Clinical trial NCT02265744
Conditions: Lupus
Sponsor: Bristol-Myers Squibb
Start date: 2014-11-13; Completion date: 2017-11-30
Enrollment: 730 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Study evaluating the safety and efficacy of a novel biologic in the treatment of systemic lupus erythematosus in male and female adults. Patients who qualify will be randomized to either active BMS-931699 or placebo for initially, up to 24 weeks. Patients who complete the initial 24 weeks of treatment and who are responding to therapy will have the option to continue receiving BMS-931699 as part of a long-term extension (LTE). Disease activity and safety will be assessed over the course of the study through laboratory values, various rating scales accepted in systemic lupus erythematosus studies and patient self reporting.

Detailed description:
1. Subjects completing Day 169 (24 weeks) on study medication may be eligible to enter an optional LTE period
2. The LTE period will remain blinded but will no longer have a placebo arm:

   * Subjects will remain on their originally assigned treatment arm unless they were on placebo
   * Subjects initially randomized to placebo arm will be automatically re-randomized into one of the existing active arms at Day 169 (24 weeks)

Arms: arm 1: 12.5mg subcutaneous (SC) injection Weekly dosing arm 2: 12.5mg SC injection Every other Week dosing arm 3: 5mg SC injection Every other Week dosing arm 4: 1.25mg SC injection Every other Week dosing arm 5: 0mg SC injection Weekly dosing
Interventions: intervention 1: BMS-931699 intervention 2: Placebo matching BMS-931699
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_000.pdf: 
Official Title of Study:  A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study 
to Evaluate the Safety and Efficacy of BMS-931699 vs Placebo on a Background of Limited Standard of 
Care in the Treatment of Subjects with Active Systemic Lupus Erythematosus 
 
NCT Number:  NCT02265744 
 
Document Date:  May 3rd, 2015   


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
SYNOPSIS
Clinical Protocol IM128027
Protocol Title: A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the 
Safety and Efficacy of BMS-931699 vs Placebo on a Background of Limited Standard of Care in the Treatment of 
Subjects with Active Systemic Lupus Erythematosus
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): BMS-931699 (active) or lulizumab pegol, administered subcutaneously, is formulated at 12.5 mg/mL 
and is provided as a liquid in single-use vials. Four treatments will be administered along with placebo treatment: 
12.5 mg weekly, 12.5 mg every other week (EOW), 5 mg EOW and 1.25mg EOW, on a background of limited 
standard of care medications. The dose levels may be modified based on the interim analysis results. The study will 
comprise a short-term period (Part 1 and Part 2) and a long-term extension (LTE) period. Treatment duration will be 
up to 24 weeks (169 days) in the short term period. Subjects completing the short term period on study medication 
may be eligible to enter the LTE period. At the time of writing there is no defined end date to the long-term 
extension period, however, the LTE provision may be further adjusted based on results from the ongoing lulizumab 
development program.
Study Phase: Phase 2
Research Hypothesis: BMS-931699 will have greater clinical efficacy compared to placebo on the British Isles 
Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) score, when added to stable 
background standard of care in subjects with active manifestations of systemic lupus erythematosus (SLE) 
including, at a minimum, elevated antinuclear antibodies, arthritis, and/or cutaneous manifestations satisfying the 
BILAG “A” or “B” criteria.
Objectives for the short-term period:
Primary Objective:
To compare the proportion of subjects who achieve BICLA response (BICLA response rate) at Day 169.
Secondary Objectives:
For Part 1 only:

To evaluate the safety and receptor occupancy (RO) when 6 to 10 subjects per arm reach 29 days (4 weeks).
For both Part 1 and Part 2:
To assess:

The safety and tolerability of treatment with BMS-931699 in subjects with active SLE

The proportion of patients who meet response criteria for the SLE Responder Index (SRI) (4), SRI(5) and 
SRI(6) at Day 169 following 24-week treatment with BMS-931699 or placebo administered on a stable 
background therapy.

The proportion of patients with SLE Responder Index [SRI(4), SRI(5) and SRI(6)] at Day 85 following 
12-week treatment with BMS-931699 or placebo administered on a stable background therapy.

The proportion of subjects with BICLA response at Day 85 following 12-week treatment with BMS-931699 or 
placebo administered on a stable background therapy

The improvement in the extent of cutaneous and mucous membrane activity, as measured by the Cutaneous 
Lupus Erythematosus Disease Area and Severity Index (CLASI) at Day 85 and Day 169

Joint tenderness and swellings by American College of Rheumatology (ACR)28 criteria at Day 85 and Day 169

The other indices of SLE activity measured at Days 29, 57, 85, 113, 141 and 169 including:

The change from baseline in overall BILAG-2004 score. A major response is defined as described in Yee et 
al 2010 (A=12; B=8; C=1; D/E=0).

The change in overall Systemic Lupus Erythematosus Disease Activity Index 2K score (SLEDAI 2K)
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The change from baseline in Physician’s Global Assessment of disease activity (MDGA) score

The systemic exposure of BMS-931699 in subjects with SLE

The cumulative corticosteroids use and immunosuppressants use over time

The immunogenicity of BMS-931699

Serum biomarkers C3, C4, anti-double-stranded deoxyribonucleic acid (anti-dsDNA), anti-nuclear antibody 
(ANA) and other autoantibodies at Day 85 and Day 169

The pharmacodynamics (PD) of BMS-931699, including assessments potentially associated with target 
engagement (including receptor occupancy [RO]).
Objectives for the long-term extension period:
Assess the long term clinical safety, tolerability and efficacy of lulizumab pegol.
Study Design:
Phase 2, parallel-arm, randomized, double-blinded, multicenter, international study, with an adaptive design. Dose
arm(s) may be adapted based on results of the planned interim analyses from Part 1 and Part 2, as follows:

Safety and RO interim analysis: safety and RO analysis will be performed when approximately 6 to 10 subjects 
per arm have reached Study Day 29. Based on the results of this analysis, dose arms(s) may be adjusted or may
be dropped.

Interim analysis for futility and dose adaptation on BICLA response, SRI response, ACR28 and some SLE 
biomarkers (such as auto-antibodies, complement levels, etc.) with possible exploratory exposure response 
analysis, will be performed when approximately 30 subjects per arm (including subjects from Part 1 and Part 2) 
have reached Study Day 85 (12 weeks) of treatment or have discontinued prior to reaching study Day 85.
Analysis will be performed by an unblinded Sponsor team, while maintaining blind at the site and subject level. 
Based on the results, the dose levels and sample size may be modified. 

Ongoing assessment of safety will be performed by an independent Data Monitoring Committee (DMC) and an 
internal unblinded safety monitoring team. Both entities may make recommendations to the Sponsor regarding 
conduct of study and dose adjustment based on safety observations.
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Overall study design
Part 1
• Limited to approximately 30 to 50 subjects (6-10 per arm).
• Interim analysis for safety and RO once 30-50 subjects have reached Day 29 (4 weeks).
• These subjects will continue study treatment beyond the interim analysis for safety and RO and 
will be treated for up to 24 weeks, and followed for 6 additional weeks after treatment is completed 
or discontinued. Treatment could be shorter if dose arm(s) are dropped. 
Intense safety monitoring by the 
DMC, in collaboration with an 
internal safety monitoring team, 
will be performed during Part 1 
and continue during Part 2.
DMC and unblinded internal 
safety monitoring activities will 
continue during long-term 
extension. 
Part 2
• Will start once cumulative safety profile is considered acceptable and RO data for 6-10 subjects 
per arm for >28 days are available and the interim analysis from Part 1 is completed. Results of the 
interim analysis in Part 1 and DMC reviews may result in treatment arm(s) modifications. 
• Each treatment arm will enroll approximately 70 subjects, including subjects from Part 1.
• Part 2 will have an interim analysis for futility once approximately 30 subjects per arm complete 
Day 85 (12 weeks), or have discontinued. As in the interim analysis from Part 1, results of the 
interim analysis in Part 2 and DMC reviews may result in treatment arm(s) modifications. 
• All subjects could be treated for up to 24 weeks and followed for 6 additional weeks after 
treatment is completed or discontinued. Treatment could be shorter if dose arm(s) are dropped. 
Long-Term Extension
• Subjects completing Day 169 (24 weeks) on study medication may be eligible to enter an optional 
long-term extension (LTE) period.
• The LTE period will remain blinded but will no longer have a placebo arm.
• Subjects will remain on their originally-assigned treatment arm unless they were on 
placebo. 
• Subjects initially randomized to placebo arm will be automatically re-randomized into one 
of the existing active arms at Day 169 (24 weeks). 
Study Design Schematic - Short-term Period (Part 1)
Day  -28
Day 1
Day 29
Interim analysis of 
Safety/RO
Screening 
– Part 1
First dose
12.5mg EOW N= 6-10
12.5mg weekly N= 6-10
5mg EOW N= 6-10
1.25mg EOW N= 6-10
Part 1 limited to a maximum of 50 patients who will be treated 
for up to 24 weeks and may be followed for 6 additional weeks, 
unless the Safety/RO analysis indicates one or more arms 
should be dropped.
Placebo weekly N= 6-10
FU Day 42 #
6 weeks 
safety 
follow-up
Day 169
End of Treatment
24 weeks treatment
6 weeks FUP
4 weeks 
screening
# Will not apply to subjects entering LTE.
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Study Design Schematic - Short-term Period (Part 2)
Day -28
Day 1
24 weeks treatment period
Day 169
Day 85
Clinical efficacy
(BICLA, SRI, 
SLEDAI, BILAG, 
CLASI, ACR28)
Futility analysis 
(ACR28, auto-antibodies, 
complement, biomarkers,  
BICLA/SRI)
Screening 
- Part 2
First dose
12.5mg EOW N= 60-64*
12.5mg weekly N= 60-64*
5mg EOW N= 60-64*
1.25mg EOW N= 60-64*
FU Day 42 #
6 weeks 
safety 
follow-up
* Treatment arm may or may not be included based on Part 1 Day 29 Interim Analysis.
# Will not apply to subjects entering LTE.
24 weeks treatment
Placebo weekly N= 60-64*
6 weeks FUP
New dosing regimen  N=70*
4 weeks 
screening
Study Design Schematic - Long-term extension Period
24 weeks treatment period
Day 169
End of Part 2
Start of LTE
12.5mg EOW *
12.5mg weekly *
5mg EOW *
1.25mg EOW *
FU Day 42
6 Weeks 
Safety 
Follow-up #
* Treatment arm may or may not be included based on Interim Analyses.
Subjects in the placebo arm will be re-randomized to existing active treatment arms at Day 169.
# FU Day 42 to occur after last dose of study medication, whether last dose is in short term or long term periods.
24 weeks of treatment
Placebo weekly
New dosing regimen *
New dosing regimen *
No currently-defined treatment period

12.5mg EOW * 
12.5mg weekly * 
5mg EOW *
1.25mg EOW * 
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Duration of Study:
Short-term Period: 28 days (4 weeks) of screening, 168 days (24 weeks) of treatment, 42 days (6 weeks) of safety 
follow-up, for a total of approximately 238 days (34 weeks). Subjects randomized into either Part 1 or Part 2 will be 
treated for up to 24 weeks and will have the same procedures performed and will follow the same visit schedule. If 
subject is eligible and opts to continue into LTE, the 42-day follow-up visit will not be performed after the 
short-term period is completed and subject will enter LTE directly.  If subject opts not to enter LTE then a follow-up 
visit will be completed 42 days after end of treatment. At the time of writing there is no defined end date to the 
long-term extension period, however, the LTE provision may be further adjusted based on results from the ongoing 
lulizumab development program. Subjects discontinuing treatment during the LTE period will complete the 
follow-up visit approximately 6 weeks after receiving their last dose of study medication.
Number of Subjects:
Approximately 450 subjects will need to be screened to randomize approximately 350 subjects. Utilizing a 
1:1:1:1:1 randomization scheme resulting in approximately 70 subjects in the each treatment arm. If the day 85
interim analysis suggests an additional dose arm at a lower dose level needs to be added, then up to 40 additional 
subjects may be randomized. 
Approximately 125 sites will participate in this study, which will be conducted globally and should include, but will 
not be limited to, participation of countries located in North America and Europe.
Study Population: Male and female subjects, ages 18-70 years inclusive, satisfying the SLE classification criteria 
of the American College of Rheumatology (1982), as revised by the College in 1997, with elevated titer of 
anti-nuclear antibodies at Screening, active features of SLE, including at least one adjudicated BILAG B or greater 
due to arthritis and/or inflammatory skin disease. Unless intolerant, subjects must be on background therapy for 
12 weeks, on a stable dose for at least 8 weeks, with at least one steroid sparing agent, including azathioprine 
(AZA), leflunomide, methotrexate (MTX), anti-malarial agents, mycophenolate mofetil/ mycophenolic acid, which 
must remain on stable dose throughout the study. Prednisone is not required; however, if subject is taking 
prednisone (or prednisone-equivalent), the maximum dose must not exceed 30mg/day of prednisone (or prednisone 
equivalent) at screening for a subject to be eligible and must be at a maximum of 10mg/day for at least 5 days prior 
to Day 1. Subjects must not have SLE manifestations or other disorders expected to require increase in 
corticosteroids (CS) during the study. 
Women of childbearing potential (WOCBP) must not be nursing or pregnant and must be using an acceptable 
method of contraception for at least 4 weeks before dosing. WOCBP must have a negative pregnancy test within 
24 hours prior to dosing with study medication
Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational [Medicinal] 
Products (Non-IP/Non-IMP) as listed:
Study Drug for IM128027
Medication 
Potency 
IP/Non-IP 
BMS-931699
12.5mg/mL
IP
Study Assessments:

Efficacy assessments: will include BILAG-2004 Index, SLEDAI 2K, Physician’s Global Assessment of Disease 
Activity (MDGA), Subject’s Global Assessment of Disease Activity (PGA), ACR28 - joint count, FACIT - F, 
CLASI, SLICC/ACR Damage Index, SF-36, Coomb’s test-direct. 

Safety assessments will be based on medical review of adverse event reports and the results of vital sign 
measurements, ECGs, physical examinations, and clinical laboratory tests. The incidence of observed adverse 
events will be tabulated and reviewed for potential significance and clinical importance. Ongoing assessment of 
safety will be performed by an independent Data Monitoring Committee (DMC). The DMC may make 
recommendations to the Sponsor regarding conduct of study based on safety observations.
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lulizumab pegol

Pharmacokinetic parameters: Ctrough will be derived from serum BMS-931699 concentration versus time data. 

 
 
 
Statistical Considerations:
Sample Size: The sample size calculation is based on power to compare the proportion of subjects who achieve 
BICLA response (the BICLA response rate) at Day 169 between BMS-931699 and placebo arms. With a one-sided 
continuity corrected chi-squared test at significance level 0.05, data from 70 randomized and treated subjects per 
arm will provide at least 89% power to detect a 25% increase in the BICLA response rate in the active treatment 
arms (ie. 50% response rate in BMS active arms) compared to the placebo and provide 74% power to detect 20% 
increase in the BICLA response rate in the active treatment arm (ie, 45% response rate in BMS active arm) 
compared to the placebo, assuming that the placebo arm has 25% response rate which is reasonable based on the 
EMBLEM phase 2 trial result.1 No adjustment will be made for multiplicity. Subjects who discontinue 
treatment/study prior to Day 169 will contribute to the data that will be analyzed for BICLA response at Day 169 
(discontinuation will indicate no BICLA response). Therefore, no adjustment will be made for discontinuations.
The primary efficacy analysis will be conducted on all randomized patients who received at least one dose of the 
study drug. In order to get 70 randomized and treated subjects per arm, an adequate numbers of subjects need to 
meet the inclusion/exclusion criteria at screening.
If the interim analysis for futility and dose adaption suggests an additional dose arm at a lower dose level needs to be 
added, then up to 40 additional subjects may be randomized.
Endpoints for Short term Period:
Primary Endpoint

Proportion of subjects who achieve BICLA response (BICLA response rate) at Day 169.
Secondary Endpoints
Safety

Incidence and severity of all Adverse Events (AEs), Serious AEs (SAEs), and pre-established Events of Special 
Interest

Incidence and severity of clinically significant changes in vital signs

Incidence and severity of clinically significant ECG abnormalities

Incidence and severity of clinically significant abnormalities in general laboratory tests
Efficacy

Proportion of subjects who meet response criteria for the SLE Responder Index [SRI(4), SRI(5) and SRI(6)] at 
Day 169

Proportion of subjects who meet response criteria for the SLE Responder Index [SRI(4), SRI(5) and SRI(6)] at 
Day 85

Proportion of subjects with BICLA response at Day 85

Change from baseline in CLASI score at Day 85 and Day 169

Percentage of subjects with an improvement of >4 or a decrease of >50% from baseline in their CLASI score 
at Day 85 and Day 169
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Change from baseline in arthritis, as assessed by ACR28-joint count of tender and swollen joints at Day 85 and 
at Day 169

The change from baseline in the following other indices SLE activity over time:

The overall BILAG-2004 score

The overall SLEDAI-2K score

The overall MDGA score

The cumulative corticosteroid and immunosuppressant use over time
Pharmacokinetic

Ctrough: Trough level serum concentration of BMS-931699 at time points specified in Table 5.5.1-1.
Immunogenicity

Proportion of subjects with BMS-931699 induced antibody response over time points specified in Table 5.5.1-1.
 
Endpoints for Long term Extension Period:
During the LTE period, the following endpoints will be assessed cumulatively (safety) and over time (efficacy).
Safety Endpoints

Incidence and severity of all Adverse Events (AEs), Serious AEs, and pre-established Events of Special Interest 

Incidence and severity of clinically significant abnormalities in general laboratory tests
Efficacy Endpoints

Proportion of subjects who achieve BICLA response (BICLA response rate)

Proportion of subjects who meet response criteria for the SLE Responder Index (SRI) [SRI(4), SRI(5) and 
SRI(6)]

CLASI score 

ACR 28 joint count of tender and swollen joints

Overall BILAG-2004 score

Overall SLEDAI-2K score

Overall MDGA score

The cumulative corticosteroid and immunosuppressant use

Proportion of patients reaching a Major Clinical Response and Partial Clinical Response

Fatigue, based on the FACIT

Quality of life, based on SF-36
Pharmacokinetic Endpoints

Ctrough: Trough level serum concentration of BMS-931699 at time points specified in Section 5.5.
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Immunogenicity

Proportion of subjects with BMS-931699 induced antibody response
Analyses for the Short-term Period:
Primary analysis:
The Chi-square tests will be used to compare the BICLA response rates at Day 169 between each of the active 
treatment arms and the placebo arm. The Chi-square p-value will be provided for each comparison between the 
active treatment and the placebo arm. In addition, the difference of the response rates between each active treatment 
and placebo will be estimated and their corresponding 90% confidence interval will be calculated. No adjustment 
will be made for multiplicity.
Secondary analysis:
Efficacy analysis:

Proportion of subjects who meet response criteria for the SLE Responder Index [SRI(4)], SRI(5) and SRI(6)] at 
Day 169

Proportion of subjects who meet response criteria for the SLE Responder Index [SRI(4)], SRI(5) and SRI(6)] at 
Day 85

Proportion of subjects with BICLA response at Day 85

Percentage of subjects with an improvement of > 4 or a decrease of > 50% from baseline in their CLASI score 
at Day 85 and Day 169
For each of the above endpoints, the estimate and its corresponding 90% confidence interval will be calculated for 
the difference of the proportions between each active treatment arm and the placebo arm at the specified visit, 
similar to the primary analysis.
For each of the following endpoints, the mixed effect model will be fit with treatment and visit as the fixed effects 
and measurements within each subject as the repeated measurements. The baseline value will be added into the 
model as a covariate if necessary. Based on the mixed effect model, the estimate and 90% confidence interval will 
be calculated for the difference between each active treatment and the placebo at each specified visit.

Change from baseline in CLASI score at Day 85 and Day 169

Change from baseline in arthritis, as assessed by ACR28-joint count of tender and swollen joints at Day 85 and 
at Day 169

The change from baseline in the following other indices SLE activity over time:

The overall BILAG-2004 score

The overall SLEDAI-2K score

The overall MDGA score
In addition, the cumulative corticosteroid and immunosuppressant use over time will be summarized. 
Safety analysis:
All recorded adverse events will be listed and tabulated by system organ class, preferred term and treatment. Vital 
signs and clinical laboratory test results will be listed and summarized by treatment. Any significant physical 
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examination findings, and clinical laboratory results will be listed. ECG readings will be evaluated by the 
investigator and abnormalities, if present, will be listed. The pre-established Events of Special Interest will be listed 
and summarized.
PK analysis:
Ctrough will be summarized by dose and study day. 
Immunogenicity analysis
Proportion of subjects with BMS-931699-induced antibody response and titers over time will be summarized. 
 
 
 
Interim analysis:
Interim Analysis for Safety/RO at Day 29
When at least 6 subjects per arm have reached Day 29, an interim analysis (IA) for safety and RO will be performed.
The safety analysis will focus on incidence and severity of all adverse events (AEs), serious AEs and pre-established 
Events of Special Interest such as infection AEs and any other safety analysis requested by DMC. For RO: the 
median RO at Day 29 for each treatment arm will be calculated. Based on the results of this interim analysis, a 
decision will be taken regarding the doses that will be carried forward into Part 2 of the study. Specifically, dosing 
regimens originally included in Part 1 may be discontinued and/or new dosing regimens may be added according to 
the following criteria:
Safety:
The DMC in conjunction with an unblinded internal monitoring team may require one or more doses to be 
discontinued if stopping criteria are met or other safety signals arise that the Medical Monitor and/or DMC consider 
of sufficient concern.
Receptor Occupancy:

If median RO of any dose is < 20%, the sponsor may consider dropping that dose;

If the median RO for all doses is > 90%, the sponsor may consider adding or replacing a dose in Part 2 of the 
study to ensure an adequate pharmacodynamic range (dose not to exceed 12.5 mg weekly).
Dose decrease and/or reduction of frequency of administration may also be considered if RO results fall outside the 
parameters indicated above. This adjustment may occur for safety reasons or in case unforeseen RO profiles 
observed in SLE patients. The decision to adjust dose and/or frequency will be taken after review of the data by the 
clinical team.
Interim analysis for futility and dose adaptation at Day 85:
After 30 subjects per treatment arm (including the subjects from Part 1) have completed at least 84 days of the 
treatment period or discontinued the treatment, an interim analysis will be conducted to assess the futility of the 
BMS-931699 dose arms and the overall safety. The results of the interim analysis will be reviewed by an unblinded 
sponsor team who will provide recommendations to the blinded study team. The blinded study team will make the 
decision. The unblinded BMS team may recommend to:

Maintain the current design;

Drop a certain dose arm(s) and equally randomize the remaining unallocated subjects to the remaining arms;

Stop the study if all dose arms need to be dropped for safety or futility reasons.
The interim analysis for futility and dose adaption will be performed on the BICLA response at Day 85 and 
Day 169, of those 30 subjects per arm who have completed 85 days of treatment or discontinued the treatment, using 
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a Bayesian predictive approach.2 This analysis assumes that the BICLA response at Day 85 and at Day 169 in the 
subjects who have not yet been observed will be similar to those observed for the subjects included in the interim 
analysis at Day 85 and Day 169, respectively. As such, the unobserved data will be simulated from the predictive 
distribution conditional on the interim data and the prior distribution of the treatment difference (using a 
non-informative prior). Under the Bayesian framework, the posterior distribution of the treatment difference 
(BMS-931699 active dose – Placebo) will be constructed to determine the predictive probability of a successful 
outcome (ie, reach statistical significance) at Day 169. Based on computer simulations of the operating 
characteristics of the study design, the futility threshold in this interim analysis is set to 0.2. For the comparison of 
interest, if the predictive probability of a successful outcome at the planned end of the trial falls below 0.2, that 
BMS-931699 dose arm is deemed futile in terms of BICLA response. However, the final futility will also 
incorporate the results from SRI(4), ACR28 and some biomarkers (C3, C4, ANA and anti-dsDNA). 
The proposed stopping rules at the interim analysis, based on the futility assessment and the overall safety 
assessment, are as follows:

Rule 1: Drop the futile dose arm(s) and the dose arm cannot be dropped until the lower dose arm has been 
dropped.

Rule 2: Drop the dose arm(s) with safety issues identified;

Rule 3: If safety issues are identified in all dose arms or all dose arms are futile, stop the study.
In case dosing arms are dropped following the interim analysis, the remaining unallocated subjects will be 
randomized into the remaining arms.
If the predictive probability of success for each active arm versus placebo is greater than or equal to 0.9, then the 
BMS team may also recommend adding an additional dose arm at lower dose level than current active doses to 
explore a suboptimal dose.
In that case, the remaining unallocated subjects with up to 40 additional subjects will be randomized into the 
remaining arms and the new dose arm based on the new randomizations schedule.
Analyses for the long-term extension period:
The LTE period starts when a subject receives at least one post Day 169 dose. The analysis based on this period is 
descriptive in nature.
Populations of Analysis
All Subjects who received at least one dose post Day 169. 
Demographics and Baseline Characteristics
Categorical parameters will be summarized using frequency counts and percentages. Continuous parameters will be 
summarized through means, SD, median, and range. The baseline (Day 1) is defined as the start of study medication 
(the same as baseline in Double-blind period). The baseline results will be based on LTE analysis population.
Efficacy Analyses
For continuous secondary endpoints (e.g. SLEDAI, MDGA etc.) point estimates and 90% confidence intervals for 
mean change from baseline to subsequent time points (in LTE period) within each treatment groups will be 
provided. For binary endpoints (BICLA Response, SRI(X) etc.), point estimates and 90% confidence intervals (CIs) 
will be provided using normal approximation within each treatment group. The assessment windows for LTE period 
will be based on the first LTE dose date; the baseline to assess responses or changes still refers to the Day 1 
assessment (the same as baseline in Short-term Period). The results will be presented by treatment groups. All 
Analyses will be based on as-observed data; hence no imputation will be implemented. No statistical testing 
including p-value computation will be performed.
Safety Analyses
The evaluation of long term safety of the selected dose(s) will be based on clinical adverse events, vital signs and 
laboratory abnormalities reported during the LTE period. Frequency distributions and individual listings of all 
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adverse events and laboratory marked abnormalities will be generated based on As Treated population. The results 
will be presented by treatment groups.
Immunogenicity
The incidence of a positive response of anti-BMS-931699 antibodies during the LTE period will be summarized by 
treatment groups.
Pharmacokinetic Analyses
The descriptive summary of PK parameters will be provided by visits and by treatment groups during the LTE 
period.
Pharmacodynamic Analyses
The descriptive summary of selected PD and selected biomarkers will be provided by visits and by treatment groups 
during the LTE period.
Outcomes Research Analyses
Not applicable.
The details of the analyses, endpoints and grouping schemes (treatment groups) will be provided in the long-term 
statistical analysis plan (LTE SAP).
 
 
 
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lulizumab pegol
 
 
1.2
Research Hypothesis 
BMS-931699 will have greater clinical efficacy compared to placebo on the British Isles Lupus 
Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) score, when added 
to stable background standard of care in patients with active manifestations of systemic lupus 
erythematosus (SLE) including, at a minimum, elevated antinuclear antibodies, arthritis, and/or 
cutaneous manifestations satisfying the BILAG “A” or “B” criteria.
1.3
Objectives(s)
1.3.1
Primary Objectives
To compare the proportion of patients who achieve BICLA response (BICLA response rate) at 
Day 169.
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BICLA is defined as:

British Isle Lupus Assessment Group improvement, defined as BILAG As at Baseline 
improved to B/C/D, and BILAG Bs at baseline improved to C/D, and no BILAG worsening 
in other BILAG organ systems such that there are no new BILAG As or greater than 1 new 
BILAG B; and

No worsening in the SLEDAI-2K total score compared to Baseline (defined as no increase in 
SLEDAI total score); and

No worsening in the physician’s global assessment (MDGA) of disease activity 
(“no worsening” is defined as less than 10% worsening, equivalent to a 10mm increase on a 
100mm visual analog scale [VAS]) compared to Baseline.

No changes in concomitant medications according to the following criteria: 

No increase of or addition of a new immunosuppressant agent (azathioprine, 
mycophenolic acid/mycophenolate mofetil, methotrexate, anti-malarial, leflunomide)
over baseline levels.

No increase in corticosteroid dose above baseline level outside of those allowed per 
protocol.
1.3.2
Secondary Objectives
Short-term period Part 1 only:

To evaluate the safety and RO when 6 to 10 subjects per arm reach 29 days (4 weeks).
Short-term period Part 1 and Part 2:
To assess:

The safety and tolerability of treatment with BMS-931699 in patients with active SLE

The proportion of patients who meet response criteria for the SLE Responder Index(4) 
[SRI(4)], SRI(5) and SRI(6) at Day 169.
Note: An SRI(X) Response is defined as:

a reduction in Day 1 SLEDAI-2K disease activity score of X points; 

no worsening of disease (defined as an increase of 30mm on a 100mm VAS from 
Day 1 as measured by the MDGA; and

no new BILAG-2004 Index A organ system score and no more than one new or 
worsening BILAG-2004 Index B organ system scores

The proportion of patients with SLE Responder Index [SRI(4), SRI(5) and SRI(6)] at Day 85.

The proportion of patients with a BICLA response at Day 85.

The improvement in the extent of cutaneous and mucous membrane activity, as measured by 
the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) at Day 85 
and Day 169
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
Joint tenderness and swellings as measured by the by American College of Rheumatology 
(ACR)28 at Day 85 and Day 169

The other indices of SLE activity measured at Days 29, 57, 85, 113, 141 and 169 including:

The change from baseline in overall BILAG-2004 score. A major response is defined as 
described in Yee et al 2010 (A=12, B=8, C=1, D/E=0).11

The change in overall Systemic Lupus Erythematosus Disease Activity Index 2K score 
(SLEDAI 2K)

The change from baseline in Physician’s Global Assessment of disease activity (MDGA) 
score

The systemic exposure of BMS-931699 in patients with SLE

The cumulative corticosteroids use and immunosuppressants use over time

The immunogenicity of BMS-931699

Serum biomarkers C3, C4, anti-double-stranded deoxyribonucleic acid (anti-dsDNA), 
anti-nuclear antibody (ANA) and other autoantibodies at Day 85 and Day 169

The pharmacodynamics (PD) of BMS-931699, including assessments potentially associated 
with target engagement [including receptor occupancy (RO)].
Note: Although all efforts must be made to collect all RO samples required per protocol, it 
may not be possible for a site to obtain samples from subjects located in certain participating 
regions due to stability and processing issues. Site MUST consult with the Medical Monitor 
prior to deciding not to collect RO samples. 
 
 
 
 
 
 
 
 
 
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lulizumab pegol
 
 
 
 
 
 
 
 
1.3.4
Long-Term Extension Period Objectives
Assess the long term clinical safety, tolerability and efficacy of lulizumab pegol.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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lulizumab pegol
 
 
 
 
 
 
 
 
 
 
o  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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lulizumab pegol
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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similar to the reported plasma volume, indicating very limited extravascular distribution. The 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a 
 
 
 
 
 
 
 
 
 
 
 
16
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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lulizumab pegol
The MAD study IM128003 was performed in 24 subjects (3 cohorts of 8 subjects) treated for 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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lulizumab pegol
 
 
 
 
Intense safety monitoring will be put in place during the entire study (short-term and long-term 
extension periods), allowing early detection of any safety signals. Specifically, the following
measures will be put in place:

Patients will undergo safety evaluation at each clinic visit.

Investigator will conduct safety evaluation before dosing.

Continuous internal data review by unblinded clinical monitoring team. 

Monitoring team to refer to independent external DMC any safety issue deemed to be of 
relevance. 

Independent external DMC to meet at regular intervals throughout the entire study to review
all data (frequency to be determined in conjunction with DMC).

Stopping rules to be implemented under DMC guidance.
DMC and internal safety monitoring activities initiated in Part 1 will continue into Part 2
and will be ongoing until the end of the study, including the long-term extension.
In summary, the potential overall benefit ratio for BMS-931699 treated subjects in this trial 
appears favorable. In order to minimize the overall risk to participating subjects, this protocol has 
inclusion and exclusion criteria appropriate to the population and proposed treatments, 
exclusionary screening tests [chest x-ray, Quantiferon Gold testing (or other interferon gamma 
release assay test, such as T-SPOT) wherever appropriate, risk factor/age specific breast 
screening, medical history], and specific follow-up safety assessments. In addition, the AEs and 
SAEs will be reviewed on an ongoing basis by the medical monitors and pharmacovigilance 
group to look for trends and any safety issues.
2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Conference on Harmonisation (ICH) and in accordance with the ethical principles 
underlying European Union Directive 2001/20/EC and the United States Code of Federal 
Regulations, Title 21, Part 50 (21CFR50).
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
All potential serious breaches must be reported to BMS immediately. A serious breach is a 
breach of the conditions and principles of GCP in connection with the study or the protocol, 
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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 or BMS should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
2.3
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives
(as per country guidelines) are clearly and fully informed about the purpose, potential risks, and
other critical issues regarding clinical studies in which the subject volunteers to participate. 
BMS will provide the investigator with an appropriate (ie, Global or Local) sample informed 
consent form(s) which will include all elements required by ICH, GCP and applicable regulatory 
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:

Provide a copy of the consent form(s) and written information about the study in the 
language in which the subject is most proficient prior to clinical study participation. The 
language must be non-technical and easily understood. 

Allow time necessary for subject or subject's legally acceptable representative to inquire 
about the details of the study.

Obtain an informed consent signed and personally dated by the subject or the subject's 
legally acceptable representative and by the person who conducted the informed consent 
discussion. 

Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent 
form(s) and any other information to be provided to the subjects, prior to the beginning of the 
study, and after any revisions are completed for new information.
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
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(s) must also include a statement that BMS and regulatory authorities have 
direct access to subject records. 
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to 
refuse participation in, or to be withdrawn from, the clinical study at any time should be 
considered by the investigator.
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a Phase 2, parallel-arm, randomized, double-blinded, multicenter, international study, 
with an adaptive design.
The study will comprise a short-term period (Part 1 and Part 2), and a long-term extension (LTE) 
period.
Part 1 of the short-term period will focus on assessing safety and RO and will be limited to a 
maximum of 50 patients (approximately 6-10 patients/arm) who will be included in the 
Safety/RO interim analysis (IA). These patients will continue study treatment beyond the IA for 
Safety/RO and be treated for up to 24 weeks and be followed for 6 additional weeks after 
treatment is completed. Treatment could be shorter if IA for Safety/RO analysis indicates one or 
more arms should be dropped.
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lulizumab pegol
Part 2 of the short-term period will start once cumulative safety profile is considered acceptable 
and RO data for 6-10 subjects per cohort dosed for >28 days is available and the interim analysis
from Part 1 is completed. Approximately 300 subjects will be randomized into this part of the 
study (number of patient to be randomized into Part 2 may increase based on the results of the 
futility interim analysis). 
All subjects will undergo screening evaluations to determine eligibility and allow down titration 
of prednisone (or prednisone equivalent) prior to administration of study medication. The 
screening period will have a duration of approximately 28 days (+/- 2 days). All eligibility 
criteria must be met prior to Day 1. In the event of technical difficulties leading inconclusive 
assessments that would go beyond the allowed window, the study medical monitor must be 
consulted prior to conducting Day 1. On Day 1, eligibility of subjects will be confirmed and
eligible subjects will receive their first dose of study medication.
Dose may be adapted based on results of the planned interim analyses from Part 1 and Part 2, as 
follows:

Safety and RO interim analysis: safety and RO analysis will be performed when 
approximately 6 to 10 subjects per arm have reached Study Day 29. Based on the results of 
this analysis, dose arms(s) may be adjusted or may be dropped.

Interim analysis for futility and dose adaptation on BICLA response, SRI response, 
ACR28 and some SLE biomarkers (such as auto-antibodies, complement levels, etc.) with 
possible exploratory exposure response analysis, will be performed when approximately 
30 subjects per arm have reached Study Day 85 (12 weeks), including subjects from Part 1 
and Part 2, of treatment or have discontinued prior to reaching study Day 85). Analysis will
be performed by an unblinded Sponsor team, while maintaining blind at the site and subject
level. Based on the results, the dose levels and sample size may be modified.

Ongoing assessment of safety will be performed by an independent Data Monitoring 
Committee (DMC) and an internal unblinded safety monitoring team. Both entities may 
make recommendations to the Sponsor regarding conduct of study and dose adjustment based 
on safety observations.
Following interim analyses and DMC reviews, dose arm(s) may be modified based on the 
results, as follows:

If one or more arms are added, future randomizations will include the new arm(s). 

If one or more arms are dropped for safety reasons, randomization into that arm will be 
terminated and all subjects currently randomized to that or those arm(s) will be discontinued
from receiving study medication.

If one or more arms are dropped due to inadequate RO, there will be no new randomizations 
into that dose arm; subjects currently randomized may continue at the Investigator discretion. 
The long-term extension (LTE) period is optional and will include eligible subjects who have 
completed Day 169 (week 24) of treatment and consent to participate. This period of the study 
will remain blinded but will no longer have a placebo arm. Eligible subjects will remain on their 
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lulizumab pegol
originally-assigned dose arm, unless they were on the placebo arm during the short-term period. 
Placebo-arm subjects will be re-randomized into one of the existing active arms at Day 169
(24 weeks). Re-randomization of the placebo subjects will be done by IVRS and only the 
unblinded pharmacist/drug preparer will know the new randomization arm. The LTE will remain 
blinded to the study team and study personnel. 
The long-term extension period will not have interim analyses for dose adaptation. However, the 
BMS unblinded safety committee will continue to review the safety data and discuss it with the 
DMC (also unblinded), as needed. During their evaluation of adverse events, if a significant 
safety concern is identified, these two committees may propose that one or more dose arms are 
dropped. If one or more dose arms are dropped for safety reasons, all subjects currently receiving 
that or those dose(s) will be discontinued from receiving study medication.
The study design schematics are presented in Figure 3.1-1, Figure 3.1-2, Figure 3.1-3, and Figure 
3.1-4.
Figure 3.1-1:
Overall Study Design
Part 1
• Limited to approximately 30 to 50 subjects (6-10 per arm).
• Interim analysis for safety and RO once 30-50 subjects have reached Day 29 (4 weeks).
• These subjects will continue study treatment beyond the interim analysis for safety and RO and 
will be treated for up to 24 weeks, and followed for 6 additional weeks after treatment is completed 
or discontinued. Treatment could be shorter if dose arm(s) are dropped. 
Intense safety monitoring by the 
DMC, in collaboration with an 
internal safety monitoring team, 
will be performed during Part 1 
and continue during Part 2.
DMC and unblinded internal 
safety monitoring activities will 
continue during long-term 
extension. 
Part 2
• Will start once cumulative safety profile is considered acceptable and RO data for 6-10 subjects 
per arm for >28 days are available and the interim analysis from Part 1 is completed. Results of the 
interim analysis in Part 1 and DMC reviews may result in treatment arm(s) modifications. 
• Each treatment arm will enroll approximately 70 subjects, including subjects from Part 1.
• Part 2 will have an interim analysis for futility once approximately 30 subjects per arm complete 
Day 85 (12 weeks), or have discontinued. As in the interim analysis from Part 1, results of the 
interim analysis in Part 2 and DMC reviews may result in treatment arm(s) modifications. 
• All subjects could be treated for up to 24 weeks and followed for 6 additional weeks after 
treatment is completed or discontinued. Treatment could be shorter if dose arm(s) are dropped. 
Long-Term Extension
• Subjects completing Day 169 (24 weeks) on study medication may be eligible to enter an optional 
long-term extension (LTE) period.
• The LTE period will remain blinded but will no longer have a placebo arm.
• Subjects will remain on their originally-assigned treatment arm unless they were on 
placebo. 
• Subjects initially randomized to placebo arm will be automatically re-randomized into one 
of the existing active arms at Day 169 (24 weeks). 
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Figure 3.1-2:
Study Design Schematic - Part 1
Figure 3.1-3:
Study Design Schematic - Part 2
Day  -28
Day 1
Day 29
Interim analysis of 
Safety/RO
Screening 
– Part 1
First dose
12.5mg EOW N= 6-10
12.5mg weekly N= 6-10
5mg EOW N= 6-10
1.25mg EOW N= 6-10
Part 1 limited to a maximum of 50 patients who will be treated 
for up to 24 weeks and may be followed for 6 additional weeks, 
unless the Safety/RO analysis indicates one or more arms 
should be dropped.
Placebo weekly N= 6-10
FU Day 42 #
6 weeks 
safety 
follow-up
Day 169
End of Treatment
24 weeks treatment
6 weeks FUP
4 weeks 
screening
# Will not apply to subjects entering LTE.
Day -28
Day 1
24 weeks treatment period
Day 169
Day 85
Clinical efficacy
(BICLA, SRI, 
SLEDAI, BILAG, 
CLASI, ACR28)
Futility analysis 
(ACR28, auto-antibodies, 
complement, biomarkers,  
BICLA/SRI)
Screening 
- Part 2
First dose
12.5mg EOW N= 60-64*
12.5mg weekly N= 60-64*
5mg EOW N= 60-64*
1.25mg EOW N= 60-64*
FU Day 42 #
6 weeks 
safety 
follow-up
* Treatment arm may or may not be included based on Part 1 Day 29 Interim Analysis.
# Will not apply to subjects entering LTE.
24 weeks treatment
Placebo weekly N= 60-64*
6 weeks FUP
New dosing regimen  N=70*
4 weeks 
screening
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lulizumab pegol
Figure 3.1-4:
Long-Term Extension Schematic
Physical examinations, vital sign measurements, 12-lead electrocardiograms (ECG), and clinical 
laboratory evaluations will be performed at selected times throughout the study. Subjects will be 
closely monitored for adverse events throughout the study. Blood will be collected for 
pharmacokinetic (PK) and pharmacodynamic measurements as well as for safety monitoring. 
The approximate duration of the short-term period (Parts 1 and 2) of the study is 238 days 
(34 weeks), including: 28 days (4 weeks) of screening, 168 days (24 weeks) of treatment, and 
42 days (6 weeks) of safety follow-up. If subject is eligible and opts to continue into LTE, the 
42-day follow-up visit will not be performed after the short-term period is completed and subject 
will enter LTE directly. If subject opts not to enter LTE then a follow-up visit will be completed 
42 days after end of treatment. At the time of writing there is no defined end date to the 
long-term extension period, however, the LTE provision may be further adjusted based on results 
from the ongoing lulizumab development program. Subjects discontinuing treatment during the 
LTE period will complete the follow-up visit approximately 6 weeks after receiving their last 
dose of study medication.
Subjects randomized in the short-term period (either Part 1 or Part 2) will be treated for up to 
24 weeks, will have the same procedures performed and will follow the same visit schedule. All 
subjects will account for the approximately 350 subjects planned to be randomized in this study.
24 weeks treatment period
Day 169
End of Part 2
Start of LTE
12.5mg EOW *
12.5mg weekly *
5mg EOW *
1.25mg EOW *
FU Day 42
6 Weeks 
Safety 
Follow-up #
* Treatment arm may or may not be included based on Interim Analyses.
Subjects in the placebo arm will be re-randomized to existing active treatment arms at Day 169.
# FU Day 42 to occur after last dose of study medication, whether last dose is in short term or long term periods.
24 weeks of treatment
Placebo weekly
New dosing regimen *
New dosing regimen *
No currently-defined treatment period

12.5mg EOW * 
12.5mg weekly * 
5mg EOW *
1.25mg EOW * 
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Approximately 125 sites will participate in this study, which will be conducted globally and 
should include, but will not be limited to, participation of countries located in North America and 
Europe.
Subjects who discontinue from the study will have one follow-up visit, approximately 42 days 
(6 weeks) after receiving their last dose of study medication, to perform safety assessments. 
During this period, when subjects are no longer receiving study drug, it is recommended that 
they are not treated with other biologic therapy, due to the compound’s half-life. However, this 
decision remains at the investigator’s discretion. If the study drug becomes commercially 
available, and if the subject chooses to receive treatment with the commercial product, then the 
subsequent post-dose follow-up visits are not required.
3.2
Post Study Access to Therapy
At the time of writing there is no defined end date to the LTE period, however, the LTE 
provision may be further adjusted based on results from the ongoing lulizumab pegol 
development program. At the conclusion of the study, subjects who continue to demonstrate 
clinical benefit will be eligible to receive BMS supplied study drug. Study drug may 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 drug if any of the following occur: a) the 
marketing application is rejected by responsible health authority; b) the study is terminated due 
to safety concerns; c) the subject can obtain medication from a government sponsored or private 
health program; d) BMS terminates development of the drug; or e) therapeutic alternatives 
become available in the local market.
3.3
Study Population
Men or women (not nursing or pregnant), ages 18-70 years inclusive, who meet the ACR criteria 
for the classification of Systemic Lupus Erythematosus (see Appendix 3).
For entry into the short-term period of the study, the following criteria MUST be met prior to 
dosing on Day 1. No exceptions will be granted.
For entry into the long-term extension, subjects must remain on study medication, complete the 
short-term period (up to 24 weeks of treatment), and sign a new informed consent.
3.3.1
Inclusion Criteria
1. Signed Written Informed Consent
a) Subjects must be willing to participate in the study and sign the informed consent.
b) Subjects must be willing and able to complete all study specified procedures and visits.
2. Target Population
a) Subjects must have SLE as defined by meeting 4 of the 11 classification criteria of the 
American College of Rheumatology for the classification of SLE, either sequentially or 
coincident. The 4 criteria need not be present at study entry, but have occurred at some 
time during the course of the disease and be documented.
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b) Subject Re-screening: This study permits the re-screening of a subject that has 
discontinued the study as a pre-treatment failure (ie, subject has not been randomized / 
has not been treated). If re-screened, the subject must be re-consented.
Note (1): If a subject is being considered for re-screening, a full screening visit must be 
performed again.
Note (2): A subject can only be re-screened once (eg, if re-screening for the same subject fails, 
no additional re-screening is allowed).
c) At screening:
i)
Subjects must have elevated ANA 1:80 via immunofluorescent assay at the central 
laboratory or anti-dsDNA or anti-Sm above the normal level as determined by the 
central laboratory.
Note: For inclusion criterion 2c-i: If central laboratory results are negative and positive results 
are documented at the site, a single repeat of the central laboratory values is allowed. If the 
central laboratory repeat is negative, the patient is not eligible to be randomized.
ii) Subjects must have a SLEDAI 6 to be eligible. At least 4 of the points must be 
attributable to clinical criteria including at least one of the following clinical 
parameters: arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, vasculitis 
and excluding points from lupus headache and organic brain syndrome. Must be 
confirmed by the External Adjudication Committee.
Note: On Day 1, the SLEDAI 2K must be ≥4 including points from at least one of the following 
clinical components: arthritis, rash, myositis, mucosal ulcers, pleurisy, pericarditis, vasculitis, 
and fever and excluding parameters which require central laboratory results (hematuria, pyuria, 
urinary casts, proteinuria, positive anti-dsDNA, decreased complement, thrombocytopenia and 
leukopenia). Points from lupus headache and organic brain syndrome are excluded.
iii) Subjects must have at least one of the following manifestations of SLE, as defined by 
the BILAG criteria as modified for use in this study, which must be confirmed by the 
External Adjudication Committee:
(1) BILAG A or B score in the Mucocutaneous body system
(2) BILAG A or B score in the Musculoskeletal body system due to active 
polyarthritis defined as follows:
(a) “BILAG A”: severe arthritis (BILAG #41) manifested by observed active 
synovitis in 2 joints with marked loss of functional range of movements and 
significant impairment of basic activities of daily living, that has been present 
on several days cumulatively over the past 4 weeks, including at the time of 
the screening visit. Basic ADLs are defined as the following activities which 
require assistance or assistive devices (at least one must be present and 
documented in source): ambulation, toileting, grooming including bathing, 
dressing, feeding oneself (not responsive to steroids up to 10 mg/day, 
antimalarials, NSAIDs).
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(b) “BILAG B”: Moderate arthritis or tendonitis or tenosynovitis (BILAG #42) 
defined as tendonitis/tenosynovitis or active synovitis in 1 joint (observed or 
through history) with some loss of functional range of movements which lead 
to some loss of functional range of motion as manifested by effects on 
instrumental ADLs (such as cooking, driving, using the telephone or 
computer, shopping, cleaning, etc.) which has been present on several days 
over the last 4 weeks and is present at the time of the screening visit.
(3) if only one “B” and no “A” score is present in the Mucocutaneous body system or 
in the Musculoskeletal body system due to arthritis, then at least one B must be 
present in the other body systems for a total of 2 “B” BILAG body system scores.
iv) Unless intolerant, subjects must be currently receiving at least one of the following
steroid-sparing agents for a minimum of 12 weeks, and at stable dose for at least 
8 weeks (56 days) prior to signing consent:
Azathioprine (AZA), chloroquine, hydroxychloroquine, methotrexate (MTX), 
leflunomide, mycophenolate mofetil/mycophenolic acid*. Subjects must remain 
on stable dose throughout the study#.
*Subjects who are receiving mycophenolic acid/mycophenolate mofetil may 
participate in the study only if mycophenolate mofetil therapy is given as a 
maintenance therapy and up to a maximum of 2 g/day (or mycopheloate acid dose 
equivalent); in subjects of African ancestry, 3 g/day (or mycopheloate acid dose 
equivalent) may be administered at the Investigator’s discretion.
v) Prednisone is not required; however, if subject is taking prednisone (or prednisone-
equivalent), dose cannot exceed 30 mg/day at screening for a subject to be eligible 
and must be stable at a maximum of 10 mg/day for at least 5 days prior to Day 1 
(randomization). Refer to Appendix 1 for a list of prednisone-equivalents.
vi) Any other immunossuppressive or biologic drug will require washout periods 
indicated in Appendix 2 prior to signing consent.
vii) If subjects receive chronic therapy with NSAIDs (including marketed COX-2 
inhibitors), doses must be stable for 14 days prior to first dose of study medication on 
Day 1 (randomization) and are recommended to remain stable throughout the study.
Note: NSAIDs should be withheld for at least 12 hours prior to visits where BILAG, 
SLEDAI 2K, joint counts, CLASI and MDGA will be assessed. 
3. Age and Reproductive Status
a) Males and Females, ages 18 to 70 years, inclusive
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 
24 hours prior to the start of study drug.
c) Women must not be breastfeeding
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration 
of treatment with study drug(s) BMS-931699 plus 5 half-lives of study drug 
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BMS-931699 (7 days) plus 30 days (duration of ovulatory cycle) for a total of 65 days
post-treatment completion.
e) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug(s) BMS-931699 
plus 5 half-lives of the study drug (7 days) plus 90 days (duration of sperm turnover) for 
a total of 125 days post-treatment completion.
f)
Azoospermic males and WOCBP who are continuously not heterosexually active are 
exempt from contraceptive requirements. However they must still 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 WOCBP and male subjects who are sexually active with WOCBP on 
the use of highly effective methods of contraception. Highly effective methods of contraception 
have a failure rate of < 1% when used consistently and correctly.
At a minimum, subjects must agree to the use of one method of highly effective contraception as 
listed below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION

Male condoms with spermicide

Hormonal methods of contraception including combined oral contraceptive pills, vaginal 
ring, injectables, implants and intrauterine devices (IUDs) such as Mirenaby WOCBP 
subject or male subject’s WOCBP partner. Female partners of male subjects participating in 
the study may use hormone based contraceptives as one of the acceptable methods of 
contraception since they will not be receiving study drug 

IUDs, such as ParaGard

Tubal ligation

Vasectomy

Complete Abstinence*
*Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an 
acceptable form of contraception for all study drugs. Female subjects must continue to have 
pregnancy tests. Acceptable alternate methods of highly effective contraception must be 
discussed in the event that the subject chooses to forego complete abstinence
3.3.2
Exclusion Criteria
1. Target Disease Exceptions
a) Subjects with drug-induced SLE, rather than “idiopathic” SLE.
b) Subjects with other autoimmune disease [(for example rheumatoid arthritis (RA), 
multiple sclerosis (MS)].
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Note: Subjects with type I diabetes mellitus, thyroid autoimmune disease and
secondary Sjögren syndrome are eligible.
c) Subjects with primary anti-phospholipid antibody syndrome as the sole or primary 
feature of their SLE or SLE-like syndrome should be excluded. However, subjects 
with secondary anti-phospholipid syndrome may be included in the study, unless they 
have had a serious thrombotic event (pulmonary embolism, stroke, deep vein 
thrombosis) within one year prior to signing consent. Subjects on chronic anti-
coagulant therapy can be enrolled in the study.
2. Medical History and Concurrent Diseases
a) Any major surgery within 6 weeks of study drug administration (Day 1) or any elective 
surgery planned during the course of the study.
b) The following subjects will not be allowed in this study:
i)
Subjects with any history or risk for tuberculosis (TB), specifically subjects with:
(1) Current clinical, radiographic or laboratory evidence of active TB
(2) History of active TB within the last 3 years, unless there is documentation that 
prior anti-TB treatment was appropriate in duration and type according to current 
World Health Organization Guidelines.
(3) Latent TB defined as Positive QFG or other diagnostic test in the absence of 
clinical manifestations, unless subject has received at least 1 month treatment with 
Isoniazid, or other agents recommended by local Health Authority guidelines, and 
an interferon gamma release assay (IGRA) test, eg, QFG or T-Spot, is negative
before Day 1.
(4) Positive QFG test (or other diagnostic test) at screening or within 3 months prior 
to Day 1 is acceptable as long as there is documentation of a negative result by 
Day 1. - Criterion no longer applicable per Protocol Amendment no.6
ii) Subjects with active or unstable lupus neuropsychiatric manifestations, including but 
not limited to any condition defined by BILAG “A” criteria, with the exception of 
mononeuritis multiplex and polyneuropathy, which are allowed.
iii) Subjects with active, severe, lupus nephritis (WHO class III, IV) which requires or 
may require treatment with cytotoxic agents or high dose corticosteroids. Subjects
with prior, controlled renal disease with residual proteinuria up to 3g/day or a urine 
protein/creatinine ratio of 3 mg/mg or 339 mg/mmol are allowed.
iv) Subjects with herpes zoster that resolved less than 2 months prior to screening.
v) Subjects with evidence (as assessed by the Investigator) of active or latent bacterial or 
viral infections at the time of potential screening, including subjects with evidence of 
Human Immunodeficiency Virus (HIV) infection as defined by positivity of HIV-1
and HIV-2 antibody.
vi) Subjects currently on hydroxychloroquine or chloroquine with evidence of 
retinopathy within 6 months of screening or who have had no ophthalmologic 
evaluation within one year of screening and will not have this examination done or 
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who are unwilling or unable to have regular ophthalmologic examinations while 
participating in the study.
c) Concomitant illness that, in the opinion of the investigator, is likely to require additional 
systemic glucocorticosteroid therapy during the study, (eg, asthma) is exclusionary. 
However, treatment for asthma with inhalational corticosteroid therapy is allowed.
d) Female subjects with a breast cancer screening suspicious for malignancy, and in whom 
the possibility of malignancy cannot be reasonably excluded following additional 
clinical, laboratory or other diagnostic evaluations.
e) Subjects with a history of cancer within the last five years (other than non-melanoma skin 
cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be 
removed prior to randomization (Day 1 treatment). Carcinoma in situ, treated with 
definitive surgical intervention, is allowed.
f)
Subjects with any acute and/or chronic serious bacterial or viral infection (such as 
pneumonia, renal infection and sinusitis). Documentation of resolution must be available 
in medical chart prior to Day 1 (randomization).
g) Donation of blood to a blood bank or in a clinical study (except a screening visit) within 
4 weeks of study drug administration (within 2 weeks for plasma only).
h) Blood transfusion within 4 weeks of study drug administration.
i)
Inability to be venipunctured and/or tolerate venous access.
j)
Any other sound medical, psychiatric and/or social reason as determined by the 
investigator.
3. Physical and Laboratory Test Findings
a) Evidence of organ dysfunction or any clinically significant deviation from normal in 
physical examination, vital signs, ECG or clinical laboratory determinations beyond what 
is consistent with the target population.
b) Positive hepatitis-B surface antigen
c) Positive hepatitis-C antibody with positive Recombinant ImmunoBlot Assay (RIBA) or 
Polymerase Chain Reaction (PCR)
d) White blood cells (WBC) < 1,200/mm3 (1.2 x 109/L)
e) Platelets < 50,000/mm3 (50 x 109/L)
f)
Hemoglobin < 8g/dL or < 7g/dL if due to hemolytic anemia related to SLE
g) Proteinuria > 3.0g/day (3000 mg/day) or equivalent level of proteinuria as assessed by 
protein/creatinine ratio (3 mg/mg or 339 mg/mmol).
h) serum creatinine > 2.0 mg/dL
i)
Active urinary sediment defined as the following:
i)
RBC casts
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j)
Serum alanine aminotransferase (ALT) > 2x upper limit of normal (ULN), unless 
explicitly related to lupus based on the Investigator’s judgment.
k) Serum aspartate aminotransferase (AST) > 2xULN, unless explicitly related to lupus 
based on the Investigator’s judgment.
l)
Positive urine screen for illegal drugs of abuse, except if these drugs are prescribed by the 
treating physician (must be documented), and except for other drugs that are not illegal 
within the country or region.
m) Any other laboratory test results that, in the opinion of the Investigator, might place 
subject at unacceptable risk for participating in this study.
4. Allergies and Adverse Drug Reaction
a) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
5. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
c) Inability to comply with restrictions and prohibited activities/treatments as listed in 
Section 3.4
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 in the absence of other biological or physiological causes. In addition, 
famales under the age of 55 years must have a documented serum follicle stimulating hormone, 
(FSH) level > 40mIU/mL to confirm menopause.
Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgment in checking serum FSH levels. If the serum FSH level is > 40 mlU/ml at any time 
during the washout period, the woman can be considered postmenopausal. 

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
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Other parenteral products may require washout periods as long as 6 months.
3.3.4
Criteria for Long-Term Extension
Subjects who enter the short-term period according to the eligibility criteria outlined in 
Sections 3.3.1 and 3.3.2, and who complete 24 weeks on study medication are eligible for 
participation in the LTE period. The LTE period will remain blinded but will no longer be 
placebo controlled, as subjects completing Day 169 in the placebo arm will be re-randomized to 
existing active arms. 
A separate informed consent must be signed to enter the LTE period.
The class and dose of background therapies is recommended to remain the same as in the short 
term period. However, temporary rescue therapy with prednisone (or prednisone equivalent) to 
transiently manage SLE disease activity may be instituted. The increase in prednisone should not 
exceed a total daily dose of 20 mg, and must return to the previous stable dose within 14 days. 
Subjects requiring more than 14 days of rescue therapy will be discontinued.
The use of cyclophosphamide, any intravenous, any intra-articular or biologic agent remains
prohibited during LTE. Any changes to or new concomitant therapies must be recorded on the 
CRF.   
 
 
 
 
 
 
 
 
 
 
 
 
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3.4.2
Other Restrictions and Precautions
Active SLE and its treatment are associated with increased risk of infection. Subjects should be 
provided information about the signs of the most common serious infections (eg, pneumonia, 
sepsis) and must have the knowledge and means to access appropriate medical care.
3.5
Discontinuation of Subjects following any Treatment with Study Drug
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:

Subject’s request to stop study treatment and/or participation in the study

Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the 
best interest of the subject

Termination of the study by Bristol-Myers Squibb (BMS)

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness

Unblinding a subject for any reason (emergency or non-emergency)

Development of new active manifestations of lupus requiring treatment with any 
non-protocol approved medications during the study.

Inability or subject’s failure to comply with the protocol requirements.

Subject who misses more than 3 consecutive weekly doses.

Pregnancy

Treated with prednisone (or prednisone equivalent) at a total daily dose exceeding 20 mg
and/or for more than 7 days (short-term period) or more than 14 days (long-term extension 
period). 
Patients should discontinue from study, perform End of Treatment and Follow-up Day 42 visits, 
and receive standard of care according to local guidelines.
In the case of pregnancy, the investigator must immediately notify the BMS Medical 
Monitor/designee of this event. If any female subject becomes pregnant she will be immediately 
discontinued from the study.
All subjects who discontinue investigational product 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).
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If study drug is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate CRF page.
3.6
Post Study Drug Follow up
In this study, assessment of lupus disease activity is a key endpoint of the study. Post study 
follow-up is of critical importance and is essential to preserving subject safety and the integrity 
of the study. Subjects who discontinue study drug must continue to be followed for collection of 
outcome and/or survival follow-up data as required and in line with Section 5 until death or the 
conclusion of the study.
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug will remain in the study and must continue to be 
followed for protocol specified follow-up procedures. The only exception to this is when a 
subject specifically withdraws consent for any further contact with him/her or persons previously 
authorized by subject to provide this information. Subjects should notify the investigator of the 
decision to withdraw consent from future follow-up in writing, whenever possible. The 
withdrawal of consent should be explained in detail in the medical records by the investigator, as 
to whether the withdrawal is from further treatment with study drug only or also from study 
procedures and/or post treatment study follow-up, and entered on the appropriate CRF page. In 
the event that vital status (whether the subject is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed in 
accordance with local law.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. Lost to 
follow-up is defined by the inability to reach the subject after a minimum of three documented 
phone calls, faxes, or emails as well as lack of response by subject to one registered mail letter. 
All attempts should be documented in the subject’s medical records. If it is determined that the 
subject has died, the site will use permissible local methods to obtain the date and cause of death.
If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the subject’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining subject’s contact 
information or other public vital status data necessary to complete the follow-up portion of the 
study. The site staff and representative will consult publicly available sources, such as public 
health registries and databases, in order to obtain updated contact information. If after all 
attempts, the subject remains lost to follow-up, then the last known alive date as determined by 
the investigator should be reported and documented in the subject’s medical records.
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4
STUDY DRUG
Study drug includes both Investigational [Medicinal] Product (IP/IMP) and Non-investigational 
[Medicinal] Product (Non-IP/Non-IMP) and can consist of the following:

All products, active or placebo, being tested or used as a comparator in a clinical trial. 

Study required premedication, and 

Other drugs administered as part of the study that are critical to claims of efficacy 
(eg, background therapy, rescue medications)

Diagnostic agents: (such as glucose for glucose challenge) given as part of the protocol 
requirements must also be included in the dosing data collection.
BMS-931699 or a lookalike placebo will be administered weekly as a SC single injection
solution. Table 4-1 below indicates the total dose, formulation strength, and number of vials for 
each treatment arm.
Table 4-1:
Treatment Administration
Treatment
Total Daily Dose
Formulation Strength
Number of Vials
1
1.25 mg SC EOW
12.5mg/mL
1
2
5 mg SC EOW
12.5 mg/mL
1
3
12.5 mg SC EOW
12.5mg/mL
1
4
12.5 mg SC Weekly
12.5mg/mL
1
5
Placebo
Placebo
NSS
On Day 1, each subject will receive a single SC dose of either BMS-931699 or placebo.
There are no restrictions related to food and fluid intake associated with BMS-931699 known at 
this point.
Product description and storage information is described in Table 4-2.
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Table 4-2:
Study Drugs for BMS-931699
Product Description Class and 
Dosage Form
Potency
IP/Non-IMP
Blinded or 
Open Label
Packaging/Appearance
Storage Conditions
(per label)
BMS-931699-1* Injection. The 
composition of the drug product is 
12.5 mg/mL BMS-931699 in 20 
mM phosphate, pH 5.9, with 5% 
(w/v) sorbitol. 
12.5 mg/mL
IP
Open Label
3 cc vial with 13mm opening, 1-panel, 
open label. Appearance clear to slightly 
opalescent, colorless to pale yellow 
solution, 3 cc vial with 13mm opening, 1-
panel, open label. Appearance clear to 
slightly opalescent, colorless to pale yellow 
solution, which may contain a few white or 
translucent particles.
Store refrigerated 
2-8°C (36-46 °F). 
Protect from light, 
protect from freezing.
* The clinical label will reflect the product name as “BMS-931699-01” to be linked with the product description on the vial.
For study drugs not provided by BMS and obtained commercially by the site or subject, storage should be in accordance with the 
product label.
Preparation instructions will be provided separately to the site. 
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4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form. The 
investigational product should be stored in a secure area according to local regulations. It is the 
responsibility of the investigator to ensure that investigational product is only dispensed to study 
subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations. 
In this protocol, investigational product is BMS-931699 Injection.
4.2
Non-investigational Product
There are no non-investigational products in this study.
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the study drug arise, the study drug should not be 
dispensed and contact BMS immediately.
Please refer to section 9.2.2 for information on investigation product record retention and 
Section 4.8 for return and destruction instructions.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained 
that includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
Preparation for Subcutaneous (SC) Use:
For SC dosing, no dilution of the drug product solution (12.5 mg/mL) will be required for doses 
of 12.5mg. However, doses of 5mg and 1.25mg will require dilution. A commercially available 
appropriately sized sterile needle and appropriate syringe should be used for withdrawal and 
administration (refer to the pharmacy reference instruction document for further details on the 
subcutaneous preparation and administration for materials and instructions, provided separately). 
The placebo for BMS-931699 injection is normal saline solution, which is administered in a 
similar fashion as described for the BMS-931699 injection. Normal saline to use as placebo will 
not be provided by the Sponsor.
After withdrawal into an appropriate sized syringe, the product must be administered within 
4 hours. If not dosed immediately, filled syringes should be kept at 2°- 8° C (36°- 46° F) with 
protection from light prior to use. 
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Study personnel will administer the dose to the subject. The primary point of injection should be 
one of the upper arms; however other points of injections are acceptable. The subjects should be 
monitored for at least 1 hour after each injection for potential reactions.
4.4
Method of Assigning Subject Identification
Subjects will be randomized to receive either BMS-931699 or placebo according to a computer-
generated randomization scheme prepared by a Randomization Coordinator within the Drug 
Supply Management Department of BMS Research and Development. 
During the Screening visit, the investigative site will call into the enrollment option of the 
Interactive Voice Response System (IVRS) designated by BMS for assignment of a 5-digit 
subject number that will be unique across all sites. Enrolled subjects, including those not dosed, 
will be assigned sequential subject numbers starting with 00001, eg, 00001, 00002, 00003.... 
00010. The patient identification number (PID) will ultimately be comprised of the site number 
and subject number. For example, the first subject screened (ie, enrolled) at site number 1, will 
have a PID of 0001 00001. Once it is determined that the subject meets the eligibility criteria 
following the Screening visit, the investigative site will call the IVRS to randomize the subject 
into the treatment period. 
4.5
Selection and Timing of Dose for Each Subject
4.5.1
Double-blind Administration of BMS-931699 or Placebo
On Day 1, subjects will be randomized to one of the following dosing arms in a 1:1:1:1:1 
randomization scheme:

BMS-931699 at 12.5 mg weekly sub-cutaneous (SC) injection

BMS-931699 at 12.5 mg every other week (EOW) SC injection

BMS-931699 at 5 mg EOW SC injection

BMS-931699 at 1.25 mg EOW SC injection

Placebo SC injection (short-term period only)
The Pharmacist (or qualified drug preparation person) will know the randomized assignments 
and will prepare the appropriate dose of active BMS-931699 or placebo accordingly. The 
prepared drug must be supplied to study personnel in a manner such that neither study personnel 
nor subjects will be aware of whether they receive active drug or placebo. 
Every randomized subject will be required to come to the clinic/research center weekly to be 
dosed. This will ensure double-blind is maintained despite the variability of regimens. Subjects 
randomized to weekly subcutaneous injections of either placebo or BMS-931699 will be dosed 
weekly as per schedule and subjects randomized to one of the every other week arms will be 
alternating between receiving a subcutaneous injection of BMS-931699 one week and one of 
placebo the following week.
Every randomized subject will be required to remain on site for at least 1 hour after each dose to 
ensure safety.
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4.5.1.1
Administration Window
A subject’s scheduled dosing may be administered within 2 days of the target day to adjust for 
the subject’s and/or the site personnel’s convenience. 
Refer to Section 4.5.2.1 for dose modifications in the presence of an adverse event. 
4.5.2
Dose modifications
4.5.2.1
BMS-931699 or Placebo
Dose Modifications in the Absence of Adverse Events
In the absence of adverse events, subjects will complete their scheduled injection as prescribed 
by protocol. A subject’s scheduled dosing may be administered within ± 2 days of the target day 
to adjust for the subject’s and/or the site personnel’s convenience.

If the study medication cannot be administered within 2 days of the target date, that 
scheduled dose should be skipped, which means subject will miss one (1) dose. The next 
dose of study medication should then be administered on the next targeted administration day
(2 days) as originally planned. For example, the Day 15 dose could not be administered 
until Day 17 and subject comes to the study site to receive it on Day 19. The planned Day 15
dose should not be given at Day 19 and the next dose will be administered on Day 22
(2 days). In this example, one missed dose will be reported in the eCRF.
Dose Modifications for Adverse Events
If there is evidence of toxicity (eg, abnormal laboratory tests or clinical adverse events) that, in 
the judgment of the Investigator, could place the subject at increased risk, study drug 
administration should be interrupted. Subjects may be considered eligible to receive further study 
medication treatment only if full resolution of the adverse event is documented, as follows: 

If the adverse event completely resolves and the study medication is administered within 
2 days of the target date, the next dose should be administered on the originally planned 
dosing day with no missed doses.

If the adverse event completely resolves but study medication cannot be administered within 
2 days of the target date, that scheduled dose should be skipped (which means subject will 
miss one (1) dose). The next dose of study medication should then be administered on the 
next targeted administration day as originally planned (2 days). For example, the Day 15
dose could not be administered until Day 17 and adverse event resolution occurs on Day 19. 
The planned Day 15 dose should not be given at Day 19 and the next dose will be 
administered on Day 22 (2 days). In this example, one missed dose will be reported in the 
eCRF.
4.5.3
Corticosteroids (Prednisone or Prednisone Equivalent) Dosing

Prior to Randomization: Corticosteroids (prednisone or prednisone equivalent; refer to 
Appendix 1) may be used in accordance with the Investigator’s clinical judgment and best 
standard of care. A maximum daily dose of 30mg/day is acceptable to be eligible for the 
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Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
study and start screening; however, daily dose must be tapered down to a maximum of 
10mg/day for at least 5 days prior to Day 1 (randomization day).

Study Day 1 (randomization day): subjects requiring the use of prednisone (or prednisone 
equivalent) will be on a maximum dose of 10mg/day.

Post Day 1 (after initiation of study therapy): 

For subjects who flare or need to increase their prednisone (or prednisone equivalent) to 
control disease activity a one-time increase of up to a maximum daily dose of 20 mg/day
for up to 2 consecutive days will be allowed to transiently manage disease activity.

A subject who requires a total daily dose of prednisone (or prednisone equivalent) 
exceeding 20 mg/day or who has another flare after the first rescue therapy, will be 
considered a treatment failure.

A subject who meets the treatment failure criteria as described above may continue on 
study medication; however, a subject requiring more than 20 mg/day of prednisone 
(or prednisone equivalent) for more than 7 days in the short-term period, or more than 
14 days in the long-term extension period, will be discontinued.
Tapering of steroids during the course of the study is encouraged and should be evaluated 
at all visits. Once subject has received the first dose of study drug, prednisone 
(or prednisone-equivalent) may be tapered down at the discretion of the Investigator.
4.5.4
Rescue Therapy
4.5.4.1
Short- Term Period
A one-time increase of up to a maximum daily dose of 20 mg/day for up to 2 consecutive days 
will be allowed to transiently manage disease activity and will not be considered a treatment 
failure. 

A subject who requires a total daily dose of prednisone (or prednisone equivalent) 
exceeding 20 mg/day or who has another flare after the first rescue therapy, will be 
considered a treatment failure. 

A subject who meets the treatment failure criteria based on prednisone use may continue 
on study medication; however, a subject requiring more than 20 mg/day of prednisone 
(or prednisone equivalent) for more than 7 days in the short-term period, will be 
discontinued.
The use of rescue therapies other than prednisone (or prednisone equivalent), such as 
cyclophosphamide, any intravenous, any intra-articular or biologic agent is prohibited.
Any changes to or new concomitant therapies must be recorded on the CRF.
4.5.4.2
Long-Term Extension Period
The class and dose of background therapies is recommended to remain the same as in the short 
term period. However, temporary rescue therapy with prednisone (or prednisone equivalent) to 
transiently manage SLE disease activity may be instituted. The increase in prednisone should not 
2.0
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Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
exceed a total daily dose of 20 mg, and must return to the previous stable dose within 14 days. 
Subjects requiring more than 20 mg/day for more than 14 days of rescue therapy will be 
discontinued from the LTE.
The use of rescue therapies other than prednisone (or prednisone equivalent), such as 
cyclophosphamide, any intravenous, any intra-articular or biologic agent remains prohibited 
during LTE. 
Any changes to or new concomitant therapies must be recorded on the CRF.
4.6
Blinding/Unblinding
4.6.1
Blinding at the Study Sites
The subjects and clinical assessor(s) will not be aware of which treatment is being administered 
to the subjects enrolled in the study. The pharmacist (or qualified drug preparation person) will 
be unblinded to study medication (BMS-931699 or placebo).
The pharmacist (or qualified drug preparation person) will know the randomization assignments 
and prepare the appropriate dose of active BMS-931699 or placebo accordingly. The prepared 
drug must be supplied to study personnel in a manner such that neither study personnel nor 
subjects will be aware of whether they receive active drug or placebo.
4.6.2
Unblinding of the Study Sites
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 investigatory always has ultimate authority for 
the decision to unblind. The Principal Investigator should only call in for emergency unblinding 
AFTER the decision to discontinue the subject has been made.
For this study, the method of unblinding for emergency purposes is IVRS.
For information on how to unblind in an emergency, consult the IVRS manual.
In cases of accidental unblinding, contact the Medical Monitor and ensure every attempt is made 
to preserve the blind.
Any request to unblind a subject for non-emergency purposes should be discussed with the 
Medical Monitor.
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Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
In case of an emergency, the Investigator(s) has unrestricted access to randomization information 
via the Interactive Voice Response System (IVRS) and is capable of breaking the blind through 
the IVRS system without prior approval from sponsor. Following the unblinding the Investigator 
shall notify the Medical Monitor and/or Study Director.
4.7
Treatment Compliance
Subject will be dosed at the study site where documentation of injection and compliance will be 
maintained.
4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as 
partially used study drug containers, vials and syringes may be destroyed on site. 
Any unused study drugs can only be destroyed after being inspected and reconciled by the 
responsible BMS Study Monitor unless study drug containers must be immediately destroyed as 
required for safety, or to meet local regulations (eg, cytotoxics or biologics). 
On-site destruction is allowed provided the following minimal standards are 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.
If conditions for destruction cannot be met the responsible BMS Study Monitor will make 
arrangements for return of study drug.
It is the investigator’s responsibility to arrange for disposal of all empty containers, 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.
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused 
and/or partially used study drug that was supplied by BMS must be returned to BMS. The return 
of study drug will be arranged by the responsible Study Monitor. 
Arrangements for the return of study drug will be made by the responsible Study Monitor.
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Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Retained Samples for Bioavailability / Bioequivalence
Not applicable
5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Study assessments and procedures are presented in Table 5.1-1, Table 5.1-2 and Table 5.1-3. 
These study assessments apply to all subjects, whether they are included in Part 1 or Part 2 
of this study.
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Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-1:
Screening Procedural Outline (IM128027)
Procedure
Screening
Visit
Notes
Eligibility Assessments
Informed Consent
X
A subject is considered enrolled/screened only when a protocol specific informed consent is signed.
Enroll subject (contact IVRS)
X
Inclusion/Exclusion Criteria
X
Medical history
X
Include any toxicities or allergy related to previous treatments.
ACR criteria for SLE form
X
See Appendix 3
BILAG-2004 Index
X
See Appendix 4
SLEDAI-2K
X
See Appendix 5
Physician’s Global Assessment of 
Disease Activity
X
ACR28 - joint count
X
CLASI
X
See Appendix 6
Coomb’s test-direct
X
Stabilize/Withdraw prohibited 
medications (if necessary)
X
Safety Assessments
X
Physical Examination (PE)
X
Include breast physical exam. See Section 5.3.4 of the protocol for more details
Physical Measurements
X
Includes height and weight
Vital Signs
X
Includes body temperature, respiratory rate, seated and standing blood pressure and heart rate. 
Blood pressure and heart rate should be measured after the subject has been resting quietly for at 
least 5 minutes.
Electrocardiogram (ECGs)
X
ECGs should be recorded after the subject has been supine for at least 5 minutes. 
Chest x-ray (CXR)
X
No need to repeat if chest x-ray performed within 6 months of screening and documentation of the 
results is available at the site.
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Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-1:
Screening Procedural Outline (IM128027)
Procedure
Screening
Visit
Notes
Confirm and document that breast cancer 
and cervical cancer screening are up to 
date according to local guidelines 
(females only)
X
Laboratory safety tests
X
Includes blood and urine samples. Subjects are required to fast for at least 10 hours prior to the 
collection of specimens for clinical laboratory tests.
Spot urine for protein/creatinine ratio
X
TB screening
X
In accordance with BMS standard testing. See Section 5.3.3 of the protocol for more details.
Hepatitis B surface antigen and Hepatitis 
C antibody
X
CMV and EBV
X
Serum complement (C3, C4)
X
ANA, Anti ds-DNA antibodies and Sm 
auto-antibodies
X
HIV
X
Urine Drug Test
X
Pregnancy Test (for WOCBP only)
X
Serum pregnancy test to be performed only if urine test is positive or un-interpretable
Adverse Event Reporting
X
Monitor for Serious Adverse Events
X
All SAEs must be collected from the date of subject’s written consent until 42 days post 
discontinuation of dosing or completion of subject’s participation in the study if the last scheduled 
visit occurs at a later time.
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v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-2:
Short-Term Procedural Outline (IM128027)
Procedure / Visit Day
(2 days is allowed for all 
visits, including Day 1)
D 1
D 15 
D 29
D 57
D 85
D 113
D 141
EOT 
/ 
D 169
FU
D 42*
(FUP 
no.1 
visit) 
Dosing 
Every Week 
(in addition 
to Visits 
assessing 
disease 
activity)
Notes
Confirm inclusion and 
exclusion criteria are met 
prior to dosing
X
Efficacy Assessments
BILAG-2004 Index
X
X
X
X
X
X
X
X
See Appendix 4
SLEDAI 2K
X
X
X
X
X
X
X
X
See Appendix 5
Physician’s Global 
Assessment of Disease 
Activity (MDGA)
X
X
X
X
X
X
X
X
Subject’s Global Assessment 
of Disease Activity (PGA)
X
X
X
X
X
X
X
X
ACR28 - joint count
X
X
X
X
X
X
X
X
FACIT - F
X
X
X
X
X
X
X
X
X
See Appendix 9
CLASI
X
X
X
X
X
X
X
X
See Appendix 6
SLICC/ACR Damage Index
X
X
See Appendix 7
SF-36
X
X
X
X
X
X
X
X
See Appendix 8
Coomb’s test-direct
X
X
X
X
X
X
X
X
Safety Assessments
Targeted PE
X
X
X
X
X
X
X
X
X
See Section 5.3.4 of the 
protocol for more details
2.0
Approved
930080471
2.0
v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-2:
Short-Term Procedural Outline (IM128027)
Procedure / Visit Day
(2 days is allowed for all 
visits, including Day 1)
D 1
D 15 
D 29
D 57
D 85
D 113
D 141
EOT 
/ 
D 169
FU
D 42*
(FUP 
no.1 
visit) 
Dosing 
Every Week 
(in addition 
to Visits 
assessing 
disease 
activity)
Notes
Spot urine for protein / 
creatinine ratio
X
X
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
X
X
X
Includes body temperature, 
respiratory rate, seated and 
standing blood pressure and 
heart rate. Blood pressure and 
heart rate should be measured 
after the subject has been 
resting quietly for at least 
5 minutes.
ECGs
X a
X
X
a ECG must be performed 
prior to dosing on Day 1
Urine Pregnancy Test 
(WOCBP only)
Xb
X
X
X
X
X
X
Xc
X
b Negative pregnancy test 
must be confirmed within 
24hrs prior to dosing. 
c WOCBP patients must be 
sent home with a home 
pregnancy kit to self-
performed approximately 
28days after the Day 169 
visit.
- Serum pregnancy test to be 
performed only if urine test is 
positive or un-interpretable
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Approved
930080471
2.0
v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-2:
Short-Term Procedural Outline (IM128027)
Procedure / Visit Day
(2 days is allowed for all 
visits, including Day 1)
D 1
D 15 
D 29
D 57
D 85
D 113
D 141
EOT 
/ 
D 169
FU
D 42*
(FUP 
no.1 
visit) 
Dosing 
Every Week 
(in addition 
to Visits 
assessing 
disease 
activity)
Notes
Laboratory safety tests
X
X
X
X
X
X
X
X
X
Include blood and urine 
samples. Subjects are 
required to fast for at least 
10 hours prior to the 
collection of specimens for 
clinical laboratory tests.
CMV and EBV
X
X
Adverse Event Reporting
Monitor for Non-Serious 
Adverse Events
X
X
X
X
X
X
X
X
X
X
Monitor for Serious Adverse 
Events
X
X
X
X
X
X
X
X
X
X
All SAEs must be collected 
from the date of subject’s 
written consent until 42 days 
post discontinuation of dosing 
or completion of subject’s 
participation in the study if 
the last scheduled visit occurs 
at a later time.
PK Assessments
PK Sampling
X
X
X
X
X
X
X
X
X
See Table 5.5.3 for additional 
PK collection instructions.
2.0
Approved
930080471
2.0
v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-2:
Short-Term Procedural Outline (IM128027)
Procedure / Visit Day
(2 days is allowed for all 
visits, including Day 1)
D 1
D 15 
D 29
D 57
D 85
D 113
D 141
EOT 
/ 
D 169
FU
D 42*
(FUP 
no.1 
visit) 
Dosing 
Every Week 
(in addition 
to Visits 
assessing 
disease 
activity)
Notes
Immunogenicity 
(anti-BMS-931699 antibody)
X
X
X
X
X
X
 
 
 
 
 
 
 
 
 
 
 
 
 
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v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-2:
Short-Term Procedural Outline (IM128027)
Procedure / Visit Day
(2 days is allowed for all 
visits, including Day 1)
D 1
D 15 
D 29
D 57
D 85
D 113
D 141
EOT 
/ 
D 169
FU
D 42*
(FUP 
no.1 
visit) 
Dosing 
Every Week 
(in addition 
to Visits 
assessing 
disease 
activity)
Notes
Serum cytokines and 
 
 
Abbreviations: D = Day, EOT = End of Treatment
* Only to be performed if subject is discontinued early or if subject is not entering the LTE after completing 24-weeks of study medication
2.0
Approved
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2.0
v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-3:
Long-term Extension Procedural Outline (IM128027)
Procedure / Visit Day
(2 days is allowed for all visits, 
including LTE Day 1)
LTE
Day 11
Monthly 
Visits2
Every 3 
Months 
Visits2
EOT
in 
LTE
FU
Day 42
After 
EOT
Dosing Every 
Week (in 
addition to
Office Visits)3
Notes
 
 
 
Efficacy Assessments
BILAG-2004 Index
X*
X
X
X
See Appendix 4
SLEDAI 2K
X*
X
X
X
See Appendix 5
Physician’s Global Assessment of 
Disease Activity (MDGA)
X*
X
X
X
Subject’s Global Assessment of 
Disease Activity (PGA)
X*
X
X
X
ACR28 - joint count
X*
X
X
X
FACIT - F
X*
X
X
X
See Appendix 9
CLASI
X*
X
X
X
See Appendix 6
SLICC/ACR Damage Index
X*
X
X
See Appendix 7
SF-36
X*
X
X
X
See Appendix 8
Coomb’s test-direct
X*
X
X
X
Safety Assessments
Targeted PE
X*
X
X
X
See Section 5.3.4 of the 
protocol for more details
Spot urine for protein / creatinine ratio
X*
X
X
X
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v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-3:
Long-term Extension Procedural Outline (IM128027)
Procedure / Visit Day
(2 days is allowed for all visits, 
including LTE Day 1)
LTE
Day 11
Monthly 
Visits2
Every 3 
Months 
Visits2
EOT
in 
LTE
FU
Day 42
After 
EOT
Dosing Every 
Week (in 
addition to
Office Visits)3
Notes
Vital Signs
X*
X
X
X
X
Includes body temperature, 
respiratory rate, seated and 
standing blood pressure and 
heart rate. Blood pressure 
and heart rate should be 
measured after the subject 
has been resting quietly for 
at least 5 minutes.
Urine Pregnancy Test (WOCBP only)
X*
X
X
X
b Negative pregnancy test 
must be confirmed within 
24hrs prior to dosing. 
c WOCBP patients must be 
sent home with a home 
pregnancy kit to self-
performed approximately 
28days after receiving their 
last dose of study 
medication.
- Serum pregnancy test to be 
performed only if urine test 
is positive or un-
interpretable
2.0
Approved
930080471
2.0
v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-3:
Long-term Extension Procedural Outline (IM128027)
Procedure / Visit Day
(2 days is allowed for all visits, 
including LTE Day 1)
LTE
Day 11
Monthly 
Visits2
Every 3 
Months 
Visits2
EOT
in 
LTE
FU
Day 42
After 
EOT
Dosing Every 
Week (in 
addition to
Office Visits)3
Notes
Laboratory safety tests
X*
X
X
X
Include blood and urine 
samples. Subjects are 
required to fast for at least 
10 hours prior to the 
collection of specimens for 
clinical laboratory tests.
Adverse Event Reporting
Monitor for Non-Serious Adverse 
Events
X*
X
X
X
X
Monitor for Serious Adverse Events
X*
X
X
X
X
All SAEs must be collected 
from the date of subject’s 
written consent until 42 
days post discontinuation of 
dosing or completion of 
subject’s participation in the 
study if the last scheduled 
visit occurs at a later time.
PK Assessments
PK Sampling
X*
X*
X
X
* PK Samples will be 
collected every 3 months 
during the LTE period, 
based on 1st dose received 
in LTE.
PK samples will also be 
collected at EOT whenever 
it occurs, despite of visit 
schedule.
2.0
Approved
930080471
2.0
v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-3:
Long-term Extension Procedural Outline (IM128027)
Procedure / Visit Day
(2 days is allowed for all visits, 
including LTE Day 1)
LTE
Day 11
Monthly 
Visits2
Every 3 
Months 
Visits2
EOT
in 
LTE
FU
Day 42
After 
EOT
Dosing Every 
Week (in 
addition to
Office Visits)3
Notes
Immunogenicity 
(anti-BMS-931699 antibody)
X*
X**
X
X
** Immunogenicity Samples 
will be collected every 3 
months during the LTE 
period, based on 1st dose 
received in LTE. 
Immunogenicity samples 
will also be collected at 
EOT whenever it occurs, 
despite of visit schedule.
 
 
 
2.0
Approved
930080471
2.0
v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Table 5.1-3:
Long-term Extension Procedural Outline (IM128027)
Procedure / Visit Day
(2 days is allowed for all visits, 
including LTE Day 1)
LTE
Day 11
Monthly 
Visits2
Every 3 
Months 
Visits2
EOT
in 
LTE
FU
Day 42
After 
EOT
Dosing Every 
Week (in 
addition to
Office Visits)3
Notes
 
 
  
 
Abbreviations: D = Day, EOT = End of Treatment
1 Study procedures performed on Day 169 of the Short-Term period will be used as the starting point for LTE Day 1 procedures. They do not need to be performed twice. These are marked with an 
asterisk star (*).
2 Starting point for calculating the visits in LTE is the day subject performs Day 1 of the LTE.
3 Weekly SC injection required until Futility Interim Analysis. Frequency may change after the Futility Interim Analysis.
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Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
5.1.1
Retesting During Screening
5.1.2
Period
A single-retesting of laboratory parameters and/or other assessments during Screening period 
will be permitted (in addition to any parameters that require a confirmatory value), only if 
medically indicated, if there is evidence a laboratory sample was mislabeled, was inadequately 
processed and/or deteriorated in transit to the central laboratory.
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. This will also apply to subjects who are being re-screened.
5.2
Study Materials
The site will provide all required materials for the tests performed locally (ie, relevant clinical 
laboratory tests). The site will have available a well-calibrated scale for recording body weight, a 
12-lead ECG machine, and a calibrated sphygmomanometer and thermometer for vital signs 
assessments. The site will have urine collection containers, a centrifuge, a heated plaque, a 
monitored and alarmed refrigerator, and freezer (-20°C or below), as well as containers and dry 
ice for shipment and storage of blood and urine samples. The site will provide all materials 
required for accurate source documentation of study activities.
BMS will provide a BMS-approved protocol and any amendments or administrative letters 
(if required), and investigator brochure. Case report forms (electronic or hard copy) will be 
provided by BMS. Ten centimeter rulers will be provided by BMS for measurement of the 
Physician and Subject’s Global Assessment of disease activity on the Case Report Form.
All Investigator sites within this study will use an Electronic Data Capture (EDC) tool to submit 
study data to BMS. Electronic Case Report Forms (eCRFs) will be prepared for all data 
collection fields at Investigator sites, except for fields specific to Pregnancy Forms. Pregnancy 
Forms will be submitted to BMS using paper CRFs. Subject Quality of Life Questionnaires will 
be completed by the subject and the information will then be entered with the EDC tool by the 
investigational site staff. Physician Global Assessment of disease activity worksheet will be 
completed by the investigator and will then be entered with the EDC tool. Subject completed 
Quality of Life Questionnaires will be retained at the investigational site. 
Study supplies and documents (eg, electronic Case Reports Forms, patient drug logs, etc.) will be 
provided to the study center by BMS. Urine pregnancy test kits, laboratory specimen collection 
kits and instructions for collection will be provided by central laboratory vendor. IVRS 
worksheets and instruction manuals will be provided by the IVRS vendor.
5.3
Safety Assessments
On Day 1, the results of all assessments must be reviewed to assure that eligibility requirements 
are met before contacting the Central Randomization System for the subject’s randomization 
assignment.
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930080471
2.0
v


Clinical Protocol
IM128027
BMS-931699
lulizumab pegol
Subjects who discontinue from the double-blind treatment period should have “End of Treatment 
Visit” procedures performed and should return to the clinical for the “Follow-Up Visit” 
approximately 42 days after the “End of Treatment Visit”. All procedures required for these 
visits should be completed as well as collection of concomitant medication information.
All assessments should be performed or administered prior to study drug administration 
unless otherwise indicated. Furthermore, patient’s assessments (ie FACIT-F, SF-36 and 
Subject’s Global Assessment) must be performed prior to all other assessments.
Every effort must be made to ensure the same evaluator will complete the assessments for each 
subject at all visits.
Only data for the procedures and assessments specified in this protocol should be submitted to 
BMS on a case report form. Additional procedures and assessments may be performed as part of 
your institutional or medical practice standard of care; however, data for these assessments 
should remain in the subject’s medical record and should not be provided to BMS, unless 
specifically requested from the sponsor.
Safety Outcome Measures: Safety assessments will be based on medical review of adverse 
event reports and the results of vital sign measurements, ECGs, physical examinations, and 
clinical laboratory tests. The incidence of observed adverse events will be tabulated and 
reviewed for potential significance and clinical importance.
Ongoing assessment of safety will be performed by an independent Data Monitoring Committee 
(DMC) and an internal safety monitoring team. Both entities may make recommendations to the 
Sponsor regarding conduct of study and dose adjustment based on safety observations.
Titers of anti-CMV and EBV antibodies will be obtained at baseline, 12 weeks and 24 weeks to 
monitor for viral reactivation.
5.3.1
Imaging Assessment for the Study
Not applicable.
5.3.2
Laboratory Test Assessments
For the short-term period (Part 1 and Part 2), a central laboratory will perform the analyses and 
will provide reference ranges for these tests.
Clinical Laboratory Testing
Blood and/or urine samples will be obtained prior to injection at all visits from each subject 
entered in this study. Any laboratory test result that the Investigator considers clinically 
relevant should be recorded on the appropriate Adverse Event page of the CRF
(see Section 6.3 Laboratory Test Result Abnormalities).
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For the Lipid Panel, a fasting sample is required. At least 10 hours prior to the collection 
time, subjects should not consume food; only water is allowed. Subjects with an abnormal Lipid 
Panel may be referred back to their primary care provider for further management if warranted.
Urine or serum pregnancy tests will be performed within 24 hours prior to dosing, for all 
WOCBP. If any female subject becomes pregnant she will be immediately discontinued from the 
study.
If a WOCBP advises the investigational staff that she has had amenorrhea for 12 consecutive 
months while the study is ongoing and menopause is a diagnostic consideration, a serum follicle 
stimulating hormone (FSH) level should be taken and testing performed at the central laboratory 
to determine if her FSH level is > 40 mIU/mL. After the level has been confirmed and the 
diagnosis of menopause has been determined by a treating physician, pregnancy testing at each 
visit will no longer be required for the subject as she is no longer of child-bearing potential. 
If additional or follow-up monitoring of subject safety, eg, potential toxicity or features of 
active SLE is required, the investigator may obtain samples for additional laboratory tests 
if deemed necessary after discussion with the BMS study team.
Hematology (CBC)
Hemoglobin
Hematocrit
Platelet count 
Total WBC count, including differential
RBC
Total Iron Binding Capacity
Manual differential (separate smear) and Reticulocyte count
Blood Chemistry (Chemistry Panel):
Sodium 
Creatinine
Potassium 
Blood urea nitrogen (BUN)
Chloride 
Total bilirubin
Total Protein 
Direct Bilirubin
Albumin 
Alanine aminotransferase (ALT)
Calcium 
Aspartate aminotransferase (AST)
Phosphorous 
Gamma-glutamyltransferase (GGT)
Glucose 
Alkaline phosphatase
Creatine Kinase
Lipid Panel (Fasted Sample Mandatory):
Total-Cholesterol 
HDL-Cholesterol
LDL-Cholesterol 
Triglycerides
Coomb’s test-direct
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Tuberculosis test (performed at screening only)
Urine drug screen (performed at screening only)
Serum complement:
C3
C4
Urine sample (clean catch):
pH
Protein
Glucose
Blood
Microscopic examination for Cells, Casts, Bacteria 
Spot urine collection:
Urine protein
Urine creatinine
Hepatitis screen (performed at screening only):
Hepatitis B surface antigen

if positive, reflex to HBV DNA PCR (Hepatitis B Virus PCR)

Hepatitis B core antibody

if positive, reflex to HBV DNA PCR (Hepatitis B Virus PCR)

Hepatitis C Virus antibody

if low- positive, reflex to HCV RNA PCR (Hepatitis C Virus), quantitative
Subjects with positive PCR (defined as ANY detected virus, not as > LLQ) will be designated as 
Screen Failure.
HIV screen: antibody anti-HIV 1 and 2 (performed at screening only):
Cytomegalovirus (CMV) (Short-Term Treatment period only)
Epstein-Barr virus (EBV) (Short-Term Treatment period only)
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. If any female subject becomes 
pregnant, she will be discharged from the study. Urine pregnancy tests will be processed locally. 
FSH test will be performed for female subjects who become menopausal after entry into the trial.
Immunoglobulin Determination:
Quantitative Immunoglobulins (IgG, IgA, IgM)
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Autoimmune Serology:
Anti-nuclear antibody 
Anti-double stranded (ds) DNA antibodies
Antiphospholipid antibodies (IgG, IgA, IgM)
Anti-Ro (SS-A) antibodies
Anti-La (SS-B) antibodies
Anti-RNP antibodies
Anti-Sm antibodies
Serum Proteomics (cytokines, chemokines): Serum SST tube
Whole Blood RNA Collection: Blood samples in PAXgene® tubes
Urine Proteomics Collection: 100mL urine (Short-Term period only)
Leukocyte phenotype: Peripheral blood sample (Short-Term period only)
PBMC collection (except in Asia and South Africa since transition time between site and 
analyzing laboratory is expected to exceed the stability of the sample). (Short-Term period only)
Receptor Occupancy (RO): Peripheral blood sample
Immunogenicity determination: Anti-BMS-931699 antibody
In addition, the investigator will obtain samples for additional laboratory tests if deemed 
necessary for monitoring subject safety, eg, potential toxicity or features of active SLE.
Blood and Urine Specimen Collection, Processing and Shipping 
Detailed instructions on the collection, processing and shipping of all blood and urine samples 
will be provided to the Investigator in a separate manual at or before the time of study initiation.
5.3.3
Tuberculosis Screening and Chest X-Ray
A chest x-ray (CXR) and physical examination (PE) are considered part of the process to assess a 
subject’s eligibility as outlined in Section 3.3.2.
CXR at the screening visit is required if not already performed within 6 months of obtaining 
written informed consent or if documentation is not on file.
In addition to a complete physical examination and medical history to evaluate exposure to 
tuberculosis, all subjects will have a screening test, an interferon gamma release assay 
[(IGRA) eg, T-spot®, QuantiFERON®], preferably performed centrally. If unable to obtain 
central lab results (eg, repeated test due to indeterminate result), an IGRA test could be obtained 
locally, after consultation with the study medical monitor.
Subjects with a positive screening test will not be eligible for the study unless they have 
completed at least four (4) weeks of treatment for latent TB prior to dosing of study drug, and the 
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subject has a negative chest X-ray done at screening that reveals no evidence of active TB and a 
negative IGRA test (Quantiferon or T-Spot) is confirmed prior to Day 1.
5.3.4
Physical Examination
Complete and/or interim physical examinations may be performed by a Doctor of Medicine 
(MD), or someone who is authorized to perform the examinations by training and has been 
delegated this task by the principal investigator. While the interim physical examination may not 
be as comprehensive as the initial full examination, key aspects of the interim examination 
should evaluate important body systems as clinically indicated. These body systems can include 
lymph nodes, liver, spleen, and breast at the discretion of the examiner. An interim physical 
examination may note any changes in the subject’s condition (body systems) since the last 
assessment and does not preclude examination of any of the body systems as clinically indicated.
Every effort should be made to ensure the same evaluator will complete the physical examination 
for each subject at all visits throughout the study. Documentation of who performed the 
examination is to be recorded in source notes.
5.4
Efficacy Assessments
Clinical assessments of response should be performed by the same assessor(s) and at 
approximately the same time of day throughout the duration of the study. 
5.4.1
Primary Efficacy Assessment
5.4.1.1
Short-Term Period
Primary efficacy assessment is a composite endpoint, the BICLA, which includes BILAG-2004, 
SLEDAI-2K (30 day)20, Physician Global Assessment of disease activity (MDGA) and no 
treatment failure. The BILAG-2004 index was selected as the central score on the basis of its 
comprehensiveness, ability to capture partial improvement, and the clinical relevance of its 
scoring system. BILAG assessments will be performed by the investigators, and grades will be 
determined by an independent central reader group.
5.4.1.2
Long-Term Extension Period
Primary efficacy assessments during the long-term extension will be the same as in the 
short-term period, in order to assess long-term durability of response.
5.4.2
Secondary Efficacy Assessments
5.4.2.1
Short-Term Period
Training and instruction on BILAG 2004 index assessment will be provided and discussed at the 
Investigator’s Meeting or at workshops. The response measure (BILAG) will be reviewed and 
discussed with the investigational staff at the Investigator Meeting or other forum as a method of 
standardizing the grading between the investigational staffs. All Investigative site personnel 
performing BILAG evaluations must be trained and certified. 
The BILAG index measures and reports disease activity in different organs/systems separately. 
The BILAG score is calculated for each of nine systems depending on the clinical features 
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present and whether they are new, worse, the same or improving in the last 4 weeks compared 
with previously. A BILAG “A” represents the presence of one or more serious features of lupus. 
A BILAG “B” represents more moderate features of the disease. A BILAG “C” includes only 
mild symptomatic features. A BILAG “D” represents only prior activity with no current 
symptoms due to active lupus. A BILAG “E” represents an organ that has never been involved. 
Assessments used to determine BILAG score must be performed by the Investigator, or a 
BILAG certified (an individual who has passed the BMS sponsored BILAG Certification Test) 
Sub-Investigator. The Sub-Investigator may be a Doctor of Medicine (MD), or someone who is 
authorized to perform the examinations by training and has been delegated this task by the 
principal investigator. Changes in therapy based on any clinical or laboratory assessment must be 
approved by the Investigator or a MD/DO Sub-Investigator.
5.4.2.2
Long-Term Extension Period
Secondary efficacy assessments during the long-term extension will be the same as in the short-
term period, in order to assess long-term durability of response.
5.5
Pharmacokinetic Assessments
5.5.1
Short-Term Period
Pharmacokinetics of BMS-931699 will be derived from serum concentration versus time data. 
The pharmacokinetic parameters to be reported include Ctrough (ng/mL), which will be 
measured from serum samples collected as defined Table 5.5.3.
Additional blood samples will be obtained according to Table 5.5.3, which specifies pre-dose 
samples as well as post-dose samples on Day 46 and Day 48. If both post-dose samples cannot 
be obtained at these times (ie, Days 46 + Day 48), the 2 samples may be obtained on (Days 60 + 
Day 62) OR (Days 74 + Day76). 
Population PK (PPK) analysis maybe performed using PK data from the current proposed study 
in SLE patients. Results of the PPK analysis may also be used to characterize the 
exposure-response (E-R) relationship in BMS-931699 by means of the individual model 
predicted exposure and efficacy/safety data. Further, the effect of covariates (demographic and 
clinical) on efficacy/safety may be explored in the E-R analyses. Results of the PPK and E-R 
analyses will be reported separately if performed.
5.5.2
Long-Term Extension Period
Immunogenicity and PK blood samples will be obtained every three months during the LTE 
period. 
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5.5.3
Pharmacokinetics: Collection and Processing
Table 5.5.3 lists the sampling schedule to be followed for the assessment of pharmacokinetics. 
Further details of blood collection and processing will be provided to the site in the procedure 
manual.
Table 5.5.3:
Pharmacokinetic Sampling Schedule for BMS-931699
Study Day of 
Sample Collection
Event
Time 
(Relative To BMS-
931699 Dose)
Hour: Min
BMS-931699
Pharmacokinetic Blood 
Sample
BMS-931699
Immunogenicity 
Sample
1
Pre-dose
00:00
X
X
15
Pre-dose
00:00
X
X
29
Pre-dose
00:00
X
X
43
Pre-dose
00:00
X
46 (1 day)a
72:00
X
48 (1 day) a
120:00
X
50
Pre-dose 
00:00
X
57
Pre-dose
00:00
X
64
Pre-dose
00:00
X
71
Pre-dose
00:00
X
78
Pre-dose
00:00
X
85
Pre-dose
00:00
X
X
113
Pre-dose
00:00
X
141
Pre-dose
00:00
X
169/End of 
Treatment
168:00
X
X
Long-term extension
Pre-dose
Every 3 months
X
X
Follow up Day 42
after EOT
42 Days after end of 
treatment
X
X
AEb
X
X
a Day 46 and Day 48 post-dose PK samples are planned for the same dosing interval. A dosing interval is the time 
between two doses, in this study, dosing interval is a week. Sites should plan ahead with patients to ensure these 
samples are collected during the same dosing interval. If patients cannot have post-dose PK samples collected on 
Day 46 and Day 48, the 2 samples may be obtained on (Day 60 +Day 62) OR (Day 74 + Day 76). The exact 
dosing time and sampling time should be recorded accordingly.
b PK and immunogenicity samples to be drawn for subjects who experience an AE leading to discontinuation of 
study treatment. 
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5.5.4
Pharmacokinetic Sample Analyses
The serum samples will be analyzed for BMS-931699 by a validated LC-MS/MS assay. 
Pharmacokinetic samples collected from a subject who received placebo will not be analyzed.
In addition, serum samples will be archived for potential exposure biomarker response analysis, 
if the need arises and to the extent possible.
5.5.5
Immunogenicity Assessments
The immunogenic potential of the study medication will be assessed based on levels of 
anti-BMS-931699 antibodies. Serum samples will be obtained at visits defined in Table 5.1-3. 
Only samples from the active treatment arms will be analyzed.
Validated sensitive, electrochemiluminescence (ECL) immunoassay method will be used to 
measure titers of anti- BMS-931699 antibodies in serum.
5.5.6
Labeling and Shipping of Biological Samples
Detailed instructions for the pharmacokinetic blood collection, labeling, processing, storage, and 
shipping will be provided to the site in the laboratory manual.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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.
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.
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 
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questioned regarding the specific occurrence of one or more AEs). BMS, as sponsor of the study, 
commits to declare safety events in accordance with the regulation in force in each country.
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

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)
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
medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (eg, lack of housing, economic 
inadequacy, caregiver respite, family circumstances, administrative reason).

Admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the Investigator 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 42 days of discontinuation of dosing.
The investigator should 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 should 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 should 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 BMS 
(or designee) within 24 hours. 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. The paper forms should be used and submitted immediately, only 
in the event the electronic system is unavailable for transmission. When paper forms are used, 
the original paper forms are to remain on site.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports should include the same investigator term(s) initially reported.) 
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If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, a follow-up SAE report should be sent within 24 hours to the BMS 
(or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs should be followed to resolution or stabilization.
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 (paper or electronic) as appropriate:

Any laboratory test result that is clinically significant or meets the definition of an SAE 

Any laboratory test result abnormality that required the subject to have study drug 
discontinued or interrupted

Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy.
It is expected that whenever 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 investigational product, 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 BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance 
Form to BMS Designee within 24 hours and in accordance with SAE reporting procedures 
described in Section 6.1.1.
If any female subject becomes pregnant she will be immediately discontinued from the study. 
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In the rare event that the benefit of continuing study drug is thought to outweigh the risk, after 
consultation with BMS, the pregnant subject may continue study drug after a thorough 
discussion of benefits and risk with the subject.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (eg, x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated.
The investigator must immediately notify the BMS (or designee) Medical Monitor of this event 
and complete and forward a Pregnancy Surveillance Form to BMS (or designee) within 24 hours 
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 
BMS. 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)
Whenever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, 
meeting the defined criteria, must be reported as SAEs (see Section 6.1.1 for reporting details).
Potential drug induced liver injury is defined as: 
1. AT (ALT or AST) elevation > 3 times upper limit of normal (ULN)
AND 
2. Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND 
3. No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic.
6.7
Other Safety Considerations
Any 
significant 
worsening
noted 
during 
interim 
or 
final 
physical 
examinations, 
electrocardiogram, x-ray filming, any other potential safety assessment required or not required 
by protocol should also be recorded as a nonserious or serious AE, as appropriate, and reported 
accordingly.
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6.7.1
AE’s of Special Interest
Although there are no identified risks for BMS-931699, BMS has developed a list of events of 
special interest for the BMS-931699 program based on the known biologic class effects, the 
mechanism of action of BMS-931699, overall potential consequences of immunosuppression, 
and preliminary data from unblinded clinical trials. Event categories of special interest for this 
study may include, but are not limited to:

Infections

Autoimmunity

Malignancies

Injection-related reactions
Note: Another event of special interest based on the biologic class effect, albeit not an adverse 
event in itself, is Immunogenicity, which will be monitored during the entire study. Adverse 
events in subjects who develop anti-BMS-931699 antibodies will be monitored as AE’s of 
special interest.
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
An external Data Monitoring Committee (DMC) will be used in this study. The Committee’s 
scope of responsibility will be limited to monitoring safety by masked treatment group; 
Committee may request treatment codes and/or efficacy summaries if indicated for safety/benefit 
assessment. The Committee will comprise 1 biostatistician and 2 clinicians with expertise in 
SLE.
Data summaries and listings will be provided to the DMC to facilitate their safety and efficacy 
assessment at the regularly scheduled times as well as on an ad hoc basis if needed. DMC data 
monitoring will commence when 5 subjects have been dosed. From that time, DMC monitoring 
will be performed approximately every 6-8weeks (during Part 1) and quarterly during Part 2 
(with the agreement of DMC and BMS, this schedule may be changed depending on the rate of 
subject accrual). The DMC will review safety data including serious adverse events and events 
of special interest (eg, infections), focusing on early signal detection. The DMC will also 
evaluate the rates of observed increases of clinical disease activity of SLE and opportunistic 
infections compared to the background rates expected in this study population based on a review 
of the relevant literature. Further details on the content and methods of data reports to the DMC 
will be outlined in the Charter of that Committee along with the processes and procedures the 
committee will follow.
In collaboration with the DMC, an unblinded internal safety monitoring team will review the 
safety data throughout the study and will provide recommendations to the blinded study team.
An Adjudication Committee will be used in this study. Scope of responsibility will include, but 
will not be limited to, adjudication of SLE eligibility criteria, new “A” and “B” BILAG flares
and cross-validation of the instruments used in this study to assess the disease being studied. 
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Further details on the content and methods of data reports by the Adjudication Committee will be 
outlined in the Charter of that Committee along with the processes and procedures the 
Committee will follow.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
The sample size calculation is based on power to compare the proportion of subjects who 
achieve BICLA response (the BICLA response rate) at Day 169 between BMS-931699 dose arm 
and placebo arm. With a one-sided continuity corrected chi-squared test at significance 
level 0.05, data from 70 randomized and treated subjects per arm will provide at least 89% power 
to detect a 25% increase in the BICLA response rate in the active treatment arm(s) [(ie, 50% 
response rate in BMS active arm(s)] compared to placebo, and provide 74% power to detect a 
20% increase in the BICLA response rate in the active treatment arm(s) [(ie, 45% response rate 
in BMS active arm)] compared to placebo, assuming that the placebo arm has 25% response rate 
which is reasonable based on the EMBLEM phase 2 trial results21. No adjustment will be made 
for multiplicity. Subjects who discontinue treatment/study prior to Day 169 will contribute to the 
data that will be analyzed for BICLA response at Day 169 (discontinuation will indicate no 
BICLA response). Therefore, no adjustment will be made for discontinuations.
The primary efficacy analysis will be conducted on all randomized patients who received at least 
one dose of the study drug. In order to get 70 randomized and treated subjects per arm, an 
adequate number of subjects will need to meet the inclusion/exclusion criteria at screening.
If the interim analysis for futility and dose adaptation suggests that an additional dose arm (at a 
lower dose level) needs to be added, then up to 40 additional subjects may be randomized.
8.2
Populations for Analyses

All Enrolled Subjects, defined as all subjects who sign an informed consent;

All Randomized Subjects, defined as all subjects who are randomized to a treatment; 

All Treated Subjects, defined as all subjects who receive at least one dose of study treatment;

Biomarker Analysis Population, defined as all subjects that receive any study medication and 
have at least 1 post-treatment biomarker measurement. 

Pharmacokinetic Population, defined as all subjects who receive any study medication and 
have any available concentration-time data. 

Immunogenicity Population, defined as all subjects who receive study drug and have at least 
1 post treatment immunogenicity measurement.
All subjects who receive at least one dose of study treatment (all treated subjects) will be 
included in the safety analysis population and the efficacy analysis population. However, the 
subjects from Part 1 who are randomized to a treatment arm that is discontinued based on the 
Part 1 Safety/RO analysis will be excluded from the efficacy analysis. More details will be 
provided in the statistical analysis plan.
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8.3
Endpoints for Short Term Period
8.3.1
Primary Endpoint(s)
The primary objective (to compare the BICLA response rate at Day 169) will be measured by the 
following primary endpoint: 
Proportion of subjects who achieve BICLA response (BICLA response rate) at Day 169.
8.3.2
Secondary Endpoint(s)
8.3.2.1
Efficacy Endpoints

Proportion of subjects who meet response criteria for the SLE Responder Index(4) [SRI(4)], 
SRI(5) and SRI(6) at Day 169

Proportion of subjects who meet response criteria for the SLE Responder Index(4) [SRI(4)], 
SRI(5) and SRI(6) at Day 85

Proportion of subjects with BICLA response at Day 85

Change from baseline in CLASI score at Day 85 and Day 169

Percentage of subjects with an improvement of >4 or a decrease of >50% from baseline in 
their CLASI score at Day 85 and Day 169

Change from baseline in arthritis, as assessed by American College of Rheumatology (ACR) 
28-joint count of tender and swollen joints at Day 85 and at Day 169

The change from baseline in the following other indices SLE activity over time:

The overall BILAG-2004 score

The overall SLEDAI-2K score

The overall MDGA score

The cumulative corticosteroid and immunosuppressant use over time
8.3.2.2
Safety Endpoints

Incidence and severity of all Adverse Events (AEs), Serious AEs, and pre-established Events 
of Special Interest

Incidence and severity of clinically significant changes in vital signs

Incidence and severity of clinically significant electrocardiogram (ECG) abnormalities

Incidence and severity of clinically significant abnormalities in general laboratory tests
8.3.2.3
Pharmacokinetic Endpoints
Ctrough: Trough level serum concentration of BMS-931699 at time points specified in
Section 5.5.
 
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8.3.2.5
Immunogenicity
Proportion of subjects with BMS-931699 induced antibody response at visit specified in Table 
5.5.3.
 
 
 
 
 
 
 
 
 
 
 
8.4
Endpoints for Long-term Extension Period
During the LTE period, the following endpoints will be assessed cumulatively (safety) and over 
time (efficacy).
8.4.1
Safety Endpoints

Incidence and severity of all Adverse Events (AEs), Serious AEs, and pre-established Events 
of Special Interest

Incidence and severity of clinically significant abnormalities in general laboratory tests
8.4.2
Efficacy Endpoints

Proportion of subjects who achieve BICLA response (BICLA response rate)

Proportion of subjects who meet response criteria for the SLE Responder Index (SRI) 
[SRI(4), SRI(5) and SRI(6)]
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
CLASI score

ACR 28 joint count of tender and swollen joints

Overall BILAG-2004 score

Overall SLEDAI-2K score

Overall MDGA score

The cumulative corticosteroid and immunosuppressant use

Proportion of patients reaching a Major Clinical Response and Partial Clinical Response

Fatigue, based on the FACIT

Quality of life, based on SF-36
8.4.3
Pharmacokinetic Endpoints
Ctrough: Trough level serum concentration of BMS-931699 at time points specified in 
Section 5.5.
 
8.4.5
Immunogenicity
Proportion of subjects with BMS-931699 induced antibody response at visits defined in Table 
5.1-3
8.5
Analyses for the Short-Term Period
8.5.1
Demographics and Baseline Characteristics
Frequency distributions of gender and race will be tabulated. Summary statistics for age, body 
weight, height, and Body Mass Index (BMI) will be tabulated.
8.5.2
Efficacy Analyses
Primary efficacy analysis:
The Chi-square tests will be used to compare the BICLA response rates at Day 169 between each 
of the active treatment arms and the placebo arm. The Chi-square p-value will be provided for 
each comparison between the active treatment and the placebo arm. In addition, the difference of 
the response rates between each active treatment and the placebo will be estimated and their 
corresponding 90% confidence interval will be calculated. No adjustment will be made for 
multiplicity.
Secondary efficacy analysis:

Proportion of subjects who meet response criteria for the SLE Responder Index(4) [SRI(4)], 
SRI(5) and SRI(6) at Day 169
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
Proportion of subjects who meet response criteria for the SLE Responder Index(4) [SRI(4)], 
SRI(5) and SRI(6) at Day 85

Proportion of subjects with BICLA response at Day 85

Percentage of subjects with an improvement of > 4 or a decrease of > 50% from baseline in 
their CLASI score at Day 85 and Day 169
For each of the above endpoints, the estimate and its corresponding 90% confidence interval will 
be calculated for the difference of the proportions between each active treatment arm and the 
placebo arm at the specified visit, similar to the primary analysis.
For each of the following endpoints, the mixed effect model will be fit with treatment and visit as 
the fixed effects and measurements within each subject as the repeated measurements. The 
baseline value will be added into the model as a covariate if necessary. Based on the mixed effect 
model, the estimate and 90% confidence interval will be calculated for the difference between 
each active treatment and the placebo at each specified visit.

Change from baseline in CLASI score at Day 85 and Day 169

Change from baseline in arthritis, as assessed by ACR28-joint count of tender and swollen 
joints at Day 85 and at Day 169

The change from baseline in the following other indices SLE activity over time:

The overall BILAG-2004 score

The overall SLEDAI-2K score

The overall MDGA score
In addition, the cumulative corticosteroid and immunosuppressant use over time will be 
summarized.
8.5.3
Safety Analyses
All recorded adverse events will be listed and tabulated by system organ class, preferred term 
and treatment. Vital signs and clinical laboratory test results will be listed and summarized by 
treatment. Any significant physical examination findings, and clinical laboratory results will be 
listed. ECG readings will be evaluated by the investigator and abnormalities, if present, will be 
listed. The pre-established Events of Special Interest will be listed and summarized.
8.5.4
Pharmacokinetic Analyses
Ctrough will be summarized by dose and study day.
 
 
 
 
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8.5.7
Outcomes Research Analyses
Not applicable.
8.5.8
Other Analyses 
8.5.8.1
Immunogenicity Analysis
Proportion of subjects with BMS-931699 induced antibody response and titers over time will be 
summarized. 
8.6
Interim Analyses
8.6.1
Interim Safety/RO Real Time Analysis at Day 29
When at least 6 patients per treatment arm have either reached Study Day 29 or discontinued, an 
interim analysis (IA) for safety and RO will be performed. The safety analysis will focus on 
incidence and severity of all adverse events (AEs), serious AEs and pre-established Events of 
Special Interest such as infection AEs and any other safety analysis requested by DMC. For RO: 
the median RO at Day 29 for each treatment arm will be calculated. Based on the results of this 
interim analysis, a decision will be taken regarding the doses that will be carried forward into 
Part 2 of the study. Specifically, dosing regimens originally included in Part 1 may be 
discontinued and/or new dosing regimens may be added according to the following criteria:
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Safety:
The DMC in conjunction with an unblinded internal monitoring team may require one or more 
doses to be discontinued if stopping criteria are met or other safety signals arise that the Medical 
Monitor and/or DMC consider of sufficient concern.
Receptor Occupancy:

If median RO of any dose is < 20%, the sponsor may consider dropping that dose

If the median RO for all doses is > 90% the sponsor may consider adding or replacing a dose 
in Part 2 of the study to ensure an adequate pharmacodynamic range (dose not to exceed 
12.5 mg weekly)
Dose decrease and/or reduction of frequency of administration may also be considered if RO 
results fall outside the parameters indicated above. This adjustment may occur for safety reasons 
or in case unforeseen RO profiles observed in SLE patients. The decision to adjust dose and/or 
frequency will be taken after review of the data by the clinical team.
8.6.2
Interim Analysis for Futility and Dose Adaption at Day 85
After 30 subjects per treatment arm (including the subjects from Part 1) have completed at least 
84 days of the treatment period or discontinued the treatment, an interim analysis will be 
conducted to assess the futility of the BMS-931699 dose arms and the overall safety. The results 
of the interim analysis will be reviewed by an unblinded sponsor team who will provide 
recommendations to the blinded study team. The blinded study team will make the decision. The 
unblinded BMS team may recommend to:

maintain the current design;

drop a certain dose arm(s) and equally randomize the remaining unallocated subjects to the 
remaining arms;

stop the study if all dose arms need to be dropped for safety or futility reasons.
The interim analysis for futility and dose adaption will be performed on the BICLA response at 
Day 85 of those 30 subjects per arm and BICLA response at Day 169 of those subjects who have 
completed 168 days of treatment or discontinued the treatment using a Bayesian predictive 
approach.22 This analysis assumes that the BICLA at Day 85 and at Day 169 in the subjects who 
have not yet been observed will be similar to what were observed for the subjects included at the 
interim analysis at Day 85 and Day 169, respectively. As such the unobserved data will be 
simulated from the predictive distribution conditional on the interim data and the prior 
distribution of the treatment difference (using a non-informative prior). Under the Bayesian 
framework, the posterior distribution of the treatment difference (BMS-931699 active dose –
Placebo) will be constructed to determine the predictive probability of a successful outcome 
(ie, reach statistical significance) at the planned end of the trial for each dose arm. Based on 
computer simulations of the operating characteristics of the study design, the futility threshold in 
this interim analysis is set to 0.2. For the comparison of interest, if the predictive probability of a 
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successful outcome at the planned end of the trial falls below 0.2, that BMS-931699 dose arm is 
deemed futile in terms of BICLA response. However, the final futility will also incorporate the 
results from SRI(4), ACR28 and some biomarkers (C3, C4, ANA and anti-dsDNA). 
The proposed stopping rules at the interim analysis, based on the futility assessment and the 
overall safety assessment, are as follows:

Rule 1: Drop the futile dose arm(s) and the dose arm cannot be dropped until the lower dose 
arm has been dropped.

Rule 2: Drop the dose arm(s) with safety issues identified;

Rule 3: If safety issues are identified in all dose arms or all dose arms are futile, stop the 
study.
In case dosing arms are dropped following the interim analysis, the remaining unallocated 
subjects will be randomized into the remaining arms.
If the predictive probability of success for each active arm versus placebo is greater than or equal 
to 0.9, then the BMS team may also recommend adding an additional dose arm at lower dose 
level than current active doses to explore the suboptimal dose.
In that case, the remaining un-allocated subjects with up to 40 additional subjects will be 
randomized into the remaining arms and the new dose arm based on the new randomizations 
schedule.
8.7.1
Analysis for the Long-Term Extension Period
The LTE period starts when a subject receives at least one post Day 169 dose. The analysis based 
on this period is descriptive in nature.
8.7.1.1
Populations of Analysis
All Subjects who received at least one dose post Day 169. 
8.7.1.2
Demographics and Baseline Characteristics
Categorical parameters will be summarized using frequency counts and percentages. Continuous 
parameters will be summarized through means, SD, median, and range. The baseline (Day 1) is 
defined as the start of study medication (the same as the baseline in the short-term period). The 
baseline results will be based on LTE analysis population.
8.7.1.3
Efficacy Analyses
For continuous secondary endpoints (eg, SLEDAI, MDGA etc.) point estimates and 90% 
confidence intervals for mean change from baseline to subsequent time points (in LTE period) 
within each treatment groups will be provided. For binary endpoints (BICLA Response, SRI(X) 
etc.), point estimates and 90% confidence intervals (CIs) will be provided using normal 
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approximation within each treatment group. The assessment windows for LTE period will be 
based on the first LTE dose date; the baseline to assess responses or changes still refers to the 
Day 1 assessment (the same as the baseline in the short-term period). The results will be 
presented by treatment groups. All analyses will be based on as-observed data; hence no 
imputation will be implemented. No statistical testing including p-value computation will be 
performed.
8.7.1.4
Safety Analyses
The evaluation of long term safety of the selected dose(s) will be based on clinical adverse 
events, vital signs and laboratory abnormalities reported during the LTE period. Frequency 
distributions and individual listings of all adverse events and laboratory marked abnormalities 
will be generated based on As Treated population. The results will be presented by treatment 
groups.
8.7.1.5
Immunogenicity
The incidence of a positive response of anti-BMS-931699 antibodies during the LTE period will 
be summarized by treatment groups.
8.7.1.6
Pharmacokinetic Analyses
The descriptive summary of PK parameters will be provided by visits and by treatment groups 
during the LTE period.
8.7.1.7
Pharmacodynamic Analyses
The descriptive summary of selected PD and selected biomarkers will be provided by visits and 
by treatment groups during the LTE period.
8.7.1.8
Outcomes Research Analyses
Not applicable.
The details of the analyses, endpoints and grouping schemes (treatment groups) will be provided 
in the long-term extension statistical analysis plan (LTE SAP).
9
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The study shall be conducted as described in this approved protocol. All revisions to the protocol 
must be discussed with, and be prepared by, BMS. The investigator should not implement any 
deviation or change to the protocol without prior review and documented approval/favorable 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
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If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior 
to obtaining IRB/IEC approval/favorable opinion, as soon as possible the deviation or change 
will be submitted to:

IRB/IEC for review and approval/favorable opinion

BMS

Regulatory Authority(ies), if required by local regulations
Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) 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/screening.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS 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 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. 
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).
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When paper records from such systems are used in place of electronic format to perform 
regulated activities, such paper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original. 
9.1.3
Investigational Site Training
Bristol-Myers Squibb will provide quality investigational staff training prior to study initiation. 
Training topics will include but are not limited to: GCP, AE reporting, study details and 
procedure, electronic CRFs, study documentation, informed consent, and enrollment of WOCBP.
9.2
Records
9.2.1
Records Retention
The investigator 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, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study.
BMS will notify the investigator when the study records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, IRB). Notice of such 
transfer will be given in writing to BMS.
9.2.2
Study Drug Records 
It is the responsibility of the investigator to ensure that a current disposition record of study drug 
(inventoried and dispensed) is maintained at the study site. 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.
BMS will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
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9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the BMS electronic data capture tool, electronic CRFs will be prepared for all 
data collection fields except for fields specific to SAEs and pregnancy, which will be reported on 
the paper or electronic SAE form and Pregnancy Surveillance form, respectively. Spaces may be 
left blank only in those circumstances permitted by study-specific CRF completion guidelines 
provided by BMS.
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, including any paper or electronic SAE/pregnancy CRFs, must be promptly 
reviewed, signed, and dated by the investigator or qualified physician who is a subinvestigator 
and who is delegated this task on the Delegation of Authority Form .For electronic CRFs, review 
and approval/signature is completed electronically through the BMS electronic data capture tool.
The investigator must retain a copy of the CRFs including records of the changes and 
corrections.
Each individual electronically signing electronic CRFs must meet BMS training requirements 
and must only access the BMS electronic data capture tool using the unique user account 
provided by BMS. User accounts are not to be shared or reassigned to other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report. 
For this protocol, the Signatory Investigator will be selected as appropriate based on the 
following criteria:
External Principal Investigator designated at protocol development
National Coordinating Investigator 
Study Steering Committee chair or their designee
Subject recruitment (eg, among the top quartile of enrollers)
Involvement in trial design
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Regional representation (eg, among top quartile of enrollers from a specified region or country)
Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS. Any publications 
or abstracts arising from this study require approval by BMS prior to publication or presentation 
and must adhere to BMS’s publication requirements as set forth in the approved clinical trial 
agreement (CTA). All draft publications, including abstracts or detailed summaries of any 
proposed presentations, must be submitted to BMS at the earliest practicable time for review, but 
at any event not less than 30 days before submission or presentation unless otherwise set forth in 
the CTA. BMS shall have the right to delete any confidential or proprietary information 
contained in any proposed presentation or abstract and may delay publication for up to 60 days 
for purposes of filing a patent application.
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10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
If one form of contraception is required, Complete 
Abstinence is defined as complete avoidance of heterosexual 
intercourse and is an acceptable form of contraception for all 
study drugs. Female subjects must continue to have 
pregnancy tests. Acceptable alternate methods of highly 
effective contraception must be discussed in the event that 
the subject chooses to forego complete abstinence.
If two forms of contraception is required, Complete 
abstinence is defined as complete avoidance of heterosexual 
intercourse and is an acceptable form of contraception for all 
study drugs. Subjects who choose complete abstinence are 
not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. 
Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject 
chooses to forego complete abstinence.
Expanded definition Complete abstinence as defined as 
complete avoidance of heterosexual intercourse is an 
acceptable form of contraception for all study drugs. This 
also means that abstinence is the preferred and usual lifestyle 
of the 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. Subjects who choose complete abstinence 
are not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. 
Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject 
chooses to forego complete abstinence.
Medical Research
Those scientific activities which cannot be reasonably 
anticipated at the time of trial design, for which we would 
like to collect and/or retain samples from study participants. 
Examples of Medical Research include, but are not limited 
to, new assay development and validation, companion 
diagnostic development, new hypotheses in the interaction of 
drug and the human body, and exploration of emerging 
science in the understanding of disease.
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10.1
List of Abbreviations
Term
Definition
ACR
American College of Rheumatology
ADA
anti-drug antibodies
ADLs
activities of daily living
AE
adverse event
ALT
alanine aminotransferase
ANA
antinuclear antibodies
ANC
absolute neutrophil count
Anti-Sm
Anti-Smith antibodies
APC
antigen presenting cells
APL
antiphospholipids
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AT
aminotransaminases
AUC
area under the concentration-time curve

azathioprine
-HCG
beta-human chorionic gonadotrophin
BA/BE
bioavailability/bioequivalence
BICLA
BILAG-based Composite Lupus Assessment
BID, bid
bis in die, twice daily
BILAG
British Isles Lupus Assessment Group
BLQ
below limit of quantification 
BMI
body mass index
BMS
Bristol-Myers Squibb
BP
blood pressure
BUN
blood urea nitrogen
C
Celsius
Ca++
calcium
Cavg
average concentration
CBC
complete blood count
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Term
Definition
Cexpected-tau
expected concentration in a dosing interval
CFR
Code of Federal Regulations 
CHO
chinese hamster ovary
CI
confidence interval
CIA
collagen-induced arthritis
C1-
chloride
CLASI
Cutaneous Lupus Erythematosus Disease Area and Severity Index
CLcr
creatinine clearance
CLT
total body clearance
CLTp
total plasma clearance
cm
centimeter
Cmax, CMAX
maximum observed concentration
Cmin, CMIN
trough observed concentration
CMV
cytomegalovirus
CNS
central nervous system
cpm
counts per minute
CRC
Clinical Research Center
CRF
Case Report Form, paper or electronic
CS
corticosteroids
Ctrough
trough observed plasma concentration
CV
coefficient of variation
CXR
chest x-ray
CYP
cytochrome p-450
dAb
domain antibody
D/C
discontinue
DC
dendritic cell
dL
deciliter
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
ds-DNA
double-stranded deoxyribonucleic acid
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lulizumab pegol
Term
Definition
DSM IV
Diagnostic and Statistical Manual of Mental Disorders (4th Edition)
EA
extent of absorption
EAE
experimental autoimmune encephalitis
EBV
Epstein-Barr virus
EC50
effective concentration of drug or antibody which induces a response 
halfway between the baseline and maximum after a specified exposure 
time
ECG
electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EEG
electroencephalogram
eg
exempli gratia (for example)
ePPND
enhanced prenatal/postnatal toxicology
ESR
Expedited Safety Report
FACIT-F
Functional Assessment of Chronic Illness Therapy - Fatigue
FBDS
formulated bulk drug substance
FDA
Food and Drug Administration
FIH
first in human
FSH
follicle stimulating hormone
g
gram
GC
gas chromatography
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GFR
glomerular filtration rate
h
hour
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCO3
-
bicarbonate
HIV
Human Immunodeficiency Virus
HR
heart rate
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lulizumab pegol
Term
Definition
HRT
hormone replacement therapy
IA
Interim Analysis
ICD
International Classification of Diseases
ICH
International Conference on Harmonisation 
ie
id est (that is)
IEC
Independent Ethics Committee
IgG
immunoglobulin G
IgM
immunoglobulin M
IFN
interferon
IL
interleukin
IM
intramuscular
IMP
investigational medicinal products
IND
Investigational New Drug
IRB
Institutional Review Board
IU
International Unit
K
slope of the terminal phase of the log concentration-time curve
K3EDTA
potassium ethylenediaminetetraacetic acid
K+
potassium
kg
kilogram
KLH
keyhole limpet hemocyanin
L
liter
LBA
ligand binding assay
LCV
lymphocryptovirus
LLOQ
lower limit of quantification
LOD
limit of detection
LTE
Long-Term Extension
mAb
monoclonal antibody
MABEL
minimal anticipated biological effect level
MAD
multiple ascending dose
MBP
myelin basic protein
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Term
Definition
MCB
master cell bank
MDGA
Physician’s Global Assessment of Disease Activity
mg
milligram
Mg++
magnesium
min
minute
mL
milliliter
mmHg
millimeters of mercury
MOA
mode of action
MOG
myelin oligodendrocyte glycoprotein
MR
medical research
MRT
mean residence time
MS
multiple scelorosis
MTD
maximum tolerated dose

methotrexate
W
molecular weight
g
microgram
N
number of subjects or observations
Na+
sodium
N/A
not applicable
Ng
nanogram
NHV
normal healthy volunteer
NIMP
non-investigational medicinal products 
NOAEL
no observed adverse effect level
NSAID
Non-steroidal anti-inflammatory drug
NSS
Normal saline solution
OVA
ovalbumin
PBMC
peripheral blood mononuclear cell
PBS
phosphate buffered saline
PD
pharmacodynamics
PGA
Subject’s Global Assessment of Disease Activity
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Term
Definition
PK
pharmacokinetics
POC
proof of concept
QC
quality control
QFG
QuantiFERON-TB Gold assay
R2
coefficient of determination
RA
rhumatoid arthritis
RBC
red blood cell
RO
receptor occupancy
SAD
single ascending dose
SAE
serious adverse event
SC
subcutaneous
SD
standard deviation
SF-36
Short Form (36)
SLE
systemic lupus erythematosus
SLEDAI
Systemic Lupus Erythematosus Disease Activity Index
SLICC/ACR 
Damage Index
Systemic Lupus International Collaborating Clinics/American College of 
Rheumatology Damage Index
SOP
Standard Operating Procedures
SRI
SLE Responder Index
ST
serine and threonine
Subj
subject
t
temperature
T
time
TAO
Trial Access Online, the BMS implementation of an EDC capability
TCR
T-cell receptor
TDAR
T-cell dependent antibody response
T-HALF
Half life
TID, tid
ter in die, three times a day
Tmax, TMAX
time of maximum observed concentration
TNF
tumor necrosis factor
T-Regs
regulatory T-lymphocytes
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Term
Definition
ULN
upper limit of normal
VAS
visual analog scale
VH
variable regions of the heavy chain of a human antibody
VL
variable regions of the light chain of a human antibody
Vss
volume of distribution at steady-state
WHO
World Health Organization
WOCBP
women of childbearing potential
WT
wild type
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lulizumab pegol
APPENDIX 1
COMMONLY USED CORTICOSTEROID EQUIVALENTS
Medication
Dose Equivalence
Prednisone
20mg
Cortisone
100mg
Hydrocortisone
80mg
Prednisolone
20mg
Methylprednisolone
16mg
Triamcinolone
16mg
Budesonide
4mg
Dexamethasone
3mg
Bethamethasone
2.4mg
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APPENDIX 3
THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF 
SYSTEMIC LUPUS ERYTHEMATOSUS1,2
Criterion
Definition
1) Malar rash
Fixed erythema, flat or raised, over the malar eminences, tending to spare the 
nasolabial folds
2) Discoid rash
Erythematous raised patches with adherent keratotic scaling and follicular 
plugging; atrophic scarring may occur in older lesions
3) Photosensitivity
Skin rash as a result of unusual reaction to sunlight, by patient history or 
physician observation
4) Oral ulcers
Oral or nasopharyngeal ulceration, usually painless, observed by physician 
5) Arthritis
Nonerosive arthritis involving 2 or more peripheral joints, characterized by 
tenderness, swelling, or effusion
6) Serositis
a) Pleuritis--convincing history of pleuritic pain or rubbing heard by a physician 
or evidence of pleural effusion 
OR 
b) Pericarditis--documented by ECG or rub or evidence of pericardial effusion
7) Renal disorder
a) Persistent proteinuria greater than 0.5 grams per day or greater than 3 + if 
quantitation not performed 
OR 
b) Cellular casts--may be red cell, hemoglobin, granular, tubular, or mixed 
8) Neurologic 
a) Seizures--in the absence of offending drugs or known metabolic disorder 
derangements; eg, uremia, ketoacidosis, or electrolyte imbalance 
OR 
b) Psychosis--in the absence of offending drugs or known metabolic 
derangements, eg, uremia, ketoacidosis, or electrolyte imbalance 
9) Hematologic disorder
a)
Hemolytic anemia--with reticulocytosis 
OR 
b) Leukopenia--less than 4,000/mm3 total on 2 or more occasions 
OR 
c) Lymphopenia--less than 1,500/mm3 on 2 or more occasions 
OR 
d) Thrombocytopenia--less than 100,000/mm3 in the absence of offending drugs
10) Immunologic disorder 
a) Anti-DNA: antibody to native DNA in abnormal titer 
OR 
b)
Anti-Sm: presence of antibody to Sm nuclear antigen 
OR 
c)
Positive finding of anti-phospholipid antibodies based:
1) an abnormal serum level of IgG or IgM anti-cardiolipin antibodies,
2) a positive test result for lupus anticoagulant using a standard method, or
3) a false positive serologic test for syphilis known to be positive for at least 
6 months and confirmed by Treponema pallidum immobilization or 
fluorescent treponemal antibody absorption test.
11) Antinuclear antibody
An abnormal titer of antinuclear antibody by immunofluorescence or an 
equivalent assay at any point in time and in the absence of drugs known to be 
associated with "drug-induced lupus" syndrome
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lulizumab pegol
*
The proposed classification is based on 11 criteria. For the purpose of identifying 
patients in clinical studies, a person shall be said to have systemic lupus erythematosus if 
any 4 or more of the 11 criteria are present, serially or simultaneously, during any 
interval of observation. 
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Page:
1
Protocol Number:
IM128027
IND Number:
110,787
EUDRACT Number
2014-002184-14
Date:
28-Apr-2015
Protocol IM128027: A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-
Controlled Study to Evaluate the Safety and Efficacy of lulizumab pegol vs Placebo on a 
Background of Limited Standard of Care in the Treatment of Subjects with Active Systemic 
Lupus Erythematosus
Amendment Number 06
Site Number: All
Study Director/Central Medical Monitor
Lara Pupim, MD, MSCI
Bristol-Myers Squibb Research and Development
This protocol amendment contains information that is confidential and proprietary to 
Bristol-Myers Squibb (BMS). 
This amendment must be maintained with the referenced protocol.
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Protocol Amendment 06
IM128027
BMS-931699
lulizumab pegol
 
 
 
Changes to the Protocol: 
1. Title Page and Protocol Header: updated generic name of the investigational drug from anti-
cd28dab to lulizumab pegol 
2. Synopsis, Investigational Product(s), Dose and Mode of Administration, Duration of 
Treatment with Investigational Product(s): updated to add the generic name lulizumab pegol 
and to include the LTE.
3. Synopsis, Research Hypothesis; Section1.2 Research Hypothesis: corrected a typographical 
error to cutaneous from cutanenous
4. Synopsis, Objectives: updated to separate the Short-Term Period Objectives from those of 
the LTE
5. Synopsis, Primary Objective; Section 8.3.1 Primary Endpoints: deleted the fragment 
"following 24-week treatment with BMS-931699 or placebo administered on a stable 
background therapy", as BICLA will be assessed at Day 169 for subjects who have 
completed Day 169 or discontinued, ie subjects who have discontinue will count as 
non-responders.
6. Synopsis, Secondary Objectives; Section 1.3.2 Secondary Objectives: clarified the objectives 
of Parts 1 and 2 of the study and added objectives for the LTE
7. Synopsis, Study Design, Duration of the Study:
a) updated to clarify the dose adaptation plans and to include the LTE
b) updated Study Schematics to include the LTE
c) added a new figure, Study Design Schematic - Long-Term Extension Period, to show the 
LTE schema
d) added new paragraphs to describe the LTE and clarify when the 42 days Follow Up visit 
will be performed
e) Synopsis, Number of Subjects: updated to clarify when the number of participating 
subjects could be increased 
8. Synopsis, Study Population: corrected 1 month to 8 weeks of stable background therapy and 
updated to clarify the allowed background therapy for consistency with protocol
9. Synopsis, Study Assessments: 
a) reorganized for category to increase clarity
b) “soluble receptors” removed from the biomarkers being assessed 
c) updated the list of biomarkers being assessed to increase clarity
10. Synopsis, Sample Size and Section 8.1 Sample Size Determination: updated to clarify how 
Discontinuations will be managed in the analysis
11. Synopsis, Endpoints and Analyses: updated for clarity and to support the LTE
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12.
 
13.
 
 
 
 
15. Section 1.3.1 Primary Objectives: 
a) deleted the fragment "following 24-week treatment with BMS-931699 or placebo 
administered on a stable background therapy", as BICLA will be assessed at Day 169 for 
subjects who have completed Day 169 or discontinued, ie subjects who have discontinue 
will count as non-responders.
b) added mycophenolate acid/mycophenolate mofetil and leflunomide to the list of 
immunosuppressant agents that must remain stable
16. Section 1.3.2 Secondary Objectives: 
a) deleted the fragment "following 24-week treatment with BMS-931699 or placebo 
administered on a stable background therapy", as objectives will be assessed for subjects 
who have completed Day 169 or discontinued, ie subjects who have discontinue will 
count as non-responders.
b) removed “pain” as only tenderness and swelling are assessed in the ACR28 used in this 
study.
 
18. Section 1.3.4 Long-Term Extension Period Objectives: new section to support the LTE
19. Section 1.5 Overall Risk/Benefit Assessment: 
a) updated to include the LTE
b) updated to clarify the acceptable tuberculosis screening tests
20. Section 3.1 Study Design and Duration:
a) updated to clarify the dose adaptation plans, to clarify duration of screening period and 
Day 1 visit window and, to include the LTE
b) updated Figure 3.1-1 Overall Study Design to include the LTE
c) added a new figure, Figure 3.1-4 Long-Term Extension Schematic, to show the LTE 
schema
d) added new paragraphs to describe the LTE and clarify when the 42 days Follow Up visit 
will be performed
21. Section 3.2 Post Study Access to Therapy: updated to specify that the LTE has no end date at 
this point but that this could change based on results obtained from the development program 
of lulizumab pegol
22. Section 3.3 Study Population: added sentence summarizing the requirements for entry into 
the LTE.
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23. Section 3.3.1 Inclusion Criteria: 
a) corrected criterion 2.c)i) to clarify the targeted patient population 
b) corrected criterion 2.c)iv) to add mycophenolate acid/mycophenolate mofetil as a 
permitted immunosuppressant agent and also include leflunomide (for consistency with 
the synopsis) and to add the requirement to follow the mycophenolate mofetil (MMF) 
insert package in case of neutropenia (for subjects taking MMF)
c) corrected criterion 2.c)v) to clarify that prednisone (or prednisone equivalent) is allowed 
but not required
d) corrected criterion 2.c)vi) to clarify that washout periods must be fulfilled prior to signing 
consent
e) corrected criterion 2.c)vii) to clarify that the requirement for stable NSAIDs only applies 
for chronic use and correct a typographical error in the MDGA acronym.
24. Section 3.3.2 Exclusion Criteria: 
a) clarified exceptions to exclusion criterion 1.b) and 1.c)
b) removed exclusion criterion 2.b)i (4) as it is included in 2.b)i (3)
c) corrected a typographical error in exclusion criterion 2.b)ii) to mononeuritis from 
mononeritis
d) updated exclusion criterion 2.b)v) to clarify the HIV antibodies being tested
e) clarified exceptions to exclusion criterion 3.l)
25. Section 3.3.4 Criteria for Long-term Extension: new section to include the LTE
26. Section 3.4.1 Prohibited and/or Restricted Treatments; Appendix 2 Washout Times of 
Medications Based on 5 Half-Lives: 
a) reformatted the section to avoid duplication of information in text and in Appendix 2. For 
clarity, required washout or recovery times are now all contained in Appendix 2 and not 
repeated in text.
b) deleted restriction of mycophenolate mofetil, which is now an acceptable background 
immunossuppressant in the study.
c) added the requirement to follow the mycophenolate mofetil (MMF) insert package in 
case of neutropenia (for subjects taking MMF)
d) added sentence to clarify when influenza and pneumococcal vaccine can be administered 
e) deleted restriction of planned elective surgery from this section as it is part of the 
inclusion and exclusion criteria section.
f)
added some clarity around the management of concomitant medications
27. Section 3.5 Discontinuation of Subjects following any Treatment with Study Drug: 
a) clarified the requirement for discontinuation related to excessive use of prednisone 
(or prednisone equivalent).
b) added Pregnancy 
28. Section 3.5 Discontinuation of Subjects following any Treatment with Study Drug; Section 
6.4 Pregnancy: clarified that females that become pregnancy will be immediately 
discontinued from the study
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29. Section 4 Study Drug: 
a) removed the requirement to dose BMS-931699 in the morning 
b) Table 4.1 Treatment Administration: corrected to capture that placebo is not a vial but 
normal saline solution (NSS)
30. Section 4.3 Storage and Dispensing: 
a) corrected name of document referred to in paragraph 5 from Preparation for 
Subcutaneous Use to Pharmacy Reference Instruction
b) removed preparation details that can be found in more details in the Pharmacy Reference 
Instructions
c) updated to clarify that subjects must remain at the site for at least 1 hour after each 
injection, consistent with Section 4.5.1
31. Section 4.4 Method of Assigning Subject Identification: corrected to remove “within each 
panel” as there are no panels in this study
32. Section 4.5.1 Administration of BMS-931699 or placebo: 
a) added double-blind to heading for clarity
b) corrected the information pertaining to the 12.5mg weekly dose from BMS-931688 to 
BMS-931699
c) added that Placebo injection only applies to the Short-Term period of the study
33. Section 4.5.2 Dose modifications: clarified the management of the dose modifications
34. Section 4.5.3 Corticosteroids (Prednisone or Prednisone Equivalent) Dosing: clarified the 
management of dose modifications during the study
35. Section 4.5.4 Rescue Therapy: new section added for clarity on protocol allowance as rescue 
therapy and to define when subjects who require rescue therapy will be discontinued.
36. Section 4.6.2 Unblinding of the Study Sites: removed the last 2 paragraphs since the 
information was not pertaining to the unblinding of the study sites 
37. Section 5.1 Flow Chart/Time and Events Schedule: 
a) Table 5.1-1 Screening Procedural Outline (IM128027): corrected Notes for ACR criteria 
for SLE form to be Appendix 3
b) Table 5.1-1 Screening Procedural Outline (IM128027): corrected Procedures to add that 
breast/cervical cancer screening must also be documented
c) Table 5.1-1 Screening Procedural Outline (IM128027): removed Ro (SS-A), La (SS-B), 
RNP and APL from samples collected at screening as these assessments are not required 
for eligibility
d) Table 5.1-2 Short-Term Procedural Outline (IM128027): updated to clarify the +/- 2 days 
window also applies to Day 1 visit
e) Table 5.1-2 Short-Term Procedural Outline (IM128027): removed Total soluble CD28 
from procedures performed during the study
f)
Table 5.1-2 Short-Term Procedural Outline (IM128027): added a footnote to specify 
when the 42 days Follow Up visit should be conducted
g) Table 5.1-3 Long-Term Extension Procedural Outline (IM128027): new table to outline 
procedures for LTE
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38. Section 5.2 Study materials: updated to remove the requirement for a refrigerated centrifuge
39. Section 5.3.2 Laboratory Test Assessments: updated to clarify the laboratory tests being 
assessed, to include the LTE and add HIV screen at the screening visit only (since this was 
omitted in the initial version of the protocol)
40. Section 5.3.3 Tuberculosis Screening and Chest X-Ray: updated to clarify that a confirmed 
negative IGRA test is required prior to Day 1
41. Section 5.4.1 Primary Efficacy Assessment: updated to include the LTE
a) Section 5.4.1.1 Short-Term Period: new section to separate the Short-Term Period
Efficacy Assessment from the LTE
b) Section 5.4.1.2 Long-Term Extension Period: new section added to include the LTE
42. Section 5.4.2 Secondary Efficacy Assessments: updated to include the LTE
a) Section 5.4.2.1 Short-Term Period: new section to separate the Short-Term Period 
Efficacy Assessment from the LTE
b) Section 5.4.2.2 Long-Term Extension Period: new section added to include the LTE
43. Section 5.5 Pharmacokinetic Assessments: updated to include the LTE
a) Section 5.5.1 Short-Term Period: added new section to separate the Short-Term Period 
Pharmacokinetic Assessment from the LTE, removed specific timepoints and referred to 
Table 5.5.1-1 for consistency
b) Section 5.5.2 Long-Term Extension Period: new section added to include the LTE
44. Section 5.5.1 Pharmacokinetics: Collection and Processing: 
a) renumbered to Section 5.5.3 
b) Table 5.5.1-1 Pharmacokinetic Sampling Schedule for BMS-931699 renumbered to 
Table 5.5.3-1
c) Table 5.5.1-1 (renumbered to Table 5.5.3-1) updated to include collection schedule for 
LTE
d) added footnote b to Table 5.5.1-1 (renumbered to Table 5.5.3-1) to clarity that for AEs 
samples are to be drawn only for subjects that experience an AE leading to 
discontinuation of study treatment
45. Section 
5.5.2 
Pharmacokinetic 
Sample 
Analyses
renumbered 
to 
Section 
5.5.4 
Pharmacokinetic Sample Analyses
46. Section 5.5.3 Immunogenicity Assessments: renumbered to Section 5.5.5 and updated for
clarity
47. Section 5.5.4 Labeling and Shipping of Biological Samples renumbered to Section 5.5.6 
Labeling and Shipping of Biological Samples
49. Section 5.7.1 Blood-Based (RNA) Assessments: updated to clarify the planned RNA analysis
 
51. Section 5.8 Outcomes Research Assessment: removed subsection on hospitalization and 
emergency room visits
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52. Section 6 Adverse Events: updated to clarify the reporting of safety events to comply with 
countries requirements
53. Section 6.1.1 Serious Adverse Event Collecting and Reporting: updated to 42 days (from 30) 
for consistency with the Time & Event Table, the half-life of lulizumab pegol and the 
estimated receptor occupancy.
54. Section 6.7.1 AE’s of Special Interest: 
a) updated to remove Immunogenicity from the list and clarify how it will be monitored
b) updated to clarify that Injection-related reactions will be monitored to include local and 
systemic reactions, instead of Injection-site reactions
55. Section 8.3 Endpoints: renamed 8.3 Endpoints for Short-Term Period to differentiate from 
Endpoints for the LTE
 
57. Section 8.4 Endpoints for Long-Term Extension Period: new section to include the LTE
a) Section 8.4.1 Safety Endpoints: new section to include the LTE
b) Section 8.4.2 Efficacy Endpoints: new section to include the LTE
c) Section 8.4.3 Pharmacokinetic Endpoints: new section to include the LTE
e) Section 8.4.5 Immunogenicity: new section to include the LTE
58. Section 8.4 Analyses: renumbered and changed to Section 8.5 Analyses for Short-Term 
Period
a) Section 8.4.1 Demographics and Baseline Characteristics renumbered Section 8.5.1 
Demographics and Baseline Characteristics
b) Section 8.4.2 Efficacy Analyses renumbered Section 8.5.2 Efficacy Analyses
c) Section 8.4.3 Safety Analyses renumbered Section 8.5.3 Safety Analyses
d) Section 8.4.4 Pharmacokinetic Analyses renumbered Section 8.5.4 Pharmacokinetic 
Analyses
g) Section 8.4.7 Outcomes Research Analyses renumbered Section 8.5.7 Outcomes 
Research Analyses
h) Section 8.4.8 Other Analyses renumbered Section 8.5.8 Other Analyses
i)
Section 8.4.8.1 Immunogenicity Analysis renumbered to Section 8.5.8.1 Immunogenicity 
Analysis
59. Section 8.5 Interim Analyses renumbered Section 8.6 Interim Analyses
a) Section 8.5.1 Interim Safety/RO Real Time Analysis at Day 29 renumbered Section 8.6.1 
Interim Safety/RO Real Time Analysis at Day 29
b) Section 8.5.2 Interim Analysis for Futility and Dose Adaption at Day 85 renumbered 
Section 8.6.2 Interim Analysis for Futility and Dose Adaption at Day 85
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61. Section 10.1 List of Abbreviations: updated to add Anti-SM, LTE and NSS and remove 
MMF
62. Appendix 2 Washout Times of Medications Based on 5 Half-Lives:
a) renamed Washout or Recovery Times Required Prior to Screening 
b) updated for clarity and consistency with other sections
63. Appendix 5 Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) 
Disease Activity Questionnaire: corrected the period of time the manifestation must be 
present within from 10 days to 30 days, for consistency with other sections
Please maintain a copy of this amendment with your protocol. Please provide a copy to 
your Investigational Review Board / Ethics Committee, unless agreed otherwise with BMS.
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SAP_001.pdf: 
Official Title of Study:  A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study 
to Evaluate the Safety and Efficacy of BMS-931699 vs Placebo on a Background of Limited Standard of 
Care in the Treatment of Subjects with Active Systemic Lupus Erythematosus 
 
NCT Number:  NCT02265744 
 
Document Date:  June 28, 2016   


STATISTICAL ANALYSIS PLAN
(SHORT-TERM PERIOD)
A PHASE 2, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF BMS-
931699 VS. PLACEBO ON A BACKGROUND OF LIMITED STANDARD OF CARE IN 
THE TREATMENT OF SUBJECTS WITH ACTIVE SYSTEMIC LUPUS 
ERYTHEMATOSUS
PROTOCOL IM128-027
VERSION 2.0
4
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Statistical Analysis Plan
IM128-027 
BMS-931699
v2.0
2
TABLE OF CONTENTS
TABLE OF CONTENTS.................................................................................................................2
LIST OF TABLES...........................................................................................................................4
LIST OF FIGURES .........................................................................................................................5
1
2
STUDY DESCRIPTION..............................................................................................7
2.1
Study Design.................................................................................................................7
2.2
Treatment Assignment................................................................................................12
2.3
Blinding and Unblinding ............................................................................................13
2.3.1
Blinding at the Study Sites..........................................................................................13
2.3.2
Unblinding of the Study Sites......................................................................................13
2.3.3
Other Unblinding Information....................................................................................13
2.4
Protocol Amendments ................................................................................................14
3
OBJECTIVES.............................................................................................................15
3.1
Primary Objective.......................................................................................................15
3.2
Secondary Objectives .................................................................................................15
3.3
4
ENDPOINTS ..............................................................................................................16
4.1
Primary Efficacy Endpoint(s).....................................................................................16
4.2
Secondary  Efficacy Endpoint(s)................................................................................16
4.3
Safety Endpoints.........................................................................................................17
4.4
Pharmacokinetic Endpoints ........................................................................................17
4.5
4.6
Immunogenicity..........................................................................................................18
4.7
5
SAMPLE SIZE AND POWER ..................................................................................18
6
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS 
FOR ANALYSES.......................................................................................................19
6.1
Study Periods..............................................................................................................19
6.2
Treatment Regimens...................................................................................................19
6.3
Populations for Analyses ............................................................................................19
7
STATISTICAL ANALYSES.....................................................................................20
7.1
General Methods.........................................................................................................20
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7.2
Study Conduct ............................................................................................................21
7.3
Study Population.........................................................................................................22
7.3.1
Subject Disposition.....................................................................................................22
7.3.2
Demography and Baseline Characteristics................................................................22
7.3.3
Medical History and Prior Medication ......................................................................23
7.4
Extent of Exposure .....................................................................................................23
7.4.1
Study Therapy.............................................................................................................23
7.4.2
Discontinuations from Study Therapy ........................................................................24
7.4.3
Treatment Compliance................................................................................................24
7.4.4
7.4.5
Immunosuppressant  Medication................................................................................24
7.4.6
Corticosteroids ...........................................................................................................24
7.5
Efficacy.......................................................................................................................24
7.5.1
Primary Efficacy Endpoints in the Short-term Period ...............................................25
7.5.2
Secondary Efficacy Endpoints in the Short-term Period............................................25
7.5.3
Subgroup Analyses......................................................................................................25
7.5.4
Sensitivity Analyses.....................................................................................................26
7.5.5
Per-Protocol (PP) Analyses .......................................................................................26
7.6
Safety..........................................................................................................................26
7.6.1
Adverse Events............................................................................................................27
7.6.2
Adverse Events of Interest ..........................................................................................28
7.6.3
Deaths.........................................................................................................................29
7.6.4
Other Serious Adverse Events ....................................................................................29
7.6.5
Adverse Events Leading to Discontinuation of Study Therapy ..................................29
7.6.6
Multiple Occurrences of Adverse Events....................................................................29
7.6.7
Summaries of Laboratory Data ..................................................................................30
7.6.8
Other Safety Considerations.......................................................................................30
7.7
Pharmacokinetic Analysis ..........................................................................................31
7.8
7.9
Immunogenicity Analysis...........................................................................................32
7.9.1
Immunogenicity Frequency ........................................................................................32
7.10
Interim Analyses.........................................................................................................33
7.10.1
Interim Safety/RO Analysis at Day 29........................................................................33
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7.10.2
Interim Analysis for Futility and Dose Adaptation at Day 85....................................34
7.11
7.11.1
7.11.2
Time to event Analysis ................................................................................................35
7.11.3
7.11.4
Immunogenicity and PK/Efficacy/Safety ....................................................................36
7.11.5
Exposure-Response Analysis ......................................................................................36
7.11.6
Analysis for the PK Sub-Study....................................................................................36
8
CONVENTIONS........................................................................................................37
8.1
Calculations of Key Measures....................................................................................37
8.1.1
Evaluation of BICLA response ...................................................................................37
8.1.2
Evaluation of SRI(X)...................................................................................................38
8.1.3
Evaluation of Major Clinical Response and Partial Clinical Response ....................40
8.1.4
Evaluation of Flare and Severity of Flare..................................................................40
8.1.5
Evaluation of SF-36 Summary Functions and Components.......................................40
8.2
Baseline Measures ......................................................................................................40
8.3
Missing Measurements...............................................................................................41
8.4
Missing, Unknown or Partial Dates............................................................................41
8.5
Day Ranges for Analysis of Time Points ...................................................................41
9
CONTENT OF REPORTS.........................................................................................42
10
APPENDIX 1   RELEVANT PROTOCOL DEVIATIONS ......................................42
11
APPENDIX 2  DOCUMENT REVISION HISTORY...............................................43
12
LIST OF TABLES
Table 2.4-1:
Protocol Amendments................................................................................14
Table 7.1-1:
Planned Efficacy Analyses ........................................................................20
Table 7.6.8.2-1:
Vital signs criteria......................................................................................31
Table 8.5-1:
Days Ranges for Assessments at Every Scheduled Visits During 
the Short-term Period.................................................................................42
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LIST OF FIGURES
Figure 2.1-1:
Overall Study Design...................................................................................9
Figure 2.1-2:
Study Design Schematic - Part 1 ...............................................................10
Figure 2.1-3:
Study Design Schematic - Part 2 ...............................................................10
Figure 2.1-4:
Long-Term Extension Schematic ..............................................................11
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Schedule of Analyses:
The following analyses will be performed:

An interim analysis for the safety/RO at Day 29 of Part 1 when at least 6 patients per 
treatment arm have either reached Study Day 29 or discontinued (refer to the details in 
Section 7.5.5);

An interim analysis for futility and dose adaptation will be performed when approximately
30 patients per treatment arm (including the patients from part 1) have completed at least 84 
days of treatment period or discontinued the treatment;

A final analysis will be performed after the last treated subject in the study reaches the end of 
the short-term period. 
2
STUDY DESCRIPTION
2.1
Study Design
This is a Phase 2, parallel-arm, randomized, double-blinded, multicenter, international study, 
with an adaptive design. 
The study will comprise a short-term period (Part 1 and Part 2), and a long-term extension (LTE) 
period. This SAP covers the short-term period of the study.
Part 1 of the short-term period will focus on assessing safety and RO and will be limited to a 
maximum of 50 patients (approximately 6-10 patients/arm) who will be included in the 
Safety/RO interim analysis (IA). These patients will continue study treatment beyond the IA for 
Safety/RO and be treated for up to 24 weeks and be followed for 6 additional weeks after 
treatment is completed. Treatment could be shorter if IA for Safety/RO analysis indicates one or 
more arms should be dropped.
Part 2 of the short-term period will start once cumulative safety profile is considered acceptable 
and RO data for 6-10 subjects per cohort dosed for >28 days is available and the interim analysis 
from Part 1 is completed. Approximately 300 subjects will be randomized into this part of the 
study (number of patient to be randomized into Part 2 may increase based on the results of the 
futility interim analysis). 
All subjects will undergo screening evaluations to determine eligibility and allow down titration 
of prednisone (or prednisone equivalent) prior to administration of study medication. The 
screening period will have a duration of approximately 28 days (+/- 2 days). All eligibility 
criteria must be met prior to Day 1. In the event of technical difficulties leading inconclusive 
assessments that would go beyond the allowed window, the study medical monitor must be 
consulted prior to conducting Day 1. On Day 1, eligibility of subjects will be confirmed and 
eligible subjects will receive their first dose of study medication.
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Dose may be adapted based on results of the planned interim analyses from Part 1 and Part 2, as 
follows:

Safety and RO interim analysis: safety and RO analysis will be performed when 
approximately 6 to 10 subjects per arm have reached Study Day 29. Based on the 
results of this analysis, dose arms(s) may be adjusted or may be dropped. 

Interim analysis for futility and dose adaptation on BICLA response, SRI 
response, ACR28 and some SLE biomarkers (such as auto-antibodies, 
complement levels, etc.) with possible exploratory exposure response analysis, 
will be performed when approximately 30 subjects per arm have reached Study 
Day 85 (12 weeks), including subjects from Part 1 and Part 2, of treatment or 
have discontinued prior to reaching study Day 85). Analysis will be performed by 
an unblinded Sponsor team, while maintaining blind at the site and subject level. 
Based on the results, the dose levels and sample size may be modified. 

Ongoing assessment of safety will be performed by an independent Data 
Monitoring Committee (DMC) and an internal unblinded safety monitoring team. 
Both entities may make recommendations to the Sponsor regarding conduct of 
study and dose adjustment based on safety observations.
Following interim analyses and DMC reviews, dose arm(s) may be modified based on the 
results, as follows:

If one or more arms are added, future randomizations will include the new arm(s). 

If one or more arms are dropped for safety reasons, randomization into that arm 
will be terminated and all subjects currently randomized to that or those arm(s) 
will be discontinued from receiving study medication.

If one or more arms are dropped due to inadequate RO, there will be no new 
randomizations into that dose arm; subjects currently randomized may continue at 
the Investigator discretion. 
The long-term extension (LTE) period is optional and will include eligible subjects who have 
completed Day 169 (week 24) of treatment and consent to participate. This period of the study 
will remain blinded but will no longer have a placebo arm. Eligible subjects will remain on their 
originally-assigned dose arm, unless they were on the placebo arm during the short-term period. 
Placebo-arm subjects will be re-randomized into one of the existing active arms at Day 169 
(24 weeks). Re-randomization of the placebo subjects will be done by IVRS and only the 
unblinded pharmacist/drug preparer will know the new randomization arm. The LTE will remain 
blinded to the study team and study personnel. 
The long-term extension period will not have interim analyses for dose adaptation. However, the 
BMS unblinded safety committee will continue to review the safety data and discuss it with the 
DMC (also unblinded), as needed. During their evaluation of adverse events, if a significant 
safety concern is identified, these two committees may propose that one or more dose arms are 
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Approximately 125 sites will participate in this study, which will be conducted globally and 
should include, but will not be limited to, participation of countries located in North America and 
Europe.
Subjects who discontinue from the study will have one follow-up visit, approximately 42 days 
(6 weeks) after receiving their last dose of study medication, to perform safety assessments. 
During this period, when subjects are no longer receiving study drug, it is recommended that 
they are not treated with other biologic therapy, due to the compound’s half-life. However, this 
decision remains at the investigator’s discretion. If the study drug becomes commercially 
available, and if the subject chooses to receive treatment with the commercial product, then the 
subsequent post-dose follow-up visits are not required.
For more details, refer to the study protocol.
2.2
Treatment Assignment
After completion of all screening evaluations and confirmation of eligibility, subjects will be 
randomized on Day 1 to one of the following dosing arms in a 1:1:1:1:1 ratio in Part 1 of the 
study design: BMS-931699 at 12.5mg weekly sub-cutaneous (SC) injection, BMS-931699 at 
12.5mg every other week (EOW) SC injection, BMS-931699 at 5mg EOW SC injection, BMS-
931699 at 1.25mg EOW SC injection, or Placebo SC injection. The randomization ratio and the 
treatment arms may be modified based on the results from the two interim analyses defined in 
Section 7.6. 
In this study, subjects will be randomized to receive one of the treatments according to a 
computer-generated randomization scheme prepared by a Randomization Coordinator within the 
Drug Supply Management Department of BMS Research and Development.
During the Screening visit, the investigative site will call into the enrollment option of the 
Interactive Voice Response System (IVRS) designated by BMS for assignment of a 5-digit 
subject number that will be unique across all sites. Enrolled subjects, including those not dosed, 
will be assigned sequential subject numbers starting with 00001, 00002, 00003.... 00010. The 
patient identification number (PID) will ultimately be comprised of the site number and subject 
number. For example, the first subject screened (i.e., enrolled) at site number 1, will have a PID 
of 0001 00001.Once it is determined that the subject meets the eligibility criteria following the 
Screening visit, the investigative site will call the IVRS to randomize the subject into the 
treatment period.
Every randomized subject will be required to come to the clinic/research center weekly to be 
dosed. This will ensure double-blind is maintained despite the variability of regimens. Subjects 
randomized to weekly subcutaneous injections of either placebo or BMS-931699 will be dosed 
weekly as per schedule and subjects randomized to one of the every other week arm will be 
alternating between receiving a subcutaneous injection of BMS-931699 one week and one of 
placebo the following week.
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2.3
Blinding and Unblinding
2.3.1
Blinding at the Study Sites
The subjects and clinical assessor(s) will not be aware of which treatment is being administered 
to the subjects enrolled in the study. The pharmacist (or qualified drug preparation person) will 
be unblinded to study medication (BMS-931699 or placebo).
The pharmacist (or qualified drug preparation person) will know the randomization assignments 
and prepare the appropriate dose of active BMS-931699 or placebo accordingly. The prepared 
drug must be supplied to study personnel in a manner such that neither study personnel nor 
subjects will be aware of whether they receive active drug or placebo.
2.3.2
Unblinding of the Study Sites
Blinding of treatment assignment is critical to the integrity of this clinical study. However, in the 
event of a medical emergency or pregnancy in an individual subject in which knowledge of the 
investigational product is critical to the subject’s management, the blind for that subject may be 
broken by the investigator. The subject’s safety takes priority over any other considerations in 
determining if a treatment assignment should be unblinded.
Before breaking the blind of an individual subject’s treatment, the investigator should determine 
that the unblinded information is necessary, i.e., that it will alter the subject’s immediate 
management. In many cases, particularly when the emergency is clearly not related to the 
investigational product, the problem may be properly managed by assuming that the subject is 
receiving active product. It is highly desirable that the decision to unblind treatment assignment 
be discussed with the Medical Monitor, but the investigatory always has ultimate authority for 
the decision to unblind. The Principal Investigator should only call in for emergency unblinding 
AFTER the decision to discontinue the subject has been made.
For this study, the method of unblinding for emergency purposes is IVRS.
For information on how to unblind in an emergency, consult the IVRS manual.
In cases of accidental unblinding, contact the Medical Monitor and ensure every attempt is made 
to preserve the blind.
Any request to unblind a subject for non-emergency purposes should be discussed with the 
Medical Monitor.
In case of an emergency, the Investigator(s) has unrestricted access to randomization information 
via the Interactive Voice Response System (IVRS) and is capable of breaking the blind through 
the IVRS system without prior approval from sponsor. Following the unblinding the Investigator 
shall notify the Medical Monitor and/or Study Director.
2.3.3
Other Unblinding Information
For analysis of pharmacokinetic and anti-BMS-931699 samples, the Bioanalytical Sciences 
Group at BMS, and/or the designated vendor performing the analysis will be unblinded to the 
randomized treatment assignments in order to minimize unnecessary analysis of samples from 
control group subjects.
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In collaboration with the DMC, an unblinded internal safety monitoring team, which is 
independent of the study team, will review the safety data throughout the study and will provide 
recommendations to the blinded study team. Therefore, the unblinded internal safety monitoring 
team can be unblinded. The unblinded internal safety monitoring team will have members from 
the Global Pharmacovigilance and Epidemiology group (GPV&E) within BMS.
The following BMS personnel will form the unblinded team (Independent of the blinded study 
team): one or more GPV&E physicians, one or more PK scientists, pharmacometrics analysts, 
one or more statisticians and programmers.
 
 
 
 
 
 
 
2.4
Protocol Amendments
Table 2.4-1:
Protocol Amendments
Amendment 
No.
Amendment 
Date
Main Purpose of Amendment
1
20-AUG-2014
Pharmacogenetics amendment
2
24-SEP-2014
Brazil specific amendment
3
16-DEC-2014
Japan specific amendment
4
11-FEB-2015
Argentina specific amendment
5
16-MAR-2015
Japan specific amendment to add Exclusion Criteria regarding 
Laboratory Test of Hepatitis-B and Allergies
6
28-APR-2015
Revised Protocol no.1 (adding LTE, allowing MMF, edits, 
adding clarity)
7
29-JUN-2015
Canada specific amendment to limit LTE to 1yr (until further 
data are available)
8
01-Oct-15
Removing RNA testing (Site 152 (Japan) only)
9
22-Apr-16
To add intensive PK blood sample collections and also add 
sparse receptor occupancy samples in the PK substudy
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3
OBJECTIVES
3.1
Primary Objective
To compare the proportion of patients who achieve BICLA response (BICLA response rate) at 
Day 169 following 24-week treatment with BMS-931699 or placebo administered on a stable 
background therapy.
3.2
Secondary Objectives
To assess:

The safety and tolerability of treatment with BMS-931699 in patients with 
active SLE

The proportion of patients who meet response criteria for the SLE Responder 
Index (4) [SRI (4)], SRI(5), and SRI(6)] at Day 169 following 24-week 
treatment with BMS-931699 or placebo administered on a stable background 
therapy.

The proportion of patients with SLE Responder Index [SRI(4), SRI(5), and 
SRI(6)] at Day 85 following 12-week treatment with BMS-931699 or placebo 
administered on a stable background therapy.

The proportion of patients with a BICLA response at Day 85 following 12-
week treatment with BMS-931699 or placebo administered on a stable 
background therapy.

The improvement in the extent of cutaneous and mucous membrane activity, 
as measured by the Cutaneous Lupus Erythematosus Disease Area and 
Severity Index (CLASI) at Day 85 and Day 169

Joint pain, tenderness and swellings as measured by the by American College 
of Rheumatology (ACR)28 at Day 85 and Day 169

The other indices of SLE activity measured at Days 29, 57, 85, 113, 141, and 
169 including:
The change from baseline in overall BILAG-2004 score. A major response 
is defined as described in Yee et. al. 2010 (A=12; B=8; C=1; D/E=0).2
The change in overall Systemic Lupus Erythematosus Disease Activity 
Index 2K score (SLEDAI 2K)
The change from baseline in Physician’s Global Assessment of disease 
activity (MDGA) score

The systemic exposure of BMS-931699 in patients with SLE

The cumulative corticosteroids use and immunosuppressant use over time

The immunogenicity of BMS-931699

Serum biomarkers C3, C4, anti-double-stranded deoxyribonucleic acid (anti-
dsDNA), anti-nuclear antibody (ANA) and other autoantibodies at Day 85 and 
Day 169
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
Percentage of subjects with an improvement of at least 4 or an improvement 
of at least 50% from baseline in their CLASI score at Day 85 and Day 169

Proportion of subjects with an improvement of at least 4 or an improvement of 
at least 20% from baseline in their CLASI score at Day 85 and Day 169          

Change from baseline in arthritis, as assessed by American College of 
Rheumatology (ACR) 28 joint counts of tender, swollen, and as well as active 
joints, i.e. those that are both tender and swollen at Day 85 and at Day 169

The change from baseline in the following other indices SLE activity over 
time:
The overall BILAG-2004 score
The overall SLEDAI-2K score
The overall MDGA (Physician’s Global Assessment of Disease Activity) 
score

Change from baseline in SLICC/ACR Damage Index

The cumulative corticosteroid and immunosuppressant use over time
4.3
Safety Endpoints

Incidence and severity of all Adverse Events (AEs), Serious AEs (SAE), and 
Events of Special Interest (EOSI) pre-established in Section 6.7.1 of the 
protocol (including but not limited to Infections, Autoimmunity, Malignancies 
and Injection site reactions)

Incidence and severity of clinically significant changes in vital signs

Incidence and severity of clinically significant electrocardiogram (ECG) 
abnormalities

Incidence and severity of clinically significant abnormalities in general 
laboratory tests
4.4
Pharmacokinetic Endpoints
Ctrough: Trough level serum concentration of BMS-931699 at time points specified in Section
5.5 of the protocol.
 
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If the interim analysis for futility and dose adaptation suggests an additional dose arm at a lower 
dose level needs to be added, then up to 40 additional subjects may be randomized.
6
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS FOR 
ANALYSES
6.1
Study Periods
The following periods are defined in this SAP for the purpose of analyses and reporting.
Pre-treatment period: It covers the time period which starts from the day of enrollment and 
lasts until the initiation of the randomized double-blind treatment period.
Short-term period (ST): It starts at the time of the first dose of blinded treatment (BMS-931699 
or placebo, regardless if it was received during Part 1 or Part 2 of study design) and continues up 
to the start of the first long-term extension dose (Day 169). For subjects who discontinue during 
the short-term period or do not enter the long-term extension period, it continues up to 42 days 
post last dose.
Long-term extension period (LTE): It starts at the first dose date of long-term extension (Day 
169) and continues up to 42 days post the last study dosing date (LTE dose). Cutoffs may be 
applied for interim locks.
6.2
Treatment Regimens
All subjects will receive BMS-931699 or Placebo every week (double-dummy).

BMS-931699 at 12.5mg weekly sub-cutaneous (SC) injection

BMS-931699 at 12.5mg every other week (EOW) SC injection

BMS-931699 at 5mg EOW SC injection

BMS-931699 at 1.25mg EOW SC injection

Placebo SC injection (every week)
Subjects randomized to weekly subcutaneous injections of either placebo or BMS-931699 will 
be dosed weekly as per schedule and subjects randomized to one of the every other week arm 
will be alternating between receiving a subcutaneous injection of BMS-931699 one week and 
one of placebo the following week.
There may be an instance of new treatment group as per study design. Also one or more 
treatment arms (other than Placebo) may be dropped based on interim analyses.
For more details, see study design in IM128-027 Protocol.
6.3
Populations for Analyses

All Enrolled Subjects: All subjects who signed an informed consent.

All Randomized Subjects: All subjects who are randomized to a treatment.
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
Modified Intent-to-Treat (MITT) Analysis Population: All randomized 
subjects who have received at least one dose of the study medication. Subjects 
will be grouped according to the treatment to which they were randomized by 
IVRS at the start of the study. The MITT analysis population will also be 
referred to as “All Randomized and Treated Subjects”.

As-Treated Analysis Population: All Subjects who have received at least one 
dose of study medication. Subjects will be grouped according to the 
treatments to which they are randomized, except in cases where a subject 
receives a different treatment for the entire course of short term period. In this
case, the subject will be analyzed and presented by the treatment they actually 
received.

Efficacy Analysis Population: This is a subset of the MITT Analysis 
Population where the subjects from Part 1 who are randomized to a treatment 
arm and discontinued based on the Part 1 Safety/RO analysis are excluded. 
All efficacy results that involve statistical comparison or modeling will be 
based on this analysis population unless otherwise specified.

Biomarker Analysis Population: All subjects who receive any study 
medication and have at least one post-treatment biomarker measurement. 

Pharmacokinetic Population: All subjects who received BMS-931699 and 
have any available concentration-time data. 

Immunogenicity Population: All subjects who receive any study medication
and have at least one post treatment immunogenicity assessment.
7
STATISTICAL ANALYSES
7.1
General Methods
The table below provides an overview of the efficacy analyses to be performed.  
Table 7.1-1:
Planned Efficacy Analyses
Measure of Interest (Primary 
and Secondary Efficacy 
Endpoints):
Analysis Method
Primary endpoint (Binary): BICLA 
response rate at Day 169
Binary endpoints :  SRI(X) [ X= 4, 
5, 6, 8] at Day 85 and Day 169, 
BICLA response rate at Day 85, 
CLASI Response at Day 85 and 
Day 169
Chi-Square test, one sided p-value will be provided. Point estimates and 
90% CI of treatment difference. No multiplicity adjustments.
Point estimate and 90% CI of response rate, point estimates and 90% CI 
of treatment difference 
Continuous endpoints: CLASI, 
BILAG-2004, SLEDAI-2K, 
MDGA, ACR 28 [tender, swollen, 
and active,    (i.e. joints that are 
both tender and swollen) joint 
Mixed model analysis, point estimates and 90% CI for mean change from 
baseline within treatment groups, point estimates and 90% CI for mean 
change from baseline between treatment groups (BMS vs. PLA)
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Table 7.1-1:
Planned Efficacy Analyses
Measure of Interest (Primary 
and Secondary Efficacy 
Endpoints):
Analysis Method
Counts]
The Chi-square tests will be used to compare the BICLA response rates at Day 169 between each 
of the active treatment arms and the placebo arm. The Chi-square p-value will be provided for 
each comparison between the active treatment and the placebo arm. In addition, the difference of 
the response rates between each active treatment and the placebo arm will be estimated and their 
corresponding 90% confidence interval will be calculated. No adjustment will be made for 
multiplicity.
For each of the binary endpoints, the estimate and its corresponding 90% confidence interval will 
be calculated for the difference of the proportions between each active treatment arm and the 
placebo arm at the specified visit, similar to the primary analysis except no p-values will be 
provided.
The construction of confidence intervals for binary variables will be based on normal 
approximation if the number of the events in each individual treatment arm is at least 5. 
Otherwise, confidence interval using an exact method will be provided. The exact confidence 
intervals for binary variable within treatment group and between treatment groups will be 
constructed.
For each of the continuous endpoints, the mixed model will be fit with treatment, visit, and 
treatment-by-visit interaction as the fixed effects and measurements within each subject as the 
repeated measurements. The baseline value will be added into the model as a covariate if 
necessary. Based on the mixed model, the estimate and 90% confidence interval will be 
calculated for the difference between each active treatment and the placebo at each specified 
visit.
The results will be presented by the following grouping scheme in different periods, unless 
otherwise specified. 

Pre-treatment period: Only one group: All enrolled subjects.

Short-term period (ST): The results will be presented by treatment groups. 
7.2
Study Conduct
Relevant protocol deviations, which could have an impact on the primary/key efficacy endpoint, 
will be identified for all subjects who are randomized and receive study medication during the 
double-blind period. Details of relevant protocol deviations are provided in Appendix 1. 
All subjects with relevant protocol deviations that could affect the primary efficacy will be 
identified prior to database lock and unblinding of treatment assignment. All relevant protocol 
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deviations will be listed and summarized by treatment group. The subjects identified as relevant 
protocol deviation will not be excluded from any analysis population described in Section 6.3. If 
at least 10% of total subjects in all treatment arms in the efficacy analysis population 
demonstrate relevant protocol deviations, a per-protocol analysis may be performed.
7.3
Study Population
Frequency distributions or summary statistics of data pertaining to subject disposition, 
demographic characteristics, baseline disease characteristics, and medical history will be 
tabulated and displayed by treatment group.  No statistical test will be carried out for comparison 
of any baseline measures among treatment groups.
These presentations will be provided by randomized treatment group for the MITT analysis 
population, unless specified otherwise. 
7.3.1
Subject Disposition
The number of subjects enrolled into the study at screening, the number of subjects randomized, 
the number of subjects entering the short-term period (ST) and the number of subjects who 
complete the ST period will be summarized by treatment groups. The number of subjects
discontinuing from the ST period (subject disposition) will also be summarized, together with 
the reasons for discontinuation, taken from the CRF status pages. The subject disposition for the 
ST period will be based on the MITT analysis population.
7.3.2
Demography and Baseline Characteristics
Demographic and baseline disease characteristics will be summarized by randomized treatment 
group and overall based on the MITT analysis populations. For continuous variables, they will 
be summarized using means, standard deviations and ranges.  The distribution of categorical 
variables such as gender, race etc. will be summarized by treatment group using frequency and 
percentage. 
Demographic characteristics include the following: 

Age in years

Weight in kg

Gender: Male, Female

Race

Ethnicity (Hispanic and Non-Hispanic)

Region (North America, South America, Europe and Asia)

Stratification [Japan vs. Non-Japan, MMF use (Y/N)]

Baseline clinical characteristics include the following: 

Time from First Diagnosis of SLE (years)

Tender Joint Counts 

Swollen Joint Counts
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
Active (Both Tender and Swollen) Joint Counts 

BILAG classifications and numerical scores

SLEDAI-2K Score 

CLASI Score

Physician’s global assessment of disease activity (MDGA)

Subject’s global assessment of disease activity (PGA)

SLICC/ACR damage index

Total corticosteroid daily dose (prednisone equivalent) at baseline
7.3.3
Medical History and Prior Medication
Medical history and prior medication information before the first study medication will be 
summarized by treatment group using relative frequencies. Listings of medical history and prior 
medication will be presented. The results will be based on the MITT analysis population.
7.4
Extent of Exposure
7.4.1
Study Therapy
In general, extent of exposure during ST will be summarized for the As-treated analysis 
population in two ways: 

by the number of study drug injections: Frequency distribution of number of 
injections will be summarized

by the number of days: the subject is known to be on study drug, ignoring any 
dosing interruptions
In general, exposure to study drug during the short-term period (ST) is calculated as follows: 
1. The subjects who enter in the long-term extension period (LTE) within 7 days 
of the last study medication in ST,
Exposure (in days) = (date of first study medication in LTE - date of first study 
medication in ST).
2. All other subjects (including the subjects who discontinue early, complete the 
ST but do not enter in the LTE or enter LTE after 7 days post the last dose of 
the ST):
Exposure (in days) = date of last study medication in ST - date of first study 
medication in ST + 7
Note that, the offset of 7 days represents the dosing interval of 7 days. 
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The frequency will be presented according to the duration ranges (in days) : <=28, 29-56, 57-84 
and so on.
7.4.2
Discontinuations from Study Therapy
Discontinuation from study therapy is defined as subject’s termination of the study medication 
without resumption prior to study completion. Note that, subjects are to be discontinued if more 
than 3 consecutive doses of study medication are missed. Discontinuation from study therapy 
during the ST period will be summarized by reason for the premature termination, taken from the 
study status case report form (CRF) pages. These summaries will be provided based on the 
MITT analysis population by randomized treatment group and overall.
7.4.3
Treatment Compliance
The CRF for this study will capture information on injections of the study medication. All 
subjects who skip any study drug injection will be listed. The number of subjects with missed 
injections (excluding missed injections due to premature discontinuation from the study) by 
number of missed injections will be summarized based on the As-treated analysis population for 
the ST period by treatment groups.
 
7.4.5
Immunosuppressant  Medication
For the purpose of this analysis plan, the term DMARDs will refer to non-biologic DMARDs. 
Immunosuppressant medications summaries will be provided to present the medication use of 
corticosteroids, NSAIDs, and DMARDs. Number and percent of subjects receiving 
corticosteroids, NSAIDs, and DMARDs will be summarized by treatment group for MITT 
analysis population during the ST period. 
A comprehensive listing of all concomitant medications including immunosuppressant will be 
also provided for the MITT analysis population.
7.4.6
Corticosteroids
The average daily corticosteroid dose (prednisone equivalent) and its change from baseline will 
be summarized over time by treatment group for the ST period.
7.5
Efficacy
The efficacy analyses will be performed using the efficacy analysis population. The results will 
be grouped by “as randomized” treatment groups, unless otherwise specified. No formal 
statistical testing was pre-specified for other efficacy endpoints except the primary endpoint of 
BICLA response at Day 169. The analyses of binary endpoints and continuous endpoints will be 
provided over time including the milestone visits (e.g. Day 85, Day 169 etc.). 
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7.5.1
Primary Efficacy Endpoints in the Short-term Period
The primary efficacy endpoint is BICLA response rate at Day 169.
The Chi-square tests will be used to compare the BICLA response rates at Day 169 between each 
of the active treatment arms and the placebo arm. The Chi-square p-value will be provided for 
each comparison between the active treatment and the placebo arm. No adjustment will be made 
for multiplicity. In addition, the difference of the response rates between each active treatment 
and the placebo will be estimated and their corresponding 90% confidence interval will be 
calculated for Day 169 visit and other applicable visits. 
The point estimate for BICLA response rate along with 90% confidence interval will be 
calculated for each treatment arm for each applicable visit.
All subjects who prematurely discontinue the trial after receiving study medication will have
missing data imputed as non-responder at all scheduled protocol visits subsequent to the point of
discontinuation. The analysis will be performed based on Efficacy Analysis Population. More
details of imputation rule for classification of binary response status are provided in Sections 8.3,
8.1.1, and 8.1.2.
For BICLA, the number of responders, together with the rescue status (with or without one-time 
rescue allowed per protocol) will be summarized by treatment group. At the same time, the 
number of nonresponders will be summarized by treatment group, together with the reasons for 
nonresponse.
7.5.2
Secondary Efficacy Endpoints in the Short-term Period
For each of the binary endpoints (SRI(X) etc.), the estimate and its corresponding 90% 
confidence interval will be calculated for the difference of the proportions between each active 
treatment arm and the placebo arm for each applicable visit, similar to the primary analysis 
except no p-values will be provided.
For each of the continuous endpoints (BILAG-2004, SLEDAI, MDGA, CLASI, etc.), the mixed 
model will be fit with treatment, visit, and treatment-by-visit interaction as the fixed effects and 
measurements within each subject as the repeated measurements. The baseline value will be 
added into the model as a covariate if necessary. Based on the mixed model, the estimate and 
90% confidence interval will be calculated for the difference between each active treatment and 
the placebo at each specified visit. No p-values will be provided. In addition, Descriptive 
summary statistics of mean change from baseline and 90% confidence interval for each treatment 
arm will be provided. The missing data in continuous measures will be handled via utilization of 
mixed model procedure in SAS.
7.5.3
Subgroup Analyses
The subgroup analyses of the primary and selected secondary endpoints ((SRI (X): X = 4, 6.)) 
will be performed within the following predefined subgroup (Non-Japan subjects). If the value of 
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the grouping variable cannot be determined for a subject, the subject will be excluded from the 
corresponding subgroup analysis. 
In addition, other subgroup analyses may be performed on primary and selected secondary 
endpoints as post-hoc analysis. 
7.5.4
Sensitivity Analyses
Sensitivity analysis for the primary endpoint: Adjustment for the randomization strata using 
Cochran-Mantel-Haenszel (CMH) methods will be applied on the primary endpoint. 
If at least 15-20% of total subjects through all treatment arms in the efficacy analysis population 
discontinued due to any reasons other than Lack of Efficacy (LOE), AE or Unknown reason, a 
sensitivity analysis may be performed. The subjects who have missing response due to premature 
discontinuation with reasons other than LOE, AE or Unknown will be excluded from the 
analyses, hence defining the sensitivity analysis population. The sensitivity analysis will be 
carried out for the primary and selected secondary endpoints (SRI (X): X = 4, 6.) based on the 
sensitivity analysis population.
7.5.5
Per-Protocol (PP) Analyses
If at least 10% of total subjects in all treatment arms in the efficacy analysis population 
demonstrate relevant protocol deviations, a per-protocol analysis may be performed. A per-
protocol analysis will be carried out for the primary and selected secondary endpoints (SRI (X): 
X = 4, 6.) based on the per-protocol (PP) analysis population. A Per-protocol (PP) analysis 
population will exclude all subjects with at least one relevant protocol deviation (defined in 
Appendix 1) from the efficacy analysis population based on the following rules.

The subjects satisfying eligibility criteria deviation in Appendix 1 will be excluded from the 
PP analysis population completely. 

The subjects satisfying incorrect dosing criteria deviation in Appendix 1 will be excluded 
from the PP analysis population partially (only the data after deviation occurs will be 
excluded from the per-protocol (PP) analysis.)
7.6
Safety
Analysis of all safety data will follow the BMS standard safety data conventions4 5 and 
supplements to the standard conventions as defined in this document.
The evaluation of drug safety is based primarily on clinical AE, laboratory abnormalities and 
vital signs reported during the study.
The summaries of AEs and laboratory marked abnormality during the ST period will be provided 
by treatment groups. AEs and laboratory marked abnormalities will be included in the summary 
tables based on ST period if the onset date is on or after the first dose date and event occurs 
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within the ST period for continuing subjects or within 42 days post last dose date for 
discontinued subjects.
Frequency distribution and individual listings of all AEs will be generated. Laboratory marked 
abnormality using pre-defined abnormality criteria will also be descriptively summarized. There 
will be no statistical testing of group difference with respect to frequencies of AEs or laboratory 
marked abnormalities.
All recorded adverse events will be listed and tabulated by system organ class, preferred term, 
treatment and overall. Any physical examination findings will be listed. ECG, vital signs and 
clinical laboratory test results and corresponding change from baseline values will be listed and 
summarized by treatment. Values for ECG, vital signs and clinical laboratory test results outside 
the pre-specified criteria will also be listed and summarized. ECG readings will be evaluated by 
the Investigator and abnormalities, if present, will be listed.  
Unless otherwise specified, baseline is defined as the last non-missing result with a collection 
date-time less than the date-time of the first dose of study medication, for laboratory results, vital 
signs and ECG.
Presentations for the ST period will be provided by “as treated” treatment group for the as-
treated analysis population, unless otherwise specified.
7.6.1
Adverse Events
The investigator will determine the intensity of each AE as mild, moderate, severe, or very 
severe. In addition, the investigator will determine the relationship of the AE to the 
administration of the study drug.
All AEs are coded and grouped into Preferred Terms (PT) by System Organ Class (SOC), using 
the latest approved version of the Medical Dictionary for Regulatory Activities (MedDRA) at the 
time of database lock.  Listings and summaries will be based on the resulting SOCs and PTs.
AEs will be included in the frequency tabulations if they occur while a subject is on study 
medication up to and including 42 days after the last dose of study medication. These AE 
summaries will be based on proportions, which represent the number of subjects experiencing 
the AEs divided by the number of subjects received with at least 1 dose of study medication in 
the current period.
All AE listings will indicate the unique subject identifier, age, gender, current treatment, the date 
of onset, the date of resolution, day of onset relative to the start of treatment, action taken, 
investigator’s assessment of severity and relationship to study drug. Additional listings will be 
provided for adverse events leading to discontinuation and adverse events without recorded 
resolution. Summaries of adverse events will include adverse events, adverse events by intensity 
and adverse events by relationship.  
Where a subject has the same adverse event, based on preferred terminology, reported multiple 
times in a single analysis period, the subject will only be counted once at the preferred 
terminology level in adverse event frequency tables.
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Where a subject has multiple adverse events within the same system organ class in a single 
analysis period, the subject will only be counted once at the system organ class level in adverse 
event frequency tables.
When a subject has the same adverse event, based on preferred terminology, reported multiple 
times in a single analysis period, the following criteria, in order of precedence, will be used to 
select the event to be included in summary tables:

Relationship to study medication

Intensity of event

Onset date and time
When reporting adverse events by intensity, in addition to providing a summary table based on 
the event selection criteria detailed above, summary tables will also be provided based on the 
most intense event during the analysis period - independent of relationship to study medication. 
For these tables, the following criteria, in order of precedence, will be used to select the event to 
be included in summary tables:

Intensity of event

Onset date and time
Subjects will only be counted once in the ‘Total’ at their maximum intensity, regardless of SOC 
or PT.
Any reported AEs that occur more than 42 days after the last dose of study drug will be excluded 
from safety summaries. Any reported AEs that occur more than 42 days post the last dose of 
study drug will appear in the listing. 
Summary information (the number and percent of subjects by treatment) will be tabulated for the 
following AEs: 

All AEs including clinical and laboratory AEs

Most common AEs (reported in 5% of subjects or more in any treatment 
group)

All related events

Serious AEs (SAEs)

Discontinuations due to AEs
Laboratory AEs are laboratory changes identified by the investigator as AEs and thus reported on 
the AE pages of the eCRF.
7.6.2
Adverse Events of Interest 
The following adverse events of special interest will be listed and summarized by treatment 
groups during the ST period. 
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
Infections: All reported infections and infestations within the SOC: Infections 
and infestations. The severity of serious infections will be summarized. In 
addition, a listing of opportunistic infections will be provided.

Malignancy: All reported events defined in MedDRA Maintenance and 
Support Services Organization (MSSO) Structured MedDRA Query (SMQ) 
list.

Autoimmunity: All reported events defined in pre-specified MedDRA code of 
autoimmune disorders.

Injection Reactions (Local and Systemic): All reported events defined in pre-
specified MedDRA code of injection reactions (Local and Systemic).
7.6.3
Deaths
All AEs with the outcome of death reported during the study will be listed. All reported deaths 
after a subject is enrolled will be listed separately by subject.
7.6.4
Other Serious Adverse Events
SAEs are captured on an eCRF page. All SAEs and related SAEs will be summarized by 
treatment group and listed.
7.6.5
Adverse Events Leading to Discontinuation of Study Therapy
AEs leading to discontinuation of study drug are identified on the eCRF will be listed and 
summarize.
7.6.6
Multiple Occurrences of Adverse Events
Several descriptive summaries of adverse events that takes into account the number of 
occurrences that an AE was reported by individual patients will be provided.  In order to prepare 
these summaries, the CRF data will be processed according to standard BMS algorithms to 
categorize each line of patient data as a new occurrence or a continuation of an existing event. 
This determination will be based upon onset and resolution dates. Each line of patient data will 
represent the maximum severity observed as well as the last known assessed relationship to study 
medication by the investigator.  
The number and proportion of subjects who experienced an AE once or multiple times (0 Events, 
1 Events, 2-3 Events, >=4 Events) will be summarized by treatment groups for most common 
AE (at least 5% subject in any treatment group) and event of special interest, infections.
Listing displaying the unique instances of all AEs will be provided.
Note: The unique instances of all AEs will be generated after duplicates have been eliminated 
and overlapping and contiguous occurrences of the same event have been collapsed.
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7.6.7
Summaries of Laboratory Data
The results of all protocol-specified clinical laboratory tests, as well as laboratory results outside 
of the normal range, will be listed. Scheduled laboratory measurements and corresponding 
change from baseline values will be summarized by treatment and nominal visit for each 
laboratory test for the MITT analysis population. 
The frequency of subjects with any marked laboratory abnormality (based on sponsor defined 
criteria) will be presented by laboratory test during the ST period. The results are based on the 
As-treated analysis population. The criteria used for classifying laboratory test results as 
markedly abnormal will be listed. 
7.6.8
Other Safety Considerations
7.6.8.1
ECG
Summary statistics (n, mean, standard deviation, median, minimum, and maximum) will be 
presented for each ECG parameters and the corresponding changes from baseline by treatment 
and visit. The baseline value is defined as the last measurement before the first dose. ECG 
readings will be evaluated by the Investigator and abnormalities, if present, will be listed.  
The frequency distribution of subjects’ maximum recorded post-dose QTcF, PR, QRS and 
QTcF will be tabulated by treatment and summarized within the CSR text for the following 
ranges:
For QTcF:  QTcF ≤ 450 msec, 450 msec < QTcF ≤ 480 msec, 480 msec < QTcF ≤ 500 msec, 
QTcF > 500 msec
For PR: PR ≤ 200 msec, PR > 200 msec
For QRS: QRS ≤ 120 msec, QRS > 120 msec
For QTcF: QTcF ≤ 30 msec, 30 msec < QTcF ≤ 60 msec, QTcF > 60 msec
Individual QTcF, PR, QRS or QTcF values meeting these criteria will be flagged in the data 
listing.
7.6.8.2
Vital Sign
Vital signs parameters (systolic blood pressure, diastolic blood pressure, heart rate, respiratory 
rate and body temperature) will be listed. Summaries of vital sign parameters will be provided 
for each vital sign parameter at corresponding visits by treatment and respective changes from 
baseline. Subjects with vital signs outside of a pre-specified range will also be listed.
The following criteria will be used to determine vital sign results that are outside of a pre-
specified range, where changes from baseline are based on matched postural positions and are 
calculated as parameter value - baseline parameter value:
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Table 7.6.8.2-1:
Vital signs criteria
Vital sign
Criteria
Heart Rate(bpm)
Value > 100 and change from baseline > 30, or
Value < 55 and change from baseline < -15
Systolic BP(mmHg)
Value > 140 and change from baseline > 20, or
Value < 90 and change from baseline < -20
Diastolic BP(mmHg) 
Value > 90 and change from baseline > 10, or
Value < 55 and change from baseline < -10
Respiration(breaths/min)
Value > 16 or change from baseline > 10
Temperature (°C)
Value > 38.3°C or change from baseline > 1.6°C
7.6.8.3
Conventions of ECG Data
All available non-missing values of ECG parameters should be used in the listings, 
summarizations, and analyses. However, if QTcF is missing and RR in seconds is available, then 
QTcF will be calculated as 
3
/
1
RR
QT
QTcF 
.
If both QTcF and RR in seconds are missing, then QTcF will be calculated as


3
/
1
60
RATE
HEART
QT
QTcF 
.
7.6.8.4
Physical Examination Findings
All physical examination abnormal findings will be listed per subject by visit. 
7.7
Pharmacokinetic Analysis 
Summary statistics of Ctrough (mean, SD, geometric mean, % CV, median, min, and max) for 
the PK analysis population will be provided by treatment and study day.
Similar statistics will be provided for post-dose concentration on Day 46 and Day 48.
The listing of Concentration of BMS-931699 by treatment and study day will also be provided.
 
 
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7.9
Immunogenicity Analysis
Serum for anti-BMS-931699 antibody titers will be drawn at Day 1, and during the ST period.
Subjects who discontinue study medication will have a serum samples collected at the early 
termination visit and 42 days after the last dose of study medication (42 days follow up). Lack of 
immunogenicity is defined as the absence of a positive response. 
For all summaries and listings unless specified otherwise, an anti-drug antibody (ADA) positive 
relative to baseline immunogenicity response is defined as:
1) a missing baseline immunogenicity measurement and a positive laboratory reported 
immunogenicity response post-baseline
2) a negative laboratory reported baseline immunogenicity response and a positive 
laboratory reported immunogenicity response post-baseline
3) A positive laboratory reported baseline immunogenicity response and a positive 
laboratory reported immunogenicity response post-baseline that has a titer value of 4 fold
or greater than the baseline titer value.
All other immunogenicity measurements will be classified as negative immunogenicity response.  
In addition, persistent anti-drug antibody is defined as anti-drug antibody positive occurrence 
relative baseline detected at 2 or more consecutive time points at least 3 months apart.
Immunogenicity Frequencies
7.9.1
Immunogenicity Frequency
The number (and percentage) of anti-drug antibody positive subjects relative to baseline will be 
provided. Similar analyses will be performed for persistent anti-drug antibody positive subjects
(relative to baseline).
The number (and percentage) of subjects whose last sample is the only anti-drug antibody
positive sample relative to baseline will be presented also.
A listing of titer values for all ADA positive subjects (laboratory reported) will be provided for 
antibodies against the domain antibody portion of the drug.
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7.10
Interim Analyses
7.10.1
Interim Safety/RO Analysis at Day 29
When at least 6 patients per treatment arm have either reached Study Day 29 or discontinued, an 
interim analysis (IA) for safety and RO will be performed. The safety analysis will focus on 
incidence and severity of all adverse events (AEs), serious AEs and pre-established Events of 
Special Interest such as infection AEs and any other safety analysis requested by DMC. A 
separate document, DMC charter, describes the scope of these analyses. For RO: the median RO 
at Day 29 for each treatment arm will be calculated. Based on the results of this interim analysis, 
a decision will be taken regarding the doses that will be carried forward into Part 2 of the study. 
Specifically, dosing regimens originally included in Part 1 may be discontinued and/or new 
dosing regimens may be added according to the following criteria:
Safety:
The DMC in conjunction with an unblinded internal monitoring team (The details of the 
members are provided in Section 2.3.2) may require one or more doses to be discontinued if 
stopping criteria are met or other safety signals arise that the Medical Monitor and/or DMC 
consider of sufficient concern.
Receptor Occupancy:

If median RO of any dose is <20%, the sponsor may consider dropping that 
dose

If the median RO for all doses is >90% the sponsor may consider adding or 
replacing a dose in Part 2 of the study to ensure an adequate 
pharmacodynamic range (dose not to exceed 12.5 mg weekly)
Dose decrease and/or reduction of frequency of administration may also be considered if RO 
results fall outside the parameters indicated above. This adjustment may occur for safety reasons 
or in case unforeseen RO profiles observed in SLE patients. The decision to adjust dose and/or 
frequency will be taken after review of the data by the clinical team. Any decision related to 
safety reasons will be taken in conjunction with DMC recommendations.
RO analysis in interim analyses 1 will be done by a Pharmacokinetic scientist or a 
Pharmacometrics analyst. If dose/doses are adjusted based on this RO analysis, then the interim 
analyses results may be included in CSR as an appendix.
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7.10.2
Interim Analysis for Futility and Dose Adaptation at Day 85
After 30 subjects per treatment arm (including the subjects from Part 1) have completed at least 
84 days of the treatment period or discontinued the treatment, an interim analysis will be 
conducted to assess the futility of the BMS-931699 dose arms and the overall safety. The results 
of the interim analysis will be reviewed by an unblinded sponsor team (Independent of the study 
team) who will provide recommendations to the blinded study team. The details of the members 
are provided in Section 2.3.2. The blinded study team will make the decision. The unblinded 
BMS team may recommend to:

maintain the current design;

drop a certain dose arm(s) and equally randomize the remaining unallocated 
subjects to the remaining arms;

stop the study if all dose arms need to be dropped for safety or futility reasons.
Any decision related to safety reasons will be taken in conjunction with DMC recommendations.
The interim analysis for futility and dose adaption will be performed on the BICLA response at 
Day 85 of those 30 subjects per arm and BICLA response at Day 169 of those subjects who have 
completed 168 days of treatment or discontinued the treatment using a Bayesian predictive 
approach.6 This analysis assumes that the BICLA at Day 85 and at Day 169 in the subjects who 
have not yet been observed will be similar to what were observed for the subjects included at the 
interim analysis at Day 85 and Day 169, respectively. As such the unobserved data will be 
simulated from the predictive distribution conditional on the interim data and the prior 
distribution of the treatment difference (using a non-informative prior). Under the Bayesian 
framework, the posterior distribution of the treatment difference (BMS-931699 active dose –
Placebo) will be constructed to determine the predictive probability of a successful outcome 
(i.e., reach statistical significance) at the planned end of the trial for each dose arm. Based on 
computer simulations of the operating characteristics of the study design, the futility threshold in 
this interim analysis is set to 0.2. For the comparison of interest, if the predictive probability of a 
successful outcome at the planned end of the trial falls below 0.2, that BMS-931699 dose arm is 
deemed futile in terms of BICLA response. However, the final futility will also incorporate the 
results from the efficacy endpoints such as but not limited to SRI(4), ACR28 and some 
biomarkers such as but not limited to C3, C4, ANA and anti-dsDNA. The final decisions will be 
made based on the discussions using the pre-specified rules in the Interim Analysis SAP and/or
the evidence from the totality of the data.
The proposed stopping rules at the interim analysis, based on the futility assessment and the 
overall safety assessment, are as follows:

Rule 1: Drop the futile dose arm(s) and the dose arm cannot be dropped until 
the lower dose arm has been dropped.

Rule 2: Drop the dose arm(s) with safety issues identified;
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
Rule 3: If safety issues are identified in all dose arms or all dose arms are 
futile, stop the study.
In case dosing arms are dropped following the interim analysis, the remaining unallocated 
subjects will be randomized into the remaining arms.
If the predictive probability of success for each active arm versus placebo is greater than or equal 
to 0.9, then the BMS team may also recommend adding an additional dose arm at lower dose 
level than current active doses to explore the suboptimal dose.
In that case, the remaining un-allocated subjects with up to 40 additional subjects will be 
randomized into the remaining arms and the new dose arm based on the new randomizations 
schedule.
A separate document, Interim Analysis SAP, has been developed in order to provide a set of rules
with clarifying details as a guidance to make any decisions about the dose adaptation. 
 
 
 
 
 
 
 
 
7.11.2
Time to event Analysis
Time to treatment failure and time to first flare as assessed by new BILAG 2004 index flare 
definition will be summarized. For those time to event endpoints, if necessary, the point estimate 
and its 90% confidence interval for the hazard ratio of each active treatment arm versus placebo 
will be calculated based on the Cox proportional hazards models. In addition, the distribution of 
time to the occurrence of event will be estimated using Kaplan-Meier method. The analysis will 
be based on the Efficacy Analysis Population.
Treatment failure is defined as non-protocol treatment i.e., new or increased immunosuppressive 
treatment or antimalarials; or parenteral corticosteroids; or protocol prohibited dose of oral 
corticosteroid; or premature discontinuation from study treatment. 
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7.11.4
Immunogenicity and PK/Efficacy/Safety
A listing of drug concentration with immunogenicity assessment at each pre-specified time point 
will be provided for each individual subject who has positive immunogenicity response
(laboratory reported ADA positive).
Efficacy listings for all anti-drug antibody positive subjects (laboratory reported ADA positive) 
may be provided.
Listings of AEs, SAEs, and local injection site events for all anti-drug antibody positive 
(laboratory reported ADA positive) subjects will be provided.  
A list of neutralizing positive subjects (subjects with at least one ADA positive sample relative 
to baseline with neutralizing antibodies detected) will be provided also.
Depending on the incidence of ADA positive relative to baseline observed in SLE patients within 
this trial, individual plots of Ctrough with ADA status may be generated for all subjects with 
ADA positive relative to baseline.
7.11.5
Exposure-Response Analysis
The PK data obtained from this study may be pooled with data from other studies to perform an 
integrated population PK (PPK) analysis (including assessment of covariate effects on PK), as 
well as exposure-response analysis for selected safety and efficacy endpoints. These analyses 
will be described in a separate report(s).
7.11.6
Analysis for the PK Sub-Study
As specified in the amendment 9 of the protocol, participation for PK sub-study is voluntary. 
While there is no minimum required number of subjects, every effort will be made to enroll 
approximately 4 subjects/arm in the ST study (ie approximately 20 subjects total) and 
approximately 6 subjects/arm in the LTE (ie approximately 30 subjects total). This sample size is 
expected to provide sufficient data to adequately estimate PK parameters for lulizumab in this 
patient population. Subjects will be asked to read, understand, and sign an informed consent 
form designed for the purpose of collecting the additional PK/RO samples. 
Pharmacokinetics Analysis
All PK summaries and analysis will be done separately for first dose exposure and steady state 
exposure:
Summary statistics will be provided for all PK parameters by treatment groups for first dose 
exposure and steady state exposure. Geometric means and coefficients of variation (CV) will be 
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provided for Cmax, AUC(TAU), and C(Day15). Medians and ranges will be provided for Tmax. 
Mean and standard deviation may be provided for T-HALF and CLT/F. Additionally, scatter 
plots of AUC(TAU), Cmax and C(Day 15) versus dose for the three every 2 weeks treatment 
groups (1.25 mg, 5 mg and 12.5 mg every 2 weeks) to assess the dose-dependency. All plots will 
be provided separately for first dose exposure and steady state exposure.
A statistical analysis using a power model will be performed to assess dose proportionality in 
AUC(TAU), Cmax and C(Day 15) for only the three every 2 weeks treatment groups (1.25 mg, 5 
mg and 12.5 mg every 2 weeks). The analyses will be carried out separately for first dose 
exposure and steady state exposure.
In addition, a listing will be provided for all PK parameters and lulizumab concentration.
Receptor Occupancy Analysis:
Medians and ranges will be presented for RO by Day for all treatment groups in each subgroup. 
Box plots of RO by Day will be provided for all treatment groups in ST and LTE.
Immunogenicity Analysis:
The number and percentage of subjects will be summarized for each treatment, and the 
corresponding antibody titer values will be listed. Exploratory plots or analysis might be 
conducted to evaluate the impact of immunogenicity on PK of lulizumab.
All other safety, efficacy and biomarker observations that are being planned in the main study 
protocol will be reported in the clinical study report of the main study.
8
CONVENTIONS
8.1
Calculations of Key Measures
8.1.1
Evaluation of BICLA response
BICLA response is defined based on the following components:

British Isle Lupus Assessment Group improvement, defined as BILAG ‘A’s at 
Baseline improved to ‘B’/’C’/’D’, and BILAG ‘B’s at baseline improved to 
‘C’/’D’, and no BILAG worsening in other BILAG organ systems such that 
there are no new BILAG ‘A’s or greater than 1 new BILAG ‘B’; and,

No worsening in the SLEDAI-2K total score compared to Baseline (defined as 
no increase in SLEDAI total score); and,

No worsening in the physician’s global assessment (MDGA) of disease 
activity (“no worsening” is defined as less than 10% worsening, equivalent to 
a 10mm increase on a 100mm visual analog scale [VAS]) compared to 
Baseline; and,

No changes in concomitant medications according to the following criteria: 

No increase of or addition of a new immunosuppressant agent 
(azathioprine, methotrexate, anti-malarial) over baseline levels 
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
No increase in corticosteroid dose above baseline level outside of those 
allowed per protocol.
If a subject failed any of the above criteria above, the BICLA response status of the subjects will 
be set to non-responder.
For the determination of missing BICLA response status, all subjects who prematurely 
discontinue from the study medication will be imputed as non-responder at all scheduled efficacy
visits subsequent to the point of discontinuation.
If any subject has at most one missing component (e.g. MDGA for BICLA) at a given efficacy
visit not due to premature discontinuation, the component-wise response status will be imputed 
based on the following rules.

If the given visit is not the last scheduled efficacy visit (Day 169), imputation will depend 
on the observed responses from the immediate previous efficacy visit and the immediate 
next efficacy visit within 28 days of the current visit date. 

If the given visit is the last scheduled efficacy visit (Day 169), the imputation will depend 
on the observed responses at the previous 2 consecutive efficacy visits (within 56 days). 

If a subject has response (at component level) at both efficacy visits, the missing response 
status at current visit will be imputed as responder. Otherwise, response status will be set 
to non-responder.
The BICLA response status (composite) for a subject who has more than one component (e.g.
MDGA and SLEDAI-2K are missing for BICLA) missing at a given efficacy visit not due to 
premature discontinuation will be imputed as non-responder. 
After any imputation above or none, if for some reason the BICLA response status still cannot be 
determined, including the case where baseline data is missing, then its value will be set to non-
responder.
8.1.2
Evaluation of SRI(X)
In addition to BICLA, a novel endpoint, the SLE Responder Index [SRI] with a modification
used as a primary endpoint in the Anifrolumab study, the results of which were presented and 
published as an abstract at the American College of Rheumatology (ACR) National Meeting in 
November, 20157. The basic difference between the SRI defined in our protocol and the SRI in 
the Anifrolumab study is the addition of a fourth component of the endpoint. The original 
definition of SRI in the protocol does not include the fourth component based on the use of 
restricted medications.
The use of restricted medications is an important confounding factor when we analyze the 
endpoints such as BICLA, and SRI(X). Hence an additional component based on the use of 
restricted medications (same as the 4th component in the definition of BICLA) is deemed 
necessary to incorporate into the original definition of SRI (X) in the protocol. The modification 
to the existing definition of SRI is described below.
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An SRI(X) [X= 4, 5, 6, and 8] response @ Day T (e.g. T = 85, 169) is defined as:

a reduction in Day 1 SLEDAI-2K disease activity score of ≥ X points at 
Day T; and,

no worsening of disease (defined as an increase of ≥ 10mm on a 100mm 
VAS from Day 1 as measured by the MDGA up to time T; and,

no new BILAG-2004 Index ‘A’ organ system score and no more than one 
new or worsening BILAG-2004 Index ‘B’ organ system scores up to time 
T ; and, 

No changes in concomitant medications according to the following 
criteria: 
o
No increase of or addition of a new immunosuppressant agent (azathioprine, 
methotrexate, anti-malarial) over baseline levels 
o
No increase in corticosteroid dose above baseline level outside of those allowed 
per protocol.
If a subject failed any of the above criteria, the SRI(X) response status of the subjects will be set 
to non-responder. 
For the determination of missing SRI(X) response status, all subjects who prematurely 
discontinue from the study medication will be imputed as a non-responder at all scheduled 
efficacy visits subsequent to the point of discontinuation. 
If any subject has at most one missing component (e.g. MDGA for SRI(X)) at a given efficacy
visit not due to premature discontinuation, the component-wise response status will be imputed 
based on the following rules.

If the given visit is not the last scheduled efficacy visit (Day 169), imputation will depend 
on the observed responses from the immediate previous efficacy visit and the immediate 
next efficacy visit within 28 days of the current visit date. 

If the given visit is the last scheduled efficacy visit (Day 169), the imputation will depend 
on the observed responses at the previous 2 consecutive efficacy visits (within 56 days). 

If a subject has response (at component level) at both efficacy visits, the missing response 
status at current visit will be imputed as responder. Otherwise, response status will be set 
to non-responder.
The SRI(X) response status (composite) for a subject who has more than one component (e.g.
MDGA and SLEDAI-2K are missing for SRI(X)) missing at a given (efficacy) visit not due to 
premature discontinuation will be imputed as non-responder. 
After any imputation above or none, if for some reason the SRI(X) response status still cannot be 
determined, including the case where baseline data is missing, then its value will be set to non-
responder.
Note that, the corrected threshold is 10mm in the second component of SRI(X) instead of 30mm 
(as in the original protocol) on a 100mm VAS of MDGA. The correct threshold is used in the 
definition of SRI(X) in this section.
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8.1.3
Evaluation of Major Clinical Response and Partial Clinical Response
Major and Partial Clinical responses are defined as:

Major Clinical Response: a patient with BILAG C scores or better at 6 
months with no new BILAG A or BILAG B scores AND maintenance of 
response with no new BILAG A or B scores between 6 and 12 months.

Partial Clinical Response: a patient with BILAG C scores or better at 6 
months with no new BILAG A or BILAG B scores and maintenance of 
response without a flare for 4 months.
If a subject is not meeting any of the above criteria, the response status will be set to non-
responder.
If a subject has any missing data at a particular visit, the subject will be excluded from the 
analysis at that particular visit. The details will be provided in the LTE SAP.
8.1.4
Evaluation of Flare and Severity of Flare
Flare and severity of flare based on new BILAG 2004 is defined as follows:

Severe flare is any BILAG 2004 “A” score in any system due to items that are 
new or worse. 

Moderate flare is two or more “B” scores that are new or worse. 

Mild flare would be any patient with a single “B” score due to items that are 
new or worse or in those with three or more “C scores due to items that are 
new or worse. 

Anyone without these criteria would be categorized as no flare

If a subject has any missing data at a particular visit, the subject will be 
excluded from the analysis at that particular visit.
8.1.5
Evaluation of SF-36 Summary Functions and Components
The SF-36 is composed of 36 items measuring 8 health concepts: Physical Functioning, Role-
physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-emotional, and Mental 
Health. These 8 scales form 2 summary scores: (1) Physical Component Summary (PCS) and (2) 
Mental Component Summary (MCS).  Scoring conventions for the SF-36 scales and components 
are documented in “SF Health Outcomes TM Scoring Software User’s Guide”8.
8.2
Baseline Measures
The baseline value is the last assessment taken prior to the first dose of study medication. In 
general, the baseline value is the assessment taken on study Day 1 before the administration of 
study medication unless otherwise specified.
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If a measurement on Day 1 (baseline) is missing, the last assessment taken at the screening 
period prior to the first dose of study medication will be used.
8.3
Missing Measurements
For listings of binary response efficacy variables, missing values will be presented as missing.  
For determination of binary response variables, handling of missing values for BICLA and 
SRI(X) responses is addressed in Sections 8.1.1 and 8.1.2 unless otherwise specified.
If the response cannot be assessed due to missing data or a subject’s early discontinuation, the 
following conventions will be implemented in a sequence:

Any subject who prematurely discontinues the trial during the Short-term 
period after receiving study medication will have data imputed as non-
responder at all scheduled protocol visits subsequent to the point of 
discontinuation up to the end of the Short-term period.

After any imputation above or none, if for some reason the binary variable 
still cannot be determined, including the case where baseline data is missing, 
then its value will be set to non-responder.
For the analysis of continuous efficacy variables, mixed model will be used based on assumption 
of data being missing at random. Subjects with only baseline observations will be excluded from 
any changes from baseline analyses.
For safety, PK and immunogenicity measures and biomarkers, missing values will not be 
imputed.
8.4
Missing, Unknown or Partial Dates
The BMS safety guidelines for conventions relating to the handling of missing or partial dates 
and the determination of appropriate default values in such cases (in particular, for concomitant 
medication dose start-dates and end-dates and AE onset dates) will be utilized.  
8.5
Day Ranges for Analysis of Time Points
Subjects who do not always adhere strictly to the visit schedule timing in the protocol. Therefore 
the designation of visits during the Short-term period of the study will be based on the day of 
evaluation relative to the trial (day of first study medication = study Day 1) rather than the 
nominal visit recorded in the eCRF. Mutually exclusive relative day windows are defined below 
to provide derived visits that correspond to the post-baseline time points. If a visit falls outside of 
the pre-specified visit windows, then the data collected at that visit will not be assigned a derived 
visit but will remain in the derived data sets. Determination of baseline values is addressed in 
Section 8.2.
If a subject has more than 1 visit where a measurement is recorded within a window, the 
measurement closest to the target day will be used.  In case of 2 visits being equidistant from the 
target, the later measurement will be used in analyses. Exceptions to these rules apply to 
immunogenicity where the least favorable value (toward a positive response) in the window will 
be used.
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For subjects who discontinue from study therapy prematurely, assessments performed after the 
last dose of the study drug will be included in the efficacy datasets provided that these 
assessments are made within 28 days of the last dose. 
Designation of visits for efficacy assessments, immunogenicity samples and receptor occupancy 
samples during the Short-term period is tabulated below.
Table 8.5-1:
Days Ranges for Assessments at Every Scheduled Visits During the 
Short-term Period
Visit
Target 
Day
BILAG-
2004, 
SLEDAI 
2K, 
MDGA, 
PGA, 
ACR28, 
CLASI, 
SF-36, 
Coomb’s 
test-
direct
FACIT, 
C3, C4
SLICC
Anti-
dsDNA
CRP, 
IgG,
IgA,
IgM
Immuno-
genicity 
(Anti-
BMS-
931699), 
Cytokine
s
ANA, 
Auto-
antibodie
s
Baseline
/Day 1
1
1
1
1
1
1
1
1
D15
15
8-21
8-21
D29
29
15-43
22-43
15-43
22-57
15-43
D57
57
44-71
44-71
44-71
D85
85
72-99
72-99
72-99
72-99
58-127
72-99
D113
113
100-127
100-127
100-127
D141
141
128-155
128-155
128-155
D169
169
156-190*
156-190*
156-190*
156-190*
156-190*
128-190*
156-190*
* For subjects who enroll in long-term extension (LTE) period, the upper inclusive limit of this window is the start of LTE dose.
9
CONTENT OF REPORTS
The results of the study conducted by Protocol IM128-027 will be presented in a standard BMS 
CSR appendix.  Key results and any unanticipated findings that are unusual for this study will be 
identified.  A meeting for the initial dissemination of study results will be held after database 
locked.  Attendees at this meeting will review all efficacy and safety summaries and listings and 
will identify key results that should be highlighted in the CSR.
10
APPENDIX 1   RELEVANT PROTOCOL DEVIATIONS
Eligibility Deviations:

Subjects who do not have SLE as defined by meeting 4 of the 11 classification 
criteria of the American College of Rheumatology for the classification of 
SLE, either sequentially or coincident at screening
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
Subjects who do not have one ‘A’ in Musculoskeletal or Mucocutaneous body 
systems or two ‘B’s in BILAG  score (at least one in Musculoskeletal or 
Mucocutaneous body systems and one in any  other body system) at screening

Elevated ANA<1:80 and anti-dsDNA is not positive and anti-Sm is not 
positive at screening

Subjects who have SLEDAI < 6 at screening 

Subjects who receive more than 10mg/day of prednisone (or prednisone 
equivalent) at randomization day (Day 1)
Incorrect Dosing:

At least 4 consecutive doses are missed prior to the Day 169 and not 
discontinued as per protocol
11
APPENDIX 2  DOCUMENT REVISION HISTORY
Version
Statistician
Date
Notes/Revisions
1.0
Pranab K. Mitra 01/16/2015
Original version
2.0
Xiaoni Liu
Pranab K Mitra
04/28/2016Incorporated the changes needed for the Protocol amendments.
Revised the relevant deviation criteria.
Modified the definition of SRI(X) by adding one component based 
on restricted medication into the composite response.
Fixed several typos in the text.
Further clarified the analysis and the convention sections. 
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