo arm will be evaluated 
and their corresponding two-sided 95% confidence intervals will be provided.

Proportion of subjects with a 3 point improvement from baseline in ESSDAI at Week 12

Proportion of subjects with a 1 point improvement from baseline in ESSPRI at Week 12

Proportion of subjects with both 3 point improvement from baseline in ESSDAI and 1 point improvement 
from baseline in ESSPRI at Week 12
Similar to the primary endpoint, the following continuous secondary endpoints will be analyzed using the MMRM 
method:

Change from baseline in ESSPRI scores at Week 4, 8 and, 12

Change from baseline in score of each individual ESSPRI components (Dryness, Fatigue, and Pain) at Weeks 4, 
8, and 12

Change from baseline in mouth dryness as measured by unstimulated and stimulated salivary flow rate at 
Weeks 4, 8, and 12

Change from baseline in eye dryness as measured by ocular surface staining, Schirmer’s test, and tear break-up 
time test at Weeks 4, 8, and 12
Analyses for other outcomes research assessments will be discussed in Outcome Research Analyses section.
 
 
 
Safety analyses:
All recorded adverse events will be listed and tabulated by system organ class, preferred term, and treatment. Vital 
signs and clinical laboratory test results will be listed and summarized by treatment. Any significant physical 
examination findings and clinical laboratory results will be listed. ECG readings will be evaluated by the 
investigator, and abnormalities, if present, will be listed. Any pre-established Events of Special Interest will be listed 
and summarized.
Interim analysis:
One interim analysis will be conducted when at least 30 subjects reach Week 12 (complete 12 weeks of treatment) 
and complete specified assessments for ESSDAI. 
The interim analysis will be conducted in a fully blinded manner such that treatment group assignments of study 
subjects are not known and are not used in any manner in the analysis. Specifically, a blinded examination of the 
variance of the primary endpoint will be performed and compared to the assumption used in planning the study. If 
this comparison suggests the initial assumption is substantially too low, the total study sample size may be increased 
by up to 45 additional subjects (ie, to a maximum of 120 subjects in total) to maintain the desired study power. 
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Regardless of the outcome from the blinded examination of variability, the study sample size will not be decreased. 
Details on the blinded sample size re-estimation will be given in the statistical analysis plan.
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1 INTRODUCTION AND STUDY RATIONALE ..................................................... 
1.1 Study Rationale ................................................................................................. 
1.2 Research Hypothesis ......................................................................................... 
1.3 Objectives(s) ..................................................................................................... 
1.3.1 Primary Objective .................................................................................... 
1.3.2 Secondary Objectives ............................................................................... 
1.3.3 Exploratory Objectives ............................................................................ 
1.4 Product Development Background ................................................................... 
1.4.1 Pharmacology .......................................................................................... 
1.4.1.1 Lulizumab Pharmacology ............................................................... 
1.4.1.2 BMS-986142 (BTK inhibitor) Pharmacology ................................. 
1.4.2 Toxicity ..................................................................................................... 
1.4.2.1 Lulizumab Toxicity .......................................................................... 
1.4.2.2 BMS-986142 (BTK inhibitor) Toxicity............................................ 
1.4.3 Preclinical Metabolism and Pharmacokinetics ....................................... 
1.4.3.1 Lulizumab ........................................................................................ 
1.4.3.2 BMS-986142 (BTK inhibitor) ......................................................... 
1.4.4 Clinical Pharmacology and Safety .......................................................... 
1.4.4.1 Lulizumab ........................................................................................ 
1.4.4.2 BMS-986142 (BTK inhibitor) ......................................................... 
1.4.5 Dose Selection Rationale ......................................................................... 
1.4.5.1 Lulizumab ........................................................................................ 
1.4.5.2 BMS-986142 (BTK inhibitor) ......................................................... 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
1.5.1 BMS-986142 Risk/Benefit Assessment ..................................................... 
1.5.2 Lulizumab Risk/Benefit Assessment ......................................................... 
1.5.3 Overall Risk/Benefit Assessment .............................................................. 
2 ETHICAL CONSIDERATIONS ............................................................................... 
2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
3 INVESTIGATIONAL PLAN .................................................................................... 
3.1 Study Design and Duration ............................................................................... 
3.2 Post Study Access to Therapy ........................................................................... 
3.3 Study Population ............................................................................................... 
3.3.1 Inclusion Criteria ..................................................................................... 
3.3.2 Exclusion Criteria .................................................................................... 
3.3.3 Women of Childbearing Potential ........................................................... 
3.4 Concomitant Treatments ................................................................................... 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
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3.4.1.1 Restricted/Prohibited Treatments Prior to 
Enrollment/Randomization ................................................................... 
3.4.1.2 Restricted/Prohibited Treatments During Double-Blind Treatment 
Period .................................................................................................... 
3.4.1.3 Potential DDI Risks with BMS-986142 .......................................... 
3.4.2 Other Restrictions and Precautions ......................................................... 
3.4.2.1 Vaccinations .................................................................................... 
3.4.2.2 Infections ......................................................................................... 
3.5 Discontinuation of Subjects Following Treatment with Study Drug................ 
3.6 Post Study Drug Follow up ............................................................................... 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up .................................................................................... 
4 STUDY DRUG .......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.2 Non-Investigational Product ............................................................................. 
4.3 Storage and Dispensing..................................................................................... 
4.4 Method of Assigning Subject Identification ..................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction of Study Drug ................................................................................ 
4.9 Retained Samples for Bioavailability / Bioequivalence ................................... 
5 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening or Lead-in Period ....................................... 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Imaging Assessment for the Study............................................................ 
5.3.2 Laboratory Testing................................................................................... 
5.3.3 Tuberculosis Screening ............................................................................ 
5.3.4 Physical Exams ........................................................................................ 
5.3.5 Electrocardiograms ................................................................................. 
5.4 Efficacy Assessments ........................................................................................ 
5.4.1 Primary Efficacy Assessment ................................................................... 
5.4.2 Secondary Efficacy Assessments .............................................................. 
5.4.2.1 Ophthalmologic Assessments .......................................................... 
5.4.2.2 Salivary Flow .................................................................................. 
5.4.3 Exploratory Efficacy Assessment ............................................................. 
5.4.4 Clinical Assessor Requirements ............................................................... 
5.5 Pharmacokinetic Assessments .......................................................................... 
5.6 Exploratory Biomarker Assessments ................................................................ 
5.6.1 Additional Research ................................................................................. 
5.7 Outcomes Research Assessments ..................................................................... 
5.8 Other Assessments ............................................................................................ 
5.8.1 Immunogenicity Assessments ................................................................... 
6 ADVERSE EVENTS ................................................................................................. 
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BMS-931699 and BMS-986142
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anti cd-28 (lulizumab); btk inhibitor
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6.1 Serious Adverse Events .................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting .................................... 
6.2 Nonserious Adverse Events .............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting .............................. 
6.3 Laboratory Test Result Abnormalities .............................................................. 
6.4 Pregnancy .......................................................................................................... 
6.5 Overdose ........................................................................................................... 
6.6 Potential Drug Induced Liver Injury (DILI) ..................................................... 
6.7 Other Safety Considerations ............................................................................. 
7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
................................................................................................................................. 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoint(s) ................................................................................ 
8.3.2 Secondary Endpoint(s) ............................................................................. 
8.3.3 Exploratory Endpoint(s) .......................................................................... 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.2.1 Primary Efficacy Analyses .............................................................. 
8.4.2.2 Secondary Efficacy Analyses .......................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses ....................................................................... 
8.4.5 Biomarker Analyses ................................................................................. 
8.4.6 Outcomes Research Analyses .................................................................. 
8.4.7 Other Analyses ......................................................................................... 
8.4.7.1 Immunogenicity Analyses ................................................................ 
8.5 Interim Analyses ............................................................................................... 
9 STUDY MANAGEMENT ........................................................................................ 
9.1 Compliance ....................................................................................................... 
9.1.1 Compliance with the Protocol and Protocol Revisions ........................... 
9.1.2 Monitoring ............................................................................................... 
9.1.2.1 Source Documentation .................................................................... 
9.1.3 Investigational Site Training.................................................................... 
9.2 Records ............................................................................................................. 
9.2.1 Records Retention .................................................................................... 
9.2.2 Study Drug Records ................................................................................. 
9.2.3 Case Report Forms .................................................................................. 
9.3 Clinical Study Report and Publications ............................................................ 
10 GLOSSARY OF TERMS ........................................................................................ 
11 LIST OF ABBREVIATIONS .................................................................................. 
12 REFERENCES ........................................................................................................ 
APPENDIX 1 METHODS OF CONTRACEPTION ................................................... 
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APPENDIX 2 2016 ACR-EULAR CLASSIFICATION CRITERIA FOR PRIMARY 
SJÖGREN’S SYNDROME .................................................................................... 
 
APPENDIX 3 EULAR SJÖGREN’S SYNDROME DISEASE ACTIVITY INDEX 
(ESSDAI) ................................................................................................................ 
 
APPENDIX 4 EULAR SJÖGREN’S SYDROME PATIENT REPORTED INDEX 
(ESSPRI) ................................................................................................................. 
 
APPENDIX 5 SUBJECT’S GLOBAL ASSESSMENT OF DISEASE ACTIVITY 
(SUBGDA) ............................................................................................................. 
 
APPENDIX 6 PHYSICIAN’S GLOBAL ASSESSMENT OF DISEASE ACTIVITY 
(PHYGDA) ............................................................................................................. 
 
APPENDIX 7 ORAL DRYNESS NUMERIC RATING SCALE (ORAL NRS) ........ 
 
APPENDIX 8 OCULAR DRYNESS NUMERIC RATING SCALE (OCULAR NRS)
.................................................................................................................................
APPENDIX 9 VAGINAL DRYNESS NUMERIC RATING SCALE (VAGINAL 
NRS) ....................................................................................................................... 
 
APPENDIX 10 PATIENT REPORTED OUTCOMES MEASUREMENT 
INFORMATION SYSTEM (PROMIS) V1.0-FATIGUE SHORT FORM 8A ...... 
 
APPENDIX 11 FEMALE SEXUAL FUNCTION INDEX (FSFI) .............................. 
 
APPENDIX 12 SHORT FORM HEALTH SURVEY (SF-36) ACUTE VERSION 2  
 
APPENDIX 13 WORK PRODUCTIVITY AND ACTIVITY IMPAIRMENT (WPAI  
 GH) ........................................................................................................................ 
 
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anti cd-28 (lulizumab); btk inhibitor
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
1
INTRODUCTION AND STUDY RATIONALE
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7,8
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Revised Protocol No.: 02
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Revised Protocol No.: 02
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.2
Research Hypothesis
Treatment with BMS-931699 (lulizumab) or BMS-986142 for 12 weeks is more effective than 
placebo in decreasing the ESSDAI score in subjects with moderate to severe pSS.
1.3
Objectives(s)
1.3.1
Primary Objective
To evaluate the efficacy of treatment with either lulizumab or BMS-986142 versus placebo in 
subjects with moderate to severe pSS as measured by the change from baseline in ESSDAI at 
Week 12 between active treatment arms (lulizumab or BMS-986142, respectively) and the 
placebo arm.
1.3.2
Secondary Objectives
To assess the:

Change from baseline in ESSPRI score at Week 12

Proportion of subjects with a 3 point improvement from baseline in ESSDAI at Week 12

Proportion of subjects with a 1 point improvement from baseline in ESSPRI at Week 12

Proportion of subjects with both 3 points improvement in ESSDAI and 1 point 
improvement in ESSPRI from baseline at Week 12

Change from baseline in ESSDAI scores at Week 4 and Week 8

Change from baseline in ESSPRI scores at Week 4 and Week 8

Change from baseline in ESSPRI components (Dryness, Fatigue, and Pain) at Weeks 4, 8,
and 12
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor

Change from baseline in unstimulated and stimulated salivary flow rate at Weeks 4, 8, and 12

Change from baseline in ocular surface staining, Schirmer’s test, and tear break-up time test
at Weeks 4, 8, and 12

Safety and tolerability of lulizumab or BMS-986142 in subjects with moderate to severe pSS, 
as measured by adverse events, laboratory parameters, vital signs, physical exams, and ECGs

Change from baseline in patient and physician assessments of disease activity:

Patient Numeric Rating Scale (NRS) scores for mouth, eye and vaginal dryness (see 
Appendices 7, 8 and 9)

Subject global assessment of disease activity (SubGDA, see Appendix 5) and physician 
global assessment of disease activity (phyGDA, see Appendix 6)

Short Form - 36 acute (SF-36 acute, see Appendix 12)

Female Sexual Function Index (FSFI, see Appendix 11)

Work participation and activity impairment questionnaire (WPAI, see Appendix 13)

PROMIS Fatigue Short Form (see Appendix 10)

 
 
 
 
 
 
 
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
 
 
 
 
 
 
 
 
 
 
2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Conference on Harmonisation (ICH) and in accordance with the ethical principles 
underlying European Union Directive 2001/20/EC and the United States Code of Federal 
Regulations, Title 21, Part 50 (21CFR50).
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
All potential serious breaches must be reported to BMS 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).
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
2.2
Institutional Review Board/Independent Ethics Committee
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, subject recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects. The 
investigator or BMS should also provide the IRB/IEC with a copy of the IB or product labeling 
information to be provided to subjects and any updates.
The investigator or BMS should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
2.3
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate.
In situations where consent cannot be given to subjects, their legally acceptable representatives 
(as per country guidelines) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the subject volunteers to participate.
BMS will provide the investigator with an appropriate (ie, Global or Local) sample informed 
consent form which will include all elements required by ICH, GCP and applicable regulatory 
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:

Provide a copy of the consent form and written information about the study in the language 
in which the subject is most proficient prior to clinical study participation. The language 
must be non-technical and easily understood

Allow time necessary for subject or subject's legally acceptable representative to inquire 
about the details of the study

Obtain an informed consent signed and personally dated by the subject or the subject's 
legally acceptable representative and by the person who conducted the informed consent 
discussion

Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent 
form and any other information to be provided to the subjects, prior to the beginning of the 
study, and after any revisions are completed for new information

If informed consent is initially given by a subject’s legally acceptable representative or 
legal guardian, and the subject subsequently becomes capable of making and 
communicating his or her informed consent during the study, consent must additionally be 
obtained from the subject.

Revise the informed consent whenever important new information becomes available that 
is relevant to the subject's consent. The investigator, or a person designated by the 
investigator, should fully inform the subject or the subject's legally acceptable 
representative or legal guardian, of all pertinent aspects of the study and of any new 
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
information relevant to the subject's willingness to continue participation in the study. This 
communication should be documented.
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the subjects' signed ICF 
and, in the US, the subjects’ signed HIPAA Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to subject records. 
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a 12-week randomized, double-blind, placebo-controlled, parallel group study with 
adaptive design features based on an interim analysis (IA). The study will initially have a 28-day 
screening period followed by up to 12 weeks of double-blind treatment with either lulizumab, 
BMS-986142, or a matching placebo.
Screening period:
The standard duration of the Screening Period is up to 28 days (4 weeks), with up to two 
Screening Visits allowed for subjects who require adjustment of oral corticosteroids or who are 
taking HCQ. Subjects who are on oral corticosteroids at a dose higher than 10 mg/day will 
require a taper at the beginning of the Screening Period to a stable dose of no more than 
10 mg/day of prednisone (or equivalent) for least 14 days prior to dosing (Day -14), and will 
need to be reevaluated prior to randomization (Day 1). Subjects who are taking HCQ at 
screening who meet the study criteria will be required to return for a second visit during the 
screening period to collect baseline HCQ PK samples as described in Section 5.5 (these subjects 
should bring their daily dose of HCQ to the clinical site to be administered at the site). Should 
more time be needed, the duration of the Screening Period may be extended up to another week 
(total of 35 days or 5 weeks) depending on dose stabilization, technical issues, or subject 
scheduling. Study procedures will occur as specified in Table 5.1-1.
Double-blind treatment period:
Upon meeting the Inclusion/Exclusion criteria, approximately 75 subjects with moderate to 
severe pSS will be equally randomized to 1 of 3 treatment arms (lulizumab, BMS-986142, or 
matching placebos) for up to 12 weeks of treatment, followed by a 6 week follow-up period after 
completion 
of
treatment. 
During 
this 
period, 
the 
dose
of 
oral 
corticosteroids, 
hydroxychloroquine, pilocarpine, cevimeline, cyclosporine eye drops, lifitegrast, autologous 
serum eye drops, oral and ocular lubricants and/or NSAIDs should remain stable. No additional 
immunosuppressive medications may be started unless indicated for the treatment of adverse 
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
events. Analgesics are permitted with certain restrictions (see Section 3.4.1.2). Study procedures 
will occur as specified in Table 5.1-2, Table 5.5-1, and Table 5.6-1.
If a subject discontinues early from treatment, all procedures scheduled for the End of 
Week 12/End of treatment visit should be performed at the time of actual discontinuation/end of 
treatment.  At the end of the double blind treatment period, alternate therapies for Sjögren’s 
syndrome should be discussed with subjects.
Interim analysis:
An IA of all accumulated primary endpoint (ESSDAI) data up to Week 12 will be performed 
after at least 30 subjects reach Week 12 (complete 12 weeks of treatment) and complete the 
specified assessments for the Week 12 ESSDAI score. The interim analysis will be conducted in 
a fully blinded manner, such that treatment group assignments of study subjects are not known 
and are not used in any manner in the analysis. A blinded examination of the variance of the 
primary endpoint will be performed and compared to the assumption used in planning the study. 
Based on the results, the study sample size may be increased to maintain adequate statistical 
power. The blinded IA will not interfere or alter any subject’s treatment, that is, subjects who 
were enrolled before the IA is completed will continue the originally assigned treatment arm if 
they have received at least 1 treatment and the dose is considered safe.
Follow-Up Period:
After completion of the double-blind treatment period or early discontinuation from the study, all 
subjects will continued to be followed for an additional 6 week safety follow-up period. There 
will be two post treatment Follow-Up visits at Week 15 (or 3 weeks after early discontinuation)
and Week 18 (or 6 weeks after early discontinuation). Study procedures will occur as specified in 
Table 5.1-2.
The study design schematic is presented in Figure 3.1-1.
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Figure 3.1-1:
Study Design Schematic
The approximate duration of the study is up to a 5-week screening period (35 days), a 12-week 
double-blind treatment period (84 days), and 6 weeks of follow up (42 days), for a total of up to 
23 weeks (161 days).
The start of the trial is defined as the date of the first Screening Visit for the first subject 
screened. The end of the trial is defined as the date of the last visit or scheduled procedure shown 
in the Time & Events schedule for the last subject. Study completion is defined as the final date 
when the data from the last safety follow-up visit for the last subject has been received at BMS 
and the study is considered clinically complete.
3.2
Post Study Access to Therapy
At the end of the study, BMS will not continue to provide BMS supplied study drug to 
subjects/investigators unless BMS chooses to extend the study. The investigator should ensure 
that the subject receives appropriate standard of care to treat the condition under study. Pending 
appropriate preclinical and clinical data to support further drug development, BMS may 
authorize a study extension, or another mechanism to provide study drug to subjects who 
received clinical benefit in this study at the discretion of BMS. BMS reserves the right to 
terminate access to BMS supplied study drug if any of the following occur: a) the marketing 
application is rejected by responsible health authority; b) the study is terminated due to safety 
concerns; c) the subject can obtain medication from a government sponsored or private health 
program; d) BMS terminates development of the drug; or e) therapeutic alternatives become 
available in the local market.
3.3
Study Population
For entry into the study, the following criteria MUST be met.
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
3.3.1
Inclusion Criteria
1. Signed Written Informed Consent
a) Subjects from whom signed written consent for participation in this study has been 
obtained
2. Target Population
a) Subjects diagnosed or classified as having moderate to severe pSS (primary Sjögren’s 
syndrome is defined as Sjögren’s syndrome in the absence of another autoimmune 
disease or rheumatologic condition) based on the 2016 ACR-EULAR Classification 
Criteria (see Appendix 2) for pSS, with disease duration from time since diagnosis of at 
least 16 weeks prior to the Screening Visit
b) ESSDAI 5, including disease activity (any score > 0) in at least one of the following 
domains: Glandular, Articular, Hematological, Biological, Lymphadenopathy
c) Positive anti-SS-A/Ro or anti-SS-B/La autoantibody
d) Unstimulated whole saliva secretion > 0.01 ml/min
e) Prednisone or other oral corticosteroid use is not required, however, if subject is taking 
prednisone (or prednisone-equivalent), dose must be tapered to a maximum of 10 mg/day 
for at least 14 days prior to Day 1 (randomization)
f)
Subject Re-enrollment: This study permits the re-enrollment of a subject that has 
discontinued the study as a pre-treatment failure (ie, subject has not been randomized / 
has not been treated). If re-enrolled, the subject must be re-consented
3. Age and Reproductive Status
a) Males and Females, ages 18 to 70 years old, inclusive, at the time of randomization
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 
24 hours prior to the start of study drug
c) Women must not be pregnant or breastfeeding
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration 
of treatment with lulizumab or BMS-986142 plus 5 half-lives of the active treatment with 
the longest half-life given treatment will be blinded (lulizumab [half-life of 7 days]), plus 
30 days (duration of ovulatory cycle) for a total of 65 days post treatment completion
e) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of treatment with lulizumab or BMS-986142 
plus 5 half-lives of the active treatment with the longest half-life given treatment will be 
blinded (lulizumab [half-life of 7 days]) for a total of 35 days post-treatment completion. 
In addition, male subjects must be willing to refrain from sperm donation during this time
f)
Azoospermic males and WOCBP who are continuously not heterosexually active are 
exempt from contraceptive requirements. However, WOCBP must still undergo 
pregnancy testing as described in this section
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy.
Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on 
the use of highly effective methods of contraception (Refer to Appendix 1 for a list of acceptable 
methods), which have a failure rate of < 1% when used consistently and correctly.
3.3.2
Exclusion Criteria
1. Target Disease Exceptions
a) Secondary Sjögren's syndrome
b) Other systemic autoimmune disease (eg, RA, SLE, multiple sclerosis [MS], vasculitis)
c) Subjects with a condition that, in the opinion of the Investigator, may confound the 
diagnosis of pSS, including but not limited to: head and neck radiation, graft versus host 
disease, lymphoma, prior or current diagnosis of sarcoidosis, chronic viral diseases such 
as HIV, HTLV, or HCV, or IgG4 disease
d) Very severe pSS or severe complications of pSS at the time of the screening visit, 
including but not limited to:
i)
severe or ESSDAI Renal Domain High Activity - renal disease including but not 
limited to interstitial nephritis, glomerulonephritis, nephrotic syndrome with 
proteinuria > 3 gm/day and/or serum creatinine 2.0 mg/dL
ii) severe or ESSDAI CNS or PNS Domain High Activity - neurologic disease including 
but not limited to central or peripheral neuropathy or CNS vasculitis
iii) severe or ESSDAI Pulmonary Domain High Activity - pulmonary disease including 
but not limited to interstitial pneumonitis or obstructive bronchiolitis
iv) severe or ESSDAI Cutaneous Domain High Activity - documented vasculitis (mild 
isolated cutaneous vasculitis is not a contraindication)
v) lymphoma or other lymphoproliferative disease
vi) cryoglobulinemia with neurological, renal or visceral involvement
vii)severe or ESSDAI Muscular Domain High Activity - myositis
viii)
any complication requiring corticosteroid therapy 1 mg/kg during the 30 days 
preceding the screening visit
e) Subjects with an acutely infected salivary gland within 30 days of the screening visit
2. Medical History and Concurrent Diseases
a) Subjects at risk for tuberculosis (TB). Specifically, subjects with: 
i)
Current clinical, radiographic or laboratory evidence of active TB
ii) A history of active TB within the last 3 years, even if treated
iii) A history of active TB greater than 3 years ago unless there is documentation that the 
prior anti-TB treatment was appropriate in duration and type
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
iv) Therapy for latent TB which has not been completed as per local country guidelines
v) Positive interferon gamma release assay (IGRA) for TB unless proper treatment is 
documented as above
b) Subjects with any bacterial infection within the last 60 days prior to screening 
(enrollment), unless treated and resolved with antibiotics, or any chronic or history of 
recurrent bacterial infection (such as chronic pyelonephritis, osteomyelitis and 
bronchiectasis)
c) Subjects who have a history of systemic fungal infections (such as histoplasmosis, 
blastomycosis, or coccidiodomycosis)
d) Subjects with history of recurrent herpes zoster (more than 1 episode) or disseminated 
(more than 1 dermatome) herpes zoster or disseminated herpes simplex, or ophthalmic 
zoster will be excluded. Symptoms of herpes zoster or herpes simplex must have resolved 
more than 60 days prior to screening visit (enrollment)
e) Subjects with evidence (as assessed by the investigator) of active or latent bacterial or 
viral infection at the time of potential enrollment, including subjects with history or 
evidence of Human Immunodeficiency Virus (HIV) infection or who have a positive HIV 
test at screening
f)
Any significant concurrent medical condition at the time of screening or baseline visit, 
including, but not limited to, the following:
i)
Any major illness/condition or evidence of an unstable clinical condition (eg, renal, 
hepatic, 
hematologic, 
gastrointestinal, 
endocrine, 
pulmonary 
or 
active 
infection/infectious illness) that, in the Investigator’s judgment will substantially 
increase the risk to the subject if he or she participates in the study
ii) Cancer or lymphoproliferative disease within the previous 5 years (other than 
resected cutaneous basal cell or squamous cell carcinoma that has been treated with 
no evidence of recurrence). Subjects with a history of lymphoma at any time are 
excluded
iii) Female subjects with a breast cancer screening suspicious for malignancy, and in 
whom the possibility of malignancy cannot be reasonably excluded following 
additional clinical, laboratory or other diagnostic evaluations
iv) Class III or IV congestive heart failure as defined by the New York Heart Association
v) Acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) and/or 
any history of significant cerebrovascular disease within 24 weeks before screening
vi) Liver cirrhosis or other underlying liver disease (eg, non-alcoholic steatohepatitis, 
primary sclerosing cholangitis, primary biliary cirrhosis/cholangitis)
vii)Any significant coagulation or platelet function disorders (eg, von Willebrand’s 
disease)
viii)
Any gastrointestinal condition that could impact study drug absorption
ix) Any other concomitant medical conditions that, in the opinion of the investigator, 
might place the subject at unacceptable risk for participation in this study
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
g) Major surgical intervention or scheduled surgery during the 8 weeks preceding 
enrollment
h) Subjects currently on hydroxychloroquine who cannot provide documentation of an 
ophthalmologic evaluation (including evaluation of the retina) or who have evidence of 
retinopathy within 6 months of screening
i)
Donation of blood to a blood bank or in a clinical study (except a screening visit) within 
4 weeks of study drug administration (within 2 weeks for plasma only)
j)
Blood transfusion within 4 weeks of study drug administration
k) Inability to be venipunctured and/or tolerate venous access
l)
Subjects with a history of (within 12 months of signing the consent), or known current 
problems with drug or alcohol abuse
m) Subjects with a history or suspicion of unreliability, poor cooperation, or non-compliance 
with medical treatment
n) Subjects who have received treatment with an investigational drug within 12 weeks or 
less than 5 terminal half-lives of elimination (whichever is longer) of randomization 
(Day 1)
o) Live vaccine administration to subjects within 30 days of enrollment, during the 
screening or study periods, or for 8 weeks after completion of dosing
p) Subjects who are unwilling or have difficulty swallowing oral tablets
3. Physical and Laboratory Test Findings
a) Subjects with positive HBsAg, or subjects with positive anti-HBc antibody with 
detectable quantitative HBV DNA. Subjects with negative HBsAg but with high risk for 
latent HBV infection (including subjects with known family history of HBV infection, 
HBV carrier, personal medical history of hepatitis or blood transfusion history) should be 
tested for quantitative HBV DNA at the investigator’s discretion. Subjects with positive 
quantitative HBV DNA are excluded from the study
b) Hepatitis C antibody-positive subjects who are also HCV positive by confirmatory testing 
such as PCR
c) Positive HIV test
d) Have any clinically significant laboratory abnormalities (confirmed by repeat testing) 
including but not limited to:
i)
Hepatic
(1) ALT 2 x ULN (Upper limit of normal)
(2) AST 2 x ULN
(3) Total bilirubin 1.5 x ULN
ii) Hematology
(1) WBC count < 3000/mm3 (3.0 x 109/L)
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
(2) Hemoglobin < 9 g/dL
(3) Absolute neutrophil count < 1000/mm3 (1.0 x 109/L)
(4) Platelets < 100,000/mm3 (100 x 109/L)
iii) Creatinine 2.0 mg/dL
e) Subjects with a positive TB IGRA (such as QuantiferonTB Gold, Refer to 
Section 3.3.2 #2a)
f)
Any other significant laboratory abnormalities that, in the opinion of the Investigator, 
might place the subject at unacceptable risk for participation in this study (please discuss 
with BMS Medical Monitor if there are any questions in regards to inclusion/exclusion 
criteria)
4. Allergies and Adverse Drug Reaction
a) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)
5. Prior and Concomitant Medications
a) Oral corticosteroids > 10 mg/day within 14 days of dosing (Day 1), or corticosteroid 
therapy 1 mg/kg during the 4 weeks preceding enrollment 
b) Intravenous, intramuscular or intra-articular corticosteroids within 4 weeks of enrollment
c) Treatment started or an unstable dose of non-steroidal anti-inflammatory drugs 
(NSAIDs), pilocarpine, cevimeline (Evoxac), topical corticosteroid eye preparations,
lifitegrast (Xiidra), autologous serum eye drops, or cyclosporine eye drops (Restasis) 
within 14 days of dosing (doses must be held for at least 12 hours prior to any study visit 
after Screening)
d) Use of methotrexate, cyclophosphamide, cyclosporine, tacrolimus, azathioprine, 
mycophenolate mofetil (MMF) or leflunomide within 12 weeks of enrollment
e) Treatment started or an unstable dose of hydroxychloroquine (Plaquenil) within 
8 weeks of enrollment. Doses higher than 400 mg/day are not permitted. Use of other 
antimalarials (eg, chloroquine, quinacrine) is not permitted
f)
Use of rituximab within 6 months prior to enrollment or lack of recovery of 
CD19+ B cells to > 10/l at screening in any subject with prior rituximab use
g) Previous treatment with other biologics either marketed or in development (eg, abatacept, 
tocilizumab, belimumab, TNF inhibitors) within 6 months prior to enrollment
h) Subjects are not permitted to have new installation of lacrimal punctum plugs within 4 
weeks of randomization (Day 1) or during the course of the study. Subjects with existing 
lacrimal punctum plugs are permitted to enroll, and have these plugs replaced as
necessary during the study
6. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific 
circumstances a person who has been imprisoned may be included or permitted to 
continue as a subject. Strict conditions apply and Bristol-Myers Squibb approval is 
required)
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b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
c) Inability to comply with restrictions and prohibited treatments as listed in Section 3.4
d) Adults under guardianship or protection
e) Participation in another interventional therapeutic trial (treatment underway or in study 
follow-up period)
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
3.3.3
Women of Childbearing Potential
A woman of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) and is not postmenopausal. Menopause 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 > 40mIU/mL to confirm menopause.
*Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgement in checking serum FSH levels. If the serum FSH level is > 40 mIU/ml at any time 
during the washout period, the woman can be considered postmenopausal:

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.
3.4
Concomitant Treatments
3.4.1
Prohibited and/or Restricted Treatments
Restricted treatment for the different study periods are detailed below:
3.4.1.1
Restricted/Prohibited Treatments Prior to Enrollment/Randomization

Oral corticosteroids > 10 mg/day within 14 days of dosing (Day 1), or corticosteroid therapy 
1 mg/kg during the 4 weeks preceding enrollment

Intravenous, intramuscular or intra-articular corticosteroids within 4 weeks of enrollment.
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anti cd-28 (lulizumab); btk inhibitor

Treatment started or an unstable dose of NSAIDs, pilocarpine, cevimeline (Evoxac),
topical corticosteroid eye preparations, lifitegrast (Xiidra), cyclosporine eye drops 
(Restasis) or autologous serum eye drops within 14 days of dosing (dose must be held for 
at least 12 hours prior to any study visit after Screening)

Artificial tears and/or saliva are permitted, but must be held on the day of study visit

Use of methotrexate, cyclophosphamide, cyclosporine, tacrolimus, azathioprine, MMF or 
leflunomide within 12 weeks of enrollment

Treatment started or an unstable dose of hydroxychloroquine (Plaquenil) within 8 weeks of 
enrollment. Doses higher than 400 mg/day are not permitted. Use of other antimalarials 
(chloroquine, quinacrine) is not permitted

Use of rituximab within 6 months prior to enrollment or lack of recovery of CD19+ B cells 
> 10/l at screening in any subject with prior rituximab use

Previous treatment with other biologics either marketed or in development (eg, abatacept, 
tocilizumab, belimumab, TNF inhibitors) within 6 months prior to enrollment

Live vaccine administration to subjects within 30 days of enrollment, during the screening or 
study periods, or for 8 weeks after completion of dosing
3.4.1.2
Restricted/Prohibited Treatments During Double-Blind Treatment
Period
All restrictions during the double-blind period only apply to the management of symptoms for 
pSS.
For concomitant treatments for other conditions, see Section 3.4.1.3. Some of the drugs used for 
other conditions may result in drug interactions and may be prohibited or restricted. Any 
medication initiated during the treatment period should be discussed with the BMS Medical 
Monitor. 
Hydroxychloroquine (Plaquenil)
All subjects who enter the screening period on hydroxychloroquine must remain on a stable dose 
of no more than 400 mg daily from the time of signing the informed consent for the duration of 
the study. New initiation of hydroxychloroquine, a daily dose > 400 mg/day, or a change in the 
dose of hydroxychloroquine is not permitted during the screening or dosing periods. The use of 
other antimalarials is not permitted.
Steroids
All subjects taking oral prednisone or its equivalent during screening must remain at a dose 
10 mg/day for the entirety of the dosing period. Intra-articular, intramuscular (IM) or 
intravenous (IV) corticosteroid injections, or initiation of topical corticosteroid eye preparations
are not permitted during the screening or dosing periods unless required for treatment of adverse 
events in consultation with the BMS Medical Monitor.
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anti cd-28 (lulizumab); btk inhibitor
Ocular and Oral Lubricants
Subjects who enter the screening period on a stable dose of pilocarpine, cevimeline (Evoxac), 
topical corticosteroid eye preparations, cyclosporine eye drops (Restasis), lifitegrast (Xiidra), 
or autologous serum eye drops are permitted to remain on these medications during the screening 
and dosing period, but must hold the dose(s) for at least 12 hours prior to any study visit until all 
study assessments are completed. These medications may not be initiated during the screening or 
dosing period. Artificial tears and saliva are permitted but must be held on the day of a study 
visit until all study assessments are completed.
Analgesics and NSAIDs

NSAIDS doses should remain stable with the exception of decreases being permitted due to 
related adverse events, such as gastric toxicity.

Analgesics

Acetaminophen (paracetamol) maximal dose 2 g/day
NOTE: combination products including acetaminophen and narcotic analgesics 
(eg, acetaminophen with codeine phosphate, acetaminophen with propoxyphene 
napsylate, acetaminophen with oxycodone HCl, acetaminophen with hydrocodone 
bitartrate, etc.) are allowed provided the acetaminophen component dosage is accounted 
for in the maximum of 2 g/day

Narcotic analgesics must not exceed 30 mg/day of morphine or its equivalent

Tramadol doses must be stable

Acetylsalicylic acid is allowed in low doses (eg, 100 mg/day) for cardiovascular 
prophylaxis
Immunosuppressives
The following medications are prohibited during the screening, dosing and follow-up periods:

methotrexate

cyclophosphamide

leflunomide

azathioprine

cyclosporine

tacrolimus

MMF

rituximab

belimumab

tocilizumab
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anti cd-28 (lulizumab); btk inhibitor

All investigational and approved biologic therapies (including but not limited to abatacept, 
etanercept, anakinra, infliximab, etc.)

Use of any investigational drug other than study medication
Hormonal Contraceptives:
The use of hormonal contraceptives (oral, via implant/depot or via eluting IUD) are prohibited as 
a method of highly effective contraception due to safety concerns from transient liver function 
test elevations observed in the drug-drug interactions study (IM006032) with BMS-986142 and a 
combination oral contraceptive (ethinyl estradiol and the norethindrone acetate). In the study, a 
total of 10 of 16 subjects that were dosed with the oral contraceptive and BMS-986142 in 
combination had mild to moderate elevations of transaminases without an associated increase of 
total bilirubin. The majority of ALT elevations were < 3xULN. The maximum increase occurred 
in one subject with an ALT 5.8x ULN without accompanying total bilirubin elevation. Most 
subjects had no symptoms, however, 3 subjects had nausea, 2 subjects had vomiting and 1 had 
chills. All of the elevated transaminase levels returned to baseline. An evaluation of the cause of 
the transaminase elevation is ongoing, but no marked changes in the exposures of BMS-986142 
or the components of the oral contraceptive were observed in a preliminary assessment of the 
data (i.e. no pharmacokinetic drug-drug interaction occurred during co-administration).
In addition, the use of oral or implantable estrogen-based hormone replacement therapy is also 
prohibited until additional drug interaction data becomes available. See Section 3.4.1.3.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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anti cd-28 (lulizumab); btk inhibitor
 
 
 
 
 
 
 
 
3.4.2.2
Infections
Subjects who develop significant infectious complications during the study should be treated 
appropriately and have study medication withheld and restarted only when the infection is 
clinically resolved and the investigator considers it appropriate.
3.5
Discontinuation of Subjects Following Treatment with Study Drug
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:

Subject’s request to stop study treatment or withdrawal of informed consent

Any clinical adverse event (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 by Bristol-Myers Squibb (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

Unblinding a subject for any reason (emergency or non-emergency)

Use of prohibited medication

Development of new active manifestations of pSS requiring treatment with any non-protocol 
approved medications during the study

Inability or subject's failure to comply with the protocol requirements

Pregnancy

Male subjects must discontinue treatment if their female partners become pregnant during the 
trial. After discontinuation, male subjects are required to continue using a highly effective 
method of contraception for a total of 35 days post-treatment completion

Severe (eg, Grade 3), drug-related AEs of infection, bleeding events/coagulopathy, or 
injection site reactions
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BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor

ANC < 500/mm3, confirmed by repeat

Potential drug induced liver injury (see Section 6.6 for definition)
In the case of pregnancy, the investigator must immediately notify the BMS Medical 
Monitor/designee of this event. In most cases, the study drug will be permanently discontinued in 
an appropriate manner (eg, dose tapering if necessary for subject safety). Please call the BMS 
Medical Monitor/designee within 24 hours of awareness of the pregnancy. If the investigator 
determines a possible favorable benefit/risk ratio that warrants continuation of study drug, a 
discussion between the investigator and the BMS Medical Monitor/designee must occur.
All subjects who discontinue study drug should comply with protocol specified follow-up 
procedures as outlined in Section 5. 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).
If study drug 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 case report form (CRF) page.
3.6
Post Study Drug Follow up
In this study, ESSDAI and ESSPRI as well as other efficacy measures at Week 12 are key 
endpoints of the study. Post study follow-up is of critical importance and is essential to 
preserving subject safety and the integrity of the study. Subjects who discontinue study drug
must continue to be followed for collection of outcome and/or survival follow-up data as 
required and in line with Section 5 until death or the conclusion of the study subject’s 
participation in the specified follow up period of the study, whichever comes first.
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug 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. 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 drug only or also from study 
procedures and/or post treatment study follow-up, and entered on the appropriate CRF page. In 
the event that vital status (whether the subject is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed in 
accordance with local law.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost to 
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follow-up is defined by the inability to reach the subject after a minimum of three documented 
phone calls, faxes, or emails as well as lack of response by subject to one registered mail letter. 
All attempts should be documented in the subject’s medical records. If it is determined that the 
subject has died, the site will use permissible local methods to obtain the date and cause of death.
If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the subject’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining subject’s contact 
information or other public vital status data necessary to complete the follow-up portion of the 
study. The site staff and representative will consult publicly available sources, such as public 
health registries and databases, in order to obtain updated contact information. If after all 
attempts, the subject remains lost to follow-up, then the last known alive date as determined by 
the investigator should be reported and documented in the subject’s medical records.
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anti cd-28 (lulizumab); btk inhibitor
4
STUDY DRUG
Study drug
includes
both Investigational [Medicinal] Product
(IP/IMP)
and
Non-investigational [Medicinal] Product
(Non-IP/Non-IMP) and can consist of the following:

All products, active or placebo, being tested or used as a comparator in a clinical trial

Study required premedication, and 

Other drugs administered as part of the study that are critical to claims of efficacy (eg, background therapy, rescue medications)

Diagnostic agents: (such as glucose for glucose challenge) given as part of the protocol requirements must also be included in the 
dosing data collection
Table 4-1:
Study Drugs for IM128035
Product Description / Class and 
Dosage Form
Potency
IP/
Non-IMP
Blinded or 
Open-Label
Packaging/ Appearance
Storage Conditions
(per label)
BMS-931699-01 Injectiona The 
composition of the drug product is 
12.5 mg/mL, BMS-931699
(lulizumab) in 20 mM phosphate, 
pH 5.9, with 5% (w/v) sorbitol
12.5 
mg/mL
IP
Open-Label
3 cc vial with 13mm opening, 
1-panel / Open-label
Appearance clear to slightly 
opalescent, colorless to pale yellow 
solution
Store refrigerated 2 – 8 °C 
Protect from light, Protect 
from freezing
BMS-986142-01 Film Coated 
Tablet
50 mg
IP
Blinded 
Label
Plain, yellow, round film coated 
tablet
HDPE Bottle
Store refrigerated 2 – 8 °C 
Store in a tightly closed 
container
Placebo for BMS-986142-01 Film 
Coated Tablet, 50mg
Placebo
IP
Blinded 
Label
Plain, yellow, round film coated 
tablet
HDPE Bottle
Store refrigerated 2 – 8 °C 
Store in a tightly closed 
container
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BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Table 4-1:
Study Drugs for IM128035
Product Description / Class and 
Dosage Form
Potency
IP/
Non-IMP
Blinded or 
Open-Label
Packaging/ Appearance
Storage Conditions
(per label)
BMS-986142-01 Film Coated 
Tablet
150 mg
IP 
Blinded 
Label
Plain, yellow, oval film coated 
tablet
HDPE Bottle
Store refrigerated 2 – 8 °C 
Store in a tightly closed 
container
Placebo for BMS-986142-01 Film 
Coated Tablet, 150mg
Placebo
IP
Blinded 
Label
Plain, yellow, oval film coated 
tablet
HDPE Bottle
Store refrigerated 2 – 8 °C 
Store in a tightly closed 
container
a The clinical label will reflect the product name as “BMS-931699-01” to be linked with the product description on the vial
BMS will provide BMS-931699-01, BMS-986142-01 and matching placebo for BMS-986142-01 tablets to all investigating sites. For 
study drugs not provided by BMS and obtained commercially by the site, storage should be in accordance with the product label
(eg, normal saline placebo for BMS-931699)
Pharmacy dosing manual will be provided separately to the sites.
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4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
In this protocol, investigational products (also described in Table 4-1) are: 

BMS-931699/lulizumab injection (12.5mg/vial, 12.5mg/mL) for subcutaneous administration

BMS-986142 50mg tablet (round) for oral administration

BMS-986142 150 mg tablet (oval) for oral administration

Matching Placebo for BMS-986142 50 mg tablet (round) for oral administration

Matching Placebo for BMS-986142 150 mg tablet (oval) for oral administration
The placebo for BMS-931699/lulizumab injection is normal saline solution. The investigational 
sites will provide the normal saline for preparation of placebo BMS-931699/lulizumab.
4.2
Non-Investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or 
therapeutic reasons, as components of the standard of care for a given diagnosis, may be
considered as non-investigational products.
In this protocol, non-investigational product(s) include, but are not limited to:

Hydroxychloroquine (Plaquenil)

Prednisone or other oral corticosteroids

Pilocarpine, cevimeline (Evoxac), cyclosporine eye drops (Restasis)

NSAIDs & analgesics

Ocular and oral lubricants (artificial tears or saliva)
The Sponsor will not be providing these medications since they are part of subject’s standard of 
care.
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
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anti cd-28 (lulizumab); btk inhibitor
regarding the quality or appearance of the study drug arise, the study drug should not be 
dispensed and contact BMS immediately.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Please refer to Section 9.2.2 for guidance on IP records and documentation and Section 4.8 for 
return and destruction instructions.
Investigational product documentation (whether supplied by BMS or not) must be maintained 
that includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
Please refer to the current versions of the IBs and/or pharmacy reference sheets for complete 
storage, handling, dispensing information for BMS-931699/lulizumab and BMS-986142.
Lulizumab:
Preparation for Subcutaneous (SC) Use for BMS-931699/lulizumab
For SC dosing, no dilution of drug product solution (12.5 mg/mL) will be required for the 
12.5 mg dose. A commercially available appropriately sized sterile needle and appropriate 
syringe should be used for withdrawal from vial and administration (refer to the pharmacy 
dosing manual for further details on the subcutaneous preparation and administration for 
materials and instructions, which is provided separately).
The placebo for lulizumab injection is normal saline injection, which is administered in a similar 
fashion as described for the lulizumab injection. The normal saline to use as placebo will not be 
provided by the Sponsor. 
Lulizumab injection should be stored at 2 – 8 °C with protection from light and protection from 
freezing. After withdrawal into an appropriate sized syringe, the product must be administered 
within 4 hours. If not dosed immediately, filled syringes should be kept at 2 – 8 °C with 
protection from light and freezing prior to use.
Study personnel will administer the dose to the subject. The primary point of injection should be 
one of the upper arms; however, other points of injections are acceptable, such as stomach or 
thighs. The same injection site should not be used for consecutive study drug administration. The 
subjects should be monitored for at least 1 hour after each injection for potential reactions.
BMS-986142:
BMS-986142 bottles should be stored at 2 – 8 °C and stored in a tightly closed container. 
Please refer to the current version of the IB and/or pharmacy dosing manual for complete 
storage, handling and dispensing information for lulizumab and BMS-986142.
4.4
Method of Assigning Subject Identification
At the time of the screening visit, immediately after written informed consent is obtained and
before performing any study-related procedures, the investigator or coordinator will call into the 
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Interactive Voice Response System (IVRS or IWRS) designated by BMS for assignment of a 
5 digit subject number that will be unique across all sites. Enrolled subjects, including those not 
dosed, will be assigned unique sequential subject numbers by the IVRS/IWRS system starting 
with 00001, 00002, 00003, etc. for identification throughout the study. This subject number must 
not be reused for any other participant in the study.
After completion of all screening evaluations, on Day 1, all eligible subjects will be randomly 
assigned to 1 of 3 treatment arms (lulizumab, BMS-986142, or placebo) in an equal ratio. To 
randomize a subject, a phone call will be placed into the randomization option of the 
IVRS/IWRS in order to obtain a subject’s randomized treatment assignment. Randomization will 
be assigned in the order in which subjects qualify for treatment, not in the order of study 
enrollment. The IVRS will be available 24 hours a day, 7 days a week, via a toll-free number
(or via the internet for IWRS). Randomization will be stratified by hydroxychloroquine 
(Plaquenil) and oral corticosteroid use.
Specific instructions (including an enrollment/randomization worksheet) for the central 
enrollment and randomization procedure using an IVRS/IWRS will be provided to the site.
Randomized schedules will be generated and kept by the Randomization Group within Drug 
Supply Management of Bristol-Myers Squibb.
At all study visits when study drug is dispensed, each subject will be assigned specific container 
numbers by the IVRS/IWRS. Container numbers will be assigned non-sequentially and will 
correspond to the numbers printed on the containers and bottles containing study drug, and will 
be recorded on the appropriate eCRF.
4.5
Selection and Timing of Dose for Each Subject
All drug dosing should occur after all study-related assessments, including blood draws, 
are completed. Refer to Section 5.3 for additional information on the order of procedures.
After randomization, study drug will be dispensed according to the assignment by the 
IVRS/IWRS system. Study drugs are blinded and will be supplied in bottles for BMS-986142 
and its matching placebo for home administration. Doses of lulizumab or matching placebo are 
to be administered subcutaneously in the clinic or by a health care professional (eg, visiting 
nurse) in the home if approved by local IRB/EC and the investigator. Doses of BMS-986142 at 
350 mg or matching placebo are to be administered orally q24h (one time/day) with water and 
may be taken with or without food. Three tablets, one tablet from Bottle A and two tablets from 
Bottle B, will be taken all at the same time, once/day every day. Subjects should be instructed to 
bring their oral study drug (BMS-986142 or placebo) to be taken at the investigational site at 
every scheduled visit (eg, weekly if home visits are not performed) to avoid confusion about the 
timing of dose administration, given the frequency of PK assessments and study procedures 
during the study. On Day 1 and at Weeks 2, 4, 6, 8, and 10, study drug will be administered in 
the morning at the study site and after blood samples have been collected and questionnaires 
have been completed. For subjects who are on a stable dose of HCQ, subjects must also bring 
their HCQ dose to the site on Day 1, Day 8, Week 2 (Day 15), Week 4 (Day 29) and Week 12 
(Day 85) of the study as well as the two follow up visits at Week 15 (Day 106) and Week 18 
Revised Protocol No.: 02
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
(Day 127), as the HCQ dose will be administered at the same time as the study drugs in the 
morning at the study site to enable pre-dose PK samples to be taken. Two post-dose PK samples 
(2 and 4 hours after dosing) for HCQ and study drugs will also be collected at the Day 8 visit. 
However, at other visits, drug should be taken at approximately the same time each day.
For BMS-986142 and matching placebo, each subject will be dispensed a set of two (2) bottles 
every two weeks during treatment. Bottle A contains 17 tablets and Bottle B contains 34 tablets 
of blinded study drug. The 3 additional tablets in Bottle A and the additional 6 tablets in Bottle B
allow for a +/- 3 day window between each visit in the double-blind phase of the study. All study 
drug bottles (empty or full) that were dispensed to the subject must be brought back to the study 
site by the subject at Weeks 1, 2, 4, 6, 8, 10, and 12 during the double-blind period for drug 
reconciliation/compliance assessments.
4.6
Blinding/Unblinding
Blinding of treatment assignment is critical to the integrity of this clinical study. However, in the 
event of a medical emergency or pregnancy in an individual subject in which knowledge of the 
investigational product is critical to the subject's management, the blind for that subject may be 
broken by the investigator. The subject’s safety takes priority over any other considerations in 
determining if a treatment assignment should be unblinded.
Before breaking the blind of an individual subject's treatment, the investigator should determine
that the unblinded information is necessary, ie, that it will alter the subject's immediate 
management. In many cases, particularly when the emergency is clearly not related to the 
investigational product, the problem may be properly managed by assuming that the subject is 
receiving one of the active products. It is highly desirable that the decision to unblind treatment 
assignment be discussed with the BMS Medical Monitor, but the investigator always has 
ultimate authority for the decision to unblind. The Principal Investigator should only call in for 
emergency unblinding AFTER the decision to discontinue the subject has been made.
For this study, the method of unblinding for emergency purposes is IVRS/IWRS. For 
information on how to un-blind in an emergency, consult the IVRS/IWRS manual.
In cases of any accidental unblinding, contact the BMS 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 
Medical Monitor.
In case of an emergency, the Investigator(s) has unrestricted access to randomization information 
via the Interactive Voice Response System (IVRS/IWRS) and is capable of breaking the blind 
through the IVRS/IWRS system without prior approval from sponsor. Following the unblinding,
the Investigator should notify the BMS Medical Monitor.
The Bioanalytical Sciences section or its designate will be unblinded to the randomized 
treatment assignments in order to minimize unnecessary analysis of samples from control group 
subjects. 
Revised Protocol No.: 02
Date: 13-Feb-2017
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Interim Analysis:
The interim analysis will be conducted in a fully blinded manner such that treatment group 
assignments of study subjects are not known and are not used in any manner in the analysis.
4.7
Treatment Compliance
The investigator or designated study personnel will maintain a drug accountability log of all 
study drug(s) received, dispensed, destroyed and the amount returned to the Sponsor or supply 
depot. The drug supplies will be inventoried and accounted for throughout the study. The drug 
accountability log will be reviewed by the study monitor during site visits and at the completion 
of the study.
Study drug lulizumab or placebo will be administered via SC injection in the clinical facility. 
The treatment compliance in this study for lulizumab will be done at the study site where 
documentation of injection and compliance will be maintained.
Study drug BMS-986142 or placebo will be administered orally at home by the subjects or on 
site during clinic visits. The treatment compliance in this study for BMS-986142 will be 
determined by counts of returned tablets of study drug and information providing by questioning 
the subject.
4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as 
partially used study drug containers, vials, and syringes may be destroyed on site.
If...
Then...
IP supplied by BMS (including its vendors)
Any unused IP supplied by BMS can only be destroyed 
after being inspected and reconciled by the responsible 
Study Monitor unless IP containers must be 
immediately destroyed as required for safety, or to 
meet local regulations (eg, cytotoxics or biologics).
If IP will be returned, the return will be arranged by the 
responsible Study Monitor.
IP sourced by site, not supplied by BMS (or its 
vendors) (examples include IP sourced from the sites 
stock or commercial supply, or a specialty pharmacy)
It is the investigator’s or designee’s responsibility to 
dispose of all containers according to the institutional 
guidelines and procedures.
It is the investigator’s or designee’s responsibility to arrange for disposal, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept. The following minimal standards must be met:

On-site disposal practices must not expose humans to risks from the drug.

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.
Revised Protocol No.: 02
Date: 13-Feb-2017
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor

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 IP provided by BMS (or its vendors). Destruction of non-IP sourced 
by the site, not supplied by BMS, is solely the responsibility of the investigator or designee.
Please refer to Section 9.2.2 for additional guidance on IP records and documentation.
4.9
Retained Samples for Bioavailability / Bioequivalence
Not applicable.
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Table 5.1-1:
Screening Procedural Outline (IM128035)a
Procedure
Screening
Visit 1
Screening
Visit 2b
Notes
Eligibility Assessments
Informed Consent
X
Inclusion/Exclusion Criteria
X
X
Medical History
X
Enroll subjects (contact Central 
Randomization System) 
X
Contact IVRS/IWRS for subject number after signing consent. If subject does not 
meet eligibility criteria, contact IVRS/IWRS to screen fail subject.
Concomitant Medication review
X
X
See Section 3.4
Hydroxychloroquine (if used) must be at a stable dose for 8 weeks prior to screening. 
Corticosteroids (if used) must be 10 mg/day for at least 14 days prior to dosing; no 
changes to other medications within 14 days of dosing.
ESSDAI
X
See Section 5.4.1
Unstimulated salivary flow
X
See Section 5.4.2.2
Anti-SSA/Ro and anti-SSB/La
autoantibody
X
Safety Assessments
Physical Examination
X
Targeted Physical Examination
X
targeted PE for steroid taper visits only (not HCQ)
Vital Signs
X
X
Height and weight
X
ECG
X
Chest X-Ray
X
Required only if not performed within 6 months of signing informed consent and/or if 
documentation of previous CXR is not on file. See Section 5.3.3.
Revised Protocol No.: 02
Date: 13-Feb-2017
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Table 5.1-1:
Screening Procedural Outline (IM128035)a
Procedure
Screening
Visit 1
Screening
Visit 2b
Notes
Safety Laboratory Tests 
X
At least 10 hour fast required prior to collection of sample. Must include complete 
blood count with differential, chemistries, liver function tests, PT/PTT, 
amylase/lipase and urinalysis.
TBNK profile
X
For subjects who have been treated with rituximab in the past. Must be reviewed for 
CD19+ B cell count > 10/l prior to dosing on Day 1.
TB Screening
X
See Section 5.3.3
HBsAg, HBcAb
X
May also include reflex HBV DNA testing where required locally
HCV antibody
X
If positive, reflex to HCV confirmation test such as PCR
HIV test
X
Performed locally or centrally per local regulations
Pregnancy Test (WOCBP only) or 
FSH (to confirm menopause)
X
Serum pregnancy test to be performed only if urine test is positive or un-interpretable, 
or if necessary as per local/institutional requirements.
Hydroxychloroquine PK sampling 
(subjects on HCQ only)
X
Subjects should bring their HCQ dose to the clinic for screening Visit 2 to be taken in 
the clinic. Serial PK sampling at 0hr, 2hr, 4hr after HCQ dosing.
a Screening window is 28 days (4 weeks), an additional 7 days (1 week) may be added if necessary; see Section 3.1 for information
b Required for any subject who requires a taper of oral corticosteroids during the screening period to 10 mg/day of prednisone (or equivalent) or any subject 
on HCQ
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Date: 13-Feb-2017
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Table 5.1-2:
Short-term Procedural Outline (IM128035)
Procedure
During Treatmenta
End of 
Trta,b
FU
#1a
FU
#2a
Notes
Day 1
(Baseline)
Day 8
(Week 1)
Day 15
(Week 2)
Day 22c
(Week 3)
Day 29
(Week 4)
Day 36c
(Week 5)
Day 43
(Week 6)
Day 50c
(Week 7)
Day 57
(Week 8)
Day 64c
(Week 9)
Day 71
(Week 10)
Day 78c
(Week 11)
Day 85
(Week 12)
Day 106
(Week 15)
Day 127
(Week 18)
Eligibility Assessments
Inclusion / 
Exclusion Criteria
X
Safety Assessments
Physical 
Examination
X
X
X
Targeted Physical 
Examination
X
X
X
X
X
X
X
See Section 5.3.4
Concomitant 
Medication Review
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECG
X
X
X
Safety Laboratory 
Tests
X
X
X
X
X
X
X
X
X
At least 10 hour fast 
required prior to 
collection of sample.
Must include complete 
blood count with 
differential, chemistry, 
liver function tests, and 
urinalysis. 
Fasting lipid panel
X
X
X
X
At least 10 hour fast 
required prior to 
collection of sample.
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Date: 13-Feb-2017
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Table 5.1-2:
Short-term Procedural Outline (IM128035)
Procedure
During Treatmenta
End of 
Trta,b
FU
#1a
FU
#2a
Notes
Day 1
(Baseline)
Day 8
(Week 1)
Day 15
(Week 2)
Day 22c
(Week 3)
Day 29
(Week 4)
Day 36c
(Week 5)
Day 43
(Week 6)
Day 50c
(Week 7)
Day 57
(Week 8)
Day 64c
(Week 9)
Day 71
(Week 10)
Day 78c
(Week 11)
Day 85
(Week 12)
Day 106
(Week 15)
Day 127
(Week 18)
Pregnancy Test 
(WOCBP only)
X
X
X
X
X
Negative pregnancy test 
must be confirmed 
within 24 hrs prior to 
dosing.
Serum pregnancy test to 
be performed only if 
urine test is positive or 
un-interpretable or if 
necessary per 
local/institutional 
requirements.
Adverse Event Assessment
Monitor for 
Non-Serious 
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Monitor for Serious 
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
All SAEs must be 
collected from the date 
of subject’s written 
consent until 42 days 
post discontinuation of 
dosing or completion of 
subject’s participation in 
the study if the last 
scheduled visit occurs at 
a later time.
Revised Protocol No.: 02
Date: 13-Feb-2017
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Table 5.1-2:
Short-term Procedural Outline (IM128035)
Procedure
During Treatmenta
End of 
Trta,b
FU
#1a
FU
#2a
Notes
Day 1
(Baseline)
Day 8
(Week 1)
Day 15
(Week 2)
Day 22c
(Week 3)
Day 29
(Week 4)
Day 36c
(Week 5)
Day 43
(Week 6)
Day 50c
(Week 7)
Day 57
(Week 8)
Day 64c
(Week 9)
Day 71
(Week 10)
Day 78c
(Week 11)
Day 85
(Week 12)
Day 106
(Week 15)
Day 127
(Week 18)
Biomarker Assessments
Target Engagement 
/ Receptor 
Occupancy
X
X
X
X
See Section 5.6
Clinical Biomarkers
X
X
X
X
X
Includes ANA, IgM RF, 
SSA, SSB, Complement 
(CH50, C3, C4), 
Immunoglobulins (IgG, 
IgA, IgM), B2M, ESR, 
hsCRP and soluble free 
light chains
See Section 5.6
Whole Blood RNA 
X
X
X
See Section 5.6
Whole Blood 
Immuno-
phenotyping
X
X
X
See Section 5.6
Serum Biomarkers
X
X
X
X
See Section 5.6
Salivary 
Biomarkers
X
X
X
X
See Section 5.6
PBMC Collection
X
X
X
X
See Section 5.6
Revised Protocol No.: 02
Date: 13-Feb-2017
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Table 5.1-2:
Short-term Procedural Outline (IM128035)
Procedure
During Treatmenta
End of 
Trta,b
FU
#1a
FU
#2a
Notes
Day 1
(Baseline)
Day 8
(Week 1)
Day 15
(Week 2)
Day 22c
(Week 3)
Day 29
(Week 4)
Day 36c
(Week 5)
Day 43
(Week 6)
Day 50c
(Week 7)
Day 57
(Week 8)
Day 64c
(Week 9)
Day 71
(Week 10)
Day 78c
(Week 11)
Day 85
(Week 12)
Day 106
(Week 15)
Day 127
(Week 18)
Optional Lip or 
Parotid Salivary 
Gland Biopsy with 
Salivary Gland 
RNA collectiond
X
X
Lip or parotid salivary 
gland biopsy may be 
performed but same type 
must be performed at 
each timepoint.
See Section 5.4.3
PK Assessments
PK sampling for 
lulizumab/
BMS-986142
X
X
X
X
X
X
X
X
Subjects should bring 
their BMS-986142 dose 
to every clinic visit.
See Section 5.5
PK sampling for 
hydroxychloroquine
X
X
X
X
X
X
X
See Section 5.5. Subjects 
should bring their HCQ 
dose to the clinic on PK 
sampling days. Serial PK 
sampling at 0hr, 2hr, 4hr 
on Day 8.
Immunogenicity
X
X
X
X
X
See Section 5.8.1
Efficacy Assessments
ESSDAI
X
X
X
X
X
X
X
X
See Section 5.4.1.
ESSPRI
X
X
X
X
X
X
X
X
See Section 5.7
Schirmer’s Teste
X
X
X
X
See Section 5.4.2.1
Ocular Surface 
X
X
X
X
See Section 5.4.2.1
Revised Protocol No.: 02
Date: 13-Feb-2017
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Table 5.1-2:
Short-term Procedural Outline (IM128035)
Procedure
During Treatmenta
End of 
Trta,b
FU
#1a
FU
#2a
Notes
Day 1
(Baseline)
Day 8
(Week 1)
Day 15
(Week 2)
Day 22c
(Week 3)
Day 29
(Week 4)
Day 36c
(Week 5)
Day 43
(Week 6)
Day 50c
(Week 7)
Day 57
(Week 8)
Day 64c
(Week 9)
Day 71
(Week 10)
Day 78c
(Week 11)
Day 85
(Week 12)
Day 106
(Week 15)
Day 127
(Week 18)
Staininge
Tear Break-up Time 
Teste
X
X
X
X
See Section 5.4.2.1
Unstimulated and 
Stimulated Salivary 
Flow
X
X
X
X
Subjects should refrain 
from eating/drinking for 
90 min prior to tests. 
Specimens should be 
retained in separate 
containers for biomarker 
analysis.
See Section 5.4.2.2
Sicca symptoms 
Numeric Rating 
Scales (NRS) 
X
X
X
X
X
X
X
X
Oral, ocular & vaginal 
dryness scales.
See Section 5.7
phyGDA 
X
X
X
X
X
X
X
X
See Section 5.7
subGDA 
X
X
X
X
X
X
X
X
See Section 5.7
PROMIS Fatigue 
SF
X
X
X
X
X
See Section 5.7
SF-36 (acute)
X
X
X
X
X
See Section 5.7
Female Sexual 
Function Index 
(FSFI)
X
X
X
X
X
See Section 5.7
Work Participation 
X
X
X
X
X
See Section 5.7
Revised Protocol No.: 02
Date: 13-Feb-2017
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Table 5.1-2:
Short-term Procedural Outline (IM128035)
Procedure
During Treatmenta
End of 
Trta,b
FU
#1a
FU
#2a
Notes
Day 1
(Baseline)
Day 8
(Week 1)
Day 15
(Week 2)
Day 22c
(Week 3)
Day 29
(Week 4)
Day 36c
(Week 5)
Day 43
(Week 6)
Day 50c
(Week 7)
Day 57
(Week 8)
Day 64c
(Week 9)
Day 71
(Week 10)
Day 78c
(Week 11)
Day 85
(Week 12)
Day 106
(Week 15)
Day 127
(Week 18)
and Activity 
Impairment 
Questionnaire 
(WPAI) 
Study Drug
Randomize through 
IVRS/IWRS system
X
Dispense supplies 
of BMS-986142 or 
matched placebo for 
home 
administration
X
X
X
X
X
X
Daily dosing of 
BMS-986142 or matched 
placebo at home or in the 
clinic. Subject should 
bring dose to the clinic 
to be administered at the 
site on study visit days.
Dosing of 
subcutaneous 
lulizumab or 
matched placebo
X
X
X
X
X
X
X
X
X
X
X
X
Subjects should be 
observed in the clinic for 
2 hours after dosing on 
Day 1, then 1 hour after 
dosing for subsequent 
doses.
Reconciliation of 
oral Study 
Medication
(BMS-986142 or 
matched placebo)
X
X
X
X
X
X
X
Revised Protocol No.: 02
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
a Visit window of 3 days
b All procedures scheduled for the End of Week 12/End of treatment visit should be performed at the time of actual discontinuation/end of treatment.
c May be a home visit conducted by visiting health care professional if approved by IRB and investigator. If visit is a home visit, the subject’s signs and 
symptoms will be assessed.
d Biopsy procedure window of 5 days (5 days prior to dosing only for Day 1/baseline biopsy)
e Ophthalmologic procedure window of 5 days (5 days prior to dosing only for Day 1/baseline assessments), all assessments must be performed at same visit
In the event multiple assessments are required at the same study visit, the assessments should be performed in the following order 
whenever possible:
1) Disease activity assessments (eg, ESSDAI, ESSPRI, symptom scales)
2) Vital signs, physical exams, ECGs
3) Salivary flow assessments
4) Blood draws for safety labs, pre-dose PK assessments and biomarker assessments
5) Administration of study medication(s) and HCQ (if applicable)
6) Post-dose PK assessments (if applicable)
7) Ophthalmologic assessments (if performed on the same visit day)
8) Optional lip or parotid salivary gland biopsy
Revised Protocol No.: 02
Date: 13-Feb-2017
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
5.1.1
Retesting During Screening or Lead-in Period
Retesting of laboratory parameters and/or other assessments within any single Screening or 
Lead-in period will be permitted (in addition to any parameters that require a confirmatory 
value).
Any new result will override the previous result (ie, the most current result prior to 
Randomization) and is the value by which study inclusion will be assessed, as it represents the 
subject’s most current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified subjects. Consultation 
with the BMS Medical Monitor may be needed to identify whether repeat testing of any
particular parameter is clinically relevant.
5.2
Study Materials
The site will provide all required materials for the tests performed locally (ie, relevant clinical 
laboratory tests). The site will have available a well-calibrated scale(s) and/or balance(s) for 
recording body weight and weight of the pre- and post-salivary flow collection tubes and 
moistened gauze (if using), a 12-lead ECG machine, and a calibrated sphygmomanometer and 
thermometer for vital signs assessments. The site will have urine collection containers, a 
refrigerated centrifuge, a heating block, a monitored and alarmed refrigerator, and freezer (-20°C 
or below), as well as containers and dry ice for shipment and storage of blood and urine samples. 
The site will provide all materials required for accurate source documentation of study activities.
Subjects will be provided with cooler bags and gel packs for transporting BMS-986142/matched 
placebo as it needs to be kept refrigerated.
BMS will provide a BMS-approved protocol and any amendments or administrative letters 
(if required), and IBs. Case report forms (electronic or hard copy) will be provided by BMS. 
Ten centimeter rulers will be provided by BMS for measurement of the Physician and Subject’s 
Global Assessment of disease activity on the Case Report Form.
All Investigator sites within this study will use an Electronic Data Capture (EDC) tool to submit 
study data to BMS. Electronic Case Report Forms (eCRFs) will be prepared for all data 
collection fields at Investigator sites, except for fields specific to Pregnancy Forms. Pregnancy 
Forms will be submitted to BMS using paper CRFs. Subject ESSPRI, Subject Global 
Assessment of disease activity worksheet, sicca symptoms NRS scales, fatigue, sexual function, 
and quality of life questionnaires will be completed by the subject and the information will then 
be entered with the EDC tool by the investigational site staff. ESSDAI and Physician Global 
Assessment of disease activity worksheet will be completed by the investigator and will then be 
entered with the EDC tool. Subject completed scales and questionnaires will be retained at the 
investigational site.  Examples of the worksheets, scales and questionnaires that BMS will 
provide are included in Appendices 3 - 13, however the country specific translations may include 
slight customizations as per local requirements (eg, removal of the BMS logo).  Translation 
certificates are available upon request.
Revised Protocol No.: 02
Date: 13-Feb-2017
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Clinical Protocol
IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Study supplies and documents (eg, electronic Case Reports Forms, patient drug logs, etc.) will be 
provided to the study center by BMS. Urine pregnancy test kits, laboratory specimen collection 
kits and instructions for collection will be provided by central laboratory vendor. IVRS/IWRS
worksheets and instruction manuals will be provided by the IVRS/IWRS vendor.
5.3
Safety Assessments
All subjects who receive at least one dose of study medication will be evaluated for safety 
parameters. Additionally, any occurrence of an SAE from the time of consent until 42 days 
post-discontinuation of study drug dosing will be documented. Any occurrence of non-serious 
AEs will be collected from first dose of study drug until 42 days post discontinuation of dosing.
Safety assessments include the following:

Adverse Events

Safety laboratory tests

Physical examination

Vital signs

ECGs
On Day 1, the results of all assessments must be reviewed to assure that eligibility requirements 
are met before contacting the Central Randomization System for the subject’s randomization 
assignment. All assessments should be performed or administered prior to study drug 
administration unless otherwise indicated. Furthermore, patient scales, questionnaires and 
disease activity assessments (ie, ESSPRI, fatigue, quality of life and VAS/NRS scales) must be 
performed prior to all other assessments. Every effort must be made to ensure the same evaluator 
will complete the assessments for each subject at all visits.
After completion of patient scales, questionnaires and disease activity assessments, vital signs 
collection (blood pressure, heart rate, respiration rate, temperature), physical exams (when 
applicable), ECGs (when applicable), salivary flow assessments (when applicable), safety 
laboratory assessments, and pre-dose PK and laboratory biomarker assessments will occur before
the first dose of study medication is given from the assigned kit. At subsequent visits, this same 
order of assessments should be followed prior to the administration of the dose of assigned study 
drug. Subjects will be observed at the site for a minimum of 2 hours after receiving their first 
dose of study medication (tablet and injections) on Day 1. The observation period should be 
extended if clinically indicated. At subsequent visits subjects should be observed for 1 hour post-
injection.
Subjects who discontinue from the double-blind treatment period should have “End of Treatment 
Visit” procedures performed and should return to the clinical for the “Follow-Up Visits” 
approximately 21 and 42 days after the “End of Treatment Visit”. All procedures required for 
these visits should be completed as well as collection of concomitant medication information.
Only data for the procedures and assessments specified in this protocol should be submitted to 
BMS on a case report form. Additional procedures and assessments may be performed as part of 
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your institutional or medical practice standard of care; however, data for these assessments 
should remain in the subject’s medical record and should not be provided to BMS, unless 
specifically requested from the sponsor.
Safety assessments will be based on medical review of adverse event reports and the results of 
vital sign measurements, ECGs, physical examinations, and clinical laboratory tests. The severity 
of observed adverse events will be graded by National Cancer Institute’s Common Terminology 
Criteria for Adverse Events (NCI CTCAE) version 4.03. The incidence of observed adverse 
events will be tabulated and reviewed for potential significance and clinical importance.
Ongoing assessment of safety will be performed by an independent Data Monitoring Committee 
(DMC). The DMC may make recommendations to the Sponsor regarding conduct of the study 
based on safety observations.
5.3.1
Imaging Assessment for the Study
Not Applicable.
5.3.2
Laboratory Testing
A central/local laboratory will perform the analyses and will provide reference ranges for these 
tests.
All scheduled, routine safety laboratory testing should be performed after a minimum 10 hour 
fast. Detailed instructions on the collection, processing, and shipping of all blood and urine 
samples will be provided to the investigator in a separate manual at or before the time of study 
initiation.
The following clinical laboratory tests will be performed:
Hematology
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
TBNK for CD19+ B cell count (screening only, for subjects with prior rituximab use)
PT/PTT (screening only)
Serum Chemistry
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Total bilirubin
Direct bilirubin
Alkaline phosphatase
Lactate dehydrogenase (LDH)
Creatinine
Blood Urea Nitrogen (BUN)
Uric acid
Fasting glucose
Lipase (screening only)
Total Protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatine kinase
Amylase (screening only)
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Fasting lipid panel: total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides (Day 1, Week 8,
Week 12 and Follow-Up Week 18 only)
ESR (local test)
hsCRP
Urinalysis
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Reflex to microscopic examination of the sediment if blood, protein or leukocytes esterase are positive on 
the dipstick
Spot urine protein/creatinine ratio [UPCR] (screening only, in subjects with clinical suspicion of nephrotic 
syndrome or clinically significant protein on urinalysis)
Serology
Serum for hepatitis C antibody, hepatitis B surface antigen, hepatitis B core antibody (screening only)
HIV testing (screening only, may be performed locally or via central lab per local requirements)
Auto-immune serology: ANA, Anti-SSA/Ro, Anti-SSB/La, Rheumatoid Factor
Immunoglobulin levels: IgM, IgA, and IgG
Complement levels (C3, C4, CH50)
Other Analyses
IGRA/TB Test
Pregnancy test (WOCBP only; urine test, serum test only to be performed if urine test is positive or un-
interpretable, or if necessary as per local/institutional requirements).
Follicle stimulating hormone (FSH): (screening only, for post-menopausal women only, see Section 3.3.3) 
Results of all laboratory tests required by this protocol must be provided to BMS, either recorded 
on the laboratory pages of the CRF or by another mechanism as agreed upon between the 
investigator and BMS (eg, provided electronically). If the units of a test result differ from those 
printed on the CRF, the recorded laboratory values must specify the correct units. Any abnormal 
laboratory test result considered clinically significant by the investigator must be recorded on the 
appropriate AE page of the CRF (see Section 6.1.1).
5.3.3
Tuberculosis Screening
A chest x-ray (CXR) and physical examination (PE) are considered part of the process to assess a 
subject’s eligibility as outlined in Section 3.3.2.
CXR at the screening visit is required if not already performed within 6 months of obtaining 
written informed consent or if documentation of the X-ray result is not on file.
In addition to a complete physical examination and medical history to evaluate exposure to 
tuberculosis, all subjects will have a screening test, an interferon gamma release assay [(IGRA) 
eg, QuantiFERON TB Gold®], preferably performed centrally. T-Spot® testing (if available) 
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may be used as a reflex test in the event of an indeterminate result of the QuantiFERON TB 
Gold® test. If unable to obtain central lab results (eg, repeated test due to indeterminate result), 
an IGRA test could be obtained locally, after consultation with the BMS Medical Monitor.
Indeterminate tests may be repeated once in an effort to obtain a definitive negative or positive 
result. If two indeterminate tests are recorded subject should be excluded from study 
participation.
Subjects with a positive screening test will not be eligible for the study unless they can provide 
documentation of completion of approved treatment for latent TB prior to dosing of study drug, 
and the subject has a negative chest X-ray done at screening that reveals no evidence of 
active TB.
5.3.4
Physical Exams
A complete medical history and physical exam will be obtained at the screening visit.
Complete and/or targeted/interim physical examinations may be performed by a Doctor of 
Medicine (MD), Doctor of Osteopathy (DO), Physician’s Assistant (PA), or Nurse Practitioner 
(NP). While the targeted/interim physical examination may not be as comprehensive as the initial 
full examination, key aspects of the targeted/interim examination should evaluate important body 
systems as clinically indicated. These body systems include at a minimum, the heart, lungs, 
abdomen, lymph nodes and skin. Evaluation of liver, spleen, breast and other body systems is at 
the discretion of the examiner. A targeted/interim 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 body systems as clinically indicated.
Every effort should be made to ensure the same evaluator will complete the physical examination 
for each subject at specified visits throughout the study. Documentation of who performed the 
examination is to be recorded in source notes.
5.3.5
Electrocardiograms
A standard 12-lead ECG will be recorded at the times noted in the Time and Events Table 5.1-1
and Table 5.1-2.
5.4
Efficacy Assessments
All assessments should be performed prior to dosing.
5.4.1
Primary Efficacy Assessment
The primary efficacy endpoint is change from baseline ESSDAI score at Week 12. The EULAR 
Sjögren’s Syndrome Disease Activity Index (ESSDAI) is a systemic disease activity index that 
was designed to measure disease activity in subjects with pSS (see Appendix 3).63 The ESSDAI 
is now frequently used as a primary endpoint to measure disease activity in clinical studies. BMS 
will provide the appropriate versions of the assessment scale for use by the site. Sites should only 
use the versions of the scale provided by BMS for this study. Investigators should assess the 
ESSDAI parameters as described by Seror et al.64 The ESSDAI will be completed at the visits 
noted in the Time and Events Table 5.1-1 and Table 5.1-2. Results from each assessment will be 
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recorded in site source records as well as entered into the corresponding eCRF provided by BMS 
or designee.
5.4.2
Secondary Efficacy Assessments
5.4.2.1
Ophthalmologic Assessments
The following procedures should be performed at baseline/Day 1, Week 4, Week 8, and Week 12
by an ophthalmologist or optometrist experienced in the diagnosis and treatment of Sjögren’s 
syndrome subjects and according to the methods described in Whitcher, et al.65 A visit window 
of 5 days to perform the ophthalmologic assessments is acceptable (baseline/Day 1 assessment 
can be performed up to 5 days prior to dosing only), but all assessments must be performed 
during the same visit. The use of alternative ocular dyes may be permitted per local standards 
and/or regulations, and after consultation with the BMS Medical Monitor.

Schirmer’s test: The test (without anaesthesia) is performed by placing a narrow calibrated 
filter-paper strip in the inferior cul-de-sac of each eye. Aqueous tear production is measured 
by the length in millimeters that the strip wets during the 5 minute test period

Tear break-up time (TBUT): Determined by instilling fluorescein dye and evaluating the 
stability of the pre-corneal tear film. After several blinks, the tear film is examined using a 
broad beam of the slit-lamp (biomicroscope) with a cobalt blue filter. The TBUT, defined as 
the time in seconds between the subjects’s last blink and the first appearance of a random dry 
spot on the corneal surface, is measured 3 times and the mean value is recorded

Ocular surface staining: The test is performed by instillation of fluorescein dye and either 
lissamine green or Rose bengal dye to stain the cornea and conjunctiva, respectively. After 
instilling the dye, the ocular surface is examined through a slit lamp (biomicroscope) the 
staining pattern is recorded per the method described in Whitcher, et al65
The results from each of the above procedures will be recorded in site source records as well as 
entered into the corresponding eCRF provided by BMS or designee.
5.4.2.2
Salivary Flow
Whole unstimulated and stimulated salivary flow will be assessed at Screening (unstimulated 
only), baseline/Day 1, Week 4, Week 8, and Week 12. Subjects should refrain from eating or 
drinking for at least 90 minutes prior to the test procedures. Any saliva collected should be 
transferred to the appropriate container containing protease inhibitor cocktail, including notation 
as to whether it is a stimulated or unstimulated sample, for saliva biomarker assessments on 
Days 1, 29, 57 and 85 (see Section 5.6). Stimulated and unstimulated samples must not be 
combined or pooled into a single collection container.

Unstimulated salivary flow: Subjects should sit quietly, without talking or chewing, and spit 
any saliva that accumulates in the floor of the mouth during a period of 5 minutes into a 
pre-weighed tube

Stimulated whole salivary flow: Subjects should chew on a piece of paraffin (wax) or (sites 
accustomed to using pre-weighed, moistened gauze as the stimulant may continue to use this 
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method, although it is not preferred due to the potential retention/loss of the saliva sample for 
biomarker testing within the gauze) for 10 minutes, during which the accumulated saliva is 
measured by spitting into a pre-weighed tube (and/or by weight of the chewed gauze, if 
applicable).
The results from each of the above procedures will be recorded in site source records as well as 
entered into the corresponding eCRF provided by BMS or designee.
 
 
 
 
 
 
 
 
 
 
5.4.4
Clinical Assessor Requirements
The ESSDAI, and the Physicians Global Assessment of Disease Activity (phyGDA) can be 
performed by the investigator or sub-investigator. The sub-investigator may be a Doctor of 
Medicine (MD) or Doctor of Osteopathy (DO), Physician’s Assistant (PA) or Nurse Practitioner 
(NP). The below requirements also pertain to the ophthalmologic procedures (refer to 
Section 5.4.2).
For each assessment: 1) Every effort should be made to ensure the same assessor is used for a 
given subject throughout the study, and 2) The clinical assessor cannot be unblinded to study 
medication assignment or the subject.
Visits should be scheduled with the availability of the assessor taken into account. If the assessor 
is unable to complete the evaluation, then another qualified individual can take the place of the 
initial evaluator, as long as the restrictions, described above, are still met and all efforts are made 
to assure consistency between subject evaluations.
5.5
Pharmacokinetic Assessments
Pharmacokinetics of lulizumab and BMS-986142 will be derived from plasma/serum 
concentration versus time. The pharmacokinetic parameters to be assessed include Ctrough 
(ng/mL).
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The serum samples from subjects dosed with lulizumab will be analyzed for lulizumab by a 
validated LC-MS/MS assay. The plasma samples from subjects dosed with BMS-986142 will be 
analyzed for BMS-986142 by a validated LC-MS/MS assay. 
Pharmacokinetic samples collected from a subject who received placebo only for both drugs will 
not be analyzed. In addition, serum or plasma samples will be archived for potential exposure 
biomarker response analysis, if the need arises and to the extent possible.
Individual subject PK parameter values will be derived by non-compartmental methods by a 
validated PK analysis program. Actual times will be used for the analyses.
Table 5.5-1 lists the sampling schedule to be followed for the assessment of PK for subjects who 
are not on hydroxychloroquine (HCQ, Plaquenil). Further details of blood collection and 
processing will be provided to the site in the procedure manual.
On Day 1 and Day 8, it is important that the SC dose and oral dose are given to the subjects at 
the same time to make sure the PK samples are taken at the planned hours relative to dosing.
Table 5.5-1:
Lulizumab and BMS-986142 Pharmacokinetic(PK) and 
Immunogenicity(IMG) Sampling Schedule for Subjects NOT 
on Plaquenil
Study Day
Time 
(Relative to Dosing)
Hour
Time 
(Relative to Dosing)
Hour: Min
PK
Blood Sample
IMG 
Sample
1
Predose
00:00
X
X
1
2:00
Xa
8
Predose
00:00
X
8
2:00
Xa
15
Predose
00:00
X
29
Predose
00:00
X
X
57
Predose
00:00
X
85/End of Treatment 
(EOT)
168:00 for 
Lulizumab & 
Predose sample for 
BMS-986142
X
X
Follow up Day 21 after 
EOT
(Day 106)
672:00 for 
Lulizumab & 504:00 
for BMS-986142
X
X
Follow up Day 42 after 
EOT
(Day 127)
1176:00 for 
Lulizumab & 
1008:00 for 
BMS-986142
X
X
AE leading to 
discontinuationb
X
X
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a Only one tube of plasma sample will be taken. This sample is intended to evaluate BMS-986142 PK.
b PK and immunogenicity samples to be drawn for subjects who experience an AE leading to discontinuation of 
study treatment.
For each PK blood draw, one tube for serum sample and one tube for plasma sample will be 
taken.
Table 5.5-2 lists the sampling schedule to be followed for the assessment of PK for subjects who 
are on a stable dose of hydroxychloroquine (HCQ, Plaquenil). Serial blood PK samples of 
HCQ will be taken during Screening (subjects taking HCQ who have met all entry criteria must 
return for Screening Visit #2 for this collection), on Day 8 and Day 29 in addition to lulizumab 
and BMS-986142 blood PK samples. 
For sampling time points that only lulizumab and BMS-986142 PK samples are collected, one 
tube for serum sample and one tube for plasma sample will be taken.
For sampling time points that both lulizumab/BMS-986142 and HCQ PK samples are collected, 
one tube for serum sample, one tube for plasma sample and one tube for HCQ whole blood 
sample will be taken. Except for the 2 and 4 hours samples on Day 8, only one plasma tube 
sample for BMS-986142 and one whole blood tube for HCQ will be taken.
Trough level HCQ blood PK samples will be taken on Day 1, Day 15, Day 29, Day 85 and at the 
two follow-up visits on Days 106 and 127 (Table 5.5-2). Subjects should bring their daily dose of 
HCQ to the clinical site on these days to be administered at the site.
On Day 8, it is important that the dosing of study drug (a SC injection and an oral dose) and the 
HCQ are given to the subjects at the same time to make sure the PK samples are taken at the 
planned hours relative to dosing. 
Pharmacokinetics of HCQ will be derived from whole blood concentration versus time. The 
pharmacokinetic parameters to be assessed include Cmax, and AUC (0-4h) at Screening
(Visit #2) and Day 8. Ctrough will be assessed on screening day, Day 1, Day 8, Day 15, Day 29,
and at the two follow-up visits on Days 106 and 127.
Table 5.5-2:
Lulizumab, BMS-986142, and HCQ Pharmacokinetic and 
Immunogenicity Sampling Schedule for Subjects on Plaquenil®
Study Day
Time 
(Relative Oral 
Dosing of 
HCQ)
Hour
Time 
(Relative to 
Dosing)
Hour: Min
HCQ PK
Blood Sample
BMS-986142 and 
Lulizumab
PK Blood Sample
IMG 
Sample
Screening
(Visit #2)
Predose
00:00
X
Screening
(Visit #2)
2:00
X
Screening
4:00
X
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Table 5.5-2:
Lulizumab, BMS-986142, and HCQ Pharmacokinetic and 
Immunogenicity Sampling Schedule for Subjects on Plaquenil®
Study Day
Time 
(Relative Oral 
Dosing of 
HCQ)
Hour
Time 
(Relative to 
Dosing)
Hour: Min
HCQ PK
Blood Sample
BMS-986142 and 
Lulizumab
PK Blood Sample
IMG 
Sample
(Visit #2)
1
Predose
00:00
X
X
X
1
02:00
Xa
8
Predose
00:00
X
X
8
2:00
X
Xa
8
4:00
X
Xa
15
Predose
00:00
X
X
29
Predose
00:00
X
X
X
57
Predose
0:00
X
85/End of 
Treatment of 
Lulizumab and 
BMS-986142
(EOT)
Predose
00:00
X
X
X
Follow up Day 21 
after EOT
(Day 106)
Predose
00:00
X
X
X
Follow up Day 42 
after EOT
(Day 127)
Predose
00:00
X
X
X
AE leading to 
discontinuationb
X
X
X
a Only one tube of plasma sample will be taken. This sample is intended to evaluate BMS-986142 PK.
b PK samples to be drawn for subjects who experience an AE leading to discontinuation of study treatment.
The whole blood samples will be analyzed for HCQ by a validated LC-MS/MS assay. Cmax, 
AUC (0-4), and Ctrough will be compared within the same subjects among screening, Day 8, and 
Day 29.
 
 
 
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Table 5.6-1:
 
 
 
 
 
 
5.6.1
Additional Research
This protocol will include residual sample storage for additional research (AR).
For All US sites:
Additional research is required for all study participants, except where prohibited by IRBs/ethics 
committees, or academic/institutional requirements. Where one or more of these exceptions 
occurs, participation in the additional research should be encouraged but will not be a condition 
of overall study participation. 

If the IRB/ethics committees and site agree to the mandatory additional research retention 
and/or collection, then the study participant must agree to the mandatory additional research 
as a requirement for inclusion in the study.

If optional participation is permitted and approved, then the study participants may opt out of 
the additional research retention and/or collection.
For non-US Sites:
Additional research is optional for all study participants, except where retention and/or collection 
is prohibited by local laws or regulations, ethics committees, or institutional requirements. 
This collection for additional research is intended to expand the translational R&D capability at 
Bristol-Myers Squibb, and will support as yet undefined research aims that will advance our 
understanding of disease and options for treatment. It may also be used to support health 
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authority requests for analysis, and advancement of pharmacodiagnostic development to better 
target drugs to the right patients.  This may also include genetic/genomic exploration aimed at 
exploring disease pathways, progression and response to treatment etc.
Sample Collection and Storage
All requests for access to samples or data for additional research will be vetted through a diverse 
committee of the study sponsor’s senior leaders in Research and Development (or designee) to 
ensure the research supports appropriate and well-defined scientific research activities.

Residual samples from biomarker, biopsy and PK sample collections (see Table 5.6.1-1) will 
also be retained for additional research purposes
Samples kept for future research will be stored at the BMS Biorepository in NJ, USA or an 
independent, BMS-approved storage vendor.

The manager of these samples will ensure they are properly used throughout their usable life 
and will destroy the samples at the end of the scheduled storage period, no longer than fifteen 
(15) years after the end of the study or the maximum allowed by applicable law.

Transfers of samples by research sponsor to third parties will be subject to the recipient’s 
agreement to establish similar storage procedures.
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the Investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual.
Further details of sample collection and processing will be provided to the site in the procedure 
manual.
Table 5.6.1-1:
Residual Sample Retention for Additional 
Research Schedule
Sample Type
Timepoints for which residual samples will be retained
PK
All
Whole Blood
All
Blood RNA  
All
PBMCs
All
Serum
All
Saliva
All
Biopsy
All
Biopsy RNA
All
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5.7
Outcomes Research Assessments
Questionnaires and investigator/subject assessments will be completed, prior to study drug 
administration, on either paper forms or an electronic tablet (ePRO) and information gathered on 
this device will serve as the source document where possible. BMS will provide the appropriate 
versions of the assessment scales for use by the site. Sites should only use the versions of the 
scales provided by BMS for this study.
The following additional symptom scales and patient reported outcome measures will be 
collected:
Completed by Investigator (at baseline/Day 1 and Days 15, 29, 43, 57, 71, 85, and Follow-up 
Day 127):

Physician global assessment of disease activity (phyGDA, See Appendix 6)
Completed by subject (at baseline/Day 1 and Days 15, 29, 43, 57, 71, 85, and Follow-up 
Day 127):

ESSPRI (see Appendix 4)

Numeric rating scales (see Appendices 7, 8, and 9) for ocular, oral and vaginal dryness
(females only)

Subject global assessment of disease activity (SubGDA, See Appendix 5)
Completed by subject (at baseline/Day 1 and Days 29, 57, 85, and Follow-up Day 127)

PROMIS Fatigue Short Form (see Appendix 10)

Female Sexual Function Index (FSFI, see Appendix 11)

Short Form-36 acute (SF-36 acute, see Appendix 12)

Work Participation Activity Index (WPAI, see Appendix 13)
 
 
 
 
 
6
ADVERSE EVENTS
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 
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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. Severity of all adverse events will be graded by using the National Cancer Institute’s 
Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
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.
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs).
Sponsor or designee will be reporting adverse events to regulatory authorities and ethics 
committees according to local applicable laws including European Directive 2001/20/EC and 
FDA Code of Federal Regulations 21 CFR Parts 312 and 320.
6.1
Serious Adverse Events
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: 

results in death

is life-threatening (defined as an event 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)

results in persistent or significant disability/incapacity

is a congenital anomaly/birth defect

is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [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 6.6 for the definition of potential DILI.)
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Suspected transmission of an infectious agent (eg, pathogenic or nonpathogenic) via the study 
drug 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 6.1.1 for reporting pregnancies).
Any component of a study endpoint that is considered related to study therapy (eg, death is an 
endpoint, if death occurred due to anaphylaxis, anaphylaxis must be reported) should be reported 
as SAE (see Section 6.1.1 for reporting details).
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 

a visit to the emergency room or other hospital department < 24 hours, that does not result in 
admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status 
(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)
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the Investigator Brochures (IBs) represent the Reference Safety 
Information to determine expectedness of serious adverse events for expedited reporting. 
Following the subject’s written consent to participate in the study, all SAEs, whether related or 
not related to study drug, must be collected, including those thought to be associated with 
protocol-specified procedures. All SAEs must be collected that occur during the screening period 
from the date of subject’s written consent until 42 days post discontinuation of dosing.
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure.
An SAE report must be completed for any event where doubt exists regarding its seriousness.
If the investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship must be specified in the narrative section of the SAE Report Form.
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SAEs, whether related or not related to study drug, and pregnancies must be reported to BMS 
(or designee) within 24 hours of awareness of the event. SAEs must be recorded on the SAE 
Report Form; pregnancies on a Pregnancy Surveillance Form (electronic or paper forms).
The preferred method for SAE data reporting collection is through the eCRF. The paper 
SAE/pregnancy surveillance forms are only intended as a back-up option when the eCRF system 
is not functioning. In this case, the paper forms are to be transmitted via email or confirmed 
facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. In the event the electronic system is unavailable for transmission, 
paper forms must be used and submitted immediately. When paper forms are used, the original 
paper forms are to remain on site.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact
Information list.
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.
BMS will be reporting adverse events to regulatory authorities and ethics committees according 
to local applicable laws including European Directive 2001/20/EC and FDA Code of Federal 
Regulations 21 CFR Parts 312 and 320. A SUSAR (Suspected, Unexpected Serious Adverse 
Reaction) is a subset of SAEs and will be reported to the appropriate regulatory authorities and 
investigators following local and global guidelines and requirements.
6.2
Nonserious Adverse Events
A nonserious adverse event is an AE not classified as serious.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. Nonserious 
AE information should also be collected from the start of a placebo lead-in period or other 
observational period intended to establish a baseline status for the subjects.
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment 
as appropriate. All identified nonserious AEs must be recorded and described on the nonserious 
AE page of the CRF (paper or electronic). 
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Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (electronic) as appropriate. Paper forms are only intended as a 
back-up 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 drug 
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).
6.4
Pregnancy
If, following initiation of the study drug, it is subsequently discovered that a study subject is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half-lives after product administration (35 days for lulizumab), the investigator must 
immediately notify the BMS 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 Section 6.1.1.
In most cases, the study drug will be permanently discontinued in an appropriate manner 
(eg, dose tapering if necessary for subject safety). Please call the BMS Medical Monitor or 
designee within 24 hours of awareness of the pregnancy.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form. In 
order for BMS to collect any pregnancy surveillance information from the female partner, the 
female partner must sign an informed consent form for disclosure of this information. 
Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important. All occurrences of overdose must be 
reported as an SAE (see Section 6.1.1 for reporting details).
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6.6
Potential Drug Induced Liver Injury (DILI)
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 Section 6.1.1 for reporting details).
Potential drug induced liver injury is defined as:
1. AT (ALT or AST) elevation > 3 times upper limit of normal (ULN)
AND
2. Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase)
AND
3. No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic
6.7
Other Safety Considerations
Any 
significant 
worsening 
noted 
during 
interim 
or 
final 
physical 
examinations, 
electrocardiogram (ECG), x-ray filming, any other potential safety assessment required or not 
required by protocol should also be recorded as a nonserious or serious AE, as appropriate, and 
reported accordingly.
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
A Data Monitoring Committee (DMC) will monitor overall safety data regularly to ensure that 
the benefits and risks of study participation remain acceptable. Based on the regular reviews of 
emerging data, the DMC may recommend to the Sponsor alteration and/or termination of the 
trial or a treatment group, or cessation of further enrollment into a treatment group.
Data summaries and listings will be provided to the DMC to facilitate their safety assessment at 
the regularly scheduled times as well as on an ad hoc basis if needed. The DMC will review 
safety data including SAEs and events of special interest, focusing on early signal detection. 
Further details on the frequency, content, and methods of data reports to the DMC will be 
outlined in the Charter of that Committee along with the processes and procedures the committee 
will follow.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
The sample size calculation is based on the power to compare change from baseline in ESSDAI 
at Week 12 between active treatment arms (lulizumab or BMS-986142) and the placebo arm. 
With a two-sided two-sample t-test at significance level 0.05, data from 25 treated subjects per 
arm will provide approximately 90% power to detect a placebo-adjusted 3-point decrease from 
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baseline for each active treatment group, assuming common standard deviations of 3.2.66 In 
addition, the Hochberg’s step-up procedure will be used to adjust the multiplicity due to the 
comparison of two active treatment arms (lulizumab or BMS-986142) to the placebo arm. 
The primary efficacy analysis will be conducted on all randomized subjects who received at least 
one dose of study drug.
An interim analysis will be conducted after at least 30 subjects reach Week 12 (complete 
12 weeks of treatment) and complete the specified assessments for ESSDAI. The interim 
analysis will be conducted in a fully blinded manner such that treatment group assignments of 
study subjects are not known and are not used in any manner in the analysis. A blinded 
examination of the variance of the primary endpoint will be performed and compared to the 
assumption used in planning the study. If this comparison suggests the initial assumption was 
substantially too low, the total study sample size may be increased by up to 45 additional 
subjects (ie, to a maximum of 120 subjects in total) to maintain adequate study power.67,68,69
Regardless of the outcome from the blinded examination of variability, the study sample size 
will not be decreased. A maximum study sample size of 120 subjects in total, ie, 40 subjects per 
arm, can provide each active treatment arm 79% power to detect a placebo-adjusted 3-point 
decrease from baseline for common standard deviations as large as 4.8, using a two-sided 
two-sample t-test comparing each active treatment arm to placebo at significant level 0.05.
8.2
Populations for Analyses

All Enrolled Subjects, defined as all subjects who sign an informed consent

All Randomized Subjects, defined as all subjects who were randomized to a treatment group

Modified Intent-to-Treat (MITT) Analysis Population: All randomized subjects who have 
received at least one dose of the study medication. Subjects will be grouped according to the 
treatment to which they were randomized by IVRS/IWRS at the start of the study

As-Treated Analysis Population: All Subjects who have received at least one dose of study 
medication. Subjects will be grouped according to the treatment that they actually received as 
opposed to the treatment to which they were randomized. Subjects will be grouped on an as 
randomized basis unless the subject received the incorrect medication for the entire period of 
treatment. In that case, the subject will be analyzed in the treatment group associated with the 
incorrect medication he/she received

Biomarker Analysis Population, defined as all subjects that receive any study medication and 
have at least 1 post-treatment biomarker measurement

Pharmacokinetic Population, defined as all subjects who receive any study medication and 
have any available concentration-time data

Immunogenicity Population, defined as all subjects who receive study drug and have at least 
1 post treatment immunogenicity measurement
Analyses performed for all randomized subjects will be according to the as randomized groups, 
that is, subjects are categorized to the group to which they were assigned by the IVRS/IWRS. 
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Efficacy and safety analyses will be performed using the MITT Analysis Population and the As 
Treated Analysis Population respectively.
8.3
Endpoints
8.3.1
Primary Endpoint(s)
The primary endpoint is to compare the change from baseline in ESSDAI score at week 12 
between active treatment arms (lulizumab or BMS-986142) and the placebo arm.
8.3.2
Secondary Endpoint(s)

Change from baseline in ESSPRI score at Week 12

Proportions of subjects with 3 points of improvement from baseline in ESSDAI at Week 12

Proportions of subjects with 1 point of improvement from baseline in ESSPRI at Week 12

Proportion of subjects with both 3 points improvement in ESSDAI and 1 point 
improvement in ESSPRI from baseline at Week 12

Change from baseline in:

ESSDAI scores at Week 4 and Week 8

ESSPRI scores at Week 4 and Week 8

ESSPRI individual component (Dryness, Fatigue, and Pain) scores at Weeks 4, 8, and 12

Unstimulated and stimulated salivary flow rate at Weeks 4, 8, and 12

Ocular surface staining, Schrimer’s test, and the tear break-up time test at Weeks 4, 8, 
and 12

Safety and tolerability of lulizumab or BMS-986142 in subjects with moderate to severe pSS, 
as measured by AEs, laboratory parameters, vital signs, physical exams, and ECGs

Subject and physician assessments of disease activity:

Numeric rating scale (NRS) for mouth, eye and vaginal dryness

Subject global assessment of disease activity (SubGDA) and physician global assessment 
of disease activity (phyGDA), 

Short Form-36 (SF-36)

Female Sexual Function Index (FSFI)

Work participation and activity impairment questionnaire (WPAI)

PROMIS Fatigue Short Form

Trough concentrations of BMS-931699 and BMS-986142 at time points specified in Section 
5.5
 
 
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8.4
Analyses
8.4.1
Demographics and Baseline Characteristics
Demographic and baseline disease characteristics of all randomized subjects who received at 
least one dose of study medication will be summarized. For continuous variables, they will be 
summarized using means, medians, standard deviations and ranges. The distribution of 
categorical variables will be summarized by treatment group using frequency and percentage.
8.4.2
Efficacy Analyses
8.4.2.1
Primary Efficacy Analyses
The mixed effects model with repeated measures (MMRM) will be used to model the change 
from baseline in ESSDAI score over time for all treatment arms. Details of the model will be 
given in the statistical analysis plan. The least square means of the differences of Week 12 
change in ESSDAI from baseline between each active treatment and the placebo will be 
estimated and their corresponding two-sided 95% confidence intervals will be provided. In 
addition, as part of the secondary objective, similar outputs will be provided for the changes in 
ESSDAI score at Weeks 4 and 8.
The Hochberg’s step-up procedure will be used to adjust the multiplicity due to the comparison 
of two active treatments (lulizumab or BMS-986142) to the placebo arm in the primary endpoint 
(ie, change from baseline in ESSDAI at Week 12). The corresponding adjusted p-values for the 
Hochberg procedure will be provided.
8.4.2.2
Secondary Efficacy Analyses
For all secondary endpoints, no multiplicity adjustment will be applied, and nominal p-values 
may be provided if applicable. For each of the following categorical secondary endpoints, the 
estimate and its corresponding two-sided 95% confidence interval will be calculated for the 
proportion for each treatment arm. In addition, as exploratory analyses, differences of the 
proportions between each active treatment arm and the placebo arm will be evaluated and their 
corresponding two-sided 95% confidence intervals will be provided.

Proportion of subjects with a 3 point improvement from baseline in ESSDAI at Week 12
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
Proportion of subjects with a 1 point improvement from baseline in ESSPRI at Week 12

Proportion of subjects with both 3 point improvement from baseline in ESSDAI and 
1 point improvement from baseline in ESSPRI at Week 12
Similar to the primary endpoint, the following continuous secondary endpoints will be analyzed 
using the MMRM method:

Change from baseline in ESSPRI scores at Week 4, 8, and, 12

Change from baseline in score of each individual ESSPRI components (Dryness, Fatigue, 
and Pain) at Weeks 4, 8, and 12

Change from baseline in mouth dryness as measured by unstimulated and stimulated 
salivary flow rate at Weeks 4, 8, and 12

Change from baseline in eye dryness as measured by ocular surface staining, Schirmer’s 
test, and tear break-up time test at Weeks 4, 8, and 12
Analyses for other outcomes research assessments will be discussed in Outcome Research 
Analyses section.
Exploratory endpoints may be summarized descriptively for each treatment arm for the absolute 
value and change (or percent change) from baseline whenever applicable and appropriate.
Moreover, if applicable and appropriate, modeling techniques such as the MMRM method may 
be used for exploratory endpoints (eg, ESSDAI domains) as well.
8.4.3
Safety Analyses
All recorded adverse events will be listed and tabulated by system organ class, preferred term,
and treatment. Vital signs and clinical laboratory test results will be listed and summarized by 
treatment. Any significant physical examination findings, and clinical laboratory results will be 
listed. ECG readings will be evaluated by the investigator and abnormalities, if present, will be 
listed. Any pre-established Events of Special Interest will be listed and summarized.
 
 
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8.4.6
Outcomes Research Analyses
Descriptive summary statistics will be provided for absolute value and change (or percent 
change) from baseline in primary measures as well as eligible sub-domain scores for all the 
following outcome research assessments:

Numeric Rating Scale (NRS) scores for mouth, eye and vaginal dryness

Subject global assessment of disease activity (SubGDA) and physician global assessment of 
disease activity (phyGDA)

Short Form - 36 acute (SF-36 acute)

Female Sexual Function Index (FSFI)

Work participation and activity impairment questionnaire (WPAI)

PROMIS Fatigue Short Form
In addition, the MMRM method or other modelling methods may be applied to changes from 
baseline in primary measures (eg, total scores) of the above outcome research measures 
whenever appropriate. Details for those analyses will be provided in the statistical analysis plan.
8.4.7
Other Analyses 
After the database lock, exposures predicted from population PK model may be used to conduct 
exposure-response analysis for improvement of endpoint scores (ESSDAI and ESSPRI), clinical 
response, clinical remission, safety end points as well as biomarkers to guide dose selection and 
study designs for future subject
studies. Results of population PK analyses and 
exposure-response will be reported separately.
Cmax and AUC(0-4h) of hydroxychloroquine (Plaquenil) will be compared for Screening, 
Day 8 and Day 29.
 
8.5
Interim Analyses
One interim analysis will be conducted when at least 30 subjects reach Week 12 (complete 
12 weeks of treatment) and complete the specified assessments for the Week 12 ESSDAI score.
The interim analysis will be conducted in a fully blinded manner such that treatment group 
assignments of study subjects are not known and are not used in any manner in the analysis.
Specifically, a blinded examination of the variance of the primary endpoint will be performed 
and compared to the assumption used in planning the study. If this comparison suggests the 
initial assumption is substantially too low, the total study sample size may be increased by up to 
45 additional subjects (ie, to a maximum of 120 subjects in total) to maintain adequate study 
power.67,68,69 Regardless of the outcome from the blinded examination of variability, the study 
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sample size will not be decreased. Details on the blinded sample size re-estimation will be given 
in the statistical analysis plan.
9
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local health authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects. If a deviation or change to a protocol is implemented to eliminate an 
immediate hazard(s) prior to obtaining relevant approval/favorable opinion(s), the deviation or 
change will be submitted as soon as possible to:

IRB/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 
IRB(s)/IEC(s) and if applicable, also by local health authority, must be sent to BMS. If an 
amendment substantially alters the study design or increases the potential risk to the subject: (1) 
the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS or designated representatives will review data centrally to identify potential issues to 
determine a schedule of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare 
them with source documents, discuss the conduct of the study with the investigator, and verify 
that the facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the 
source documents: This includes the subject’s Global Assessment of Disease Activity, the 
Physician Global Assessment of Disease Activity, the PROMIS fatigue scale, the SF-36, and the 
WPAI.
In addition, the study may be evaluated by BMS internal auditors and government inspectors 
who must be allowed access to CRFs, source documents, other study files, and study facilities. 
BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory 
authorities, and promptly forward copies of inspection reports to BMS or designee.
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9.1.2.1
Source Documentation
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or 
entered electronically. If source data are created (first entered), modified, maintained, archived, 
retrieved, or transmitted electronically via computerized systems (and/or any other kind of 
electronic devices) as part of regulated clinical trial activities, such systems must be compliant 
with all applicable laws and regulations governing use of electronic records and/or electronic 
signatures. Such systems may include, but are not limited to, electronic medical/health records 
(EMRs/EHRs), adverse event tracking/reporting, protocol required assessments, and/or drug 
accountability records).
When paper records from such systems are used in place of electronic format to perform 
regulated activities, 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.
9.1.3
Investigational Site Training
Bristol-Myers Squibb will provide quality investigational staff training prior to study initiation. 
Training topics will include but are not limited to: GCP, AE reporting, study details and 
procedure, electronic CRFs, study documentation, informed consent, and enrollment of WOCBP.
9.2
Records
9.2.1
Records Retention
The investigator (or head of the study site in Japan) 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 (or head of the study site in Japan) must contact BMS or designee prior to destroying 
any records associated with the study.
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee.
9.2.2
Study Drug Records 
Records for IP and the following non-investigational product(s): not applicable (whether 
supplied by BMS, its vendors, or the site) must substantiate IP integrity and traceability from 
receipt, preparation, administration, and through destruction or return. Records must be made 
available for review at the request of BMS/designee or a Health Authority.
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If...
Then...
Supplied by BMS (or its vendors):
Records or logs must comply with applicable regulations and 
guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number

amount dispensed to and returned by each subject, 
including unique subject identifiers

amount transferred to another area/site for dispensing or 
storage

nonstudy disposition (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

dates and initials of person responsible for Investigational
Product dispensing/accountability, as per the Delegation 
of Authority Form.
BMS will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the BMS 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 paper or electronic SAE form and Pregnancy Surveillance form, respectively. If electronic 
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anti cd-28 (lulizumab); btk inhibitor
SAE form is not available, a paper SAE form can be used. Spaces may be left blank only in those 
circumstances permitted by study-specific CRF completion guidelines provided by BMS.
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs.
The completed CRF, including any paper or electronic SAE/pregnancy CRFs, must be promptly 
reviewed, signed, and dated by the investigator or qualified physician who is a subinvestigator
and who is delegated this task on the Delegation of Authority Form. Subinvestigators in Japan 
may not be delegated the CRF approval task. For electronic CRFs, review and approval/signature 
is completed electronically through the BMS electronic data capture tool. The investigator must 
retain a copy of the CRFs including records of the changes and corrections.
Each individual electronically signing electronic CRFs must meet BMS or designee training 
requirements and must only access the BMS electronic data capture tool using the unique user
account provided by BMS. User accounts are not to be shared or reassigned to other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report.
For this protocol, the Signatory Investigator will be selected as appropriate based on the 
following criteria:

External Principal Investigator designated at protocol development

National Coordinating Investigator 

Study Steering Committee chair or their designee

Subject recruitment (eg, among the top quartile of enrollers)

Involvement in trial design

Regional representation (eg, among top quartile of enrollers from a specified region or 
country)

Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS. Any publications 
or abstracts arising from this study must adhere to the publication requirements set forth in the 
clinical trial agreement (CTA) governing participation in the study. These requirements include, 
but are not limited to, submitting proposed publications to BMS 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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BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
If one form of contraception is required, Complete Abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Female subjects must continue 
to have pregnancy tests. Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject chooses to 
forego complete abstinence.
If two forms of contraception is required, Complete abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Subjects who choose complete 
abstinence are not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. Acceptable 
alternate methods of highly effective contraception must be discussed in 
the event that the subject chooses to forego complete abstinence.
Expanded definition Complete abstinence as defined as complete 
avoidance of heterosexual intercourse is an acceptable form of 
contraception for all study drugs. This also means that abstinence is the 
preferred and usual lifestyle of the subject. This does not mean periodic 
abstinence (eg, calendar, ovulation, symptothermal, profession of 
abstinence for entry into a clinical trial, post-ovulation methods) and 
withdrawal, which are not acceptable methods of contraception. Subjects 
who choose complete abstinence are not required to use a second method 
of contraception, but female subjects must continue to have pregnancy 
tests. Acceptable alternate methods of highly effective contraception must 
be discussed in the event that the subject chooses to forego complete 
abstinence.
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anti cd-28 (lulizumab); btk inhibitor
11
LIST OF ABBREVIATIONS
Term
Definition
AE
adverse event
ACLS
advanced cardiac life support
ACR
American College of Rheumatology
AI
accumulation index
AI_AUC
AUC Accumulation Index; ratio of AUC(TAU) at steady state to 
AUC(TAU) after the first dose
AI_Cmax
Cmax Accumulation Index; ratio of Cmax at steady state to Cmax after 
the first dose
AI_Ctau
Ctau Accumulation Index; ratio of Ctau at steady state to Ctau after the 
first dose
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ANOVA
analysis of variance
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AT
aminotransaminases
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-T)
area under the concentration-time curve from time zero to the time of the 
last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in one dosing interval
A-V
atrioventricular
-HCG
beta-human chorionic gonadotrophin
BA/BE
bioavailability/bioequivalence
%BE
percent biliary excretion
BID, bid
bis in die, twice daily
BLQ
below limit of quantification 
BMI
body mass index
BMS
Bristol-Myers Squibb
BP
blood pressure
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anti cd-28 (lulizumab); btk inhibitor
Term
Definition
BRt
Total amount recovered in bile
%BRt
Total percent of administered dose recovered in bile
BUN
blood urea nitrogen
C
Celsius
C12
concentration at 12 hours
C24
concentration at 24 hours
Ca++
calcium
Cavg
average concentration
CBC
complete blood count
Cexpected-tau
expected concentration in a dosing interval
CFR
Code of Federal Regulations 
CI
confidence interval
C1-
chloride
CLcr
creatinine clearance
CLD
Dialysate clearance of drug from plasma/serum
CLNR
nonrenal clearance
CLR
renal clearance
CLT
total body clearance
CLT/F (or CLT)
apparent total body clearance
CLT/F/fu or 
CLT/fu
Apparent clearance of free drug or clearance of free if (if IV)
cm
centimeter
Cmax, CMAX
maximum observed concentration
Cmin, CMIN
trough observed concentration
CNS
Central nervous system
CRC
Clinical Research Center
CRF
Case Report Form, paper or electronic
Ct
Expected concentration at a certain time, usually at the end of an 
expected future dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctau
Concentration in a dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
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anti cd-28 (lulizumab); btk inhibitor
Term
Definition
Ctrough
Trough observed plasma or serum concentration
CV
coefficient of variation
CYP
cytochrome p-450
D/C
discontinue
dL
deciliter
DMC
Data Monitoring Committee
DRt
Total amount recovered in dialysate
%DRt
Total percent of administered dose recovered in dialysate
DSM IV
Diagnostic and Statistical Manual of Mental Disorders (4th Edition)
EA
extent of absorption
ECG
electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EEG
electroencephalogram
eg
exempli gratia (for example)
ESR
Erythrocyte Sedimentation Rate
ESR
Expedited Safety Report
ESSDAI
EULAR SS Disease Activity Index
ESSPRI
EULAR SS Patient-Related Index
EULAR
European League Against Rheumatism
F
bioavailability
Fb
fraction of bound drug
FDA
Food and Drug Administration
FI
fluctuation Index ([Cmax-Ctau)/Cavg])
FRt
total amount recovered in feces
%FRt
total percent of administered dose recovered in feces
FSH
follicle stimulating hormone
FSFI
Female Sexual Function Index
%FE
percent fecal excretion
fu
fraction of unbound drug
g
gram
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anti cd-28 (lulizumab); btk inhibitor
Term
Definition
GC
gas chromatography
GCP
Good Clinical Practice
G criteria
adjusted R2 value of terminal elimination phase
GGT
gamma-glutamyl transferase
GFR
glomerular filtration rate
h
hour
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCO3-
bicarbonate
HIV
Human Immunodeficiency Virus
HR
heart rate
HRT
hormone replacement therapy
IA
Interim analysis
ICD
International Classification of Diseases
ICH
International Conference on Harmonisation 
ie
id est (that is)
IEC
Independent Ethics Committee
IMP
investigational medicinal products
IND
Investigational New Drug Exemption
IRB
Institutional Review Board
IU
International Unit
IV
intravenous
K
slope of the terminal phase of the log concentration-time curve
K3EDTA
potassium ethylenediaminetetraacetic acid
K+
potassium
kg
kilogram
z
terminal disposition rate constant
L
liter
LC
liquid chromatography
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IM128035
BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Term
Definition
LDH
lactate dehydrogenase
ln
natural logarithm
Lz_Start
The time point starting the log-linear elimination phase defining ther 
terminal half life
Lz_End
The time point ending the log-linear elimination phase defining the 
terminal half life
Lz_N
Number of time points in the log-linear elimination phase defining the 
terminal half life
mg
milligram
Mg++
magnesium
MIC
minimum inhibitory concentration
min
minute
mL
milliliter
mmHg
millimeters of mercury
MR_AUC(0-T)
Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for 
molecular weight
MR_AUC(INF)
Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for 
molecular weight
MR_AUC(TAU)
Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for 
molecular weight
MR_Cmax
Ratio of metabolite Cmax to parent Cmax, corrected for molecular 
weight
MR_Ctau
Ratio of metabolite Ctau to parent Ctau, corrected for molecular weight
MRT
mean residence time
MS
mass spectrometry
MTD
maximum tolerated dose
g
microgram
N
number of subjects or observations
Na+
sodium
N/A
not applicable
ng
nanogram
NIMP
non-investigational medicinal products 
NSAID
nonsteroidal anti-inflammatory drug
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BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Term
Definition
pAUCe
Extrapolated partial AUC from last quantifiable concentration to infinity
Pb
percent of bound drug
PD
pharmacodynamics
phyGDA
Physician global assess of disease activity
PK
pharmacokinetics
PO
per os (by mouth route of administration)
PROMIS Fatigue 
SF
Patient Reported Outcomes Measurement Information System Fatigue 
Short Form
pSS
Primary Sjögren’s syndrome
PT
prothrombin time
PTT
partial thromboplastin time
Pu
percent of unbound drug
QC
quality control
QD, qd
quaque die, once daily
R2
coefficient of determination
RA
Rheumatoid Arthritis
RBC
red blood cell
SAE
serious adverse event
SD
standard deviation
SF-36
Short Form – 36 acute
SLE
Systemic lupus erythematosus
SOP
Standard Operating Procedures
sp.
species
Subj
subject
SubGDA
Subject global assessment of disease activity
t
temperature
T
time
TAO
Trial Access Online, the BMS implementation of an EDC capability
T-HALF
Half life
T-HALFeff_AUC
Effective elimination half life that explains the degree of AUC 
accumulation observed
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BMS-931699 and BMS-986142
anti cd-28 (lulizumab); btk inhibitor
Term
Definition
T-HALFeff_Cmax
Effective elimination half life that explains the degree of Cmax 
accumulation observed)
TID, tid
ter in die, three times a day
Tmax, TMAX
time of maximum observed concentration
TR_AUC(0-T)
AUC(0-T) treatment ratio
TR_AUC(INF)
AUC(INF) treatment ratio
TR_Cmax
Cmax treatment ratio
UPCR
Urine protein/creatinine ratio
UR
urinary recovery
%UR
percent urinary recovery
URt
total amount recovered in urine
%URt
total percent of administered dose recovered in urine
UV
ultraviolet
Vss/F (or Vss)
apparent volume of distribution at steady state
Vz
Volume of distribution of terminal phase (if IV and if multi-exponential 
decline)
W
washout
WBC
white blood cell
WHO
World Health Organization
WOCBP
women of childbearing potential
WPAI
Work Participation and Activity Impairment Questionnaire
x g
times gravity
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anti cd-28 (lulizumab); btk inhibitor
APPENDIX 1
METHODS OF CONTRACEPTION
At a minimum, subjects must agree to use one highly effective method of contraception (or one 
highly effective plus one less effective method, as per local country regulations) as listed below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
Highly effective methods of contraception have a failure rate of < 1% when used consistently 
and correctly. WOCBP and female partners of male subjects are expected to use one of the 
highly effective methods of contraception listed below. Male subjects must inform their female 
partners who are WOCBP of the contraceptive requirements of the protocol and are expected to 
adhere to using contraception with their partner.

Non-hormonal intrauterine devices (IUDs) such as ParaGard

Bilateral tubal occlusion

Vasectomised partner with documented azoospermia 90 days after procedure
o
Vasectomized partner is a highly effective birth control method provided that partner 
is the sole sexual partner of the WOCBP trial participant and that the vasectomized 
partner has received medical assessment of surgical success

Complete abstinence
o
Complete abstinence is defined as the complete avoidance of heterosexual 
intercourse. (refer to Glossary of Terms)
o
Complete abstinence is an acceptable form of contraception for all study drugs and 
must be used throughout the duration of the study treatment plus 5 half-lives of the 
investigational drug plus 30 days for women (65 additional days) and 5 half-lives of 
the investigational drug for men (35 additional days)
o
It is not necessary to use any other method of contraception when complete 
abstinence is elected
o
Subjects who choose complete abstinence must continue to have pregnancy tests, as 
specified in Table 5.1-1 and Table 5.1-2
o
Acceptable alternate methods of highly effective contraception must be discussed in 
the event that the subject 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 EFFECTIVE METHODS OF CONTRACEPTION

Diaphragm with spermicide

Cervical cap with spermicide

Vaginal sponge with spermicide

Male or female condom with or without spermicide*
* A male and a female condom must not be used together.
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anti cd-28 (lulizumab); btk inhibitor
UNACCEPTABLE METHODS OF CONTRACEPTION

Periodic abstinence (calendar, symptothermal, post-ovulation methods)

Withdrawal (coitus interruptus)

Spermicide only

Lactation amenorrhea method (LAM)
HORMONE-BASED METHODS OF CONTRACEPTION

Hormone-based contraception for study subjects who are WOCBP is prohibited due to the 
lack of data available for potential drug-drug interactions between BMS-986142 and 
hormonal contraceptives

Female partners of male subjects participating in the study may use hormone-based 
contraceptives as one of the acceptable methods of contraception since they will not be 
receiving study drug
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SAP_001.pdf: 
 
 
 
Official Title of Study:  A PHASE II, RANDOMIZED, MULTI-CENTER, DOUBLE-BLIND, PLACEBO 
CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF BMS- 
931699 (LULIZUMAB) OR BMS-986142 IN SUBJECTS WITH MODERATE TO 
SEVERE PRIMARY SJOGREN'S SYNDROME 
 
 
NCT Number:  NCT02843659 
 
 
Document Date:  May 15, 2017   


STATISTICAL ANALYSIS PLAN
FOR CLINICAL STUDY REPORT
A PHASE II, RANDOMIZED, MULTI-CENTER, DOUBLE-BLIND, PLACEBO 
CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF BMS-
931699 (LULIZUMAB) OR BMS-986142 IN SUBJECTS WITH MODERATE TO 
SEVERE PRIMARY SJOGREN'S SYNDROME
PROTOCOL(S) IM128-035
VERSION # 1.0
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Statistical Analysis Plan
IM128-035
BMS-931699 AND BMS-986142
anti cd-28 (lulizumab); btk inhibitor
2
TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN FOR CLINICAL STUDY REPORT ...................................1
TABLE OF CONTENTS............................................................................................................2
LIST OF TABLES......................................................................................................................6
LIST OF FIGURES ....................................................................................................................7
1
BACKGROUND AND RATIONALE......................................................................8
1.1
Study Rationale ........................................................................................................9
2
STUDY DESCRIPTION ........................................................................................12
2.1
Study Design ..........................................................................................................12
2.2
Treatment Assignment............................................................................................14
2.3
Blinding and Unblinding.........................................................................................15
2.4
Protocol Amendments.............................................................................................16
2.5
Data Monitoring Committee and Other External Committees .................................16
3
OBJECTIVES ........................................................................................................16
3.1
Primary...................................................................................................................16
3.2
Secondary...............................................................................................................16
3.3
Exploratory.............................................................................................................17
4
ENDPOINTS..........................................................................................................18
4.1
Primary Endpoint(s) ...............................................................................................18
4.2
Secondary Endpoint(s)............................................................................................18
4.3
Exploratory Endpoint(s)..........................................................................................18
5
SAMPLE SIZE AND POWER...............................................................................19
6
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS 
FOR ANALYSES ..................................................................................................19
6.1
Study Periods..........................................................................................................19
6.2
Treatment Regimens...............................................................................................20
6.3
Populations for Analyses ........................................................................................20
7
STATISTICAL ANALYSES..................................................................................21
7.1
General Methods ....................................................................................................21
7.1.1
Change from Baseline.............................................................................................21
7.1.2
Percent Change from Baseline................................................................................21
7.1.3
Descriptive Summaries of Continuous Variables.....................................................23
7.1.4
Descriptive Summaries of Categorical Variables....................................................23
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BMS-931699 AND BMS-986142
anti cd-28 (lulizumab); btk inhibitor
3
7.1.5
Mixed effects Model with Repeated Measures .........................................................23
7.1.5.1
Model Specification................................................................................................23
7.1.5.2
Model Assumption Assessment................................................................................24
7.1.6
Kaplan-Meier Curve and Estimates for Time-to-Event Analyses .............................25
7.1.7
Test for Proportion of Subjects with a Characteristic at Visit t................................25
7.2
Study Conduct........................................................................................................26
7.3
Study Population ....................................................................................................26
7.3.1
Subject Disposition.................................................................................................26
7.3.2
Demography and Baseline Characteristics .............................................................27
7.3.3
General Medical History ........................................................................................29
7.3.4
Prior (Current) Medication ....................................................................................29
7.4
Extent of Exposure .................................................................................................30
7.4.1
Study Therapy.........................................................................................................30
7.4.2
Discontinuations from Study Therapy .....................................................................31
7.4.3
Treatment Compliance............................................................................................31
7.4.4
Concomitant Medication.........................................................................................31
7.4.5
Immunosuppressant Medication..............................................................................32
7.4.6
Corticosteroids.......................................................................................................32
7.4.7
Narcotic analgesics ................................................................................................32
7.4.8
Anticoagulants........................................................................................................32
7.5
Efficacy..................................................................................................................32
7.5.1
Primary efficacy analysis........................................................................................32
7.5.2
Secondary and Exploratory Efficacy Analyses ........................................................33
7.5.2.1
Categorical Endpoints............................................................................................33
7.5.2.2
Continuous Endpoints.............................................................................................33
7.6
Safety.....................................................................................................................34
7.6.1
Adverse Events .......................................................................................................35
7.6.1.1
Adverse Events .......................................................................................................35
7.6.1.2
Deaths ....................................................................................................................36
7.6.2
Laboratory evaluation ............................................................................................37
7.6.2.1
Marked Laboratory Abnormalities..........................................................................37
7.6.2.2
Change from Baseline for Selected Laboratory Parameters Over Time...................37
7.6.2.3
Pregnancy Test Results...........................................................................................38
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Statistical Analysis Plan
IM128-035
BMS-931699 AND BMS-986142
anti cd-28 (lulizumab); btk inhibitor
4
7.6.3
Electrocardiogram..................................................................................................38
7.6.4
Vital Sign................................................................................................................39
7.6.5
Physical Examination Findings...............................................................................40
7.7
Pharmacokinetic Analyses ......................................................................................40
7.8
Outcomes Research Analyses .................................................................................40
7.9
Biomarker Analyses ...............................................................................................41
7.9.1
Clinical, serum, saliva biomarkers..........................................................................41
7.9.2
Biopsies..................................................................................................................42
7.10
Immunogenicity Analyses.......................................................................................42
7.11
Interim Analyses.....................................................................................................43
8
CONVENTIONS....................................................................................................44
8.1
Time from first diagnosis of Sjogren’s syndrome....................................................44
8.2
Analysis Window for Longitudinal Assessments ....................................................45
8.2.1
Baseline Value........................................................................................................45
8.2.2
Longitudinal Assessments .......................................................................................45
8.3
Post-Treatment Efficacy and Safety Observations...................................................46
8.3.1
Missing and Multiple Measurements.......................................................................47
8.4
Assignment of Doses to Adverse Events and Laboratory Assessments....................47
8.4.1
Treatment at Onset of an Adverse Event .................................................................49
8.4.2
Treatment at the Time of a Laboratory Assessment .................................................49
8.5
Non-study Medications...........................................................................................49
8.6
EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).............................49
8.7
EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI)..............................50
8.8
Salivary flow rate ...................................................................................................51
8.9
Schirmer’s test........................................................................................................51
8.10
Tear break-up time..................................................................................................52
8.11
Ocular surface staining ...........................................................................................52
8.12
Numeric Rating Scale (NRS) scores .......................................................................52
8.13
Visual analog scale .................................................................................................52
8.14
Short Form-36 (SF-36) ...........................................................................................52
8.15
Female Sexual Function Index (FSFI).....................................................................52
8.16
Work Productivity and Activity Impairment (WPAI - GH) .....................................53
8.17
PROMIS Fatigue Short Form 8a.............................................................................54
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Statistical Analysis Plan
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BMS-931699 AND BMS-986142
anti cd-28 (lulizumab); btk inhibitor
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8.18
Counting rules for adverse events ...........................................................................56
8.18.1
At Subject Level......................................................................................................56
8.18.2
At Event Level.........................................................................................................56
8.19
Conventions of ECG Data.......................................................................................57
8.20
Percent Compliance Calculation .............................................................................57
8.21
Strip Sign for Selected Laboratory Data..................................................................57
8.22
United States Conventional Units and Standard International Units for 
Laboratory Data......................................................................................................58
8.23
Laboratory evaluations ...........................................................................................58
9
CONTENT OF REPORTS .....................................................................................58
APPENDIX 1
RELEVANT PROTOCOL DEVIATIONS.............................................59
APPENDIX 2
GEOGRAPHIC REGIONS ....................................................................60
APPENDIX 3
MARKED LABORATORY ABNORMALITIES CRITERIA................61
APPENDIX 4
DOCUMENT HISTORY .......................................................................67
10
REFERENCES.......................................................................................................68
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Statistical Analysis Plan
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BMS-931699 AND BMS-986142
anti cd-28 (lulizumab); btk inhibitor
6
LIST OF TABLES
Table 7.1.2-1:
Formulae Used to Transform Back onto the Original Scale the 
Estimates of Percent Change from Baseline Analyzed as 
Geometric Mean.....................................................................................21
Table 7.1.5.2-2:
Contrast Coefficients for the treatment-by-baseline interaction for 
visit 85 estimates....................................................................................24
Table 7.3.2-2:
Demographic and Baseline Characteristics .............................................28
Table 7.6.3-2:
Electrocardiogram Parameter Categorization..........................................39
Table 7.6.4-2:
Vital signs criteria ..................................................................................39
Table 7.9.1-2:
Categorical classifications for ANA........................................................42
Table 8.2.2-1:
Visit Windows for Double-Blind Treatment Period ................................45
Table 8.2.2-2:
Visit Windows for the Follow-Up Period................................................46
Table 8.6-2:
The EULAR Sjögren's Syndrome Disease Activity Index 
(ESSDAI) scoring algorithm...................................................................50
Table 8.15-2:
Scoring algorithm for Female Sexual Function Index (FSFI) ..................53
Table 8.17-2:
PROMIS Fatigue 8a Short Form Conversion Table ................................54
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LIST OF FIGURES
Figure 1-1:
Pathogenic Mechanisms in Sjögren's Syndrome........................................9
Figure 2.1-1:
Study Design Schematic.........................................................................14
Figure 8.3-1:
The EULAR Sjögren's Syndrome Patient Reported Index 
(ESSPRI)................................................................................................51
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Schedule of Analyses:
The following analyses will be performed:

One interim analysis will be conducted when at least 30 subjects reach Week 12 (complete 
12 weeks of treatment) and complete the specified assessments for the Week 12 ESSDAI 
score. The interim analysis will be conducted in a fully blinded manner such that treatment 
group assignments of study subjects are not known and are not used in any manner in the 
analysis. Specifically, a blinded examination of the variance of the primary endpoint will be 
performed and compared to the assumption used in planning the study. If this comparison 
suggests the initial assumption is substantially too low, the total study sample size may be 
increased by up to 45 additional subjects (i.e., to a maximum of 120 subjects in total) to 
maintain adequate study power..24,25,26 Regardless of the outcome from the blinded 
examination of variability, the study sample size will not be decreased. Details on the blinded 
sample size re-estimation will be given in the statistical analysis plan.

A final analysis will be performed after the last treated subject in the study reaches the end of 
the study.
2
STUDY DESCRIPTION
2.1
Study Design
This is a 12-week randomized, double-blind, placebo-controlled, parallel group study with 
adaptive design features based on an interim analysis (IA). The study will initially have a 28-day 
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screening period followed by up to 12 weeks of double-blind treatment with either lulizumab, 
BMS-986142, or a matching placebo.
Screening period:
The standard duration of the Screening Period is up to 28 days (4 weeks), with up to two 
Screening Visits allowed for subjects who require adjustment of oral corticosteroids or who are 
taking hydroxychloroquine (HCQ). Subjects who are on oral corticosteroids at a dose higher than 
10 mg/day will require a taper at the beginning of the Screening Period to a stable dose of no 
more than 10 mg/day of prednisone (or equivalent) for least 14 days prior to dosing (Day -14), 
and will need to be reevaluated prior to randomization (Day 1). Subjects who are taking HCQ at 
screening who meet the study criteria will be required to return for a second visit during the 
screening period to collect baseline HCQ PK samples as described in protocol Section 5.5 (these 
subjects should bring their daily dose of HCQ to the clinical site to be administered at the site). 
Should more time be needed, the duration of the Screening Period may be extended up to another 
week (total of 35 days or 5 weeks) depending on dose stabilization, technical issues, or subject 
scheduling. Study procedures will occur as specified in protocol Table 5.1-1.
Double-blind treatment period:
Upon meeting the Inclusion/Exclusion criteria, approximately 75 subjects with moderate to 
severe pSS will be equally randomized to 1 of 3 treatment arms (lulizumab, BMS-986142, or 
matching placebos) for up to 12 weeks of treatment, followed by a 6 week follow-up period after 
completion 
of 
treatment. 
During 
this 
period, 
the 
dose 
of 
oral 
corticosteroids, 
hydroxychloroquine, pilocarpine, cevimeline, cyclosporine eye drops, lifitegrast, autologous 
serum eye drops, oral and ocular lubricants and/or NSAIDs should remain stable. No additional 
immunosuppressive medications may be started unless indicated for the treatment of adverse 
events. Analgesics are permitted with certain restrictions (see protocol Section 3.3). Study 
procedures will occur as specified in protocol Table 5.1-2, Table 5.5-1, and Table 5.6-1.
If a subject discontinues early from treatment, all procedures scheduled for the End of 
Week 12/End of treatment visit should be performed at the time of actual discontinuation/end of 
treatment. At the end of the double blind treatment period, alternate therapies for Sjögren’s 
syndrome should be discussed with subjects.
Interim analysis:
An interim analysis of all accumulated primary endpoint (ESSDAI) data up to Week 12 will be 
performed after at least 30 subjects reach Week 12 (complete 12 weeks of treatment) and 
complete the specified assessments for the Week 12 ESSDAI score. The interim analysis will be 
conducted in a fully blinded manner, such that treatment group assignments of study subjects are 
not known and are not used in any manner in the analysis. A blinded examination of the variance 
of the primary endpoint will be performed and compared to the assumption used in planning the 
study. Based on the results, the study sample size may be increased to maintain adequate 
statistical power. The blinded interim analysis will not interfere or alter any subject’s treatment, 
that is, subjects who were enrolled before the IA is completed will continue the originally 
assigned treatment arm if they have received at least 1 treatment and the dose is considered safe.
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Follow-Up Period:
After completion of the double-blind treatment period or early discontinuation from the study, all 
subjects will continued to be followed for an additional 6 week safety follow-up period. There 
will be two post treatment Follow-Up visits at Week 15 (or 3 weeks after early discontinuation) 
and Week 18 (or 6 weeks after early discontinuation). Study procedures will occur as specified in 
protocol Table 5.1-2.
The study design schematic is presented in Figure 2.1-1.
Figure 2.1-1:
Study Design Schematic
The approximate duration of the study is up to a 5-week screening period (35 days), a 12-week 
double-blind treatment period (84 days), and 6 weeks of follow up (42 days), for a total of up to 
23 weeks (161 days).
The start of the trial is defined as the date of the first Screening Visit for the first subject 
screened. The end of the trial is defined as the date of the last visit or scheduled procedure shown 
in the Time & Events schedule for the last subject. Study completion is defined as the final date 
when the data from the last safety follow-up visit for the last subject has been received at BMS 
and the study is considered clinically complete.
2.2
Treatment Assignment
At the time of the screening visit, immediately after written informed consent is obtained and 
before performing any study-related procedures, the investigator or coordinator will call into the 
Interactive Voice Response System (IVRS or IWRS) designated by BMS for assignment of a 
5 digit subject number that will be unique across all sites. Enrolled subjects, including those not 
dosed, will be assigned unique sequential subject numbers by the IVRS/IWRS system starting 
with 00001, 00002, 00003, etc. for identification throughout the study. This subject number must 
not be reused for any other participant in the study.
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After completion of all screening evaluations, on Day 1, all eligible subjects will be randomly 
assigned to 1 of 3 treatment arms (lulizumab, BMS-986142, or placebo) in an equal ratio. To 
randomize a subject, a phone call will be placed into the randomization option of the 
IVRS/IWRS in order to obtain a subject’s randomized treatment assignment. Randomization will 
be assigned in the order in which subjects qualify for treatment, not in the order of study 
enrollment. The IVRS will be available 24 hours a day, 7 days a week, via a toll-free number 
(or via the internet for IWRS). Randomization will be stratified by hydroxychloroquine 
(Plaquenil) and oral corticosteroid use.
Specific instructions (including an enrollment/randomization worksheet) for the central 
enrollment and randomization procedure using an IVRS/IWRS will be provided to the site.
Randomized schedules will be generated and kept by the Randomization Group within Drug 
Supply Management of Bristol-Myers Squibb.
At all study visits when study drug is dispensed, each subject will be assigned specific container 
numbers by the IVRS/IWRS. Container numbers will be assigned non-sequentially and will 
correspond to the numbers printed on the containers and bottles containing study drug, and will 
be recorded on the appropriate eCRF.
2.3
Blinding and Unblinding
Blinding of treatment assignment is critical to the integrity of this clinical study. However, in the 
event of a medical emergency or pregnancy in an individual subject in which knowledge of the 
investigational product is critical to the subject's management, the blind for that subject may be 
broken by the investigator. The subject’s safety takes priority over any other considerations in 
determining if a treatment assignment should be unblinded.
Before breaking the blind of an individual subject's treatment, the investigator should determine 
that the unblinded information is necessary, i.e., that it will alter the subject's immediate 
management. In many cases, particularly when the emergency is clearly not related to the 
investigational product, the problem may be properly managed by assuming that the subject is 
receiving one of the active products. It is highly desirable that the decision to unblind treatment 
assignment be discussed with the BMS Medical Monitor, but the investigator always has 
ultimate authority for the decision to unblind. The Principal Investigator should only call in for 
emergency unblinding after the decision to discontinue the subject has been made.
For this study, the method of unblinding for emergency purposes is IVRS/IWRS. For 
information on how to un-blind in an emergency, consult the IVRS/IWRS manual.
In cases of any accidental unblinding, contact the BMS 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 
Medical Monitor.
In case of an emergency, the Investigator(s) has unrestricted access to randomization information 
via the Interactive Voice Response System (IVRS/IWRS) and is capable of breaking the blind 
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through the IVRS/IWRS system without prior approval from sponsor. Following the unblinding, 
the Investigator should notify the BMS Medical Monitor.
The Bioanalytical Sciences section or its designate will be unblinded to the randomized 
treatment assignments in order to minimize unnecessary analysis of samples from control group 
subjects.
Interim Analysis:
The interim analysis will be conducted in a fully blinded manner such that treatment group 
assignments of study subjects are not known and are not used in any manner in the analysis.
2.4
Protocol Amendments
There have been two protocol amendments and two administrative letters in the study protocol, 
which do not affect the analysis.
2.5
Data Monitoring Committee and Other External Committees
A Data Monitoring Committee (DMC) will monitor overall safety data regularly to ensure that 
the benefits and risks of study participation remain acceptable. Based on the regular reviews of 
emerging data, the DMC may recommend to the Sponsor alteration and/or termination of the 
trial or a treatment group, or cessation of further enrollment into a treatment group.
Data summaries and listings will be provided to the DMC to facilitate their safety assessment at 
the regularly scheduled times as well as on an ad hoc basis if needed. The DMC will review 
safety data including SAEs and events of special interest, focusing on early signal detection. 
Further details on the frequency, content, and methods of data reports to the DMC will be 
outlined in the Charter of that Committee along with the processes and procedures the committee 
will follow.
3
OBJECTIVES
3.1
Primary
To evaluate the efficacy of treatment with either lulizumab or BMS-986142 versus placebo in 
subjects with moderate to severe pSS as measured by the change from baseline in ESSDAI at 
Week 12 between active treatment arms (lulizumab or BMS-986142, respectively) and the 
placebo arm.
3.2
Secondary
To assess the:

Change from baseline in ESSPRI score at Week 12

Proportion of subjects with a 3 point improvement from baseline in ESSDAI at Week 12

Proportion of subjects with a 1 point improvement from baseline in ESSPRI at Week 12

Proportion of subjects with both 3 points improvement in ESSDAI and 1 point 
improvement in ESSPRI from baseline at Week 12
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
Change from baseline in ESSDAI scores at Week 4 and Week 8

Change from baseline in ESSPRI scores at Week 4 and Week 8

Change from baseline in ESSPRI components (Dryness, Fatigue, and Pain) at Weeks 4, 8, 
and 12

Change from baseline in unstimulated and stimulated salivary flow rate at Weeks 4, 8, and 12

Change from baseline in ocular surface staining, Schirmer’s test, and tear break-up time test 
at Weeks 4, 8, and 12

Safety and tolerability of lulizumab or BMS-986142 in subjects with moderate to severe pSS, 
as measured by adverse events, laboratory parameters, vital signs, physical exams, and ECGs

Change from baseline in patient and physician assessments of disease activity:

Patient Numeric Rating Scale (NRS) scores for mouth, eye and vaginal dryness (see 
Appendices 7, 8 and 9)

Subject global assessment of disease activity (SubGDA, see Appendix 5) and physician 
global assessment of disease activity (phyGDA, see Appendix 6)

Short Form - 36 acute (SF-36 acute, see Appendix 12)

Female Sexual Function Index (FSFI, see Appendix 11)

Work participation and activity impairment questionnaire (WPAI, see Appendix 13)

PROMIS Fatigue Short Form (see Appendix 10)

Trough concentrations of lulizumab and BMS-986142 in pSS subjects
 
 
 
 
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4
ENDPOINTS
4.1
Primary Endpoint(s)
The primary endpoint is to compare the change from baseline in ESSDAI score at week 12 
between active treatment arms (lulizumab or BMS-986142) and the placebo arm.
4.2
Secondary Endpoint(s)

Change from baseline in ESSPRI score at Week 12

Proportions of subjects with 3 points of improvement from baseline in ESSDAI at Week 12

Proportions of subjects with 1 point of improvement from baseline in ESSPRI at Week 12

Proportion of subjects with both 3 points improvement in ESSDAI and 1 point 
improvement in ESSPRI from baseline at Week 12

Change from baseline in:

ESSDAI scores at Week 4 and Week 8

ESSPRI scores at Week 4 and Week 8

ESSPRI individual component (Dryness, Fatigue, and Pain) scores at Weeks 4, 8, and 12

Unstimulated and stimulated salivary flow rate at Weeks 4, 8, and 12

Ocular surface staining, Schirmer’s test, and the tear break-up time test at Weeks 4, 8, 
and 12

Safety and tolerability of lulizumab or BMS-986142 in subjects with moderate to severe pSS,
as measured by AEs, laboratory parameters, vital signs, physical exams, and ECGs

Subject and physician assessments of disease activity:

Numeric rating scale (NRS) for mouth, eye and vaginal dryness

Subject global assessment of disease activity (SubGDA) and physician global assessment 
of disease activity (phyGDA),

Short Form-36 (SF-36)

Female Sexual Function Index (FSFI)

Work participation and activity impairment questionnaire (WPAI)

PROMIS Fatigue Short Form

Trough concentrations of BMS-931699 and BMS-986142 at time points specified in protocol 
Section 5.5
 
 
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5
SAMPLE SIZE AND POWER
The sample size calculation is based on the power to compare change from baseline in ESSDAI 
at Week 12 between active treatment arms (lulizumab or BMS-986142) and the placebo arm. 
With a two-sided two-sample t-test at significance level 0.05, data from 25 treated subjects per 
arm will provide approximately 90% power to detect a placebo-adjusted 3-point decrease from 
baseline for each active treatment group, assuming common standard deviations of 3.2.27 In 
addition, the Hochberg’s step-up procedure will be used to adjust the multiplicity due to the 
comparison of two active treatment arms (lulizumab or BMS-986142) to the placebo arm.
The primary efficacy analysis will be conducted on all randomized subjects who received at least 
one dose of study drug.
An interim analysis will be conducted after at least 30 subjects reach Week 12 (complete 
12 weeks of treatment) and complete the specified assessments for ESSDAI. The interim 
analysis will be conducted in a fully blinded manner such that treatment group assignments of 
study subjects are not known and are not used in any manner in the analysis. A blinded 
examination of the variance of the primary endpoint will be performed and compared to the 
assumption used in planning the study. If this comparison suggests the initial assumption was 
substantially too low, the total study sample size may be increased by up to 45 additional 
subjects (i.e., to a maximum of 120 subjects in total) to maintain adequate study power.28,29,30
Regardless of the outcome from the blinded examination of variability, the study sample size 
will not be decreased. A maximum study sample size of 120 subjects in total, i.e., 40 subjects per 
arm, can provide each active treatment arm 79% power to detect a placebo-adjusted 3-point 
decrease from baseline for common standard deviations as large as 4.8, using a two-sided 
two-sample t-test comparing each active treatment arm to placebo at significant level 0.05.
6
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS FOR 
ANALYSES
6.1
Study Periods
The following periods are defined in this SAP for the purpose of analyses and reporting.

Pre-treatment period: It covers the time period which starts from the day of enrollment and 
lasts until the initiation of the randomized double-blind treatment period.
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
Double-blind treatment and follow-up periods: It starts at the time of the first dose of 
blinded treatment and continues up to 42 days post last dose.
6.2
Treatment Regimens
All subjects will receive one of the following treatments:

BMS-931699/lulizumab injection 12.5mg for subcutaneous administration weekly

BMS-986142 350mg for oral administration daily

Matching placebos
For analysis, subjects will appear in the “as randomized” treatment group, which is defined as 
the treatment group to which a subject was randomized at the start of the double-blind treatment 
period (even if the treatment they received was different).
The “as treated” treatment group is the same as the “as randomized” treatment group, except in 
cases where information was available which indicated that a subject received a different 
treatment for the entire course of their participation in the study (or period). In this case, the “as 
treated” treatment group is set to the treatment the subject actually received. In cases where a 
subject never received the treatment as assigned by randomization, then the “as treated” 
treatment group is the first treatment received.
6.3
Populations for Analyses

All Enrolled Subjects, defined as all subjects who sign an informed consent

All Randomized Subjects, defined as all subjects who were randomized to a treatment group

Modified Intent-to-Treat (MITT) Analysis Population: All randomized subjects who have 
received at least one dose of the study medication. Subjects will be grouped according to the 
treatment to which they were randomized by IVRS/IWRS at the start of the study

As-Treated Analysis Population: All Subjects who have received at least one dose of study 
medication. Subjects will be grouped according to the treatment that they actually received as 
opposed to the treatment to which they were randomized. Subjects will be grouped on an as 
randomized basis unless the subject received the incorrect medication for the entire period of 
treatment. In that case, the subject will be analyzed in the treatment group associated with the 
incorrect medication he/she received

Biomarker Analysis Population, defined as all subjects that receive any study medication and 
have at least 1 post-treatment biomarker measurement

Pharmacokinetic Population, defined as all subjects who receive any study medication and 
have any available concentration-time data

Immunogenicity Population, defined as all subjects who receive study drug and have at least 
1 post treatment immunogenicity measurement
Analyses performed for all randomized subjects will be according to the as randomized groups, 
that is, subjects are categorized to the group to which they were assigned by the IVRS/IWRS. 
Efficacy and safety analyses will be performed using the MITT Analysis Population and the As 
Treated Analysis Population respectively.
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7
STATISTICAL ANALYSES
7.1
General Methods
7.1.1
Change from Baseline
Change from baseline to any Visit t in double-blind treatment period is defined as follows:
CVisit t = MVisit t - Mbaseline
where:

CVisit t is the change from baseline at Visit t,

MVisit t is the measurement at Visit t,

Mbaseline is the measurement at baseline.
The “Visit t” and baseline to which a measurement belongs is determined using the conventions 
described in Section 8.1.
7.1.2
Percent Change from Baseline
Percent change from baseline to any Visit t in double-blind treatment period is defined as 
follows:
PVisit t =100×(MVisit t - Mbaseline) / Mbaseline .
Where

PVisit t is the percent change from baseline at Visit t,

MVisit t is the measurement at Visit t,

Mbaseline is the measurement at baseline.
The “Visit t” and baseline to which a measurement belongs is determined using the conventions 
described in Section 8.1.
For analyses of parameters in terms of percent change from baseline to Visit t, values will first be 
transformed to natural logarithms (Ln) and the results will be expressed as geometric mean 
percent changes from baseline. Analysis will be performed using the logarithms of the post-
baseline to baseline ratios. Subsequently, the estimates from the analysis will be back-
transformed to original values for reporting in the tables using the formulae detailed in Table 
7.1.2-1.
Table 7.1.2-1:
Formulae Used to Transform Back onto the Original Scale the 
Estimates of Percent Change from Baseline Analyzed as Geometric 
Mean
Quantity
Computation method
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Table 7.1.2-1:
Formulae Used to Transform Back onto the Original Scale the 
Estimates of Percent Change from Baseline Analyzed as Geometric 
Mean
Quantity
Computation method
Geometric mean of the Visit t to baseline ratio 
Exp(mean change from baseline in natural logarithm)
Mean percent change from baseline
100 [exp(mean change from baseline in natural 
logarithm*) – 1]
Standard error of mean percent change from baseline
100 exp(mean change from baseline in natural 
logarithm) standard error of mean change from 
baseline in natural logarithm*
– or, equivalently –
100 Geometric mean of the Visit t to baseline ratio 
standard error of mean change from baseline in natural 
logarithm*
Lower confidence limit for mean percent change from 
baseline
100 [exp(lower confidence limit for mean change from 
baseline in natural logarithm*) – 1]
Upper confidence limit for mean percent change from 
baseline
100 [exp(upper confidence limit for mean change from 
baseline in natural logarithm*) – 1]
Adjusted geometric mean of the Visit t to baseline ratio
exp(Adjusted mean change from baseline in natural 
logarithm*)
Adjusted mean percent change from baseline
100 [exp(Adjusted mean change from baseline in 
natural logarithm*) – 1]
Standard error of adjusted mean percent change from 
baseline
100 exp(Adjusted mean change from baseline in 
natural logarithm) standard error of mean change from 
baseline in natural logarithm*
– or, equivalently –
100 adjusted geometric mean of the Visit t to baseline 
ratio standard error of mean change from baseline in 
natural logarithm*
Lower confidence limit for adjusted mean percent 
change from baseline
100 [exp(lower confidence limit for adjusted mean 
change from baseline in natural logarithm*) – 1]
Upper confidence limit for adjusted mean percent 
change from baseline
100 [exp(upper confidence limit for adjusted mean 
change from baseline in natural logarithm*) – 1]
Adjusted geometric mean of the Visit t to baseline ratio 
achieved with each dapagliflozin treatment arm relative 
to that achieved with Control, expressed as a percent 
difference.
Please note that for the SAS output, a shorter text will be 
used:
Adjusted GM of Visit t/Baseline for each dapagliflozin 
treatment arm relative to Control, in % difference.
100 (((adjusted mean percent change for dapagliflozin 
treatment arm +100)/(adjusted mean percent change for 
Control +100)) – 1)
– or, equivalently –
100 (exp(difference in adjusted mean change from 
baseline between dapagliflozin treatment arm and 
Control in natural logarithm*) – 1)
*Change in natural logarithm refers to a calculated difference between two values after performing a natural 
logarithmic transformation on each.
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7.1.3
Descriptive Summaries of Continuous Variables
Descriptive summaries of continuous variables in terms of baseline values, change or percent 
change from baseline values will be provided by treatment group and overall, as applicable.
These summaries may include the estimations of means, medians, standard deviations and 
ranges, as applicable.
7.1.4
Descriptive Summaries of Categorical Variables
Descriptive summaries of categorical variables will consist of frequencies and percentages for 
each treatment group and overall, as applicable.
7.1.5
Mixed effects Model with Repeated Measures
7.1.5.1
Model Specification
A mixed effect model with repeated measures analysis using ‘direct likelihood’ will be 
performed. The SAS procedure PROC MIXED will be used.
The dependent variable will be the change from baseline to each Visit t included in the model for 
efficacy endpoints examining changes from baseline. For analyses of parameters in terms of
percent change from baseline at Visit t, values will first be transformed to logarithms and the 
results will be expressed as geometric mean percent changes from baseline. The dependent 
variable will be the natural logarithms (Ln) of the post-baseline to baseline ratios. The model 
estimates will be back transformed to original values using the formulae detailed in Table 7.1.2-
1.
The preferred model will include the fixed categorical effects of treatment, visit, randomization 
stratification factors (i.e. one term for each combination of the stratification factors of 
hydroxychloroquine and oral corticosteroid use based on IVRS) and treatment-by-visit
interaction, as well as the continuous fixed covariates of baseline measurement and baseline 
measurement-by-visit interaction. For parameters analyzed as percent change from baseline, the 
natural logarithm of the baseline values will be used in the above model specification. An 
unstructured matrix for the within-subject error variance-covariance will be used. The 
denominator degrees of freedom will be calculated according to the Kenward-Roger method.
In case of non-convergence of the preferred model or memory space issues the following back-
up models are defined:
1) The first backup model is the same as the preferred model but the Kenward-Roger method 
will be replaced by Satterthwaite approximation.
2) The second backup model is the same as the preferred model but without the term for 
baseline measurement-by-visit interaction.
The second back-up model will only be provided if the first back-up model does not converge or 
has memory issues.
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The model will provide least-squares mean estimates, standard errors and 2-sided 95% 
confidence intervals for mean change at all time points within and between treatments. Where 
applicable, for specific visits, the t-statistic corresponding to the Type III sums of squares for the 
differences in the least squares means will be used to obtain p-values for treatment group 
comparisons.
7.1.5.2
Model Assumption Assessment
The assumptions underlying the longitudinal repeated measures analysis model will be checked, 
if specified in Section 7.5. This section also details the steps to follow in case these assumptions 
would not be satisfied.
Assessment of Treatment-by-Baseline Interaction:
Treatment-by-baseline interaction will be assessed for the Visit 85 estimates. In the model 
defined in 7.1.5.1, the interaction will be tested by including the treatment-by-baseline 
interaction.
The following contrast statements will be used of testing for interaction.

Contrast coefficients for all visits but Visit 85 will be zero.

Contrast coefficients at Visit 85 are presented in Table 7.1.5.2-2.
Table 7.1.5.2-2:
Contrast Coefficients for the treatment-by-baseline interaction for 
visit 85 estimates
Treatment by baseline interaction
Contrast Coefficients
Lulizumab by baseline value
1
BMS-986142 by baseline value
0
Placebo by baseline value
-1
Lulizumab by baseline value
0
BMS-986142 by baseline value
1
Placebo by baseline value
-1
The test for interaction will be performed at the 0.10 level of significance. If significant, the 
interaction will be assessed as qualitative or quantitative. Assessment of the interaction type will 
be based on regression lines plotted for each treatment group. The intercepts and slopes for these 
regression plots will be obtained from the analysis model including the interaction term. The 
intercepts will be estimated by the least squares means. The abscissa of the plots will range from 
the minimum baseline value from all subjects included in the analysis to the maximum baseline 
value.
If the regression lines do not cross, or the crossing is judged not severe (i.e., the crossing occurs 
near the boundary or beyond the range of baseline values), then the interaction will be considered 
quantitative and this does not compromise the validity of the treatment comparisons. In this case, 
the treatment comparisons will be made using the model without the interaction term.
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Otherwise, the interaction will be considered qualitative and treatment comparisons will not be 
presented as a result of the complete model. In this case, the impact of the baseline value on 
treatment effect will be investigated by summarizing the data in subsets defined by baseline 
categories.
Assessment of Treatment-by-Randomization Stratification Factor Interaction: 
Treatment-by-combination of stratification factors interaction for estimates at Visit 85 will be 
assessed using method described below. In the model defined in 7.1.5.1, the interactions will be 
tested by including the treatment-by-combination of stratification factor interaction and 
appropriate contrast statement for testing the interaction in the visit 85 estimates. Contrast 
coefficients for all visits but Visit 85 will be zero. The tests for interaction will be performed at 
the 0.10 level of significance.
Outlier Detection:
Specifically, an outlier is defined as an observation with a residual that is more than three times 
the interquartile range above the 75th percentile or below the 25th percentile. Outliers will be 
identified based on diagnostics performed for the primary efficacy outcome measure using 
standardized residuals from the mixed effect model with repeated measurement. These 
diagnostics will be based on the box plot. If outliers are present, then additional sensitivity 
analyses will be performed with the outliers excluded, in order to assess their impact on the 
results.
Adjustments for baseline imbalances:
Adjustments for baseline imbalances between treatment groups in the longitudinal repeated 
measures model may be performed as a sensitivity analysis: baseline characteristics for which a 
clinically important imbalance exists between the treatments will be identified. If such 
imbalances exist, an adjustment will be performed by including the corresponding baseline 
characteristics as additional covariates in the longitudinal repeated measures model. This will 
allow the assessment of the importance of these imbalances on the treatment group comparisons.
7.1.6
Kaplan-Meier Curve and Estimates for Time-to-Event Analyses
Kaplan-Meier plots31 of time to event variables will be displayed by treatment group. Unless 
otherwise specified, the plot will be presented only when there are at least 5 events in one 
treatment group. Additionally, a table will accompany the plot and will display the Kaplan-Meier 
estimates of the cumulative proportion (with 95% CI calculated based on Greenwood’s method32
when applicable) of subjects with event at specific time points by treatment group. If the 
estimated lower bound of 95% CI is below 0 or the estimated upper bound of 95% CI is over 1, 
then it will be restricted to 0 or 1 respectively.
7.1.7
Test for Proportion of Subjects with a Characteristic at Visit t
In cases that a comparisons between proportions is needed, the Chi-square test will be used to 
compare the proportions between each of the active treatment arms and the placebo arm. The 
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Chi-square p-value will be provided for each comparison between the active treatment and the 
placebo arm. In addition, the difference of in proportions between each active treatment and the 
placebo arm will be estimated and their corresponding 95% confidence interval will be 
calculated.
The construction of confidence intervals for binary variables will be based on normal 
approximation if the number of the events in each individual treatment arm is at least 5. 
Otherwise, confidence interval using an exact method will be provided. The exact confidence 
intervals for binary variable within treatment group and between treatment groups will be 
constructed.
7.2
Study Conduct
Relevant protocol deviations, which could have an impact on the primary/key efficacy endpoint, 
will be identified for all subjects who are randomized and receive study medication during the 
double-blind period. Details of relevant protocol deviations are provided in APPENDIX 1.
All subjects with relevant protocol deviations that could affect the primary efficacy will be 
identified prior to database lock and unblinding of treatment assignment. All relevant protocol 
deviations will be listed and summarized by treatment group. The subjects identified with
relevant protocol deviation will not be excluded from any analysis population described in 
Section 6.3. If at least 10% of total subjects in all treatment arms in the efficacy analysis 
population demonstrate relevant protocol deviations, a per-protocol analysis may be performed.
The per-protocol analysis will exclude data from subjects with relevant protocol deviations as 
specified in APPENDIX 1.
7.3
Study Population
7.3.1
Subject Disposition
The disposition of subjects will be summarized for the pre-treatment period, double-blind 
treatment and follow-up periods.
The summary of subject disposition for the pre-treatment period will be based on all enrolled 
subjects. It will include a summary of the:

number of subjects enrolled

number (percentage) of subjects randomized

number (percentage) of subjects not randomized

number of subjects randomized and treated by treatment group

number of subjects randomized but not treated by treatment group

number (percentage) of subjects per reason for not being randomized.
Percentages will be on all enrolled subjects. The reasons for not being randomized will also be 
listed, for those subjects that were not randomized.
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The summary of subject disposition for the double-blind treatment period will be based on the 
MITT analysis population and will summarize by treatment group the:

number (percentage) of subjects completing the double-blind treatment period

number (percentage) of subjects not completing the double-blind treatment period (i.e. early 
discontinued subjects)

number (percentage) of subjects per reason for not completing the double-blind treatment 
period (i.e. reasons for early discontinuation)

number (percentage) of subjects continuing in the study (i.e. entering in the follow-up period)

number (percentage) of subjects not continuing in the study (i.e. not entering in the follow-up 
period)

number (percentage) of subjects per reason for not continuing in the study
Percentages will be on all randomized and treated subjects. The reasons for not completing the 
double-blind treatment period or for not continuing in the study will also be listed, for those 
subjects that either did not complete the double-blind treatment period or did not continue in the 
study.
The summary of subject disposition for the follow-up period will be based on the MITT analysis 
population for those subjects that have entered the follow-up period (based on information on the 
status page at the end of double-blind treatment) and will summarize by randomized treatment 
group the:

number (percentage) of subjects completing the follow-up period

number (percentage) of subjects not completing the follow-up period

number (percentage) of subjects per reason for not completing the follow-up period
Percentages will be on all subjects entering the follow-up period. The reasons for not completing 
the follow-up period will also be listed, for those subjects that did not complete the follow-up 
period.
The number of subjects enrolled, randomized, and treated will be summarized by country and 
study site.
7.3.2
Demography and Baseline Characteristics
Demographic and baseline disease characteristics will be summarized by randomized treatment 
group and overall based on the MITT analysis populations. For continuous variables, they will be 
summarized using means, standard deviations and ranges, based on non-missing observations
(see Section 7.1.3). The distribution of categorical variables will be summarized by treatment 
group using frequency and percentage (see Section 7.1.4). For categorical variables, percentages 
will be calculated out of the total number of subjects in the data set, overall and by treatment 
group (i.e., each denominator includes the number of subjects with missing/unknown values for 
the characteristic).
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Table 7.3.2-2:
Demographic and Baseline Characteristics
Characteristic
Summarized as
Categories
Age (years)
Categorical and Continuous
< 65yrs
≥ 65yrs
Gender
Categorical
Male
Female
Female Age
Categorical
50yrs
> 50yrs
Race
Categorical
White
Black or African American
Asian
Other
Ethnicity
(to be summarized only for USA 
subjects)
Categorical
Hispanic/Latino
Non Hispanic/Latino
Region
Categorical
North America
South America
Europe
Asia
(see APPENDIX 2)
Total Body Weight (kg)
Continuous
Time from First Diagnosis of 
Sjogren’s syndrome (years)
Continuous
Randomization stratification factors 
as recorded on IVRS
Categorical
Hydroxychloroquine use (YES/NO)
Oral corticosteroid use (YES/NO)
Combinations of both:
Hydroxychloroquine use and Oral 
corticosteroid use
Hydroxychloroquine use and No 
oral corticosteroid use
No hydroxychloroquine use and 
Oral corticosteroid use
No hydroxychloroquine use and No 
oral corticosteroid use
Randomization stratification factors 
as recorded on eCRF
Categorical
Hydroxychloroquine use (YES/NO)
Oral corticosteroid use (YES/NO)
Combinations of both:
Hydroxychloroquine use and Oral 
corticosteroid use
Hydroxychloroquine use and No 
oral corticosteroid use
No hydroxychloroquine use and 
Oral corticosteroid use
No hydroxychloroquine use and No 
oral corticosteroid use
Number of 2015 ACR-EULAR 
Classification Criteria met
Continuous
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Table 7.3.2-2:
Demographic and Baseline Characteristics
Characteristic
Summarized as
Categories
ESSDAI Total Score
Continuous
ESSDAI Constitutional Domain 
Score
Continuous
ESSDAI Lymphadenopathy Domain 
Score
Continuous
ESSDAI Glandular Domain Score
Continuous
ESSDAI Articular Domain Score
Continuous
ESSDAI Cutaneous Domain Score
Continuous
ESSDAI Pulmonary Domain Score
Continuous
ESSDAI Renal Domain Score
Continuous
ESSDAI Muscular Domain Score
Continuous
ESSDAI Peripheral Nervous System 
(PNS) Domain Score
Continuous
ESSDAI Central Nervous System 
(CNS) Domain Score
Continuous
ESSDAI Haematological Domain 
Score
Continuous
ESSDAI Biological Domain Score
Continuous
ESSPRI
Continuous
Unstimulated whole saliva secretion
Continuous
Stimulated whole saliva secretion
Continuous
Schirmer’s Test moisture measure 
for both eyes
Continuous
Vaginal dryness numeric rating scale
Continuous
Physician’s global assessment of 
disease activity (MDGA)
Continuous
Subject’s global assessment of 
disease activity (PGA)
Continuous
7.3.3
General Medical History
The number (percent) of subjects with general medical history findings before the first study 
medication will be summarized by treatment group and overall using the MITT analysis 
population. A corresponding listing of medical history findings will be provided.
7.3.4
Prior (Current) Medication
Prior (current) medications are defined as medications with a start date prior to the first day of 
double-blind treatment period and without a stop date prior to the consent date, i.e. current 
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medication will be any medication with at least 1 dose taken on or after the day of consent date 
up to the day prior to the first dose of study medication.
Prior medication information before the first study medication will be summarized by drug class 
and (generic) drug name and by treatment group using relative frequencies. Listings of prior 
medication will be presented. The results will be based on the MITT analysis population.
Missing and partial date handling of start and stop dates of prior medications, is described in 
Section 8.5. The World Health Organization (WHO) dictionary is used to code non-study 
medications.
7.4
Extent of Exposure
7.4.1
Study Therapy
The extent of exposure during the double-blind treatment period will be summarized for the As-
treated analysis population in the following ways:

by the number of days the subject is known to be on study drug, ignoring any dosing 
interruptions, 
using 
the 
formula 
below:
Exposure (in days) = (date of last study medication) - (date of first study medication)
For Lulizumab or matching placebo, the date of last study medication corresponds to the last 
date of study medication + 7 days (the offset of 7 days represents the dosing interval of 7 
days).
For BMS-986142 or matching placebo, the date of last study medication corresponds to the 
last date of study medication +1.
Because subjects receive either lulizumab or BMS-986142 together with the corresponding 
matching placebo for each medication

the date/time of first study medication will be the earliest of the dates/times of first 
administration of BMS-986142 or Lulizumab or matching placebo. 

the date/time of last study medication will be the maximum of last study medication
date/time as described above for each medication.
The frequency will be presented according to the duration ranges (in days) : 1-28, 29-56, 57-
84 and >=85.

by the number of Lulizumab or matching placebo study drug injections. The frequency will 
be presented using the following ranges in the total number of injections: 1-4, 5-8, 9-12, >12.

by the number of BMS-986142 or matching placebo doses. The frequency will be presented 
using the same ranges as for the summary of number of days.
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In addition to the frequencies mentioned above, the mean, standard deviation, median, minimum 
and maximum values will be summarized for all the above mentioned ways of summarizing 
extend of exposure.
7.4.2
Discontinuations from Study Therapy
Discontinuation from study therapy is defined as subject’s termination of the study medication 
without resumption prior to study completion. Section 3.5 of the protocol mentions the reasons 
for which a subject must discontinue treatment.
Discontinuation from study therapy during the double-blind period is capture on the study status 
case report form (CRF) pages. For the analysis of discontinuations from study therapy refer to 
section 7.3.1.
7.4.3
Treatment Compliance
The CRF for this study will capture information on injections of the Lulizumab or matching 
placebo and doses of BMS-986142 or matching placebo.
The number of subjects with missed injections or doses (excluding missed injections or doses 
due to premature discontinuation from the study) will be summarized by number of missed 
injections or doses based on the As-treated analysis population for the ST period by treatment 
groups. The summary will be produced separately for missed injections and missed doses. A 
corresponding listing for all subjects who skip either any injection or dose will be produced.
 
 
 
 
 
 
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7.4.5
Immunosuppressant Medication
Immunosuppressant medications summaries will be provided to present the medication use of 
corticosteroids, NSAIDs (non-steroidal anti-inflammatory drugs), and non-biologic DMARDs
(non-biologic disease-modifying antirheumatic drugs).
This summary will include both prior and concomitant medications (see sections 7.3.4 and 7.4.4
for definitions, respectively).
The number and percent of subjects receiving corticosteroids, NSAIDs, and DMARDs will be 
summarized by treatment group for MITT analysis population.
7.4.6
Corticosteroids
The average daily corticosteroid dose (prednisone equivalent) and its change from baseline will 
be summarized over time by treatment group for the double-blind period using the MITT 
analysis population.
7.4.7
Narcotic analgesics
A summary of use of narcotic analgesics will be provided. This summary will include both prior 
and concomitant medications (see sections 7.3.4 and 7.4.4 for definitions, respectively). The 
number and percent of subjects receiving narcotic analgesics will be summarized by treatment 
group for MITT analysis population.
7.4.8
Anticoagulants
A summary of use of anticoagulants will be provided. This summary will include only prior 
medications (see sections 7.3.4 for definition). The number and percent of subjects receiving 
anticoagulants as prior medication will be summarized by treatment group for MITT analysis 
population.
7.5
Efficacy
Unless otherwise specified, all efficacy analyses will be produced using the MITT analysis 
population.
7.5.1
Primary efficacy analysis
The EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) is a systemic disease 
activity index that was designed to measure disease activity in subjects with pSS (see Protocol 
Appendix 3).33 The ESSDAI parameters are assessed by the investigators and the results from 
each assessment are recorded in site source records as well as entered into the corresponding 
eCRF. The ESSDAI total score will be calculated as described in section 8.6
The primary efficacy endpoint is change from baseline ESSDAI score at Week 12.
The mixed effects model with repeated measures (MMRM) will be used to model the change 
from baseline in ESSDAI score over time for all treatment arms. Details of the model are 
presented in section 7.1.5.1.
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The least square means of the differences of Week 12 change in ESSDAI from baseline between 
each active treatment and the placebo will be estimated and their corresponding two-sided 95% 
confidence intervals will be provided.
The Hochberg’s step-up procedure will be used to adjust the multiplicity due to the comparison 
of two active treatments (lulizumab or BMS-986142) to the placebo arm. The corresponding 
adjusted p-values for the Hochberg procedure will be provided.
The model assumption assessment will be performed following the methodology described in 
section 7.1.5.2.
In addition, the same model will be used to provide estimates for the changes in ESSDAI score at
each time point of assessment as per protocol.
In case that more than 10% of subjects in any treatment group have a relevant protocol deviation, 
leading to exclusion of efficacy data, then this analysis will be repeated excluding efficacy data 
from subjects with relevant protocol deviations, as described in APPENDIX 1.
7.5.2
Secondary and Exploratory Efficacy Analyses
For all secondary endpoints, no multiplicity adjustment will be applied. Nominal p-values will be 
provided.
7.5.2.1
Categorical Endpoints
For each of the following categorical secondary endpoints, the estimate and its corresponding 
two-sided 95% confidence interval will be calculated for the proportion for each treatment arm. 
In addition, differences of the proportions between each active treatment arm and the placebo 
arm will be evaluated and their corresponding two-sided 95% confidence intervals and nominal 
p-values will be provided.

Proportion of subjects with a 3 point improvement from baseline in ESSDAI at Week 12

Proportion of subjects with a 1 point improvement from baseline in ESSPRI at Week 12

Proportion of subjects with both 3 point improvement from baseline in ESSDAI and 
1 point improvement from baseline in ESSPRI at Week 12
The subjects that have discontinued the study prematurely or have missing assessments for 
ESSDAI or ESSPRI at Week 12, they will be counted in these analyses as having no 
improvement since baseline.
The same analysis will be repeated at each timepoint of assessment of ESSDAI and ESSPRI as 
per protocol. For these analyses no nominal p-values will be produced.
For the calculation of ESSDAI refer to section 8.6. For the calculation of ESSPRI refer to section 
0.
7.5.2.2
Continuous Endpoints
The change from baseline in the following continuous endpoints will be analyzed with mixed 
effects model with repeated measures (MMRM) as described in section 7.1.5.1. The model will 
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include all assessments for each parameters as defined in the protocol. Nominal p-values will be 
provided for those endpoints that are defined as secondary endpoints in the protocol.

Change from baseline in ESSDAI scores at each time point of assessment. The change from 
baseline at Week 4, 8, are defined as secondary endpoints as per protocol. The change from 
baseline at Week 12 is the primary efficacy endpoint (see section 7.5.1). See Section 8.6 for 
calculation of ESSDAI.

Change from baseline in ESSDAI domain scores at each time point of assessment. This is 
considered as an exploratory efficacy endpoint. The scores for the ESSDAI domains 
Glandular, Articular, Hematological, Biological, Lymphadenopathy, Pulmonary and 
Constitutional  will be analyzed with mixed effect models. The scores for the ESSDAI 
domains Central Nervous System (CNS), Cutaneous, Muscular, Peripheral Nervous System 
(PNS) and Renal will be analyzed with summary statistics. See Section 8.6 for calculation of 
ESSDAI domain scores.

Change from baseline in ESSPRI scores at each time point of assessment. The change from 
baseline at Week 4, 8, and, 12 are defined as secondary endpoints as per protocol. See 
Section 0 for calculation of ESSPRI.

Change from baseline in score of each individual ESSPRI components (Dryness, Fatigue, 
and Pain) at each time point of assessment. The change from baseline at Weeks 4, 8, and 12
are defined as secondary endpoints as per protocol. See Section 0 for calculation of 
individual ESSPRI components.

Change from baseline in mouth dryness as measured by unstimulated and stimulated salivary 
flow rate at Weeks 4, 8, and 12. See Section 8.8 for calculation of salivary flow rate.
Change from baseline in eye dryness as measured by ocular surface staining (see section 
8.11) , Schirmer’s test (see section 8.9), and tear break-up (see section 8.10) time test at 
Weeks 4, 8, and 12. These analysis will be repeated for each eye separately and combining 
information for the two eyes taking the average of test values on the same visit.
The analyses of secondary endpoints that refer to outcome reported measurements are described 
in section 7.8. The analysis of Trough concentrations of study drugs are described in section 7.7.
7.6
Safety
The safety analysis endpoints described in this section are considered as secondary endpoints. 
For their analysis, there will be no statistical testing of group.
Analysis of all safety data will follow the BMS standard safety data conventions34 35 and 
supplements to the standard conventions as defined in this document.
All summaries of safety parameters during the double-blind period will be provided by treatment 
groups. All safety assessments will be included in the summary tables if the onset date is on or 
after the first dose date and the event occurs within the double-blind period or within 42 days 
post last dose date.
Presentations for the double-blind period will be provided by “as treated” treatment group for the 
as-treated analysis population, unless otherwise specified.
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7.6.1
Adverse Events
All AEs are coded and grouped into Preferred Terms (PT) by System Organ Class (SOC), using 
the latest approved version of the Medical Dictionary for Regulatory Activities (MedDRA) at the 
time of database lock. Listings and summaries will be based on the resulting SOCs and PTs.
AEs will be included in the frequency tabulations if they occur while a subject is on study 
medication up to and including 42 days after the last dose of study medication of either active 
medications or matching placebos. These AE summaries will be based on proportions, which 
represent the number of subjects experiencing the AEs divided by the number of subjects 
received with at least 1 dose of study medication.
In summaries by SOC and PT, AEs will be sorted by decreasing frequency within each SOC and 
PT according to the Lulizumab group. In summaries by PT, AEs will be sorted by decreasing 
frequency within PT according to the Lulizumab group. Counting rules for adverse events are 
described in section 8.18.
All adverse events listings will indicate the unique subject identifier, age, gender, current 
treatment, the date of onset, the date of resolution, day of onset relative to the start of treatment, 
action taken, investigator’s assessment of severity and relationship to study drug.
Laboratory AEs are laboratory changes identified by the investigator as AEs and thus reported on 
the AE pages of the eCRF.
7.6.1.1
Adverse Events
All serious and non-serious adverse events with onset during the double-blind treatment period 
will be summarized by SOC, PT, and treatment group and overall. These summaries will be 
produced for:

all adverse events

adverse events related to the administration of the study drug, as determined by the 
investigator

adverse events leading to discontinuation of study medication, as indicated in the eCRF. This 
analysis will include events independently of the time distance the last dose date.

most common adverse events (reported in 10% of subjects or more in any treatment group)

all serious adverse events, as captured on special CRF pages

all serious adverse events related to the administration of the study drug, as captured on 
special CRF pages

adverse events by intensity, as determined by the investigator
The following adverse events of special interest will be summarized by PT and treatment groups 
during the double-blind period. A subject listing will also be provided.

Infections: All reported infections and infestations within the SOC: Infections and 
infestations. The severity of serious infections will be summarized. In addition, a listing of 
opportunistic infections will be provided.
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
Injection Reactions (Local and Systemic): All reported events defined in pre-specified 
MedDRA code of local and systemic injection reactions.
Additionally, a subject listing will be provided for the following adverse events of special 
interest that occurred during the double-blind period:

Malignancy: All reported events defined in MedDRA Maintenance and Support Services 
Organization (MSSO) Structured MedDRA Query (SMQ) list.

Autoimmunity: All reported events defined in pre-specified MedDRA code of autoimmune 
disorders.

Transaminases Increased: All reported events defined in MedDRA Maintenance and Support 
Services Organization (MSSO) Structured MedDRA Query (SMQ) list. of “Drug related 
hepatic disorders - comprehensive search (SMQ)”
In addition, the number and proportion of subjects who experienced an AE once or multiple 
times (0 Events, 1 Events, 2-3 Events, >=4 Events) will be summarized by PT and treatment 
groups for most common AE (at least 5% subject in any treatment group) and events of special 
interest of infections. This analyses will be performed following the counting rules for unique 
adverse events as described section 8.18.2.
The following subject listings will be produced for:

all reported adverse events, displaying all events (including pre-treatment events) that 
occurred at any time point during the study for subjects that received at least one dose of 
double-blind medication

all unique instances of adverse events (see section 8.18.2), displaying all events (including 
pre-treatment events) that occurred at any time point during the study for subjects that 
received at least one dose of double-blind medication

all serious adverse events, which will also be used for the purpose of clinical trial 
transparence for posting at public websites (e.g., NIH’s www.ClinialTrials.gov)

listing of most common non-serious AEs, for the purpose of clinical trial transparency for 
posting at public websites (e.g., NIH’s www.ClinialTrials.gov)

adverse events leading to discontinuation of study medication

all infections

all malignancies

all autoimmune disorders

local injection reactions

systemic injection reactions
In addition, all SAEs will be described in narratives, regardless of investigator assessment of 
causality.
7.6.1.2
Deaths
All deaths recorded on the status page, the AE page, or SAE page (with a death date, cause of 
death, outcome or SAE categorization present) of the CRF will be considered a death in the 
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analyses. Any deaths that occur during the study will be described in depth as narrative in the 
CSR. All Adverse events with the outcome of death reported during the study will be listed.
7.6.2
Laboratory evaluation
Unless otherwise specified, laboratory data obtained after the start of study medication dosing up 
to and including 42 days after the last double-blind dosing date will be considered as obtained 
during the double-blind treatment period.
7.6.2.1
Marked Laboratory Abnormalities
Laboratory marked abnormality using pre-defined abnormality criteria will also be descriptively 
summarized (see APPENDIX 3). The results of all protocol-specified clinical laboratory tests, as 
well as laboratory results outside of the normal range, will be listed.
The frequency of subjects with any marked laboratory abnormality will be presented by 
laboratory test during the double-blind treatment period. The results are based on the As-treated 
analysis population.
The criteria used for classifying laboratory test results as markedly abnormal will be listed.
7.6.2.2
Change from Baseline for Selected Laboratory Parameters Over Time
Scheduled laboratory measurements and corresponding change from baseline values will be 
summarized by treatment and nominal visit for each laboratory test for the As Treated analysis 
population using descriptive statistics (see section 7.1.3). Visit windows are provided in Section 
8.1 in order to link each laboratory test to a scheduled visit. The following laboratory parameters 
will be analyzed:

Hemoglobin

Hematocrit

Total leukocyte count

Basophils Count

Eosinophils Count

Lymphocytes Count

Monocytes Count

Neutrophils Count

Platelet count

Aspartate aminotransferase (AST)

Alanine aminotransferase (ALT)

Total bilirubin

Direct bilirubin

Alkaline phosphatase

Lactate dehydrogenase (LDH)
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
Creatinine

Blood Urea Nitrogen (BUN)

Uric acid

glucose at fasting state

Total Protein

Albumin

Sodium

Potassium

Chloride

Calcium

Phosphorus

Magnesium

Creatine kinase

Total cholesterol at fasting state

HDL-cholesterol at fasting state

LDL-cholesterol at fasting state

Triglycerides at fasting state

ESR (local test)

hsCRP

Urine Protein

Urine Glucose

Urine Blood

Urine Specific gravity

Urine pH
As per protocol all laboratory parameter mentioned above are part of the safety laboratory test 
panel and are supposed to be assessed with the subject at fasting state. However for analysis 
purposes all data will be considered for analysis, even if the subject was not in a fasting state, 
unless if it is mentioned otherwise above. In these cases, only those measurement where the 
subject was on fasting state will be considered for analysis.
7.6.2.3
Pregnancy Test Results
A by-subject listing of positive pregnancy test results will be provided using the As-treated 
analysis population.
7.6.3
Electrocardiogram
Summary statistics (n, mean, standard deviation, median, minimum, and maximum) will be 
presented for each ECG parameters and the corresponding changes from baseline by treatment 
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and visit. ECG readings will be evaluated by the Investigator and abnormalities, if present, will 
be listed.
The frequency distribution of subjects’ maximum recorded post-dose QTcF, PR, QRS and 
QTcF (see section 8.19) will be tabulated by treatment and summarized within the CSR text for 
the ranges in Table 7.6.3-2. Individual QTcF, PR, QRS or QTcF values meeting these criteria 
will be flagged in the data listing.
Table 7.6.3-2:
Electrocardiogram Parameter Categorization
Parameter
Categorization
QTcF (msec)
=< 450
450 < to =< 480
480 < to =< 500
> 500
PR (msec)
=< 200
> 200
QRS (msec)
=< 120
> 120
Change from baseline in QTcF (msec)
=< 30
30 < TO =< 60
> 60
7.6.4
Vital Sign
Vital signs parameters (systolic blood pressure, diastolic blood pressure, heart rate, respiratory 
rate and body temperature) will be listed. Summaries of vital sign parameters will be provided 
for each vital sign parameter at corresponding visits by treatment and respective changes from 
baseline. Subjects with vital signs outside of a pre-specified range will also be listed.
The following criteria will be used to determine vital sign results that are outside of a pre-
specified range, where changes from baseline are based on matched postural positions and are 
calculated as parameter value - baseline parameter value:
Table 7.6.4-2:
Vital signs criteria
Vital sign
Criteria
Heart Rate(bpm)
Value > 100 and change from baseline > 30, or
Value < 55 and change from baseline < -15
Systolic BP(mmHg)
Value > 140 and change from baseline > 20, or
Value < 90 and change from baseline < -20
Diastolic BP(mmHg) 
Value > 90 and change from baseline > 10, or
Value < 55 and change from baseline < -10
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Table 7.6.4-2:
Vital signs criteria
Vital sign
Criteria
Respiration(breaths/min)
Value > 16 or change from baseline > 10
Temperature (°C)
Value > 38.3°C or change from baseline > 1.6°C
7.6.5
Physical Examination Findings
All physical examination abnormal findings will be listed per subject by visit.
 
 
 
 
 
 
 
 
 
 
 
7.8
Outcomes Research Analyses
The outcome research analysis endpoints described in this section are considered as secondary 
endpoints. For their analysis, no multiplicity adjustment will be applied and no p-values will be 
provided.
Descriptive summary statistics (see section 7.1.3) will be provided for absolute value and change 
(or percent change) from baseline to all assessments as described in the protocol for primary 
measures the following outcome research assessments:

Numeric Rating Scale (NRS) scores for mouth, eye and vaginal dryness (see section 8.12). 
Each of these scores will be analyzed separately.

Subject global assessment of disease activity (SubGDA) and physician global assessment of 
disease activity (phyGDA) will be analyzed separately (see section 8.13)
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
Short Form - 36 acute (SF-36 acute) (see section 8.14). Both the physical and mental scales 
as well as the individual sub-scales will be analyzed.

Female Sexual Function Index (FSFI) (see section 8.15). Both the full scale score and the 
individual domain scores will be analyzed.

Work participation and activity impairment questionnaire (WPAI) (see section 8.16). Percent 
work time missed due to health, percent impairment while working due to health, percent 
overall work impairment due to health and percent activity impairment due to health will be 
analyzed.

PROMIS Fatigue Short Form 8a (see section 8.17).
If deemed necessary after observing results from the analyses described above, the MMRM 
method or other modelling methods may be applied to changes from baseline in primary 
measures (e.g., total scores) of the above outcome research measures.
7.9
Biomarker Analyses
 
 
 
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7.9.2
Biopsies
The focus scores of lip or parotic gland biopsies and the corresponding changes from baseline 
will be summarized by treatment and visit using descriptive statistics (see section 7.1.3). Visit 
windows are provided in Section 8.1 in order to link each score test to a scheduled visit. 
A subject listing of all lip or parotic gland biopsy findings will be provided.
 
 
 
 
 
  
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7.11
Interim Analyses
One interim analysis will be conducted when at least 30 subjects reach Week 12 (complete 
12 weeks of treatment) and complete the specified assessments for the Week 12 ESSDAI score. 
The interim analysis will be conducted in a fully blinded manner such that treatment group 
assignments of study subjects are not known and are not used in any manner in the analysis. 
Specifically, a blinded examination of the variance of the primary endpoint will be performed 
and compared to the assumption used in planning the study. If this comparison suggests the 
initial assumption is substantially too low, the total study sample size may be increased by up to 
45 additional subjects (i.e., to a maximum of 120 subjects in total) to maintain adequate study 
power.28 29 30 Regardless of the outcome from the blinded examination of variability, the study 
sample size will not be decreased.
The blinded examination of the variance will be based on the following assumptions:

the placebo adjusted change from baseline at Week 12 for both active treatment arms 
(lulizumab or BMS-986142) will be  3 ESSDAI points

the change from baseline at Week 12 will be the same for both active treatment arms.
The calculation of the blinded examination of the variance will include randomized subjects who 
received at least one dose of study drug with non missing ESSDAI assessment both for baseline 
and Week 12. Subjects will be considered for analysis if their Week 12 assessment occur while 
on double-blind study medication.
The estimate of the blinded examination of the variance 
2
blinded
S
will be computed using the 
formula mentioned by Kieser and Friede (2000)36:
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








3
1
2
2
2
1
3
i
i
pooled
blinded
n
n
S
S


where:

2
pooled
S
is the variance of change from baseline at Week 12 in ESSDAI as calculated based on 
all subjects included in the interim analysis

n is the number of subjects included in the interim analysis (across all treatment groups)

iis the assumed change from baseline at Week 12 for each of the 3 arms

is the assumed overall mean. For this calculation it is assumed to be average of 
iacross 
all treatment groups
Since 
iand , the 





3
1
2
i
i


will be approximated by the term below:
2
986142
2
986142
986142
2
986142
3
3
3

































Placebo
BMS
Lulizumab
Placebo
Placebo
BMS
Lulizumab
BMS
Placebo
BMS
Lulizumab
Lulizumab












where 
Lulizumab

= 
986142

MS

=3 ESSDAI points and 
Placebo

=0.
The common standard deviation will be estimated based on the estimate of the blinded 
examination of the variance. 
The common standard deviation will be compared against the initial study assumptions for 
sample size estimation (see section 5). Would it be substantially larger than the initially planned, 
the sample size for the study will be re-estimated taking into consideration the maintenance of 
adequate power for the study (see section 5). 
The final decision on sample size and power for this study will be made by BMS senior 
management.
8
CONVENTIONS
8.1
Time from first diagnosis of Sjogren’s syndrome
The time from first diagnosis of Sjogren’s syndrome of T1DM is calculated as the number of 
years from the diagnosis date to informed consent date:
(1 + consent date - diagnosis date) / 365.25.
If the date of diagnosis is partially missing, the following rules will take effect:
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
Missing day, but month and year are present: the day will be imputed as the 15th day of the 
month.

Missing day and month, but year is present: the day and month will be imputed as 30 June of 
the year (provided that the imputed date is less than the consent date).

Missing year, but day and month are present: No imputations will occur, and the subject will 
be excluded from all related summaries.

Missing day, month and year: No imputations will occur, and the subject will be excluded 
from all related summaries.

If any such imputed date falls after the consent date, then the diagnosis date will be taken as 
equal to the consent date.
In cases that these dates are presented in listings, only the portion of the date of diagnosis 
actually observed, rather than imputed dates, will be displayed in listings. 
8.2
Analysis Window for Longitudinal Assessments
8.2.1
Baseline Value
For each subject, the baseline value of a parameter is defined as the last assessment of that 
parameter on or prior to the date/time of the first dose of the double-blind study medication.
If time is of measurement of a parameter or time of first dose are missing, then the baseline value 
is defined as the last assessment of that parameter on or prior to the date of the first dose of the 
double-blind study medication.
8.2.2
Longitudinal Assessments
Day 1 for the double-blind treatment period is the start date of double-blind treatment 
medication. The observation closest to the target day (and time where applicable) is the 
measurement used in the analysis for each scheduled visit. 
The following visit windows will apply for all measurements in the double-blind treatment and 
follow-up periods:
Table 8.2.2-1:
Visit Windows for Double-Blind Treatment Period
Visit
Target Day
Day Range
Day 8 (Week 1)
8
Post-baseline - 11*
Day 15 (Week 2)
15
12 - 18*
Day 22 (Week 3)
22
19 - 25*
Day 29 (Week 4)
29
26 - 32*
Day 36 (Week 5)
36
33 - 39*
Day 43 (Week 6)
43
40 - 46*
Day 50 (Week 7)
50
47 - 53*
Day 57 (Week 8)
57
54 - 60*
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Table 8.2.2-1:
Visit Windows for Double-Blind Treatment Period
Visit
Target Day
Day Range
Day 64 (Week 9)
64
61 - 67*
Day 71 (Week 10)
71
68 - 74*
Day 78 (Week 11)
78
75 - 81*
Day 85 (Week 12)
85
82 - 95*
* see section 8.3 for the definition of double-blind treatment period
Day 1 for the follow-up period is the day after the last day of double-blind treatment period (see 
section 7.4.1 for definition of last day of double-blind treatment period). The observation closest 
to the target day (and time where applicable) is the measurement used in the analysis for each 
scheduled visit. Because of the definition of post double-blind treatment observations that may 
still fall in the double-blind period (see Section 8.3) the early days during the follow-up period 
may actually provide data that are still considered as occurring during double-blind period.
Table 8.2.2-2:
Visit Windows for the Follow-Up Period
Visit
Target Day in Follow-up Period
Day Range in Follow-up Period
Day 106 (Week 15)
21
Post double-blind treatment - 31
Day 127 (Week 18)
42
32 - latest assessment
The use of post double-blind treatment observations that may still fall in the double-blind period 
is specified in Section 8.3. 
For all parameters, if a subject has more than one measurement included within a window, the 
assessment closest to the target day will be used. In case of ties between observations located on 
different sides of the target day, the earlier assessment will be used. In case of ties located on the 
same side of the target day (i.e. more than one value for the same day but different time), the 
value with the earlier entry date/time will be used.
8.3
Post-Treatment Efficacy and Safety Observations
While efficacy and safety observations will be listed regardless of whether the subject was taking 
blinded study drug, observations may not contribute to summaries/analyses if they are measured 
after the last dose of double-blind study medication as indicated below:

all efficacy, clinical biomarkers and outcome research will be included in the analyses of 
double-blind period if measured on or prior to 28th day after the last dose date of lulizumab 
or matching placebo or on or prior to the 2nd day after the last dose date of BMS-986142 or 
matching placebo, whichever is latest. These windows are based on the four half-life times of 
each active medication (7 days for lulizumab, 11 hours for BMS-986142).
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
all vital signs, pharmacokinetic, and immunogenicity assessments will be included in the 
analyses of double-blind period if measured on or prior to 21th day after the last dose date of 
lulizumab or matching placebo or on or prior to the 2nd day after the last dose date of BMS-
986142 or matching placebo, whichever is latest. These windows are based on the three half-
life times of each active medication (7 days for lulizumab, 11 hours for BMS-986142). These 
windows are different from the rest of the parameters because of the protocol visit schedule 
at 21 days since the end of the double-blind period.

all adverse events will be included in the analyses of double-blind period if measured on or 
prior to 42th day after the last dose date of lulizumab or matching placebo or on or prior to 
the 3rd day after the last dose date of BMS-986142 or matching placebo, whichever is latest.
These windows are based on the six half-life times of each active medication (7 days for 
lulizumab, 11 hours for BMS-986142).

all safety laboratory and lipid parameter will be included in the analyses of double-blind 
period if measured on or prior to 28th day after the last dose date of lulizumab or matching 
placebo or on or prior to the 2nd day after the last dose date of BMS-986142 or matching 
placebo, whichever is latest. These windows are based on the four half-life times of each 
active medication (7 days for lulizumab, 11 hours for BMS-986142). These windows are 
different from the rest of the safety parameters because of the protocol visit schedule at 42 
days since the end of the double-blind period.
8.3.1
Missing and Multiple Measurements
For listings of efficacy, safety, pharmacokinetic, biomarkers, immunogenicity, outcome research 
measures, missing values will be represented as not reported.
For all analyses and summaries of efficacy, safety, outcome research measures, missing values 
will not be imputed.
Some laboratory samples may be inadvertently analyzed multiple times for the same test, 
producing multiple lab results on the same collection date and time for the same subject. The 
selection of laboratory result for analysis for this subject will follow BMS global standard.
All blood pressure measurements will be included in the summaries/analysis independently of 
the position they were measured, e.g., sitting, supine, standing.
8.4
Assignment of Doses to Adverse Events and Laboratory Assessments
In case of missing dates and/or times, prior to assigning the treatment that the subject received at 
the onset of an AE or at the time of a laboratory assessment, imputation rules will be applied as 
follows:
For AEs, a missing or incomplete onset date will be imputed according to the following 
conventions:

If the onset date for an AE is missing or incomplete, an imputed date will be derived to slot 
the event to an appropriate analysis period. This derived date will not be reported in summary 
tables or listings. Every effort will be made to determine the actual onset date for the event or 
to obtain a reliable estimate for the onset date from the investigator.
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
If an onset date is missing, the derived onset date will be calculated as the first non-missing 
valid date from the following list (in order of precedence):

First active study medication date

Consent date

Visit date corresponding to the visit at which the event was reported.

If a valid non-missing date is not available for any of these dates, the derived onset date 
will be set to missing.

If an onset date is incomplete, the derived onset date will be calculated using the following 
algorithm:

Calculate a surrogate date as the first non-missing valid date from the following list (in 
order of precedence):
First active study medication date
Consent date
Visit date corresponding to the visit at which the event was reported
If a valid non-missing date is not available for any of these dates, the surrogate date 
will be set to missing.

Based on the information provided, set the derived date to the earliest possible date. If 
only a year is provided, set the derived date to January first of that year. If a year and 
month is provided, set the derived date to the first day of that month.

If the surrogate date is non-missing then:
If the derived date is on or after the surrogate date use the derived date as calculated
If the derived date is prior to the surrogate date and the surrogate date is consistent 
with the partial data provided for the onset date, use the surrogate date as the derived 
date
If the derived date is prior to the surrogate date and the surrogate date is not 
consistent with the partial data provided for the onset date then set the derived onset 
date to be the latest possible date based on the partial onset date information 
provided. If only a year is provided, set the derived date to December 31st of that 
year. If a year and month is provided, set the derived date to the last day of that 
month.

If all three dates used to determine the surrogate date are missing, then based on the 
information provided, set the derived date to the earliest possible date. If only a year is 
provided, set the derived date to January first of that year. If a year and month is 
provided, set the derived date to the first day of that month.
A drug treatment file will be created, containing any starting and stopping dose as well as 
intermediate dose changes within each study period, with dates and times as recorded on the 
CRF.  In this context,

the date of the first dose of study medication is defined as the earliest start date with number 
of tablets > 0 or injections > 0 reported on the study medication page. 

the date of the last dose of study medication is defined as the latest start or stop date with 
number of tablets > 0 or injections > 0 reported on the study medication page.
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
if a dosing time is missing for a starting dose of study drug in a study period or a dose 
change, then it is defaulted to 9:00. 

if there’s a gap in the dosing information, then the dosing time corresponding to the start date 
of the gap, is defaulted to 00:00.
If a dosing time is missing for a last stop dosing date for the study drug in a study period, then it 
is defaulted to 23:59. 
8.4.1
Treatment at Onset of an Adverse Event
Both onset date and (if requested) onset time of an AE will be compared to the dosing 
information. Treatment will then be the dose at the last observation for a subject in the dosing 
file where the AE onset date/time is not earlier than the dose date/time.
8.4.2
Treatment at the Time of a Laboratory Assessment
Laboratory draw date and time will both be compared to the dosing information. Treatment at the 
time of the laboratory assessment will then be the dose at the last observation for a subject in the 
dosing file where the laboratory date/time is not earlier than the dose date/time.
8.5
Non-study Medications
Start and stop date of all non-study medications are collected on the CRF. In order to classify 
medication as prior or concomitant, partial, missing or invalid start and stop dates will be 
imputed where possible as follows:

If the reported start date is missing or invalid and the informed consent date is not missing or 
invalid, then the imputed start date is set equal to the informed consent date. If the consent 
date is missing or invalid and the birth date is not missing or invalid, then the imputed start 
date is set equal to the birth date. If the start date, the consent date and the birth date are all 
invalid or missing, then the imputed start date is set equal to missing.

If the reported start date is partially entered, then the imputed start date is set equal to the 
earliest possible reported start date based on the partial entered reported start date.

If the reported end date is missing, continuing, unknown or invalid, then the imputed end 
date is set equal to the most recent database extraction date.

If the reported end date of the medication is partial, then the imputed end date is set equal to 
the last possible reported end date based on the partial entered reported end date.
Imputed dates will not appear on the listings of non-study medication.
8.6
EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)
The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as 
the sum of scores for activity level for each domain.33 The scores and the domains are presented 
in Table 8.6-2.
The ESSDAI domain scores will be calculated using the values presented in in Table 8.6-2 for 
each domain separately.
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Table 8.6-2:
The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) 
scoring algorithm
Domain
Score for activity level
Constitutional
No=0, Low=3, Moderate=6
Lymphadenopathy
No=0, Low=4, Moderate=8, High=12
Glandular
No=0, Low=2, Moderate=4
Articular
No=0, Low=2, Moderate=4, High=6
Cutaneous
No=0, Low=3, Moderate=6, High=9
Pulmonary
No=0, Low=5, Moderate=10, High=15
Renal
No=0, Low=5, Moderate=10, High=15
Muscular
No=0, Low=6, Moderate=12, High=18
Peripheral Nervous System (PNS)
No=0, Low=5, Moderate=10, High=15
Central Nervous System (CNS)
No=0, Moderate=10, High=15
Haematological
No=0, Low=2, Moderate=4, High=6
Biological
No=0, Low=1, Moderate=2
Information extracted from Table 1 in Seror R, Theander E, Brun JG, et al. Ann Rheum Dis, 2015;74:859–866. 33
 
 
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8.18
Counting rules for adverse events
8.18.1
At Subject Level
Where a subject has multiple adverse events within the same system organ class in a single 
analysis period, the subject will only be counted once at the system organ class level in adverse 
event frequency tables.
When a subject has the same adverse event, based on preferred terminology, reported multiple 
times in a single analysis period, the following criteria, in order of precedence, will be used to 
select the event to be included in summary tables:

Relationship to study medication

Intensity of event

Onset date and time
When assessing relationship to study medication, relationship as reported by the investigator, 
events will be reported as related or not to study medication. Related events will take precedence 
over unrelated events in determining the event to include in summary tables.
More intense events will take precedence over less intense events in determining the event to 
include in summary tables.
Earlier onset date-time events will take precedence over late onset date-time events in 
determining the onset to include in summary tables.
When reporting adverse events by intensity, in addition to providing a summary table based on 
the event selection criteria detailed above, summary tables will also be provided based on the 
most intense event during the analysis period - independent of relationship to study medication. 
For these tables, the following criteria, in order of precedence, will be used to select the event to 
be included in summary tables:

Intensity of event

Onset date and time
Subjects will only be counted once in the ‘Total’ at their maximum intensity, regardless of SOC 
or PT.
8.18.2
At Event Level
At event level, each unique AE record will be counted. Unique AE record can be obtained by 
collapsing all AE records following a standard algorithm. The CRF data will be processed 
according to standard BMS algorithms to categorize each line of patient data as a new 
occurrence or a continuation of an existing event. This determination will be based upon onset 
and resolution dates. Each line of patient data will represent the maximum severity observed as 
well as the last known assessed relationship to study medication by the investigator.
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8.19
Conventions of ECG Data
All available non-missing values of ECG parameters should be used in the listings, 
summarizations, and analyses. However, if QTcF is missing and RR in seconds is available, then 
QTcF will be calculated as
3
/1
RR
QT
QTcF 
.
If both QTcF and RR in seconds are missing, then QTcF will be calculated as


3
/
1
60
RATE
HEART
QT
QTcF 
8.20
Percent Compliance Calculation
Percent compliance for the double-blind study medication during the double-blind treatment
period is defined for each subject as the number of tablets and injections taken, divided by the 
number of tablets that should have been taken.
For BMS-986142, the number of tablets that should have been taken is calculated as 1 + the 
number of days from the first double-blind treatment period dose recorded in the “Record of 
Study Medication” to the last double-blind treatment dose, times the prescribed daily dose (i.e. 2 
tablets per day, one from each bottle). The number of tablets taken is the total number of tablets 
recorded (sum of bottle 1 and bottle 2) as taken based on the CRF, summed over the days 
counted when calculating the number of tablets that should have been taken, including the day of 
the last double-blind treatment dose.
For Lulizumab, the same calculation will be used. The number of injections that should have 
been administered is calculated as 1 + the number of days from the first double-blind treatment 
period dose recorded in the “Record of Study Medication” to the last double-blind treatment dose
divided by 7. The number of injections administered is the total number of injections recorded as 
administered based on the CRF, summed over the days counted when calculating the number of 
injections that should have been administered, including the day of the last double-blind 
treatment dose.
8.21
Strip Sign for Selected Laboratory Data
For selected laboratory test values that have been received with an operator sign as a part of the 
result (>, , <, or ), a process to strip the operator sign will be applied and the resulting numeric 
values will be used for data analysis. The raw value with operator will remain as such on the 
CRF (or in the electronic record) and in the database. 
The applicable impacted laboratory tests and applicable operator signs will be identified during 
the course of the study and study monitoring. For laboratory parameters not included in any 
statistical analyses, operator signs will not be stripped and the value will counted as missing.
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8.22
United States Conventional Units and Standard International Units for 
Laboratory Data
Unless otherwise specified, all analyses of laboratory data (independently of being safety or 
efficacy) will be performed in both United States Conventional Units (US) and Standard 
International Units (SI). Conversion between US and SI, and vice versa, will be performed using 
the BMS standard conversion factors.
8.23
Laboratory evaluations
All laboratory evaluations performed by central laboratories and local laboratories that are 
included in the database will be included in summary tables and in the listings.
9
CONTENT OF REPORTS
The results of the study conducted by Protocol IM128-035 will be presented in a standard BMS 
CSR appendix. Key results and any unanticipated findings that are unusual for this study will be 
identified. A meeting for the initial dissemination of study results will be held after database 
locked. Attendees at this meeting will review all efficacy and safety summaries and listings and 
will identify key results that should be highlighted in the CSR.
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APPENDIX 1
RELEVANT PROTOCOL DEVIATIONS
Number
Relevant Protocol Deviation Criteria
Exclusion Level
1
Randomized subjects who do not have moderate to severe primary Sjögren’s 
syndrome, defined is defined as Sjögren’s syndrome in the absence of another 
autoimmune disease or rheumatologic condition) based on the 2015 ACR-
EULAR Classification Criteria.
Complete exclusion
2
Randomized subjects without ESSDAI 5, including disease activity (any score 
> 0) in at least one of the following domains: Glandular, Articular, 
Hematological, Biological, Lymphadenopathy.
Complete exclusion
3
Randomized subjects without Positive anti-SS-A/Ro or anti-SS-B/La 
autoantibody.
Complete exclusion
4
Randomized subjects who received more than 10mg/day of prednisone (or 
prednisone equivalent) for at least 14 days prior to Day 1 (randomization).
Complete exclusion
5
Randomized subjects who did not receive at least 4 consecutive doses of 
Lulizumab or matching placebo.
Partial exclusion
(Efficacy data after 
the 21th day of the 
interruption will be 
excluded)
6
Randomized subjects who did not receive BMS-986142 or matching placebo for 
at least 14 consecutive days.
Partial exclusion
(Efficacy data after 
the 14th day of the 
interruption will be 
excluded)
7
Randomized subjects to placebo receiving active medication dose of Lulizumab 
for at least 4 doses and BMS-986142 for at least 14 doses.
Partial exclusion
(Efficacy data from 
the first dose date 
of active 
medication will be
excluded)
8
Randomized subjects receiving initiating or increasing the baseline dose (if 
already in such a medication) in any of the protocol specified list of restricted 
and prohibited treatments during double-blind treatment period.
Partial exclusion
(Efficacy data from 
the first dose date 
of restricted or 
protocol 
medication will be 
excluded)
9
Randomized subjects less than 80% or more than 120% compliant with any of 
the double-blind treatment regimens.
Complete exclusion
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APPENDIX 2
GEOGRAPHIC REGIONS
Geographic Region
Countries
North America
United States
Puerto Rico
Mexico
South America
Chile
Colombia
Peru
Europe
France
Germany 
Netherlands
Russia
Greece
Romania
Hungary
Italy
Poland
South Africa
Oceania
Australia
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APPENDIX 3
MARKED LABORATORY ABNORMALITIES CRITERIA
Laboratory 
parameter
Code
Low Criterion 
High Criterion
US units
SI units
US units
SI units
Hemoglobin
HB
< BASELINE -
0.3 g/dL
< BASELINE -3 
g/L
< 7 G/DL
< 70 G/L
Hematocrit
HCT
< 0.75*BASELINE
Erythrocytes
RBC
< 0.75*BASELINE
Platelet Count
PLAT
< 0.5*BASELINE AND  <100 x10*9 
c/L IF BASELINE < LLN
>1.5*ULN IF LLN <= BASELINE <= 
ULN
<0.67*LLN IF LLN <= BASELINE 
<= ULN
<50 x10*9 c/L
Leukocytes
WBC
<0.75*LLN IF LLN <= BASELINE 
<= ULN
> 1.25*ULN IF LLN <= BASELINE 
<= ULN
<0.8*BASELINE IF BASELINE < 
LLN
>ULN IF BASELINE < LLN
< LLN IF BASELINE > ULN
> 1.2*BASELINE IF BASELINE > 
ULN
<2.0 x10*3 c/uL
<2.0 x10*9 c/L
Neutrophils + 
Bands (absolute)
PMNBA
<1.000 x10*3 
c/uL
<1.000 x10*9 c/L
Eosinophils 
(absolute)
EOSA
> 0.750 x10*3 
c/uL
> 0.750 x10*9 
c/L
Basophils 
(absolute)
BASOA
>0.400 x10*3 
c/uL
>0.400 x10*9 c/L
Monocytes 
(absolute)
MONOA
> 2.000 x10*3 
c/uL
> 2.000 x10*9 
c/L
Lymphocytes 
(absolute)
LYMPA
< 0.750 x10*3 
c/uL
< 0.750 x10*9 
c/L
> 7.500 x10*3 
c/uL
> 7.500 x10*9 
c/L
<0.5 x10*3 c/uL
<0.5 x10*9 c/L
Blasts (relative)
BLAST
>0 %
>0
PT Ratio
PTR
> 1.33*BASELINE
aPTT Ratio
APTTR
> 1.33*BASELINE
Intl Normalized 
Ratio
INR
> 1.33*BASELINE
Alkaline 
Phosphatase
ALP
> 2*ULN IF LLN <= BASELINE <= 
ULN
> 3*BASELINE IF BASELINE > 
ULN
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Laboratory 
parameter
Code
Low Criterion 
High Criterion
US units
SI units
US units
SI units
>5.0 xULN
Aspartate 
Aminotransferase
AST
> 3*ULN IF LLN <= BASELINE <= 
ULN
> 4*BASELINE IF BASELINE > 
ULN
>5.0 xULN
Alanine 
Aminotransferase
ALT
> 3*ULN IF LLN <= BASELINE <= 
ULN
> 4*BASELINE IF BASELINE > 
ULN
>5.0 xULN
G-Glutamyl 
Transferase
GGT
> 2*ULN IF LLN <= BASELINE <= 
ULN
> 3*BASELINE IF BASELINE > 
ULN
Bilirubin, Total
TBILI
> 2*ULN IF LLN <= BASELINE <= 
ULN
> 4*BASELINE IF BASELINE > 
ULN
>3.0 xULN
Bilirubin, Direct
DBILI
> 1.5*ULN IF LLN <= BASELINE 
<= ULN
> 2*BASELINE IF BASELINE > 
ULN
Blood Urea 
Nitrogen
BUN
> 2*BASELINE
Creatinine
CREAT
> 1.5*BASELINE
>3.0 xULN
Protein/Creatinine 
Ratio
PRCRR
> 4 mg/mg
> 4519.8 
mg/mmol
Creatinine 
Clearance
CRCL
< 0.67*BASELINE
Sodium, Serum
NA
< 0.95*LLN IF LLN <= BASELINE 
<= ULN
> 1.05*ULN IF LLN <= BASELINE 
<= ULN
< 0.95*BASELINE IF BASELINE < 
LLN
> ULN IF BASELINE < LLN
< LLN IF BASELINE > ULN
> 1.05*BASELINE IF BASELINE > 
ULN
< 130 mEq/L
< 130 mmol/L
> 155 mEq/L
> 155 mmol/L
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Laboratory 
parameter
Code
Low Criterion 
High Criterion
US units
SI units
US units
SI units
Potassium, Serum
K
< 0.9*LLN IF LLN <= BASELINE <= 
ULN
> 1.1*ULN IF LLN <= BASELINE 
<= ULN
< 0.9*BASELINE IF BASELINE < 
LLN
> ULN IF BASELINE < LLN
< LLN IF BASELINE > ULN
> 1.1*BASELINE IF BASELINE > 
ULN
< 2.5 mEq/L
< 2.5 mmol/L
> 6.0 mEq/L
> 6.0 mmol/L
Chloride, Serum
CL
< 0.9*LLN IF LLN <= BASELINE <= 
ULN
> 1.1*ULN IF LLN <= BASELINE 
<= ULN
< 0.9*BASELINE IF BASELINE < 
LLN
> ULN IF BASELINE < LLN
< LLN IF BASELINE > ULN
> 1.1*BASELINE IF BASELINE > 
ULN
Carbon Dioxide, 
Total
CO2
< 0.75*LLN IF LLN <= BASELINE 
<= ULN
> 1.25*ULN IF LLN <= BASELINE 
<= ULN
< 0.75*BASELINE IF BASELINE < 
LLN
> ULN IF BASELINE < LLN
< LLN IF BASELINE > ULN
> 1.25*BASELINE IF BASELINE > 
ULN
Bicarbonate
HCO3
< 0.75*LLN IF LLN <= BASELINE 
<= ULN
> 1.25*ULN IF LLN <= BASELINE 
<= ULN
< 0.75*BASELINE IF BASELINE < 
LLN
>ULN IF BASELINE < LLN
<LLN IF BASELINE > ULN
> 1.25*BASELINE IF BASELINE > 
ULN
Calcium
CA
< 0.8*LLN IF LLN <= BASELINE <= 
ULN
> 1.2*ULN IF LLN <= BASELINE 
<= ULN
< 0.75*BASELINE IF BASELINE < 
LLN
>ULN IF BASELINE < LLN
<LLN IF BASELINE > ULN
> 1.25*BASELINE IF BASELINE > 
ULN
< 7 mg/dL
< 1.75 mmol/L
> 12.5 mg/dL
> 3.13 mmol/L
Phosphorus, 
Inorganic
PHOS
< 0.75*LLN IF LLN <= BASELINE 
<= ULN
> 1.25*ULN IF LLN <= BASELINE 
<= ULN
< 0.67*BASELINE IF BASELINE < 
LLN
>ULN IF BASELINE < LLN
< LLN IF BASELINE > ULN
> 1.33*BASELINE IF BASELINE > 
ULN
< 2.0 mg/dL
< 0.65 mmol/L
Magnesium, 
MG
< 0.6*LLN IF LLN <= BASELINE <= 
> 2.0*ULN IF LLN <= BASELINE 
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Laboratory 
parameter
Code
Low Criterion 
High Criterion
US units
SI units
US units
SI units
Serum
ULN
<= ULN
< 0.67*BASELINE IF BASELINE < 
LLN
>ULN IF BASELINE < LLN
<LLN IF BASELINE > ULN
> 2.0*BASELINE IF BASELINE > 
ULN
Glucose, Serum
GLUC
< 65 mg/dL
< 3.6 mmol/L
> 220 mg/dL
> 12.2 mmol/L
Glucose, Fasting 
Serum
GLUCF
< 0.8*LLN IF LLN <= BASELINE <= 
ULN
> 1.5*ULN IF LLN <= BASELINE 
<= ULN
< 0.8*BASELINE IF BASELINE < 
LLN
>ULN  IF BASELINE < LLN
< LLN  IF BASELINE > ULN
> 2.0*BASELINE IF BASELINE > 
ULN
Protein, Total
TPRO
< 0.9*LLN IF LLN <= BASELINE <= 
ULN
> 1.1*ULN IF LLN <= BASELINE 
<= ULN
< 0.9*BASELINE IF BASELINE < 
LLN
>ULN IF BASELINE < LLN
<LLN IF BASELINE > ULN
> 1.1*BASELINE IF BASELINE > 
ULN
Albumin
ALB
< 0.9*LLN IF LLN <= BASELINE <= 
ULN
< 0.75*BASELINE IF BASELINE < 
LLN
< 2 g/dL
< 20 g/L
Cholesterol, Total
CHOL
> 2*BASELINE
Triglycerides, 
Fasting
TRIGF
>= 2.0*ULN IF LLN <= BASELINE 
<= ULN
> 2.0*BASELINE IF BASELINE > 
ULN
Amylase, Total
AMYL
> 3*ULN IF LLN <= BASELINE <=
ULN
> 4*BASELINE IF BASELINE > 
ULN
Creatinine 
Phosphokinase
CK
> 4*BASELINE
Uric Acid
URIC
> 1.5*ULN IF LLN <= BASELINE 
<= ULN
> 2*BASELINE IF BASELINE > 
ULN
Lactate 
Dehydrogenase
LD
> 1.5*ULN IF LLN <= BASELINE 
<= ULN
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Laboratory 
parameter
Code
Low Criterion 
High Criterion
US units
SI units
US units
SI units
> 3*BASELINE IF BASELINE > 
ULN
Protein, Urine
UPRO
>= 2 IF MISSING BASELINE
VA >= 4
>= 2 IF 0=< BASELINE =<0.5
>= 3 IF BASELINE = 1
>= 4 IF 2=< BASELINE =<3
Glucose, Urine
UGLU
>= 2 IF MISSING BASELINE
VA >= 4
>= 2 IF 0=< BASELINE =<0.5
>= 3 IF BASELINE = 1
>= 4 IF 2=< BASELINE =<3
Ketones, Urine
UKET
>= 2 IF MISSING BASELINE
>= 4
>= 2 IF 0=< BASELINE =<0.5
>= 3 IF BASELINE = 1
>= 4 IF 2=< BASELINE =<3
Blood, Urine
UBLD
>= 2 IF MISSING BASELINE
>= 4
>= 2 IF 0=< BASELINE =<0.5
>= 3 IF BASELINE = 1
>= 4 IF 2=< BASELINE =<3
Leukocyte 
Esterase, Urine
ULEUK
>= 2 IF MISSING BASELINE
>= 4
>= 2 IF 0=< BASELINE =<0.5
>= 3 IF BASELINE = 1
>= 4 IF 2=< BASELINE =<3
RBC, Urine
URBC
>= 2 hpf IF MISSING BASELINE
>= 4 hpf
>= 2 hpf IF 0=< BASELINE =<0.5 
hpf
>= 3 hpf IF BASELINE = 1 hpf
>= 4 hpf IF 2 hpf =< BASELINE =<3 
hpf
WBC, Urine
UWBC
>= 2 hpf IF MISSING BASELINE
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Laboratory 
parameter
Code
Low Criterion 
High Criterion
US units
SI units
US units
SI units
>= 4 hpf
>= 2 hpf IF 0=< BASELINE =<0.5 
hpf
>= 3 hpf IF BASELINE = 1 hpf
>= 4 hpf IF 2 hpf =< BASELINE =<3 
hpf
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APPENDIX 4
DOCUMENT HISTORY
Version
Statistician
Date
Notes/Revisions
1.0
Alexandros-
Georgios 
Chalamandaris
30 October 
2016
Original version
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