Conditions: Polymyositis Dermatomyositis Autoimmune Necrotizing Myopathy Overlap Myositis Juvenile Myositis Above the Age of 18
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 149
Healthy volunteers: no

Brief summary:
Trial to Evaluate the Efficacy and Safety of Abatacept subcutaneous (SC) in Combination With Standard Therapy Compared to Standard Therapy Alone in Improving Disease Activity in Adults With Active Idiopathic Inflammatory Myopathy

Detailed description:

Arms:
arm 1: Abatacept subcutaneous weekly in addition to the subject's current standard treatment for 24 weeks followed by a 28 week open-label period of abatacept treatment plus the subject's current standard treatment. arm 2: Placebo of Abatacept subcutaneous weekly in addition to the subject's current standard treatment for 24 weeks followed by a 28 week open-label period of abatacept treatment plus the subject's current standard treatment.

Interventions: intervention 1: Abatacept subcutaneous intervention 2: Placebo
Intervention descriptions: intervention 1: Specified dose of Abatacept subcutaneous on specified days intervention 2: Placebo of Abatacept subcutaneous

Protocol document:
Prot_004.pdf: 


Clinical Protocol
IM101611
BMS-188667
abatacept
Revised Protocol No.: 04
Date: 01-Feb-2019
2
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply 
to partners to which BMS has transferred obligations, eg, a Contract Research Organization 
(CRO).
Replace all previous version(s) of the protocol with this revised protocol and please provide a copy 
of this revised protocol to all study personnel under your supervision, and archive the previous 
versions.
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Revised Protocol No.: 04
Date: 01-Feb-2019
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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 04
01-Feb-2019
Incorporates Amendments 03, 04, 05, and 06.
Revised 
Protocol 03
09-May-2018
This protocol revision is to clarify language, adjust criteria to 
improve subject selection and clarify allowable concomitant 
medication.
Revised 
Protocol 02
10-Mar-2017
Incorporates Amendment 02 and Administrative Letter 01
Amendment 02
10-Mar-2017
This amendment clarifies the target population (Inclusion/Exclusion 
criteria), randomization stratification criteria
, 
study procedures and sub-studies, training requirements for site staff, 
the process for adjudication, the duration of samples retention for 
additional research and the duration of post drug follow-up.  This 
amendment also updates the IND number and contact information 
for a new medical monitor..
Administrative 
Letter 01
26-Jan-2017
This administrative letter corrects the study schematic, eliminates 
inconsistencies in the standard treatment instructions and sample 
collection conditions and clarifies that exploratory sub-study results 
for the MRI muscle biopsies will not be provided to the sites or 
subjects. 
Revised 
Protocol 01
20-Oct-2016
Incorporates Amendment 01
Amendment 01
20-Oct-2016
This amendment corrects several inconsistencies and clarifies 
several study procedures. It also incorporates feedback from the 
FDA and CHMP regarding the study population and study design
Original 
Protocol
08-Jul-2016
Not applicable
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SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 04
Section Number & Title
Description of Change
Renumbered Section 3.1.6, 
Post-Treatment Follow-up 
Period
Added information for the Open Label 
Extension Period for Japan and the Long 
Term Extension Period (from 
Amendments 04 and 06).
Section 3.3.1, Inclusion 
Criteria, 2) Target Population, 
e)ii)
Added MPA is a formulation for 
mycophenolate and therefore acceptable 
as an allowed immunosuppressant (from 
Amendment 06).
Section 3.3.2, Exclusion 
Criteria, 3) Physical and 
Laboratory Test Findings, a)
Added information regarding hepatitis B 
exclusion (from Amendment 03).
Section 3.4.1.1, Standard 
Treatment, second bullet
Added MPA is a formulation for 
mycophenolate and therefore acceptable 
as an allowed immunosuppressant (from 
Amendment 06).
Section 3.4.2.1, Prohibited 
Medications
Added statement that provisions for 
prohibited medication will continue 
during the long-term open label extension 
period (Amendment 05).
Section 3.5, Discontinuation 
of Subjects following any 
Treatment with Study Drug, 
4th paragraph, 10th bullet
Added information that subjects missing 5 
or more consecutive doses of abatacept 
for any reason between Week 24 and 
Week 76 should be discontinued (from 
Amendment 04)..
Section 4.4, Method of 
Assigning Subject 
Identification
Added information for subjects in the 
Open Label Extension Period for Japan 
and the Long Term Extension Period
(from Amendments 04 and 06).
Section 4.5.1, Abatacept 
Treatment, 2nd paragraph
Added information for subjects in the 
Open Label Extension Period for Japan 
and the Long Term Extension Period
(from Amendments 04 and 06).
Section 5.1, Flow Chart/Time 
and Events Schedule, Table 
5.1-1
Added autoantibody testing at screening 
to be tested centrally if requested by sites 
in Brazil, Mexico, and the U.S. (from 
Amendment 06).
 
Section 5.1, Flow Chart/Time 
and Events Schedule
Added Tables 5.1-5 and 5.1-6 and 
renumbered former 5.1-5 to be 5.1-7
(from Amendment 06).
Section 5.1, Flow Chart/Time 
and Events Schedule, Table 
5.1-5, Open Label Extension 
for Japan, Table Note c
Modified information to indicate the 
efficacy assessments may be recorded on 
paper if the electronic tablet (ePRO) is 
unavailable/not functioning for 
transmission of the data (from 
Amendment 06).
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SYNOPSIS
Clinical Protocol IM101611
Protocol Title: A Phase 3, Randomized, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Abatacept 
SC with Standard Treatment Compared to Standard Treatment Alone in Improving Disease Activity in Adults with 
Active Idiopathic Inflammatory Myopathy (IIM)
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): 
Subjects receive investigational products for a period of 4.5 years. Investigational products are defined as:
•
Abatacept SC 125 mg in 1 ml pre-filled syringes
•
Placebo to match abatacept SC in 1 ml pre-filled syringes [24 weeks (6 months) in the double-blind period]
Study Phase: III
Research Hypothesis: Subcutaneous abatacept (125 mg weekly) in combination with standard treatment will achieve 
a higher rate of responders, defined as the percentage of subjects who achieve the IMACS DOI (International Myositis 
Assessment and Clinical Studies - definition of improvement), after 24 weeks of treatment versus standard treatment 
alone in adult subjects with active IIM.
Objectives: 
Primary Objective
The primary objective for this study is to compare the clinical efficacy of weekly abatacept in combination with 
standard treatment to standard treatment alone by assessing the percentage of subjects who achieve the IMACS DOI 
by Wk 24 compared to baseline, defined as:
•
An improvement of ≥20% in 3 IMACS core measures, AND
•
No more than 2 IMACS core measure scores worsen by ≥25%, AND
•
Manual Muscle Test (MMT-8) may not decrease by ≥25%
Secondary Objectives
1)
To assess the clinical efficacy of weekly abatacept in combination with standard treatment to standard treatment 
alone by assessing the change in muscle endurance test using the Myositis Function Index (FI-2) from baseline 
to Wk 24. 
2)
To assess the efficacy of abatacept in combination with standard treatment to standard treatment alone by 
assessing the mean change in functional disability using the Health Assessment Questionnaire-Disability Index 
(HAQ-DI) from baseline to Wk 24.
3)
To assess the efficacy of abatacept in combination with standard treatment to standard treatment alone by 
assessing the mean change in extra-muscular disease activity as defined by Myositis Disease Activity Assessment 
Tool (MDAAT) from baseline to Wk 24. 
4)
To assess the efficacy of abatacept in combination with standard treatment to standard treatment alone in 
achieving improvement on the Myositis Response Criteria by assessing the mean change from baseline to Wk 24.
Study Design: This is a 24 week, randomized, double-blind, placebo-controlled, multicenter, study in subjects with 
active Idiopathic Inflammatory Myopathy (IIM: eg, Dermatomyositis [DM], Polymyositis [PM], autoimmune 
necrotizing myopathy; see Section 3.3.1 Inclusion Criteria, (2) Target Population), on standard background treatment. 
In addition to the 24 week double blind period, the study includes a 28 week open-label treatment period during which 
all subjects will receive SC abatacept, an additional 24 weeks open label period of SC abatacept with continued therapy 
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from the original OL period for sites in Japan, and a 3 year long term extension of SC abatacept (156 weeks) with 
background treatment for all subjects except subjects in the U.S. and the Czech Republic.
The Primary Endpoint occurs at Wk 24, however assessments will be made throughout both periods to evaluate safety 
and efficacy.
Double-Blind Period (Day 1 - Week 24)
During this period, approximately 150 subjects will be randomized to one of two parallel treatment arms in a 1:1 ratio. 
The treatment arms are as follows: 
Arm A: Active abatacept SC (125 mg) weekly + standard treatment
Arm B: Placebo abatacept SC weekly + standard treatment  
Open-Label Period (Week 24 - Week 52) 
After Week 24, all subjects will receive abatacept plus standard therapy.
Open-Label Extension Period (Week 52-Week 76 -- for Japanese only subjects
For Japan subjects will receive abatacept plus standard therapy.
Long Term Extension (3 years)
All subjects (excluding subjects randomized from the U.S. and the Czech Republic) will receive abatacept plus 
standard therapy.
Rescue Therapy
Subjects who meet the criteria for worsening between Wk 12 and Wk 24 will be eligible for rescue therapy. See 
Section 3.1.4 for details. In the Open-Label Period, subjects may adjust background treatment at any time.
Study Population: Men and women (not nursing or pregnant) ≥18 years old who have active idiopathic inflammatory 
myositis.  
Key Inclusion criteria: Target population
a)
Diagnosis of Definite or Probable IIM (DM or PM) based on the Bohan and Peter classification criteria (outlined 
in Appendix 3) 
i)
Subjects with dermatomyositis (DM) must also have a confirmed myositis-associated rash (Gottron’s 
papules or a heliotrope rash preferably confirmed by skin biopsy) and 2 or more of the remaining 4 
criteria.
ii)
Subjects with a diagnosis of IIM other than DM include PM, autoimmune necrotizing myopathy, 
myositis in association with another connective tissue disease (overlap myositis) and juvenile myositis 
subjects above the age of 18. These subjects must have a prior muscle biopsy diagnostic for IIM or a 
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positive test for at least one myositis-specific autoantibody (anti-aminoacyl-tRNA synthetases (Jo-1, 
PL-7, PL-12, EJ, OJ, KS, Zo, YRS), anti-Mi-2, anti-SRP, anti-TIF1-γ, anti-NXP-2, anti-MDA5, anti-
SAE, anti-HMGCR). For subjects with overlap myositis, the myositis must be the principal clinically 
active manifestation of their disease.
Where applicable, documentation of prior skin biopsy, muscle biopsy, and autoantibody results must be 
obtained and retained by the site
b)
Demonstrable muscle weakness measured by the MMT-8 of ≤135 units and any 3 of the following:
i)
MMT-8 ≤125 units
ii)
Physician’s global assessment (PGA) VAS ≥2 cm
iii) Subject’s global assessment (SGA) VAS ≥2 cm
iv) HAQ-DI ≥0.5
v)
One or more muscle enzyme (CK, aldolase, LDH, AST, ALT) ≥1.3 times upper limit of normal (ULN)
vi) MDAAT Extramuscular Global Activity VAS ≥2 cm
c)
Demonstration of currently active IIM will be determined by an adjudication committee (Section 7.1) unless the 
subject has any one of the following:
i.
an active myositis-associated rash (Gottron’s papules or heliotrope rash), or
ii.
a recent (within 3 months prior to signing informed consent) biopsy, magnetic resonance imaging (MRI), 
or electromyogram (EMG) demonstrating active disease, or
iii.
an elevated CK > 5 times the upper limit of normal at screening with no alternate explanation or cause
d)
Active disease despite adequate prior treatment experience with corticosteroids, immunosuppressants, or 
biologics as determined by the investigator
e)
The subject must be on background standard treatment for IIM (Section 3.4.1.1). The standard treatments that are 
allowed as background treatment for IIM includes:
i.
Corticosteroids alone (Section 3.4.1.2), or
ii.
One of the following immunosuppressants: methotrexate, azathioprine, mycophenalate mofetil, 
tacrolimus, or cyclosporine (combinations of these treatments are not allowed), or
iii.
A combination of corticosteroids and one of the above immunosuppressants
•
If using corticosteroids for IIM, the subject must have been on corticosteroids for at least 12 weeks prior to 
randomization and a stable dose of corticosteroids for at least 4 weeks prior to randomization.   
•
If using immunosuppressants other than azathioprine, the subject must have been on the same medication 
for at least 12 weeks and a stable dose for at least 4 weeks prior to randomization.  
•
If using azathioprine, the subject must have been on azathioprine for at least 24 weeks with a stable dose 
for at least 12 weeks prior to randomization.
Key Exclusion criteria: Medical history and concurrent diseases
a)
Subjects with Inclusion Body Myositis or myositis other than IIM, e.g. drug-induced myositis and PM associated 
with HIV.
b)
Subjects treated with penicillamine or zidovudine in the past 3 months.
c)
Subjects treated with rituximab in the 6 months prior to randomization (there must be laboratory results indicating 
the presence of circulating B cells [CD19+]). Any other biologic treatment in the past 3 months or immune 
globulin (intravenous [IVIG] or subcutaneous [SCIG]) in the past 3 months prior to randomization..
d)
Subjects with uncontrolled or rapidly progressive interstitial lung disease (at the discretion of the investigator)
e)
Subjects with severe muscle damage (Myositis Damage Index > 7/10), permanent weakness due to a non-IIM 
cause, or myositis with cardiac involvement
f)
Cancer-associated myositis (myositis diagnosed within 2 years of a diagnosis of cancer). See criteria (2i)
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g)
Subjects who are known to be positive for the anti-TIF-1 (p155/140) autoantibody prior to randomization who 
were diagnosed with IIM < 1 year prior to randomization.
h)
Subjects at risk for tuberculosis 
i)
Subjects with recent acute infection requiring antibiotics 
j)
Subjects with history of chronic or recurrent bacterial or viral infections
k)
Subjects with active systemic fungal infections (eg, histoplasmosis, blastomycosis, or coccidiomycosis)
l)
Subjects who have a present malignancy or have had a previous malignancy within the last 5 years prior to 
screening (except for a documented history of cured non-metastatic squamous or basal cell skin carcinoma or 
cervical carcinoma in situ).  Additional screening requirements for malignancy are outlined in Sections 3.3.2 and 
3.3.4.
Study Assessments: See Section 5 of the protocol for detailed information regarding study assessments.
Statistical Considerations:
Sample Size: A sample size of 150 subjects (75 subjects per treatment group) is planned based on the primary 
comparison of the proportion of subjects with IMACS DOI (as defined under the primary objective) at Day 169 
(Week 24) between the SC abatacept group and the placebo group on a background of standard treatment.
A sample size of 150 subjects randomized in a 1:1 ratio to the SC abatacept group and placebo group will yield a 
power of approximately 90% to detect a treatment difference of 27% in the rate of IMACS DOI between the 
2 treatment groups based on a continuity corrected chi-squared test. This power estimate assumes a two-sided alpha 
level of 5%, IMACS DOI rate of 60% in the abatacept group and 33% in the placebo group.
The 60% estimate of IMACS DOI in the abatacept group was based on reported rates of IMACS DOI in studies of 
patients with Myositis on combination therapy with another biologic agent36. It is expected that the rate of IMACS 
DOI on abatacept in combination with standard treatment should be similar to that observed with the use of another 
biologic agent in combination with standard treatment. Randomization will be stratified globally by 3 stratification 
variables: (1) Dermatomyositis (DM) vs non-DM IIM, (2) presence or absence of Interstitial Lung Disease (ILD), (3) 
Japan vs rest of world (ROW).
Endpoints:
Primary Endpoint  
•
Proportion of subjects who achieve IMACS DOI at Week 24 without rescue
Secondary Endpoints 
•
Mean change in muscle endurance using the myositis function index (FI-2) from baseline to Weeks 12 and 24. 
•
Mean change in Health Assessment Questionnaire-Disability Index (HAQ-DI) from baseline to Weeks 12 and 
24.
•
Mean change in Myositis Disease Activity Assessment Tool (MDAAT) from baseline to Weeks 12 and 24.
•
Mean change in Myositis Response Criteria score from baseline to Weeks 12 and 24.
Safety Endpoints
•
All adverse events (AEs/SAEs)
•
AEs of interest (serious infections, malignancies, injection site reactions, systemic reactions)
•
Laboratory test abnormalities
Analyses:
To assess the primary endpoint for this study an analysis (Week 24 Analysis) will be performed once all subjects 
complete their Week 24 visit assessments or discontinue prematurely prior to Week 24. The Week 24 analysis will 
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include analyses of the primary, secondary and exploratory endpoints. The primary comparison of proportion of 
subjects in IMACS DOI at Week 24 between the abatacept and placebo arms will be assessed using a logistic 
regression model. The logistic regression model will include baseline IMACS (continuous variable) and 
randomization stratification variables of diagnosis (Dermatomyositis [DM] vs non-DM IIM), Interstitial Lung disease 
status (present vs. absent), Japan vs. ROW to account for randomization stratification. All subjects who discontinue 
prematurely prior to reaching the Week 24 assessment visit, will be considered as not achieving IMACS DOI for the 
primary analysis. No formal statistical testing will be conducted for analyses related to the secondary and exploratory 
endpoints. Appropriate summary statistics will be provided for the analysis of each endpoint.
Safety summaries for the Week 24 analysis will include all adverse events (AEs) reported during the Double-Blind 
Period and presented by treatment groups (abatacept vs. placebo). AEs will be summarized from the first dose date in 
the study up to first dose date in the Open-Label Period or last dose date in the Double-Blind Period + 56 days for 
subjects who prematurely discontinued the study during the Double-Blind Period.
In accordance with an intent-to-treat approach, all available data from all subjects who receive at least one infusion of 
a treatment regimen being assessed at any time will be included in the safety and efficacy analyses. Detailed definition 
of population for analyses will be included in the protocol.
An analyses will be performed for the study once all subjects complete their week 52 assessment and/or all follow-up 
visits up to 168 days post last dose visit.
An analysis for the long-term efficacy and safety for subjects from Japan will be performed including data collected 
up to Week 76.
A final analysis will be performed for the study when all subjects complete the long-term open label extension and/or 
the follow-up period of the study.
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APPENDIX 1 HIGHLY EFFECTIVE METHODS OF CONTRACEPTION ............. 
APPENDIX 2 LABORATORY GUIDELINES: PATIENT STUDIES (REVISED 
AUGUST 13, 1999) ................................................................................................ 
APPENDIX 3 BOHAN AND PETER CLASSIFICATION CRITERIA ..................... 
APPENDIX 4 REVISED PROTOCOL SUMMARY OF CHANGE HISTORY ........ 
124
126
128
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1.2
Research Hypothesis 
Subcutaneous abatacept (125 mg weekly) in combination with standard treatment will achieve a 
higher rate of responders, defined as the percentage of subjects who achieve the IMACS DOI, after 
24 weeks of treatment versus standard treatment alone in adult subjects with active IIM.
1.3
Objectives(s)
1.3.1
Primary Objectives
The primary objective for this study is to compare the clinical efficacy of weekly abatacept in 
combination with standard treatment to standard treatment alone by assessing the percentage of 
subjects who achieve the IMACS DOI by Wk 24 compared to baseline, defined as:
•
An improvement of ≥20% in 3 IMACS core measures, AND
•
No more than 2 IMACS core measure scores worsen by ≥25%, AND
•
Manual Muscle Test (MMT-8) may not decrease by ≥25%
1.3.2
Secondary Objectives
1) To assess the clinical efficacy of weekly abatacept in combination with standard treatment to 
standard treatment alone by assessing the change in muscle endurance test using the Myositis 
Function Index (FI-2) from baseline to Wk 24. 
2) To assess the efficacy of abatacept in combination with standard treatment to standard 
treatment alone by assessing the mean change in functional disability using the Health 
Assessment Questionnaire-Disability Index (HAQ-DI) from baseline to Wk 24.
3) To assess the efficacy of abatacept in combination with standard treatment to standard 
treatment alone by assessing the mean change in extra-muscular disease activity as defined by 
Myositis Disease Activity Assessment Tool (MDAAT) from baseline to Wk 24. 
4) To assess the efficacy of abatacept in combination with standard treatment to standard 
treatment alone in achieving improvement on the Myositis Response Criteria by assessing the 
mean change from baseline to Wk 24.
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2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Conference on Harmonisation (ICH) and in accordance with the ethical principles 
underlying European Union Directive 2001/20/EC and the United States Code of Federal 
Regulations, Title 21, Part 50 (21CFR50) and applicable local requirements.
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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 Sponsor or designee immediately. If required as 
per local regulation, serious breaches will be reported by Sponsor or designee to applicable 
authorities. A breach of the conditions and principles of Good Clinical Practice (GCP) (occurring 
in any country) in connection with that trial or the protocol related to the trial which is likely to 
affect to a significant degree the safety or physical or mental integrity of 1 or more subjects of the 
trial or the scientific value of the trial.
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 (e.g., 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 
(e.g., advertisements), and any other written information to be provided to subjects. The 
investigator, Sponsor or designee should also provide the IRB/IEC with a copy of the Investigator 
Brochure or product labeling information to be provided to subjects and any updates. 
The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (e.g., 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 by subjects, their legally acceptable representatives
(as per country guidelines) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the subject volunteers to participate. 
Sponsor or designee will provide the investigator with an appropriate (i.e., Global or Local) sample 
informed consent form which will include all elements required by ICH, GCP and applicable 
regulatory requirements. The sample informed consent form will adhere to the ethical principles 
that have their origin in the Declaration of Helsinki.
Investigators must:
•
Provide a copy of the consent form and written information about the study in the language in 
which the subject is most proficient prior to clinical study participation. The language must be 
non-technical and easily understood. 
•
Allow time necessary for the subject or the subject's legally acceptable representative to inquire 
about the details of the study.
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•
Obtain an informed consent signed and personally dated by the subject or the subject's legally 
acceptable representative and by the person who conducted the informed consent discussion. 
•
Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent form 
and any other information to be provided to the subjects, prior to the beginning of the study, 
and after any revisions are completed for new information.
•
If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the subject.
•
Revise the informed consent whenever important new information becomes available that is 
relevant to the subject's consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
subject's willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules applicable to regulatory requirements, the subjects' signed ICF and, in the 
US, the subjects’ signed HIPAA Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to subject records. 
Subjects unable to give their written consent (e.g., due to 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.
For minors, according to local regulations, one or both parents or a legally acceptable 
representative must be informed of the study procedures and must sign the informed consent form 
approved for the study prior to clinical study participation.  In such cases, records on the 
relationship between the subject and the proxy consenter should be maintained with those of the 
consent.  The explicit wish of a minor who is capable of forming an opinion and assessing this 
information to refuse participation in, or to be withdrawn from, the clinical study at any time should 
be considered by the investigation.
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
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3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a 24 week, Phase 3, randomized, double-blind, placebo-controlled, multicenter, study in 
subjects with active Idiopathic Inflammatory Myopathy (IIM; eg, DM, PM, autoimmune 
necrotizing myopathy; see Section 3.3.1) on standard background treatment.  
In addition to the 24-week double-blind period, the study includes a 28 week open-label treatment 
period during which all subjects will receive SC abatacept with background treatment, an 
additional 24 weeks open label of SC abatacept with continued therapy from the original OL period
for subjects in Japan, and a 3 year long term extension of SC abatacept (156 weeks) with 
background treatment for all subjects except subjects in the U.S. and the Czech Republic. 
The primary objective for this study is to compare the clinical efficacy of weekly abatacept in 
combination with standard treatment to standard treatment alone by assessing the percentage of
subjects who achieve the IMACS DOI after 24 weeks of treatment versus standard treatment alone 
in adult subjects with active IIM. The study design schematic is presented in Figure 3.1-1.
Figure 3.1-1:
Study Design Schematic
The start of the trial is defined as the first visit for the first subject screened. The end of the trial is 
defined as the last visit or scheduled procedure shown in the Time & Events schedule for the last 
subject. Study completion is defined as the final date on which data for the primary endpoint was
or is expected to be collected.
3.1.1
Screening Period
Eligibility will be based on specified inclusion and exclusion criteria, medical history, disease 
activity and safety assessments (see Table 5.1-1). Randomization must occur within four weeks of 
signing the informed consent. However, subjects may extend the screening period beyond 4 weeks, 
but not beyond a total of 6 weeks (42 days), from the signing of the informed consent. 
Subjects who extend the screening period beyond 4 weeks may be required to repeat some 
screening assessments. If more than 6 weeks is required, e.g. initiation of treatment for latent TB, 
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a subject should be screen failed and re-enrolled when appropriate. Screening for malignancy is 
expected to have been performed prior to the Screening Period (Section 3.3.4).
3.1.2
Double-Blind Period (Day 1 - Week 24)
During this period, approximately 150 subjects will be randomized in a 1:1 ratio to one of two 
parallel arms in a double-blinded manner as follows (see Table 5.1-2):
Arm A: Active abatacept SC (125 mg) weekly + standard treatment
Arm B: Placebo abatacept SC weekly + standard treatment
At the time of randomization, subjects must be on a stable background treatment (“standard 
treatment” see Section 3.4.1.1) for IIM. No adjustment in background treatment will be allowed 
during this Period. Randomization will be stratified globally by 3 stratification variables: 
(1) Dermatomyositis (DM) vs non-DM IIM, and (2) presence or absence of interstitial lung disease 
(ILD), (3) Japan vs Rest of World (ROW). 
Rescue therapy will be available for subjects who meet the disease worsening criteria during the 
double-blind period as defined in Section 3.1.4.
During this period, subjects who have clinically active or relevant interstitial lung disease (ILD) 
or anti-synthetase syndrome as determined by the investigator must undergo pulmonary function 
testing and high-resolution CT (HRCT) scan of the chest during screening (prior to Day 1) and 
may have repeat pulmonary function testing (PFT) and HRCT scan at Wk 24. (See Section 5.3.6
and Section 5.3.7.2) 
Subjects who participate in the sub-study of MRI muscle (thighs) imaging will have an MRI 
performed during screening (prior to Day 1) and Wk 24. See Section 5.8.2
Subjects who participate in the sub-study of muscle biopsy will have a muscle biopsy performed 
during screening (prior to Day 1) and Wk 24. See Section 5.8.3
Subjects who discontinue treatment with study medication during the Double-blind Period will 
complete the Early Termination visit (which is the same visit as Day 169 visit) (See Table 5.1-2). 
These subjects must also return on the previously scheduled Double-blind Period Day 169 to 
complete the Post-Study Drug Efficacy Visit (see Table 5.1-4). The purpose of this visit is to assess 
all aspects of disease activity to ascertain the impact of study participation for regulatory review. 
Subjects must also complete 2 follow-up visits (85 and 169 days after the last dose) during the 24 
week post-treatment follow-up period, to perform safety and laboratory assessments (See Table 
5.1-7 Post-Treatment Follow-Up Period). This Period begins on the day of the Early Termination 
visit and applies only to subjects who do not start commercial abatacept therapy.
3.1.3
Open-Label Period (Week 24 - Week 52) and Open-Label Extension 
Period (Week 52 - Week 76) for Japan
The 24-week Double-Blind Period is followed by a 28 week open-label abatacept treatment period 
(Open-Label Period, see Table 5.1-3). During this period, subjects initially randomized to receive 
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the combination of abatacept and standard treatment will continue this regimen. Subjects who are 
initially assigned to receive standard treatment alone will be switched to standard treatment plus 
abatacept.
There will also be a 24 weeks (168 days) open label extension for subjects randomized in Japan.
Background treatment may be adjusted (including the dose of corticosteroids and 
immunosuppressants) at any time during this period. Use of immune globulin (intravenous [IVIG] 
or subcutaneous [SCIG] is permitted during this period. Addition of any other prohibited 
medication (Section 3.4.2.1) is not permitted.
During this period, subjects who have clinically active or relevant interstitial lung disease (ILD) 
or anti-synthetase syndrome as determined by the investigator, may have to repeat pulmonary 
function testing and HRCT scan of the chest at Wk 52. (See Section 5.3.6 and Section 5.3.7.2) and 
at Wk 76 for Japan.
Subjects who participate in the sub-study of MRI muscle (thigh) imaging will have an MRI 
performed at Wk 52. See Section 5.8.2
Subjects who discontinue treatment with abatacept during the Open-Label Period or Open Label 
Extension for Japan will complete the Early Termination visit for the OL (See Table 5.1-3 day 365 
is also the OL ET) and 2 follow-up visits during the 24 week post-treatment follow-up period, to 
perform safety and laboratory assessments. (See Table 5.1-7). If the subject receives treatment 
with an alternate source of abatacept (Post-Study Drug Program [PSDP] or Commercial), 
completing this post-treatment follow-up period is not required. 
Treatment with other biologic therapy is not recommended for at least 70 days (∼5 half-lives of 
abatacept follow-up period.
3.1.4
Long Term Open Label Extension for Subjects Randomized in 
Countries Other than the U.S. and the Czech Republic
There will be a three year long term extension period for subjects randomized in countries other 
than the U.S. and the Czech Republic.
All subjects alone will receive standard treatment plus abatacept.
Subjects who discontinue treatment with abatacept during the Long Term Extension Open-Label 
Period will complete the Early Termination visit for the OL and two follow-up visits to perform 
safety and laboratory assessments. (See Table 5.1-7). If the subject receives treatment with an 
alternate source of abatacept (Post-Study Drug Program [PSDP] or Commercial), completing this 
post-treatment follow-up period is not required. 
3.1.5
Rescue Therapy
Double-Blind Period (Day 1 to Wk 24)
Subjects in either treatment group who meet the criteria for worsening at any visit between 
Weeks 12 and 24 are permitted to use rescue therapy. Rescue is not permitted before Week 12 and 
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subjects who require a change in therapy due to worsening of their disease must discontinue from 
the study. Beginning at Week 12, if a subject meets criteria for worsening, the investigator will be 
notified by means of a Disease Worsening Report generated after efficacy assessments are 
completed and uploaded via an electronic tablet (ePRO).
The use of rescue therapy is at the discretion of the investigator; however, rescue treatment may 
not be abatacept or a prohibited medication (See Section 3.4.2.1). Allowable medication are 
restricted to allowable concomitant medication (Section 3.4.1.1 Standard Treatment). Rescue 
therapy includes increases in dose of current therapy, addition of therapy and change in therapy, 
all with some restrictions such that allowable rescue therapy meets the criteria for allowable 
standard treatment. The following changes are allowable as rescue therapy:
1) Subjects on corticosteroid (CS) alone can:
a) increase dose (to no more than 30 mg/day of prednisone or prednisone equivalent [3.4.1.2
Corticosteroid medications]), or 
b) initiate an allowable immunosuppressant, with or without increase in CS, or
c) discontinue CS and initiate an allowable immunosuppressant (Section 3.4.1.1 Standard 
Treatment)
2) Subjects on allowable immunosuppressant (MTX, AZA, MMF, MPA, tacrolimus, or 
cyclosporine) alone can: 
a) increase dose of the current immunosuppressant, or
b) stop current immunosuppressant and start a new allowable immunosuppressant, or 
c) add CS (Section 3.4.1.2 Corticosteroid medications)
3) Subjects on allowable immunosuppressant and CS can:
a) increase dose of immunosuppressant, or
b) increase dose of CS (Section 3.4.1.2 Corticosteroid medications) , or
c) increase dose of both (following guidelines), or
d) stop current immunosuppressant and start a new allowable immunosuppressant with or 
without increase in CS.
Rescued subjects will remain blinded to study medication through Week 24 and will begin 
Open-Label abatacept after Week 24, however they will be considered not to have achieved the 
IMACS DOI for the purpose of the primary efficacy analysis. 
The criteria for worsening are:
1) Physician’s global assessment worsening by ≥2 cm on the VAS and worsening of ≥20% on 
the MMT-8 score compared to baseline, or
2) Physician’s global assessment worsening by ≥2 cm on the VAS and  global extramuscular 
activity worsening by ≥2 cm on the MDAAT Extramuscular Global Activity VAS compared 
to baseline, or
3) Any 3 of 6 IMACS components worsening by ≥30% compared to baseline on 2 consecutive 
visits
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Subjects who fail rescue therapy, as determined by the investigator, must discontinue from the 
study. These subjects must follow the same T&E schedule for other subjects who early terminate 
in the double-blind treatment period (see Section 3.1.2)
Open-Label Period (Wk 24 to Wk 52 or to Wk 76 for Japan)
There is no rescue treatment in the Open-Label Period. Background treatment may be adjusted as 
described in Section 3.1.3.
Long Term Extension (3 Years Treatment for subjects randomized in countries other than the U.S. 
and the Czech Republic)
Background treatment may be adjusted as described in Section 3.1.3.
3.1.6
Post-Treatment Follow-Up Period
The Post-Treatment Follow-Up Period (see Table 5.1-7) will last 24 weeks (169 days).  The Post-
Treatment Follow-Up is required for subjects who discontinue study treatment and do not start 
abatacept from an alternative source.  This applies to subjects who either complete or early 
terminate any of the study periods (DB, OL, OL-EXT, or LTE). The purpose of this Period is to 
perform safety and laboratory assessments.
3.2
Post-Study Access to Study Drug
At the conclusion of the study, participants who continue to demonstrate clinical benefit with study 
drug, ie abatacept, will be eligible to receive BMS supplied study drug as part of the a Post-Study 
Drug Program (PSDP). Study drug will be provided via an extension of the study, a rollover study 
requiring approval by responsible health authority and ethics committee or through another 
mechanism at the discretion of BMS. BMS reserves the right to terminate access to BMS supplied 
study drug if any of the following occur: a) the study is terminated due to safety concerns; b) the 
development of abatacept for this indication is terminated for other reasons, including but not 
limited to lack of efficacy and/or not meeting the study objectives; c) the participant can obtain 
medication from a government sponsored or private health program. In all cases BMS will follow 
local regulation.
Treatment codes will be provided to the investigators after completion of the study.
3.3
Study Population
For entry into the study, the following criteria MUST be met.
3.3.1
Inclusion Criteria
1) Signed Written Informed Consent
a) Subject is willing to participate in the study and has signed the informed consent. See 
Section 2.3
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2) Target Population
a) Diagnosis of Definite or Probable IIM (DM or PM) based on the Bohan and Peter 
classification criteria (outlined in Appendix 3)
i)
Subjects with dermatomyositis (DM) must also have a confirmed myositis-associated 
rash (Gottron’s papules or a heliotrope rash preferably confirmed by skin biopsy) and 
2 or more of the remaining 4 criteria.
ii) Subjects with a diagnosis of IIM other than dermatomyositis include PM, autoimmune 
necrotizing myopathy, myositis in association with another connective tissue disease 
(overlap myositis) and juvenile myositis subjects above the age of 18. These subjects 
must have a prior muscle biopsy diagnostic for IIM or a prior positive test for at least 
one myositis-specific autoantibody (anti-aminoacyl-tRNA synthetases (Jo-1, PL-7, 
PL-12, EJ, OJ, KS, Zo, YRS), anti-Mi-2, anti-SRP, anti-TIF1-γ, anti-NXP-2, 
anti-MDA5, anti-SAE, anti-HMGCR). For subjects with overlap myositis, the myositis 
must be the principal clinically active manifestation of their disease.
Where applicable, documentation of prior skin biopsy, muscle biopsy, and 
autoantibody results must be obtained and retained by the site
b) Demonstrable muscle weakness measured by the MMT-8 of ≤135 units and any 3 of the 
following:
i)
MMT-8 ≤125 units
ii) Physician’s global assessment (PGA) VAS ≥2 cm
iii) Subject’s global assessment (SGA) VAS ≥2 cm
iv) HAQ-DI ≥0.5
v) One or more muscle enzyme (CK, aldolase, LDH, AST, ALT) ≥1.3 times upper limit 
of normal (ULN)
vi) MDAAT Extramuscular Global Activity VAS ≥2 cm
c) Demonstration of currently active IIM will be determined by an adjudication committee 
(Section 7.1) unless the subject has any one of the following:
i)
an active myositis-associated rash (Gottron’s papules or heliotrope rash), or
ii) a recent (within 3 months prior to signing informed consent) biopsy, magnetic 
resonance imaging (MRI), or electromyogram (EMG) demonstrating active disease 
(documentation must be obtained and retained by the site), or
iii) an elevated CK > 5 times the upper limit of normal at screening with no alternate 
explanation or cause
d) Active disease despite adequate prior treatment experience with corticosteroids,
immunosuppressants, or biologics as determined by the investigator
e) The subject must be on background standard treatment for IIM (Section 3.4.1.1). The 
standard treatments that are allowed as background treatment for IIM includes:
i)
Corticosteroids alone (Section 3.4.1.2), or
ii) One of the following immunosuppressants: methotrexate, azathioprine, mycophenolate
[any formulation of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)], 
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tacrolimus, or cyclosporine (combinations of these treatments are not allowed during 
the Double-Blind Period), or
iii) A combination of corticosteroids and one of the above immunosuppressants
•
If using corticosteroids for IIM, the subject must have been on corticosteroids for 
at least 12 weeks prior to randomization and a stable dose of corticosteroids for at 
least 4 weeks prior to randomization.   
•
If using immunosuppressants other than azathioprine, the subject must have been 
on the same medication for at least 12 weeks and a stable dose for at least 4 weeks 
prior to randomization.  
•
If using azathioprine, the subject must have been on azathioprine for at least 
24 weeks with a stable dose for at least 12 weeks prior to randomization.
f)
Subject Re-enrollment: This study permits one re-enrollment of a subject that has 
discontinued the study as a pre-treatment failure (ie, “screen failure”, the subject has not 
been randomized /has not been treated) for any reason (see Section 5.1.1). 
3) Age and Reproductive Status
a) Men and Women, age ≥18 or age of majority
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours 
prior to the start of study drug.
c) Women must not be breastfeeding
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration 
of treatment with study drug(s) (abatacept) plus 5 half-lives of study drug (70 days) plus 
30 days (duration of ovulatory cycle) for a total of 100 days post-treatment completion
e) Men who are sexually active with WOCBP must agree to follow instructions for method(s) 
of contraception for the duration of treatment with study drug(s) (abatacept) plus 
5 half-lives of the study drug (70 days) plus 90 days (duration of sperm turnover) for a total 
of 160 days post-treatment completion. In addition, male subjects must be willing to refrain 
from sperm donation during this time. 
f)
Azoospermic males are exempt from contraceptive requirements. WOCBP who are 
continuously not heterosexually active are also exempt from contraceptive requirements, 
and still must undergo pregnancy testing as described in this section.
Investigators shall counsel WOCBP, and male subjects who are sexually active with WOCBP, on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
Investigators shall advise on the use of highly effective methods of contraception (Appendix 1), 
which have a failure rate of < 1% when used consistently and correctly. It is expected that 
investigators will refer to the Product Insert, as well as local regulations and guidelines for 
prevention of pregnancy appropriate for the standard background treatment being used by 
individual subjects. 
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3.3.2
Exclusion Criteria
1) Target Disease Exceptions
a) Subjects with Inclusion Body Myositis, or myositis other than IIM, eg, drug-induced 
myositis and PM associated with HIV.
b) Subjects treated with penicillamine or zidovudine in the past 3 months.
c) Subjects treated with rituximab in the 6 months prior to randomization (there must be 
laboratory results indicating the presence of circulating B cells (CD19+). Any other 
biologic treatment in the past 3 months or immune globulin (intravenous [IVIG] or 
subcutaneous [SCIG]) in the past 3 months prior to randomization.
d) Subjects with uncontrolled or rapidly progressive interstitial lung disease (at the discretion 
of the investigator).
e) Subjects with severe muscle damage (Physician VAS for muscle damage in Myositis 
Damage Index > 7 cm on a 10 cm scale), permanent weakness due to a non-IIM cause 
(eg. stroke), or myositis with cardiac involvement.
f)
Cancer-associated myositis (myositis diagnosed within 2 years of a diagnosis of cancer). 
See criteria (2i)
g) Subjects who are known to be positive for the anti-TIF1-γ (p155/140) autoantibody prior 
to randomization who were diagnosed with IIM < 1 year prior to randomization.
2) Medical History and Concurrent Diseases
a) Subjects with severe pulmonary disease due to IIM requiring supplemental oxygen or who 
have required mechanical breathing assistance (ventilator) within 1 year of signing 
informed consent. 
b) Subjects who, at the discretion of the investigator, have severe muscle damage evidenced 
by severe, clinically apparent muscle atrophy, or persistent weakness without evidence of 
active inflammatory disease.
c) Subjects at risk for tuberculosis (TB) defined as follows:
i)
Current clinical, radiographic or laboratory evidence of active TB, even if currently 
being treated. Chest X-rays (posterior/anterior and lateral) obtained within the 6 months 
prior to screening and TB testing (IFN-γ release assay or PPD) performed in the past 
month prior to screening will be accepted; however, a copy of the reports must be 
placed in the subject binder.
ii) A history of active or latent TB unless there is documentation that the subject had 
received prior anti-TB treatment that was appropriate in duration and type according to 
local health authority guidelines.
iii) Subjects with a positive TB screening test indicative of latent TB will not be eligible 
for the study unless they:
(1) Have no evidence of current TB based on chest X-ray performed during the 
screening period and by history and physical exam, and
(2) They are currently being treated for latent TB or the site has documentation of 
successful prior treatment of latent TB. Treatment regimens should be dictated by 
local guidelines as long as the treatment dose and duration meet or exceed local 
health authority guidelines. If permitted by local guidelines regarding treatment 
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with biologic medications, subjects with latent TB may be randomized prior to 
completion of treatment as long as they have completed at least 4 weeks of 
treatment and they have no evidence of current TB on chest X-ray at screening.
iv) In some cases, subjects with a positive TB screening test, but no clinical or radiologic 
evidence of active disease may not require treatment to be eligible for the study 
(eg, positive TB screening test due to fully treated prior infection). All such cases 
require approval by the Medical Monitor.
d) Subjects with recent acute infection defined as:
i)
Any acute infection within 60 days prior to randomization that required hospitalization 
or treatment with parenteral antibiotics 
ii) Any acute infection within 30 days prior to randomization that required oral 
antimicrobial or antiviral therapy
e) Subjects with history of chronic or recurrent bacterial infection (such as chronic 
pyelonephritis, osteomyelitis, bronchiectasis, infection of a joint prosthesis or artificial 
joint) or serious latent viral infections at the time of enrollment, including subjects with 
evidence of Immunodeficiency Virus (HIV) infection
f)
Subjects with active systemic fungal infections (eg, histoplasmosis, blastomycosis, or 
coccidiomycosis)
g) Subjects with history of recurrent herpes zoster (more than 1 episode/year) or disseminated 
(more than 1 dermatome) herpes zoster or disseminated herpes simplex, or ophthalmic 
zoster will be excluded. Symptoms of herpes zoster or herpes simplex must have resolved 
more than 60 days prior to signing informed consent.
h) Subjects with history of primary or secondary immunodeficiency
i)
Subjects who have 1) a present malignancy or 2) a previous malignancy within the last 
5 years prior to screening (except documented history of cured non-metastatic squamous 
or basal cell skin carcinoma or cervical carcinoma in situ). Subjects who had a screening 
procedure that is suspicious for malignancy, and in whom the possibility of malignancy 
cannot be reasonably excluded following additional clinical, laboratory or other diagnostic 
evaluations. Additional screening recommendations for malignancy are outlined in 
Section 3.3.4.
j)
Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, 
gastrointestinal, pulmonary, psychiatric, cardiac, neurological, or cerebral disease 
including severe and uncontrolled infections, such as sepsis and opportunistic infections. 
Concomitant medical conditions that, in the opinion of the investigator, might place the 
subject at unacceptable risk for participation in this study
k) Subjects who have received any live vaccines within 3 months of the study drug 
administration or are scheduled to receive live vaccines during the study. Study subjects 
also should not be administered a live virus vaccine for a minimum of 3 months following 
the last dose of study medication. Subjects who are in close contact with others who have 
received a live vaccine (e.g., live polio vaccine) may be enrolled at the investigator’s 
discretion.
l)
Subjects who have undergone a major surgical procedure, or any surgery that involves the 
placement of a device or implant, within the 60 days prior to randomization.
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m) Subjects with a history of (within 12 months of signing informed consent), or known 
current problems with drug or alcohol abuse history or known cirrhosis including alcoholic 
cirrhosis
n) Subjects who are impaired, incapacitated, or incapable of completing study related 
assessments
o) Subjects who have previously been treated with abatacept.
3) Physical and Laboratory Test Findings
a) Hepatitis B surface antigen (HBsAg)-positive, or
Hepatitis B core antibody 
(HBcAb)-positive subjects with detectable Hepatitis B viral DNA, and where required by 
local regulations or standard practice Hepatitis B surface antibody (HBsAb)-positive 
subjects with detectable Hepatitis B viral DNA.
NOTE:  For Japan only subjects
Subjects at risk for Hepatitis B virus (HBV), specifically subjects with:
(1) Hepatitis B surface antigen (+)
(2) Hepatitis B surface antigen (-) but Hepatitis B surface antibody (+) or Hepatitis B 
core antibody (+) with Hepatitis B virus DNA ൒1.1 Log copy /mLሺ20 IU /mLሻ.
     Subjects who are negative HBs antigen but positive anti-HBs antibody or positive anti-
HBc antibody with Hepatitis B virus DNA < 2.l Log copy /mL (20 IU /mL) can be 
enrolled in the study but must undergo periodic monitoring of HBV DNA and liver 
enzumes such as AST and ALT.  Monitoring should be performed on a monthly basis 
after initiation of treatment, for six months.  After 6 months, interval and duration 
should be decided at the investigator’s discretion and in accordance with local 
guidelines.
b) Hepatitis C antibody (HcAb)-positive subjects with detectable Hepatitis C viral RNA
c) Hemoglobin (Hgb) < 8.5 g/dl
d) White Blood Count (WBC) < 3,000/mm3 (3 x 109/L)
e) Platelets < 100,000/mm3 (100 x 109/L)
f)
Creatinine clearance < 50 mL/min (Cockroft-Gault method)
g) Serum ALT or AST > 2 times upper limit of normal not due to IIM.
h) Any laboratory test results that, in the opinion of the investigator, might place the subject 
at unacceptable risk for participation in this study
4) Allergies and Adverse Drug Reaction
a) Hypersensitivity to abatacept or one of its excipients
5) Other Exclusion Criteria
a) Subjects who are unable to complete study procedures
b) Subjects with a history or suspicion of unreliability, poor cooperation, or non-compliance 
with medical treatment
c) Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific 
circumstances a person who has been imprisoned may be included or permitted to continue 
as a subject. Strict conditions apply and Bristol-Myers Squibb approval is required.
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d) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
6) MRI Contraindications (for MRI sub-study only)
For a subject who intends to participate in the MRI sub-study, the radiologist at the site’s MRI 
facility is responsible for determining if a subject is contraindicated from having this 
procedure. If the subject is contraindicated, the subject must be dropped from the MRI sub-
study. The following is a list of some common conditions that may preclude the subject from 
having MRI of the hands or wrists. However, this should not be used as a substitute for local 
clinical standards of care. The ultimate decision to perform an MRI on an individual subject in 
the MRI sub-study rests with the site radiologist, the investigator, and the standard set by the 
local Ethics Committee:
a) Subjects who have a history of claustrophobia.
b) Subjects who have a physical limitation related to fitting in the bore of the magnet (ie, body 
weight in excess of 250 pounds or 113.4 kilograms).
c) Subjects with tattoos on the area to be imaged.
d) Subjects who have a history of allergic reaction to contrast agents
e) Subjects who had exposure to a radiological contrast agent within the 72 hours prior to the 
MRI examination.
f)
Subjects who have joint replacements in the leg that is being evaluated by the MRI 
examination.
g) Subjects with a pacemaker, epicardial pacemaker wires, MRI-incompatible cardiac valve 
prostheses, 
MRI-incompatible 
vascular 
clips 
less 
than 
two-months 
old, 
or 
MRI-incompatible aneurysm clips of any age. 
h) Subjects with MRI-incompatible cochlear implants.
i)
Subjects with spinal nerve stimulators.
j)
Subjects with an infusion pump.
k) Subjects with metallic fragments in the eyes/orbits or in the vicinity of the brain or major 
neurovascular structures of the body, subjects with an employment history which involves 
exposure to welding, or subjects who have shrapnel any place in their body.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
3.3.3
Women of Childbearing Potential
Women of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in 
a woman over age 45 years in the absence of other biological or physiological causes. In addition, 
females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level 
> 40 mIU/mL to confirm menopause.
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*Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic 
FSH level. The duration of the washout period is a function of the type of HRT used. The duration 
of the washout period below are suggested guidelines and the investigators should use their 
judgement in checking serum FSH levels. 
•
1 week minimum for vaginal hormonal products (rings, creams, gels)
•
4 week minimum for transdermal products
•
8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months. If the serum FSH level 
is > 40 mIU/ml at any time during the washout period, the woman can be considered 
postmenopausal.
3.3.4
Screening for Malignancy
It is recommended that all subjects should have been assessed for age and gender appropriate 
malignancy (e.g. breast cancer, gynecologic cancers, prostate cancer, and colon cancer) and any 
other malignancy for which an individual subject is at an increased risk at the investigator’s 
discretion (e.g., lung cancer) prior to enrollment. 
All subjects who were diagnosed with IIM in the past year must have been screened for occult 
malignancy at the discretion of the investigator. 
Subjects who are anti-TIF1-γ (p155/140) autoantibody positive and are more than 1 year from IIM 
diagnosis must also have undergone screening for occult malignancy in the last year at the 
discretion of the investigator.58 .
Testing can include any of the following, at the discretion of the investigator:
•
Chest imaging (chest CT required for subjects with a history of smoking, CXR acceptable for 
all other subjects)
•
Abdominal imaging (CT or ultrasound)
•
Laboratory testing: alpha-fetoprotein, CA-125
•
Documented skin exam for malignancy
•
Screening for gastrointestinal malignancy (e.g., stool analysis for occult blood, colonoscopy, 
sigmoidoscopy)
•
Screening for breast cancer (e.g., imaging [mammography or MRI]) for female subjects over 
the age of 40
•
Screening for cervical cancer (e.g., Pap test and human papillomavirus [HPV] testing) for all 
female subjects
•
Screening for prostate cancer (e.g., digital rectal exam, Prostate Specific Antigen testing) for 
all male subjects over the age of 40
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All subjects who discontinue study drug at any time throughout the study, require visits to assess 
safety and immunogenicity at Day 85 and Day 169 after the last dose of study drug (see Table 5.1-
7). For subjects who discontinue during the Double-Blind Period, if either the Day 85 or Day 169 
visit falls within ± 14 days of the Week 24 Post-Study Drug Efficacy Visit (Table 5.1-4), only 
perform  immunogenicity and pharmacokinetic blood samples (Table 5.1-7) along with the Post-
Study Drug Efficacy Visit.
The only exception to this requirement is when a subject withdraws consent for all study 
procedures including post-treatment study follow-up or loses the ability to consent freely (ie, is 
imprisoned or involuntarily incarcerated for the treatment of either a psychiatric or physical 
illness).
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:
•
Subject’s request to stop study treatment
•
Subject withdraws consent  
•
Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the best 
interest of the subject
•
Pregnancy (see additional instruction below)
•
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 (e.g., infectious disease) illness
•
Use of prohibited medication
•
Subjects who fail rescue therapy, as judged by the investigator, between Wk 12 and Wk 24
•
Subjects who, during the course of the study, require mechanical breathing assistance 
(ventilator) due to myositis, ILD, or another pulmonary cause.  Temporary mechanical 
breathing assistance during a procedure or elective surgery is permitted.
•
Missed Doses
−
Missed 4 or more doses of abatacept/placebo for any reason during the first 24 weeks 
(Double-Blind Period)
−
Missed 3 or more consecutive doses of abatacept/placebo for any reason during the first 
24 weeks (Double-Blind Period)
−
Missed 6 or more doses of abatacept for any reason between Week 24 and Week 52 
(Open-Label Period)
−
Missed 5 or more consecutive doses of abatacept for any reason between Week 24 and 
Week 52 (Open-Label Period) or Week 76 (for subjects randomized in Japan)
•
Significant non-compliance with protocol (i.e., procedures, assessments, medication, etc.). The 
investigator should discuss such issues with the BMS Medical Monitor.
•
Participation in another clinical trial with an investigational product.  
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In the case of pregnancy, the investigator must immediately notify the Sponsor or designee of this 
event. In most cases, the study drug will be permanently discontinued in an appropriate manner. 
Please contact the Sponsor or designee within 24 hours of awareness of the pregnancy. If the 
investigator determines a possible favorable benefit/risk ratio that warrants continuation of study 
drug, a discussion between the investigator and the Sponsor or designee must occur.
If study drug is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate case report form (CRF) page.
3.6
Post-Study Drug Study Follow up
Subjects who withdraw consent (according to Section 3.6.1) or are lost to follow-up (according to 
Section 3.6.2) will not be followed in this study; all other subjects will continue to be followed for 
collection of follow-up data as required and in line with Section 5, Study Procedures and 
Assessments.
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, if possible. The withdrawal of 
consent should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is from further treatment with study drug only or also from study procedures and/or 
post treatment study follow-up, and entered on the appropriate CRF page. In the event that vital 
status (whether the subject is alive or dead) is being measured, publicly available information 
should be used to determine vital status only as appropriately directed in accordance with local 
law.
3.6.2
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 a 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, 
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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.
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:
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Table 4-1:
Study Drugs for IM101611
Product Description / 
Class and Dosage Form
Potency
IP/Non-IMP
Blinded or Open-
Label
Packaging / Appearance
Storage Conditions
(per label)
Abatacept Injection / 
Subcutaneous
125 mg/syringe
(125 mg/mL)
IP
Blinded/Open Label
Clear to slightly opalescent, 
colorless to pale yellow solution, 
essentially free of particulate 
matter on visual inspection
Store refrigerated, 2-8 °C 
(36-46 °F); protect from 
light; protect from 
freezing
Placebo to match 
Abatacept Injection / 
Subcutaneous
NA
IP
Blinded
Clear to slightly opalescent, 
colorless to pale yellow solution, 
essentially free of particulate 
matter on visual inspection
Store refrigerated, 2-8 °C 
(36-46 °F); protect from 
light; protect from 
freezing
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4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined a pharmaceutical form of an active substance or placebo being tested or used as a reference 
in a clinical study, including products already with a marketing authorization but used or 
assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations. 
In this protocol, investigational products are:
•
Abatacept SC 125 mg in 1 ml pre-filled syringes
•
Placebo to match abatacept SC in 1 ml pre-filled syringes
BMS will supply the investigational products (also referred to as “study medication”), described 
above. 
4.2
Non-investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as non-
investigational products. 
4.3
Storage of Study Drug
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the study drug arise, the study drug should not be dispensed 
and contact BMS immediately.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Please refer to Section 9.2.2 for guidance on IP records and documentation.
Investigational product documentation (whether supplied by BMS or not) must be maintained 
which 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 (e.g., required diluents, administration sets).
4.4
Method of Assigning Subject Identification
At the time of enrollment, immediately after written informed consent is obtained and before 
performing any study-related procedures, each subject will be assigned a unique sequential subject 
number for identification throughout the study. Any subject number must not be reused for any 
other participant. The physician/coordinator must contact the Central Randomization System 
(IVRS) to enroll each subject into a centralized database at the time of signing consent.
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After completion of all screening evaluations, concomitant medication adjustment and/or 
stabilization, all eligible subjects will be randomized into the 24-week double-blinded treatment 
period (Double-Blind Period), followed by a 28 week open-label abatacept treatment period 
(Open-Label Period).  Subjects randomized in Japan will have an additional 24 week open label 
period.  Also subjects from all countries except the U.S. and the Czech Republic will have a 3 
years long term open label extension with SC abatacept.
Randomization schedules will be generated and kept by the Randomization Group within Drug 
Supply Management of Bristol-Myers Squibb. Randomization treatment will be assigned using a 
Central Randomization System in the order in which subjects qualify for treatment, not in the order 
of study enrollment. Subjects will be randomized to abatacept SC or abatacept SC placebo in a 1:1 
ratio. To maintain a 1:1 randomization between the abatacept SC and placebo SC arms within 
subjects from Japan, the study randomization will be stratified by Japan vs. Rest of World (ROW).
Specific instructions for randomization into the Central Randomization System will be provided 
in a separate manual.
4.5
Selection and Timing of Dose for Each Subject
On “Office Visit” days, study medication should be administered AFTER all assessments, 
including blood draws for assessment of immunogenicity and drug concentrations.
4.5.1
Abatacept Treatment
Abatacept (125 mg) or matching placebo will be administered subcutaneously (SC) once per week. 
See Section 5.1.1.1 for dosing windows. On Day 1, subjects and/or personal caregivers will be 
trained in self-administration of SC injections using pre-filled syringes. Administration of 
abatacept may be performed by the physician or medical staff at the study site for training purpose 
through Week 4 if needed. All subsequent injections will be self-administered or administered by 
a personal caregiver. Medical staff can act as a caregiver only when the subject cannot 
self-administer and does not have access to a personal caregiver. Training should be performed by 
investigational site personnel that are considered qualified trainers by the Investigator. Subjects or 
their caregivers will be trained using instructions that will be provided by BMS or designee.
The last dose of SC abatacept/placebo for the Double-Blind Period will be administered in 
Week 23 while the last dose of SC abatacept for the Open-Label Period will be administered in 
Week 51.  For subjects randomized from Japan, the last dose of SC abatacept in the Open Label 
Period will be at Week 75.  Also, for subjects (all countries except the U.S. and the Czech 
Republic) participating in the long term open label extension period, the last dose of SC abatacept 
will be at Day 1086.
Injections sites may include the upper arms (outside area), thigh, or abdomen. When possible, 
injection sites and/or sides of the body should be rotated every week. The upper arm injection site 
should be used only by caregivers and not for self-administration.
To ensure compliance and to monitor technique “office visit” SC injections should be administered 
in the presence of a qualified investigational staff.
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4.5.2
Standard Treatment
Subjects must be on background standard treatment for IIM (see Section 3.4.1).
4.5.3
Dose Modifications
4.5.3.1
Dose Modifications in the Absence of Adverse Events
Every effort should be made to give all study medications within ± 3 days of the target date during 
the treatment periods. The last dose before each office visit should be administered at least 4 days 
before the scheduled visit date. If study medication is not received within the dosing window, this 
dose should be skipped and the next dose must then be administered on the next scheduled target 
administration day.
4.5.3.2
Dose Modifications Due to Adverse Events
If abnormal laboratory test results or clinical adverse events indicate toxicity that, in the judgment 
of the investigator, could place the subject at risk, study drug administration should be interrupted 
and the investigator should notify the BMS Medical Monitor. Subjects may receive further study 
medication treatment only if full resolution of the adverse event or abnormal laboratory finding is 
documented.  
If a dose is skipped, the next SC injection should be administered on the subsequent targeted 
administration day.
4.6
Blinding/Unblinding
Blinding of treatment assignment is critical to the integrity of this clinical study. However, in the 
event of a medical emergency or pregnancy in an individual subject in which knowledge of the 
investigational product is critical to the subject's management, the blind for that subject may be 
broken by the investigator. The subject’s safety takes priority over any other considerations in 
determining if a treatment assignment should be unblinded.
Before breaking the blind of an individual subject's treatment, the investigator should determine 
that the unblinded information is necessary, ie, that it will alter the subject's immediate 
management. In many cases, particularly when the emergency is clearly not related to the 
investigational product, the problem may be properly managed by assuming that the subject is 
receiving active product. It is highly desirable that the decision to unblind treatment assignment 
be discussed with the Medical Monitor, but the investigator always has ultimate authority for the 
decision to unblind. The Principal Investigator should only call in for emergency unblinding 
AFTER the decision to discontinue the subject has been made.
For this study, the method of unblinding for emergency purposes is the Central Randomization 
System (IVRS).
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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4.7
Treatment Compliance
Treatment compliance for study medication will be assessed by the following:
1) Phone call reminders by the site staff.
2) Visual inspection of the contents of the sharps containers, which subjects will bring to their 
office visits.
3) Completion of subject diary cards to document administration of study medications between 
office visits.
4) Review and monitoring of proper administration technique by investigational site staff at office 
visits.
Subjects who miss doses may be required to discontinue from the study (see Section 3.5). 
Therefore, reinforcement of proper treatment compliance at every study visit is encouraged.
4.8
Destruction or Return of Investigational Product
For this study, IP (those supplied by BMS, a vendor or sourced by the investigator) such as partially 
used study drug containers, vials and syringes may be destroyed on site. 
If...
Then...
IP supplied by BMS (including its vendors)
Any unused IP supplied by BMS can only be 
destroyed after being inspected and reconciled 
by the responsible Study Monitor unless IP 
containers must be immediately destroyed as 
required for safety, or to meet local regulations 
(e.g., cytotoxics or biologics).
If IP will be returned, the return will be 
arranged by the responsible Study Monitor.
IP sourced by site, not supplied by BMS (or its 
vendors) (examples include IP sourced from 
the sites stock or commercial supply, or a 
specialty pharmacy)
It 
is 
the 
investigator’s 
or 
designee’s
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
It is the investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 
The following minimal standards must be met:
•
On-site disposal practices must not expose humans to risks from the drug.
•
On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.
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•
Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.
•
Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor 
must be documented.
•
Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers.
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for the return of IP provided by BMS (or its vendors). Destruction of non-IP sourced by the site, 
not supplied by BMS, is solely the responsibility of the investigator or designee.
Please refer to Section 9.2.2 for additional guidance on IP records and documentation.
4.9
Retained Samples for Bioavailability / Bioequivalence
Not Applicable.
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Table 5.1-6:
Long Term Open-Label Period (all countries except U.S. and the Czech Republic)
Day 1 (same day as last visit in OL Period)
Phone Visits (Day 29, 57, 113, 141, 197, 
225. 281, 309, and 337)
Quarterly Visits (Days 85 and 253)
6 Months Visits (Day 169 and 365)
Phone Visits (Day 393, 421, 477, 505, 
561, 589, 645, 673, and 701)
Quarterly Visits (Days 449 and 617)
6 Months Visits (Day 533 and 729)
Phone Visits (Day 757, 785 , 841, 869, 
925, 953,  1009. 1037, and 1065)
QuarterlyVisits Visit (Day 813 and 981)
6  Month Visit (Day 897)
Day 1093/ET Visit
Notes
Study Administration
Informed Consent
X
Enroll subject in the 3 Year
Extension Period through IWRS
X
Dispense pregnancy kits for 
home use to WOCBP
X
X
X
X
X
X
X
Sufficient pregnancy kits should be 
dispensed to subjects to allow for pregnancy 
testing every 4 weeks.
Dispense SC abataept and diary 
kits
X
X
X
X
X
X
X
Sufficient SC abatacept should be dispensed 
to allow for weekly SC dosing.
Review of diary cards
X
X
X
X
X
X
X
X
X
X
Dosing of SC Abatacept 
X
X
X
X
X
X
X
X
X
X
SC Abatacept will injected weekly.
Reconciliation of SC Abatacept
X
X
X
X
X
X
X
Safety Assessments
Targeted Physical Examination
X
X
X
X
X
X
X
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Table 5.1-6:
Long Term Open-Label Period (all countries except U.S. and the Czech Republic)
Day 1 (same day as last visit in OL Period)
Phone Visits (Day 29, 57, 113, 141, 197, 
225. 281, 309, and 337)
Quarterly Visits (Days 85 and 253)
6 Months Visits (Day 169 and 365)
Phone Visits (Day 393, 421, 477, 505, 
561, 589, 645, 673, and 701)
Quarterly Visits (Days 449 and 617)
6 Months Visits (Day 533 and 729)
Phone Visits (Day 757, 785 , 841, 869, 
925, 953,  1009. 1037, and 1065)
QuarterlyVisits Visit (Day 813 and 981)
6  Month Visit (Day 897)
Day 1093/ET Visit
Notes
Adverse Event Monitoring
X
X
X
X
X
X
X
X
X
X
Laboratory Testing
Hematology Panel
X
X
X
X
Chemistry Panel
X
X
X
X
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Table 5.1-7:
Post-Treatment Follow-Up Period (only performed for subjects that discontinue study treatment and do 
not start Post-Study Drug Program (PSDP) or commercial abatacept)
Visit (± 14 days)
85 Days after 
Last Dose
169 Days after 
Last Dose
Notes
Safety Assessments
Vital Signs
X
X
Adverse Event Monitoring
X
X
LaboratoryAssessments
Urine pregnancy test
X
X
Testing performed locally on WOCBP subjects only
 
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5.1.1
Retesting During Screening or Lead-in Period / Rescreening
Retesting
Retesting of laboratory parameters and/or other assessments within any single Screening period 
will be permitted (in addition to any parameters that require a confirmatory value).
Any new result will override the previous result (i.e., the most current result prior to 
Randomization) and is the value by which study inclusion will be assessed, as it represents the 
subject’s most current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified subjects. The Medical 
Monitor can be consulted if needed to discuss whether repeat testing of any particular parameter 
is clinically relevant.
Rescreening
Subjects that are screen failures may be considered for re-screening if the investigator feels a 
change in status may render the subject eligible. Medical monitor approval is required if screen 
failure was related to safety concern. Rescreens are not permitted within the four weeks after 
signing the first informed consent. The subject will need to sign a new informed consent and be 
re-enrolled with a new subject number via the IVRS. Some tests, such as chest X-ray, may not 
need to be repeated if they were performed within the protocol defined window.
5.1.1.1
Study Drug Administration Windows
SC injections of study medication may be administered ± 3 days of the target day. Subjects who 
miss the dose window should skip the SC injection and wait until the next targeted administration 
day.
If abnormal laboratory test results or clinical AEs indicate toxicity that, in the judgment of the 
investigator, could place the subjects at risk, study medication administration should be withheld. 
Subjects may receive further study medication only if resolution of the AE or abnormal laboratory 
finding is documented or, at a minimum, the subject’s status returns to what it was at baseline. The 
investigator can contact the BMS Study Medical Monitor to discuss as needed.
5.1.2
Order of Study Assessments
It is strongly encouraged that study assessments be performed in the following order:
1) Patient reported outcomes (PROs) questionnaires
2) AE collection
3) Vital signs
4) Muscle strength assessments
5) Other investigator assessments
6) Blood draws
7) Study drug administration (when applicable)
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5.2
Study Materials
•
Diary cards to record SC weekly dosing administration and the monthly pregnancy test results 
for WOCBPs (mandatory)
•
Written instructions on how to use the SC syringes
•
eCRF instructions
•
Pregnancy Surveillance Forms
•
Source documents (paper or electronic device)
•
Drug Inventory binder (optional)
•
Interactive Voice Response System (IVRS) worksheets
•
Laboratory test kits for all required laboratory testing
•
Cooler bags and gel packs will be provided to assist subjects in transporting study drug
•
Sharps containers will be provided to assist subjects in disposing of used SC syringes
•
Tote bags to transport cooler bags, sharp containers and study drug
•
For WOCBP urine pregnancy kits/instructions will be provided to be used between office 
visits.
•
HRCT and MRI Imaging Manuals
•
Actigraphy device Manuals
•
Metronome, wrist weights, step stool
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.
Subjects who terminate treatment early should complete the appropriate Early Termination Visit 
(Table 5.1-2, Table 5.1-3, Table 5.1.-5, and Table 5.1-6) and the Post Treatment Follow-
up Visits (Table 5.1-7). The Early Termination Visit should be as soon as possible after the 
last dose of study medication.
All assessments should be performed or administered prior to study drug administration unless 
otherwise indicated.
Only data for the procedures and assessments specified in this protocol should be submitted to 
BMS on a case report form. Additional procedures and assessments may be performed as part of 
the standard of care; however, data for these assessments should remain in the subject’s medical 
record and should not be provided to BMS, unless specifically requested from BMS.
Only results of central laboratory assessments relevant to clinical care will be sent to the sites 
(Section 5.3.5). All other clinical assessments done as part of this study, including PFTs, HRCT, 
MRI of the thighs and muscle biopsies will not be read centrally for return to the site. These must 
be read locally following usual and customary practices for clinical assessments and reviewed by 
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investigators as required by the protocol for safety assessments (ie, PFT and HRCT) or as deemed 
necessary by investigators for those not required by the protocol (ie, MRI or muscle biopsy). 
Reports generated from central analysis of these will not be clinical in nature and will not be sent 
to sites for review.
Subjects who have clinically active or relevant Interstitial Lung Disease (ILD) as determined by 
the investigator prior to randomization must undergo pulmonary function testing (PFT) and 
imaging by High Resolution CT scan (HRCT). The target populations are described and the testing 
are outlined in Section 5.3.6 and Section 5.3.7.2, respectively.
5.3.1
Physical Examination
Physical examinations preferably should be performed by a qualified physician or Doctor of 
Medicine (MD). Where permitted by local practice and guidelines a qualified Doctor of 
Osteopathy (DO), Physician Assistant (PA), or Nurse Practitioner (NP) may perform the physical 
examination. 
The physical examination should include examination of the heart, lungs, abdomen, the lymph 
nodes, liver, spleen and skin. A physical examination may note any changes in the subject’s 
condition (body systems) since the last assessment and does not preclude examination of any other 
body systems as clinically indicated. Any new findings after Day 1 should be reported as (S)AE.
5.3.2
Physical Measurements
Weight and height is to be recorded at screening. Weight is to be recorded as noted in Table 5.1-
2, Table 5.1-3, and Table 5.1-5, thereafter.
5.3.3
Vital Signs
Vital signs (seated blood pressure, heart rate, and temperature) will be recorded during every office 
visit and prior to dose administration, when applicable. Blood pressure and heart rate should be 
measured after the subject has been seated quietly for at least 5 minutes.
5.3.4
TB Screening
A chest X-ray and physical examination are considered part of the process to assess a subject’s 
eligibility. In addition to a chest X-ray that does not show any evidence or suspicion of latent TB, 
a tuberculin test will be performed and interpreted according to local country Health Authorities 
and/or Medical Society guidelines. Some guidelines have specific recommendations for subjects 
who are to receive biologics or immunosuppressant therapies (eg, RA experience with biologic 
agents),60,61 (outside the US sites, local guidelines endorsed by medical societies on PPD testing 
in subjects with RA being treated with biologics may also apply) or who are immunocompromised 
and who have had prior BCG vaccination(s).62 Tuberculin skin testing is not contraindicated for 
persons who have been vaccinated with BCG. An interferon gamma release assay 
(eg, QuantiFERON Gold or Tspot/ELISpot) is an acceptable alternative when skin testing for 
tuberculosis (ie, PPD) is not appropriate. TB screening test may be performed by qualified 
personnel at the central laboratory or by a qualified local laboratory. If TB test has been performed 
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within 4 weeks prior to informed consent and clear documentation is available, the test result may 
be used to screen for eligibility. 
5.3.5
Laboratory Assessments
All laboratory assessments will be analyzed centrally except where noted.
Blood and/or urine samples will be obtained at all visits noted in Time and Events Schedule. Any 
laboratory test result that the investigator considers clinically relevant should be recorded on the 
appropriate Adverse Event page of the CRF (see Appendix 2).
5.3.5.1
Hematology Panel
•
Hemoglobin
•
Total WBC count, including differential
•
Platelet count
5.3.5.2
Chemistry Panel
•
Sodium 
•
Blood urea nitrogen (BUN)
•
Potassium 
•
Total bilirubin
•
Chloride 
•
Alanine aminotransferase (ALT)
•
Total Protein 
•
Aspartate aminotransferase (AST)
•
Albumin 
•
Gamma-glutamyltransferase (GGT)
•
Calcium 
•
Alkaline phosphatase
•
Phosphorus 
•
LDH
•
Glucose
•
Creatine kinase (CK)
•
Aldolase 
•
Creatinine
5.3.5.3
Antibody Panels
•
Quantitative Immunoglobulins (IgG, IgA, IgM)
•
Anti-nuclear antibody (ANA) panel
•
Myositis-specific autoantibodies (eg. Jo-1, PL-12, PL-7, OJ, EJ, SRP, Mi-2, TIF1-γ, MDA5, 
NXP2)
•
Myositis-associated autoantibodies (eg. PM/Scl, Ku, SS-A, U1 RNP, U2 snRNP, fibrillarin U3 
RNP)
5.3.5.4
Complement
•
C3
•
C4
•
CH50
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5.3.5.5
Urinalysis
•
pH
•
Protein
•
Glucose
•
Blood
5.3.5.6
Hepatitis Screen
•
Hepatitis B surface antigen, hepatitis B core antibody. If positive, reflex Hepatitis B viral DNA 
testing must be performed. Where required by local regulations or standard practice Hepatitis 
B viral DNA testing also must be performed on Hepatitis B suface antibody (HBsAb)-positive 
subjects.
•
Hepatitis C antibody. If positive, reflex HCV RNA testing must be performed
NOTE:  For Japan only subjects
•
Hepatitis B surface antigen, hepatitis B core antibody (hepatitis B surface antibody, where 
required by local guidelines).  If negative HBs antigen but positive anti-HBc antibody or 
positive anti-HBs antibody, reflex Hepatitis B viral DNA treating must be performed.
5.3.5.7
Pregnancy Tests
Urine/serum pregnancy tests (minimum sensitivity 25 IU/L of β-HCG) must be performed, with a 
negative result, for all WOCBP within 24 hours prior to dosing for visits specified in Table 5.1-2,
Table 5.1-3, Table 5.1-5, Table 5.1-6 and every 4 weeks in the Follow up period, Table 5.1-7. 
Urine tests are the preferred method and must be performed unless serum is required by local 
regulations. A serum test must be performed for confirmation of any positive urine test result. 
Urine tests can be processed locally and can be self-administered by the subject between office 
visits, if permitted by local regulations. If any female subject becomes pregnant, she will stop 
receiving study treatment immediately and enter the Post Treatment Follow-up Period. A 
pregnancy surveillance form will be completed and submitted to Bristol-Myers Squibb. Serum 
pregnancy tests will be processed centrally.
5.3.5.8
HIV Testing
HIV testing will be performed centrally unless prohibited by local regulation, guidelines, or 
standard practice.
5.3.5.9
Fungal Infection and Pulmonary Fibrosis Test 
The (1 to 3)-β-D-glucan and KL-6 test will only be performed in regions and/or countries where 
it is considered the local standard of care at the screening visit. This test should be analyzed locally.
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5.3.6
Pulmonary Function Testing
To assess the safety and efficacy of abatacept in IIM subjects with interstitial lung disease (ILD), 
pulmonary function testing including FEV1, FVC, and DLCO will be performed on all subjects 
who have clinically active or relevant Interstitial Lung Disease (ILD) or anti-synthetase syndrome 
at baseline (define in 5.3.7.2). Testing will be obtained at baseline (prior to Day 1), Week 24, Week 
52 and Week 76 (or early termination) for subjects with ILD. PFT will be performed and read 
locally and reviewed by the sites for clinical decision making. No central clinical report will be 
generated for return to the site.
5.3.7
Imaging Assessment for the Study
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the Study Investigator as per 
standard medical/clinical judgment. Images will be submitted to the imaging core lab for central 
analysis as specified below.
5.3.7.1
X-ray Assessment
A posterior-anterior and lateral chest X-ray, performed during screening, is required for all subjects 
unless performed within 6 months prior to obtaining written informed consent and documentation 
of the earlier X-ray is on file. Investigators must ensure that the results of the chest X-ray satisfy 
criteria for eligibility. The chest X-ray result will be recorded on the appropriate page of the eCRF. 
This assessment will not be evaluated by a central lab.
5.3.7.2
High-Resolution Computed Tomography (HRCT) Chest
HRCT of the chest will be obtained to evaluate the extent of lung fibrosis at baseline (prior to 
Day 1) for subjects who are identified by the investigator as having clinically active or relevant 
Interstitial Lung Disease (ILD) or anti-synthetase syndrome at baseline (defined as the presence 
of anti-synthetase autoantibody and at least 2 of the following: ILD, inflammatory myositis or 
inflammatory polyarthritis).
Subjects with clinically active or relevant ILD will be defined as those who have: 
1) clinical symptoms of ILD at baseline and/or during the study, or
2) worsening ILD, at baseline and/or during the study, as per the treating physician assessment 
necessitating a treatment change (with documented worsening of at least 2 the following 
parameters: patient’s report of worsening dyspnea, worsening in severity of ground glass 
opacities (GGO), reticulation or honeycombing or fibrosis on chest HRCT or a decline in the 
FVC% > 10%) within last 6 months, or
3) new onset of ILD (within 3 months of study entry), or
4) a clinically relevant decrease in lung function on Pulmonary Function Testing (at the discretion 
of the investigator)
Subjects with ILD who are evaluated with a HRCT at baseline will also have repeat HRCT 
performed at Weeks 24, 52, and 76 (or early termination).
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honeycombing in non-septal, linear, plate-like, and sub-pleural patterns.66 However, it is not 
uncommon for consolidation to progress to frank fibrosis.67
HRCT has been applied in multiple clinical studies of lung fibrosis for drug development, serving 
as an inclusion criterion, a predictive marker of positive treatment response, and/or efficacy 
readout. A computer-assisted diagnosis (CAD) score to quantify lung fibrosis as the percentage 
involvement of reticulation patterns based on texture measures from HRCT has been developed 
and validated as a measure of quantitative lung fibrosis (QLF) and a potential surrogate imaging 
marker. CAD scores of QLF have been successfully applied as outcome measurements to test 
treatment efficacy in ILD trials. Compared with visual assessments, CAD scores have been shown 
to improve objectivity, sensitivity, and repeatability when measuring quantitative changes in lung 
features.
5.4
Efficacy Assessments
Questionnaires and investigator/subject assessments will be completed prior to study drug 
administration. If captured on an electronic tablet (ePRO), this device will serve as the source 
document.
5.4.1
Clinical Assessments for the Study
5.4.1.1
IMACS Definition of Improvement (DOI)
The IMACS DOI is:
•
An improvement of ≥20% from baseline in 3 IMACS core measures, AND
•
No more than 2 IMACS core measure scores worsen by ≥25% from baseline, AND
•
Manual Muscle Test (MMT-8) may not decrease by ≥25% from baseline
IMACS core measures are:
•
Physician Global Assessment of Disease Activity (PGA)
•
Patient (Subject) Global Assessment of Disease Activity (SGA)
•
Manual Muscle Test (MMT-8)
•
Health Assessment Questionnaire-Disability Index (HAQ-DI)
•
Muscle Enzyme levels
•
Myositis Disease Activity Assessment Tool (MDAAT) Extramuscular Global Activity 
The muscle enzymes of interest are creatine kinase (CK), aldolase, AST, ALT, and LDH. To assess 
the DOI the most abnormal lab value (% above ULN) at baseline will be determined. The 
subsequent change from baseline for this lab value will be used to determine if the patient has met 
the DOI at each time point indicated (Table 5.1-2, Table 5.1-3, and Table 5.1-5).
To assess the criteria for worsening, the change from baseline will be determined for all 5 lab 
values at each time-point indicated (Table 5.1-2, Table 5.1-3. and Table 5.1-5). The lab value with 
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the greatest percent increase from baseline for each will be used to determine if the patient has met 
the criteria for worsening respectively (Section 3.1.5).
Descriptions of the other core measures are below.
5.4.1.2
Assessments Performed by Medical Staff
The investigator or sub-investigator performing this assessment should have appropriate medical 
credentials and/or should be individuals with appropriate scientific/medical background who are 
experienced in performing myositis disease activity assessments. The sub-investigator preferably 
should be a qualified physician or Doctor of Medicine (MD). Where permitted by local practice 
and guidelines, a qualified Doctor of Osteopathy (DO), Physician Assistant (PA), or Nurse 
Practitioner (NP) may perform the Physicians Global Assessment if they have substantial 
experience assessing patients with IIM. All other non-PGA assessments may be performed by 
study site personnel that have appropriate relevant clinical or technical training (eg, RN or physical 
therapist) and are trained to perform the specific IIM study assessments. All individuals that 
perform study assessments must be recorded in the study file along with their educational 
background, work experience and training.
Physicians Global Assessment of Disease Activity (PGA)
This tool measures the global evaluation by the treating physician of the overall disease activity of 
the patient at the time of assessment using a 10 cm visual analogue scale that can be performed by 
the investigator or sub-investigator. 
Manual Muscle Test (MMT-8)
This tool assesses muscle strength using a 0 - 10 point scale. A set of 7 designated muscles is tested 
bilaterally plus axial (neck flexor) testing, so that the potential MMT-8 score ranges from 0 - 150. 
The designated muscles tested will be:
•
Neck flexors
•
Deltoid middle
•
Biceps brachii
•
Gluteus maximus
•
Gluteus medius
•
Quadriceps
•
Wrist extensors
•
Ankle dorsiflexors
Myositis Disease Activity Assessment Tool (MDAAT)
This is a combined tool that captures the physician’s assessment of disease activity of various 
organ systems using (1) a 0-4 scale and (2) a visual analog scale (VAS). It assesses the clinical 
features of each organ system based upon:
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a) The presence of clinical features or symptoms within the previous 4 weeks that are due to 
active disease (i.e., use your clinical judgment to determine how active the myositis-
associated clinical feature has been within the previous 4 weeks)
b) The judgment that the feature is due to the myositis disease process (ie, clinical findings 
known or suspected to be due to another disease process or due to therapy should NOT be 
considered in this evaluation)
c) The concept that disease activity is defined as a potentially reversible finding
d) A clinical, functional, and laboratory assessment for each organ system
The scoring system is based primarily on the physician’s intention to treat (Categories A – E). In 
some cases, a patient may meet the clinical manifestations of a particularly category, but the 
treatment does not match the intention to treat of that particular category; in those cases, the 
category matching the clinical symptoms should be marked. If more than one clinical symptom is 
present within a system, and different categories would be scored for each, mark the category that 
is most severe. 
Myositis Function Index (FI-2)
The FI-2 is a functional outcome developed for patients with adult polymyositis or 
dermatomyositis assessing muscle endurance in seven muscle groups. Each muscle group is scored 
as the number of correctly performed repetitions with 60 or 120 maximal number of repetitions 
depending on muscle group. The FI-2 is a further development of the original Functional Index 
(FI) and has been validated as to content and construct validity and intra- and inter-rater reliability. 
The FI-2 can be performed on both right and left sides requiring a maximum of 33 minutes, or just 
on the dominant side which takes 21 minutes 
Myositis Damage Index (MDI)
This tool measures the degree of disease damage of all organ systems. It is composed of a series 
of organ-specific questions relating to the presence or absence of a given sign or symptom or 
problem to measure the extent of damage, and an overall rating of the disease damage of each 
system using a 10 cm. visual analogue scale to measure the severity of damage 
Myositis Response Criteria (MRC)68
This Myositis Response Criteria (MRC) algorithm generates a continuous total improvement score 
(range 0-100) based on the sum of the absolute % change in the 6 core domains (weighted) used 
in the IMACS DOI. It also defines cut points for minimal (≥20 point increase), moderate (≥40 
points), and major (≥60 points) improvement in disease.
Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
This tool assesses the improvement in skin disease activity in subjects with dermatomyositis. Four 
domains are evaluated including 1) disease activity and damage in 15 anatomic locations, 
2) presence of Gottron’s papules on the hands, 3) periungual changes, and 4) alopecia. A total 
activity score and damage score are calculated. 
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5.4.1.3
Patient Reported Outcomes
Subjects will complete the Patient Global Assessment of Disease Activity, HAQ-DI, PROMIS 
Fatigue, and SF-36 in the ePRO device. All of these patient reported outcomes should be 
performed prior to all other assessments.
Patient (Subject) Global Assessment of Disease Activity (SGA)
This tool measures the global evaluation by the subject of their overall disease activity at the time 
of assessment using a 10 cm visual analogue scale.
Health Assessment Questionnaire Disability Index (HAQ/HAQ-DI)
Scoring conventions are based on the Standard Disability Index of HAQ/HAQ-DI, using the 
20 response items. The HAQ-DI takes into account the subject’s use of aids, devices, or assistance 
in the scoring algorithm for a disability category. For each of the 8 disability categories there is an 
“aids/devices” companion variable that is used to record the type of assistance, if any, a subject 
uses for his/her usual activities. If either “aids/devices” and/or “assistance from another person” 
are checked for a disability category, the score for this category is set to “2” (much difficulty), if 
the original score was “0” (no difficulty) or “1” (some difficulty). The HAQ-DI is then calculated 
by summing the adjusted categories scores and dividing by the number of categories answered. 
Details of the HAQ-DI scoring conventions are documented in Fries et al69 and Ramey et al70. 
The HAQ is based on a scale of 0-3. 
Patient Reported Outcomes Measurement Information System (PROMIS) - SF Fatigue v1.0 Adult 
Form 8a 
The Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 
8a will be used to capture fatigue. The PROMIS project was established as part of the National 
Institutes of Health Roadmap Initiative to create item banks which are publically available, 
efficient, precise, and valid across a variety of diseases to assess PROs (www.nihpromis.org).
The PROMIS Fatigue instrument evaluates a range of self-reported symptoms, from mild 
subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion 
that likely decreases one’s ability to execute daily activities and function normally in family or 
social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) 
and the impact of fatigue on physical, mental, and social activities.
In this study, the static form of eight questions will be used. The Fatigue short form is universal 
rather than disease-specific. It assesses fatigue over the past seven days.
 
 
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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 (e.g., 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 (e.g., death is an 
endpoint, if death occurred due to anaphylaxis, anaphylaxis must be reported) should be reported 
as SAE (see Section 6.1.1 for reporting details).
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 
•
a visit to the emergency room or other hospital department < 24 hours, that does not result in 
admission (unless considered an important medical or life-threatening event)
•
elective surgery, planned prior to signing consent
•
admissions as per protocol for a planned medical/surgical procedure
•
routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)
•
medical/surgical admission other than to remedy ill health and planned prior to entry into the 
study. Appropriate documentation is required in these cases
•
admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (e.g., 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
Section 5.5.1 in the Investigator Brochure (IB) represent the Reference Safety Information to 
determine expectedness of serious adverse events for expedited reporting. Following the subject’s 
written consent to participate in the study, all SAEs, whether related or not related to study drug, 
must be collected, including those thought to be associated with protocol-specified procedures. All 
SAEs must be collected that occur during the screening period through 24 weeks after
discontinuation of dosing.
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure. 
An SAE report must be completed for any event where doubt exists regarding its seriousness. 
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If the investigator believes that an SAE is not related to study drug, but is potentially related to the 
conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship must be specified in the narrative section of the SAE Report Form.
SAEs, whether related or not related to study treatment, and Pregnancies must be reported to BMS 
(or designee) immediately within 24 hours of awareness of the event. 
SAEs must be recorded on the SAE Report Form. The required method for SAE data reporting is 
through the eCRF. The paper SAE Report Form is only intended as a back-up option when the 
electronic data capture (EDC) system is unavailable /not functioning for transmission of the eCRF 
to BMS (or designee). In this case, the paper form is transmitted via email or confirmed facsimile 
(fax) transmission. When paper forms are used, the original paper forms are to remain on site. 
Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted via email 
or confirmed facsimile (fax) transmission.
 
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, the SAE report must be updated and submitted within 24 hours to Sponsor or 
designee using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
BMS will be reporting adverse events to regulatory authorities and ethics committees according to 
local applicable laws including European Directive 2001/20/EC and FDA Code of Federal 
Regulations 21 CFR Parts 312 and 320. A SUSAR (Suspected, Unexpected Serious Adverse 
Reaction) is a subset of SAEs and will be reported to the appropriate regulatory authorities and 
investigators following local and global guidelines and requirements.
6.2
Nonserious Adverse Events
A nonserious adverse event is an AE not classified as serious.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. Nonserious 
AE information should also be collected from the start of a placebo lead-in period or other 
observational period intended to establish a baseline status for the subjects.
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment as 
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appropriate. All identified nonserious AEs must be recorded and described on the nonserious AE 
page of the CRF (paper or electronic). 
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities that 
are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form electronic) as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning.
•
Any laboratory test result that is clinically significant or meets the definition of an SAE 
•
Any laboratory test result abnormality that required the subject to have study drug discontinued 
or interrupted
•
Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (e.g., anemia versus low hemoglobin value).
6.4
Pregnancy
If, following initiation of the study drug, it is subsequently discovered that a study subject is 
pregnant or may have been pregnant at the time of study exposure, including during at least 5 half-
lives after product administration, the investigator must immediately notify the Sponsor or 
designee of this event and complete and forward a Pregnancy Surveillance Form to BMS Designee 
within 24 hours of awareness of the event and in accordance with SAE reporting procedures 
described in Section 6.1.1.
In most cases, the study drug will be permanently discontinued in an appropriate manner (eg, dose 
tapering if necessary for subject safety). Please call the Sponsor or designee within 24 hours of 
awareness of the pregnancy.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject.
The investigator must immediately notify the Sponsor or designee of this event and complete and 
forward a Pregnancy Surveillance Form to Sponsor or designee within 24 hours of awareness of 
the event and in accordance with SAE reporting procedures described in Section 6.1.1. 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
Sponsor or designee. In order for BMS to collect any pregnancy surveillance information from the 
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female partner, the female partner must sign an informed consent form for disclosure of this 
information. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. All occurrences of overdose must be 
reported as an SAE (see Section 6.1.1 for reporting details.).
6.6
Potential Drug Induced Liver Injury (DILI)
Specific criteria for identifying potential DILI have not been identified for this protocol. Standard 
medical practice in identifying and monitoring hepatic issues should be followed.
6.7
Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, electrocardiogram, 
X-ray filming, 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.
For Japan only subjects, malfunctions of the pre-filled syringes containing study drug should be 
reported to the sponsor via designated form (electronic system).  SAEs or events that could lead to 
an SAE that occurred as a result of the malfunction should be reported to the sponsor within 24 
hours of awareness of the event.
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
7.1
Adjudication Committee
An adjudication committee will be established to determine eligibility of subjects with regard to 
the requirement that subjects have active disease at the time of screening when they do not have 
at least one of the 3 identified clinical findings: 1) active myositis-associated rash (Gottron’s 
papules or heliotrope rash), or 2) a muscle biopsy, MRI or EMG within 3 months demonstrating
active disease or 3) elevated CK > 5 times the upper limit of normal with no alternate explanation 
or cause (see Section 3.3.1). The committee will be composed of experts in the treatment and study 
of IIM who will evaluate all relevant material including, but not limited to, medical history, IIM 
history (such as disease duration and type), laboratory results (including muscle enzyme levels and 
auto-antibodies), medication history (including dose, duration, number of current and prior 
therapies), and available imaging, EMG, and biopsy results. Sites will complete the Active Disease 
Adjudication Form and submit with supporting documentation. Further details on the processes 
and procedures the committee will follow will be outlined in the Charter of that committee.
7.2
Data Monitoring Committee
A Data Monitoring Committee will be established to provide oversight of safety and efficacy 
considerations in Study IM101611 and to provide advice to BMS regarding actions the committee
deems necessary for the continuing protection of subjects enrolled in the study. Further details on 
the content and method 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.
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8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
A sample size of 150 subjects (75 subjects per treatment group) is planned based on the primary 
comparison of the proportion of subjects with IMACS DOI (as defined under the primary 
objective) at Day 169 (Week 24) between the SC abatacept group and the placebo group on a 
background of standard treatment.
A sample size of 150 subjects randomized in a 1:1 ratio to the SC abatacept group and placebo 
group will yield a power of approximately 90% to detect a treatment difference of 27% in the rate 
of IMACS DOI between the 2 treatment groups based on a continuity corrected chi-squared test. 
This power estimate assumes a two-sided alpha level of 5%, IMACS DOI rate of 60% in the 
abatacept group and 33% in the placebo group.
The 60% estimate of IMACS DOI in the abatacept group was based on reported rates of IMACS 
DOI in studies of patients with Myositis on combination therapy with another biologic agent36. It 
is expected that the rate of IMACS DOI on abatacept in combination with standard treatment 
should be similar to that observed with the use of another biologic agent in combination with 
standard treatment. Table 8.1-1 below presents the power estimates for other considerations of 
proportion of subjects in IMAC DOI in the abatacept group assuming the total sample size of 
150 subjects. Randomization will be stratified globally by 3 stratification variables: (1) disease 
diagnosis (Dermatomyositis [DM] vs non-DM IIM), (2) Interstitial Lung Disease (ILD) (present 
vs absent), (3) Japan vs ROW.
Table 8.1-1:
Estimates of Power for Various Assumed Rates of IMACS DOI at 
Week 24 Assuming Total Sample Size of 150
Aba Rate
Placebo Rate
Delta
Power (%)
50%
20%
30%
96
25%
25%
85
55%
25%
30%
95
30%
25%
84
60%
25%
35%
~ 99
30%
30%
95
35%
25%
83
8.2
Populations for Analyses
Efficacy endpoints will be summarized according to the Intent-to-Treat (ITT) population and 
safety endpoints will be summarized according to the As-Treated population. These populations 
are described briefly below along with the Per-protocol population
 
.
•
Intent-to-Treat Analysis Population
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The Intent-to-Treat (ITT) Analysis Population is defined to include all subjects randomized 
into the study for whom Case Report Form (CRF) data indicate that at least one dose of study 
medication (abatacept or placebo) is administered during the Double-Blind Period. 
All subjects who are randomized but never received study medication are to be excluded. 
Given the blinded nature of this study, it is reasonable to assume that subjects who discontinue 
prior to the receipt of study medication do so for reasons unrelated to study medication. 
Subjects are grouped according to the treatments to which they are randomized by IVRS. 
ITT Analysis Population is also referred to as ‘All Randomized and Treated Subjects’. 
•
As-Treated Analysis Population
The As-Treated Analysis Population contain all subjects for whom CRF data indicate that at 
least one dose of study medication was administered during Double-Blind Period. 
Subjects are grouped according to the treatments to which they are randomized, except in cases 
where information are available, which indicate that a subject receives a different treatment for 
the entire course of Double-Blind Period. In this case, the subject will be presented by the 
treatment they actually received. 
The As-Treated Analysis Population will also be referred as ‘All Treated Subjects’.
•
Per-Protocol Analysis Population
The Per-protocol Analysis Population is defined as a subset of the ITT Analysis Population 
which excludes subjects who have relevant protocol deviations during the double-blind study 
period. Relevant protocol deviations are those protocol deviations that might affect the primary 
efficacy endpoint of the study. A programmable list of relevant protocol deviations will be 
included in the Statistical Analysis Plan and approved prior to the Double-Blind Period 
database lock.
The Per-protocol Analysis Population will only be used if more than 10% of the subjects in 
either treatment group have relevant protocol deviations. In such a case, the analysis of the 
primary efficacy endpoint will be repeated in the Per-protocol Analysis Population.
 
 
•
Open-label Abatacept Treated Population 
The open-label abatacept treated population will contain all subjects for whom CRF data 
indicate that at least one dose of study medication was administered during the Open-Label 
Period. All Week 52 analyses will be performed using this population.
•
Subjects randomized in Japan Open-label Abatacept Treated Population
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secondary endpoint measures at Day 169 (week 24), no formal statistical testing will be conducted 
for any of the efficacy analyses related to the secondary endpoints at other time points and on any 
of exploratory endpoints. Appropriate summary statistics will be provided for the analysis of each 
endpoint.
The Week 52 analysis will be performed once all subjects complete 52 weeks of treatment in the 
study and/or follow-up visits whichever is later. The Week 52 analysis will include summaries of 
AEs reported during the study up to 56 days post last dose date in the study for all subjects. Efficacy 
endpoints will be summarized over time during the open-label period for the week 52 analysis. 
The 52 week analysis will be performed using the open-label treated analysis population. Nominal 
p-values will provided for the secondary endpoint measures at Day 169 (week 24), no formal 
statistical testing will be conducted for any of the efficacy analyses related to the secondary 
endpoints at other time points and on any of exploratory endpoints. Appropriate summary statistics 
will be provided for the analysis of each endpoint.
An analysis using only Japanese sites will performed once all subjects complete 76 weeks of 
treatment in the study.
A final analysis will be performed when subjects complete the 3 year long term extension and/or 
follow-up visits whichever is later.
8.4.1
Demographics and Baseline Characteristics
Frequency distributions and summary statistics of all demographic variables and baseline 
characteristics will be presented by treatment arm using the ITT population. Detail of baseline 
characteristics to be presented will be included in the SAP.
8.4.2
Efficacy Analyses
8.4.2.1
Primary Efficacy Analysis
The primary comparison of proportion of subjects in IMACS DOI at Week 24 between the SC 
abatacept and placebo groups will be assessed using a logistic regression model. To account for 
randomization stratification, the logistic regression model will adjust for the randomization 
stratification variables of disease diagnosis (Dermatomyositis [DM] vs non-DM IIM), Interstitial 
Lung disease status (present vs. absent), and Japan vs. ROW; baseline MMT8, baseline MDAAT, 
baseline PGA (continuous) and treatment group will also be included in the model. Point estimate 
of the adjusted Odds Ratios (OR) of the odds of achieving IMACS DOI in the abatacept arm 
compared to the placebo arm, corresponding 95% CI and p-value will be provided. The proportion 
of subjects in IMACS DOI in each treatment group and corresponding 95% CI will also be 
provided. All subjects who discontinue study medication prematurely prior to reaching the Week 
24 assessment visit, will be considered as not achieving IMACS DOI for the primary analysis. 
Efficacy assessments collected at week 24 on subjects who discontinue study medication prior to 
week 24 will not be included in the primary analysis of the primary endpoint, but will be included 
in a sensitivity analysis of the primary endpoint. Specification of sensitivity analyses of the primary 
endpoint under different assumptions for missing data at week 24 will be provided in the Statistical 
Analysis Plan (SAP).
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8.4.2.2
Secondary Efficacy Analysis
In addition to the primary efficacy endpoint, analyses related to the secondary and exploratory 
endpoints will also be included in the Week 24 analysis. The secondary efficacy assessment of 
change from baseline in muscle endurance using FI-2 up to Day 169 (Week 24) will be assessed 
using a longitudinal (repeated measure) mixed model including treatment group, baseline FI-2 
value and randomization stratification factors: diagnosis (DM vs non-DM IIM), ILD, Japan vs 
ROW, time (study days in which FI-2 is measured), time by baseline FI-2 and time by treatment 
interactions as fixed effects and subject as a random effect. Adjusted mean, SE, 95% CI for 
adjusted mean difference between treatment arms will be provided. A similar mixed model will 
also be used to assess the change from baseline in HAQ-DI up to Day 169 (Week 24). The model 
will include treatment group, baseline value HAQ-DI value, randomization stratification factors: 
disease diagnosis (DM vs non-DM IIM ILD, Region (Japan vs ROW), time (study days in which 
HAQ-DI is measured), time by baseline HAQ-DI and time by treatment interactions as fixed 
effects and subject as a random effect. Adjusted mean, SE, 95% CI for adjusted mean difference 
between treatment arms will also be provided.  
The secondary efficacy assessment of change from baseline in MDAAT value will also be assessed 
using a longitudinal (repeated measure) mixed model including treatment group, baseline value 
MDAAT value, randomization stratification factors: disease diagnosis (DM vs non-DM IIM), ILD, 
Region (Japan vs ROW), time (study days in which MDAAT is measured), time by baseline 
MDAAT and time by treatment interactions as fixed effects and subject as a random effect. 
Adjusted mean, SE, 95% CI for adjusted mean difference between treatment arms will also be 
provided.
A similar mixed model will also be used to assess the change from baseline in Myositis Response 
Criteria (MRC) score up to Day 169 (Week 24). The mixed model will include treatment arm, 
baseline MRC score and randomization stratification factors: disease diagnosis (DM vs non-DM 
IIM), ILD (absent vs present), Region (Japan vs ROW), time (study days in which MRC is 
measured), time by baseline MRC score and time by treatment interactions as fixed effects and 
subject as a random effect. Adjusted mean, SE, 95% CI for adjusted mean difference between 
treatment arms will be provided.
Nominal p-values will be provided for the secondary efficacy endpoints at Day 169 ie, mean 
change from baseline at Day 169 for each of the secondary endpoints: FI-2, HAQ-DI, MDAAT 
and MRC. The mixed longitudinal model will account for any missing values on any of the 
secondary efficacy endpoints. All construction of CIs for differences in response rates between 
treatment groups will be based on minimum risk weights to account for randomization 
stratification factors, unless otherwise noted. All construction of CIs for response rates within 
treatment group will be based on normal approximation, unless otherwise noted.  
Efficacy assessments collected at week 24 on subjects who discontinue study medication prior to 
week 24 will not be included in the primary analyses of the secondary endpoints, but will be 
included in a sensitivity analysis of the secondary endpoints. The mixed longitudinal model will 
be considered the primary analyses for all the continuous secondary endpoints, specifications of 
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8.4.3
Safety Analyses
For the Week 24 analysis, frequency distribution of all adverse events (AEs) reported during 
Period I of the study will be presented by the 2 treatment arms (abatacept vs. placebo). AEs will 
be summarized from the first dose date in the study up to first dose date in the Open-Label Period 
or last dose date in the Double-Blind Period + 56 days for subjects who prematurely discontinued 
the study during the Double-Blind Period. Summary of AEs of special interest will also be 
provided, details and analyses of the AEs of special interest will be provided in the SAP. Individual 
listings of AEs indicating treatment arms will also be generated. Changes in clinical laboratory test 
results from baseline will be summarized by treatment group. Laboratory marked abnormality 
using pre-defined abnormality criteria will also be descriptively summarized by treatment group. 
In general, there will be no statistical testing of group difference with respect to frequencies of 
AEs or laboratory marked abnormalities, except otherwise specified in the SAP. All safety 
analyses in the Week 24 analysis will be performed using the as-treated analysis population. 
 
 
 
 
 
 
 
 
8.4.6
Outcomes Research Analyses
The changes from baseline in Fatigue (PROMIS) and SF-36 will be summarized by treatment 
group. The treatment differences in adjusted mean changes from baseline for each measure, along 
with the corresponding 95% two-sided CI, will be based on a repeated measure mixed model and 
will be presented at each scheduled study visit at which the PROMIS Fatigue or SF-36 assessment 
was done. The mixed model will include baseline measurement, treatment group, randomization 
stratification factors: diagnosis (DM vs non-DM IIM), ILD (present vs absent), Japan vs ROW, 
time (study days in which variable was measured), time by baseline value of variable and time by 
treatment as fixed effects and subject as a random effect], adjusted mean, SE, 95% CI for adjusted 
mean difference between treatment groups will be provided.
8.4.7
Week 52 Analysis 
The final study (Week 52 analysis) for all study sites will be performed when all subjects have 
completed a total of 52 weeks on treatment in the study (ie. completed the Open-Label Period) 
and/or the follow-up period of the study. The Week 52 analysis will include efficacy and safety 
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analyses. No formal statistical testing will be conducted for any of the efficacy analyses included 
in the final Week 52 analysis, appropriate summary statistics will be provided. Safety summaries 
will include events reported from the start of the Open-Label Period up to 56 days post last dose 
date in the Open-Label Period. Cumulative abatacept safety summaries will also be provided for 
all subjects who received abatacept at any time during the study. The cumulative safety summaries 
will include all AEs reported from the first dose date of abatacept up to 56 days post the last dose 
date of abatacept in the study. 
 
The Week 52 analyses will be based on open-
label treated analysis population except for the cumulative abatacept safety summaries which will 
be based all subjects who received at least one dose of abatacept at any time during the study.
8.4.8
Week 76 Japan Only Analysis
The analysis for the assessment of long-term efficacy and safety for subjects from Japan will be 
performed including data collected up to Week 76.
8.4.9
Long Term Open Label Extension (3 Years)
The analysis will be performed when all subjects have completed a total of 3 years open label 
treatment in the Long Term Open-Label Extension and/or the follow-up period of the study.  The 
analysis will include safety.  No formal statistical testing will be conducted; appropriate summary 
statistics will be provided.  Safety summaries will include events reported from the start of the 
Long Term Open-Label Period up to 56 days post last dose date.
Cumulative abatacept safety summaries will also be provided for all subjects who received 
abatacept at any time during the study.  The cumulative safety summaries will include all AEs 
reported from the first dose of abatacept up to 56 days post the last dose of abatacept in the study.
The analyses will be based on open-label treated analysis population except for the cumulative 
abatacept safety summaries which will be based on all subjects who received at least one dose of 
abatacept at any time during the study.
8.5
Interim Analyses
Not Applicable
9
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local health authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects. If a deviation or change to a protocol is implemented to eliminate an 
immediate hazard(s) prior to obtaining relevant approval/favorable opinion(s), the deviation or 
change will be submitted as soon as possible to:
•
IRB/IEC 
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•
Regulatory Authority(ies), if applicable by local regulations per national requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local health authority, must be sent to BMS. If an 
amendment substantially alters the study design or increases the potential risk to the subject: (1) the 
consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS or designee representatives will review data centrally to identify potential issues to determine 
a schedule of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the source 
documents:
In addition, the study may be evaluated by BMS or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to BMS or designee. 
9.1.2.1
Source Documentation
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (EMRs/EHRs), 
adverse event tracking/reporting, protocol required assessments, and/or drug accountability 
records).
When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original. 
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9.2
Records
9.2.1
Records Retention
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator (or head of the study site in Japan) must contact BMS or designee prior to destroying 
any records associated with the study.
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (e.g., relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (e.g., another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee.
9.2.2
Study Drug Records 
Records for IP (whether supplied by BMS, its vendors, or the site) must substantiate IP integrity 
and traceability from receipt, preparation, administration, and through destruction or return. 
Records must be made available for review at the request of BMS/designee or a Health Authority.
If...
Then...
Supplied by BMS 
(or its vendors):
•
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
•
non-study disposition (e.g., lost, wasted) 
•
amount destroyed at study site, if applicable
•
amount returned to BMS
•
retain samples for bioavailability/bioequivalence, if applicable 
•
dates and initials of person responsible for Investigational Product 
dispensing/accountability, as per the Delegation of Authority Form.
Sourced by site, and 
not supplied by 
BMS or its vendors 
(examples include IP 
sourced from the 
sites stock or 
commercial supply, 
The investigator or designee accepts responsibility for documenting 
traceability and study drug integrity in accordance with requirements 
applicable under law and the SOPs/standards of the sourcing pharmacy. 
These records should include:
•
label identification number or batch number 
•
amount dispensed to and returned by each subject, including unique 
subject identifiers
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If...
Then...
or a specialty 
pharmacy)
•
date and initials of person responsible for Investigational Product 
dispensing/accountability, as per the Delegation of Authority Form.
BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements.
9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
be reported on the electronic SAE form and Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used. Spaces may be left blank 
only in those circumstances permitted by study-specific CRF completion guidelines provided by 
Sponsor of designee. 
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a sub-investigator and who is delegated this task on the 
Delegation of Authority Form. Sub-investigators in Japan may not be delegated the CRF approval 
task. For electronic CRFs, review and approval/signature is completed electronically through the 
BMS electronic data capture tool. The investigator must retain a copy of the CRFs including 
records of the changes and corrections.
Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the BMS electronic data capture tool using the unique user
account provided by Sponsor or designee. User accounts are not to be shared or reassigned to other 
individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report. 
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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 (e.g., among the top quartile of enrollers)
•
Involvement in trial design
•
Regional representation (e.g., among top quartile of enrollers from a specified region or 
country)
•
Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTA) governing [Study site or Investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
BMS or designee at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTA.
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10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
Complete Abstinence is defined as complete avoidance of heterosexual 
intercourse and is an acceptable form of contraception for all study drugs. 
This also means that abstinence is the preferred and usual lifestyle of the 
patient. This does not mean periodic abstinence (e.g., calendar, ovulation, 
symptothermal, profession of abstinence for entry into a clinical trial, 
post-ovulation methods) and withdrawal, which are not acceptable 
methods of contraception. Women must continue to have pregnancy tests. 
Acceptable alternate methods of highly or less effective contraception’s 
must be discussed in the event that the subject chooses to forego complete 
abstinence.
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11
LIST OF ABBREVIATIONS
Term
Definition
ACR
American College of Rheumatology
ACTH
adrenal corticotropic hormone
ADR
adverse drug reaction
AE
adverse event
ALT
alanine aminotransferase (SGPT - serum glutamic pyruvate 
transaminase)
ARDS
acute respiratory distress syndrome
AST
aspartate aminotransferase (SGOT - serum glutamic oxaloacetic 
transaminase)
AZA
Azathioprine
β-HCG
beta-human chorionic gonadotrophin
BA/BE
bioavailability/bioequivalence
BCG
Bacillus Calmette–Guérin
BMS
Bristol-Myers Squibb
BP
blood pressure
BUN
blood urea nitrogen
C
Celsius
CA
Contrast Agent
CAD
Computer assisted diagnosis
CDASI
Cutaneous Dermatomyositis Disease Area and Severity Index
CDC ACIP
Center for Disease Control Advisory Committee on Immunization 
Practices
CFR
Code of Federal Regulations 
CI
confidence interval
cm
Centimeter
COPD
Chronic Obstructive Pulmonary Disease
CPK/CK
creatine phosphokinase
CRF
Case Report Form, paper or electronic
CT
computed tomography
CXR
chest X-ray
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Term
Definition
DAD
diffuse alveolar damage
D/C
Discontinue
DILI
Drug Induced Liver Injury
DLCO
diffuse capacity for carbon monoxide
DM
Dermatomyositis
DMARD
disease-modifying antirheumatic drug
DNA
Deoxyribonucleic Acid
DOI
Definition of Improvement
ECG
Electrocardiogram
ECL
Electrochemiluminescence
eCRF
electronic Case Report Form
EDC
electronic Data Capture
e.g.
exempli gratia (for example)
EIA
Enzyme Immunoassay
EMG
Electromyography
ER
exposure response
EU
European Union
FDA
Food and Drug Administration
FEV1
forced expiratory volume in 1 second
FI-2
Myositis Function Index
FSH
follicle stimulating hormone
FVC
forced vital capacity
g
Gram
GCP
Good Clinical Practice
GGO
Ground Glass Opacities
GGT
gamma-glutamyl transferase
HAQ-DI
Health Assessment Questionnaire-Disability Index
HBcAb
Hepatitis B core antibody
HBsAg
Hepatitis B surface antigen
HcAb
Hepatitis C antibody
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Term
Definition
HCV
Hepatitis C virus
HIPAA
Health Insurance Portability and Accountability Act 
HIV
Human Immunodeficiency Virus
HPV
Human papilloma virus
HRCT
high-resolution computed tomography
HRT
hormone replacement therapy
ICH
International Conference on Harmonization 
i.e.
id est (that is)
IEC
Independent Ethics Committee
IIM
Idiopathic Inflammatory Myopathy; Idiopathic Inflammatory Myositis
ILD
interstitial lung disease 
IMACS
International Myositis Assessment and Clinical Studies group
IMACS DOI
IMACS Definition of Improvement
IMP
investigational medicinal products
IND
Investigational New Drug Exemption
INH
Isoniazid
IRB
Institutional Review Board
ISR/T
investigator sponsored research/trial
ITT
intent-to-treat
IU
International Unit
IV
Intravenous
IVIG
Intravenous Immunoglobulin
IVRS
interactive voice response system
JIA
juvenile idiopathic arthritis
Kg, kg
Kilogram
L
Liter
LDH
lactate dehydrogenase
LT
long term
MDAAT
Myositis Disease Activity Assessment Tool
MDI
Myositis Damage Index
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Term
Definition
mg
Milligram
μg
Microgram
MHC
major histocompatibility complex
min
Minute
mL
Milliliter
mmHg
millimeters of mercury
MMR
Measles, mumps and rubella
MMT
Manual Muscle Test
MOA
Mode of Action
MRC
Myositis response criteria
MRI
magnetic resonance imaging
MSD
meso-scale discovery
MTX
Methotrexate
N
number of subjects or observations
N/A
not applicable
NIMP
non-investigational medicinal products 
NSAID
nonsteroidal anti-inflammatory drug
NSIP
nonspecific interstitial pneumonia
OP
organizing pneumonia
OR
odds ratio
PBMC
Peripheral Blood Mononuclear Cell
PD
Pharmacodynamics
PFT
Pulmonary Function Testing
PGA
Physician Global Assessment of Disease Activity
PK
Pharmacokinetics
PM
Polymyositis
PPD
Purified Protein Derivative
PRO (ePRO)
Patient-Reported Outcomes (electronic Patient-Reported Outcomes)
PROMIS
Patient-Reported Outcomes Measurement Information System 
QLF
quantitative lung fibrosis
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Term
Definition
RA
Rheumatoid Arthritis
RBC
red blood cell
RNA
Ribonucleic Acid
ROW
Rest of World
SAE
serious adverse event
SC
Subcutaneous
SCIG
Subcutaneous immunoglobulin
SD
standard deviation
SGA
Patient (Subject) Global Assessment of Disease Activity
SOC
system organ class
ST
short term
Subj
Subject
TB
Tuberculosis
UIP
usual interstitial pneumonia
ULN
Upper-Limit of Normal
UV
Ultraviolet
VAS
visual analog scale
WBC
white blood cell
Wk, wk
Week
WOCBP
women of childbearing potential
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APPENDIX 1
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
At a minimum, subjects must agree to use one highly effective method of contraception as listed 
below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
Highly effective methods of contraception have a failure rate of < 1% when used consistently and 
correctly. WOCBP and female partners of male subjects, who are WOCBP, are expected to use 
one of the highly effective methods of contraception listed below. Male subjects must inform their 
female partners who are WOCBP of the contraceptive requirements of the protocol and are 
expected to adhere to using contraception with their partner. Contraception methods are as follows:
1. Progestogen only hormonal contraception associated with inhibition of ovulation.
2. Hormonal methods of contraception including oral contraceptive pills containing combined 
estrogen + progesterone, vaginal ring, injectables, implants and intrauterine devices (IUDs) 
such as MirenaÒ
3. Nonhormonal IUDs, such as ParaGardÒ 
4. Bilateral tubal occlusion
5. Vasectomised partner with documented azoospermia 90 days after procedure
•
Vasectomised partner is a highly effective birth control method provided that partner is the 
sole sexual partner of the WOCBP trial participant and that the vasectomised partner has 
received medical assessment of the surgical success.
6. Intrauterine hormone-releasing system (IUS).
7. Complete abstinence
•
Complete abstinence is defined as the complete avoidance of heterosexual intercourse 
(refer to Glossary of Terms)
•
Complete abstinence is an acceptable form of contraception for all study drugs and must 
be used throughout the duration of the study treatment (plus 5 half-lives of the 
investigational drug plus 30 days).
•
It is not necessary to use any other method of contraception when complete abstinence is 
elected.
•
Subjects who choose complete abstinence must continue to have pregnancy tests as 
specified in Section 5.1.
•
Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the subject chooses to forego complete abstinence.
•
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the subject.
Local laws and regulations may require use of alternative and/or additional contraception methods.
UNACCEPTABLE METHODS OF CONTRACEPTION
1. Periodic abstinence (calendar, symptothermal, post-ovulation methods)
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2. Withdrawal (coitus interruptus)
3. Spermicide only
4. Lactation amenorrhea method (LAM)
TREATMENT WITH TERATOGENIC CONCOMITANT MEDICATION
Males and females taking a concomitant teratogenic medication should follow contraception
guidelines and duration described in the label for the concomitant medication in addition to those
required for abatacept.
 
 
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APPENDIX 2
LABORATORY GUIDELINES: PATIENT STUDIES (REVISED 
AUGUST 13, 1999) 
Laboratory test results, which meet these criteria, and the Investigator feels is clinically relevant 
should be described on the Adverse Event Form. Those which are judged to be SERIOUS events 
require the completion of a Serious Adverse Event Form (see Sections 6.1.1 and 6.3).
[NOTE:  LLN = lower limit of normal; ULN = upper limit of normal.]
albumin - < 0.9 x LLN or if pretreatment value is < LLN, < 0.75 x pretreatment
alkaline phosphatase - > 2 x ULN; or if pretreatment >ULN, 3 x pretreatment value
basophils (%) - > 3% if 0-1% pretreatment, > 3 x pretreatment value if pretreatment > 1%
bilirubin
a.
direct - > 1.5 x ULN, or if pretreatment above ULN, > 2 x pretreatment
b.
total - > 2 x upper limit of normal, or if pretreatment above ULN, > 4 x pretreatment 
value
blasts - > 0
blood urea nitrogen (BUN) - > 2 x pretreatment
calcium - < 0.8 x LLN or > 1.2 x ULN; < 0.75 x pretreatment if pretreatment below LLN, or >
1.25 x pretreatment if pretreatment above ULN; > ULN if < LLN pretreatment, or < LLN if > ULN 
pretreatment
chloride - < 0.9 x LLN or > 1.1 x ULN; or < 0.9 x pretreatment if pretreatment below LLN, or >
1.1 x pretreatment if pretreatment above ULN; > ULN if < LLN pretreatment, or < LLN if > ULN 
pretreatment
creatinine - > 1.5 x pretreatment value
eosinophils (%) - > 3 x pretreatment and > 8% if pretreatment normal; if pretreatment > ULN, >
3 x pretreatment
erythrocytes - < 0.75 x pretreatment value
glucose - < 0.8 x LLN or > 1.5 x ULN; if pretreatment < LLN then < 0.8 x pretreatment; if 
pretreatment > ULN then > 2 x pretreatment; < LLN if > ULN pretreatment, or > ULN if < LLN 
pretreatment
hematocrit - < 0.75 x pretreatment
hemoglobin - > 3 g/dL decrease from pretreatment value
lactic dehydrogenase (LDH) - > 1.5 x ULN; if pretreatment value is above ULN, > 3 x 
pretreatment value
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leukocyte (WBC) count - < 0.75 x LLN or > 1.25 x ULN; < 0.8 x pretreatment if pretreatment <
LLN or > 1.2 x pretreatment if pretreatment > ULN; > ULN if pretreatment < LLN or < LLN if >
ULN pretreatment
lymphocytes (%) - < 0.5 x LLN or > 2.0 x ULN, or
< 0.5 x pretreatment if below LLN 
pretreatment; > 2.0 x pretreatment if above ULN pretreatment.  > ULN if < LLN pretreatment, or 
< LLN if > ULN pretreatment
monocytes (%) - > 2 x ULN; > 2 x pretreatment if pretreatment above ULN
neutrophil count (neutrophils+bands) - < 0.67 x pretreatment if pretreatment < 1000/mm3; 
otherwise, < 1000/mm3.
phosphate - < 0.75 x LLN or > 1.25 x ULN; < 0.67 x pretreatment value if below LLN 
pretreatment, or > 1.33 x pretreatment if above ULN pretreatment; > ULN if < LLN pretreatment, 
or < LLN if > ULN pretreatment
platelet count - < 0.67 x LLN or > 1.5 x ULN; if below normal pretreatment, < 0.5 x pretreatment 
value and < 100,000/mm3
potassium - < 0.9 x LLN or > 1.1 x ULN; < 0.9 x pretreatment if pretreatment below LLN, or >
1.1 x pretreatment if pretreatment above ULN; > ULN if < LLN pretreatment, or < LLN if > ULN 
pretreatment
protein, total - < 0.9 x LLN or > 1.1 x ULN; <0.9 x pretreatment if below LLN pretreatment, or 
> 1.1 x ULN if above ULN pretreatment; > ULN if < LLN pretreatment, or < LLN if > ULN 
pretreatment
SGOT and SGPT (ASAT and ALAT) - > 3 x upper limit of normal; if pretreatment above ULN, 
> 4 x pretreatment value
sodium - < 0.95 x LLN or > 1.05 x ULN; < 0.95 x pretreatment if below LLN pretreatment, > 1.05
x pretreatment if above ULN pretreatment; > ULN if < LLN pretreatment, or < LLN if > ULN 
pretreatment
uric acid - > 1.5 x ULN; if pretreatment above ULN, > 2 x pretreatment value
urinalysis
a) urinary protein - > 1 gram/24 hours and 2 x pretreatment value
b) urinary RBC - > 5/HPF or, > 4 x pretreatment if pretreatment value 5/HPF
c) urinary WBC - > 5/HPF or, > 4x pretreatment if 5/HPF pretreatment
d) creatinine clearance (glomerular filtration rate) - < 0.67 x pretreatment value
e) urine dipstick measurements:  Protein, blood, sugar, and acetone- 2+, or if 1+
pretreatment, 2 x pretreatment. Do not evaluate protein if quantitative protein 
determination done
stool hemoccult - positive if negative pretreatment
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Summary of Key Changes of Revised Protocol 03
Section Number & Title
Description of Change
2.1 Good Clinical Practice 
(3rd paragraph)
Incorporated 
•
‘If required as per local regulation, 
serious breaches will be reported by 
Sponsor or designee to applicable 
authorities’
•
‘(occurring in any country)’ 
•
and ‘of 1 or more subjects’.
2.2 Institutional Review 
Board/Independent Ethics 
Committee
Removed ‘BMS’ notation and added 
‘Sponsor’ & ‘designee’.
3.1.2 Double-Blind Period 
(Day 1 - Week 24)
Additional text:’ Rescue therapy will be
available for subjects who meet the 
disease worsening criteria during the 
double-blind period as defined in Section 
3.1.4.’
&
Subjects who discontinue treatment with 
study medication during the Double-blind 
Period will complete the Early 
Termination visit (which is the same visit 
as Day 169 visit) (See Table 5.1-2). These 
subjects must also return on the 
previously scheduled Double-blind Period 
Day 169 to complete the Post-Study Drug 
Efficacy Visit (see Table 5.1-4). The 
purpose of this visit is to assess all aspects 
of disease activity to ascertain the impact 
of study participation for regulatory 
review. Subjects must also complete 2 
follow-up visits (Day 85 and 169) during 
the 24 week post-treatment follow-up 
period, to perform safety and laboratory 
assessments (See Table 5.1-5 Post-
Treatment Follow-Up Period). This 
Period begins on the day of the Early 
Termination visit and applies only to 
subjects who do not start commercial 
abatacept therapy.’
3.1.3 Open-Label Period 
(Week 24 - Week 52)
Supplementary text ‘Use of immune 
globulin (intravenous [IVIG] or 
subcutaneous [SCIG] is permitted during 
this period.’
&
‘Subjects who discontinue treatment with 
abatacept during the Open-Label Period 
will complete the Early Termination visit 
for the OL (See Table 5.1-3 day 365 is 
also the OL ET) and 2 follow-up visits 
during the 24 week post-treatment follow-
up period, to perform safety and 
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Summary of Key Changes of Revised Protocol 03
Section Number & Title
Description of Change
laboratory assessments. (See Table 5.1-5). 
If the subject receives treatment with an 
alternate source of abatacept (Post-Study 
Drug Program [PSDP] or Commercial), 
completing this post-treatment follow-up 
period is not required.
Treatment with other biologic therapy is 
not recommended for at least 70 days (∼5 
half-lives of abatacept follow-up period.’
3.1.4 Rescue Therapy
Removed the following text ‘The choice 
of rescue therapy is at the discretion of the 
investigator; however, rescue treatment 
may not be abatacept or a prohibited 
medication (See Section 3.4.2.1).’ 
&
Later in the segment, added ‘The use of 
rescue therapy is at the discretion of the 
investigator; however, rescue treatment 
may not be abatacept or a prohibited 
medication (See Section 3.4.2.1). 
Allowable medication are restricted to 
allowable concomitant medication 
(Section 3.4.1.1 Standard Treatment). 
Rescue therapy includes increases in dose 
of current therapy, addition of therapy and 
change in therapy, all with some 
restrictions such that allowable rescue 
therapy meets the criteria for allowable 
standard treatment. The following 
changes are allowable as rescue therapy:’ 
and sections (1), (2) & (3).
3.1.5 Post-Treatment Follow-
Up Period
Removed sections:
•
Double-Blind Period (Day 1 to Wk 
24)
•
Open-Label Period (Wk 24 to Wk 
52)
•
Study Completion (After Wk 52).
3.2 Post Study Access to 
Therapy
Amended title to ‘3.2 Post Study Access 
to Study Drug’, and included ‘with study 
drug, ie abatacept’. 
3.3.4 Screening for 
Malignancy
Added the text ‘It is recommended that 
all’ & ‘at the discretion of the 
investigator’, at several points.
&
Last paragraph, removed ‘require 
approval by’ and added ‘may be discussed 
with’.
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Summary of Key Changes of Revised Protocol 03
Section Number & Title
Description of Change
3.4.1.1 Standard Treatment
Added the text ‘Use of immune globulin
(intravenous [IVIG] or subcutaneous 
[SCIG] is permitted during this period. 
Addition of any other prohibited 
medication (Section 3.4.2.1; except 
IVIG3.4.2.1) is not permitted’ to the last 
paragraph.
3.4.1.3 Immunosuppressant 
medications
Provided substantial text revision to 
clarify what immunosuppressants are 
permitted
3.4.2.1 Prohibited Medications
Added text ‘All prohibited medication 
must have been discontinued at least 4 
weeks prior to randomization with the 
exception of immune globulin, rituximab 
and d-penicillamine which have longer 
exclusion periods (see 3.3.2). Prohibited 
medication in this contest refers to 
immunomodulatory medications for the 
treatment of IIM which are not included 
as immunosuppressant medications 
(Section 3.4.1.3). The following list 
includes examples of specific prohibited 
medications.’
Also added/removed several therapies.
3.4.2.2 Restricted Medications
Developed second bullet-point.
3.5 Discontinuation of 
Subjects following any 
Treatment with Study Drug
Second paragraph: Provided substantial 
text revision to clarify the requirements 
for subjects that discontinue
Table 4-1: Study Drugs for 
IM101611
Added ‘Open Label’.
Table 5.1-2 Study Evaluations 
- Double-Blind Period 
(IM101611)
Added Wk 8 assessments for MMT-8 & 
MDAAT
Table 5.1-5
Revised Schedule/T&E ‘Title’.
5.4.1.2 Assessments 
Performed by Medical Staff: 
Myositis Response Criteria 
Added a ‘continuous total improvement 
score’ range ‘0-100’.
Table 5.5.1-1 Sampling 
Schedule
Amended Study Days to reflect ’85 Days 
& 169 Days after Last Dose
6.1.1 Serious Adverse Event 
Collection and Reporting
Text revised to clarify the reporting of 
SAEs and Pregnancies immediately. 
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SAP_005.pdf: 
Official Title of Study: 
A PHASE 3, RANDOMIZED, DOUBLE-BLIND CLINICAL TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF 
ABATACEPT SC WITH STANDARD TREATMENT COMPARED TO STANDARD TREATMENT ALONE IN 
IMPROVING DISEASE ACTIVITY IN ADULTS WITH ACTIVE IDIOPATHIC INFLAMMATORY MYOPATHY (IIM) 
PROTOCOL(S) IM101-611 
 
NCT Number: NCT02971683  
Document Date (Date in which document was last revised): December 15, 2020 


STATISTICAL ANALYSIS PLAN
FOR CLINICAL STUDY REPORT
A PHASE 3, RANDOMIZED, DOUBLE-BLIND CLINICAL TRIAL TO EVALUATE THE 
EFFICACY AND SAFETY OF ABATACEPT SC WITH STANDARD TREATMENT 
COMPARED TO STANDARD TREATMENT ALONE IN IMPROVING DISEASE 
ACTIVITY IN ADULTS WITH ACTIVE IDIOPATHIC INFLAMMATORY MYOPATHY 
(IIM)
PROTOCOL(S) IM101-611
VERSION # 1.0
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Statistical Analysis Plan
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abatacept
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APPENDIX 1
RELEVANT PROTOCOL DEVIATIONS.............................................52
APPENDIX 2
MYOSITIS RESPONSE CRITERIA......................................................54
APPENDIX 3
ANALYSIS PLAN FOR OPEN-LABEL, OPEN-LABEL
EXTENSION AND LONG-TERM EXTENSION PERIODS 
ANALYSIS............................................................................................56
11
STATISTICAL ANALYSES..................................................................................57
11.1
General Methods ....................................................................................................57
11.3
Study Conduct........................................................................................................58
11.4
Study Population ....................................................................................................58
11.4.1
Subject Disposition.................................................................................................58
11.4.2
Demography and Baseline Characteristics .............................................................58
11.4.3
Medical History and Prior Medication ...................................................................58
11.5
Extent of Exposure .................................................................................................59
11.5.1
Study Therapy.........................................................................................................59
11.5.1.1
Open-Label Period Exposure..................................................................................59
11.5.1.2
Open-Label Extension Period Exposure..................................................................59
11.5.1.3
Long-Term Extension Period Exposure...................................................................60
11.5.1.4
Cumulative Abatacept Exposure .............................................................................60
11.5.2
Discontinuation of Study Therapy...........................................................................60
11.5.3
Treatment Compliance............................................................................................61
11.6
Efficacy..................................................................................................................61
11.6.1
Other Efficacy Analyses..........................................................................................61
11.6.2
Additional Efficacy and Outcome Research Analyses..............................................62
11.7
Safety.....................................................................................................................64
11.8
Other Analyses .......................................................................................................66
LIST OF TABLES
Table 2.4-1:
Protocol Amendments ............................................................................10
Table 5-1:
Estimates of Power for Various Assumed Rates of IMACS DOI at 
Week 24 Assuming Total sample Size of 150 .........................................15
Table 7.1-1:
Planned Efficacy Analyses .....................................................................19
Table 7.5.6-1:
Subgroups of Interest for the Primary Efficacy Assessment of 
IMACS DOI...........................................................................................37
Table 7.6.3-1:
Definitions of Analyte Cut Points ...........................................................41
Table 8.5-1:
Day Ranges for Efficacy or Laboratory Assessments During the 
Double-Blind Period...............................................................................49
Table 8.5-2:
Day Ranges for ANA Assessments at Every Scheduled Visit 
During the Double-Blind Period .............................................................50
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Table 8.5-3:
Day Ranges for Immunogenicity Assessment at Every Scheduled 
Visit During the Double-Blind Period.....................................................50
Table 10-2:
Myositis Response Criteria.....................................................................54
Table 11.2-1:
Secondary Analyses................................................................................57
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1
BACKGROUND 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IIM who had persisting signs of active disease after treatment with glucocorticoids and one 
 
 
 
 
Research Hypothesis:
Subcutaneous abatacept (125mg weekly) in combination with standard treatment will achieve a 
higher rate of responders, defined as the percentage of subjects who achieve the IMACS DOI 
(International Myositis Assessment and Clinical Studies - definition of improvement), after 24 
weeks of treatment versus standard treatment alone in adult subjects with active IIM.
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Statistical Analysis Plan
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abatacept
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Schedule of Analyses:
The analyses for this study is scheduled to be performed at 4 separate time points:
1) End of Double-Blind period (Week 24) for all subjects.
2) End of Open-Label period (Week 52) for all subjects.
3) End of Open-Label Extension period (Week 76) for sites in Japan. The purpose is to obtain
52 week abatacept efficacy data on all Japanese subjects for submission, specifically here the
Japanese subjects originally randomized to placebo.
4) End of the study (completion of Long-Term Extension period and Follow-up period).
The Double-Blind period (Week 24) analysis will be performed once all subjects complete their 
Week 24 visit assessment or discontinue prematurely prior to Week 24. The Week 24 analysis will 
include the analyses of the primary efficacy endpoint, secondary and exploratory efficacy 
endpoints up to Week 24 and safety analyses. A subgroup analysis (selected outputs identified in 
DPP) on Japan subjects alone will be conducted for Japanese submission purposes. Actigraphy 
data and data from the Muscle Biopsy sub-study will be not be part of the initial Double-Blind 
period (Week 24) database lock and will be reported separately.
The Open-Label period (Week 52) analysis will be performed once all subjects complete 52 weeks 
of treatment in the study. A subgroup analysis (selected outputs identified in DPP) on Japan 
subjects alone will be conducted for Japanese submission purposes.
The Open-Label Extension period (Week 76) analysis will be performed, using only Japanese sites, 
once all Japanese subjects complete their Week 76 visit assessment. Selected outputs only 
identified in DPP.
The final analysis will be performed when all subjects have completed the 3 year long-term 
extension, (3.5 years for Japan subjects by including OLE data) and/or follow-up visits whichever 
is later.
This Statistical Analysis Plan provides details of the Week 24 analysis; details of the 3 other 
analyses are provided in APPENDIX 3.
In addition to these analyses, interim analyses are performed for the external, independent Data 
Monitoring Committee (DMC). The DMC was formed and charged with assessing the safety of 
Abatacept on a regular basis. The contents and methods of reports to the DMC are outlined in the 
DMC Charter6.
2
STUDY DESCRIPTION
2.1
Study Design
This is a 24-week, Phase 3, randomized, double-blind, placebo-controlled, multicenter, study in 
subjects with active Idiopathic Inflammatory Myopathy (IIM; e.g., DM, PM, autoimmune 
necrotizing myopathy) on standard background treatment. 
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In addition to the 24-week double-blind period, the study includes:
•
A 28-week open-label (OL) treatment period during which all subjects will receive SC 
abatacept with background treatment.
•
An additional 24-week open-label of SC abatacept with continued therapy from the original 
OL period for subjects in Japan.
•
A 3-year long-term extension of SC abatacept (156 weeks) with background treatment for all 
subjects except subjects in the U.S. and the Czech Republic.
The primary objective for this study is to compare the clinical efficacy of weekly abatacept in 
combination with standard treatment to standard treatment alone by assessing the percentage of 
subjects who achieve the IMACS DOI after 24 weeks of treatment versus standard treatment alone 
in adult subjects with active IIM.
Written informed consent must be provided by the subjects prior to undergoing any procedures 
during the screening phase.
Subjects who meet the study inclusion criteria enter into the 24-week Double-Blind (DB) period. 
During the DB period, approximately 150 subjects will be randomized in a 1:1 ratio to one of two 
treatment groups in a double-blinded manner as follows:
•
Group A: Active Abatacept SC (125mg) weekly + standard treatment.
•
Group B: Placebo Abatacept SC weekly + standard treatment.
At the time of randomization, subjects must be on a stable background treatment for IIM (“standard 
treatment” as defined in Section 3.4.1.1 of the protocol). No adjustment in background treatment 
will be allowed during the DB period.
During the 24-week DB period, subjects in either treatment group who meet the criteria for 
worsening (as defined in protocol Section 3.1.4) at any visit between Weeks 12 and 24 are 
permitted to use rescue therapy. The choice of rescue therapy is at the discretion of the investigator; 
however, rescue treatment may not be abatacept or a prohibited medication. Rescued subjects will 
remain blinded to study medication through Week 24 and will begin Open-Label (OL) abatacept
treatment period after Week 24, however they will be considered not to have achieved the IMACS 
DOI for the purpose of the primary efficacy analysis.
The 24-week DB period is followed by a 28-week OL abatacept treatment period (OL period). 
During this period, subjects initially randomized to receive the combination of abatacept and 
standard treatment will continue this regimen. Subjects who are initially assigned to receive 
standard treatment alone will be switched to standard treatment plus abatacept. For the purposes 
of obtaining 1 year efficacy data in all Japan subjects (specifically for placebo randomized
subjects) there will also be a 24-week open-label extension for subjects randomized in Japan.
Background treatment may be adjusted (including the dose
of corticosteroids and 
immunosuppressant’s) at any time during the OL period. Use of immune globulin (intravenous 
[IVIG] or subcutaneous [SCIG]) is permitted during this period. Addition of any other prohibited 
medication is not permitted.
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There will be a 3 year long-term extension period for subjects randomized in countries other than 
the U.S. and the Czech Republic. All subjects will receive standard treatment plus abatacept.
At the conclusion of the study, subjects who continue to demonstrate clinical benefit with study 
drug, i.e. abatacept, will be eligible to receive BMS supplied study drug based on local regulations.
In addition, subjects who discontinue treatment with study medication during the double-blind 
period will complete the Early Termination visit (which is the same visit as Day 169 visit). These 
subjects must also return for the double-blind period Day 169 post-randomization to complete the 
post-study drug efficacy visit. Subjects must also complete 2 follow-up visits (85 and 169 days 
after the last dose) during the 24-week post-treatment follow-up period, to perform safety and 
laboratory assessments. This period begins on the day of the Early Termination visit and applies 
only to subjects who do not start commercial abatacept therapy.
Subjects who discontinue treatment with abatacept during the open-label period or open-label 
extension for Japan will complete the Early Termination visit for the OL and 2 follow-up visits 
during the 24 week post-treatment follow-up period, to perform safety and laboratory assessments.
If the subject receives treatment with an alternative source of abatacept, completing this post-
treatment follow-up period is not required.
Subjects who discontinue treatment with abatacept during the long-term extension period will 
complete the Early Termination visit for the OL and two follow-up visits to perform safety and 
laboratory assessments. If the subject receives treatment with an alternative source of abatacept, 
completing this post-treatment follow-up period is not required.
2.2
Treatment Assignment
At the time of enrollment, immediately after written informed consent is obtained and before 
performing any study-related procedures, each subject will be assigned a unique sequential subject 
number beginning with 001, 002, 003, etc. for identification throughout the study by Interactive 
Recognition System (IxRS). This subject number must not be reused for any other participant in 
the study. The physician/coordinator must contact the Central Randomization System to enroll 
each subject into a centralized database at the beginning of the study (Screening Visit).
Randomization schedules were generated and kept by the Randomization Group within Drug 
Supply Management of Bristol-Myers Squibb. Each subject who is qualified for treatment is 
assigned a unique randomization number by IxRS. A randomization number will be assigned in 
the order in which subjects qualify for treatment, not in the order of study enrollment (screening 
visit).
Randomization will be stratified globally by 3 stratification variables: (1) Dermatomyositis (DM) 
vs. non-DM IIM, and (2) presence or absence of interstitial lung disease (ILD), (3) Japan vs. Rest 
of World (ROW).
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group was based on reported rates of IMACS DOI in studies of patients with Myositis on 
combination therapy with another biologic agent. It is expected that the rate of IMACS DOI on 
abatacept in combination with standard treatment should be similar to that observed with the use 
of another biologic agent in combination with standard treatment. Table 5-1 below presents the 
power estimates for other considerations of proportion of subjects in IMAC DOI in the abatacept 
group assuming the total sample size of 150 subjects. Randomization will be stratified globally by 
3 stratification variables: (1) disease diagnosis (Dermatomyositis [DM] vs. non-DM IIM), 
(2) Interstitial Lung Disease (ILD) (present vs. absent), (3) Japan vs. ROW.
Table 5-1:
Estimates of Power for Various Assumed Rates of IMACS DOI at 
Week 24 Assuming Total sample Size of 150
Abatacept Rate
Placebo Rate
Delta
Power (%)
50%
20%
30%
96
25%
25%
85
55%
25%
30%
95
30%
25%
84
60%
25%
35%
~ 99
30%
30%
95
35%
25%
83
6
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS FOR 
ANALYSES
6.1
Study Periods
There are 6 analysis periods defined for the study: the 5 study periods ((i) pre-treatment period;
(ii) 24-week DB period; (iii) the OL period; (iv) the OLE period for Japan; (v) the LTE period, 
incorporating the OLE period for Japan) and (vi) the cumulative abatacept period. These periods 
will be used in the safety summaries.
The pre-treatment period: covers the time period prior to the first dose date/time of study 
medication.
The 24-week Double-Blind period: starts at the first dose date/time of double-blind study 
medication and lasts until the last dose date of the double-blind period + 56 days if subjects 
discontinue the study during double-blind period, or until the first dose in the open-label period.
Since the dosing information for the Open-Label period, the Open-Label Extension period and the 
Long-Term Extension period is recorded on the same CRF page, it is not possible to derive the 
first/last dose for the different periods based on that CRF page. This is why start and end visit dates
from other CRF pages will be used to distinguish between these 3 periods. Start and end visit dates
are recorded for most periods, except the start of the OLE period for Japan subjects, this will be 
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assumed to be the end of the OL period. These dates will be used for deciding which dose belongs 
to which period.
The Open-Label period: starts at the first dose of the open-label period and lasts until the last 
dose date of open-label period + 56 if subjects discontinue the study during open-label period (or 
if subjects are from U.S. and Czech Republic sites), or until the first dose in the open-label 
extension period for subjects from Japanese sites, or the first dose in the long-term extension period 
for subjects from other sites.
The Open-Label Extension period (Japan subjects only): starts at the first dose of the open-
label extension period (determined as the open-label period end visit date from the CRF) and lasts
until the last dose date of open-label extension period + 56 if subjects discontinue the study during 
open-label extension period, or until the first dose in the long-term extension period.
The Long-Term Extension period (all subjects except for U.S. or Czech subjects): starts at the 
first dose of the long-term extension period and last until the last dose date of long-term extension 
period + 56.
The cumulative abatacept period: starts at the first dose date/time of abatacept and lasts until 
the last dose date of abatacept in the study + 56 days. For subjects randomized to placebo in the 
double-blind period the first dose date of abatacept will be the first dose date in the open-label 
period.
6.2
Treatment Regimens
There are 2 treatment groups in this study. Subjects will be randomized to either SC placebo or SC 
Abatacept (as randomized group) at the beginning of the study and each subject is expected to 
receive their randomized treatment (SC placebo or SC abatacept) throughout the double-blind 
period.
During the open-label period and beyond until study completion as per protocol/withdrawal all 
subjects will receive weekly SC abatacept injections.
6.3
Populations for Analyses
Efficacy endpoints will be summarized according to the Intent-to-Treat (ITT) population and 
safety endpoints will be summarized according to the as-treated analysis population. These 
populations are described briefly below along with other populations.
•
Intent-to-Treat Analysis Population:
The Intent-to-Treat (ITT) analysis Population is defined to include all subjects randomized into 
the study for whom Case Report Form (CRF) data indicate that at least one dose of study 
medication (abatacept or placebo) is administered during the double-blind period.
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All subjects who are randomized but never received study medication are to be excluded. Given 
the blinded nature of this study, it is reasonable to assume that subjects who discontinue prior to 
the receipt of study medication do so for reasons unrelated to study medication. Subjects are 
grouped according to the treatments to which they are randomized by IXRS.
ITT analysis population is also referred to as “All Randomized and Treated Subjects”.
•
As-Treated Analysis Population:
The As-Treated analysis population contains all subjects for whom CRF data indicate that at least 
one dose of study medication was administered during double-blind period.
Subjects are grouped according to the treatments to which they are randomized, except in cases 
where information is available, which indicates that a subject receives a different treatment for the 
entire course of double-blind period. In this case, the subject will be presented by the treatment 
they actually received.
The As-Treated analysis population will also be referred as “All Treated Subjects”.
•
Per-Protocol Analysis Population:
The Per-Protocol analysis population is defined as a subset of the ITT analysis population which 
excludes subjects who have relevant protocol deviations during the double-blind study period. 
Relevant protocol deviations are those protocol deviations that might affect the primary efficacy 
endpoint of the study. A programmable list of relevant protocol deviation criteria is included in 
APPENDIX 1.
The analysis of the primary efficacy endpoint will be repeated in the Per-Protocol analysis
population. The Per-Protocol analysis population will exclude subjects with at least 1 relevant 
protocol deviation.
•
Open-Label Treated Analysis Population:
The Open-Label treated analysis population will contain all subjects for whom CRF data indicate 
that at least one dose of study medication was administered during the open-label period. All 
Week 52 analyses will be performed using this population except otherwise specified.
•
Japan Open-Label Extension Treated Analysis Population:
The Japan Open-Label Extension treated analysis population will contain all subjects from Japan 
for whom CRF data indicate that at least one dose of study medication was administered during 
the open-label extension period. All Week 76 analyses will be performed using this population 
except otherwise specified.
•
Long-Term Extension Treated Analysis Population:
The Long-Term Extension treated analysis population will contain all subjects (except for U.S. or 
Czech subjects) for whom CRF data indicate that at least one dose of study medication was 
administered during the long-term extension period. All Year 3 (3.5 year in Japan subjects)
analyses will be performed using this population except otherwise specified.
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7
STATISTICAL ANALYSES
The analyses for this study is scheduled to be performed at 4 separate time points:
17) End of Double-Blind period (Week 24) for all subjects.
18) End of Open-Label period (Week 52) for all subjects.
19) End of Open-Label Extension period (Week 76) for sites in Japan.
20) And end of the study (completion of Long-Term Extension period and Follow-up period).
The double-blind period (Week 24) analysis will be performed once all subjects complete their 
Week 24 visit assessment or discontinue prematurely prior to Week 24. This analysis will include 
the analyses of the primary efficacy endpoint, secondary and exploratory efficacy endpoints up to 
Week 24 and safety analyses for the 24-week double-blind period. Safety analyses will include all 
the adverse events (AEs) reported in the study up to first dose date in the open-label period, or 56 
days after the last dose date in the double-blind period whichever is earlier. Nominal p-values will 
be provided for the secondary endpoint measures at Day 169 (Week 24), no formal statistical 
testing will be conducted for any of the efficacy analyses related to the secondary endpoints at 
other time points and on any of exploratory endpoints. Appropriate summary statistics will be 
provided for the analysis of each endpoint.
The open-label period (Week 52) analysis will be performed once all subjects complete 52 weeks 
of treatment in the study. This analysis will include summaries of AEs reported during the open-
label period. Efficacy endpoints will be summarized over time during the open-label period. No 
formal statistical testing will be conducted for any of the efficacy analyses. Appropriate summary 
statistics will be provided for the analysis of each endpoint. The 52-week analysis will be 
performed using the open-label treated analysis population. Selected outputs for the OL period 
will be detailed in the DPP.
The open-label extension period (Week 76) analysis will be performed, using only Japanese sites, 
once all subjects at Japanese sites complete 76 weeks of treatment in the study. This analysis will 
include summaries of AEs reported during the open-label extension period. Efficacy endpoints 
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Table 7.1-1:
Planned Efficacy Analyses
Measure of Interest
Analysis Method
points. In addition, nominal p-values will be provided for the secondary 
endpoints of change from baseline at Day 169 (week 24) analysis.
Differences in proportions (i.e., 
proportion of subjects achieving 
IMACS DOI at Day 169 (Week 
24), etc.) 
Point estimate of response rate, 95% CI, point estimates and 95% CI of 
treatment difference adjusted for randomization stratification factors: 
disease diagnosis (DM vs. Non-DM), ILD (absent vs. present), Region 
(Japan vs. ROW) (based on minimum risk weights).
Differences in proportions (i.e., 
proportion of subjects achieving 
IMACS DOI in myositis Ab 
negative or positive subjects, etc.)
Point estimate of response rate, 95% CI, point estimates and 95% CI of 
treatment difference adjusted for randomization stratification factors: 
disease diagnosis (DM vs. Non-DM), ILD (absent vs. present), Region 
(Japan vs. ROW) (based on minimum risk weights).
All construction of CIs for differences in response rates between treatment groups will be based 
on minimum risk weights7 to account for randomization stratification factors, unless otherwise 
noted. All construction of CIs for response rates within treatment group will be based on normal 
approximation methods, unless otherwise noted.
All construction of CIs for continuous measures will be based on a longitudinal repeated mixed 
effects model which includes treatment group, baseline value of variable, randomization 
stratification factors (diagnosis [DM vs. Non-DM], ILD [absent vs. present], Region [Japan vs.
ROW]), time (as categorical variable), and time by treatment interaction as fixed effects and 
subject as a random effect. An unstructured covariance matrix will be used to model the correlation 
of the repeated measures within each subject. The SAS procedure PROC MIXED will be used 
with the restricted maximum likelihood (REML) method for estimation and the denominator 
degrees of freedom calculated according to the Kenward Roger method. The parameter estimations 
will be based on assumption of data being missing at random (MAR) using the method of 
restrictive maximum likelihood (REML). MAR means that given the observed data (e.g. for 
patients who discontinue up to the day they discontinue), the missingness mechanism does not 
depend on the unobserved data. In other words, this analysis assumes that a patient who drops out 
has the same conditional distribution (of the unobserved data after dropout given the observed 
data) as patients who share the same observed data and do not drop out. In case of non-convergence 
of the preferred longitudinal model or memory space issues the following back-up model will be 
used: a compound symmetry (CS) covariance matrix will be used to model the correlation of the 
repeated measures with each subject.
Unless otherwise specified, summary statistics will include the following:
•
Summary statistics for continuous variables will include means, standard deviations, minima 
and maxima.
Summary statistics for qualitative or discrete variables will include the count and percentage.
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7.2
Study Conduct
Relevant protocol deviations, which could have a major impact on the interpretation of the study 
results, will be identified prior to the unblinding of the database for all subjects who are 
randomized and receive double-blind medication. 
Relevant protocol deviation criteria, including an assessment of the impact of any Covid-19 related 
deviations observed are listed in APPENDIX 1.
All subjects with relevant protocol deviations will be identified prior to the final database lock and 
unblinding of treatment assignment. All relevant protocol deviations will be listed and summarized 
by treatment group.
Following a case by case review of all incidences of Covid-19 related events (scheduling of visits, 
accurate receipt of medication) the impact of Covid-19 on the primary endpoint is considered 
minimal. The Per-Protocol analysis will exclude subjects with Covid-19 related deviations that 
could potentially impact the primary endpoint.
7.3
Study Population
Summary statistics of data pertaining to subject disposition, demographics, baseline 
characteristics, and medical history, including form of IIM, will be tabulated and displayed by 
randomized treatment group. No statistical test will be carried out for comparison of any baseline 
measurement between treatment groups.
These presentations will use the ITT analysis population and will be for “as-randomized” treatment 
regimen.
7.3.1
Subject Disposition
The disposition of subjects in the double-blind period will be presented as follows:
•
Number of subjects enrolled at screening.
•
Number of subjects randomized.
•
Number of subjects treated in the double-blind period (i.e. who received at least 1 dose of study 
drug (abatacept or placebo).
•
Number of subjects who discontinued during the double-blind period, together with reasons 
for discontinuation (taken from the eCRF status page).
•
Number of subjects who completed the double-blind period, but who did not enter the open-
label period and reason for not entering the open-label period (taken from the eCRF status 
page).
7.3.2
Demography and Baseline Disease Characteristics
Demographic and baseline disease characteristics will be summarized using the ITT analysis 
population. The summaries will be presented by as randomized treatment group and overall. 
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Continuous variables will be summarized using means and standard deviations, and categorical 
variables will be summarized using frequency distributions. The characteristics will be 
summarized based on the data captured on the CRF page, except for the randomization 
stratification which will be based on the IXRS data.
The following demographic and baseline characteristics will be summarized:
•
Age.
•
Age group (16-29, 30-39, 40-49, 50-59, ≥60 years).
•
Gender.
•
Race.
•
Ethnicity.
•
Geographic region:
−
North America: Canada and United States
−
South America: Argentina, Brazil, Chile, Columbia and Peru.
−
Europe: Italy, Romania, Russia, Spain and Turkey.
−
Asia: China, Hong Kong, Japan, Korea, and Taiwan.
−
Rest of World (ROW): Australia, Israel.
•
Weight.
•
Weight group (< 60, 60-100, > 100kg).
•
Stratification factor Region (Japan vs. ROW).
•
Stratification factor Disease diagnosis (DM vs. Non-DM).
•
Stratification factor ILD (absent vs. present).
•
Disease diagnosis: IIM type (DM, PM, autoimmune necrotizing myopathy).
•
Randomization strata, Japan/Other, Disease Diagnosis; ILD:
−
Japan/Non-DM with ILD present.
−
Japan/Non-DM with ILD absent.
−
Japan/DM with ILD present.
−
Japan/ DM with ILD absent.
−
Non-Japan/Non-DM with ILD present.
−
Non-Japan/Non-DM with ILD absent.
−
Non-Japan/DM with ILD present.
−
Non-Japan/DM with ILD absent.
•
Duration of disease in months.
•
Duration of disease by disease diagnosis (DM vs. Non-DM).
•
Medication History:
−
Number of prior medications used to treat Myositis: corticosteroids, immunosuppressant’s, 
or biologics (1, 2, 3, > 3).
−
Number of prior DMARDS.
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−
Number 
of 
current 
background 
Myositis 
medications: 
corticosteroids, 
immunosuppressant’s (1, 2, 3, > 3).
•
CK level at screening (continuous variable): number of subjects with elevated CK > 5 times 
the upper limit of normal at screening.
•
Muscle enzyme levels (CK, AST, ALT, LDH, aldolase) at baseline (continuous variable).
•
Baseline Physician’s global assessment.
•
Baseline Subject’s global assessment.
•
Baseline MMT-8.
•
Baseline HAQ-DI (continuous variable).
•
Baseline Myositis Function Index (FI-2) scores (continuous variables).
•
Baseline Extramuscular Global Activity (as assessed by MDAAT).
•
Baseline CDASI scores (continuous variables)
•
Baseline MDI scores (continuous variables).
Any imbalances between treatment groups for the characteristics described above will be assessed 
when reviewing the summary tabulations and any differences deemed clinically relevant to the 
primary efficacy comparisons may be investigated by controlling for the characteristic in a 
supplemental analysis.
7.3.3
Medical History and Prior Medication
General medical history will be provided in a listing for the ITT analysis population.
Prior medications are defined as medications a subject started to take prior to the first SC injection 
of double-blind study medication. Prior medications will be summarized for each treatment group 
by drug class, generic name for the ITT analysis population.
Medications of special interest to Myositis treatment are the following categories: steroid and other 
steroid-sparing medications based on the WHO dictionary. A summary of prior medications of 
special interest will be provided by treatment group.
7.4
Extent of Exposure
7.4.1
Study Therapy
Because dosing for the open-label period, the open-label extension period (Japan) and the long-
term extension period is collected on the same CRF, visit dates recorded on CRF pages that 
correspond to the first/last visits within these periods will be used to distinguish these periods and 
the exposure periods will be defined by visit start and end dates of visit periods recorded on the 
CRF.
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7.4.1.1
Exposure during Double-Blind Period
Extent of exposure to double-blind study drug will be summarized using the as-treated analysis 
population in two ways:
•
Number of injections.
•
Number of days a subject is known to be on study drug.
The number of injections subjects received will be based on the study medication page of the CRF 
when an injection date is present.
The number of days the subject is known to be on study drug (exposure to study drug) during 
24-week double-blind period is calculated as:
•
For subjects who discontinued during 24-week double-blind period or did not enter the open-
label period within 56 days of the last injection in the double-blind period:
•
Exposure in days = (date of last injection in the 24-week double-blind period - date of first 
injection for double-blind period + 1) + 56.
For subjects who enter open-label period within 56 days of the last injection of 24-week double-
blind period:
•
Exposure in days = (date of first injection in the open-label period - date of first injection in 
the double-blind period).
The offset of 56 days is the length of 2 regular dosing cycles and represents approximately 4 times 
the half-life of abatacept in humans.
Summaries of exposure to study drug will show the distribution of the number of injections and 
days on drug, together with the means, standard deviations, medians, minima and maxima, by 
treatment group.
7.4.1.2
Exposure during Open-Label Period
The exposure to study drug during the open-label period will be calculated as follows:
Exposure to study drug in days for subjects who discontinued open-label period prior to the 
analysis cutoff date for the 24-week analysis is calculated as:
•
Exposure in days = (date of last dose of study drug in the open-label period - date of first dose 
of study drug in open-label period + 1) + 56.
For subjects who are continuing beyond the analysis cutoff date for the 24-week analysis exposure 
is calculated as:
•
Exposure in days = (data cutoff date - date of first dose of open-label period + 1).
The data cutoff date is the date of the last data change in the database prior to the DB lock.
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7.4.1.3
Exposure during Open-Label Extension Period
The exposure to study drug during the open-label extension period will be calculated as follows:
Exposure to study drug in days for subjects who discontinued open-label extension period prior to 
the analysis cutoff date for the 28-week analysis is calculated as:
•
Exposure in days = (date of last dose of study drug in the open-label extension period - date of
first dose of study drug in open-label extension period + 1) + 56.
For subjects who are continuing beyond the analysis cutoff date for the 28-week analysis exposure 
is calculated as:
•
Exposure in days = (data cutoff date - date of first dose of open-label extension period + 1).
The start date of the OLE period is not recorded for Japan subjects but is assumed to be the end 
date of the OL period.
7.4.1.4
Exposure during Long-Term Extension Period
The exposure to study drug during the long-term extension period will be calculated as follows:
Exposure to study drug in days for subjects who discontinued long-term extension period prior to 
the analysis cutoff date for the 24-week analysis is calculated as:
•
Exposure in days = (date of last dose of study drug in the long-term extension period - date of
first dose of study drug in long-term extension period + 1) + 56.
For subjects who are continuing beyond the analysis cutoff date for the 24-week analysis exposure 
is calculated as:
•
Exposure in days = (data cutoff date - date of first dose of long-term extension period + 1).
7.4.2
Discontinuation of Study Therapy
Discontinuation from study medication is defined as subject’s termination of the study medication 
(abatacept or placebo) without resumption prior to study completion. A subject will be considered 
as discontinued from study period if and only if the subject status CRF page indicates he/she did 
not complete either of the study periods. A separate subject status CRF page is completed at 
discontinuation or end of (1) double-blind period, (2) open-label period, (3) open-label extension 
period and (4) long-term extension period.
The number of subjects who discontinue during each of the 4 analysis periods; together with the 
reasons for discontinuation will be summarized by the randomized group as described in Section 
7.3.1. The reasons for discontinuation will be taken from the subject status pages of the CRF for
each period.
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7.5.2
Primary Efficacy Analysis
The primary comparison of proportion of subjects in IMACS DOI at Week 24 between the SC 
abatacept and placebo groups will be assessed using a logistic regression model. To account for 
randomization stratification, the logistic regression model will adjust for the randomization 
stratification variables of disease diagnosis (DM vs. Non-DM), Interstitial Lung disease status 
(present vs. absent), and Japan vs. ROW; baseline MMT8 score, baseline MDAAT, baseline PGA 
and treatment group will also be included in the model. Point estimates of the adjusted Odds Ratios 
(OR) of the odds of achieving IMACS DOI in the abatacept group compared to the placebo group, 
corresponding 95% CI and p-value will be provided. Point estimates of the proportion of subjects 
in IMACS DOI in each treatment group and corresponding 95% CI will also be provided. All 
subjects who discontinue study medication prematurely prior to reaching the Week 24 assessment 
visit and/or received rescued medication at any time during the 24 week double-blind period, will 
be considered as not achieving IMACS DOI for the primary analysis. Efficacy assessments 
collected at Week 24 on subjects who discontinue study medication prior to Week 24 will not be 
included in the primary analysis of the primary endpoint, but will be included in a sensitivity 
analysis of the primary endpoint. Details of imputation rules for classification of IMACS DOI 
response for subjects with missing components of IMACS are provided in Section 8.1.9. A table 
summarizing the number of imputed values for the primary endpoint by treatment group and 
missing data pattern will be provided. A summary of number of missing IMACS core measure 
item by treatment group will also be provided for subjects whose IMACS data are missing at Week 
24 because of missing component data.
The primary estimand of the treatment difference in the proportion of subjects with IMACS DOI 
at Day 169 is the odds ratio (abatacept versus placebo) in the ITT analysis population that would 
be observed if all subjects who prematurely discontinued or received rescue medication before 
Day 169 or had missing IMACS DOI data would be non-responders.
7.5.3
Sensitivity Analyses on the Primary Endpoint
7.5.3.1
Assess Impact of Rescue Medication
Sensitivity analyses of the primary endpoint will be performed based on the following scenarios:
•
All subjects who meet criteria for disease worsening will be imputed as non-responders (i.e. 
not meeting IMACS DOI) whether they used rescue medication or not.
•
All subjects who received rescue medication but continued in the double-blind period to Day 
169 will be assessed for IMACS DOI based on their disease assessment on Day 169.
These sensitivity analyses will help assess the impact of the use of rescue medication on the 
primary endpoint.
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7.5.3.2
Tipping Point Analyses
The robustness of the results of the primary endpoint will be assessed by varying the assumption 
of the missing data at the Week 24 (Day 169) based on the tipping point approach. This analysis 
will challenge the assumption that the effect of abatacept and placebo is the same for missing data 
by varying the percentage of missing considered as non-responders in both the abatacept and the 
placebo treatment group.
The missing data will be imputed using multiple imputation assuming the data are MNAR. The 
multiple imputation will utilize a logistic regression model that includes treatment group, age, 
gender, stratification variables of disease diagnosis (DM vs. Non-DM), Interstitial Lung disease 
status (present vs. absent), and Japan vs. ROW; baseline PGA score, baseline MMT-8 score and 
baseline MDAAT. The imputation will consider various scenarios including where dropouts on 
abatacept have lower response rate than dropouts on placebo. A series of analyses will be 
performed varying the distribution of responses among the missing data in each treatment group 
until the analysis conclusion of a statistically significant treatment effect no longer holds. The 
combination of number of responses among the missing data in each treatment group that overturns 
the primary results will represent a tipping point. An interpretation of clinical plausibility of the 
assumption underlying the tipping point will be provided.
Imputed data will consist of 100 imputed datasets; for each imputed dataset the missing IMACS 
DOI response will be imputed using the LOGISITIC method with a random seed number of 
123611. Each of the imputed datasets will be analyzed using a similar logistic regression model 
used for the primary endpoint to get the estimate of odds ratio and 95% CI. Results from the 
analyses of each imputed datasets ORs and corresponding 95% CI will be combined using Rubin’s 
imputation rules (using SAS MIANALYZE procedure) to produce the pooled estimate of OR and 
corresponding 95%, a pooled p-value for the test of null hypothesis of no treatment effect (i.e. OR 
= 1).
Analyses will be conducted by varying the log odds of achieving an IMACS DOI response (i.e. 
LOGIT of the probability of IMACS DOI response) among the missing data within each treatment 
arm. Resulting p-values will be displayed in a matrix that presents a range of logits corresponding 
to varying probabilities of response for missing values in both treatment arms; starting with a logit 
corresponding to a probability of response = 0.14 (this assumes 1 response out of 7 missing data)
with increments of 0.3 on the logit until the logit is reached corresponding to a probability of 
response of .86 (this assumes 6 responses out of 7 missing data). The tipping point can then be 
identified (i.e. where a statistically significant treatment effect no longer holds). The adjustment 
in the logit function will be specified using the statement MNAR ADJUST available in SAS 9.3 
or higher.
7.5.3.3
Sensitivity Analyses Based on Day 169 Data Collected after 
Discontinuation from Study
Subjects who discontinued the study prior to the Week 24 (Day 169) assessment are required by 
protocol to return for their Week 24 study visit similar to subjects continuing in the study; in 
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addition to the tipping point analysis above, the data collected on the discontinued subjects who
did not receive rescue medication will be used to perform an additional sensitivity analysis of the 
primary endpoint. A similar model used for the primary analysis will be used; the logistic 
regression model will include randomization stratification variables of disease diagnosis (DM vs. 
Non-DM), Interstitial Lung disease status (present vs. absent), and Japan vs. ROW; baseline 
MMT-8 score, baseline MDAAT, baseline PGA and treatment group. Point estimate of the 
adjusted Odds Ratios (OR) of the odds of achieving IMACS DOI in the abatacept group compared 
to the placebo group, corresponding 95% CI will be provided, however no p-value will be 
calculated. Unadjusted point estimate of the proportion of subjects in IMACS DOI in each 
treatment group and corresponding 95% CI will also be provided. Subjects with missing Week 24 
assessment will be considered non-responders in this sensitivity analysis.
7.5.4
Secondary Efficacy Analysis
In addition to the primary efficacy endpoint, analyses related to the secondary 
 
will also be included in the Week 24 analysis. The secondary efficacy assessment of 
change from baseline in muscle endurance using FI-2 up to Day 169 (Week 24) will be assessed 
using a longitudinal (repeated measures) model including treatment group, baseline FI-2 value and 
randomization stratification factors: diagnosis (DM vs. Non-DM), ILD, Japan vs. ROW, time 
(categorical as study visit at which FI-2 is measured), time by baseline FI-2 and time by treatment 
interactions as fixed effects and subject as a random effect. Adjusted mean, SE, 95% CI for 
adjusted mean difference between treatment groups by study visit will be provided.
A similar longitudinal model will also be used to assess the change from baseline in HAQ-DI up 
to Day 169 (Week 24). The model will include treatment group, baseline value HAQ-DI value, 
randomization stratification factors: disease diagnosis (DM vs. Non-DM), ILD, Region (Japan vs.
ROW), time (categorical as study visit at which HAQ-DI is measured), time by baseline HAQ-DI 
and time by treatment interactions as fixed effects and subject as a random effect. Adjusted mean, 
SE, 95% CI for adjusted mean difference between treatment group by study visit will also be 
provided.
The secondary efficacy assessment of change from baseline in extra-muscular disease activity 
MDAAT value will also be assessed using a longitudinal (repeated measures) model including 
treatment group, baseline value extra-muscular disease activity MDAAT value, randomization 
stratification factors: disease diagnosis (DM vs. Non-DM), ILD, Region (Japan vs. ROW), time 
(categorical as study visit at which extra-muscular disease activity MDAAT is measured), time by 
baseline extra-muscular disease activity MDAAT and time by treatment interactions as fixed 
effects and subject as a random effect. Adjusted mean, SE, 95% CI for adjusted mean difference 
between treatment groups by study visit will also be provided.
A similar longitudinal model will also be used to assess the Myositis Response Criteria (MRC) 
total improvement score up to Day 169 (Week 24). The mixed model will include treatment group 
and randomization stratification factors: disease diagnosis (DM vs. Non-DM), ILD (absent vs.
present), Region (Japan vs. ROW), time (categorical as study visit at which MRC is measured) 
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and time by treatment interactions as fixed effects and subject as a random effect. Adjusted mean, 
SE, 95% CI for adjusted mean difference between treatment groups by study visit will be provided.
Nominal p-values will be provided for the secondary efficacy endpoints at Day 169 i.e. mean 
change from baseline at Day 169 for each of the secondary endpoints: FI-2, HAQ-DI, extra-
muscular disease activity MDAAT and MRC. The mixed longitudinal model will account for any 
missing values on any of the secondary efficacy endpoints.
The primary analyses of each of the secondary endpoints discussed above will be based on the data 
observed while subjects are on treatment in the study; a sensitivity analysis will be performed 
separately for each secondary endpoint that includes all the data collected at Week 24 on subjects 
who discontinue study medication prior to Week 24. Similar models as used for the primary 
analysis of these endpoints will be applied for the sensitivity analysis.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Non-DM), ILD (absent vs. present), Region (Japan vs. ROW), time (categorical as study visits at 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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All AEs are coded and grouped into Preferred Terms (PT) by System Organ Class (SOC), using 
the most current version of the Medical Dictionary for Regulatory Activities (MedDRA), at the 
time of data base lock. Listings and summaries will be based on the resulting SOCs and PTs.
All reported AEs and SAEs will be listed, indicating the subject id, treatment group, age, gender, 
race, day of onset relative to start of dosing, resolution date, investigator-assessment of relationship 
to study drug, investigator-assessment of intensity of event, action taken regarding study drug and 
whether treatment was required for the event.
All adverse events with an outcome of death will be listed.
Any AEs that occur before the first injection of double-blind study drug or more than 56 days after 
the last injection during the double-blind period will be excluded from safety summaries in the 
Week 24 analysis. However, all reported AEs, including AEs that occurred more than 56 days post 
last dose for subjects who discontinued the study during the double-blind period or completed the 
double-blind period but chose not to enter the open-label period will appear in the above mentioned 
comprehensive listing.
Summary information (the number and percent of subjects) regarding AEs (for serious and non-
serious events) will be tabulated by SOC, PT and treatment group for:
•
Serious adverse events (SAE).
•
SAEs related to study drug.
•
AEs leading to study drug discontinuation.
•
AEs related to study drug.
•
AEs related to study medication categorized by intensity.
•
Most common related AEs (reported in at least 2% of subjects in any treatment group).
•
AEs by intensity.
•
All AEs (serious or non-serious).
•
Most common (serious or non-serious) AEs (reported in at least 5% of subjects in any treatment 
group).
•
Laboratory AEs are laboratory results identified by the Investigator as AEs and thus reported 
on the AE pages of the CRF. Any such AE will be included in the respective AE summaries.
7.6.2
Adverse Events of Interest
For all adverse events of special interest, treatment groups will be compared descriptively using 
risk differences and corresponding 95% CI and presented graphically using a forest plot in 
decreasing order of risk difference.
7.6.2.1
Infections
All reported infections and infestations within the SOC: Infections and infestations occurring 
during the double-blind period are included in the summaries described in Section 7.6.1.
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7.6.2.2
Malignancy
All events in the MedDRA Maintenance and Support Services Organization (MSSO) malignancies 
Structured MedDRA Query (SMQ) list occurring during the double-blind period will be captured 
and reported. These events will be summarized by preferred term and treatment group and will 
also be listed.
7.6.2.3
Autoimmune Disorders
The frequency of pre-specified autoimmune disorders, defined using a BMS custom Autoimmune 
Disorder SMQ, occurring during the double-blind period will be provided. Autoimmune disorders 
occurring during the double-blind will also be summarized by intensity. All reported autoimmune 
disorders occurring during the double-blind period will be listed.
7.6.2.4
Injection Adverse Events
A. Systemic Injection Reactions are defined pre-specified AEs (such as hypersensitivity reactions) 
occurring during the first 24 hours after SC injection. The pre-specified list of AEs is defined using 
a BMS custom SMQ for abatacept SC program.
B. Injection Site Reaction Adverse Events: Summaries of injection site reactions will be done in 
two ways: using the pre-specified list of injection site reactions (cSMQ) and using the standard 
HLT lists for Injection site reactions, Administration site reactions NEC, and Application and 
instillation site reactions.
The number and percent of subjects experiencing the injection reactions defined in A and B above 
will be summarized by SOC and PT and treatment group. The distribution of the injection reaction 
events of interest by severity will also be provided. Serious events of interest during the double-
blind period will be summarized by SOC, PT and treatment group. Most frequent (reported in 5% 
of subjects or more in any treatment group) AEs will also be provided. All reported injection 
reactions events of interest occurring during the double-blind period will be listed.
In addition, a pre-specified local injection site reaction event of interest, defined as the AEs with 
the following PT that occur at the site of SC injection: Erythema, Pain, Pruritus, Haematoma, and 
Swelling will be summarized by severity.
7.6.3
Laboratory Data
Safety summaries based on laboratory test results include evaluation of laboratory abnormalities 
and changes in laboratory test values from baseline (baseline addressed further in Section 8.2). For
summaries of the double-blind period, laboratory data obtained during treatment or up to 56 days 
after last injection of study medication in the double-blind period but no later than the start of the 
open-label period dosing will be eligible for analyses.
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Laboratory abnormalities are identified using a pre-defined set of marked abnormality (MA) 
criteria (listed in Safety Data Convention). The frequency of subjects with laboratory MAs during 
the double-blind period based on pre-specified criteria will be tabulated by treatment group, for 
each analyte.
Laboratory measurements and their changes from baseline will be summarized by nominal visit 
and treatment group, for protocol specified analytes. Subjects who have laboratory measures at
baseline and corresponding measures on at least one scheduled visit following administration of 
study drug will be included in the laboratory analyte assessment. Note that not all subjects have 
laboratory determinations for all analytes at all visits, and therefore the sample size may vary from 
analyte to analyte at each time point.
In addition shift tables for the following laboratory tests will be provided. The categorical 
classifications of these tests will be determined based on the cut points specified below and cross-
tabulation of classification between baseline and each of the scheduled visits will be presented by 
treatment groups.
Table 7.6.3-1:
Definitions of Analyte Cut Points
Analyte (Test Code)
Cut Points
Platelet Count (PLAT)
< 100x109 c/L
≥100 x109 c/L
Alanine Aminotransferase (ALT)
< 3xULN
3 - ≤5xULN
> 5xULN
Aspartate Aminotransferase (AST)
< 3xULN
3 - ≤5xULN
> 5xULN
Neutrophils (absolute)
< 0.5x109 c/L
0.5 - ≤15x109 c/L
> 15x109 c/L
G-Glutamyl Transferase (GGT)
< 3xULN
3 - ≤5xULN
> 5xULN
7.6.4
Vital Signs
•
Summary statistics for vital sign measurements (systolic BP, diastolic BP, heart rate and body 
temperature) will be presented at study baseline, and prior and after injection by scheduled 
visit and treatment group.
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7.8
Additional Analyses to be Included in 24 Week CSR
In addition to safety summaries specified above for the 24-week double-blind period; summaries 
of all AEs, AEs of special interest (SAEs, Malignancies, Myositis related AEs and autoimmune 
events) reported in the database up to the 24-week database lock will be included in the 24-week 
study report. These AEs will be presented by the double-blind treatment groups for the cumulative 
abatacept period based on the as-treated analysis population.
8
CONVENTIONS
8.1
Calculations of Key Measures
8.1.1
IMACS DOI
IMACS DOI for the primary endpoint is defined as meeting all the following criteria:
•
An improvement of ≥20% in 3 IMACS core measures, AND
•
No more than 2 IMACS core measure scores worsen by ≥25%, AND
•
Manual Muscle Test (MMT-8) may not decrease by ≥25%.
For the exploratory analyses two modified IMACS DOI definitions will be considered:
First alternative definition
•
A1: An improvement of ≥25% in 3 IMACS core measures, AND
•
A2: No more than 2 IMACS core measure scores worsen by ≥30%, AND
•
A3: Manual Muscle Test (MMT-8) may not decrease by ≥30%.
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Second alternative definition
•
B1: An improvement of ≥30% in 3 IMACS core measures, AND
•
B2: No more than 2 IMACS core measures scores worsen by ≥35%, AND
•
B3: Manual Muscle Test (MMT-8) may not decrease by ≥35%.
For the exploratory analyses the modified IMACS DOI definition using a 25% (and 30%) cutoff 
for improvement in 3 core measures, and no more than 2 core measures worsening by 30% (and 
35%) and MMT-8 not decrease by 30% (and 35%) will be provided.
The IMACS Core measures are:
•
Physician Global Assessment of Disease Activity (PGA).
•
Patient (Subject) Global Assessment of Disease Activity (SGA).
•
Manual Muscle Test (MMT-8).
•
Health Assessment Questionnaire-Disability Index (HAQ-DI).
•
Muscle Enzyme levels.
•
Myositis Disease Activity Assessment Tool (MDAAT) Extramuscular Global Activity VAS 
(V-8 in the CRF).
8.1.2
Physician Global Assessment of Disease Activity (PGA)
Physician Global Assessment of Disease Activity (PGA) is measured using a 10cm visual analogue 
scale that can be performed by the investigator or sub-investigator.
8.1.3
Patient Global Assessment of Disease Activity (SGA)
Patient (Subject) Global Assessment of Disease Activity (SGA) is measured using a 10cm visual 
analogue scale that is performed by the subject.
8.1.4
Manual Muscle Test (MMT-8)
This tool assesses muscle strength using a 0-10 point scale. A set of 7 designated muscles is tested
bilaterally plus axial (neck flexor) testing, so that the potential MMT-8 score ranges from 0-150.
The designated muscles tested will be:
•
Neck flexors.
•
Deltoid middle.
•
Biceps brachii.
•
Gluteus maximus.
•
Gluteus medius.
•
Quadriceps.
•
Wrist extensors.
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•
Ankle dorsiflexors.
8.1.5
HAQ Disability Index
Scoring conventions for the Standard Disability Index of HAQ will be followed. The Standard 
disability index (HAQ DI) takes into account the subject’s use of aids or devices or assistance in 
the scoring algorithm for a disability category. For each of the eight disability categories there is 
an AIDS OR DEVICES companion variable(s) that is used to record the type of assistance, if any, 
a subject uses for his/her usual activities. If aids or devices and/or assistance from another person 
are checked for a disability category, the score for this category is set to 2 (much difficulty), if the 
original score is 0 (no difficulty) or 1 (some difficulty). The HAQ DI is then calculated by summing 
the adjusted categories scores and dividing by the number of categories answered. Details of the 
HAQ DI scoring conventions are documented in “The Health Assessment Questionnaire”.
8.1.6
Muscle Enzyme Levels
The muscle enzymes of interest are creatine kinase (CK), aldolase, AST, ALT, and LDH. To assess 
the DOI the most abnormal lab value (% above ULN) at baseline will be determined. The 
subsequent change from baseline for this lab value will be used to determine if the patient has met 
the criteria for the IMACS Definition of Improvement (DOI) at each time point. To assess the 
criteria for worsening, the change from baseline point will be determined for all 5 lab values at 
each time point indicated. The lab value with the greatest percent increase from baseline for each 
will be used to determine if the patient has met the criteria for worsening respectively (Section 
3.1.5 of the Protocol).
8.1.7
Extramuscular Disease Activity using Myositis Disease Activity 
Assessment Tool (MDAAT)
This is a combined tool that captures the physician’s assessment of disease activity of various 
organ systems using (1) a 0-4 scale and (2) a visual analog scale (VAS). It assesses the clinical
features of each organ system based upon:
•
The presence of clinical features or symptoms within the previous 4 weeks that are due to
active disease (i.e., use your clinical judgment to determine how active the myositis associated
clinical feature has been within the previous 4 weeks).
•
The judgment that the feature is due to the myositis disease process (i.e., clinical findings
known or suspected to be due to another disease process or due to therapy should NOT be
considered in this evaluation).
•
The concept that disease activity is defined as a potentially reversible finding.
•
A clinical, functional, and laboratory assessment for each organ system.
The scoring system is based primarily on the physician’s intention to treat (Categories A – D). In 
some cases, a patient may meet the clinical manifestations of a particularly category, but the
treatment does not match the intention to treat of that particular category; in those cases, the
category matching the clinical symptoms should be marked. If more than one clinical symptom is
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present within a system, and different categories would be scored for each, mark the category that 
is most severe.
8.1.8
IMACS Calculation
IMACS DOI will be evaluable if there are at least 5 non-missing core measures, including MMT-
8. In that case IMACS DOI status will be categorized as a response based on the available set of 
core measures satisfying the criteria mentioned above, otherwise, the status will be set as a non-
response. If MMT-8 is not available or less than 5 core measures are available then IMACS DOI 
status will be subject to the imputation methods specified in Section 8.1.9.
Higher values for each component of the IMACS core measures (excluding MMT-8) indicate 
greater severity of disease. Improvement from baseline in a core measure of the IMACS will be 
computed as the difference between the baseline (Day 1 pre-treatment) value and the value at a 
given post-baseline visit. A positive value for improvement from baseline for an individual core 
measure indicates lesser severity of disease. The IMACS DOI will be defined based on the percent 
improvement from baseline in each of the IMACS core measure listed in Section 8.1.1.
Percent improvement will be computed as the ratio of improvement from baseline to the baseline 
value times 100 for an endpoint:
% Improvement = 100 * (Improvement from Baseline) / Baseline Value
= 100 * (Baseline Value - Post-baseline Value) / Baseline Value
For MMT-8, a higher value implies a lesser severity of disease; the % reduction in muscle strength 
will also be calculated as:
100 * (Baseline Value - Post-baseline Value) / Baseline Value
8.1.9
Determination of IMACS DOI Responders
Any subject who does not meet the IMACS DOI criteria is considered a non-responder. For
IMACS DOI status that cannot be evaluated due to missing data (i.e. MMT-8 not available or less 
than 5 of the core measures available) the following conventions will be implemented:
•
For the primary analysis at Week 24, any subject who prematurely discontinues the trial after 
receiving study medication will have missing data imputed as a IMACS/DOI non-responder at 
all scheduled protocol visits subsequent to the point of discontinuation. For the sensitivity 
analysis of the primary endpoint the data collection post discontinuation from the study will 
be used in the determination of the DOI status and included in the analyses. The tipping point 
sensitivity analysis will impute the missing data as described in Section 7.5.3.2
•
Any subject for whom data are missing at a given visit not due to premature discontinuation 
will have a value for IMACS/DOI response imputed at that given visit. If the given visit is not 
the last scheduled efficacy visit (Day 169), imputation will depend on the observed responses 
from the previous scheduled visit and the next scheduled visit. If there are IMACS DOI 
responses observed at both visits, an IMACS DOI response will be imputed for the given 
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missing visit. Else, if a non-response is observed at one of the visits or a response is missing at 
one of the visits then a non-response will be imputed. If the given visit is the last scheduled 
efficacy visit (Day 169), the missing response will be imputed as non-response.
8.1.10
Myositis Function Index (FI-2)
The FI-2 is a functional outcome developed for patients with adult polymyositis or 
dermatomyositis assessing muscle endurance in seven muscle groups. Each muscle group is scored 
as the number of correctly performed repetitions with 60 or 120 maximal number of repetitions 
depending on muscle group. The FI-2 is a further development of the original Functional Index 
(FI) and has been validated as to content and construct validity and intra- and inter-rater reliability. 
The FI-2 can be performed on both right and left sides requiring a maximum of 33 minutes, or just 
on the dominant side which takes 21 minutes. If both sides are available for a given muscle set 
then the scores from both sides will first be averaged so that there is only one score per muscle set 
for the calculations below. If only one side is available then that side will be used.
The 3 types of measures for analysis will be as follows:
•
Total score based on hip flexion, shoulder flexion (R/L) and neck divided by 3.
•
Total score based on all 7 muscle sets.
•
Individual scores for all 7 muscle sets.
8.1.11
Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
This tool assesses the improvement in skin disease activity in subjects with dermatomyositis. Four 
domains are evaluated including 1) disease activity and damage in 15 anatomic locations, 2) 
presence of Gottron’s papules on the hands, 3) periungual changes, and 4) alopecia. A total activity 
score and damage score are calculated.
8.1.12
Myositis Damage Index (MDI)
This tool measures the degree of disease damage of all organ systems. It is composed of a series 
of organ-specific questions relating to the presence or absence of a given sign or symptom or 
problem to measure the extent of damage, and an overall rating of the disease damage of each
system using a 10 cm visual analogue scale to measure the severity of damage.
The MDI has 3 proposed scores: an extent of damage score, a severity of damage score and an 
extended damage score.
The proposed scoring system for the MDI extent of damage score is the sum of all 0 or 1 scores 
for the 11 individual organ systems (muscle, skeletal, cutaneous, gastrointestinal, pulmonary, 
cardiovascular, peripheral vascular, endocrine, ocular, infection, malignancy) divided by the total 
possible score (range = 0–35 in children, 0–37 for adolescents and 0–38 in adults). If one or more 
items were not assessed, the resulting score would be divided by the maximum possible score of 
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the assessed items. The categories of “other damage” and “global damage” are not included in the 
MDI extent of damage score but are scored separately.
The proposed MDI severity of damage score is the sum of the 10 cm visual analogue scale scores 
for each of the 11 individual organ systems divided by the total possible score (range = 0–110). If 
one or more organ systems were not assessed, the resulting score would be divided by the 
maximum possible score of the assessed items. The categories of “other damage” and “global 
damage” are not included in the MDI severity score but are scored separately.
The proposed MDI extended damage score is the sum of the optional items listed in italics under 
the systems muscle, skeletal, gastrointestinal, pulmonary, endocrine divided by the total possible 
score. Each optional item is scored 0 or 1, providing a range of 0–16 for the extended damage 
score. If one or more items were not assessed, the resulting score would be divided by the 
maximum possible score assessed.
8.1.13
Myositis Response Criteria
The Myositis Response Criteria (MRC) is a novel outcome measure derived by consensus for a 
conjoint analysis–based continuous model using absolute percent change in the IMACS DOI core 
set measures. A total improvement score (range 0–100) can be determined by summing scores for 
each core set measure based on improvement adjusted by relative weight for each core set measure 
(see APPENDIX 2). A total improvement score of ≥20 represents minimal improvement, a score 
of ≥40 represents moderate improvement, and a score of ≥60 represents major improvement.
8.2
Baseline Measures
For all outcome measures, the baseline value is the last assessment taken prior to first dose of study 
medication. In general, this is the assessment taken on study Day 1 before the administration of 
study medication. For some variables that are also measured during screening, if Day 1 
assessments are unavailable then the last assessments prior to Day 1 from screening assessments 
will be used as baseline value. When there is a missing baseline assessment in joint counts, it will 
not be imputed, thus, subjects are excluded from any change from baseline analysis for which they 
have a missing baseline value. No screening assessment will be imputed as baseline measurements 
for subjects who require a washout before the start of the study medication.
8.3
Missing Measurements
For listings of IMACS DOI response, imputed DOI response will be included in the listings with 
a flag to indicate the values were imputed; missing IMACS components will be presented as 
missing. For determination of IMACS DOI response, handling of missing values is addressed in 
Section 8.1.9.
For the analysis of individual components of IMACS DOI, HAQ DI and its category scores, FI-2, 
Myositis Response Criteria missing values will not be imputed. Subjects with only baseline 
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observations will be excluded from any changes from baseline analyses. Similarly for all other 
efficacy, safety, 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 do not always adhere strictly to the visit schedule timing in the protocol. Therefore the 
designation of visits during the double-blind 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 CRF. 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.
Designation of visits for efficacy or laboratory assessments performed at every scheduled visit is 
tabulated in Table 8.5-1.
Table 8.5-1:
Day Ranges for Efficacy or Laboratory Assessments During the 
Double-Blind Period
Visit 
Target Day
Assessments
Screening
< 1
< 1
Day 1 (Baseline) 
1
1**
Day 29
29
8 - 43
Day 57
57
44 - 71
Day 85 (Week 12)
85
72 - 99
Day 113
113
100 - 127
Day 141
141
128 - 155
Day 169 (Week 24)*
169
156 - 211
*Note: For subjects who continue into the open-label period of study, the upper limit of this window is the first dose 
day of the open-label period.
**Note: See Section 8.2 for baseline measures.
Designation of visits for the ANA assessments is tabulated in Table 8.5-2.
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10
DOCUMENT HISTORY
Table 10-1:
Document History
Version 
Number
Author(s)
Description
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APPENDIX 1
RELEVANT PROTOCOL DEVIATIONS
Pre-randomization
•
Myositis Activity:
−
Screening MMT-8 score of 140 or more.
−
Failure to document criteria for currently active IIM or obtain approval from adjudication 
committee.
−
Diagnosis of Inclusion Body Myositis.
•
Medication/Procedure/Other:
−
Use of rituximab within 3 months.
−
Use of immune globulin within 6 weeks.
−
Discontinuation of prohibited medication within 2 weeks.
Post-randomization
•
Medication/Procedure:
−
Use at randomization of more than 1 of the allowable immunosuppressant’s drugs in the 
Double-Blind period.
−
Use of corticosteroids above prednisone ≥35mg/day (or prednisone equivalent) for > 3 
weeks or within 2 weeks of Day 169.
−
Increase of 5 mg or more per day or initiation of more than 10 mg per day of prednisone 
(or prednisone equivalent) that is unrelated to management of an AE or permitted rescue 
therapy.
−
All prohibited medication not discontinued at least 2 weeks prior to randomization with 
the exception of immune globulin (3 months), rituximab (6 months) and d-penicillamine
(3 months). Prohibited medication in this context refers to immunomodulatory medications 
for the treatment of IIM which are not included as immunosuppressant medications. The 
following list includes examples of specific prohibited medications:
♦Adrenal Corticotropic Hormone (ACTH), including analogues.
♦Sirolimus.
♦Everolimus.
♦Mizoribine.
♦Tofacitinib or other JAK inhibitor.
−
All investigational or approved biologic DMARD therapies other than abatacept (including 
but not limited to tocilizumab, adalimumab, golimumab, certolizumab, etanercept, 
infliximab, anakinra, rituximab, etc.).
−
Use of any investigational drug other than study medication.
•
Study conduct:
−
Subject missed more than 6 consecutive doses of study medication (abatacept or placebo) 
during the Double-Blind period or missed more than 4 consecutive scheduled doses of 
study medication (abatacept or placebo) between Day 141 and Day 169.
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Covid-19 Related Deviations
•
Unable to attend both Day 141 and Day 169 assessments due to travel/other restrictions.
•
For missed doses due to Covid-19 the same rule to define those as a relevant protocol deviation 
applies as under study conduct above.
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APPENDIX 2
MYOSITIS RESPONSE CRITERIA
The final myositis response criteria for minimal, moderate and major improvement in adult 
dermatomyositis/ polymyositis (DM/PM) and combined DM/PM and juvenile DM clinical trials 
and studies. 
Table 10-2:
Myositis Response Criteria
The total improvement score is the sum of all 6 improvement scores associated with the change in 
each core set measure. A total improvement score of ≥20 represents minimal improvement, a 
score of ≥40 represents moderate improvement, and a score of ≥60 represents major 
improvement. If one of the core measures is missing then the total score will be missing.
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Improvement Score Calculation
The absolute percent change ((post-baseline value – baseline value) / range) * 100 is calculated 
for each core set measure. For muscle enzymes, the most abnormal serum muscle enzyme level at 
baseline (creatine kinase, aldolase, alanine transaminase, aspartate aminotransferase, lactate 
dehydrogenase) is used. 
The range for each of the core set measures are as follows:
Muscle Enzymes: The enzyme range was calculated based on a 90% range of enzymes from 
natural history data as follows:
Creatinine Kinase: Range = 15 times the upper limit of normal (ULN)
Aldolase: Range = 6 times the ULN
Lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase: Range = 3 times the 
ULN.
The ULN is based on what is reported in the lab dataset for each enzyme.
Ranges for other core set measures:
Physician Global Assessment of Disease Activity (PGA) VAS: Range = 10 
Patient Global Assessment of Disease Activity (SGA) VAS: Range = 10
Manual Muscle Testing (MMT-8): Range = 150
HAQ: Range = 3
Extramuscular Global Activity (using MDAAT): Range = 10
An improvement score is assigned for each core set measure based on the absolute percent change 
in the core set measure according to the definition in Table 2.1 above. These individual core set 
measure improvement scores are then totaled among the 6 core set measures to give the total 
improvement score. 
A total improvement score between 0 and 100 corresponds to the degree of improvement, with 
higher scores corresponding to a greater degree of improvement.
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APPENDIX 3
ANALYSIS PLAN FOR OPEN-LABEL, OPEN-LABEL EXTENSION 
AND LONG-TERM EXTENSION PERIODS ANALYSIS
Analyses specified in this section will be performed:
1) At the end of the open-label period, i.e. after all subjects have completed the 52-week 
assessment.
2) At the end of the open-label extension period, i.e. after all subjects have completed the 76-
week assessment (Japan sites only).
3) At the end of the long-term extension period, i.e. after all subjects have completed the 3-year 
assessment and all protocol specified follow-up visits.
For sections “Background and Rationale; Study Description; Objectives; Endpoints; Sample Size 
and Power; Study Periods, Treatment Regimens and Populations for Analyses; Conventions” and 
their subsections, see Section 1-Section 6 and Section 8 of SAP for 24-week analysis of the double-
blind study period. Any changes or modification to the analysis for the double-blind period will 
be explicitly presented.
The open-label analysis will include safety assessment for all safety data in the database at the 
time of the 52-week database lock.
The open-label extension analysis will include safety assessment for all safety data in the database 
at the time of the 76-week database lock.
The long-term extension analysis will include safety assessment for all safety data in the database 
at the time of the study final database lock.
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11.3
Study Conduct
The relevant protocol deviations are only assessed for the double-blind period and not for the other 
periods.
11.4
Study Population
Frequency distributions or summary statistics of data pertaining to subject disposition, 
demographics, baseline characteristics, and medical history will be tabulated and displayed by 
randomized treatment group for all subjects in the open-label / open-label extension / long-term 
extension periods. No statistical test will be carried out for comparison of any baseline 
measurement among treatment groups.
11.4.1
Subject Disposition
The number of subjects randomized, the number of subjects treated in the open-label / open-label 
extension / long-term extension periods, and the number of subjects who discontinued the open-
label / open-label extension / long-term extension periods, together with reasons for 
discontinuation taken from the eCRF status page, will be tabulated by randomized treatment group.
11.4.2
Demography and Baseline Characteristics
Demographic and baseline characteristics of all subjects in the open-label / Japan open-label 
extension / long-term extension treated analysis populations; summaries will be presented by the
double-blind treatment groups. Continuous variables such as age, weight, and duration of disease 
will be summarized by randomized treatment group using means, standard deviations and ranges. 
The distribution of categorical variables such as gender, race and geographic region will be 
summarized by treatment group using frequencies and percentages. See Section 7.3.2 for variables
included in these summaries. This will be based on the data captured on the CRF page, except for 
the summary of the stratification variables which is based on the IxRS data.
11.4.3
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 in open-label / Japan open-label 
extension / long-term extension treated analysis populations. Listings of medical history and prior 
medication will be presented by treatment group in the open-label / Japan open-label extension / 
long-term extension treated analysis populations.
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11.5
Extent of Exposure
11.5.1
Study Therapy
Extent of exposure to study drug in the open-label / Japan open-label extension / long-term 
extension treated analysis populations will be summarized in two ways; first, by the number of 
abatacept injections, summarizing frequency distribution of number of abatacept injections taken 
by treatment group, and second, by the number of days (or months) the subject is known to be on 
abatacept, ignoring any dosing interruptions. Exposure will be presented separately for the open-
label / open-label extension / long-term extension periods and the cumulative abatacept period.
11.5.1.1
Open-Label Period Exposure
The extent of exposure for the open-label period will be calculated and presented in days as 
follows:
•
For subjects who discontinued during the open-label period or did not enter the open-label 
extension period or the long-term extension period within 56 days of the last injection in the 
open-label period:
•
Exposure in days = (date of last injection in the open-label period - date of first open-label 
injection + 1) + 56.
For subjects who enter open-label extension or long-term extension period within 56 days of the 
last injection in the open-label period:
•
Exposure in days = (date of first injection in the open-label extension or long-term extension 
period - date of first open-label injection).
The offset of 56 days is the length of 2 regular dosing cycles and represents approximately 4 times 
the half-life of Abatacept in humans. 
Summaries of exposure to study drug will show the distribution of the number of injections and 
days on drug, together with the means, standard deviations, medians, minima and maxima, by 
treatment group.
11.5.1.2
Open-Label Extension Period Exposure
The extent of exposure for the open-label extension period will be calculated and presented in days 
as follows:
•
For subjects who discontinued during the open-label extension period or did not enter the long-
term extension period within 56 days of the last injection in the open-label extension period:
•
Exposure in days = (date of last injection in the open-label extension period - date of first open-
label extension injection + 1) + 56.
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For subjects who enter long-term extension period within 56 days of the last injection in the open-
label extension period:
•
Exposure in days = (date of first injection in the long-term extension period - date of first open-
label extension injection).
11.5.1.3
Long-Term Extension Period Exposure
The extent exposure of for the long-term extension period will be calculated and presented in days 
as follows:
Exposure in days = (date of last injection in the long-term extension period - date of first long-
term extension injection + 56).
11.5.1.4
Cumulative Abatacept Exposure
The cumulative abatacept exposure will only be computed for the final analysis (i.e. at the study 
closeout); the exposure to abatacept during the cumulative period will be calculated as follows:
Exposure in months = (date of last dose of abatacept in the study - date of first dose of abatacept 
in the study + 1 - adjustment + 56)/30.
The offset of 56 days represents approximately 4 times the half-life of abatacept in humans. 
Adjustment is the sum of the time span between:
•
the last dose of abatacept in the double-blind period and the first dose of abatacept in the open-
label period which exceeds 56 days (all sites),
•
the last dose of abatacept in the open-label period and the first dose of abatacept in the open-
label extension period which exceeds 56 days (Japan sites); or the last dose of abatacept in the 
open-label period and the first dose of abatacept in the long-term extension period which 
exceeds 56 days (all other sites but not including U.S. and Czech Republic sites),
•
the last dose of abatacept in the open-label extension period and the first dose of abatacept in 
the long-term extension period which exceeds 56 days (Japan sites).
Summaries of cumulative period exposure to study drug will show the distribution of the number 
of months on drug, together with the means, standard deviations, medians, minima and maxima, 
by treatment group. A listing of abatacept study medication dose dates will also be provided for 
the cumulative period.
11.5.2
Discontinuation of Study Therapy
Discontinuation from study therapy is defined as a subject’s termination of the study medication 
without resumption prior to study completion. The discontinuation from study therapy during the 
open-label / open-label extension / long-term extension periods will be summarized for all open-
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label / open-label extension / long-term extension periods treated subjects, by treatment group and 
the reason for premature termination, taken from the subject status eCRF page.
11.5.3
Treatment Compliance
The number of subjects who missed study medication doses (excluding missed doses due to 
premature discontinuation from the study) during open-label / open-label extension / long-term 
extension will be summarized for all open-label / open-label extension / long-term extension 
periods treated subjects, by double-blind treatment group and number of study dose missed. A 
corresponding listing of all treated subjects with missed doses during the open-label / open-label 
extension / long-term extension periods will be provided.
 
 
 
 
 
 
 
 
 
 
 
11.6
Efficacy
All efficacy analyses for the open-label / open-label extension periods will be performed using the 
open-label / Japan open-label extension treated analysis population, unless otherwise specified. 
Over time (double-blind and open-label / open-label extension visits) analyses will be performed 
for all efficacy endpoints specified in the 24 week Analysis Plan. The analyses will be as observed 
with no imputation for any missing data. No p-values will be provided for any of the open-label 
analyses.
11.6.1
Other Efficacy Analyses
IMACS DOI
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Proportion of subjects in IMACS DOI over time during the study will be presented by the double-
blind treatment groups and visit. Point estimate of response rate, 95% CI, point estimates and 95%
CI of treatment difference adjusted for randomization stratification factors: disease diagnosis (DM 
vs. Non-DM), ILD (absent vs present), Region (Japan vs ROW) (based on minimum risk weights).
Proportion of subjects who meet the ≥20% improvement from baseline over time for each of the 
core measures of IMACS (PGA, SGA, MMT-8, HAQ-DI, MDAAT and muscle enzymes) will be 
presented by double-blind treatment groups and visit. Point estimate of response rate, 95% CI, 
point estimates and 95% CI of treatment difference adjusted for randomization stratification 
factors: disease diagnosis (DM vs. Non-DM), ILD (absent vs present), Region (Japan vs ROW) 
(based on minimum risk weights).
The proportion of subjects in IMACS Minimal, Moderate and Major responses using the Myositis 
Response Criteria tool (as defined in section 8.1.11) will also be presented over time during the 
study. Point estimates and 95% CI within each treatment group for IMACS Minimal, Moderate 
and Major DOI response will be provided by visit. Differences in IMACS Minimal, Moderate and 
Major DOI response rates between the double-blind treatment groups with be provided by point 
estimate and corresponding 95% CIs based on an ordinal logistic regression model.
Additional separate longitudinal repeated mixed effects models will be used to assess the mean 
change from baseline over time in the study in each of the IMACS core measures (PGA, SGA, 
MMT-8, HAQ-DI, MDAAT and muscle enzymes). The mixed models will include double-blind 
treatment group, baseline measurement, randomization stratification factors: disease diagnosis 
(DM vs. Non-DM), ILD (absent vs present), Region (Japan vs ROW), time (study days in which 
each core measures was collected), time by baseline measurement and time by treatment 
interactions as fixed effects and subject as a random effect. Adjusted mean, SE, 95% CI for 
adjusted mean difference between treatment groups will also be provided. The estimate of baseline 
mean core measure, mean post-baseline core measure, and adjusted mean change from baseline 
core measure will be also be presented by double-blind treatment group and visit.
11.6.2
Additional Efficacy and Outcome Research Analyses
FI-2
Changes in muscle in endurance measured by FI-2 scores over time in the study will be assessed 
using a longitudinal repeated measures mixed model. The model will include baseline FI-2 score, 
double-blind treatment group, randomization stratification factors disease diagnosis (DM vs. Non-
DM), ILD (absent vs present), Region (Japan vs ROW), time and time by treatment interaction. 
The estimate of baseline mean FI-2 score, mean post-baseline FI-2 score, and adjusted mean 
change from baseline FI-2 score will be summarized by treatment group and visit. Treatment 
difference in adjusted mean changes from baseline, along with the corresponding 95% confidence 
intervals, will also be presented.
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To assess the myositis response criteria score over time during the study a longitudinal repeated 
mixed effects model will also be used. The mixed model will include double-blind treatment group 
and randomization stratification factors: disease diagnosis (DM vs. Non-DM), ILD (absent vs 
present), Region (Japan vs ROW), time (study days in which MRC is measured) and time by 
treatment interactions as fixed effects and subject as a random effect. Adjusted mean difference, 
SE, 95% CI for adjusted mean difference between treatment groups will be provided. The estimate 
of mean post-baseline MRC total improvement score will be also summarized by double-blind 
treatment group and visit.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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post-baseline MDI, and adjusted mean change from baseline MDI score will be also be presented 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.7
Safety
Unless otherwise specified, the same safety analyses for the Week 24 analysis will be performed 
for AEs that occurred during the open-label / open-label extension / long-term extension periods. 
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Additional analyses will also be provided for the cumulative Abatacept period in subjects who 
received at least one dose of Abatacept at any time during the study. The analyses in addition to 
the safety analyses for Week 24 analysis described in Section 7.6 are explicitly summarized in the 
following:
•
Incidence rates by 3-month intervals for SAEs, pre-specified infections and adverse events of 
interest (Infections, Malignancy, Autoimmune disorders) will be provided for cumulative 
abatacept period.
•
Multiple events will be reported based on unique AEs for each specific preferred term. For 
each subject and preferred term, a single record (unique AE) is used to represent multiple AEs 
when:
−
Multiple AE records have the same onset date.
−
The onset date of an event record is either the same day or 1 day later than the resolution 
date of a preceding event record (continuous events).
−
The onset date of an event record is after the onset date and prior to or on the resolution 
date of a preceding event record (overlapping events).
The unique AE record contains the earliest onset date, latest resolution date (if available), highest 
intensity, latest relationship, the most severe adverse event type (i.e., the SAE if ever reported as 
SAE), treatment required (will be yes if ever required) and highest action taken in the following 
order (highest to lowest): drug discontinued, drug interrupted, dose reduced, dose increase, none.
Multiple events will be presented for the cumulative abatacept period based on subjects who 
received at least one dose of abatacept at any time during the study.
Exposure adjusted (per 100 person-years) incidence rates of adverse events accounting for multiple 
occurrence of an event will be calculated for all AEs/SAEs which occurred during the open-label
/ open-label extension / long-term extension periods in abatacept treated subjects. The numerator 
is the number of unique events within the open-label / open-label extension / long-term extension 
periods (up to 56 days post last abatacept dose during the open-label / open-label extension / long-
term extension periods). The denominator is the overall total exposure (person-years) within each
period, which is calculated as the sum over all subjects of exposure (in days) divided by 365.25. 
The resulting incidence rate is multiplied by 100 to express the rate per 100 person-years.
As an example, if 10 patients report 7 unique episodes of headache and had a combined cumulative 
exposure of 20 years to study medication, the incidence rate is reported as 7 / 20 * (100) or 35
cases per 100 patient years of exposure.
For all SAEs, exposure adjusted per 100 person-years rates will be summarized by time-intervals 
in months: 0-3 months, 3-6 months, 7-9 months, 10-12 months and > 12 months (time-intervals 
defined as Days 1-90, Days 91-180, Days 181-270, 271-360 and > 360 Days), respectively. In 
addition, the number of subjects who experienced a SAE, once or multiple times within this period 
will be presented. The above analyses will be performed for infection and local injection site 
reaction, respectively. A subject listing of unique AEs will also be provided.
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