A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Subcutaneous Abatacept in Adults With Active Primary Sjögrens Syndrome
Phase: PHASE3
Conditions: Sjogrens Disease
Sponsor: Bristol-Myers Squibb

Page:
1
Protocol Number:
IM101603
IND Number:
BB-IND12,300
Ex-US
Non-IND
EUDRACT Number
2016-001948-19
Date:
23-Jun-2016
Revised Date:
25-Aug-2016
Clinical Protocol IM101603
A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and 
Safety of Subcutaneous Abatacept in Adults with Active Primary Sjögrens Syndrome
Revised Protocol Number: 01
Incorporates amendment(s) 01
Medical Monitor
Alyssa Johnsen, 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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Revised Protocol No.: 01
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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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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised Protocol 
01
25-Aug-2016
Incorporates Amendment 01
Amendment 01
25-Aug-2016
Changes to Protocol include:

To 
provide 
clear
differentiate
between
discontinuation 
of 
study 
treatment 
from 
discontinuation from the study.
o
Subjects 
who 
discontinue 
investigational 
product during the Double-Blind Treatment 
Period should continue to comply with all 
protocol specified procedures during the 
Double-Blind Treatment Period.
o
Define the assessments required for the 
collection of follow-up data.

To clarify inclusion/exclusion criteria

To clarify testing for stimulated salivary flow

Add allowable window for obtaining the optional 
biopsy samples.

Modify laboratory testing to limit to the most 
critical tests and to adjust for feasibility issues.

Add 
additional 
secondary 
 
 

Increase the total number of subjects targeted for 
enrollment in order to increase statistical power 
and the overall size of the safety database.

Revise appendices to include most current 
versions.

Corrections to minor typographical errors
Original Protocol
23-Jun-2016
Not applicable
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SYNOPSIS
Clinical Protocol IM101603
Protocol Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and 
Safety of Subcutaneous Abatacept in Adults with Active Primary Sjögrens Syndrome
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s):
Subjects receive investigational products for a period of 1 year. Investigational products are defined as:

Abatacept SC 125 mg in 1 mL pre-filled syringes

Placebo for abatacept SC in 1 mL pre-filled syringes
Study Phase: III
Research Hypothesis: Abatacept 125 mg, administered subcutaneously (SC) weekly will have greater efficacy than 
placebo in subjects with moderately to severely active primary Sjögren’s Syndrome (pSS) as assessed by the mean 
change from baseline in the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score after Day 169 of 
treatment.
Objectives: 
Primary Objective
To compare the mean change from baseline (Day 1) to Day 169 in ESSDAI of abatacept versus placebo in subjects 
with moderate to severe pSS. 
Secondary Objective
Key Secondary: 

To compare the mean change from baseline (Day 1) to Day 169 in EULAR Sjögren’s Syndrome Patient 
Reported Index (ESSPRI) of abatacept versus placebo in subjects with moderate to severe pSS.

To compare the mean changes from baseline (Day 1) to Day 169 in the stimulated whole salivary flow of 
abatacept versus placebo in subjects with stimulated whole salivary flow of at least 0.1 mL/min at both 
screening and baseline.
Other Secondary:

To assess the mean change from baseline at all measured time points up to Day 169 in DAS28-CRP among 
those with a tender joint count plus swollen joint count of at least 3 at baseline, among those with a tender joint 
count plus swollen joint count of less than 3 at baseline and in the full population.

To assess the mean change from baseline at all measured time points up to Day 169 in the individual 
components of DAS28-CRP among those with a tender plus swollen joint count of at least 3 at baseline, among 
those with a tender joint count plus swollen joint count of less than 3 and in the full population.

To assess the proportion of subjects who achieve a minimally clinically important improvement in ESSDAI (
3) at all measured time points up to Day 169 in the full population, among those with stimulated whole salivary 
flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary 
flow of less than 0.1 mL/min at screening or baseline.

To assess the proportion of subjects who achieve a minimally clinically important improvement in ESSDAI (
5) at all measured time points up to Day 169 in the full population, among those with stimulated whole salivary 
flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary 
flow of less than 0.1 mL/min at screening or baseline

To assess the proportion of subjects who achieve a minimally clinically important improvement in ESSPRI (
1) at all measured time points up to Day 169 in the full population, among those with stimulated whole salivary 
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flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary 
flow of less than 0.1 mL/min at screening or baseline.

To assess the mean change from baseline at all measured time points up to Day 169 in ESSDAI in the full 
population, among those with stimulated whole salivary flow of at least 0.1 mL/min at both screening and 
baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min at screening or baseline.

To assess the mean change from baseline at all measured time points up to Day 169 in ESSPRI in the full 
population, among those with stimulated whole salivary flow of at least 0.1 mL/min at both screening and 
baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min at screening or baseline.

To assess the mean change from baseline in the individual components of the ESSDAI at all measured time 
points up to Day 169 in the full population, among those with stimulated whole salivary flow of at least 
0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary flow of less than 
0.1 mL/min at screening or baseline.

To assess the mean change from baseline in the individual components of the ESSPRI at all measured time 
points up to Day 169 in the full population, among those with stimulated whole salivary flow of at least 
0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary flow of less than 
0.1 mL/min at screening or baseline.

To assess the mean change from baseline in Schirmer’s test at all measured time points up to Day 169.

To assess the mean change from baseline in ocular staining score at all measured time points up to Day 169.

To assess the mean change from baseline in tear break-up time at all measured time points up to Day 169.

To assess the mean change from baseline in unstimulated whole salivary flow at all measured time points up to 
Day 169 in the full population, among those with stimulated whole salivary flow of at least 0.1 mL/min at 
screening and baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min at 
screening or baseline.

To assess the mean change from baseline in stimulated whole salivary flow at all measured time points up to 
Day 169 in the full population, among those with stimulated whole salivary flow of at least 0.1 mL/min at 
screening and baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min at 
screening or baseline.

To assess the change in patient symptoms using the Numeric Rating Scale (NRS) for mouth dryness at all 
measured time points up to Day 169 in the full population, among those with stimulated whole salivary flow of 
at least 0.1 mL/min at screening and baseline, and among those with stimulated whole salivary flow of less than 
0.1 mL/min at screening or baseline.

To assess the mean change in patient symptoms using the Numeric Rating Scale (NRS) for eye dryness at all 
measured time points up to Day 169.

To assess the mean change in patient symptoms using the patient global assessment of disease activity at all 
measured time points up to Day 169.

To assess the mean change in the physician global assessment at all measured time points up to Day 169.

To assess the mean change in patient fatigue using PROMIS Fatigue assessment at all measured time points up 
to Day 169.

To assess the mean change in female sexual function using the Female Sexual Function Index (FSFI) at all 
measured time points up to Day 169.

To assess the mean change in patient quality of life using the SF-36 at all measured time points up to Day 169.

To assess safety and immunogenicity of abatacept.

To assess the pharmacokinetics of abatacept.
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Study Population: Men or women (not nursing or pregnant) greater than 18 years of age diagnosed with Sjögren’s 
Syndrome defined by the proposed 2015 ACR-EULAR Classification Criteria. Subjects must have a positive 
anti-SSA test at screening and an ESSDAI score of at least 5 at screening. At least 72% of subjects will be required 
to have a stimulated salivary flow of at least 0.1 mL/min at screening and randomization.
Key Inclusion criteria: 

Subjects must meet the proposed 2015 ACR/EULAR Classification Criteria for SS (Sjögren’s Syndrome), as 
specified for pSS (primary Sjögren’s Syndrome).
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
Subjects should have pSS that is refractory to symptomatic or local therapy (e.g. NSAIDs)

Subjects having an ESSDAI score of at least 5 at screening.

Subjects being anti-SS-A/Ro positive at screening.

Stimulated salivary flow of at least 0.1 mL/min at screening and randomization in at least 124 subjects (72%)
Key Exclusion criteria: 

Subjects who have a systemic autoimmune disease other than Sjögren’s syndrome, such as RA, SLE or 
systemic sclerosis, that can better explain the majority of the symptoms (ie, secondary Sjögren’s syndrome).

Subjects who have another autoimmune disease or inflammatory condition that could interfere with assessment 
of response of pSS to therapy (eg, systemic sclerosis, inflammatory bowel disease, gout).

Subjects with any other medical condition associated with clinical features overlapping those of pSS or that 
would interfere with interpretation of results, including but not limited to a history of head and neck radiation 
treatment, sarcoidosis, amyloidosis, graft-versus-host disease, hepatitis C, acquired immunodeficiency 
syndrome, and IgG4-related disease. 

Active life-threatening or organ-threatening complications of Sjögren’s-syndrome (SS) disease at the time of 
screening based on investigator evaluation including but not restricted to the following:
o
Vasculitis with renal, digestive, cardiac, pulmonary or central nervous system (CNS) involvement 
characterized as severe (note: cutaneous vasculitis is allowed)
o
Active CNS or peripheral nervous system (PNS) involvement requiring high dose steroids
o
Severe renal involvement, e.g., GFR < 60 mL/min, a serum creatinine > 2 mg/dL, or proteinuria > 3 g/day,
o
Severe pulmonary involvement, e.g., shortness of breath at rest, or pulmonary function tests demonstrating 
DLCO < 40% or FVC < 60%
o
Severe muscular involvement requiring high dose steroids
o
Lymphoma

Subjects who have previously been exposed to abatacept or anti-CD28 therapy.

Subjects who have received IV, IM, SC or intra-articular corticosteroids within 4 weeks of randomization 
(Day 1).

Subjects who have taken rituximab within 12 months prior to randomization (Day 1).

Subjects who have taken belimumab within 12 weeks prior to randomization (Day 1).

Subjects who have taken a biologic therapy other than rituximab or belimumab or any other investigational 
therapy within 12 weeks or 5 half-lives prior to randomization (Day 1), whichever is longer.

Subjects who have taken cyclophosphamide, mycophenolate mofetil (MMF)/mycophenolic acid (MPA) or 
leflunomide within 6 months of randomization (Day 1).

Subjects who have taken methotrexate within 12 weeks of randomization.

Subjects who have taken cyclosporine (systemic), azathioprine, tacrolimus, tofacitinib, mizoribine, actarit, or
bucillamine within 4 weeks of randomization (Day 1).

Subjects who have taken Intravenous Immunoglobulin (IVIG) within 4 weeks of randomization (Day 1).

Subjects who have taken diquafosol or ophthalmic rebamipide within 4 weeks prior to randomization (Day 1)

Subjects who have taken a tricyclic antidepressant drug within 4 weeks prior to randomization (Day 1).
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Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational 
[Medicinal] Products (Non-IP/Non-IMP) as listed:
Study Drug for IM101603
Product 
Description / 
Class and 
Dosage Form
Potency
IP/
Non-
IMP
Blinded or 
Open 
Label
Packaging / Appearance
Storage Conditions
(per label)
Abatacept 
Injection
125 mg/syringe
125 mg/mL
IP
Blinded
4 syringes per kit
Clear to slightly opalescent, 
colorless to pale yellow 
solution, essentially free of 
particulate matter on visual 
inspection
Store refrigerated 
2 – 8 °C
Protect from light
Protect from 
freezing
Placebo for 
abatacept 
Injection
N/A
IP
Blinded
4 syringes per kit
Clear to slightly opalescent, 
colorless to pale yellow 
solution, essentially free of 
particulate matter on visual 
inspection
Store refrigerated 
2 – 8 °C
Protect from light
Protect from 
freezing
Abatacept 
Injection
125 mg/syringe
125 mg/mL
IP
Open-Label
4 syringes per kit
Clear to slightly opalescent, 
colorless to pale yellow 
solution, essentially free of 
particulate matter on visual 
inspection
Store refrigerated 
2 – 8 °C
Protect from light
Protect from 
freezing
Study Assessments: See Section 5 of the protocol for detailed information regarding study assessments.
Study assessments include the ESSDAI, ESSPRI, whole stimulated and unstimulated salivary flow, ocular staining 
score, tear break-up time, Schirmer’s test, tender and swollen joint counts, physician global assessment, subject 
global assessment, numeric rating scale for mouth dryness and for eye dryness, PROMIS Fatigue scale, SF-36, and 
FSFI.
Statistical Considerations:
Sample Size: A hierarchical testing procedure will be applied for the primary endpoint (mean change from baseline 
in ESSDAI at Day 169) and the 2 key secondary endpoints (mean change from baseline in ESSPRI at Day 169 and 
mean change from baseline in the stimulated whole salivary flow at Day 169) to ensure the preservation of the 
overall type I error of 5%. A sample size of 172 patients (86 per arm) will achieve 98% power to detect a treatment 
difference of 3 in changes from baseline in ESSDAI at Day 169 between the abatacept and placebo group using a 
two-sided t-test with a significance level (alpha) of 0.05 and assuming a common SD of 4.8. The sample size of 86
patients per arm will achieve 90% power to detect a treatment difference of 1 in change from baseline in ESSPRI at 
Day 169 assuming a common SD of 2 and 91% power to detect a treatment difference in mean change from baseline 
of 0.165 mL/min in salivary flow in subjects with a residual salivary flow of at least 0.1 mL/min at screening and 
baseline assuming a common SD of 0.275. Taking into account the hierarchical testing procedure, the overall power 
for the primary and the 2 key secondary endpoints is at least 80%.
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Endpoints:
Primary Endpoint
The mean change from baseline (Day 1) in ESSDAI at Day 169.
Secondary Endpoint(s)
Key Secondary Endpoints

The mean change from baseline in ESSPRI at Day 169 

The mean change from baseline in the stimulated whole salivary flow at Day 169 among subjects with 
stimulated whole salivary flow of at least 0.1 mL/min at both screening and baseline.
Other Secondary Endpoints

The mean change from baseline at all measured time points up to Day 169 in the DAS28-CRP among those 
with a tender plus swollen joint count 3 at baseline, among those with a tender plus swollen joint count < 3 at 
baseline and in the full population.

The mean change from baseline at all measured time points up to Day 169 in the individual components of 
DAS28-CRP among those with a tender plus swollen joint count 3 at baseline, among those with a tender plus 
swollen joint count < 3 at baseline and in the full population.

Proportion of subjects who achieve a minimally clinically important change (of at least 3 points) in the ESSDAI 
at all measured time points up to Day 169 in the full population, among those with stimulated whole salivary 
flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary 
flow of less than 0.1 mL/min at screening or baseline.

Proportion of subjects who achieve a minimally clinically important change (of at least 5 points) in the ESSDAI 
at all measured time points up to Day 169 in the full population, among those with stimulated whole salivary 
flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary 
flow of less than 0.1 mL/min at screening or baseline.

Proportion of subjects who achieve a minimally clinically important change (of at least 1 point) in the ESSPRI 
at all measured time points up to Day 169 in the full population, among those with stimulated whole salivary 
flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary 
flow of less than 0.1 mL/min at screening or baseline.

The mean change from baseline at all measured time points up to Day 169 in the ESSDAI in the full population, 
among those with stimulated whole salivary flow of at least 0.1 mL/min at both screening and baseline, and 
among those with stimulated whole salivary flow of less than 0.1 mL/min at screening or baseline. 

The mean change from baseline at all measured time points up to Day 169 in the ESSPRI in the full population, 
among those with stimulated whole salivary flow of at least 0.1 mL/min at both screening and baseline, and 
among those with stimulated whole salivary flow of less than 0.1 mL/min at screening or baseline.

The mean change from baseline in the individual components of the ESSDAI at all measured time points up to 
Day 169 in the full population, among those with stimulated whole salivary flow of at least 0.1 mL/min at both 
screening and baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min at 
screening or baseline.

The mean change from baseline in the individual components of the ESSPRI at all measured time points up to 
Day 169 in the full population, among those with stimulated whole salivary flow of at least 0.1 mL/min at both 
screening and baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min at 
screening or baseline. 

The mean change from baseline in Schirmer’s test at all measured time points up to Day 169.
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The mean change from baseline in ocular staining score at all measured time points up to Day 169.

The mean change from baseline in tear break-up time at all measured time points up to Day 169.

The mean change from baseline in unstimulated whole salivary flow at all measured time points up to Day 169 
in the full population, among those with stimulated whole salivary flow of at least 0.1 mL/min at both screening 
and baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min at screening or 
baseline.

The mean change from baseline in stimulated whole salivary flow at all measured time points up to Day 169 in 
the full population, among those with stimulated whole salivary flow of at least 0.1 mL/min at both screening 
and baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min at screening or 
baseline. 

The mean change from baseline in patient symptoms using the Numeric Rating Scale (NRS) for mouth dryness 
at all measured time points up to Day 169 in the full population, among those with stimulated whole salivary 
flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary 
flow of less than 0.1 mL/min at screening or baseline. 

The mean change from baseline in patient symptoms using the Numeric Rating Scale (NRS) for eye dryness at 
all measured time points up to Day 169.

The mean change from baseline in subject assessment of disease activity at all measured time points up to Day 
169.

The mean change from baseline in the physician global assessment of disease activity at all measured time 
points up to Day 169.

The mean change from baseline in patient fatigue using PROMIS Fatigue assessment at all measured time 
points up to Day 169.

The mean change from baseline in female sexual function using the FSFI at all measured time points up to 
Day 169.

The mean change from baseline in patient function using SF-36 at all measured time points up to Day 169.

Geometric mean of trough concentration (Cmin) of abatacept at all measured time points.

Proportion of subjects with at least one positive immunogenicity response up to Day 169 and during 3 months 
follow up (for subjects who discontinue during the 6-months double-blind) and during the cumulative abatacept 
period and 3 months follow-up (for the cumulative abatacept population).

Safety (proportion of subjects with adverse events, deaths, SAEs, and AEs leading to discontinuation and 
proportion of laboratory marked abnormalities) up to Day 169 and during the cumulative abatacept period and 
follow-up period.
Analyses:
Efficacy Analyses
Changes from baseline over time for ESSDAI will be analyzed using a longitudinal repeated measures analysis. The 
model will include the fixed categorical effects of treatment, day (is a windowed time point), baseline corticosteroid 
use, baseline hydroxychloroquine use, stimulated salivary flow, treatment-by-day interaction, baseline corticosteroid 
use-by-day interaction, baseline hydroxychloroquine use-by-day interaction, stimulated salivary flow-by-day 
interaction as well as, the continuous fixed covariate of baseline score and baseline score-by-day interaction. An
unstructured covariance matrix will be used to represent the correlation of the repeated measures within each 
subject. The parameter estimations will be based on the assumption of data being missing at random (MAR) and 
using the method of restrictive maximum likelihood (REML). The difference in adjusted means (LSMEANS) 
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between abatacept and placebo at the primary time point, Day 169, and corresponding 95% CI and p-value based on 
the longitudinal repeated measures above will be provided.
A similar longitudinal repeated measures analysis will be provided for the key secondary endpoints, mean change 
from baseline in ESSPRI and mean change from baseline in the stimulated whole salivary flow and the other 
secondary efficacy endpoints including changes from baseline.
The binary secondary efficacy endpoints e.g., the proportion of subjects with a decrease in ESSDAI of at least 3 
from baseline to Day 169 and the proportion of subjects with a decrease in the ESSPRI of at least 1 to Day 169 will 
be analyzed with a logistic regression including treatment, corticosteroid use, hydroxychloroquine use, stimulated 
salivary flow use and baseline value in the model. The odds ratio along with its 95% confidence interval will be 
provided. A missing responder value at Day 169 due to discontinuation or for other reasons will be imputed as a 
non-responder.
Safety Analyses
The proportion (%) of subjects with adverse events, deaths, SAEs, and AEs leading to discontinuation and subjects 
with laboratory marked abnormalities up to start of the open label period for subjects continuing in the OL or up to 
last dosing date +56 days for subjects discontinuing during double blind will be provided per treatment group using 
the as-treated population. These safety endpoints will also be summarized during the cumulative abatacept period 
(from the first day of abatacept treatment in the study up to 56 days after the last abatacept treatment in the study) 
for the cumulative abatacept population. For the cumulative abatacept population all subjects will be combined in 
one group.
The proportion (%) of subjects with at least one positive immunogenicity response (relative to baseline) up to 
Day 169 and 3 months follow up (for subjects who discontinue in the Day 169 short-term period) and during the 
cumulative abatacept period and 3 months follow-up (for the cumulative abatacept population) will be summarized 
using the immunogenicity population.
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1
 
 
1.1.1 Pathophysiology of Sjögren’s Syndrome ................................................. 
1.1.2 Mechanism of Action of Abatacept .......................................................... 
 
 
1.2 Research Hypothesis ......................................................................................... 
1.3 Objectives(s) ..................................................................................................... 
1.3.1 Primary Objectives .................................................................................. 
1.3.2 Secondary Objectives ............................................................................... 
 
1.4 Product Development Background ................................................................... 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
2 ETHICAL CONSIDERATIONS ............................................................................... 
2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
3 INVESTIGATIONAL PLAN .................................................................................... 
 ............................................................................... 
3.1.1 Screening Period ...................................................................................... 
3.1.2 Double-Blind Treatment Period (Day 1 to Day 169) .............................. 
3.1.3 Open Label Extension (Day 169 to Day 365) .......................................... 
3.1.4 Post-Treatment Follow-up Period ........................................................... 
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 ........................................................... 
 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
3.4.1.1 Prohibited Treatments While Receiving Treatment with Study Drug
...............................................................................................................
3.4.1.2 Restricted Treatments While Receiving Treatment with Study Drug
...............................................................................................................
3.4.2 Other Restrictions and Precautions ......................................................... 
3.4.2.1 Immunizations ................................................................................. 
3.4.2.2 Infectious Complications ................................................................ 
3.4.2.3 Management of Possible Acute Hypersensitivity Reactions ........... 
3.5 Discontinuation of Study Therapy .................................................................... 
3.6 Discontinuation from the Study ........................................................................ 
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3.7 Post Study Drug Study Follow up .................................................................... 
3.7.1 Withdrawal of Consent ............................................................................ 
3.7.2 Lost to Follow-Up .................................................................................... 
4 STUDY DRUG .......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.2 Non-investigational Product ............................................................................. 
4.3 Storage of Study Drug ...................................................................................... 
4.4 Method of Assigning Subject Identification ..................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.5.1 Abatacept Treatment ................................................................................ 
4.5.2 Dose Modifications .................................................................................. 
4.5.2.1 Dose Modifications in the Absence of Adverse Events ................... 
4.5.2.2 Dose Modifications Due to Adverse Events .................................... 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction or Return of Investigational Product ............................................. 
4.9 Retained Samples for Bioavailability / Bioequivalence ................................... 
5 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening or Lead-in Period ....................................... 
5.1.2 Order of Study Assessments ..................................................................... 
5.1.3 Study Drug Administration Window ........................................................ 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Imaging Assessment for the Study............................................................ 
5.3.2 Physical Examination .............................................................................. 
5.3.3 Chest X-ray .............................................................................................. 
5.3.4 Physical Measurements ........................................................................... 
5.3.5 Vital Signs ................................................................................................ 
5.3.6 TB Screening ............................................................................................ 
5.3.7 Laboratory Assessments........................................................................... 
5.3.7.1 Hematology ..................................................................................... 
5.3.7.2 Blood Chemistry.............................................................................. 
5.3.7.3 Immunology ..................................................................................... 
5.3.7.4 Urinalysis ........................................................................................ 
5.3.7.5 Hepatitis Screen .............................................................................. 
5.3.7.6 Pregnancy Tests .............................................................................. 
5.3.7.7 HIV Testing ..................................................................................... 
5.3.7.8 FSH Testing .................................................................................... 
5.4 Efficacy Assessments ........................................................................................ 
5.4.1 Primary Efficacy Assessment ................................................................... 
5.4.2 Salivary Flow ........................................................................................... 
5.4.3 Ophthalmologic Assessments ................................................................... 
5.4.4 Physician’s Global Assessment of Disease Activity................................. 
5.4.5 Joint Count Assessments .......................................................................... 
5.5 Pharmacokinetic Assessments .......................................................................... 
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5.5.1 Pharmacokinetic: Blood Collection ......................................................... 
5.5.2 Pharmacokinetic: Blood Sample Processing, Labeling and Shipping .... 
5.5.3 Pharmacokinetic Sample Analysis ........................................................... 
5.5.4 Pharmacokinetic Evaluation .................................................................... 
5.6 Biomarker Assessments .................................................................................... 
 
 
 
 
 
 
 
 
5.7 Outcomes Research Assessments ..................................................................... 
5.8 Other Assessments ............................................................................................ 
5.8.1 Immunogenicity Assessments ................................................................... 
5.8.1.1 Immunogenicity: Blood Collection ................................................. 
5.8.1.2 Immunogenicity: Blood Sample Processing, Labeling, and Shipping
...............................................................................................................
5.8.1.3 Immunogenicity: Sample Analysis .................................................. 
5.9 Labial Salivary Gland or Parotid Gland Biopsy (Substudy) ............................. 
6 ADVERSE EVENTS ................................................................................................. 
6.1 Serious Adverse Events .................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting .................................... 
6.2 Nonserious Adverse Events .............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting .............................. 
6.3 Laboratory Test Result Abnormalities .............................................................. 
6.4 Pregnancy .......................................................................................................... 
6.5 Overdose ........................................................................................................... 
6.6 Potential Drug Induced Liver Injury (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) ............................................................................. 
 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses ....................................................................... 
 
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8.4.6 Outcomes Research Analyses .................................................................. 
8.4.7 Other 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 .................................................................... 
9.2 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 .................................................................................. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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1.1.1
Pathophysiology of Sjögren’s Syndrome
The salivary glands in pSS are infiltrated by T- and B-lymphocytes as well as by non-lymphoid 
cells. Epithelial cells of striated ducts are likely the targets of the autoimmune attack. Within the 
glandular tissue, inflammatory infiltrates can be organized as ectopic lymphoid tissues with 
segregated T- and B-cell areas, germinal center-like structures and high endothelial venules. B 
cell hyper-reactivity is a hallmark of pSS.6 Autoantibodies directed against the Ro/SSA and 
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La/SSB ribonucleoproteins and/or the autoantibody, RF, are frequently found in pSS patients, 
together with elevated levels of serum immunoglobulins (hypergammaglobulinemia). However, 
the pathogenic role for autoantibodies remains unclear. Effector CD4+ Th cells are known to be 
required for humoral immune responses to these protein autoantigens.7 These CD4+ Th (T 
follicular helper cells or Tfh) cells are essential for the generation of plasma cells, as well as for 
the formation of memory cells in the germinal center-like structures in the salivary glands.
 
 
 
 
 
 
pSS.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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1.2
Research Hypothesis
Abatacept 125 mg, administered subcutaneously (SC) will have greater efficacy than placebo in 
subjects with moderately to severely active pSS as assessed by the mean change from baseline in 
the ESSDAI score after Day 169 of treatment.
1.3
Objectives(s)
1.3.1
Primary Objectives
To compare the mean change from baseline (Day 1) to Day 169 in ESSDAI of abatacept versus 
placebo in subjects with moderate to severe pSS.
1.3.2
Secondary Objectives
Key Secondary Objectives
1) To compare the mean change from baseline (Day 1) to Day 169 in ESSPRI of abatacept 
versus placebo in subjects with moderate to severe pSS.
2) To compare the mean change from baseline (Day 1) to Day 169 in the stimulated whole 
salivary flow of abatacept versus placebo in those subjects with stimulated whole salivary 
flow of at least 0.1 mL/min at both screening and baseline.
Other Secondary Objectives
1) To assess the mean change from baseline at all measured time points up to Day 169 in 
DAS28-CRP among those with a tender joint count plus swollen joint count of at least 3 at 
baseline, among those with a tender joint count plus swollen joint count of less than 3 at 
baseline, and in the full population.
2) To assess the mean change from baseline at all measured time points up to Day 169 in the 
individual components of DAS28-CRP among those with a tender plus swollen joint count of 
at least 3 at baseline, among those with a tender joint count plus swollen joint count of less 
than 3, and in the full population.
3) To assess the proportion of subjects who achieve a minimally clinically important 
improvement in ESSDAI (3) at all measured time points up to Day 169 in the full 
population, among those with stimulated whole salivary flow of at least 0.1 mL/min at both 
screening and baseline, and among those with stimulated whole salivary flow of less than 0.1 
mL/min at screening or baseline.
4) To assess the proportion of subjects who achieve a minimally clinically important 
improvement in ESSDAI (5) at all measured time points up to Day 169 in the full 
population, among those with stimulated whole salivary flow of at least 0.1 mL/min at both 
screening and baseline, and among those with stimulated whole salivary flow of less than 0.1 
mL/min at screening or baseline.
5) To assess the proportion of subjects who achieve a minimally clinically important 
improvement in ESSPRI (1) at all measured time points up to Day 169 in the full 
population, among those with stimulated whole salivary flow of at least 0.1 mL/min at both 
screening and baseline, and among those with stimulated whole salivary flow of less than 0.1 
mL/min at screening or baseline.
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6) To assess the mean change from baseline at all measured time points up to Day 169 in 
ESSDAI in the full population, among those with stimulated whole salivary flow of at least 
0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary 
flow of less than 0.1 mL/min at screening or baseline.
7) To assess the mean change from baseline at all measured time points up to Day 169 in 
ESSPRI in the full population, among those with stimulated whole salivary flow of at least 
0.1 mL/min at both screening and baseline, and among those with stimulated whole salivary 
flow of less than 0.1 mL/min at screening or baseline.
8) To assess the mean change from baseline in the individual components of the ESSDAI at all 
measured time points up to Day 169 in the full population, among those with stimulated 
whole salivary flow of at least 0.1 mL/min at both screening and baseline, and among those 
with stimulated whole salivary flow of less than 0.1 mL/min at screening or baseline.
9) To assess the mean change from baseline in the individual components of the ESSPRI at all 
measured time points up to Day 169 169 in the full population, among those with stimulated 
whole salivary flow of at least 0.1 mL/min at both screening and baseline, and among those 
with stimulated whole salivary flow of less than 0.1 mL/min at screening or baseline.
10) To assess the mean change from baseline in Schirmer’s test at all measured time points up to 
Day 169.
11) To assess the mean change from baseline in ocular staining score at all measured time points
up to Day 169.
12) To assess the mean change from baseline in tear break-up time at all measured time points up 
to Day 169.
13) To assess the mean change from baseline in unstimulated whole salivary flow at all measured 
time points up to Day 169 in the full population, among those with stimulated whole salivary 
flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated 
whole salivary flow of less than 0.1 mL/min at screening or baseline.
14) To assess the mean change from baseline in stimulated whole salivary flow at all measured 
time points up to Day 169 in the full population, among those with stimulated whole salivary 
flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated 
whole salivary flow of less than 0.1 mL/min at screening or baseline.
15) To assess the change in patient symptoms using the Numeric Rating Scale (NRS) for mouth 
dryness at all measured time points up to Day 169 in the full population, among those with 
stimulated whole salivary flow of at least 0.1 mL/min at both screening and baseline, and 
among those with stimulated whole salivary flow of less than 0.1 mL/min at screening or 
baseline.
16) To assess the mean change in patient symptoms using the Numeric Rating Scale (NRS) for 
eye dryness at all measured time points up to Day 169.
17) To assess the mean change in patient symptoms using the patient global assessment of 
disease activity at all measured time points up to Day 169.
18) To assess the mean change in the physician global assessment at all measured time points up 
to Day 169.
19) To assess the mean change in patient fatigue using PROMIS Fatigue assessment at all 
measured time points up to Day 169.
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20) To assess the mean change in female sexual function using the Female Sexual Function 
Index (FSFI) at all measured time points up to Day 169.
21) To assess the mean change in patient quality of life using the SF-36 at all measured time 
points up to Day 169.
22) To assess safety and immunogenicity of abatacept.
23) To assess the pharmacokinetics of abatacept.
 
 
 
 
 
 
 
1.4
Product Development Background
Abatacept is a recombinant fusion protein consisting of the extracellular domain of human 
CTLA4 and a fragment of the Fc domain of a human IgG1 that has been modified to prevent 
complement-mediated antibody-dependent cellular cytotoxicity (hinge-CH2-CH3 domains, 
re-engineered to eliminate complement fixation capability). 
Abatacept is the first and currently the only approved drug in a class of agents termed, “selective 
costimulation modulators”. Activation of naive T cells during an immune response requires 
2 stimuli from antigen presenting cells (APC). The first signal is antigen specific and is mediated 
through the T cell receptor. The second or costimulatory signal is not antigen specific and is 
delivered following the engagement of a costimulatory ligand on the APC with a cognate 
receptor on the T cell. A key co stimulatory receptor on T cells is CD28. CD28 is constitutively 
expressed on resting T cells and binds to both B7-1 (CD80) and B7-2 (CD86) on the 
APC.14,15,16,17 A costimulatory signal is required for the full antigen-induced activation of naive 
T cells and may be required for the survival of auto-immune effector memory T cells.18,19
Abatacept binds specifically to B7-1 and B7-2 and hence inhibits the CD28-mediated co 
stimulation of T cells by these molecules.
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1.5
Overall Risk/Benefit Assessment
Clinical investigation of abatacept has been underway since 15-Aug-1995. Over 15,000 subjects 
have enrolled in clinical trials, and an estimated 10,771 of these subjects have been exposed to 
abatacept IV or SC regimens, with the majority of subjects with diagnoses of RA (8,345) or 
lupus (557).20
There is extensive safety experience with IV and SC abatacept in adults with RA. The safety 
profile of abatacept is well established and favorable.21 The total patient-years (p-y) of exposure 
in RA, as well as consistent safety profiles in non-RA clinical studies provides a high level of 
confidence in the assessment of the acceptable safety profile associated with abatacept.
Primary Sjögren’s syndrome shares features with other autoimmune diseases, such as systemic 
lupus erythematosus (SLE). Safety data are available for IV abatacept use in 121 adult subjects
with SLE from IM101042 (placebo subjects n = 59).22 This study was a 12-month exploratory 
Phase 2 study of abatacept at 10 mg/kg IV monthly in SLE subjects experiencing flares with 
active manifestations of polyarthritis, discoid lesions, or pleuritis/pericarditis. Safety data are
also available for IV abatacept in 228 adult subjects with lupus nephritis (LN) in the Phase 2, 
dose-ranging, placebo-controlled IM101075 study (placebo subjects n = 74).23 The study was 
terminated prematurely by the Sponsor during the long term extension period because the main 
primary and secondary efficacy endpoints were not met for abatacept at the end of the 
double-blind short term period.23,24 The overall safety profile of IV abatacept in SLE and LN did 
not indicate a different safety profile than in RA. 
Two open-label, single-center pilot studies have suggested efficacy of abatacept 10 mg/kg 
administered intravenously in pSS with a well-tolerated safety profile (N = 11, N = 15), as noted 
above.4,5
Based on the safety data of abatacept in RA, SLE, LN and pSS, abatacept is expected to be well-
tolerated in this pSS patient population. The mechanism of action of abatacept, as well as its 
proven efficacy in RA and its efficacy in two different open-label pilot studies in pSS, suggests 
potential efficacy for patients with pSS. There are currently no approved therapies to manage the 
systemic manifestations of pSS, and therefore the unmet need is high.
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) and applicable local requirements.
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
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All potential serious breaches must be reported to Sponsor or designee immediately. A serious 
breach is a breach of the conditions and principles of GCP in connection with the study or the 
protocol, which is likely to affect, to a significant degree, the safety or physical or mental 
integrity of the subjects of the study or the scientific value of the study.
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or 
where there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
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 Investigator Brochure 
or product labeling information to be provided to subjects and any updates. 
The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and 
other information (eg, expedited safety reports, amendments, and administrative letters)
according to regulatory requirements or institution procedures.
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. 
Sponsor or designee will provide the investigator with an appropriate (ie, Global or Local) 
sample informed consent form which will include all elements required by ICH, GCP and 
applicable regulatory requirements. The sample informed consent form will adhere to the ethical 
principles that have their origin in the Declaration of Helsinki.
Investigators must:

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
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
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 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 randomized, double-blind, placebo controlled study in subjects who have been 
diagnosed with active, moderate to severe, primary Sjögren’s Syndrome based on the proposed 
2015 ACR/EULAR Classification Criteria for pSS and have an ESSDAI disease activity score of 
at least 5 at screening. The study consists of a 28-day screening period, followed by a 169-day
double-blind period, a 197-day open-label abatacept period and a subsequent 84-day follow-up 
period.
The investigator should accept only those subjects who give a reasonable indication that they 
will complete the double-blind period of the study. All subjects who discontinue investigational 
product during the Double-Blind Treatment Period should continue to comply with protocol 
specified procedures as outlined in Section 5 - Study Assessments and Procedures. The only 
exception to this requirement is when a subject withdraws consent for all study procedures 
including post-treatment study follow-up or loses the ability to consent freely (i.e., is imprisoned 
or involuntarily incarcerated for the treatment of either a psychiatric or physical illness).
Subjects who discontinue treatment with study drug during the Double-Blind Treatment Period 
must continue to be assessed for all efficacy measures and for safety at all remaining double-
blind study visits through Week 24 (Day 169) (see Table 5.1-2). In addition, subjects who 
discontinue treatment with the study drug will require visits to assess safety and immunogenicity 
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28 and 84 days after the last dose of study drug. If these visits will fall within ± 14 days of a 
scheduled study visit, only an additional laboratory assessment (immunogenicity) may need to be 
performed at the scheduled study visit. Otherwise, the 28 Day and/or 84 Day After Last Dose of 
Study Medication follow-up visits need to be performed at the appropriate time.
The study design schematic is presented in Figure 3.1-1.
Figure 3.1-1:
Study Design Schematic
A pharmacokinetic sampling sub-study (approximately 40 subjects) will be conducted during the 
double-blind treatment period to collect additional PK samples from those subjects that sign 
consent to participate. An optional labial salivary gland or parotid gland biopsy sub-study (Day 1 
and Day 169) will also be conducted.
3.1.1
Screening Period
Eligibility will be based on specified inclusion and exclusion criteria, medical history, disease 
activity and safety assessments. The screening phase will last for a minimum of 7 days and a 
maximum of 28 days. Subjects who experience an acute infection or initiate treatment for latent 
TB may extend the screening period to 56 days. If the screening period extends beyond 28 days, 
a second screening visit will be required within 28 days prior to randomization.
Eligible subjects will have been diagnosed with Sjögren’s syndrome based on the proposed 2015 
ACR/EULAR Classification Criteria (Appendix 3) and will have an ESSDAI score of at least 
five points at screening (Appendix 6). Subjects must be anti-SSA/Ro positive at screening and at 
least 124 subjects (72%) must have a stimulated salivary flow of at least 0.1 mL/min at screening 
and randomization.
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Subjects taking hydroxychloroquine are permitted to continue this medication provided that the 
therapy has been taken for at least 12 weeks and that the dose is stable for at least 4 weeks prior 
to randomization and remains stable throughout the study. Decreases in dose or discontinuation 
is permitted for adverse events or intolerance.
Subjects receiving oral corticosteroids must be on a stable dose and at the equivalent of 10 mg 
prednisone daily for at least 4 weeks prior to randomization. Subjects may not have received an 
IM, IV or IA administration of a corticosteroid within 4 weeks prior to randomization.
Stable doses of pilocarpine, cevimeline, and cyclosporine eye preparations, as well as artificial 
tears and saliva are permitted, but must not be used for an appropriate period prior to salivary 
and ocular testing. See Section 3.4.1.2 for specified times for each assessment.
Approximately 172 subjects in total will be randomized in a 1:1 ratio to 125 mg SC weekly of 
abatacept or placebo (86 subjects per arm). Randomization will be stratified globally by current 
use of corticosteroids, current use of hydroxychloroquine, and by stimulated salivary flow 
(< 0.1 mL/min, 0.1 mL/min).
3.1.2
Double-Blind Treatment Period (Day 1 to Day 169)
On day 1, subjects will be randomized to one of two blinded parallel treatment arms in a 1:1 
ratio:
1) Abatacept for SC injection 125mg/mL in 1 mL pre-filled syringe
2) Placebo for abatacept for SC injection in 1 mL pre-filled syringe
The duration of the treatment period is 169 days.
Abatacept or matching placebo administration:
Abatacept (125 mg) or matching placebo will be administered subcutaneously (SC) once per 
week. On Day 1, subjects and/or personal caregivers will be trained in self-administration of SC 
injections using pre-filled syringes. All subsequent injections will be self-administered or 
administered by a personal caregiver, and should not be administered by the physician or 
medical staff at the study site. Medical staff can act as a caregiver only when the subject cannot 
self-administer and does not have access to a personal caregiver, see Section 4.5.1.
On “Office Visit” days, SC injections should occur AFTER all assessments, including blood
draws for assessment of immunogenicity and drug concentrations. To ensure compliance and to
monitor technique “office visit” SC injections should be conducted in the presence of a qualified
investigational staff.
3.1.3
Open Label Extension (Day 169 to Day 365)
At the end of the double blind treatment period there will be a 196 day open label extension 
(OLE). On Day 169 all subjects continuing on treatment (including those subjects who received 
placebo during the double blind period) will receive open-label abatacept SC, 125 mg weekly to 
Day 357.
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On “Office Visit” days, SC injections should occur AFTER all assessments, including blood
draws for assessment of immunogenicity and drug concentrations.
Subjects not wishing to continue on open-label abatacept have the option of discontinuing 
treatment at the end of the double-blind period and proceeding to the post-treatment follow-up 
period.
3.1.4
Post-Treatment Follow-up Period
Subjects who discontinue treatment of study drug during the open-label period or complete the 
study will have two follow-up visits 28 and 84 days after the last treatment visit, to perform 
safety and laboratory assessments, including immunogenicity testing. Subjects who discontinue 
treatment with the study drug during the double-blind period will require two visits to assess 
safety and immunogenicity 28 and 84 days after the last dose of study drug. If these visits are
within ± 14 days of a scheduled study visit, only an additional laboratory assessment 
(immunogenicity) needs to be performed at the scheduled study visit. Otherwise, the follow-up 
visits as described in the Time & Events table (Table 5.1-6) need to be performed.
The start of the trial is defined as the date the first subject signs the informed consent. End of 
trial is defined as the last visit or scheduled procedure shown in the Time & Events schedule for 
the last subject. The study will continue beyond primary endpoint collection until the End of 
Trial.
3.2
Post Study Access to Therapy
At the conclusion of the study, participants who continue to demonstrate clinical benefit will be 
eligible to receive BMS supplied study treatment. Study treatment will be provided via an 
extension of the study, a rollover study requiring approval by responsible health authority and 
ethics committee or through another mechanism at the discretion of BMS. BMS reserves the 
right to terminate access to BMS supplied study treatment if any of the following occur: a) the 
study is terminated due to safety concerns; b) the development of abatacept is terminated for 
other reasons, including but not limited to lack of efficacy and/or not meeting the study 
objectives; c) the participant can obtain medication from a government sponsored or private 
health program. In all cases BMS will follow local regulations.
Treatment codes will be provided to the investigators after completion of the study.
3.3
Study Population
For entry into the study, the following criteria MUST be met.
3.3.1
Inclusion Criteria
1. Signed Written Informed Consent
a.
Subject is willing to participate and has signed informed consent.
2. Target Population
a.
Subjects must meet the proposed 2015 ACR/EULAR Classification Criteria for SS
(Sjögren’s Syndrome) (Appendix 3), as specified for pSS (primary Sjögren’s
Syndrome).
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i. If a prior labial salivary or parotid gland biopsy was performed, information 
will be reported in the CRF and the report should be obtained for the source 
documents.  
b. Subjects should have pSS that is refractory to symptomatic or local therapy 
(eg, NSAIDs).
c.
ESSDAI 5 at screening.
d. Positive anti-SSA/Ro at screening.
e.
Stimulated salivary flow of at least 0.1 mL/min at screening and randomization in at 
least 124 subjects (72%). Enrollment of subjects with less than 0.1 mL/min of 
stimulated salivary flow at screening and/or randomization may be closed after 48 of 
such subjects are randomized.
f.
Subject Re-enrollment: This study permits the re-enrollment of a subject that has 
discontinued the study as a pre-treatment failure (ie, a “screen failure”, the subject has 
not been randomized / has not been treated). If re-enrolled, the subject must be 
re-consented and will receive a new PID.
3. Age and Reproductive Status
a.
Males and Females, ages 18 (or age of majority).
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 breastfeeding.
d. Women of childbearing potential (WOCBP) must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug(s) 
(abatacept/placebo) plus 5 half-lives of study drug (70 days) plus 30 days (duration of 
ovulatory cycle) for a total of 100 days post-treatment completion.
e.
Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug(s) 
(abatacept/placebo) plus 5 half-lives of the study drug (70 days) plus 90 days (duration 
of sperm turnover) for a total of 160 days post-treatment completion. In addition, male 
subjects must be willing to refrain from sperm donation during this time.
f.
Azoospermic males are exempt from contraceptive requirements. WOCBP who are 
continuously not heterosexually active are also exempt from contraceptive 
requirements, and still must undergo pregnancy testing as described in this section.
Investigators shall counsel WOCBP, and male subjects who are sexually active with WOCBP, 
on the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
Investigators shall advise on the use of highly effective methods of contraception (Appendix 1), 
which have a failure rate of < 1% when used consistently and correctly.
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3.3.2
Exclusion Criteria
1. Target Disease Exceptions
a.
Subjects who have a systemic autoimmune disease other than Sjögren’s syndrome
(SS), such as RA, SLE, or systemic sclerosis, that can better explain the majority of 
the symptoms (ie, secondary Sjögren’s syndrome).
b. Subjects who have another autoimmune disease or inflammatory condition that could 
interfere with assessment of response of primary SS (pSS) to therapy (eg, systemic 
sclerosis, inflammatory bowel disease, gout).
c.
Subjects with any other medical condition associated with clinical features 
overlapping those of pSS or that would interfere with interpretation of results, 
including but not limited to a history of head and neck radiation treatment, sarcoidosis, 
amyloidosis, graft-versus-host disease, hepatitis C, acquired immunodeficiency 
syndrome, and IgG4-related disease.
d. Subjects with severe fibromyalgia that could interfere with the assessment of response 
of pSS to therapy.
e.
Active life-threatening or organ-threatening complications of SS disease at the time of 
screening based on investigator evaluation including but not restricted to the 
following:
i. Vasculitis with renal, digestive, cardiac, pulmonary or central nervous system 
(CNS) involvement characterized as severe (note: cutaneous vasculitis is 
allowed)
ii. Active CNS or peripheral nervous system (PNS) involvement requiring high 
dose steroids
iii. Severe renal involvement, eg, GFR < 60 mL/min, a serum creatinine 
> 2 mg/dL, or proteinuria > 3 g/day,
iv. Severe pulmonary involvement, eg, shortness of breath at rest, or pulmonary 
function tests demonstrating DLCO < 40% or FVC < 60%
v. Severe muscular involvement requiring high dose steroids
vi. Lymphoma
2. Medical History and Concurrent Diseases
a.
Subjects at risk for tuberculosis (TB) defined as follows:
i. Current clinical, radiographic or laboratory evidence of active TB, even if 
currently being treated. Chest x-rays (posterior/anterior and lateral) obtained 
within the 6 months prior to screening and TB testing (IFN-release assay or 
PPD) performed in the past month prior to screening will be accepted; 
however, a copy of the reports must be placed in the subject binder.
ii. A history of active TB unless there is documentation that the subject had 
received prior anti-TB treatment that was appropriate in duration and type
according to local health authority guidelines.
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iii. Subjects with a positive TB screening test indicative of latent TB will not be 
eligible for the study unless they:
1. Have no evidence of current TB based on chest x-ray performed during 
the screening period and by history and physical exam, and 
2. They are currently being treated for latent TB or the site has 
documentation of successful prior treatment of latent TB. Treatment 
regimens should be dictated by local guidelines as long as the treatment 
dose and duration meet or exceed local health authority guidelines. If 
permitted by local guidelines regarding treatment with biologic 
medications, subjects with latent TB may be randomized prior to 
completion of treatment as long as they have completed at least 4 
weeks of treatment and they have no evidence of current TB on chest x-
ray at screening.
b. Subjects with recent acute infection defined as:
i. Any acute infection within 60 days prior to randomization that required 
hospitalization or treatment with parenteral antibiotics.
ii. Any acute infection within 30 days prior to randomization that required oral 
antimicrobial or antiviral therapy.
c.
Subjects with history of chronic or recurrent bacterial infection (such as chronic 
pyelonephritis, osteomyelitis, and bronchiectasis etc.).
d. Subjects who have a history of systemic fungal infections (such as histoplasmosis, 
blastomycosis, or coccidiomycosis).
e.
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.
f.
Subjects with history of Human Immunodeficiency Virus (HIV) infection or who test 
positive for HIV at screening.
g. Subjects with a history of primary immunodeficiency.
h. Subjects who have a present malignancy or previous malignancy within the last 5 
years prior to screening (except documented history of cured non-metastatic squamous 
or basal cell skin carcinoma or cervical carcinoma in situ). Subjects who had a 
screening procedure that is suspicious for malignancy, and in whom the possibility of 
malignancy cannot be reasonably excluded following additional clinical, laboratory or 
other diagnostic evaluations. Subjects with a history of lymphoma
i.
Current clinical findings of severe, progressive, or uncontrolled renal, hepatic, 
hematological, 
gastrointestinal, 
pulmonary, 
psychiatric, 
cardiac, 
endocrine, 
neurological, or cerebral disease including severe and uncontrolled infections, such as 
sepsis and opportunistic infections. Concomitant medical conditions that, in the 
opinion of the investigator, might place the subject at unacceptable risk for 
participation in this study.
j.
Subjects who have received any live vaccines within 3 months of the study drug 
administration or are scheduled to receive live vaccines during the study. Study 
subjects should not be administered a live virus vaccine for a minimum of 3 months 
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following the last dose of study medication. Subjects who are in close contact with 
others who have received a live vaccine may be enrolled at the investigator’s 
discretion.
k. Subjects who have undergone a major surgical procedure within the 60 days prior to 
randomization.
l.
Subjects with a history of (within 12 months of signing informed consent), or known 
current problems with drug or alcohol abuse history or known cirrhosis including 
alcoholic cirrhosis.
m. Subjects who are impaired, incapacitated, or incapable of completing study-related 
assessments.
3. Physical and Laboratory Test Findings
a.
Hepatitis B surface antigen (HBsAg)-positive, or hepatitis B core antibody 
(HBcAb)-positive subjects with detectable hepatitis B viral DNA, and where required 
by local regulations or standard practice hepatitis B surface antibody (HBsAb)-
positive subjects with detectable hepatitis B viral DNA.
b. Hepatitis C antibody (HcAb)-positive subjects with detectable hepatitis C viral RNA
c.
Hemoglobin (Hgb) < 8.5 g/dL
d. White Blood Count (WBC) < 2,500/mm3 (2.5 x 109/L)
e.
Lymphocytes < 500/mm3 (0.5 x 109 /L)
f.
Platelets < 50,000/mm3 (50 x 109/L)
g. Subjects with serum ALT or AST > 3 times upper limit of normal unless in the 
judgment of the investigator the elevation is explicitly related to pSS and does not 
pose a risk to participation in the study.
h. Any test results that, in the opinion of the investigator, might place the subject at 
unacceptable risk for participation in this study.
4. Allergies and Adverse Drug Reaction
a.
Hypersensitivity to abatacept and/or its excipients
5. Prohibited Treatments and/or Therapies
a.
Subjects who have previously been exposed to abatacept or anti-CD28 therapy.
b. Subjects who have received IV, IM, SC or intra-articular corticosteroids within 4
weeks of randomization (Day 1).
c.
Subjects who have taken rituximab within 12 months prior to randomization (Day 1).
d. Subjects who have taken belimumab within 12 weeks prior to randomization (Day 1).
e.
Subjects who have taken a biologic therapy other than rituximab or belimumab or any 
other investigational therapy within 12 weeks or 5 half-lives prior to randomization 
(Day 1), whichever is longer.
f.
Subjects 
who 
have
taken 
cyclophosphamide, 
mycophenolate 
mofetil 
(MMF)/mycophenolic acid (MPA) or leflunomide within 6 months of randomization 
(Day 1).
g. Subjects who have taken methotrexate within 12 weeks of randomization (Day 1).
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h. Subjects who have taken cyclosporine (systemic), azathioprine, tacrolimus, tofacitinib, 
mizoribine, actarit, or bucillamine within 4 weeks of randomization (Day 1).
i.
Subjects who have taken Intravenous Immunoglobulin (IVIG) within 4 weeks of 
randomization (Day 1).
j.
Subjects who have taken diquafosol or ophthalmic rebamipide within 4 weeks prior to 
randomization (Day 1).
k. Subjects who have taken a tricyclic antidepressant drug within 4 weeks prior to 
randomization (Day 1).
l.
Subjects are not permitted to have new installation of lacrimal punctum plugs within 
4 weeks of randomization (Day 1). 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).
b. Subjects who are compulsorily detained for treatment of either a psychiatric or 
physical (eg, infectious disease) illness.
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
Women of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) 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 > 40 mIU/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.

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
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Other parenteral products may require washout periods as long as 6 months. If the serum 
FSH level is > 40 mIU/mL at any time during the washout period, the woman can be considered 
postmenopausal.
 
 
 
 
 
 
 
 
  
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Double-blind Period
Subjects are permitted to continue oral corticosteroids at doses of less than or equal to 
prednisone 10 mg daily (or equivalent) provided that the dose is stable for at least 4 weeks prior 
to randomization and remains stable throughout the double-blind period. During the double-blind 
period, decrease in dose or discontinuation of oral corticosteroids is permitted only for adverse 
events or intolerance. IM, IV, SC and intra-articular corticosteroids are not permitted. Topical 
corticosteroids are permitted throughout the study.
Open-label Period
During the open-label period, oral corticosteroids at a dose of prednisone, up to 10 mg daily, or 
equivalent, may be initiated. The dose of oral corticosteroids may be decreased for any reason, 
but the dose may not be increased above prednisone 10 mg daily (or equivalent). Intra-articular 
corticosteroids are permitted, but IM, IV and SC corticosteroids are not permitted. Topical 
corticosteroids are permitted throughout the study.
Analgesics and NSAIDs:

NSAIDs and analgesics (including topical NSAIDs) are not permitted within 12 hours before 
a joint assessment

During the double-blind period for subjects on study therapy, NSAID doses should remain 
stable, as assessed by the Investigator, with the exception of decreases being permitted due to 
related AEs, such as gastric toxicity.  

Analgesics

Acetaminophen (paracetamol) permitted if
Average dose of 3 g/day
No single dose exceeding 1 g
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 
3 g/day.

Narcotic analgesics must not exceed 30 mg/day of morphine or its equivalent.

Tramadol, gabapentin, and pregabalin are allowed but doses must be stable throughout 
double blind period for subjects on study therapy.
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3.4.2.1
Immunizations
There is limited information available regarding the effectiveness of immunizations in non-
human primates that have been treated with abatacept. Limited data are available on the effect of 
therapeutic vaccinations in subjects receiving abatacept.
Due to the risk of infection, vaccination of subjects with any live vaccine is absolutely 
contraindicated during the study drug treatment period of the study, as is the administration of 
LIVE oral polio vaccine to household contacts. The Center for Disease Control Advisory 
Committee on Immunization Practices (CDC ACIP) recommends that subjects should not be 
administered a live virus vaccination for at least 3 months after discontinuing high dose 
corticosteroid therapy (defined as more than 20 mg of prednisone per day for more than
2 weeks). In view of the long half-life of abatacept, study subjects should not be administered a 
live virus vaccine for a minimum of 3 months following the last dose of study medication.
3.4.2.2
Infectious Complications
Subjects who develop significant infectious complications during the study should be treated 
appropriately and have study medication withheld, and restarted only when clinically resolved 
and the investigator considers it appropriate.
3.4.2.3
Management of Possible Acute Hypersensitivity Reactions
Hypersensitivity resulting in severe, acute allergic reactions may occur as a result of the protein 
nature of abatacept. As defined in a recent consensus statement,25 anaphylaxis is highly likely if 
2 or more of the following occur rapidly after administration of the study drug (minutes to 
several hours):

Involvement of the skin-mucosal tissue (eg generalized hives; itching or flushing; swollen 
lips, tongue, or uvula).

Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
exploratory flow, hypoxemia).

Reduced blood pressure (BP) or associated symptoms (eg, hypotonia/collapse, syncope, and 
incontinence).

Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting).
Sites must be appropriately prepared to handle medical emergencies such as severe 
hypersensitivity including anaphylaxis. Subjects must be rapidly assessed and stabilized at the 
site and transferred to an emergency facility as required. If subjects experience symptoms of 
severe allergic reactions at home, they should be advised to seek immediate medical attention, 
including a visit to the local emergency facility, as needed. The site will provide emergency 
contact information to the subject. A blood sample for analysis of anti-abatacept antibodies 
should be obtained in case of a hypersensitivity reaction.
The decision whether to continue treatment with the study drug will be left to the medical 
judgment of the investigator. Care should be taken to treat any acute toxicity, expeditiously, 
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should they occur. Adequate equipment and trained health care personnel should be available to 
handle medical emergencies when they occur at the site.
3.5
Discontinuation of Study Therapy
Subjects who discontinue treatment with investigational product during the Double-Blind 
Treatment Period must continue to be assessed for all efficacy measures and for safety at all 
remaining double-blind study visits through Week 24 (Day 169) (see Table 5.1-2). Those 
subjects who discontinue treatment with the study drug during the double-blind period will also 
require visits to assess safety and immunogenicity at 28 and 84 days after the last dose of study 
drug. If these visits fall within ± 14 days of a scheduled double-blind study visit, only an 
additional laboratory assessment (immunogenicity) needs to be performed at the scheduled study 
visit. Otherwise, the follow-up visits need to be performed.  
Subjects who discontinue study drug during the Open-Label Treatment period 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).
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

Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continuation of study therapy is not in the best 
interest of the subject

Pregnancy

Missed Doses:

During the double-blind period, any subject who misses greater than four consecutive 
doses or greater than eight total doses must be discontinued from study therapy

During the open-label period, any subject who misses greater than six consecutive doses
or greater than ten total doses must be withdrawn from the study

Significant non-compliance with protocol (ie, procedures, assessments, medication, etc). The 
investigator should discuss such issues with the BMS Medical Monitor.

Use of prohibited medication. The investigator should discuss the use of a prohibited 
medication with the Medical Monitor prior to withdrawing a subject from study therapy
In the case of pregnancy, the investigator must immediately notify the Sponsor or 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 contact the Sponsor or 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 Sponsor or designee must occur.
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The reason for discontinuation of study drug must be documented in the subject’s medical 
records and entered on the appropriate case report form (CRF) page.
3.6
Discontinuation from the Study 
Subjects MUST discontinue the study for any of the following reasons:

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

Subject withdraws consent

Participation in another clinical trial with an investigational product 
The reason for discontinuation from the study must be documented in the subject’s medical 
records and entered on the appropriate case report form (CRF) page.
3.7
Post Study Drug Study Follow up
Subjects who discontinue study drug may continue to be followed.
Subjects who withdraw consent (according to Section 3.7.1) or are lost to follow-up (according 
to Section 3.7.2) will not be followed in this study; all other subjects will continue to be followed 
for collection of follow up data as required and in line with Section 5, Study Assessments and 
Procedures.
3.7.1
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, if 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.
3.7.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost to 
follow-up is defined by the inability to reach the subject after a minimum of three documented 
phone calls, faxes, or emails as well as lack of response by subject to one registered mail letter. 
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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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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:
Table 4-1:
Study Drugs for IM101603:
Product Description / 
Class and Dosage Form
Potency
IP/Non-IMP
Blinded or Open 
Label
Packaging / Appearance
Storage Conditions
(per label)
Abatacept Injection
125 mg/syringe
125 mg/mL
IP
Blinded
4 syringes per kit
Clear to slightly opalescent, 
colorless to pale yellow solution, 
essentially free of particulate 
matter on visual inspection
Store refrigerated 2 – 8 °C
Protect from light
Protect from freezing
Placebo for abatacept 
Injection
N/A
IP
Blinded
4 syringes per kit
Clear to slightly opalescent, 
colorless to pale yellow solution, 
essentially free of particulate 
matter on visual inspection
Store refrigerated 2 – 8 °C
Protect from light
Protect from freezing
Abatacept Injection
125 mg/syringe
125 mg/mL
IP
Open-Label
4 syringes per kit
Clear to slightly opalescent, 
colorless to pale yellow solution, 
essentially free of particulate 
matter on visual inspection
Store refrigerated 2 – 8 °C
Protect from light
Protect from freezing
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4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined as 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:

Abatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe

Placebo for abatacept for subcutaneous injection in 1 mL pre-filled syringe
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

Prednisone or other oral corticosteroids

NSAIDs and analgesics

Pilocarpine, cevimeline, cyclosporine eye drops (Restasis), lifitegrast 

Ocular and oral lubricants

Topical lubricants (skin emollients)
The Sponsor will not be providing these medications since they are part of subject’s standard of 
care.
4.3
Storage of Study Drug
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
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.
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4.4
Method of Assigning Subject Identification
At the time of enrollment, immediately after written informed consent is obtained and before any 
study-related procedures are performed, each subject will be assigned a unique, sequential 
five-digit number beginning with 00001, 00002, 00003, and so on, for identification throughout 
the study. This subject number must not be reused for any other subject. The study physician or 
research coordinator must contact the Central Randomization System to enroll each subject into 
a centralized database at the time consent is obtained. 
After completion of all screening evaluations and concomitant adjustment or stabilization, all 
eligible subjects will be randomized into the Double-Blind Treatment Phase of the study. 
Randomization schedules will be generated and kept by the Randomization Group within Drug 
Supply Management of Bristol-Myers Squibb. Randomization treatment will be assigned using a 
Central Randomization System in the order in which subjects qualify for treatment, not in the 
order of study enrollment. Subjects will be randomized on a 1:1 basis to either the abatacept 
treatment arm or the placebo treatment arm. 
Specific instructions for randomization into the Central Randomization System will be provided
in a separate manual.
4.5
Selection and Timing of Dose for Each Subject
On Office Visit days, study medication should be administered AFTER all assessments have 
been completed, including blood draws.
For subjects participating in the PK sub-study, the sample collection for PK on Day 15 should 
occur prior to dose administration.
4.5.1
Abatacept Treatment
Abatacept or matching placebo administration:
Abatacept (125 mg) or matching placebo will be administered subcutaneously (SC) once per 
week. On Day 1, subjects and/or personal caregivers will be trained in self-administration of 
SC injections using pre-filled syringes. The subject should be able to self-administer the SC 
injection between office visits or have an office-trained caregiver do so. All subsequent 
injections will be self-administered or administered by a personal caregiver. Medical staff can act 
as a caregiver only when the subject cannot self-administer and does not have access to a 
personal caregiver.
Training should be performed by investigational site personnel that are considered qualified 
trainers by the Investigator. Subjects or their caregivers will be trained using instructions that 
will be provided by BMS. 
Injections sites may include the upper arms (outside area), thigh, or abdomen. When possible, 
injection sites and/or sides of the body should be rotated every week. The upper arm injection 
site should be used only by caregivers and not for self-administration.
To ensure compliance and to monitor technique “office visit” SC injections should be 
administered in the presence of a qualified investigational staff.
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On Day 169, all subjects continuing on in the Open-label treatment period will receive abatacept, 
125 mg SC, weekly.
4.5.2
Dose Modifications
4.5.2.1
Dose Modifications in the Absence of Adverse Events
Every effort should be made to give all study medications within 3 days of the target date 
during the treatment periods. The last dose before each office visit should be administered at 
least 4 days before the scheduled visit date. If study medication is not received within the dosing 
window, this dose should be skipped and the next dose must then be administered on the next 
scheduled target administration day.
4.5.2.2
Dose Modifications Due to Adverse Events
If abnormal laboratory test results or clinical adverse events indicate toxicity that, in the 
judgment of the investigator, could place the subject at risk, study drug administration should be 
interrupted and the investigator should notify the BMS medical monitor. Subjects may receive 
further study medication treatment only if full resolution of the adverse event or abnormal 
laboratory finding is documented.
If a dose is skipped, the next SC injection should be administered on the subsequent targeted 
administration day.
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 active product. It is highly desirable that the decision to unblind treatment assignment 
be discussed with the Medical Monitor, but the investigator always has ultimate authority for the 
decision to unblind. The Principal Investigator should only call in for emergency unblinding 
AFTER the decision to discontinue the subject has been made.
For this study, the method of unblinding for emergency purposes is the Central Randomization 
System (IVRS/IWRS).
In cases of accidental unblinding, the Medical Monitor should be contacted and every attempt 
should be made to preserve the blind.
Any request to unblind a subject for non-emergency purposes should be discussed with the 
Medical Monitor.
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The BMS Bioanalytical Science Department or its designee will be unblinded to the randomized 
treatment assignments in order to accurately perform sample analysis for the PK and 
Immunogenicity samples.
4.7
Treatment Compliance
All subjects are expected to receive study therapy as outlined in the protocol. Subjects will use 
diary cards to document self-injection of study drug between clinic visits. Permitted dose 
modifications are described in Section 4.5.2. Conditions under which therapy must be 
discontinued due to non-compliance are outlined in Section 3.5.
4.8
Destruction or Return of Investigational Product
For this study, IP (those supplied by BMS, a vendor 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

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.
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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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Table 5.1-1:
Screening Procedural Outline (IM101603)
Procedure
Screening
Visita
Screening
Visit 2b
Notes
Urinalysis
X
HBsAg, anti-HBcAb (anti-HBsAb where 
required)
X
If positive, obtain HBV DNA (see Section 5.3.7.5)
Hepatitis C Antibody
X
If positive, reflex to HCV confirmation such as PCR
HIV
X
Testing performed locally, if required
Anti-Ro Antibody (anti-SSA)
X
Quantitative Immunoglobulins (IgG, 
IgA, IgM)
X
Urine/Serum Pregnancy Test
X
X
WOCBP only, see Appendix 1 for details
Disease Assessments
ESSDAI
X
X
Stimulated Salivary Flow
X
X
See Section 5.4.2
a The duration of the screening period should not exceed 28 days.
b Subjects that experience an acute infection or initiate treatment for latent TB may extend the screening period to 56 days. Under these circumstances, all 
screening procedures except subject consenting, IVRS enrollment, height/weight, immunoglobulins, urinalysis, chest x-ray, TB testing, HepB/C and HIV 
should be repeated prior to randomization.
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Table 5.1-2:
Double-Blind Treatment Period - Procedural Outline (IM101603)a,b
Procedure
Day 1 
Day 29 (Wk 4)
Day 57 (Wk 8)
Day 85 (Wk 12)
Day 113 (Wk 16)
Day 141 (Wk 20)
Day 169 (Wk 24)/
Early Term.
Notes
Quantitative Immunoglobulins (IgG, IgM, IgA)
X
X
X
X
X
hsCRP
X
X
X
X
X
X
X
ESR
X
X
X
X
X
X
X
Performed locally, kits 
provided centrally.
Rheumatoid Factor, IgM-RF
X
X
X
X
X
-2-Microglobulin (B2M)
X
X
X
X
X
Free Light Chain (FLC)
X
X
X
X
X
Complement (C3, C4, CH50)
X
X
X
X
X
Anti-Ro Antibody (anti-SSA)
X
X
X
X
X
Anti-La Antibody (anti-SSB)
X
X
X
X
X
Anti-centromere Antibody (ACA)
X
X
X
X
X
Anti-CCP2
X
X
X
X
X
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Table 5.1-2:
Double-Blind Treatment Period - Procedural Outline (IM101603)a,b
Procedure
Day 1 
Day 29 (Wk 4)
Day 57 (Wk 8)
Day 85 (Wk 12)
Day 113 (Wk 16)
Day 141 (Wk 20)
Day 169 (Wk 24)/
Early Term.
Notes
Pharmacokinetic (PK) Assessments
Pharmacokinetic (PK) Sampling
X
X
X
X
X
X
X
Samples collected predose, 
except for ET.
See additional PK sampling 
for PK sub-study (Table 5.1-
5).
See more details in Section 
5.5.1.
Immunogenicity (anti-abatacept antibody) testing
X
X
X
Samples collected pre-dose
See more details in Section 
5.5.1.  
Subjects who discontinue 
treatment with the study drug 
will require a visit to assess 
safety and immunogenicity 28 
and 84 days after the last dose 
of study drug. If the visit is 
within ± 14 days of a 
scheduled study visit, only an 
additional laboratory 
assessment for 
immunogenicity needs to be 
performed at the scheduled 
visit.
Efficacy Assessments
ESSDAI 
X
X
X
X
X
X
X
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Table 5.1-2:
Double-Blind Treatment Period - Procedural Outline (IM101603)a,b
Procedure
Day 1 
Day 29 (Wk 4)
Day 57 (Wk 8)
Day 85 (Wk 12)
Day 113 (Wk 16)
Day 141 (Wk 20)
Day 169 (Wk 24)/
Early Term.
Notes
Tender (68)/Swollen (66) Joint Count
X
X
X
X
X
X
X
Physician’s Global Assessment of Disease Activity
X
X
X
X
X
X
X
ESSPRI
X
X
X
X
X
X
X
PROMIS Fatigue 
X
X
X
X
X
X
X
Subject’s Global Assessment of Disease Activity
X
X
X
X
X
X
X
Mouth (Oral) Dryness (NRS)
X
X
X
X
X
X
X
Eye (Ocular) Dryness (NRS)
X
X
X
X
X
X
X
SF-36
X
X
X
Female Sexual Function Index (FSFI)
X
X
X
Unstimulated Salivary Flow
X
X
X
See Section 5.4.2
Stimulated Salivary Flow
X
X
X
See Section 5.4.2
Schirmer Testc
X
X
X
Tear Break-Up Timec
X
X
X
Ocular Staining Scorec
X
X
X
Study Drug
Contact IVRS/IWRS
X
X
X
X
X
X
Train subjects and/or caregiver on how to self-inject 
and how to fill out the diary cards
X
Dispense diary cards
X
X
X
X
X
X
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Table 5.1-2:
Double-Blind Treatment Period - Procedural Outline (IM101603)a,b
Procedure
Day 1 
Day 29 (Wk 4)
Day 57 (Wk 8)
Day 85 (Wk 12)
Day 113 (Wk 16)
Day 141 (Wk 20)
Day 169 (Wk 24)/
Early Term.
Notes
Collect and review diary cards
X
X
X
X
X
X
Dosing of weekly abatacept/placebo
X
X
X
X
X
X
Must be administered weekly 
between visits. See Section 4.5
No dose administered at the 
Early Termination visit
Dispense monthly abatacept/placebo
X
X
X
X
X
X
Reconciliation of abatacept/placebo monthly kits
X
X
X
X
X
X
a All visits and procedures during the Double-Blind Treatment Period must occur within 3 days of the expected visit
b All subjects who discontinue study drug during the double-blind period should continue to comply with protocol specified procedures as outlined in Table 5.1-
2. The only exception to this requirement is when a subject withdraws consent for all study procedures including post-treatment study follow-up or loses the 
ability to consent freely (i.e., is imprisoned or involuntarily incarcerated for the treatment of either a psychiatric or physical illness).
c Procedure to be performed by an ophthalmologist or optometrist experienced in the diagnosis and treatment of Sjögren’s syndrome patients. Eye assessments 
must be performed within days of the study visit. See Section 5.4.3 for additional detail.
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Table 5.1-3:
Open-Label Treatment Period Procedural Outline (IM101603)a
Procedure
Day 169 (WK 24)b
Day 197 (Wk 28)
Day 225 (Wk 32)
Day 253 (Wk 36)
Day 281 (Wk 40)
Day 309 (Wk 44)
Day 337 (Wk 48)
Day 365 (Wk 52)/ 
End of Treatment
Notes
ESR
X
X
X
X
X
X
X
Performed locally, kits provided 
centrally.
Rheumatoid Factor; IgM-RF
X
X
Free Light Chain (FLC)
X
X
-2-Microglobulin (B2M)
X
X
Complement (C3, C4, CH50)
X
X
Anti-Ro Antibody (anti-SSA)
X
X
Anti-La Antibody (anti-SSB)
X
X
Anti-centromere Antibody (ACA)
X
X
Anti-CCP2
X
X
Pharmacokinetic (PK) Assessments
Pharmacokinetic (PK) Sampling
X
No sample collection at EOT.
Immunogenicity (anti-abatacept antibody) 
testing
X
No sample collection at EOT.
Biomarker Assessments
Serum Biomarkers
X
X
See Section 5.6.3
Saliva Biomarkers
X
X
See Section 5.6.4
Blood Immunophenotyping
X
See Section 5.6.5
PBMCs
X
X
See Section 5.6.5
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Table 5.1-3:
Open-Label Treatment Period Procedural Outline (IM101603)a
Procedure
Day 169 (WK 24)b
Day 197 (Wk 28)
Day 225 (Wk 32)
Day 253 (Wk 36)
Day 281 (Wk 40)
Day 309 (Wk 44)
Day 337 (Wk 48)
Day 365 (Wk 52)/ 
End of Treatment
Notes
Efficacy Assessments
ESSDAI 
X
X
X
X
X
X
X
Tender (68)/Swollen (66) Joint Count
X
X
X
X
X
X
X
Physician’s Global Assessment of Disease
Activity
X
X
X
X
X
X
X
ESSPRI
X
X
X
X
X
X
X
PROMIS Fatigue
X
X
X
X
X
X
X
Subject’s Global Assessment of Disease 
Activity
X
X
X
X
X
X
X
Mouth (Oral) dryness (NRS)
X
X
X
X
X
X
X
Eye (Ocular) dryness (NRS)
X
X
X
X
X
X
X
SF-36
X
X
Female Sexual Function Index (FSFI)
X
X
Unstimulated Salivary Flow
X
X
Stimulated Salivary Flow
X
X
Schirmer Testc
X
X
Tear break-up timec
X
X
Ocular staining scorec
X
X
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Table 5.1-3:
Open-Label Treatment Period Procedural Outline (IM101603)a
Procedure
Day 169 (WK 24)b
Day 197 (Wk 28)
Day 225 (Wk 32)
Day 253 (Wk 36)
Day 281 (Wk 40)
Day 309 (Wk 44)
Day 337 (Wk 48)
Day 365 (Wk 52)/ 
End of Treatment
Notes
Study Drug
Contact IVRS/IWRS
X
X
X
X
X
X
X
Dispense diary cards
X
X
X
X
X
X
X
Collect and review diary cards
X
X
X
X
X
X
X
Dosing of weekly abatacept
X
X
X
X
X
X
X
Must be administered weekly 
between visits. See Section 4.5
No dose administered at the End of 
Treatment visit
Dispense monthly abatacept kits
X
X
X
X
X
X
X
Reconciliation of abatacept monthly kits
X
X
X
X
X
X
X
a All visits and procedures during the Open-label Treatment Period must occur within 3 days of the expected visit
b Same Day as Double-Blind Day 169
c Procedure to be performed by an ophthalmologist experienced in the diagnosis and treatment of Sjögren’s syndrome patients. Eye assessments must be 
performed within 5 days of the study visit.
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Table 5.1-6:
Follow-Up Period Procedural Outline for IM101603 (After Last Dose of Study Medication)a
Procedure
28 Days
84 Days
Notes
Adverse Events Assessment
X
X
Laboratory Tests
Urine/Serum Pregnancy
X
X
Serum anti-abatacept antibodies
X
X
Pharmacokinetic (PK) Samplingb
X
X
a These visits should occur 28 and 84 days after the last dose of study medication. If study medication is discontinued during the Double-Blind Treatment 
Period and the subject continues to be followed for the scheduled Double-Blind Treatment Period visits these additional visits may not be required.
b The samples for PK will be evaluated to determine serum abatacept concentration in the event there is a corresponding positive immunogenicity result
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5.1.1
Retesting During Screening or Lead-in Period
All screening procedures are to be performed within 4 weeks of the randomization visit except as 
described below.
Retesting:
A single retest of laboratory parameters and/or other assessments within any single Screening 
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 Period, 
may be repeated in an effort to find all possible well-qualified subjects. Consultation with the 
Medical Monitor may be needed to identify whether repeat testing of any particular parameter is 
clinically relevant.
Extended Screening:
Subjects that experience an acute infection or initiate treatment for latent TB may extend the 
screening period to 56 days, as long as the infection did not require hospitalization or 
administration of parenteral antibiotics agents. Under these circumstances, all screening 
procedures except IVRS enrollment, height/weight, chest x-ray, TB testing, HepB/C, HIV, 
quantitative immunoglobulins, and anti-SSA should be repeated prior to randomization.
Rescreening:
Subjects that are screen failures may be considered for re-screening if the investigator feels a 
change in status may render the subject eligible. Laboratory parameters and/or assessments that 
are included in Table 5.1-1, Screening Procedural Outline, should be repeated in an effort to find 
all possible well-qualified subjects. Consultation with the Medical Monitor may be needed to 
identify whether repeat testing of any particular parameter is clinically relevant. The subject will 
need to sign a new informed consent and be reenrolled with a new subject number via the IVRS. 
Some tests such as chest x-ray, may not need to be repeated if they were performed within the 
protocol defined window.
5.1.2
Order of Study Assessments
It is strongly encouraged that study assessments be performed in the following order:
1) Patient reported outcomes (PROs) questionnaires
2) Salivary Flow 
a) Unstimulated salivary flow
b) Stimulated salivary flow
3) Ophthalmologic Assessments - there is a 5 day window for the completion of these 
assessments
a) Schirmer test 
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b) Tear break-up time
c) Ocular staining 
4) AE collection
5) Vital signs
6) Joint assessments
7) Investigator assessments
8) Blood draws
9) Study Drug Administration
5.1.3
Study Drug Administration Window
Self-administration must be observed for compliance and technique at office visits.
Administration Windows
SC injections of study medication may be administered 3 days around the target day. Subjects 
who miss the dose window should skip the SC injection and wait until the next targeted 
administration day.
If abnormal laboratory test results or clinical assessment indicate an adverse event that, in the 
judgment of the investigator, could place the subjects at risk with continued administration of 
study medication, study medication administration should be skipped. Subjects may receive 
further study medication only if resolution of the AE or abnormal laboratory finding is 
documented or, at a minimum, the subject’s status returns to what it was at baseline.
5.2
Study Materials
The following materials will be provided for use during the trial:

Diary cards to record SC dosing administration

Written instructions on how to use the SC syringes

eCRF instructions

Pregnancy Surveillance Forms

Subject and Investigator-rated questionnaires/scales (paper)

Ruler, 10 cm for measurement of Visual Analog Scales

Drug Inventory binder (optional)

Interactive Voice Response System (IVRS) worksheets

Laboratory test kits for all required laboratory testing

Cooler bags and gel packs will be provided to assist subjects in transporting study drug

Sharps containers will be provided to assist subjects in disposing of used SC syringes

Tote bags to transport cooler bags, sharp containers and study drug
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5.3
Safety Assessments
On Day 1, the results of all assessments must be reviewed to ensure that eligibility requirements 
are met before contacting the Central Randomization System for the subject’s randomization 
assignment.
Subjects who terminate treatment early should complete the appropriate Early Termination Visit 
and the Post Drug Follow-up Visits. The Early Termination Visit should be as soon as possible 
after the last dose of study medication.
All assessments should be performed or administered prior to study drug administration unless 
otherwise indicated.
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 
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 BMS.
5.3.1
Imaging Assessment for the Study
Not Applicable.
5.3.2
Physical Examination
Physical examinations (complete and/or brief) may be performed by a Doctor of Medicine (MD), 
Doctor of Osteopathy (DO), Physician Assistant (PA), or Nurse Practitioner (NP) as allowable, 
per local regulations/guidelines.
The physical examination should include examination of the oropharynx, heart, parotid glands, 
neck (including submaxillary glands), lymph nodes, lungs, abdomen, lymph nodes, liver, spleen, 
musculoskeletal system, peripheral and central nervous systems, and skin. A physical 
examination may note any changes in the subject’s condition (body systems) since the last 
assessment and does not preclude examination of any other body systems as clinically indicated.
While the brief interim physical exam may not be as comprehensive as the initial full 
examination, key aspects of the brief interim examination should evaluate important body
systems clinically indicated. The brief physical exam should include examination of the 
oropharynx, parotid glands, neck, lymph nodes, heart, lungs, and abdomen and may include 
other relevant body systems such as the skin, musculoskeletal system, central and/or peripheral 
nervous system, liver, spleen, and breasts, at the discretion of the examiner. A brief physical 
examination may note any changes in the subject’s condition (body systems) since the last 
assessment and does not preclude examination of any other body systems as clinically indicated.
5.3.3
Chest X-ray
A posterior-anterior and lateral chest x-ray, performed during screening, is required for all 
subjects unless performed within 6 months prior to obtaining written informed consent and 
documentation of the earlier x-ray is on file. Investigators must ensure that the results of the 
chest x-ray satisfy criteria for eligibility. The chest x-ray result will be recorded on the 
appropriate page of the eCRF.
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5.3.4
Physical Measurements
Weight and height is (are) to be recorded at screening. Weight will also be recorded at Days 1, 
169, and 365.
5.3.5
Vital Signs
Vital signs (seated blood pressure, heart rate, and temperature) will be recorded during every 
office visit and prior to dose administration, when applicable. Blood pressure and heart rate 
should be measured after the subject has been seated quietly for at least 5 minutes.
5.3.6
TB Screening
Chest x-ray, history, and physical examination are considered part of the process to assess a 
subject’s eligibility. In addition to a chest x-ray that does not show any evidence or suspicion of 
TB, a tuberculin skin test or an IFNrelease assay will be performed and interpreted according to 
local country Health Authorities and/or Medical Society guidelines. Some guidelines have 
specific recommendations for subjects who are to receive biologics or immunosuppressant 
therapies (eg, RA experience with biologic agents),26,27,28 or who are immunocompromised and 
who have had prior BCG vaccination(s).29,30 Tuberculin skin testing is not contraindicated for 
persons who have been vaccinated with BCG. An interferon gamma release assay 
(eg, QuantiFERONGold or Tspot/ELISpot) is an acceptable alternative when skin testing for 
tuberculosis (ie, PPD) is not appropriate.
5.3.7
Laboratory Assessments
All laboratory assessments will be analyzed centrally except if noted otherwise.
Blood samples will be obtained at all visits noted in Time and Events Schedule. Any laboratory 
test result that the investigator considers clinically relevant should be recorded on the appropriate 
Adverse Event page of the CRF (see Appendix 8).
5.3.7.1
Hematology

Hemoglobin

Hematocrit

Total WBC count, including differential

Platelet count
5.3.7.2
Blood Chemistry

Sodium 
Creatinine

Potassium 
Blood urea nitrogen (BUN)

Chloride 
Bicarbonate

Creatine Kinase (CK)
Total bilirubin

Total Protein 
Alanine aminotransferase (ALT)

Albumin
Aspartate aminotransferase (AST)
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Calcium 
Gamma-glutamyltransferase (GGT)

Phosphorus 
Alkaline phosphatase

Glucose

hsCRP

ESR*
*Performed locally, kits provided centrally.
5.3.7.3
Immunology

Quantitative Immunoglobulins (IgG, IgA, IgM)

anti-CCP2

anti-dsDNA

Rheumatoid Factor

ANA and reflex ENA panels

-2-Microglobulin (B2M)

Free Light Chain (FLC)

Complement (C3, C4, CH50)

Anti-Ro Antibody (SSA)

Anti-La Antibody (SSB)

Anti-centromere Antibody (ACA)
5.3.7.4
Urinalysis

pH

Protein

Glucose

Blood
5.3.7.5
Hepatitis Screen
The Laboratory results must be available on Day 1 prior to dosing.

Hepatitis B surface antigen, hepatitis B core antibody (hepatitis B surface antibody, where 
required by local guidelines). If positive, reflex HBV DNA testing must be performed

Hepatitis C antibody. If positive, reflex HCV RNA testing must be performed
5.3.7.6
Pregnancy Tests
Urine/serum pregnancy tests (minimum sensitivity 25 IU/L of -HCG) must be performed for all 
WOCBP within 24 hours prior to dosing for visits specified in Section 5.1. A serum test must be 
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performed for confirmation of any positive urine test result. Urine tests can be processed locally 
and can be self-administered by the subject between office visits, if permitted by local 
regulations. If any female subject becomes pregnant, she will stop receiving study treatment 
immediately and, if pregnancy is confirmed, enter the Post Treatment Follow-up Period. A 
pregnancy surveillance form will be completed and submitted to Bristol-Myers Squibb. Serum 
pregnancy tests will be processed centrally.
5.3.7.7
HIV Testing
HIV testing (screening) will be performed locally in countries where testing is required.
5.3.7.8
FSH Testing
FSH testing must be performed to confirm menopause for female subjects under the age of 55. 
The female subject must have a serum FSH level > 40 mIU/mL in screening.
FSH testing will be performed for female subjects who become menopausal after entry into the 
study.
5.4
Efficacy Assessments
Questionnaires and investigator/subject assessments will be completed prior to study drug 
administration.
5.4.1
Primary Efficacy Assessment
The primary efficacy endpoint is the mean change from baseline in the EULAR Sjögren’s
Syndrome Disease Activity Index (ESSDAI) at Day 169 in abatacept vs placebo. The ESSDAI is 
a systemic disease activity index designed for pSS. It includes 12 domains (cutaneous, 
respiratory, renal, articular, muscular, peripheral nervous system, central nervous system, 
hematological, glandular, constitutional, lymphadenopathy & lymphoma, and biological). Each 
domain is divided into 3-4 levels of activity with different weightings at each activity level for 
individual domains.31 The definition of each activity level is provided by a detailed description 
of what should be considered in that item. When the ESSDAI is used, it should be with the 
assurance that the signs and symptoms are related to pSS and not to an underlying and/or 
associated disease. Likewise, patients with pSS may have concomitant illnesses that can mimic 
SS symptoms and organ involvement, which should be taken into account when scoring the 
ESSDAI. When assessing disease activity of an individual patient, the physician has to keep in 
mind that he/she has to exclude damage features that are irreversible. 31
Some of the activity levels within some of the domains utilize results from tests that are not 
specifically listed in this protocol. For example, skin biopsy, high-resolution computed 
tomography (HRCT) scan, pulmonary function tests (PFTs), electromyography (EMG), nerve 
conduction studies (NCS), muscle magnetic resonance imaging (MRI), muscle biopsy, and brain 
MRI. If the subject has undergone such testing to evaluate active signs and symptoms related to 
pSS, the results of these tests should be used for the ESSDAI score at screening and Day 1. If the 
relevant signs/symptoms have changed since the initial testing was performed, repeat testing 
during the screening period should be performed.
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If the ESSDAI score for a patient at Day 1 has contributions from tests not specifically required 
in this protocol, such as HRCT, PFTs, EMG, NCS, MRI, and biopsy, these tests should be 
repeated at Day 169.
If the ESSDAI score for a patient at Day 169 has contributions from tests not specifically 
required in this protocol, such as HRCT, PFTs, EMG, NCS, MRI, and biopsy, these tests should 
be repeated at Day 365.
If during the double blind period a subject develops a sign or symptom that necessitates 
additional testing not required in the protocol (eg, HRCT, PFTs, EMG, NCS, MRI, biopsy), this 
testing should be performed at the time of the sign/symptom onset, and additionally at Day 169 if 
at least 8 weeks have elapsed since prior testing. If during the open-label abatacept period a 
subject develops a sign or symptom that necessitates additional testing not required in the 
protocol this testing should be performed at the time of the sign/symptom onset, and additionally 
at Day 365, if at least 8 weeks have elapsed since prior testing.
Training and instruction on the ESSDAI will be provided at the Investigator’s Meeting or at 
other trainings and workshops. ESSDAI Assessors should have appropriate medical credentials, 
such as a Doctor of Medicine (MD)/Doctor of Osteopathy (DO), Physician Assistant (PA) or 
Nurse Practitioner (NP), and should be individuals who are experienced in the clinical care of 
patients with pSS. Visits should be scheduled with the availability of the assessor taken into 
account. It is strongly recommended that the same assessor evaluates findings in individual 
subjects throughout the study. If the assessor is unable to complete the evaluation, then another 
qualified trained individual can take the place of the initial evaluator, as long as the restrictions, 
described above, are still met. The substitute evaluator will have also examined and reviewed the 
subject with the initial assessor to ensure consistency between subject evaluations.
5.4.2
Salivary Flow
Whole unstimulated and stimulated salivary flow will be assessed at baseline (Day 1) and 
Days 85, 169, 253, 365 and early termination. The same assessor should perform salivary testing 
on the subject at each visit, if possible. Salivary assessments throughout the study should be 
performed at approximately the same time of day as the baseline salivary assessment. Subjects 
should be instructed to not use parasympathomimetic (cholinergic) agents, such as pilocarpine 
and cevimeline for the 48 hours prior to salivary assessments, and not to use artificial saliva on 
the day of the assessment. Subjects should refrain from eating, drinking, smoking or chewing 
gum for at least 90 minutes prior to the salivary test procedures.
Unstimulated Salivary Flow:
The subject‘s unstimulated whole salivary flow rate will be measured for 15 minutes. The 
subject is advised to rinse his or her mouth several times with deionized (distilled) water and 
then to relax for five minutes and minimize movement, particularly of his/her mouth. For the 
collection procedure, the subject should keep his/her head tilted forward and swallow once 
before starting the procedure to clear the mouth of excess saliva. At this point, the 15-minute 
collection period is initiated. The subject should lean his/her head forward over a pre-weighed 50 
cm3 conical tube. Subjects then expectorate, as needed, any accumulated saliva into the tube. At 
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the end of the collection period, the subject will be asked to collect any remaining saliva in 
his/her mouth and spit it into the test tube.
 
 
Refer to section 5.6.4 for additional details
Stimulated Salivary Flow:32.
A sterile 10 x 10-cm gauze sponge is first folded twice at 90 degree angles (final size 5 x 5 cm) 
and placed in a 50 cm3 conical tube and the gauze and tube are weighed. After swallowing to 
remove any preexisting oral fluid, saliva is collected by having the subject vigorously chew on 
the gauze for exactly 2 minutes, 1 chew/minute. After chewing the gauze, it is placed in the same 
tube. The amount of saliva produced in 2 minutes will be determined by subtracting the original 
weight from the weight obtained after chewing.
5.4.3
Ophthalmologic Assessments
The following procedures should be performed at baseline/Day 1, and Days 85, 169, 253, 365
and early termination by an ophthalmologist trained in the ophthalmologic assessment of patients 
with Sjögren’s Syndrome. Assessments may also be performed by an optometrist who is familiar 
with the required testing and experienced in diagnosing and treating patients with dry eyes
associated with Sjögren’s syndrome. A visit window of 5 days relative to the study visit to 
perform the ophthalmologic assessments is acceptable, but all ophthalmologic assessments must 
be performed during the
same visit.
Subjects should be instructed to not use
parasympathomimetic agents, such as pilocarpine and cevimeline for the 48 hours prior to ocular 
assessments. Subjects should not use cyclosporine, lifitegrast, or corticosteroid eye drops or 
artificial tears for 12 hours prior to the assessment. Ophthalmologic assessments performed on 
days 85, 169, 253, 365 and early termination should be performed at approximately the same 
time of day as the baseline assessment.

Schirmer’s test: The test (without anesthesia) 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 subject’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 lissamine 
green dye to stain the cornea and conjunctiva, respectively. After instilling the dye, the ocular 
surface is examined through a slit lamp (biomicroscope) and the staining pattern is recorded 
per the method described in Whitcher, et al. (Rose Bengal stain as a substitute for lissamine 
green is acceptable only in regions in which lissamine green is not available.)
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5.4.4
Physician’s Global Assessment of Disease Activity
The Physician’s Global Assessment of Disease Activity (PGA) should be performed by a Doctor 
of Medicine (MD), Doctor of Osteopathy (DO), Physician Assistant (PA) or Nurse Practitioner 
(NP) who has experience caring for patients with pSS. The assessment should be performed by 
the same individual at every visit for a given subject, if possible.
5.4.5
Joint Count Assessments
The Joint Count Assessor may perform the PGA for the same subject. For both assessments 
every effort should be made to ensure the same assessor is used for a given subject throughout 
the study.
Training and instruction on joint count assessments will be provided at the Investigator’s 
Meeting or at other trainings and workshops. 
Joint Count Assessors should have appropriate medical credentials and/or should be individuals 
with appropriate scientific/medical background who are experienced in performing joint 
assessments for the BMS Phase 3 studies. If the individual does not have medical credentials, 
documentation of their experience (preferably on a curriculum vitae) must be provided to the 
BMS site manager, and their eligibility as joint assessor must be confirmed by the BMS Medical 
Monitor before the individual’s participation in the study as Joint Count Assessor.
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. The substitute 
evaluator will have also examined and reviewed the subject with the initial assessor to ensure 
consistency between subject evaluations.
5.5
Pharmacokinetic Assessments
5.5.1
Pharmacokinetic: Blood Collection
The sampling schedule to be followed for the assessment of pharmacokinetics is listed in Table 
5.5.1-1. The actual date and time of sample collection should be recorded. Every effort should be 
made to collect PK samples as close to the protocol-specified times as possible.
All randomized subjects will have PK samples collected during the Double-Blind Treatment 
Period, Open-Label Treatment Period and the Post-Treatment Follow-up Period unless the 
subject discontinues study treatment and starts treatment with commercial abatacept.
In addition, approximately 40 randomized subjects (approximately 20 subjects randomized to 
active treatment and 20 subjects randomized to placebo) will participate in a PK sub-study.
Those subjects that sign consent to participate in the PK sub-study will have samples collected 
Days 2, 5, 15, 17, 32, and 61 (see Table 5.5.1-1). Each sub-study visit may be a home visit 
conducted by a visiting nurse or qualified healthcare professional if approved by the IRB/IEC
and investigator.
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Table 5.5.1-1:
Pharmacokinetic (PK)Sampling Schedule
Study Day
Event
Time 
(Relative to Dosing)
Hour:Min
PK Blood Sample
Immunogenicity
Sample
All 
Subjects
(N=144)
For PK 
sub-study
(N = 40)
All Subjects
(N=144)
1
predose
0
X
X
2
24:00
X
5
96:00
X
15
predose
0
X
17 
24:00 to 72:00
X
29
predose
0
X
32 
48:00 to 96:00
X
57
predose
0
X
61 
72:00 to 120:00
X
85
predose
0
X
X
113
predose
0
X
141
predose
0
X
169 or ETa
predose
0
X
X
365 or EOTa
X
X
Post-Treatment Follow-up Periodb
28
696:00 hrs
Xc
Xd
84
2016:00 hrs
Xc
Xd
a Sample collected predose, except for Early Termination (ET) and End of Treatment (EOT).
b Only for subjects discontinuing use of abatacept (off study).
c These samples will only be evaluated to determine serum abatacept concentration in the event there is a 
corresponding positive immunogenicity result.
d These samples should be collected 28 and 84 days after the last dose of study medication. If study medication is 
discontinued during the Double-Blind Treatment Period and the subject continues to be followed for the 
scheduled Double-Blind Treatment Period visits these additional samples may not be required.
The capture of precise PK sampling times relative to the actual dosing time is integral to the PK 
analysis and must be accurately recorded on the central laboratory requisition form. The date and 
time of sample collection must be recorded so that compliance with the sampling schedule can 
be confirmed.
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5.5.2
Pharmacokinetic: Blood Sample Processing, Labeling and Shipping
Detailed instructions on processing, labeling, handling, storage, and shipping of PK specimens 
for analysis will be supplied to Investigators in a separate manual at or before the time of study 
initiation.
5.5.3
Pharmacokinetic Sample Analysis
A sensitive validated enzyme immunoassay (EIA) method will be used to measure 
concentrations of abatacept in serum.
5.5.4
Pharmacokinetic Evaluation
Pharmacokinetic endpoints are presented in Section 5.5.1.
 
 
 
 
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5.7
Outcomes Research Assessments
ESSPRI
The ESSPRI (Appendix 7) is a three question patient reported symptom index for dryness, 
fatigue and pain developed for pSS. The ESSPRI was developed by a multinational panel of 
patients from European, and North and South American countries. This methodology ensured the 
inclusion of different transcultural patients’ views on the severity and the importance of their 
symptoms. Compared with the physician’s global assessment, and the existing tools Profile of 
Fatigue and Discomfort (PROFAD) and the Sicca Symptoms Inventory (SSI), the ESSPRI 
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performed satisfactorily for evaluation of patients’ symptoms in primary SS, and has the 
advantage that it is easy to use.33
NRS for mouth dryness
Numeric rating scale for mouth dryness to assess the subject’s perception of change in this 
specific symptom.
NRS for eye dryness
Numeric rating scale for eye dryness to assess the subject’s perception of change in this specific 
symptom.
Subject assessment of disease activity
Visual Analog Scale (VAS) scale to assess patient overall assessment of disease.
PROMIS fatigue assessment
The PROMIS Fatigue instrument evaluates a range of self-reported symptoms, from mild 
subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of 
exhaustion that likely decreases one’s ability to execute daily activities and function normally in 
family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and 
intensity) and the impact of fatigue on physical, mental, and social activities.
SF-36- assessment of function
SF-36 is a widely used assessment tool that is recognized as a validated instrument to measure 
quality of life in diseases such as RA. The 36-item Short Form Health Survey (SF-36) has also 
been used to assess quality of life in patients with pSS.34
Female Sexual Function Index (FSFI)
Women with pSS frequently experience vaginal dryness and dyspareunia. The FSFI is a 19-item
index that measures sexual function in six subdomains: desire, arousal, orgasm, lubrication, 
satisfaction and pain. Higher scores indicate better sexual function. The total score is calculated 
as the sum of the six domain scores and has a range of 2-36. A cut-off score of < 26.55 has been 
proposed to indicate sexual dysfunction. 35
5.8
Other Assessments
5.8.1
Immunogenicity Assessments
5.8.1.1
Immunogenicity: Blood Collection
Blood samples for determination of antibodies to abatacept, and time-matched PK samples will 
be collected at times noted in Section 5.5.1. Samples MUST be collected prior to the 
administration of study medication (SC injections) based on the collection schedule except 
during the Follow-up Period. Samples will be assayed for the presence of abatacept-specific 
antibodies.
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5.8.1.2
Immunogenicity: Blood Sample Processing, Labeling, and Shipping
Detailed instructions on processing, labeling, handling, storage, and shipping of immunogenicity 
specimen for analysis will be supplied to Investigators in a separate manual at or before the time 
of study initiation.
5.8.1.3
Immunogenicity: Sample Analysis
A validated, sensitive, electrochemiluminescence assay (ECL) method will be used to analyze
the presence of anti-abatacept antibodies in serum. Samples that are confirmed positive for 
antibodies specific to the CTLA4 region of abatacept and have abatacept serum concentrations of 
1 g/mL will be further analyzed with a validated, in vitro, cell-based bioassay to determine 
whether the sera contained abatacept neutralizing activity.
5.9
Labial Salivary Gland or Parotid Gland Biopsy (Substudy)
Sites with experience in this procedure will be asked to participate in this substudy. Optional 
biopsies should be obtained at baseline/Day 1 (a window of 28 days prior to the start of dosing to 
accommodate scheduling is acceptable) and at Day 169.  Subjects who complete treatment with 
study drug up to Day 141 of the Double-blind Treatment Period should have the biopsy obtained 
within 28 days of Day 169. 
Briefly, subjects who sign consent to participate in the biopsy substudy will have a 1.5-2 cm 
incision in the mucosa of the lower lip through the epithelium only. Blunt dissection and removal 
of the labial salivary glands will be performed and the incision will be sutured. Parotid gland 
biopsies are also acceptable if performed at sites experienced with this procedure. 
Salivary/parotid glands will be placed in container containing formalin for further processing by 
the central labs. Biopsy specimen will be read centrally for histology and examined for RNA 
expression.
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 
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.
The causal relationship to study drug is determined by a physician and should be used to assess 
all adverse events (AE). The causal relationship can be one of the following:
Related: There is a reasonable causal relationship between study drug administration and 
the AE.
Not related: There is not a reasonable causal relationship between study drug 
administration and the AE.
The term “reasonable causal relationship” means there is evidence to suggest a causal 
relationship.
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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.)
Suspected transmission of an infectious agent (eg, pathogenic or nonpathogenic) via the study 
drug is an SAE.
Although pregnancy, overdose, cancer, and potential drug induced liver injury (DILI) are not 
always serious by regulatory definition, these events must be handled as SAEs. (See 
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
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
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 5.5.1 in the Investigator Brochure (IB) represent the Reference Safety Information to 
determine expectedness of serious adverse events for expedited reporting. Following the 
subject’s written consent to participate in the study, all SAEs, whether related or not related to 
study drug, must be collected, including those thought to be associated with protocol-specified 
procedures. All SAEs must be collected that occur during the screening period and within 84 
days of discontinuation of dosing. If applicable, SAEs must be collected that relate to any later 
protocol-specified procedure (eg, a follow-up skin biopsy).
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.
SAEs, whether related or not related to study drug, and pregnancies must be reported to Sponsor 
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.
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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 Sponsor 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). 
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form electronic) as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning.

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
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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, the investigator must immediately notify the Sponsor 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 Sponsor 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.
The investigator must immediately notify the Sponsor or designee of this event and complete and 
forward a Pregnancy Surveillance Form to Sponsor or designee within 24 hours of awareness of 
the event and in accordance with SAE reporting procedures described in Section 6.1.1. 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
Sponsor or designee. 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.).
6.6
Potential Drug Induced Liver Injury (DILI)
Specific criteria for identifying potential DILI have not been identified for this protocol. 
Standard medical practice in identifying and monitoring hepatic issues should be followed.
6.7
Other Safety Considerations
Any 
significant 
worsening
noted 
during 
interim 
or 
final 
physical 
examinations, 
electrocardiogram, x-ray filming, or any other potential safety assessment required or not 
required by protocol, should also be recorded as a nonserious or serious AE, as appropriate, and 
reported accordingly.
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7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Data Monitoring Committee (DMC) will be instituted to perform safety monitoring oversight.
Details will be contained in the DMC Charter.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
A hierarchical testing procedure will be applied for the primary endpoint (change from baseline 
in ESSDAI at Day 169) and the 2 key secondary endpoints (change from baseline in ESSPRI at 
Day 169 and change from baseline in the stimulated whole salivary flow at Day 169) to ensure 
the preservation of the overall type I error of 5%. The first key secondary endpoint will only be 
tested (at a significance level of 5%) if the test for the primary endpoint is statistically significant 
at a significance level of 5%. If both the test for the primary endpoint and the first key secondary 
endpoint are statistically significant (both at a significance level of 5%), then the second key 
secondary endpoint will be tested (at a significance level of 5%).
A sample size of 172 patients (86 per arm) will achieve 98% power to detect a treatment 
difference of 3 in changes from baseline in ESSDAI at Day 169 between the abatacept and 
placebo group using a two-sided t-test with a significance level (alpha) of 0.05 and assuming a 
common SD of 4.8. The sample size of 86 patients per arm will achieve 90% power to detect a 
treatment difference of 1 in change from baseline in ESSPRI at Day 169 assuming a common SD 
of 2. Taking into account the hierarchical procedure, a sample size of 86 patients per arm will 
achieve an overall power of at least 88.2% (98% multiplied by 90%) to detect both a treatment 
difference of 3 in mean change from baseline in ESSDAI and a difference of 1 in change from 
baseline in ESSPRI at Week 24 (Day 169).
The treatment differences of 3 for ESSDAI and 1 for ESSPRI correspond to the minimal 
clinically important improvement (MCII) for ESSDAI and ESSPRI36, the key endpoints that 
address the major signs and symptoms of this disease. Estimates of the SD of mean change from 
baseline in ESSDAI derived from published results,37, range from 3.6 to 6.3. Estimates of the SD 
of mean change from baseline in ESSPRI derived from published results range from 1.7 to 2.2.,38
In addition, the power to detect a treatment difference in mean change from baseline of 
0.165 mL/min in salivary flow (approximately similar to median reported increase/min with 
abatacept by Adler et al4) in subjects with stimulated whole salivary flow at baseline of at least 
0.1 mL/min is 91%, assuming a SD of 0.275 and for a sample size of 62 subjects per arm with a 
residual salivary flow of at least 0.1 mL/min at screening and baseline.4 Taking into account the 
hierarchical procedure, a sample size of 86 patients per arm will achieve an overall power of at 
least 80.3 % (98% multiplied by 90% multiplied by 91%) to detect a treatment difference of 3 in 
mean change from baseline in ESSDAI, a difference of 1 in mean change from baseline in 
ESSPRI and a treatment difference of 0.165 mL/min in mean change from baseline in salivary 
flow( in subjects with stimulated whole salivary flow at screening and at baseline of at least 
0.1 mL/min) at Week 24 (Day 169).
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8.2
Populations for Analyses

Intent-to-treat (ITT) analysis population: all randomized subjects who receive at least one 
dose of study medication. Analyses using the ITT analysis population will group the subjects
according to the treatment group to which they are randomized.

Per-protocol (PP) analysis population: all randomized subjects who receive at least one dose 
of study medication, excluding the subjects with relevant protocol deviations. Analyses using 
the PP analysis population will group the subjects according to the treatment group to which 
they are randomized.

As-treated analysis population: all subjects who receive at least one dose of study 
medication. Analyses using the as treated analysis population will group the subjects 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 they received (“as-treated”).

Cumulative abatacept population: all randomized subject who receive at least one dose of 
abatacept during the double-blind and/or the open-label period. All subjects of the ‘As-
treated population’ will be included, except placebo subjects who never entered the open-
label period.

Immunogenicity analysis population: all subjects who receive at least one dose of study 
medication and who had at least 1 immunogenicity result reported after start of study 
medication.

Full PK analysis population: all subjects who received at least one dose of abatacept study 
medication and who had at least 1 PK result reported after start of this study medication.

Evaluable PK analysis population: this population is a subset of the PK analysis population 
and consists of the evaluable subjects for PK analysis. For all PK summaries and plots, a 
subject is evaluable for PK analysis at a specific day if the predose PK measurements were 
collected in the 4 to 10 days window after the previous SC abatacept dose and prior to the 
dose of the specific day.
8.3
Endpoints
8.3.1
Primary Endpoint(s)
The mean change from baseline (Day 1) in ESSDAI at Day 169.
8.3.2
Secondary Endpoint(s)
Key Secondary Endpoints

The mean change from baseline in ESSPRI at Day 169.

The mean change from baseline in the stimulated whole salivary flow at Day 169 among 
subjects with stimulated whole salivary flow of at least 0.1 mL/min at both screening and 
baseline.
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Other Secondary Endpoints

The mean change from baseline at all measured time points up to Day 169 in the DAS28-
CRP among those with a tender plus swollen joint count 3 at baseline, among those with a 
tender plus swollen joint count < 3 at baseline and in the full population.

The mean change from baseline at all measured time points up to Day 169 in the individual 
components of DAS28-CRP among those with a tender plus swollen joint count 3 at 
baseline, among those with a tender plus swollen joint count < 3 at baseline and in the full 
population.

Proportion of subjects who achieve a minimally clinically important change (of at least 
3 points) in the ESSDAI at all measured time points up to Day 169 in the full population, 
among those with stimulated whole salivary flow of at least 0.1 mL/min at both screening 
and baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min 
at screening or baseline.

Proportion of subjects who achieve a minimally clinically important change (of at least 
5 points) in the ESSDAI at all measured time points up to Day 169 in the full population, 
among those with stimulated whole salivary flow of at least 0.1 mL/min at both screening 
and baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min 
at screening or baseline.

Proportion of subjects who achieve a minimally clinically important change (of at least 1 
point) in the ESSPRI at all measured time points up to Day 169 in the full population, among 
those with stimulated whole salivary flow of at least 0.1 mL/min at both screening and
baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min at 
screening or baseline.

The mean change from baseline at all measured time points up to Day 169 in the ESSDAI in 
the full population, among those with stimulated whole salivary flow of at least 0.1 mL/min 
at both screening and baseline, and among those with stimulated whole salivary flow of less 
than 0.1 mL/min at screening or baseline.

The mean change from baseline at all measured time points up to Day 169 in the ESSPRI in 
the full population, among those with stimulated whole salivary flow of at least 0.1 mL/min 
at both screening and baseline, and among those with stimulated whole salivary flow of less 
than 0.1 mL/min at screening or baseline.

The mean change from baseline in the individual components of the ESSDAI at all measured 
time points up to Day 169 in the full population, among those with stimulated whole salivary 
flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated 
whole salivary flow of less than 0.1 mL/min at screening or baseline.

The mean change from baseline in the individual components of the ESSPRI at all measured 
time points up to Day 169 in the full population, among those with stimulated whole salivary 
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flow of at least 0.1 mL/min at both screening and baseline, and among those with stimulated 
whole salivary flow of less than 0.1 mL/min at screening or baseline.

The mean change from baseline in Schirmer’s test at all measured time points up to Day 169.

The mean change from baseline in ocular staining score at all measured time points up to 
Day 169.

The mean change from baseline in tear break-up time at all measured time points up to 
Day 169.

The mean change from baseline in unstimulated whole salivary flow at all measured time 
points up to Day 169 in the full population, among those with stimulated whole salivary flow 
of at least 0.1 mL/min at both screening and baseline, and among those with stimulated 
whole salivary flow of less than 0.1 mL/min at screening or baseline.

The mean change from baseline in stimulated whole salivary flow at all measured time points
up to Day 169 in the full population, among those with stimulated whole salivary flow of at 
least 0.1 mL/min at both screening and baseline, and among those with stimulated whole 
salivary flow of less than 0.1 mL/min at screening or baseline.

The mean change from baseline in patient symptoms using the Numeric Rating Scale (NRS) 
for mouth dryness at all measured time points up to Day 169 in the full population, among 
those with stimulated whole salivary flow of at least 0.1 mL/min at both screening and 
baseline, and among those with stimulated whole salivary flow of less than 0.1 mL/min at 
screening and baseline.

The mean change from baseline in patient symptoms using the Numeric Rating Scale (NRS) 
for eye dryness at all measured time points up to Day 169.

The mean change from baseline in subject assessment of disease activity at all measured time 
points up to Day 169.

The mean change from baseline in the physician global assessment of disease activity at all 
measured time points up to Day 169.

The mean change from baseline in patient fatigue using PROMIS Fatigue assessment at all 
measured time points up to Day 169.

The mean change from baseline in female sexual function using the FSFI at all measured 
time points up to Day 169.

The mean change from baseline in patient function using SF-36 at all measured time points
up to Day 169.

Geometric mean of trough concentration (Cmin) of abatacept at all measured time points.

Proportion of subjects with at least one positive immunogenicity response up to Day 169 and 
during 3 months follow up (for subjects who discontinue during the 6-months double-blind) 
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and during the cumulative abatacept period and 3 months follow-up (for the cumulative 
abatacept population).

Safety (proportion of subjects with adverse events, deaths, SAEs, and AEs leading to 
discontinuation and proportion of laboratory marked abnormalities) up to Day 169 and 
during the cumulative abatacept period and follow-up period.
 
 
 
 
 
 
8.4
Analyses
8.4.1
Demographics and Baseline Characteristics
Demography and baseline disease characteristics will be presented by randomized treatment 
group and overall for the ITT population. Continuous variables such as age and weight will be 
summarized using means, standard deviations, median and ranges. Categorical variables such as 
gender, race and region will be summarized using frequencies.
 
 
 
 
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8.4.3
Safety Analyses
The proportion (%) of subjects with adverse events, deaths, SAEs, and AEs leading to 
discontinuation and subjects with laboratory marked abnormalities up to start of open label for 
subjects continuing in the OL or up to last dosing date +56 days for subjects discontinuing 
during double blind will be provided per treatment group using the as-treated population. These 
safety endpoints will also be summarized during the cumulative abatacept period (from the first 
day of abatacept treatment in the study up to 56 days after the last abatacept treatment in the 
study) for the cumulative abatacept population. For the cumulative abatacept population all 
subjects will be combined in one group.
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The proportion (%) of subjects with at least one positive immunogenicity response (relative to 
baseline) up to Day 169 and 3 months follow up (for subjects who discontinue in the Day 169
short-term period) and during the cumulative abatacept period and 3 months follow-up (for the 
cumulative abatacept population) will be summarized using the immunogenicity population.
 
 
 
 
 
 
 
8.4.6
Outcomes Research Analyses
The mean change from baseline for outcome research endpoints (e.g., patient function using 
SF-36 and patient fatigue using PROMIS Fatigue) will be analyzed using the same approach as 
done for the mean change from baseline for efficacy endpoints.
8.4.7
Other Analyses
Not applicable.
A detailed description of the analyses in section 8.4 (including sensitivity analyses for efficacy 
endpoints and additional analyses for efficacy and safety) will be provided in the statistical 
analysis plan (SAP).
8.5
Interim Analyses
Not applicable.
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 
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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 designee representatives will review data centrally to identify potential issues to 
determine a schedule of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare 
them with source documents, discuss the conduct of the study with the investigator, and verify 
that the facilities remain acceptable. 
In addition, the study may be evaluated by BMS or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory 
authorities, and promptly forward copies of inspection reports to BMS or designee.
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 
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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.
9.2
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 (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.
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:
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If...
Then...

label identification number or batch number

amount dispensed to and returned by each subject, including 
unique subject identifiers

dates and initials of person responsible for Investigational 
Product dispensing/accountability, as per the Delegation of 
Authority Form
BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements.
9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which 
will be reported on the electronic SAE form and Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used. Spaces may be left blank 
only in those circumstances permitted by study-specific CRF completion guidelines provided by 
Sponsor of designee.
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by 
the investigator or qualified physician who is a 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 Sponsor or designee training 
requirements and must only access the BMS electronic data capture tool using the unique user
account provided by Sponsor or designee. User accounts are not to be shared or reassigned to 
other individuals.
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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 or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTA) governing [Study site or Investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
BMS or 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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10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
Complete Abstinence is defined as complete avoidance of heterosexual 
intercourse and is an acceptable form of contraception for all study drugs. 
This also means that abstinence is the preferred and usual lifestyle of the 
patient. This does not mean periodic abstinence (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. Women must continue to have pregnancy tests.
Acceptable alternate methods of highly or less effective contraception’s 
must be discussed in the event that the subject chooses to forego complete 
abstinence.
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11
LIST OF ABBREVIATIONS
Term
Definition
ABA
abatacept
ACA
Anti-centromere antibody
ACR
American College of Rheumatology
AE
adverse event
ALT
alanine aminotransferase
ANA
Anti-nuclear antibody
Anti-CCP2
anti-cyclic citrullinated peptide
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AT
aminotransaminases
AUC
area under the concentration-time curve
2M
-2-microglobulins
-HCG
beta-human chorionic gonadotrophin
BMS
Bristol-Myers Squibb
BP
blood pressure
BUN
blood urea nitrogen
C
Celsius
Ca++
calcium
CBC
complete blood count
CFR
Code of Federal Regulations 
CI
confidence interval
C1-
chloride
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, 
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Term
Definition
concentration at 12 hours, etc.)
Ctau
Concentration in a dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
Ctrough
Trough observed plasma concentration
CV
coefficient of variation
CYP
cytochrome p-450
D/C
discontinue
DILI
Drug induced liver injury
dL
deciliter
DMARD
disease-modifying anti-rheumatic drug
DO
Doctor of Osteopathy
EA
extent of absorption
ECG
electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EEG
electroencephalogram
eg
exempli gratia (for example)
EIA
enzyme immunoassay
ESR
Erythrocyte Sedimentation Rate
ESR
Expedited Safety Report
F
bioavailability
ESSDAI
EULAR Sjögren’s Syndrome Disease Activity Index
ESSPRI
EULAR Sjögren’s Syndrome Patient Reported Index
EULAR SS
European League Against Rheumatism Sjögren’s Syndrome
FDA
Food and Drug Administration
FLC
Free Light Chain
FS
Focus Score
FSFI
Female sexual function index
FSH
follicle stimulating hormone
g
gram
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
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Term
Definition
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
IBD
Inflammatory bowel disease
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
ITT
Intent to treat
IU
International Unit
IV
intravenous
IVIG
Intravenous immunoglobulin
K
slope of the terminal phase of the log concentration-time curve
K3EDTA
potassium ethylenediaminetetraacetic acid
K+
potassium
kg
kilogram
L
liter
LDH
lactate dehydrogenase
ln
natural logarithm
LN
Lupus Nephritis
Lz_Start
The time point starting the log-linear elimination phase defining ther 
terminal half life
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Term
Definition
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
MAR
Missing at random
MCII
Minimally clinically important improvement
MD
Medical Doctor
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
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 
NP
Nurse Practitioner
NRS
Numeric rating scale
NSAID
nonsteroidal anti-inflammatory drug
OSS
Ocular Surface Staining
PBMC
Peripheral Blood Mononuclear Cell
PD
pharmacodynamics
PK
pharmacokinetics
PNS
Peripheral nervous system
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Term
Definition
PO
per os (by mouth route of administration)
PROMIS Fatigue 
Patient Reported Outcomes Measurement Information System Fatigue
pSS
Primary Sjögren’s syndrome
PT
prothrombin time
PTT
partial thromboplastin time
QC
quality control
QD, qd
quaque die, once daily
R2
coefficient of determination
RA
rheumatoid arthritis
RBC
red blood cell
RF
rheumatoid factor
SAE
serious adverse event
SC
subcutaneous
SD
standard deviation
SF-36
Short Form 36
SLE
systemic lupus erythematosus
SOP
Standard Operating Procedures
sp.
species
Subj
subject
t
temperature
T
time
TAO
Trial Access Online, the BMS implementation of an EDC capability
TB
Tuberculosis
T-HALF
Half life
T-HALFeff_AUC
Effective elimination half life that explains the degree of AUC 
accumulation observed
T-HALFeff_Cmax
Effective elimination half life that explains the degree of Cmax 
accumulation observed)
TID, tid
ter in die, three times a day
Tmax, TMAX
time of maximum observed concentration
TR_AUC(0-T)
AUC(0-T) treatment ratio
TR_AUC(INF)
AUC(INF) treatment ratio
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Term
Definition
TR_Cmax
Cmax treatment ratio
UV
ultraviolet
UWS
Unstimulated Whole Salivary Flow
W
washout
WBC
white blood cell
WHO
World Health Organization
Wk
Week
WOCBP
women of childbearing potential
x g
times gravity
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APPENDIX 1
METHODS OF CONTRACEPTION
At a minimum, subjects must agree to use one highly effective method of contraception 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, who are WOCBP, 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. Contraception methods are as 
follows:
1) Progestogen only hormonal contraception associated with inhibition of ovulation.
2) Hormonal methods of contraception including oral contraceptive pills containing  combined 
estrogen + progesterone, vaginal ring, injectables, implants and intrauterine devices (IUDs) 
such as Mirena
3) Nonhormonal IUDs, such as ParaGard
4) Bilateral tubal occlusion
5) Vasectomised partner with documented azoospermia 90 days after procedure
a) Vasectomised partner is a highly effective birth control method provided that partner is 
the sole sexual partner of the WOCBP trial participant and that the vasectomised partner 
has received medical assessment of the surgical success.
6) Intrauterine hormone-releasing system (IUS).
7) Complete abstinence
a) Complete abstinence is defined as the complete avoidance of heterosexual intercourse 
(refer to Glossary of Terms)
b) 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).
c) It is not necessary to use any other method of contraception when complete abstinence is 
elected.
d) Subjects who choose complete abstinence must continue to have pregnancy tests, as 
specified in Section 6.4.
e) Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the subject chooses to forego complete abstinence.
f)
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.
Local laws and regulations may require use of alternative and/or additional contraception 
methods.
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UNACCEPTABLE METHODS OF CONTRACEPTION
1) Periodic abstinence (calendar, symptothermal, post-ovulation methods)
2) Withdrawal (coitus interruptus)
3) Spermicide only
4) Lactation amenorrhea method (LAM)
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