An Open-label Single-arm Multicenter Study to Evaluate Usability of a Subcutaneous (SC) Autoinjector (AI) for a Proposed Adalimumab Biosimilar (M923) in Subjects With Moderate to Severe Rheumatoid Arthritis (RA)
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Sponsor: Momenta Pharmaceuticals, Inc.

CLINICAL STUDY PROTOCOL
PRODUCT: M923
STUDY TITLE: An open-label single-arm multicenter study to evaluate usability of 
a subcutaneous (SC) autoinjector (AI) for a proposed adalimumab biosimilar 
(M923) in subjects with moderate to severe rheumatoid arthritis (RA)
STUDY SHORT TITLE: Usability of an AI for M923 in subjects with moderate to 
severe RA
PROTOCOL IDENTIFIER: 911502
CLINICAL TRIAL PHASE 3
AMENDMENT 1: 2016 AUG 26
Replaces: Original: 2016 JAN 29
ALL VERSIONS: 
Amendment 1: 2016 AUG 26
Original: 2016 JAN 29
OTHER ID(s)
NCT Number: NCT02722044
IND NUMBER: 115119
Study Sponsor(s):
Baxalta US Inc.
One Baxter Way
Westlake Village, CA  91362, 
UNITED STATES
Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna, 
AUSTRIA

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1. STUDY PERSONNEL
1.1 Authorized Representative (Signatory) / Responsible Party
, MD
Vice President, Clinical Development
Baxalta US Inc.
1.2 Study Organization
The name and contact information of the responsible party and individuals involved with 
the study (eg, investigator(s), Sponsor’s medical expert and study monitor, Sponsor’s 
representative(s), laboratories, steering committees, and oversight committees [including 
ethics committees (ECs)], as applicable) will be maintained by the Sponsor and provided 
to the investigator.
PPD

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2. SERIOUS ADVERSE EVENT REPORTING
The investigator will comply with applicable laws/requirements for reporting serious 
adverse events (SAEs) to the ECs. 
ALL SAEs, INCLUDING SUSARs, ARE TO BE REPORTED ON THE SERIOUS 
ADVERSE EVENT REPORT (SAER) FORM AND TRANSMITTED TO THE 
SPONSOR WITHIN 24 HOURS AFTER BECOMING AWARE OF THE EVENT.
Drug Safety contact information: see SAE Report Form. 
Refer to SAE Protocol Sections and the study team roster for further information.
For definitions and information on the assessment of these events, refer to the following:

Adverse event (AE), Section 12.1

SAE, Section 12.1.1.1

SUSARs, Section 12.1.1.2

Assessment of AEs, Section 12.1.2

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3. SYNOPSIS
INVESTIGATIONAL PRODUCT
Name of Investigational Product 
(IP)
M923, a proposed adalimumab biosimilar
Name of Active Ingredient
Adalimumab
CLINICAL CONDITION/INDICATION
!
Rheumatoid arthritis (RA)
PROTOCOL ID
911502
PROTOCOL TITLE
An open-label single-arm multicenter study to evaluate usability of a 
subcutaneous (SC) autoinjector (AI) for a proposed adalimumab 
biosimilar (M923) in subjects with moderate to severe rheumatoid 
arthritis (RA)
Short Title
Usability of an AI for M923 in subjects with moderate to severe RA
STUDY PHASE
Phase 3
PLANNED STUDY PERIOD
Initiation
2016 Q1
Primary Completion
2016 Q3
Study Completion
2017 Q1
Duration
Up to 32 weeks
STUDY OBJECTIVES AND PURPOSE
Study Purpose
The purpose of this study is to evaluate the usability of an AI for the delivery of M923 in patients with RA.
Primary Objective
Evaluate the usability of the AI as assessed by the subject using the PRE- and POST-Self-Injection 
Assessment Questionnaire (SIAQ) questionnaire.
Secondary Objectives
1. Evaluate the usability of the AI as assessed by observer rating of successful, hazard-free
self-injection as assessed by the observer assessment checklist
2. Evaluate the safety (including immunogenicity) and tolerability of M923
STUDY DESIGN
Study Type/ Classification/ 
Discipline
Usability, Safety, Immunogenicity
Control Type
No control
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Study Indication Type
Treatment
Intervention model
Single group
Blinding/Masking
Open label
Study Design
This study is an open-label, Phase 3, single-arm, multicenter study to 
evaluate the usability of an AI and safety of M923 targeting a total 
of 32 subjects with active, moderate to severe RA.
Planned Duration of Subject 
Participation
Up to 32 weeks (4-week Screening period, 4-week treatment period, 
20-week treatment extension period, and 4-week safety follow-up
period). Subjects who are inadequate responders, or who withdraw 
early or choose not to continue to the treatment extension period, 
will directly enter the 4-week safety follow-up period; all other 
subjects will enter the safety follow-up period on completion of the 
treatment extension period.
Primary Outcome Measure
Usability of the AI as assessed by the subject ratings captured in the PRE- and POST-SIAQ modules at 
Week 4
Secondary Outcome Measures
Usability
1. Observer assessment of usability by the subjects as determined by (i) ability to successfully follow
the steps in the Instructions for Use (IFU) to self-administer M923 via the AI and (ii) investigation 
of the frequency of observed or reported difficulties (‘potential hazards’) at Week 4 as well as 
change over time
2. Evaluations at Baseline and Week 2 for subject and observer assessments, as well as change over
time
Safety
1. Clinical safety and tolerability of M923 as assessed by vital signs, clinical laboratory results,
electrocardiograms (ECGs), and adverse events (AEs) (including serious adverse events [SAEs], 
AEs leading to premature withdrawal, and injection site reactions)
2. Immunogenicity of M923 assessed as proportion of subjects with evidence of seroconversion as
measured by titer of anti-drug antibody (ADA) levels over time, and proportion of subjects with
neutralizing ADAs (nADAs)
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INVESTIGATIONAL PRODUCT, DOSE AND MODE OF ADMINISTRATION
Active Product
M923, a proposed adalimumab biosimilar
Dosage form: 40 mg (0.8 mL) AI (Treatment Period)
Dosage frequency: Every 2 weeks (Q2W)
AI: 40 mg Q2W at Baseline/Day 1, Day 15 ±3 days and 
Day 29 ±3 days (Visits 2 to 4)
Mode of Administration: SC
SUBJECT SELECTION
Targeted Accrual
32 subjects enrolled from sites in the United States (US), to achieve 
30 evaluable subjects, 
Number of Groups/Arms/Cohorts
1
Inclusion Criteria
1. Subjects ≥18 years old at the time of Screening
2. Able to understand and communicate with the investigator and comply with the requirements of the
study, and must give a written, signed and dated informed consent before any study related activity
is performed.
3. RA diagnosed for at least 6 months before Screening
4. Meets classification criteria for RA by 2010 American College of Rheumatology/European League
Against Rheumatism criteria
5. Active disease defined as both DAS28-C-reactive protein (CRP) >3.2 at Screening and 4 swollen
and tender joints each on a 66/68 joint count at Screening and Baseline
6. Subjects must have at least 1 documented swollen and/or tender joint in their hand or wrist of the
dominant hand as assessed by the investigator or designated assessor
7. Must be willing and able to attempt self-administration of SC injection(s)
8. Male subjects must be willing to abstain from sexual intercourse or be willing to use a condom in
addition to having their female partner use another form of contraception such as an intra-uterine
device, barrier method (eg, diaphragm or sponge; female condom not permitted) with spermicide,
oral contraceptive, injectable progesterone, sub-dermal implant, unless their partners are infertile or
surgically sterile from the time of the first administration of IP until 3 months after the last dose, or
have been vasectomized with confirmation of sterility
9. Female subjects must have a negative pregnancy test at Screening and on admission to the clinic and
must not be lactating. Female subjects must also agree to or be one of the following for the duration
of the study until 5 months after the last dose:
a. Abstain from sexual intercourse –OR–
b. Use a method of contraception, as described in Inclusion Criterion 8, and to have their male
partner use a condom –OR–
c. Of non-childbearing potential, confirmed at Screening by fulfilling one of the following criteria:
i.
Post-menopausal, defined as amenorrhea for at least 12 months following cessation of all
exogenous hormonal treatments and with follicle-stimulating hormone (FSH) levels within
the laboratory defined post-menopausal range
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ii.
If they do not meet the previous criterion (c.i.), due to use of exogenous hormonal
treatment, they must be over 55 years of age and have had documented amenorrhea for at
least 2 years
iii.
Documentation of irreversible surgical sterilization by hysterectomy, bilateral
oophorectomy, bilateral tubal ligation (BTL; with no subsequent pregnancy at least 1 year
from BTL) or bilateral salpingectomy
Exclusion Criteria
1. Prior use of systemic tumor necrosis factor (TNF) inhibitor therapy, including other investigational
or licensed biosimilar TNF inhibitor therapies
2. Prior use of rituximab
3. Prior use of abatacept, tocilizumab, and tofacitinib within 4 weeks prior to Screening
4. Current use of a conventional disease-modifying anti-rheumatic drug (DMARD) other than the
following: methotrexate orally (≤25 mg/day), hydroxychloroquine (≤400 mg/day) or sulfasalazine
(≤3 g/day) at a stable dose for at least 4 weeks prior to Screening. If discontinued, methotrexate,
hydroxychloroquine, and sulfasalazine must have been discontinued at least 4 weeks prior to
Baseline. No other conventional DMARDs are permitted and no combination therapy is permitted.
5. Prior use of cytotoxic or alkylating agents such as, but not limited to, chlorambucil,
cyclophosphamide or immunosuppressants such as cyclosporine, tacrolimus, mycophenolate, and
azathioprine must have been discontinued for at least 90 days prior to Baseline
6. Current use of oral corticosteroids at a dose >10 mg/day prednisone or equivalent or change of dose
within 2 weeks prior to Screening
7. Current use of more than 1 nonsteroidal anti-inflammatory drug. Doses used should not be greater
than the maximum permitted per product labeling or dosing has been changed within 2 weeks prior
to Baseline.
8. Prior use of injectable corticosteroids (intramuscular [IM], intra-articular [IA], or intravenous [IV])
within 6 weeks prior to Baseline
9. Prior or current use of other self-injected drugs, eg, insulin
10. All other prior non-RA concomitant treatments must be on a stable dose for at least 4 weeks before
Baseline
11. Meets Class IV Steinbrocker criteria for disability/activities of daily living
12. Laboratory abnormalities at Screening deemed clinically significant by the investigator and/or
Sponsor:
a. Hemoglobin <8.5 g/dL for women or 9.0 g/dL for men
b. White blood cell count <3 × 109/L
c. Platelet count <100 × 109/L
d. Aspartate transaminase (AST) or alanine transaminase (ALT) >2 times the upper limit of normal
or bilirubin ≥3 mg/dL
e. Creatinine >1.6 mg/dL if female or >1.8 mg/dL if male
f.
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13. Presence of fibromyalgia (as a primary disease), another autoimmune rheumatologic illness or
inflammatory arthritis, eg, systemic lupus erythematosus, gout. The presence of secondary Sjogren’s
syndrome is permitted. At the discretion of the investigator, a patient with stable and low-grade
fibromyalgia may be included in the study if the fibromyalgia is not a primary disease and will not
interfere with the assessment of RA (specifically in the diagnosis, severity classification,
monitoring, and outcomes).
14. Joint surgery within the last 8 weeks prior to Screening
15. Severe, progressive, or uncontrolled renal, hepatic, metabolic, hematologic, gastrointestinal,
endocrine, pulmonary, cardiac or neurologic disease, including pleural effusions or ascites, which in
the opinion of the investigator would preclude the subject from adhering to or completing the study
or where participation in the study exposes the subject to unfavorable benefit/risk
16. History or presence of signs and/or symptoms or a diagnosis of a demyelinating disorder
17. History or presence of Class III or IV New York Heart Association congestive heart failure
18. History or presence of symptoms suggestive of lymphoproliferative disorders, lymphoma, leukemia,
myeloproliferative disorders, or multiple myeloma
19. Existing malignancy or history of any malignancy except adequately treated or excised
non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ, with no
more than 3 lifetime basal cell or squamous cell carcinomas
20. Chronic infections, recurrent infections (3 or more of the same infection requiring anti-infective
treatment in any rolling 12-month period); any recent infection (ie, in the last 30 days) requiring
hospitalization or any infection requiring parenteral anti-infective therapy within 30 days or oral
infective therapies within 14 days of Baseline; herpes zoster within 6 months of Baseline or more
than 2 lifetime episodes of herpes zoster; or history of systemic fungal infection or opportunistic
infection (eg, coccidioidomycosis, histoplasmosis, toxoplasmosis).
21. History or presence of human immunodeficiency virus (HIV), Hepatitis B or C virus
22. History of active tuberculosis (TB) or untreated or inadequately treated latent TB. Tuberculosis
screening requirements include negative QuantiFERON®; or purified protein derivative (PPD) and
chest imaging (ie, x-ray) within 3 months of Screening
23. Subject has been exposed to an IP within 30 days (or 5 half-lives) prior to enrollment, whichever is
longer, or is scheduled to participate in another clinical study involving an IP or investigational
device during the course of this study
24. Subject is a family member or employee of the investigator or Baxalta or its partners
STATISTICAL ANALYSIS
Sample Size Calculation
Based on discussions with the US Food and Drug Administration, a sample size of 30 was judged to be 
adequate to achieve the objectives of the study.
. Patients dropping out of the study will not be replaced.
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Planned Statistical Analysis
Usability
The primary analysis of usability will be conducted at Week 4 at the end of the 4-week treatment period 
once enrollment is completed. This will trigger the planned interim analysis and interim Clinical Study 
Report, with the database being locked after the last subject completes Week 4. The Clinical Study Report
will be supplemented with the data collected after Week 4 once the last subject completes the last visit.
Descriptive statistics for usability measurements will be presented by timepoint. Continuous responses will 
be summarized using N, mean, SD, median, minimum, and maximum. Categorical responses will be 
summarized by proportions.
Safety
Adverse events will be summarized by preferred term and system organ class. Laboratory, ECG and vital 
signs will be summarized by timepoint using N, mean, standard deviation (SD), minimum, median, and 
maximum.
Efficacy
Pharmacokinetics
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4. TABLE OF CONTENTS
1. STUDY PERSONNEL ................................................................................................. 2
1.1 Authorized Representative (Signatory) / Responsible Party .............................. 2
1.2 Study Organization................................................................................................. 2
2. SERIOUS ADVERSE EVENT REPORTING........................................................... 3
3. SYNOPSIS..................................................................................................................... 4
4. TABLE OF CONTENTS ........................................................................................... 10
5. LIST OF ABBREVIATIONS .................................................................................... 14
6. BACKGROUND INFORMATION .......................................................................... 18
6.1 Description of Investigational Product ............................................................... 18
6.2 Clinical Condition/Indication .............................................................................. 18
6.3 Population to Be Studied...................................................................................... 19
6.4 Findings from Nonclinical and Clinical Studies................................................. 19
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) 
to Human Subjects................................................................................................ 21
6.6 Compliance Statement.......................................................................................... 21
7. STUDY PURPOSE AND OBJECTIVES ................................................................. 22
7.1 Study Purpose ....................................................................................................... 22
7.2 Primary Objective................................................................................................. 22
7.3 Secondary Objectives ........................................................................................... 22
7.3.1 Usability.......................................................................................................... 22
7.3.2 Safety............................................................................................................... 22
8. STUDY DESIGN......................................................................................................... 23
8.1 Brief Summary...................................................................................................... 23
8.2 Overall Study Design............................................................................................ 23
8.3 Duration of Study Period(s) and Subject Participation .................................... 23
8.4 Outcome Measures ............................................................................................... 23
8.4.1 Primary Outcome Measure .......................................................................... 23
8.4.2 Secondary Outcome Measures ..................................................................... 24
8.4.2.1 Usability................................................................................................... 24
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8.4.2.2 Safety........................................................................................................ 24
8.5 Randomization and Blinding............................................................................... 24
8.6 Investigational Product(s).................................................................................... 25
8.6.1 Packaging, Labeling, and Storage................................................................ 25
8.6.2 Administration ............................................................................................... 25
8.6.2.1 Injection Training................................................................................... 25
8.6.3 Description of Treatment.............................................................................. 26
8.6.4 Investigational Product Accountability ....................................................... 26
8.7 Source Data ........................................................................................................... 27
9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION .......... 28
9.1 Inclusion Criteria.................................................................................................. 28
9.2 Exclusion Criteria................................................................................................. 29
9.3 Withdrawal and Discontinuation ........................................................................ 31
10. STUDY PROCEDURES .......................................................................................... 33
10.1 Informed Consent and Enrollment ................................................................... 33
10.2 Subject Identification Code................................................................................ 33
10.3 Screening and Study Visits................................................................................. 33
10.3.1 Screening Assessments ................................................................................ 33
10.3.2 Baseline Assessments................................................................................... 34
10.3.3 Visit 3 (Day 15 ±3 days) Assessments......................................................... 35
10.3.4 Visit 4 (Day 29 ±3 days) Assessments......................................................... 36
10.3.5 Treatment Extension Period Assessments................................................. 37
10.3.6 Safety follow-up ........................................................................................... 38
10.4 Medications and Non-Drug Therapies.............................................................. 38
10.5 Subject Diary and Patient-reported Outcomes................................................ 40
10.6 Subject Completion/Withdrawal....................................................................... 40
10.7 Procedures for Monitoring Subject Compliance............................................. 41
11. ASSESSMENT OF USABILITY, EFFICACY AND PHARMACOKINETICS 42
11.1 Primary Usability Assessment ........................................................................... 42
11.2 Secondary Usability Assessments...................................................................... 42
11.3 Immunogenicity Assessment.............................................................................. 42
12. ASSESSMENT OF SAFETY................................................................................... 45
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12.1 Adverse Events.................................................................................................... 45
12.1.1 Definitions..................................................................................................... 45
12.1.1.1 Serious Adverse Event.......................................................................... 45
12.1.1.2 Suspected Unexpected Serious Adverse Reaction (SUSAR)............. 46
12.1.1.3 Non-Serious Adverse Event ................................................................. 46
12.1.1.4 Unanticipated Adverse Device Effect ................................................. 46
12.1.1.5 Unexpected Adverse Events................................................................. 46
12.1.1.6 Pre-existing Diseases............................................................................. 47
12.1.2 Assessment of Adverse Events.................................................................... 47
12.1.2.1 Severity .................................................................................................. 48
12.1.2.2 Causality................................................................................................ 49
12.1.2.3 Safety Reporting ................................................................................... 49
12.1.3 Medical Device Safety reporting ................................................................ 50
12.2 Urgent Safety Measures ..................................................................................... 51
12.3 Untoward Medical Occurrences........................................................................ 51
12.4 Non-Medical Complaints ................................................................................... 52
12.5 Medical, Medication, and Non-Drug Therapy History................................... 52
12.6 Physical Examinations........................................................................................ 53
12.7 Clinical Laboratory Parameters........................................................................ 53
12.7.1 Hematology and Clinical Chemistry.......................................................... 54
12.7.2 Urinalysis...................................................................................................... 54
12.7.3 Assessment of Laboratory Values .............................................................. 54
12.7.3.1 Assessment of Abnormal Laboratory Values..................................... 54
12.7.4 Biobanking-Study Sample Storage ............................................................ 55
12.8 Vital Signs............................................................................................................ 55
12.9 Electrocardiograms ............................................................................................ 56
12.10 Local Injection Site Reaction Evaluation ....................................................... 56
13. STATISTICS............................................................................................................. 58
13.1 Sample Size and Power Calculations ................................................................ 58
13.2 Datasets and Analysis Cohorts .......................................................................... 58
13.3 Handling of Missing, Unused, and Spurious Data........................................... 58
13.4 Methods of Analysis............................................................................................ 58
13.4.1 Primary Outcome Measure......................................................................... 58
13.4.2 Secondary Outcome Measures ................................................................... 59
13.5 Planned Interim Analysis of the Study ............................................................. 60
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .................................... 60
15. QUALITY CONTROL AND QUALITY ASSURANCE...................................... 61
15.1 Investigator’s Responsibility.............................................................................. 61
15.1.1 Final Clinical Study Report........................................................................ 61
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15.2 Training ............................................................................................................... 61
15.3 Monitoring........................................................................................................... 61
15.4 Auditing ............................................................................................................... 61
15.5 Non-Compliance with the Protocol ................................................................... 62
15.6 Laboratory and Reader Standardization ......................................................... 62
16. ETHICS ..................................................................................................................... 63
16.1 Subject Privacy ................................................................................................... 63
16.2 Ethics Committee and Regulatory Authorities................................................ 63
16.3 Informed Consent ............................................................................................... 63
16.4 Data Monitoring Committee.............................................................................. 64
17. DATA HANDLING AND RECORD KEEPING................................................... 65
17.1 Confidentiality Policy ......................................................................................... 65
17.2 Study Documentation and Case Report Forms ............................................... 65
17.3 Document and Data Retention........................................................................... 65
18. FINANCING AND INSURANCE........................................................................... 66
19. PUBLICATION POLICY........................................................................................ 66
20. SUPPLEMENTS....................................................................................................... 67
20.1 Study Flow Chart................................................................................................ 67
20.2 Schedule of Study Procedures and Assessments.............................................. 68
20.3 Clinical Laboratory Assessments ...................................................................... 71
20.5 Self-Injection Assessment Checklist.................................................................. 74
20.6 Potential Hazards Checklist............................................................................... 75
21. REFERENCES.......................................................................................................... 77
22. SUMMARY OF CHANGES.................................................................................... 78
INVESTIGATOR ACKNOWLEDGEMENT.............................................................. 84
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Tables
Table 1 Injection Site Reaction Grading Scheme............................................................ 57
Table 2 Schedule of Study Procedures and Assessments................................................ 68
Table 3 Clinical Laboratory Parameters .......................................................................... 71
Figures
Figure 1 Study Design for Baxalta Clinical Study 911502.............................................. 67

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5. LIST OF ABBREVIATIONS
Abbreviation
Definition
ACPA
anti-citrullinated protein antibody
ADA
anti-drug antibody
AE
adverse event
AI
autoinjector
ALT
alanine aminotransferase
ANA
anti-nuclear antibody
anti-dsDNA
anti-double-stranded DNA
AST
aspartate aminotransferase
AUC
area under the curve
BTL
bilateral tubal ligation
CI
confidence interval
Cmax
maximum concentration
CRF
case report form
CRP
C-reactive protein
CTA
Clinical Trial Agreement
DAS28
Disease Activity Score in 28 joints
DMARDs
disease-modifying anti-rheumatic drugs
DMC
data monitoring committee
DNA
deoxyribonucleic acid
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
EDV
early discontinuation visit
EU
European Union
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
HbA1c
glycosylated hemoglobin
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Abbreviation
Definition
Continued
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IA
intra-articular
IB
Investigator's brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IFU
instructions for use
IgG1
immunoglobulin G subclass 1
IgM
immunoglobulin M
IM
intramuscular
IP
investigational product
IV
intravenous
IVRS
interactive voice response system
IWRS
interactive web response system
LTBI
latent TB infection
MTX
methotrexate
nADA
neutralizing anti-drug antibody
NMC
non-medical complaint
PA
posteroanterior
PGA
Patient Global Assessment
PK
pharmacokinetic
PPD
purified protein derivative
PRO
patient-reported outcome
Q2W
every 2 weeks
RA
rheumatoid arthritis
RF
rheumatoid factor
RSI
Reference Safety Information
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Abbreviation
Definition
Continued
SAE
serious adverse event
SAER
Serious Adverse Event Report
SC
subcutaneous
SD
standard deviation
SI
serious injuries
SIAQ
Self-injection Assessment Questionnaire
SIC
subject identification code
SUSAR
suspected unexpected serious adverse reaction
TB
Tuberculosis
TEAE
Treatment-emergent adverse event
TNF-α
tumor necrosis factor-alpha
UADE
unanticipated adverse device effect
US
United States
v
version

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6. BACKGROUND INFORMATION
6.1 Description of Investigational Product
M923 (BAX2923) is a proposed similar biological medical product (hereafter referred to 
as “proposed biosimilar”) to HUMIRA® (adalimumab, AbbVie, Inc.; hereafter referred to 
as “Humira”). Adalimumab is a recombinant human immunoglobulin G subclass 1 
(IgG1) monoclonal antibody specific for human tumor necrosis factor–alpha (TNF-α). 
Unlike etanercept, adalimumab does not bind to tumor necrosis factor–beta. Adalimumab 
was first approved by the United States (US) Food and Drug Administration in 2002 for 
treatment of rheumatoid arthritis (RA) and, later, for several other inflammatory 
conditions and has since been used widely, including in many large clinical studies. 
Hence, its effectiveness, tolerability, and safety are well established.
M923 is produced by recombinant deoxyribonucleic acid (DNA) technology in a 
.
 
 
 
 
 
 
 
 
 
 
6.2 Clinical Condition/Indication
The medical need for a biosimilar to Humira (adalimumab) is demonstrated with the 
approval and use of the originator product Humira and its place in the treatment of 
several chronic autoimmune or inflammatory diseases, including RA, juvenile idiopathic 
arthritis, psoriatic arthritis, ankylosing spondylitis, adult and pediatric Crohn’s disease, 
ulcerative colitis, hidradenitis suppurativa, and adult and pediatric plaque psoriasis.
Rheumatoid arthritis is a chronic autoimmune disease associated with approximately 
symmetrical inflammation of the joints of the hands and feet, leading to joint destruction, 
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and paraproteinemia (“rheumatoid factor”). The condition is associated with increased 
morbidity and mortality from all causes, and requires long-term treatment.2;3;4
Medication administered via SC injection offers the option of self-administration, 
providing benefits for the patient and healthcare system.5 Patients with chronic diseases,
such as RA, who are able to self-inject their medication gain control of their treatment 
schedule (within the limits of the product label) and treatment setting, thus improving 
their treatment experience.5 However, there are barriers to self-injection, including 
dexterity problems and injection anxiety, which can prevent self-injection being used 
successfully and lead to lower treatment adherence.5 This study seeks to evaluate 
usability of a SC AI for M923 in subjects with active, moderate to severe RA.
6.3 Population to Be Studied
The study will enroll 32 subjects with active, moderate to severe RA. Adult (≥18 years) 
male and female subjects will be considered to be eligible provided that they satisfy all of 
the eligibility criteria listed in Section 9.1 and Section 9.2.
6.4 Findings from Nonclinical and Clinical Studies
M923 has been characterized and compared with US- and European Union (EU)-sourced 
Humira using a battery of nonclinical in vitro assays, as well as an in vivo 
pharmacokinetics (PK) study in mice, and a PK and immunogenicity study in 
cynomolgus monkeys. The results of the pharmacology, PK, and immunogenicity 
assessments demonstrated similar biological activity of M923 and Humira. Specifically, 
the results indicated that M923 was similar to Humira in terms of binding activity for 
soluble human TNF-α, the human Fcγ receptor, human C1q complex, and the human 
neonatal Fc receptor; activity in the antibody-dependent cell-mediated cytotoxicity and 
complement-dependent cytotoxicity assays; potency in the L929 mouse fibroblast cell 
line assay; in vivo single-dose PK profile in mice and cynomolgus monkeys; and 
immunogenicity (in vivo in cynomolgus monkeys and ex vivo T-cell proliferation in 
human dendritic cells).
The PK profiles, safety, tolerability, and immunogenicity of M923, US Humira and 
EU Humira PK of M923 were evaluated in healthy volunteers in a Phase 1, randomized, 
double-blind, 3-arm, parallel-group, single-dose clinical study (Study #911301). Subjects 
received a single dose (40 mg) of M923 or Humira (US Reference Product or EU 
Reference Protein Product) and were followed-up for 71 days. Overall 324 healthy 
subjects were randomized and treated. All randomized subjects completed the study.

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Mean serum concentration-time profiles for M923 (n=107), EU Humira (n=103), and 
US Humira (n=105) were similar in the primary PK analysis set of subjects. Median time 
to maximum concentration was 144.000 hours for M923 and EU Humira and 
141.780 hours for US Humira. Geometric mean half-life was 311, 319, and 313 hours for 
M923, EU Humira, and US Humira, respectively. The geometric least-squares mean 
ratios for the primary PK parameters [Cmax (maximum concentration), AUC(area under 
the curve)(0-inf), and AUC(0-336)] and secondary PK parameters [AUC(0-672), AUC(0-840), 
AUC(0-1008), AUC(0-1344), and AUC(0-last)] were fully contained within the 90% 
confidence interval (CI) bounds of 80.00% to 125.00% for all treatment pairings. The 
secondary analyses performed utilizing PK analysis subsets based on immunogenicity 
designations (anti-drug antibody [ADA] PK analysis set and non-ADA PK analysis set; 
neutralizing ADA [nADA] PK analysis set and non-nADA PK analysis set) supported the 
primary analysis results.
Adalimumab exposure was weakly correlated with formation of confirmed ADAs and/or 
nADAs in subjects with low confirmed ADA titers. Review of individual adalimumab 
versus concentration time profiles did not reveal a consistent relationship between time of 
appearance of ADA or nADAs and time of last quantifiable adalimumab concentrations 
or with shape of the terminal phase in subjects with low titers at low titers (<1:8). ADAs
with higher titers which appeared earlier after administration tended to be associated with 
a shorter time to last quantifiable concentration and elimination half-life. These 
observations appeared to be independent of treatment.
There appeared to be a relationship of lower overall exposure (AUC) and half-life and 
higher apparent clearance (CL/F) in the presence of ADAs compared to absence of ADAs 
(ADA versus non-ADA population) and in the presence of nADAs compared to absence 
of nADAs (nADA versus non-nADA population). It should be noted that these apparent 
ADA-correlated differences were independent of treatment (M923, US Humira, or 
EU Humira).
The overall incidence of ADA and nADA was comparable in each group (78.0% and 
16.5%, respectively, for subjects on M923; 78.5% and 20.6% for EU Humira and 80.6% 
and 27.8% for US Humira).
In this study (Study #911301), M923, US Humira, and EU Humira were safe and well 
tolerated in the healthy subjects. No subjects died or withdrew from the study due to an 
AE. One subject reported SAEs of foot fracture, wound infection, and laceration as a 
result of trauma. All 3 events were assessed by the investigator as not related to study 
treatment. The percentage of subjects with at least 1 AE was comparable among the 

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3 treatment arms, ranging from 47.7% to 53.3%. Most of the AEs were considered mild 
and unrelated to treatment by the investigators. The number of subjects with severe AEs 
was low. Injection site reactions were mostly mild. No clinically significant trends over 
time or between the 3 treatment arms were observed in mean and median laboratory 
variables, vital signs measurements, and 12-lead electrocardiogram (ECG) results.
Thus, bioequivalence was demonstrated for all primary treatment comparisons 
(M923/US Humira; M923/EU Humira; EU Humira/US Humira) in Study# 911301. 
M923 was demonstrated to be well-tolerated and to have a safety profile comparable with 
those of EU Humira and US Humira after a single dose.
6.5 Evaluation of Anticipated Risks and Benefits of the Investigational Product(s) to 
Human Subjects
All risks, contraindications, precautions, dosage and administration considerations, drug 
interactions and overdose considerations that have been described for Humira apply to 
M923 (see Section 9.2 of the Investigator’s Brochure [IB] for M923). The safety profile 
of M923 is anticipated to be similar to that of Humira; however, investigators should 
carefully monitor for all AEs, including AEs not described as associated with Humira.
6.6 Compliance Statement
This study will be conducted in accordance with this protocol, the International Council 
for Harmonisation Guideline for Good Clinical Practice E6 (ICH GCP, April 1996), 
Title 21 of the US Code of Federal Regulations, the European Clinical Trial Directive 
(2001/20/EC and 2005/28/EC), and applicable national and local regulatory 
requirements.

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7. STUDY PURPOSE AND OBJECTIVES
7.1 Study Purpose
The purpose of this study is to evaluate the usability of an AI for the delivery of M923 in 
patients with RA.
7.2 Primary Objective
The primary objective of the study is to evaluate the usability of the AI as assessed by the 
subject.
7.3 Secondary Objectives
7.3.1 Usability
!
Evaluate the usability of the AI as assessed by observer rating of successful,
hazard-free self-injection as assessed by the observer assessment checklist
7.3.2 Safety
!
Evaluate the safety (including immunogenicity) and tolerability of M923
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8. STUDY DESIGN
8.1 Brief Summary
The proposed biosimilar M923 will be provided in a form for administration via an AI for 
SC self-injection in subjects with active, moderate to severe RA. The study purpose is to 
demonstrate that the AI demonstrates adequate usability.
8.2 Overall Study Design
This study is an open-label, Phase 3, single-arm, multicenter study to evaluate the 
usability of an AI and safety of M923 targeting a total of 32 subjects with active,
moderate to severe RA. The overall study design is illustrated in Figure 1.
8.3 Duration of Study Period(s) and Subject Participation
The overall duration of the study is up to 10 months from study initiation (ie, first subject 
enrolled) to study completion (ie, last subject last visit). The recruitment period is 
expected to be 4 months.
The planned duration of subject participation from enrollment to study completion for 
each subject (ie, last study visit), is up to 32 weeks (4-week Screening period, 4-week 
treatment period, 20-week treatment extension period, and 4-week safety follow-up 
period). Subjects who are considered inadequate responders, or who withdraw early or 
choose not to continue to the treatment extension period will continue for a 4-week safety 
follow-up period. All other subjects will enter the safety follow-up period on completion 
of the treatment extension period. An inadequate response is defined as a 
<20% improvement in the swollen joint count and tender joint count from Baseline to 
Week 12. Subjects with an inadequate response will be counseled about their treatment 
options and discontinue treatment at the Week 14 Visit.
8.4 Outcome Measures
8.4.1 Primary Outcome Measure
The primary outcome measure is usability of the AI as assessed by the subject ratings 
captured in the PRE- and POST-Self-injection Assessment Questionnaire (SIAQ) 
modules at Week 4 (see Section 20.4).

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8.4.2 Secondary Outcome Measures
8.4.2.1 Usability
1.
Observer assessment of usability by the subjects as determined by (i) ability to
successfully follow the steps in the Instructions for Use (IFU) to self-administer
M923 via the AI and (ii) investigation of the frequency of observed or reported
difficulties (‘potential hazards’) at Week 4 as well as change over time (see
Sections 20.4 and 20.6).
2.
Evaluations at Baseline and Week 2 for subject and observer assessments, as well
as change over time
8.4.2.2 Safety
1.
Clinical safety and tolerability of M923 as assessed by vital signs, clinical
laboratory results, ECGs, and AEs (including SAEs, AEs leading to premature
withdrawal, and injection site reactions)
2.
Immunogenicity of M923 assessed as proportion of subjects with evidence of
seroconversion as measured by titer of ADA levels over time, and proportion of
subjects with nADAs
8.5 Randomization and Blinding
This is a non-randomized, open-label, single-arm clinical study.
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8.6 Investigational Product(s)
8.6.1 Packaging, Labeling, and Storage
The investigational product (IP) for this study is M923, which is a clear, colorless, sterile 
solution for SC injection. M923 is supplied as an AI dosage form. This dosage form is a
single-use with a 1 mL capacity, which delivers 40 mg (0.8 mL) of M923 drug substance 
(proposed biosimilar adalimumab). 
 
 
 M923 for injection will be supplied by Baxalta or representative, and stored in 
compliance with Good Manufacturing Practice conditions and labeled in accordance with 
local regulations.
A sufficient quantity of 1.0 mL AIs (containing 0.8 mL as described above) containing 
40 mg M923 will be supplied to each study site by Fisher Clinical Services. Fisher will 
package and label the M923 AIs, which will be released by a Qualified Person at Fisher 
to each study site.
Individual subject treatment will be dispensed at each study site labeled in accordance 
with Good Manufacturing Practice Annex 13 requirements.
All IP should be stored in a refrigerator at to °C in the original container, protected 
from light, in a secure, temperature-controlled, locked environment with restricted access. 
Do not freeze and do not use if frozen, even if it has been thawed.
The Sponsor will be permitted upon request to audit the supplies, storage, dispensing 
procedures, and records provided that the blind of the study is not compromised.
8.6.2 Administration
M923 in AI (as supplied) will be administered via SC injection to the lower abdomen or 
thigh. There are no special requirements regarding food with respect to dosing. 
Administration is recommended to be on the same day Q2W (±3 days at Visits 2 to 
4 and ±3 days at Visits 5 to 14) and at the same time of day. Directions for use materials 
will be provided.
8.6.2.1 Injection Training
Study staff will train subjects on the SC injection procedure for the AI dosage form.
Self-injection training should be provided at Baseline (Week 0, Visit 2) prior to the first 
injection. Site staff will show the subject how to self-administer IP using the AI and 
subjects will perform their first injection under observation in the clinic. The training and 
performance of self-injection will be documented in the subject’s source documents. 
C
C
C
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If the subject requests it, additional training can be provided at Visit 3 (Week 2) prior to 
the second injection. The subject should perform the injection at Weeks 2 and 4 (Visits 3 
and 4) under observation in the clinic. Site staff should observe the injection at Weeks 0, 
2 and 4 (Visits 2 to 4) to ensure it is being performed correctly and provide re-training as 
necessary, indicated by a subject request for additional training.
Subjects are to be instructed that used AIs must be placed in a safety container provided 
by the Sponsor. This safety container should be returned to the investigational site for 
disposal once full or at the end of the study.
8.6.3 Description of Treatment
Subjects will self-administer 40 mg of M923 Q2W starting at the Baseline Visit 2.
Self-injection should occur on the same day each treatment week (±3 days at Visits 3 and
4 and could be ±3 days at Visits 5 to 14) targeting the same time of day. At Baseline and 
Weeks 2 and 4 (Visits 2 to 4), injections will be administered by the subject using the AI 
under the observation of the study site staff in the clinic after all required assessments and 
blood sample collections have been completed. Subjects should be observed for 2 hours 
post-injection at Baseline and Week 2 and for 30 minutes post-injection at Week 4. 
At any time during the study, the IP may be interrupted or discontinued at the discretion 
of the investigator based on his/her evaluation of the subject’s condition or safety. No 
dose modification is permitted for this study.
Any injection site reactions, regardless of causality, will be recorded on the AE case 
report form (CRF). Any concomitant medications, including those used to treat AE(s), 
will be recorded on the appropriate CRF.
8.6.4 Investigational Product Accountability
The investigator will ensure that the IP is stored as specified in the protocol and that the 
storage area is secured, with access limited to authorized study personnel. The 
investigator will maintain records that the IP was received, including the date received, 
drug identity code, date of manufacture or expiration date, amount received, and 
disposition. Investigational Product must be dispensed only at the study site. Records will 
be maintained that include the subject identification code (SIC), dispensation date, and 
amount dispensed. All remaining partially used and/or unused IP will be returned to the 
Sponsor or Sponsor’s representative after study completion/termination, or destroyed 
with the permission of the Sponsor in accordance with applicable laws and study site 
procedures. If IP is to be destroyed, the investigator will provide documentation in 
accordance with Sponsor’s specifications.

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8.7 Source Data
Per ICH GCP, source data are defined as all information in original records and certified 
copies of original records of clinical findings, observations, or other activities in a clinical 
study that are necessary for the reconstruction and evaluation of the study. Source data 
are contained in source documents (original records or certified copies), which may be in 
paper and/or electronic format. Source data for this study comprise the following: 
hospital records, medical records, clinical and office charts, laboratory notes, 
memoranda, subjects' diaries or evaluation checklists, outcomes reported by subjects, 
pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, subject files, and records 
kept at the pharmacy, at the laboratories and at medico-technical departments involved in 
the clinical study.
For additional information on study documentation and CRFs, see Section 17.2. The use 
of subject diaries is described in Section 10.5.

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9. SUBJECT SELECTION, WITHDRAWAL, AND DISCONTINUATION
9.1 Inclusion Criteria
Subjects who meet ALL of the following criteria are eligible for this study:
1.
Subjects ≥18 years old at the time of Screening
2.
Able to understand and communicate with the investigator and comply with the
requirements of the study, and must give a written, signed and dated informed
consent before any study related activity is performed
3.
RA diagnosed for at least 6 months before Screening
4.
Meets classification criteria for RA by 2010 American College of
Rheumatology/European League Against Rheumatism criteria
5.
Active disease defined as both DAS28-CRP >3.2 at Screening and 4 swollen and
tender joints each on a 66/68 joint count at Screening and Baseline
6.
Subjects must have at least 1 documented swollen and/or tender joint in their
hand or wrist of the dominant hand as assessed by the investigator or designated
assessor
7.
Must be willing and able to attempt self-administration of SC injection(s)
8.
Male subjects must be willing to abstain from sexual intercourse or be willing to
use a condom in addition to having their female partner use another form of
contraception such as an intra-uterine device, barrier method (eg, diaphragm or
sponge; female condom not permitted) with spermicide, oral contraceptive,
injectable progesterone, sub-dermal implant, unless their partners are infertile or
surgically sterile from the time of the first administration of IP until 3 months
after the last dose, or have been vasectomized with confirmation of sterility
9.
Female subjects must have a negative pregnancy test at Screening and on
admission to the clinic and must not be lactating. Female subjects must also agree
to or be one of the following for the duration of the study until 5 months after the
last dose:
a. Abstain from sexual intercourse –OR–
b. Use a method of contraception, as described in Inclusion Criterion 8, and to
have their male partner use a condom –OR–
c. Of non-childbearing potential, confirmed at Screening by fulfilling one of the
following criteria:
i.
Post-menopausal, defined as amenorrhea for at least 12 months following
cessation of all exogenous hormonal treatments and with

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follicle-stimulating hormone (FSH) levels within the laboratory defined 
post-menopausal range
ii.
If they do not meet the previous criterion (c.i.), due to use of exogenous
hormonal treatment, they must be over 55 years of age and have had
documented amenorrhea for at least 2 years
iii.
Documentation of irreversible surgical sterilization by hysterectomy,
bilateral oophorectomy, bilateral tubal ligation (BTL; with no subsequent
pregnancy at least 1 year from BTL) or bilateral salpingectomy
9.2 Exclusion Criteria
Subjects who meet ANY of the following criteria are not eligible for this study:
1.
Prior use of systemic TNF inhibitor therapy, including other investigational or
licensed biosimilar TNF inhibitor therapies
2.
Prior use of rituximab
3.
Prior use of abatacept, tocilizumab and tofacitinib within 4 weeks prior to
Screening
4.
Current use of a conventional disease modifying anti-rheumatic drugs (DMARD)
other than the following: methotrexate orally (≤25 mg/day), hydroxychloroquine
(≤400 mg/day) or sulfasalazine (≤3 g/day) at a stable dose for at least 4 weeks
prior to Screening. If discontinued, methotrexate, hydroxychloroquine, and
sulfasalazine must have been discontinued at least 4 weeks prior to Baseline. No
other conventional DMARDs are permitted and no combination therapy is
permitted.
5.
Prior use of cytotoxic or alkylating agents such as, but not limited to,
chlorambucil, cyclophosphamide, or immunosuppressants such as cyclosporine,
tacrolimus, mycophenolate, and azathioprine must have been discontinued for at
least 90 days prior to Baseline
6.
Current use of oral corticosteroids at a dose >10 mg/day prednisone or equivalent
or change of dose within 2 weeks prior to Screening
7.
Current use of more than 1 nonsteroidal anti-inflammatory drug. Doses used
should not be greater than the maximum permitted per product labeling or dosing
has been changed within 2 weeks prior to Baseline
8.
Prior use of injectable corticosteroids (intramuscular [IM], intra-articular [IA], or
intravenous [IV]) within 6 weeks prior to Baseline
9.
Prior or current use of other self-injected drugs, eg, insulin

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10. All other prior non-RA concomitant treatments must be on a stable dose for at
least 4 weeks before Baseline
11. Meets Class IV Steinbrocker criteria for disability/activities of daily living
12. Laboratory abnormalities at Screening deemed clinically significant by the
investigator and/or Sponsor:
a. Hemoglobin <8.5 g/dL for women or 9.0 g/dL for men
b. White blood cell count <3 × 109/L
c. Platelet count <100 × 109/L
d. Aspartate transaminase (AST) or alanine transaminase (ALT) >2 times the
upper limit of normal or bilirubin ≥3 mg/dL
e. Creatinine >1.6 mg/dL if female or >1.8 mg/dL if male
f. Proteinuria 3+ by dipstick
13. Presence of fibromyalgia (as a primary disease), another autoimmune
rheumatologic illness or inflammatory arthritis, eg, systemic lupus erythematosus,
gout. The presence of secondary Sjogren’s syndrome is permitted. At the
discretion of the investigator, a patient with stable and low-grade fibromyalgia
may be included in the study if the fibromyalgia is not a primary disease and will
not interfere with the assessment of RA (specifically in the diagnosis, severity
classification, monitoring, and outomes).
14. Joint surgery within the last 8 weeks prior to Screening
15. Severe, progressive, or uncontrolled renal, hepatic, metabolic, hematologic,
gastrointestinal, endocrine, pulmonary, cardiac or neurologic disease, including
pleural effusions or ascites, which in the opinion of the investigator would
preclude the subject from adhering to or completing the study or where
participation in the study exposes the subject to unfavorable benefit/risk
16. History or presence of signs and/or symptoms or a diagnosis of a demyelinating
disorder
17. History or presence of Class III or IV New York Heart Association congestive
heart failure
18. History or presence of symptoms suggestive of lymphoproliferative disorders,
lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma
19. Existing malignancy or history of any malignancy except adequately treated or
excised non-metastatic basal cell or squamous cell cancer of the skin or cervical
carcinoma in situ, with no more than 3 lifetime basal cell or squamous cell
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20. Chronic infections, recurrent infections (3 or more of the same infection requiring
anti-infective treatment in any rolling 12-month period); any recent infection (ie,
in the last 30 days) requiring hospitalization or any infection requiring parenteral
anti-infective therapy within 30 days or oral infective therapies within 14 days of
Baseline; herpes zoster within 6 months of Baseline or more than 2 lifetime
episodes of herpes zoster; or history of systemic fungal infection or opportunistic
infection (eg, coccidioidomycosis, histoplasmosis, toxoplasmosis)
21. History or presence of human immunodeficiency virus (HIV), Hepatitis B or C
virus
22. History of active tuberculosis (TB) or untreated or inadequately treated latent TB.
Tuberculosis screening requirements include negative QuantiFERON®; or
purified protein derivative (PPD) and chest imaging (ie, x-ray) within 3 months of
Screening
23. Subject has been exposed to an IP within 30 days (or 5 half-lives) prior to
enrollment, whichever is longer, or is scheduled to participate in another clinical
study involving an IP or investigational device during the course of this study
24. Subject is a family member or employee of the investigator or Baxalta or its
partners
9.3 Withdrawal and Discontinuation
Any subject may voluntarily withdraw consent for continued participation in the study. 
This includes collection of their data. The reason for withdrawal will be recorded on the 
End of Study CRF. Assessments to be performed at the withdrawal visit are described in 
Section 10.6 and Section 20.2.
Additionally, the investigator and Sponsor have the discretion to discontinue any subject 
from the study if, in their judgment, continued participation would pose an unacceptable 
risk for the subject.
Subjects also will be discontinued from treatment or withdrawn from further study 
participation for the following reasons:

The subject becomes pregnant. IP exposure will be discontinued. Attempts will be
made to follow the subject through completion of the pregnancy and up to 1 year
post-delivery, if feasible. The investigator will record a narrative description of
the course of the pregnancy and its outcome.

The subject misses 3 consecutive administrations after Week 4 or more than
5 total administrations of IP overall. The subject will be discontinued from
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
Subjects considered to have an inadequate response, defined as a
<20% improvement in the swollen joint count and tender joint count from
Baseline to Week 12, will be withdrawn at Week 14

AEs/SAEs that, in the investigator’s or Sponsor’s opinion, pose an unacceptable
risk for continued dosing in the subject

The subject is determined by the Sponsor or investigator to be noncompliant with
administration of IP, or despite evidence of retraining of the subject. The subject
will be withdrawn from further participation in the study.

Participation in another clinical study involving an IP during the course of the
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10. STUDY PROCEDURES
10.1 Informed Consent and Enrollment
Any patient who provides informed consent (ie, signs and dates the informed consent 
form [ICF] and assent form, if applicable) is considered a study subject and enrolled in 
the study.
10.2 Subject Identification Code
 All study documents 
(eg, CRFs, clinical documentation, sample containers, drug accountability logs, etc.) will 
be identified with the SIC. Additionally, a uniquely coded SIC(s) is permitted as long as 
it does not contain a combination of information that allows identification of a subject 
(eg, collection of a subject’s initials and birth date would not be permitted), in 
compliance with laws governing data privacy.
10.3 Screening and Study Visits
The study site is responsible for maintaining an enrollment/screening log that includes all 
subjects enrolled. The log also will serve to document the reason for screening failure. 
All screening data will be collected and reported in CRFs, regardless of screening 
outcome. If a subject is re-screened with the approval of the medical advisor or sponsor 
study physician, the End of Study CRF should be completed, and a new ICF, new SIC 
and new CRF are required for that subject.
The overall study design is illustrated in the Figure 1. Details on the procedures to be 
performed at each study visit, including Screening, can be found in Section 20.2 Schedule 
of Study Procedures and Assessments and Section 20.3 Clinical Laboratory Assessments.
10.3.1 Screening Assessments
After informed consent has been obtained, subjects will be screened on-site for eligibility 
based on the inclusion and exclusion criteria defined in Section 9.1 and Section 9.2, 
respectively. Screening must be performed within 28 days of Baseline, allowing enough 
time from Screening (Visit 1, Days -28 to Baseline) to Baseline (Visit 2, Day 1) in order 
to ensure eligibility requirements for Screening are met.
PPD

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Screening assessments conducted at Visit 1 (Days -28 to Day 0) will include the 
following:

Informed consent process

Relevant medical history including prior RA therapy

Eligibility evaluation (review of eligibility criteria)

Contact interactive web response system/interactive voice response system
(IWRS/IVRS) to enroll subject

Review of concomitant medications, including pharmacologic and
non-pharmacologic therapies

TB screening (see Section 12.5)

Joint count (see Section 20.2)

Viral serology tests for HIV, Hepatitis B virus (HBV), and Hepatitis C virus
(HCV) (see Section 12.5)

AE monitoring (see Section 12.1)

Complete physical examination (see Section 12.6)

12-lead ECG, performed prior to blood sampling (see Section 12.9)

Vital signs, performed prior to blood sampling (see Section 12.8)

Clinical laboratory assessments (hematology and clinical chemistry; see
Section 12.7.1)

Serology tests for rheumatoid factor (RF) and anti-citrullinated protein antibody
(ACPA) (see Section 12.5)

Urinalysis (see Section 12.7.2)

Serum pregnancy test (female subjects of childbearing potential only)
10.3.2 Baseline Assessments
Baseline assessments conducted at Visit 2 (Day 1) will include the following:

Eligibility evaluation reviewed (inclusion/exclusion criteria)

Contact IWRS/IVRS to assign subject to treatment

Review of concomitant medications, including pharmacologic and
non-pharmacologic therapies

Joint count (see Section 20.2)

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
AE collection (see Section 12.1)

Focused physical examination (see Section 12.6)

Vital signs, performed prior to blood sampling, within 30 minutes before and after
administration of IP (see Section 12.8)

PK and immunogenicity, with blood samples collected prior to clinical laboratory
assessments (hematology/clinical chemistry) and self-administration of IP (see
Sections 11.3 and 11.5)

Clinical laboratory assessments (hematology and clinical chemistry; see
Section 12.7.1), performed prior to self-administration of IP

Serology tests for the following ADAs: anti-nuclear antibody (ANA) and
anti-double-stranded DNA (anti-dsDNA) (see Section 11.3)

Urinalysis (see Section 12.7.2)

Urine pregnancy test (female subjects of childbearing potential only)

Patient-reported outcomes (PROs): PRE- and POST-SIAQ questionnaires to be
completed by the subject prior to and after self-administration of IP, respectively
(see Section 11.1)

Patient global assessments (see Section 11.4.2)

Self-injection training provided by study staff at the site (see Section 8.6.2.1)

Self-administration of IP following completion of all required assessments and
blood sample collections. Subjects should be observed for 2 hours post-injection.

Injection site evaluation performed by investigator (or qualified designee) before
IP administration (see Section 12.10) and 30 minutes after self-administration of
IP

Observer-reported questionnaire: assessment of subject self-injection completed
by observer. Re-training of subject provided after observation of full injection
completed as necessary (see Section 11.2).
10.3.3 Visit 3 (Day 15 ±3 days) Assessments

Review of concomitant medications, including pharmacologic and
non-pharmacologic therapies

28 joint count (see Section 11.4.1)

AE collection (see Section 12.1)

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
Vital signs, performed within 30 minutes before and after administration of IP
(see Section 12.8)

PROs: PRE- and POST-SIAQ questionnaires to be completed by the subject prior
to and after self-administration of IP, respectively (see Section 11.1)

Self-injection training provided by study staff at the site (see Section 8.6.2.1)

Self-administration of IP following completion of all required assessments.
Subjects should be observed for 2 hours post-injection.

Injection site evaluation performed by investigator (or qualified designee) before
IP administration (see Section 12.10) and 30 minutes after self-administration of
IP

Observer-reported questionnaire: assessment of subject self-injection completed
by observer. Re-training of subject provided after observation of full injection
completed as necessary (see Section 11.2).
10.3.4 Visit 4 (Day 29 ±3 days) Assessments

Review of concomitant medications, including pharmacologic and
non-pharmacologic therapies

28 joint count (see Section 11.4.1)

AE collection (see Section 12.1)

Focused physical examination (see Section 12.6)

Vital signs, performed prior to blood sampling, within 30 minutes before and after
administration of IP (see Section 12.8)

PK and immunogenicity, with blood samples collected prior to clinical laboratory
assessments (hematology/clinical chemistry) and self-administration of IP (see
Sections 11.3 and 11.5)

Clinical laboratory assessments (hematology and clinical chemistry; see
Section 12.7.1), performed prior to self-administration of IP

Urinalysis (see Section 12.7.2)

Patient global assessments (see Section 11.4.2)

Urine pregnancy test (female subjects of childbearing potential only)

PROs: PRE- and POST-SIAQ questionnaires to be completed by the subject prior
to and after self-administration of IP, respectively (see Section 11.1)

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
Self-administration of IP following completion of all required assessments and
blood sample collections. Subjects should be observed for 30 minutes
post-injection.

Injection site evaluation performed by investigator (or qualified designee) before
IP administration (see Section 12.10) and 30 minutes after self-administration of
IP

Observer-reported questionnaire: assessment of subject self-injection completed
by observer. Re-training of subject provided after observation of full injection
completed as necessary (see Section 11.2).

Drug dispensing (4 weeks’ supplies of M923 AIs)
10.3.5 Treatment Extension Period Assessments
Following Visit 4, subjects will self-administer IP at home, except at Visits 8 and 14. 
Visits will be conducted at the following timepoints (±3 days targeted) during the 
treatment extension period: Visit 5 (Week 6), Visit 6 (Week 8), Visit 7 (Week 10), Visit 8
(Week 12), Visit 9 (Week 14), Visit 10 (Week 16), Visit 11 (Week 18), Visit 12 
(Week 20), Visit 13 (Week 22), and Visit 14 (Week 24). Assessments performed at each 
study visit during the treatment extension period (except where indicated below) will 
include the following:

Contact IWRS/IVRS to confirm continuation of treatment (Visit 9 only)

Review of concomitant medications, including pharmacologic and
non-pharmacologic therapies

28 joint count at Visits 8 and 14/EDV (see Section 11.4.1)

AE collection (see Section 12.1)

Focused physical examination at Visits 8 and 14/early discontinuation visit (EDV)
(see Section 12.6)

Vital signs at Visits 8 and 14/EDV, performed prior to blood sampling (when
taken at Visits 8 and 14/EDV), within 30 minutes before and after administration
of IP (see Section 12.8)

PK and immunogenicity at Visits 8 and 14/EDV, with blood samples collected
prior to clinical laboratory assessments (hematology/clinical chemistry) and
self-administration of IP (see Sections 11.3 and 11.5)

Clinical laboratory assessments at Visits 8 and 14/EDV (hematology and clinical
chemistry; see Section 12.7.1), performed prior to self-administration of IP

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
Urinalysis at Visits 8 and 14/EDV (see Section 12.7.2)

Patient global assessment at Visits 8 and 14 (see Section 11.4.2)

Urine pregnancy test at Visits 8 and 14 (female subjects of childbearing potential
only)

Drug dispensing at Visit 8 (6 weeks’ supplies of M923 AIs)
10.3.6 Safety follow-up
On completion of the treatment extension period or at premature withdrawal, the 
following assessments will be performed during the 4-week safety follow-up period:

Contact IWRS/IVRS to record end of treatment

Review of concomitant medications, including pharmacologic and
non-pharmacologic therapies

AE collection (see Section 12.1)

Focused physical examination (see Section 12.6)

Vital signs performed prior to blood sampling (see Section 12.8)

PK and immunogenicity, with blood samples collected prior to clinical laboratory
assessments (hematology/clinical chemistry) (see Sections 11.3 and 11.5)

Clinical laboratory assessments (hematology and clinical chemistry; see
Section 12.7.1)

Serology tests for ADAs (ANA and anti-dsDNA) (see Section 11.3)
10.4 Medications and Non-Drug Therapies
During the study, subjects are expected to be on concomitant medication(s) if they are 
being treated or receiving prophylaxis for any underlying medical conditions, provided 
the medications are not considered RA therapies and subjects have been on a stable dose 
for at least 4 weeks before Baseline. Subjects may take permitted additional concomitant 
medication(s) as required for medical management during this study. All medications 
taken 4 weeks prior to Screening and concomitant medication use should be recorded in 
the appropriate CRF. Exposure to all biologic medications at any time should be 
collected.
The following medications and non-drug therapies are not permitted before study entry 
and/or during the course of the study:

Medications:

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Use of systemic TNF inhibitor therapy, including other investigational or
licensed biosimilar TNF inhibitor therapies, is not permitted
Use of rituximab is not permitted
Abatacept, tocilizumab and tofacitinib should have been discontinued at least
4 weeks prior to Screening
With the exception of methotrexate (MTX) orally (≤25 mg),
hydroxychloroquine (≤400 mg/day) or sulfasalazine (≤3 g/day) at a stable
dose for at least 4 weeks prior to Screening, no other conventional DMARDs
are permitted and no combination therapy is permitted. If discontinued, MTX,
hydroxychloroquine, and sulfasalazine must have been discontinued at least
4 weeks prior to Baseline.
Cytotoxic or alkylating agents such as, but not limited to, chlorambucil,
cyclophosphamide or immunosuppressants such as cyclosporine, tacrolimus,
mycophenolate, and azathioprine must have been discontinued for at least
90 days prior to Baseline
Injectable corticosteroids (eg, IM, IA, or IV) are not permitted within 6 weeks
prior to Baseline
Prior or current use of other self-injected drugs, eg, insulin, is not permitted

Non-drug therapies:
Joint surgery within 8 weeks of Screening
A subject who has taken any of these medications or received any of these non-drug 
therapies will be withdrawn. The subject will then enter the 4-week safety follow-up 
period as described in Section 10.3.6.
The following medications and non-drug therapies are permitted before study entry and 
during the course of the study:

Medications:
Subjects on the following conventional DMARDs should be on a stable dose
for at least 4 weeks prior to Screening: MTX orally (≤25 mg/day),
hydroxychloroquine (≤400 mg/day) or sulfasalazine (≤3 g/day)
Oral corticosteroids are permitted at a dose of ≤10 mg/day prednisone or
equivalent if the subject has been stable for at least 2 weeks prior to Screening

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Use of 1 nonsteroidal anti-inflammatory drug is permitted up to the maximum
doses permitted per labeling, provided the dose is stable for at least 2 weeks
prior to Screening
All other prior non-RA concomitant treatments must be on a stable dose for at least 
4 weeks before Baseline.
10.5 Subject Diary and Patient-reported Outcomes
A paper subject diary will be provided to each subject at Baseline to record the following 
information:
1.
Time, date, and location of IP administration, including whether the full dose was
administered and, if not, the reason why the full dose was not administered
(eg, device malfunction)
2.
IP administrator (self)
3.
AEs, including injection site reactions
4.
PROs: PRE- and POST-SIAQ questionnaires to be completed by the subject prior
to and after self-administration of IP, respectively
Subjects will be trained on use of the diary. The diary will be provided in paper format
and remain with the subject for the duration of the study. The investigator will review the 
diary for completeness and request missing information periodically and in a timely 
manner. Untoward events recorded in the diary will be reported as AEs according to the 
investigator’s discretion and clinical judgment.
The subject diary will serve as a source record and remain at the study site. Entries in the 
subject diary will be transferred into the appropriate collection device. Any entry in the 
collection device that does not correspond with an entry in the subject diary will be 
explained by the investigator in source documentation.
10.6 Subject Completion/Withdrawal
A subject is considered to have completed the study when he/she ceases active 
participation in the study because the subject has, or is presumed to have, completed all 
study procedures in accordance with the protocol (with or without protocol deviations).
Reasons for completion/discontinuation will be reported on the 
Completion/Discontinuation CRF, including: completed, screen failure, AE (eg, death), 
discontinuation by subject (eg, lost to follow-up [defined as 3 documented unsuccessful 
attempts to contact the subject], dropout), physician decision (eg, pregnancy, progressive 

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disease, non-compliance with IP/protocol violation[s], recovery), study terminated by 
Sponsor, or other (reason to be specified by the investigator, eg, technical problems). 
Regardless of the reason, all data available for the subject up to the time of 
completion/discontinuation should be recorded on the appropriate CRF.
Every effort will be made to have discontinued subjects complete the study 
completion/termination visit. If the completion/termination visit is done as an additional, 
unscheduled visit, the assessment results shall be recorded with the 
completion/termination visit. If a subject terminates participation in the study and does 
not return for the completion/termination visit, their last recorded assessments shall 
remain recorded with their last visit. The reason for discontinuation will be recorded, and 
the data collected up to the time of discontinuation will be used in the analysis and 
included in the clinical study report. If additional assessments are required, the 
assessments shall be recorded separately. Assessments to be performed at the termination 
visit (including in cases of withdrawal or discontinuation) can be found in Sections 20.2
and 20.3.
In the event of subject discontinuation due to an AE, clinical and/or laboratory 
investigations that are beyond the scope of the required study observations/assessments 
may be performed as part of the evaluation of the event. These investigations will take 
place under the direction of the investigator in consultation with the Sponsor, and the 
details of the outcome may be reported to the appropriate regulatory authorities by the 
Sponsor.
10.7 Procedures for Monitoring Subject Compliance
Subject compliance with the treatment regimen will be monitored by completion of a 
subject diary detailing the time and date of self-administration/home treatment of M923.

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11. ASSESSMENT OF USABILITY, EFFICACY AND PHARMACOKINETICS
11.1 Primary Usability Assessment
The primary outcome measure is the usability of the M923 AI as assessed by the subject 
rating on the PRE- and POST-SIAQ modules at Week 4 of the treatment period. 
Usability will be assessed using the SIAQ tool (version [v] 2.1), which is a valid, reliable 
PRO instrument in patients with RA.5
The PRE-SIAQ module (v2.1) is a 7-item questionnaire that investigates feelings about 
injections, self-confidence (regarding self-administration), and satisfaction with 
self-injection (each item graded on a 5-point scale).5 The POST-SIAQ module (v2.1) is a 
27 item questionnaire that assesses feelings about injections, self-image, self-confidence 
(regarding self-administration), pain and skin reactions during or after the injection 
(injection-site reactions), ease of use of the self-injection device, and satisfaction with 
self-injection. Each item graded on either a 5-point or 6-point scale (see Section 20.4)
Subjects will complete the PRE- and POST-SIAQ questionnaires prior to and after 
self-administration of IP, respectively, Q2W during the initial 4-week treatment period 
(see Section 20.2). This assessment should be recorded in the eCRF.
11.2 Secondary Usability Assessments
Secondary usability measures are observer assessment of usability by subjects as 
determined by (i) ability to successfully follow the steps in the IFU to self-administer 
M923 via the AI and (ii) investigation of the frequency of observed or reported 
difficulties (‘potential hazards’) at Week 4, as well as change over time. At Weeks 0, 2, 
and 4 (Visits 2 to 4), the observer should observe the subject perform self-injection and 
complete the observer questionnaire (see Sections 20.4 and 20.6). In addition, usability 
evaluations at Baseline and Week 2 will be performed for subject (completion of 
PRE- and POST-SIAQ instruments as described in Section 11.1) and observer 
assessments, as well as change over time. This assessment should be recorded in the 
eCRF.
11.3 Immunogenicity Assessment
Immunogenicity of M923 is a secondary safety outcome measure, which will be 
examined at Baseline and Weeks 4, 12 and 24 (Visits 2, 4, 8 and 14/EDV, respectively)
and the Safety Follow-up Visit, assessed as the proportion of all subjects with evidence of 
seroconversion as measured by titer of ADAs (ANA and anti-dsDNA) levels over time, 
and proportion of subjects with nADAs. Anti-drug antibody analysis will be conducted 
using a screening assay based on M923 to identify potentially positive ADA samples. 
Confirmatory assays based on Humira and M923 will be used to confirm the positive 

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status of the samples. In confirmed positive samples, a third assay will be used to 
determine the relative titer of the ADA; a subsequent neutralizing antibodies assay will 
be used to determine the presence of neutralizing antibodies and an isotyping assay will 
be performed. Blood sample processing and handling details will be presented in a 
separate laboratory manual. Serum samples will be analyzed by Quintiles BioSciences 
using validated assays.
Blood samples for immunogenicity analyses will be collected at the times and visits 
shown in the schedule of assessments in Section 20.2.
CCI

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CCI

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12. ASSESSMENT OF SAFETY
12.1 Adverse Events
12.1.1 Definitions
An AE is defined as any untoward medical occurrence in a subject administered an IP 
that does not necessarily have a causal relationship with the treatment. An AE can 
therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), 
symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), conditions (eg, peritonitis, 
bacteremia, etc.), or outcome of death temporally associated with the use of an IP, 
whether or not considered causally related to the IP.
A treatment-emergent adverse event (TEAE) is defined as any event not present prior to 
the initiation of the treatments or any event already present that worsens in either 
intensity or frequency following exposure to the treatments.
12.1.1.1 Serious Adverse Event
An SAE is defined as an untoward medical occurrence that at any dose meets one or 
more of the following criteria:
1. Outcome is fatal/results in death (including fetal death)
2. Is life-threatening – defined as an event in which the subject was, in the judgment
of the investigator, at risk of death at the time of the event; it does not refer to an
event that hypothetically might have caused death had it been more severe.
3. Requires inpatient hospitalization or results in prolongation of an existing
hospitalization – inpatient hospitalization refers to any inpatient admission,
regardless of length of stay
4. Results in persistent or significant disability/incapacity (ie, a substantial
disruption of a person’s ability to conduct normal life functions)
5. Is a congenital anomaly/birth defect
6. Is a medically important event – a medical event that may not be immediately
life-threatening or result in death or require hospitalization but may jeopardize the
subject or may require medical or surgical intervention to prevent one of the other
outcomes listed in the definitions above. Examples of such events are:
Intensive treatment in an emergency room or at home for allergic
bronchospasm, blood dyscrasias, or convulsions that do not result in
hospitalization, or development of drug dependence or drug abuse
Reviewed and confirmed seroconversion for HIV, HBV, or HCV

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Uncomplicated pregnancies, following maternal or paternal exposure to IP are not 
considered an (S)AE; however, any pregnancy complication or pregnancy termination by 
therapeutic, elective, or spontaneous abortion shall be considered an SAE.
12.1.1.2 Suspected Unexpected Serious Adverse Reaction (SUSAR)
Any suspected adverse reaction to study treatment (ie, including active comparators) that 
is both serious and unexpected.
The event(s) must meet all of the following

Suspected adverse reaction

Serious

Unexpected

Assessed as related to study treatment (see Section 12.1.2.2)
Once determined to meet the criteria for a SUSAR, a serious adverse event should be 
submitted to regulatory agencies expeditiously.
12.1.1.3 Non-Serious Adverse Event
A non-serious AE is an AE that does not meet the criteria of an SAE.
12.1.1.4 Unanticipated Adverse Device Effect
An unanticipated adverse device effect (UADE) is defined as any serious adverse 
effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the study protocol or product labeling, or any 
other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects.
12.1.1.5 Unexpected Adverse Events
An unexpected adverse event is an AE whose nature, severity, specificity, or outcome is 
not consistent with the term, representation, or description used in the Reference Safety 
Information (RSI). “Unexpected” also refers to the AEs that are mentioned in the IB as 
occurring with a class of drugs or as anticipated from the pharmacological properties of 
the product, but are not specifically mentioned as occurring with the particular product
under investigation. The expectedness of AEs will be determined by the sponsor using 
the IB as the RSI. This determination will include considerations such as the number of 
AEs previously observed, but not on the basis of what might be anticipated from the 
pharmacological properties of a product.

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12.1.1.6 Pre-existing Diseases
Pre-existing diseases that are present before entry in to the study are described in the 
medical history, and those that manifest with the same severity, frequency, or duration 
after IP exposure, will not be recorded as AEs. However, when there is an increase in the 
severity, duration, or frequency of a pre-existing disease, the event must be described on 
the AE CRF.
12.1.2 Assessment of Adverse Events
For the purposes of this study, each non-serious untoward medical occurrence reported
by a subject undergoing study-related procedure(s) before the first M923 treatment will 
be recorded on the AE CRF; for SAEs the SAE Report (SAER) form is to be used, in 
addition; however, these events will not be included in the analysis of AEs.
Each treatment-emergent AE (non-serious AE or SAE) from the first M923 exposure 
until study completion/discontinuation or 4 weeks following the last M923 treatment will
be described on the AE CRF using the medical diagnosis (preferred), or, if no diagnosis 
could be established at the time of reporting the AE, a symptom or sign, in standard 
medical terminology in order to avoid the use of vague, ambiguous, or colloquial 
expressions (see definition in Section 12.1). Each AE will be evaluated by the 
investigator for:
1. Seriousness as defined in Section 12.1.1.1
2. Severity as defined in Section 12.1.2.1
3. Causal relationship to IP exposure, study procedure, or device as defined in
Section 12.1.2.2
For each AE, the outcome (ie, recovering/resolving, recovered/resolved, 
recovered/resolved with sequelae, not recovered/not resolved, fatal, unknown) and if 
applicable action taken (ie, dose increased, dose not changed, dose reduced, drug 
interrupted, drug discontinued, not applicable, or unknown) will also be recorded on the 
AE CRF. Recovering/resolving AEs will be followed until resolution, medically
stabilized, or 4 weeks after the study completion/termination visit, whichever comes first.
If the severity rating for an ongoing AE changes before the event resolves, the original 
AE report will be revised (ie, the event will not be reported as separate AE). During the 
course of any AE, the highest severity rating will be reported.
Treatment errors (including incorrect route of administration, use of an incorrect product, 
and deviations from the protocol-defined dosing schedule), failures of expected 
pharmacological actions, and unexpected therapeutic or clinical benefits will be followed 

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with regard to occurrence of AEs, lack of efficacy, and/or other observations because 
these events may be reportable to regulatory authorities.
Any pregnancy that occurs after administration of M923 will be reported on a Pregnancy 
Report Form and followed-up at estimated date of delivery and 1 year post-delivery, if
feasible.
If an investigator becomes aware of an SAE occurring in a subject after study 
completion, the SAE must be reported on the provided SAER Form within 24 hours 
after becoming aware; no additional reporting on CRFs is necessary.
12.1.2.1 Severity
The investigator will assess the severity of each AE using his/her clinical expertise and 
judgment based on the most appropriate description below:
1. Mild
The AE is a transient discomfort and does not interfere in a significant manner
with the subject’s normal functioning level
The AE resolves spontaneously or may require minimal therapeutic
intervention
2. Moderate
The AE produces limited impairment of function and may require therapeutic
intervention
The AE produces no sequela/sequelae
3. Severe
The AE results in a marked impairment of function and may lead to temporary
inability to resume usual life pattern
The AE produces sequela/sequelae, which require (prolonged) therapeutic
intervention
These severity definitions will also be used to assess the severity of an AE with a 
study-related procedure(s), if necessary.

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12.1.2.2 Causality
Causality is a determination of whether there is a reasonable possibility that the IP is 
etiologically related to/associated with the AE. Causality assessment includes, eg, 
assessment of temporal relationships, de-challenge/re-challenge information, association 
(or lack of association) with underlying disease, presence (or absence) of a more likely 
cause, and physiological plausibility. For each AE, the investigator will assess the causal 
relationship between the IP and the AE using his/her clinical expertise and judgment 
according to the following most appropriate algorithm for the circumstances of the AE:
1. Not related (either 1 or both circumstances are met)
Has little or no temporal relationship to the IP
A more likely alternative etiology exists
2. Related (both circumstances must be met)
Follows a strong temporal relationship to the administration of IP, which may
include but is not limited to the following:
o
Reappearance of a similar reaction upon re-administration of IP (positive
re-challenge)
o
Positive results in a drug sensitivity test (skin test, etc.)
o
Toxic level of the IP as evidenced by measurement of the IP
concentrations in the blood or other bodily fluid
Another etiology is unlikely or significantly less likely
For events assessed as not related or unlikely related and occurring within 72 hours, the 
investigator shall provide the alternative etiology. These causality definitions will also be 
used to assess the relationship of an AE with a study-related procedure(s), if necessary.
12.1.2.3 Safety Reporting
Adverse events/SAEs will be assessed at all study visits as outlined in Table 2 and 
Section 12.1 above.
Adverse Events/SAEs are to be recorded on the AE page of the eCRF. Each event should 
be recorded separately.
Any SAE, including death due to any cause, which occurs during this study, whether or 
not related to the IP, must be reported immediately (within 24 hours of the study site’s 
first knowledge of the event). All SAEs must be reported via the Electronic Data Capture 
(EDC) system by completing the relevant eCRF page(s) in English. Once the SAE has 

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been recorded in the EDC system, the Sponsor and other designated recipients will be 
informed of the event automatically. For instances in which the EDC may become 
unavailable, SAEs must be reported using the back-up paper SAER Form to meet the 
24 hour timeline requirement (for contacts and instructions refer to the SAER Form). 
Once the EDC becomes available, the site must enter all SAE data as reported on the 
back-up paper SAER Form on the applicable eCRF pages.
The initial SAE information reported on the applicable eCRF pages (or back-up SAER 
Form, if applicable) must at least include the following:
1. Protocol Number
2. Subject identification number and demographics (gender, age at onset of event
and/or date of birth)
3. IP exposure
4. Medical Term for Event (Diagnosis preferably)
5. Description of the (S)AE, including:
Date of onset
(S)AE treatment (drug, dose, route of administration)
Causal relationship by the investigator
Measures taken (ie, action taken regarding IP in direct relationship to the AE)
6. Seriousness criteria (ie, death, life-threatening, or other criterion)
7. Cause of death
8. Autopsy findings (if available)
9. Name, address, fax number, email, and telephone number of the reporting
investigator (for paper SAER Forms)
12.1.3 Medical Device Safety reporting  
The IP kit contains the AI device. All Serious Injuries (SI) and UADE must be reported 
to the Sponsor as an SAE in the same process as described above.
Serious injury is defined as:
1. Life-threatening injury or illness results in permanent impairment/ damage to
body function/ structure
2. Requires medical or surgical intervention to preclude permanent impairment/
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12.2 Urgent Safety Measures
An urgent safety measure is an immediate action taken, which is not defined by the 
protocol, in order to protect subjects participating in a clinical study from immediate 
harm. Urgent safety measures may be taken by the Sponsor or clinical investigator, and 
may include any of the following: 
1. Immediate change in study design or study procedures
2. Temporary or permanent halt of a given clinical study or studies
3. Any other immediate action taken in order to protect clinical study participants
from immediate hazard to their health and safety
The investigator may take appropriate urgent safety measures in order to protect subjects 
against any immediate hazard to their health or safety. The measures should be taken 
immediately and may be taken without prior authorization from the Sponsor. In the 
event(s) of an apparent immediate hazard to the subject, the investigator will notify the 
Sponsor immediately by phone and confirm notification to the Sponsor in writing as soon 
as possible, but within 1 calendar day after the change is implemented. The Sponsor will 
also ensure the responsible Ethics Committee (EC) is notified of the urgent measures 
taken in such cases according to local regulations.
12.3 Untoward Medical Occurrences
Untoward medical occurrences that occur before the first exposure to M923 and are not 
related to study procedures are not considered AEs (according to the definition of AE, see 
Section 12.1). However, each serious untoward medical occurrence that is experienced 
before the first M923 exposure (ie, from the time of signed informed consent up to but 
not including the first M923 exposure) and is not related to study procedures will be 
described on the AE CRF and on the SAER Form. These events will not be considered as 
SAEs and will not be included in the analysis of SAEs.
For the purposes of this study, each non-serious untoward medical occurrence 
experienced by a subject undergoing Screening study-related procedure(s) before the first 
M923 exposure will be recorded on the AE CRF (see Section 12.1); these events will not 
be included in the analysis of AEs. Serious untoward medical occurrences reported
before the first administration of M923 (ie, from the time of signed informed consent up 
to but not including the first administration of M923) will be reported as an SAE.

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12.4 Non-Medical Complaints
A non-medical complaint (NMC) is any alleged product deficiency that relates to 
identity, quality, durability, reliability, safety and performance of the product but did not 
result in an AE. Non-medical complaints include but are not limited to the following:
1. A failure of a product to exhibit its expected pharmacological activity and/or
design function, eg, reconstitution difficulty
2. Missing components
3. Damage to the product or unit carton
4. A mislabeled product (eg, potential counterfeiting/tampering)
5. A bacteriological, chemical, or physical change or deterioration of the product
causing it to malfunction or to present a hazard or fail to meet label claims
Any NMCs of the product will be documented on an NMC form and reported to the 
Sponsor within 1 business day. If requested, defective product(s) will be returned to the 
Sponsor for inspection and analysis according to procedures.
12.5 Medical, Medication, and Non-Drug Therapy History
At Screening (as described in Table 2), the subject’s medical history will be described for 
the following body systems including severity (defined in Section 12.1.2.1) or surgery 
and start and end dates, if known: general; head and neck; eyes, ears, nose, and throat; 
chest/respiratory; heart/cardiovascular; gastrointestinal/liver;
musculoskeletal/extremities; neurological/psychiatric; endocrine/metabolic; 
hematologic/hematopoietic/lymphatic; dermatological; genitourinary; allergies/drug 
sensitivities; past surgeries; substance abuse; or any other diseases or disorders.
Subjects’ history of TB or exposure thereof will be reviewed at Screening. Subjects will 
be tested in absence of a TB test within previous 3 months and/or absence of a 
documented history of prior positive TB test result or active TB infection. Testing 
methods include QuantiFERON®; or PPD and chest x-ray (posteroanterior [PA] or PA 
and lateral view).
History of or current diagnosis of active TB, or untreated latent TB infection (LTBI), 
determined by a TB skin test with PPD as evidenced by induration ≥5 mm or a positive 
QuantiFERON® test performed locally, either at Screening, or documented with results
within 3 months of Screening will be documented. Subjects who have previously 
completed appropriate and documented LTBI treatment or who are undergoing current 
treatment for LTBI will not be required to be tested.

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Clinically significant chest x-ray report per investigator opinion or evidence of active TB 
on chest x-ray will be documented. Chest x-ray must have been performed in 3 months 
prior to the Screening visit or during the Screening period.
At Screening (as described in Table 2), viral serology assessments will be performed 
including the following parameters: HIV-I and -II, hepatitis B surface antigen, hepatitis B 
core antibodies, IgG and/or immunoglobulin M antibodies), and hepatitis C antibody.
Serology tests for RA-specific auto-antibodies (RF and ACPA) will also be performed at 
Screening (as described in Table 2).
All medications taken and non-drug therapies received from enrollment (up to 4 weeks 
prior to Baseline) until completion/termination will be recorded on the concomitant 
medications and non-drug therapies CRFs.
12.6 Physical Examinations
At Screening, a complete physical examination will be done that is limited to the 
following body systems: general appearance, head and neck, eyes and ears, nose and 
throat, chest, lungs, heart, abdomen, extremities and joints, lymph nodes, skin, and 
neurological. At subsequent study visits (as described in Table 2), a focused physical 
examination will be conducted, limited to include the following body systems: heart, 
lungs, abdomen, extremities, and skin, and any other assessments required to evaluate 
AEs.
At Screening, if an abnormal condition is detected, the condition will be described on the 
medical history CRF. At study visits, if a new abnormal or worsened abnormal 
pre-existing condition is detected, the condition will be described on the AE CRF. If the 
abnormal value was not deemed an AE because it was due to an error, due to a 
pre-existing disease (described in Section 12.1.1.6), not clinically significant, a symptom 
of a new/worsened condition already recorded as an AE, or due to another issue that will 
be specified, the investigator will record the justification on the source record.
12.7 Clinical Laboratory Parameters
Clinical laboratory parameters, including hematology, clinical chemistry and urinalysis, 
will be assessed at Screening (Visit 1), Baseline (Visit 2), Week 4 (Visit 4), Week 12 
(Visit 8), Week 24 (Visit 14/EDV), and the Safety Follow-up Visit (hematology and 
clinical chemistry only) (see Table 2). Blood samples for these assessments will be taken 
after ECG and vital signs assessments, after samples have been collected for PK and 
immunogenicity assessments (if applicable at a given study visit), but before 
self-administration of M923.

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12.7.1 Hematology and Clinical Chemistry
The hematology panel will consist of complete blood count (erythrocytes [ie, red blood 
cell count], hemoglobin, hematocrit, mean cell volume, and total leukocytes [ie, white 
blood cell count]) with differentials (ie, neutrophils, lymphocytes, monocytes, 
eosinophils, and basophils) and platelet counts.
The clinical chemistry panel will consist of AST, ALT, alkaline phosphatase, 
gamma-glutamyl transferase, total bilirubin, lactate dehydrogenase, creatine kinase, CRP, 
cholesterol, triglycerides, total protein, sodium, potassium, chloride, blood urea nitrogen, 
creatinine, albumin, calcium, phosphate, glucose, glycosylated hemoglobin, uric acid, and 
bicarbonate.
Blood will be obtained for assessment of hematology, clinical chemistry, immunogenicity 
(see Section 11.3), PK (see Section 11.5), viral serology and serology (see Section 12.5)
parameters at study visits as described in Table 2. A serum pregnancy test will also be 
performed at Screening in females of childbearing potential only. Hematology and 
clinical chemistry assessments will be performed on EDTA-anticoagulated whole blood 
and serum, respectively, at the central laboratory.
12.7.2 Urinalysis
The urinalysis panel will consist of leucocytes, protein, bilirubin, urobilinogen, glucose, 
ketones, blood pH, nitrite, and specific gravity. Urine microscopy will be performed only 
when clinically indicated. Urine will be obtained for assessment of urinalysis parameters 
and urine pregnancy testing (females of childbearing potential only) at study visits as 
described in Table 2. Urinalysis assessments will be performed at the central laboratory.
12.7.3 Assessment of Laboratory Values
12.7.3.1 Assessment of Abnormal Laboratory Values
The investigator’s assessment of each laboratory value will be recorded on the CRF. For 
each abnormal laboratory value, the investigator will determine whether the value is 
considered clinically significant or not. For clinically significant values, the investigator
will indicate if the value constitutes a new AE (see definition in Section 12.1, and record 
the sign, symptom, or medical diagnosis on the AE CRF), is a symptom or related to a
previously recorded AE, is due to a pre-existing disease (described in Section 12.1.1.6), 
or is due to another issue that will be specified. If the abnormal value was not clinically 
significant, the investigator will indicate the reason, ie, because it is due to a pre-existing 
disease, due to a laboratory error, or due to another issue that will be specified. 
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an abnormal value, or to monitor the course of an AE should be obtained when clinically 
indicated. Any abnormal value that persists should be followed at the discretion of the 
investigator.
Any seroconversion result for HIV, HBV, HCV, or ADAs (ANA and anti-dsDNA) shall 
be re-tested.
12.7.4 Biobanking-Study Sample Storage
Study samples and backup samples should be taken and stored appropriately for analysis
as needed. These samples may be used for re-testing, further evaluation of an AE, or 
follow-up of other test results. The following samples are planned as per Table 2:
1. Pharmacokinetic samples (see Section 11.5)
2. Immunogenicity samples (see Section 11.3)
3. Hematology and clinical chemistry samples (see Section 12.7 and 12.7.1)
4. Antinuclear antibody and anti-dsDNA samples
5. Rheumatoid factor and ACPA samples (see Section 12.5)
6. Urinalysis samples (see Section 12.7 and 12.7.2)
Samples will be stored in a coded form until completion of the study and then the 
samples will subsequently be destroyed.
12.8 Vital Signs
Vital signs will include body temperature (°C or °F), respiratory rate (breaths/min), pulse 
rate (beats/min), and systolic and diastolic blood pressure (mmHg). Height (in or cm) and 
weight (lb or kg) will also be collected.
Vital signs will be measured at Screening and within 30 minutes before and after 
administration of IP at each study visit, and at study completion/termination
(see Table 2). Blood pressure will be measured when subjects are resting in a supine
position for at least 5 minutes. Height will be measured at Screening only.
Vital sign values are to be recorded on the CRF. For each abnormal vital sign value, the 
investigator will determine whether or not to report an AE (see definition in Section 12.1
and record the medical diagnosis [preferably], symptom, or sign on the AE CRF). 
Additional tests and other evaluations required to establish the significance or etiology of 
an abnormal value, or to monitor the course of an AE should be obtained when clinically 
indicated. Any abnormal value that persists should be followed at the discretion of the 
investigator.

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12.9 Electrocardiograms
A 12-lead ECG assessment will be done at Screening, performed prior to drawing blood 
at these study visits (see Table 2).
The 12-lead ECG values are to be recorded on the CRF. For each abnormal ECG value, 
the investigator will determine whether the value is considered an AE (see definition in 
Section 12.1 and record the sign, symptom, or medical diagnosis will be recorded on the 
AE CRF). Additional tests and other evaluations required to establish the significance or 
etiology of an abnormal result, or to monitor the course of an AE should be obtained 
when clinically indicated. Any abnormal value that persists should be followed at the 
discretion of the investigator.
12.10 Local Injection Site Reaction Evaluation
Assessment for local injection site reactions site of SC injections of M923 will be
performed prior to M923 administration at these study visits (see Table 2).
Injection site evaluations will be made by clinical staff as described below; if an injection 
site reaction is observed, a physician will characterize and document the reaction as an 
AE. Injection sites will continue to be reviewed at the time points indicated in Table 2, or 
until the AE is resolved.
Injection sites will be monitored for pain, tenderness, erythema, and swelling. Each 
injection site reaction will be categorized using the intensity grading scheme presented in 
Table 1; the intensity of each resulting AE will be categorized as described in 
Section 12.1.2.1 (eg, a moderate intensity injection site reaction may be recorded as a 
mild AE if considered appropriate according to the Invesitgator’s judgement, based on 
the AE grading schemes presented in Section 12.1.2.1).

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Table 1
Injection Site Reaction Grading Scheme
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13. STATISTICS
13.1 Sample Size and Power Calculations
Based on discussions with the US Food and Drug Administration, a sample size of 30 
was judged to be adequate to achieve the objectives of the study.
 Patients dropping out of the study will not be 
replaced. 
13.2 Datasets and Analysis Cohorts
All subjects who received IP will be included in the Safety Analysis Set.
All subjects in the Safety Analysis set who have usability measurements at Week 4 will 
be included in the Usability Analysis Set.
All subjects in the Safety Analysis Set who has at least 1 post-dosing efficacy 
measurement will be included in the Efficacy Analysis Set.
Subjects in the Safety Analysis Set who have at least 1 trough serum measurement will 
be included in the PK Analysis Set.
13.3 Handling of Missing, Unused, and Spurious Data
Multiple imputation methods may be used for imputation of the continuous endpoints (ie, 
DAS28-CRP and PGA) after non-responders discontinue treatment at Week 14, including
last observation carried forward or mixed-effect modeling. Details will be provided in the 
statistical analysis plan.
13.4 Methods of Analysis
Baseline will be defined as the last scheduled visit before dosing of IP. Continuous 
Baseline and demographic characteristics will be summarized by sample size, mean, 
standard deviation (SD), minimum, median, and maximum. Categorical Baseline data 
will be summarized by number and proportions in each category.
The number of dropouts will be reported by scheduled timepoint, and reasons for 
discontinuation will be summarized by number and proportions of each reason.
13.4.1 Primary Outcome Measure
The methods of analysis for the primary outcome measure (see Section 8.4.1) are 
summarized using the Usability Analysis Set. At each scheduled time point, raw and 
change from Baseline of SIAQ will be summarized using number, mean, SD, median, 
minimum, and maximum.
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13.4.2 Secondary Outcome Measures 
The methods of analysis for the secondary safety outcome measures (see Section 8.4.2.2) 
are performed using the Safety Analysis Set.
The self-injection assessment will be coded as successful if P7, P10, and P11 of the 
self-injection assessment checklist (Section 20.4) are checked as Yes. The proportion of 
subjects with a successful self-injection will be summarized by scheduled timepoint as 
the number and proportion of successful injections; additionally, the 95% CI for the 
proportion will be constructed using Wilson’s score method. Similarly, the number and 
proportion of subjects who successfully completed all 14 instructions will be 
summarized, along with 95% CI for the proportion using Wilson’s score method.
For each potential hazard (Section 20.6) listed in the potential hazards checklist, the 
number and proportion will be summarized by scheduled timepoint.
For the purpose of summaries and listings, the durations of AEs will be calculated as 
follows: (stop day – start day) + 1 day, which yields the number of days on which the AE 
was present.
Adverse events will be summarized using number of observations and incidence of AEs 
by preferred term, and by preferred term within system organ class. Serious AEs and AEs 
leading to premature withdrawal will be listed separately.
Injection site reactions will be summarized by scheduled visit using number of 
observations and proportions.
Laboratory and ECG measurements and change from Baseline will be summarized by 
scheduled visit using number of observations, mean, SD, minimum, median, and 
maximum.
Immunogenicity will be summarized using by scheduled visit using number of 
observations, mean, SD, coefficient of variation, minimum, median, maximum, and the 
proportion of subjects with positive antibody titers, and the proportion of subjects with 
positive neutralizing antibody titers.
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13.5 Planned Interim Analysis of the Study
An interim analysis is planned to be conducted at the end of the 4-week treatment period 
once enrollment is completed. The database will be locked after the last subject 
completes the Week 4 and this interim analysis will include the primary analysis of 
usability at Week 4. An interim Clinical Study Report will be written from these results
and the Clinical Study Report will be supplemented with the data collected after Week 4 
once the last subject completes the last visit.
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
The investigator/study site will cooperate and provide direct access to study documents 
and data, including source documentation for monitoring by the study monitor, audits by 
the Sponsor or Sponsor’s representatives, review by the EC, and inspections by 
applicable regulatory authorities, as described in the Clinical Trial Agreement (CTA). If 
contacted by an applicable regulatory authority, the investigator will notify the Sponsor
of contact, cooperate with the authority, provide the Sponsor with copies of all 
documents received from the authority, and allow the Sponsor to comment on any 
responses, as described in the CTA.
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15. QUALITY CONTROL AND QUALITY ASSURANCE
15.1 Investigator’s Responsibility
The investigator will comply with the protocol (which has been approved/given favorable 
opinion by the EC), ICH GCP, and applicable national and local regulatory requirements 
as described in the CTA. The investigator is ultimately responsible for the conduct of all 
aspects of the study at the study site and verifies by signature the integrity of all data 
transmitted to the Sponsor. The term “investigator” as used in this protocol as well as in 
other study documents, refers to the investigator or authorized study personnel that the 
investigator has designated to perform certain duties. Sub-investigators or other 
authorized study personnel are eligible to sign for the investigator, except where the 
investigator’s signature is specifically required.
15.1.1 Final Clinical Study Report
The investigator, or coordinating investigator(s) for multicenter studies, will sign the 
clinical study report. The coordinating investigator will be selected before study start.
15.2 Training
The study monitor will ensure that the investigator and study site personnel understand 
all requirements of the protocol, the investigational status of the IP, and his/her regulatory 
responsibilities as an investigator. Training may be provided at an investigator’s meeting, 
at the study site, and/or by instruction manuals. In addition, the study monitor will be 
available for consultation with the investigator and will serve as the liaison between the 
study site and the Sponsor.
15.3 Monitoring
The study monitor is responsible for ensuring and verifying that each study site conducts 
the study according to the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable national and local regulatory 
guidelines/requirements. The investigator will permit the study monitor to visit the study 
site at appropriate intervals, as described in the CTA. Monitoring processes specific to 
the study will be described in the clinical monitoring plan.
15.4 Auditing
The Sponsor and/or Sponsor’s representatives may conduct audits to evaluate study 
conduct and compliance with the protocol, standard operating procedures, other written 
instructions/agreements, ICH GCP, and applicable national and local regulatory 
guidelines/requirements. The investigator will permit auditors to visit the study site, as 
described in the CTA. Auditing processes specific to the study will be described in the 
auditing plan.

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15.5 Non-Compliance with the Protocol
The investigator may deviate from the protocol only to eliminate an apparent immediate 
hazard to the subject. In the event(s) of an apparent immediate hazard to the subject, the 
investigator will notify the Sponsor immediately by phone and confirm notification to the 
Sponsor in writing as soon as possible, but within 1 calendar day after the change is 
implemented. The Sponsor (Baxalta) will also ensure the responsible EC and relevant 
competent authority is notified of the urgent measures taken in such cases according to 
local regulations.
If monitoring and/or auditing identify serious and/or persistent non-compliance with the 
protocol, the Sponsor may terminate the investigator’s participation. The Sponsor will 
notify the EC and applicable regulatory authorities of any investigator termination.
15.6 Laboratory and Reader Standardization
Not applicable; a central laboratory/reader will be used for all clinical assessments.

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16. ETHICS
16.1 Subject Privacy
The investigator will comply with applicable subject privacy regulations/guidance as 
described in the CTA.
16.2 Ethics Committee and Regulatory Authorities
Before enrollment of subjects into this study, the protocol, ICF, any promotional 
material/advertisements, and any other written information to be provided will be 
reviewed and approved/given favorable opinion by the EC and applicable regulatory 
authorities. The IB will be provided for review. The EC’s composition or a statement that 
the EC’s composition meets applicable regulatory criteria will be documented. The study 
will commence only upon the Sponsor’s receipt of approval/favorable opinion from the 
EC and, if required, upon the Sponsor’s notification of applicable regulatory 
authority(ies) approval, as described in the CTA.
If the protocol or any other information given to the subject is amended, the revised 
documents will be reviewed and approved/given favorable opinion by the EC and 
applicable regulatory authorities, where applicable. The protocol amendment will only be 
implemented upon the Sponsor’s receipt of approval and, if required, upon the Sponsor’s 
notification of applicable regulatory authority(ies) approval.
16.3 Informed Consent
Investigators will choose subjects for enrollment considering the study eligibility criteria. 
The investigator will exercise no selectivity so that no bias is introduced from this source.
All patients must sign an ICF before entering into the study according to applicable 
national and local regulatory requirements and ICH GCP. Before use, the ICF will be 
reviewed by the Sponsor and approved by the EC and regulatory authority(ies), where 
applicable (see Section 16.2). The ICF will include a comprehensive explanation of the 
proposed treatment without any exculpatory statements, in accordance with the elements 
required by ICH GCP and applicable national and local regulatory requirements. Patients
will be allowed sufficient time to consider participation in the study. By signing the ICF, 
subjects agree that they will complete all evaluations required by the study, unless they 
withdraw voluntarily or are terminated from the study for any reason.
The Sponsor will provide to the investigator in written form any new information that 
significantly bears on the subjects’ risks associated with IP exposure. The informed 
consent will be updated, if necessary. This new information and/or revised ICF, that have

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been approved by the applicable EC and regulatory authorities, where applicable, will be 
provided by the investigator to the subjects who consented to participate in the study (see 
Section 16.3).
16.4 Data Monitoring Committee
No Data Monitoring Committee (DMC) will be established for this study for the 
following reason: 
Subjects are on IP which is the same dosage and form as the product that is 
already licensed; however, the device that delivers the IP is different from the 
licensed product.
The Sponsor or designee will be responsible for reviewing accumulating data from the 
ongoing clinical study on a regular basis.

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17. DATA HANDLING AND RECORD KEEPING
17.1 Confidentiality Policy
The investigator will comply with the confidentiality policy as described in the CTA.
17.2 Study Documentation and Case Report Forms
The investigator will maintain complete and accurate paper format study documentation 
in a separate file. Study documentation may include information defined as “source data” 
(see Section 8.7), records detailing the progress of the study for each subject, signed 
ICFs, correspondence with the EC and the study monitor/Sponsor, enrollment and 
Screening information, CRFs, SAERs, laboratory reports (if applicable), and data 
clarifications requested by the Sponsor.
The investigator will comply with the procedures for data recording and reporting. Any 
corrections to paper study documentation must be performed as follows: 1) the first entry 
will be crossed out entirely, remaining legible; and 2) each correction must be dated and 
initialed by the person correcting the entry; the use of correction fluid and erasing are 
prohibited.
The investigator is responsible for the procurement of data and for the quality of data 
recorded on the CRFs. Case Report Forms will be provided in electronic form. If 
electronic format CRFs are provided by the sponsor, only authorized study site personnel 
will record or change data on the CRFs. If data are not entered on the CRFs during the 
study visit, the data will be recorded on paper, and this documentation will be considered 
source documentation. Changes to a CRF will require documentation of the reason for 
each change. An identical (electronic/paper) version of the complete set of CRFs for each 
subject will remain in the investigator file at the study site in accordance with the data 
retention policy (see Section 17.3).
The handling of data by the Sponsor, including data quality assurance, will comply with 
regulatory guidelines (eg, ICH GCP) and the standard operating procedures of the 
Sponsor. Data management and control processes specific to the study will be described 
in the data management plan.
17.3 Document and Data Retention
The investigator will retain study documentation and data (paper and electronic forms) in 
accordance with applicable regulatory requirements and the document and data retention 
policy, as described in the CTA.

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18. FINANCING AND INSURANCE
The investigator will comply with investigator financing, investigator/Sponsor insurance, 
and subject compensation policies, if applicable, as described in the CTA.
19. PUBLICATION POLICY
The investigator will comply with the publication policy as described in the CTA.

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20. SUPPLEMENTS
20.1 Study Flow Chart
Figure 1
Study Design for Baxalta Clinical Study 911502
AI=autoinjector; N=number of subjects; Q2W=every 2 weeks; RA=rheumatoid arthritis; SC=subcutaneous; SIAQ=Self-injection Assessment 
Questionnaire.
a SC injections administered at Weeks 0, 2 and 4 with SIAQ completed at each timepoint.
b Subjects who are inadequate responders, or who withdraw early or choose not to continue to the treatment extension period, will directly enter the 
4-week safety follow-up period; all other subjects will enter the safety follow-up period on completion of the treatment extension period.
c Subjects with an inadequate response will be discontinued at Week 14, based upon <20% improvement in their swollen joint count and tender joint 
count from Baseline to Week 12.
M923 AI
40 mg Q2W SC
M923 AI
40 mg Q2W SC
M923 AI
40 mg Q2W SC
(N=32)
Treatment Extension
Subjects with 
RA naïve to 
Humira without 
neutralizing 
antibodies
Discontinued subjects 
go to safety follow-up
Safety Follow-upb
Days -28 to 0
Screening
Week 0
Week 4
Primary 
analysis
Week 24
End of 
Treatment
Week 28
End of 
Study
Treatment Perioda
Week 14c
Week 12

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20.2 Schedule of Study Procedures and Assessments
Table 2
Schedule of Study Procedures and Assessments
Phase
Screening
Open-label Treatment Period/Treatment Extension
Safety 
Follow-
upa
Week
-4 to 0
0
2
4
6
8
10
12
14
16
18
20
22
24/
EDV
28
Study Dayb
-28 to 0
Baseline/1
15
29
43
57
71
85
99
113
127
141
155
169
197
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Informed consent
X
Contact IWRS/IVRSc
X
X
X
X
Medical history (including 
prior RA therapy)
X
Eligibility criteria
X
Xd
Concomitant therapye
X
X
X
X
X
X
X
TB screening
Xf
66/68 joint count
X
X
28 joint count
X
X
X
X
X
PGA
X
X
X
X
HIV, Hepatitis B and C viral 
testing
X
AE monitoring
X
X
X
X
X
X
X
Physical examination
Xg
X
X
X
X
X
12-lead ECGh
X
Vital signsi
X
X
X
X
X
X
X
PK and immunogenicityj
X
X
X
X
X
Hematology, clinical 
chemistryk
X
X
X
X
X
X
ANA, anti-dsDNA
X
X
RF, ACPA
X
Urinalysis
X
X
X
X
X
Pregnancy testl
X
X
X
X
X
SIAQm
X
X
X
Injection trainingn
X
X

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Table 2
Schedule of Study Procedures and Assessments
Phase
Screening
Open-label Treatment Period/Treatment Extension
Safety 
Follow-
upa
Week
-4 to 0
0
2
4
6
8
10
12
14
16
18
20
22
24/
EDV
28
Study Dayb
-28 to 0
Baseline/1
15
29
43
57
71
85
99
113
127
141
155
169
197
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
IP injection at officeo
X
X
X
X
X
IP injection at homeo
X
X
X
X
X
X
X
X
Injection site evaluationp
X
X
X
Observer assessment of subject 
self-injectionq
X
X
X
Drug dispensing for at home 
dosing
X
X
ACPA=anti-citrullinated protein antibody; AE=adverse event; AI=Autoinjector; ANA=antinuclear antibody; anti-dsDNA=anti-double-stranded 
deoxyribonucleic acid; ECG=electrocardiogram; EDV=early discontinuation visit; HIV=human immunodeficiency virus; IP=investigational product; 
IVRS=interactive voice response system; IWRS=interactive web response system; PA=posteroanterior; PGA=Patient Global Assessment; 
PK=pharmacokinetics; PPD=purified protein derivative; RA=rheumatoid arthritis; RF=rheumatoid factor; SIAQ=Self-Injection Assessment 
Questionnaire; TB=tuberculosis.
a Subjects who are inadequate responders, or who withdraw early or choose not to continue to the treatment extension period, will directly enter the 
4-week safety follow-up period; all other subjects will enter the safety follow-up period on completion of the treatment extension period.
b Visit windows are ±3 days at Visits 3 and 4. Reference for visit windows/study day is scheduling based on Visit 2/Baseline Visit. Visit windows 
are ±3 days at each visit from Visits 5 to 15.
c Subjects will be enrolled using the IVRS/IWRS at Screening or Baseline. The IVRS/IWRS should be contacted at Week 14 to determine which 
subjects should discontinue treatment due to non-response. At Week 28, the IVRS/IWRS should be contacted to record the end of treatment.
d Inclusion/exclusion criteria are to be reviewed before enrollment. The Screening Visit needs to occur with enough time prior to enrollment to ensure 
eligibility requirements for enrollment are met.
e Concomitant therapy will include pharmacologic and non-pharmacologic therapies.
f
Subject will be screened for TB if not tested within previous 3 months and/or does not have documented history of prior positive TB test result or 
active TB infection. Testing includes QuantiFERON®; or PPD and chest imaging (ie, x-ray) with PA or PA and lateral view. QuantiFERON® is the 
preferred testing method, with PPD used in the absence of QuantiFERON®.
g A complete physical examination will be done at Screening. All other physical examinations should be limited to include heart, lungs, abdomen, 
extremities, and skin, and any other assessments required to evaluate AEs.
Continued on Next Page

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Continued
h A 12-lead ECG should be performed before blood sampling.
i
Vital signs assessments should be performed within 30 minutes before and after administration of IP at each study visit. Vital signs should be taken
before blood sampling. Height will be measured at Screening only.
j
PK and immunogenicity blood samples are to be collected at these timepoints in all subjects. Samples should be collected predose (ie, prior to 
administering IP) and before any hematology/chemistry samples to be drawn at that visit.
k Blood samples will be taken before injection of IP, after ECG and vital signs assessments, and after PK and immunogenicity sampling if applicable.
l
Pregnancy testing is only required for female subjects of childbearing potential. A serum test will be performed at Screening; urine pregnancy tests 
will be performed at all other applicable visits.
m Subject should complete PRE-SIAQ prior to injecting, and POST-SIAQ after completing self-injection at each applicable visit.
n Self-injection training for the AI should be provided at Baseline prior to the first injection, with subjects performing the injection. If the subject 
requests it, additional training can be provided at prior to the second injection, but the subject should perform the injection.
o IP will be self-administered in the clinic after all required assessments and blood sample collections have been completed at Weeks 0, 2, and 4.
Subjects should be observed for 2 hours post-injection at Weeks 0 and 2, and for 30 minutes post-injection at Week 4. All other injections will be at
home.
p The investigator or a qualified designee will evaluate the injection site before IP administration (see Section 12.10) and 30 minutes after IP
administration.
q Observer should observe the subject perform self-injection and complete observer questionnaire. Re-training of the subject should be provided after 
observation of full injection completed as necessary and prior to next injection.

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20.3 Clinical Laboratory Assessments
Table 3
Clinical Laboratory Parameters
Panel
Parameters
Hematology
Red blood cell count
Hemoglobin
Hematocrit
Platelet count
Mean cell volume
White blood cell count (total leucocytes)
Neutrophils (absolute and %)
Lymphocytes (absolute and %)
Monocytes (absolute and %)
Eosinophils (absolute and %)
Basophils (absolute and %)
Serum biochemistry
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Alkaline phosphatase 
Gamma-glutamyl transferase
Total bilirubin
Lactate dehydrogenase
Creatine kinase
C-reactive protein (CRP)
Cholesterol
Triglycerides
Total protein
Sodium
Potassium
Chloride
Blood urea nitrogen
Creatinine
Albumin
Calcium
Phosphate
Glucose
Glycosylated hemoglobin (HbA1c)
Uric acid
Bicarbonate
Urinalysis
Leucocytes
Protein
Bilirubin
Urobilinogen
Glucose
Ketones
Blood pH
Nitrite
Specific gravity
Urine microscopy
Done only when clinically indicated
Viral serology
Hepatitis B surface antigen and hepatitis B core 
antibodies, IgG and/or immunoglobulin M antibodies
Hepatitis C antibody
Human immunodeficiency virus (HIV-I and -II)
Tuberculosis (TB)
QuantiFERON®-TB Gold test or purified protein 
derivative (PPD) and chest imaging (ie, x-ray).
Serum/urine pregnancy test
Follicle-stimulating hormone (FSH)
Beta human chorionic gonadotropin
Serology
Anti-nuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), anti-citrullinated protein antibody 
(ACPA), rheumatoid factor (RF)

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20.5 Self-Injection Assessment Checklist
No.
Instructions for Use (Indicated Steps)
Completion Required for 
Successful Administration? 
(Yes/No)
P1
Washed hands with soap and water
No
P2
Cleaned the injection site
No
P3
Removed the autoinjector from the outer box
No
P4
Checked expiration date on the autoinjector label
No
P5
Inspected the autoinjector for damage
No
P6
Inspected liquid for brown discoloration of particles
No
P7
Removed protective needle cap from autoinjector
Yes
P8
Discarded needle cap
No
P9
Pinched the skin at the injection site
No
P10
Press down on AI to insert the needle into the skin
Yes
P11
Held AI pressed fully down through second “click” sound
Yes
P12
Continued to hold down AI until 5 seconds after click
No
P13
Removed AI from injection site at 90° angle to skin.
No
P14
Disposed used autoinjector in a sharps container
No

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20.6 Potential Hazards Checklist
No.
Potential Hazarda
H1
Was there a needle stick in a critical area (eg, eye, carotid artery)?
H2
Was there a needle stick in a non-critical area?b
H3
Was any part of the device swallowed?c
H4
Was an immediate-type allergic reaction to the device material noticed?
H5
Was increased pain noticed by the subject due to a bent needle?
H6
Was a breakage of the device observed?d
H7
Was swallowing of material debris observed?c
H8
Was any other problem observed?c
H9
Was less than the full dose administered?e
a The following potential hazards were not included since these are not observable during self-injection 
observation:  microbiological contamination, wrong drug, and transfer of transmissible diseases.
b Excludes the actual injection into the appropriate injection site of the body.
c If yes, then it is to be specified.
d If yes, then it is to be specified under which circumstances breakage occurred and which parts were 
affected, and any additional problems (eg, injuries) due to the breakage are to be described.
e If yes, then it is to be specified why (eg, leakage from the injection site, early removal).

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21. REFERENCES
1.
Humira Summary of Product Characteristics. European Medicines Agency (EMA).
Last updated: 8/2015. Link to citation:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/
000481/human_med_000822.jsp&mid=WC0b01ac058001d124
2.
Sacks JJ, Helmick CG, Langmaid G. Deaths from arthritis and other rheumatic
conditions, United States, 1979-1998. J Rheumatol. 2004;31:1823-1828.
3.
Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358:903-911.
4.
Rheumatoid arthritis: The management of rheumatoid arthritis in adults. NICE
guidelines [CG79]. Published date: February 2009. Last updated: March 2015. Link
to citation: https://www.nice.org.uk/guidance/cg79
5.
Keininger D, Coteur G. Assessment of self-injection experience in patients with
rheumatoid arthritis: psychometric validation of the Self-Injection Assessment
Questionnaire (SIAQ). Health and Quality of Life Outcomes. 2011;9:2.
6.
DAS28 – Home of the Disease Activity Score and DAS28 (an instrument to
measure the disease activity in people with rheumatoid arthritis). Alternative
validated formulae. Link to citation: http://www.das-score.nl/das28/en/difference-
between-the-das-and-das28/how-to-measure-the-das28/how-to-calculate-the-
das28/alternative-validated-formulae.html
7.
Anderson JK, Zimmerman L, Caplan L, Michaud K. Measures of Rheumatoid
Arthritis Disease Activity. Arthritis Care Res (Hoboken). 2011;63(Suppl
11):S14-36.
8.
Van Tuyl LH, Boers M. Patient’s global assessment of disease activity: what are we
missing? Arthritis Rheum. 2012;64(9):2811-2813.
9.
Reeve R, Pang L, Feruson B, O’Kelly M, Berry S, and Xiao W. Rheumatoid
arthritis disease progression modeling. Therapeutic Innovation and Regulatory
Science. 2013;47(6):641-650.

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22. SUMMARY OF CHANGES
Protocol 911502 Amendment 1 2016 AUG 26
Replaces: Original: 2016 JAN 29
In this section, changes from the previous version of the Protocol, dated 2016 JAN 29, 
are described and their rationale is given.
1.
Throughout the document
Description of Change: Changes made according to the updated Baxalta protocol
template dated 2016 MAR 16.
Purpose for Change: Administrative, and to improve the readability and/or clarity
of the protocol.
2.
Throughout the document
Description of Change: At home visits were added at Weeks 6, 10, 16, 20, and 22,
and visit numbers were updated as appropriate.
Purpose for Change: Administrative, updated for consistency.
3.
Section 3. SYNOPSIS; Section 9.1 Inclusion Criteria
Description of Change: The wording “Where relevant, a legal representative will
also sign the informed study consent according to local laws and regulations.”
was removed from Inclusion criterion 2. This change was requested by the
Institutional Review Board.
Purpose for Change: Administrative, updated for clarity.
4.
Section 3. SYNOPSIS; Section 9.1, Inclusion Criteria
Description of Change: The units “mg/L” were deleted from Inclusion criterion 5
“Active disease defined as both DAS28-CRP >3.2 mg/L at Screening and
4 swollen and tender joints each on a 66/68 joint count at Screening and
Baseline”.
Purpose for Change: Administrative, correction.
5.
Section 3. SYNOPSIS; Section 9.1, Inclusion Criteria
Description of Change: Inclusion criterion 9 was updated: “Female subjects must
have a negative pregnancy test at Screening and on admission to the clinic and
must not be lactating. Female subjects must also agree to or be one of the
following for the duration of the study until 5 months after the last dose…”.
Purpose for Change: Administrative, updated for consistency with the Summary
of Product Characteristics for EU Humira.

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6.
Section 3. SYNOPSIS; Section 9.2, Exclusion Criteria
Description of Change: The wording of Exclusion criterion 13 was updated to
clarify the conditions under which patients with fibromyalgia can be included in
the study: “Presence of fibromyalgia (as a primary disease), another
autoimmune rheumatologic illness or inflammatory arthritis, eg, systemic lupus
erythematosus, gout. The presence of secondary Sjogren’s syndrome is permitted.
At the discretion of the investigator, a patient with stable and low-grade
fibromyalgia may be included in the study if the fibromyalgia is not a
primary disease and will not interfere with the assessment of RA (specifically
in the diagnosis, severity classification, monitoring, and outcomes).”
Purpose for Change: Administrative, updated for clarity.
7.
Section 5. LIST OF ABBREVIATIONS
Description of Change: The abbreviations “CTA, Clinical Trial Agreement”,
“SUSAR, suspected unexpected serious adverse reactions”, and “RSI,
Reference Safety Information” were added. The abbreviations “B19V,
parvovirus B19”, “HAV, hepatitis  A virus”, and “HEV, hepatitis E virus” were
deleted.
Purpose for Change: Administrative.
8.
Section 6.1, Description of Investigational Product
Description of Change: The M923 AI was used previously in a Phase I trial to
assess the pharmacokinetics and safety of M923 administered via AI or prefilled
syringe, in healthy subjects (clinical study protocol identifier: 911501;
NCT02675023). Text was updated to indicate that the AI is not a new device: “A
single-use, 1.0 mL autoinjector (AI; see Section 20.7) that delivers 40 mg
(0.8 mL) of M923 via SC injection will be examined in this study.”
Purpose for Change: Administrative, correction.
9.
Section 6.2, Clinical Condition/indication
Description of Change:Text describing the medical need for the IP was
condensed.
Purpose for Change: Administrative, updated for clarity.
10. Section 6.3, Population to be Studied; Section 20.1, Study Flow Chart
Description of Change: The number of subjects to be enrolled was erroneously
stated as 34 in the original protocol; this was corrected to 32 subjects.
Purpose for Change: Administrative, correction.

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11. Section 8.1, Brief Summary
Description of Change: The M923 AI was used previously in a Phase I trial to
assess the pharmacokinetics and safety of M923 administered via AI or prefilled
syringe, in healthy subjects (clinical study protocol identifier: 911501;
NCT02675023). Text was updated to indicate that the AI is not a new device:
“The proposed biosimilar M923 will be provided in a form for administration via
an AI for SC self-injection in subjects with active, moderate to severe RA.”
Purpose for Change: Administrative, correction.
12. Section 10.3.5, Treatment Extension Period Assessments
Description of Change: Wording clarified to indicate that home-dosing would not
be performed at Weeks 12 and 24/EDV “Following Visit 4, subjects will self-
administer IP at home, except at Visits 8 and 14”. Additional home-dosing visits
were added at Weeks 6, 10, 16, 20, and 22; study visit numbering was revised
accordingly: “Visits will be conducted at the following timepoints (±3 days
targeted) during the treatment extension period: Visit 5 (Week 6), Visit 6
(Week 8), Visit 7 (Week 10), Visit 8 (Week 12), Visit 9 (Week 14), Visit 10
(Week 16), Visit 11 (Week 18), Visit 12 (Week 20), Visit 13 (Week 22), and
Visit 14 (Week 24).” Additional detail was added to clarify the timings of the
following assessments: “28 joint count at Visits 8 and 14/EDV (see
Section 11.4.1)”, “Vital signs at Visits 8 and 14/EDV, performed prior to blood
sampling (when taken at Visits 8 and 14/EDV), within 30 minutes before and
after administration of IP (see Section 12.8)” and “Drug dispensing at Visit 8 (6
weeks’ supplies of M923 AIs)”.
Purpose for Change: Administrative, updated for clarity.
13. Section 10.5, Subject Diary and Patient-reported Outcomes; Section 16.3,
Informed consent
Description of Change: The wording “and/or legally authorized representatives”
was removed from subject informed consent statements. This change was
requested by the Institutional Review Board.
Purpose for Change: Administrative, updated for clarity.
14. Section 11.1, Primary Usability Assessment
Description of Change: The version number of the SIAQ tool was updated from
v2.0 to v2.1.
Purpose for Change: Administrative, correction.

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15.
Purpose for Change: Administrative, updated for clarity.
16. Section 12.1.2, Assessment of Adverse Events
Description of Change: Text was updated to account for SAEs that could occur
during the pre-exposire period: “For the purposes of this study, each non-serious
untoward medical occurrence reported by a subject undergoing study-related
procedure(s) before the first M923 treatment will be recorded on the AE CRF; for
SAEs the SAE Report (SAER) form is to be used, in addition; however, these
events will not be included in the analysis of AEs.”
Purpose for Change: Administrative, updated for clarity.
17. Section 12.1.2, Assessment of Adverse Events
Description of Change: Text was updated to reflect the 4-week Safety Follow-Up:
“Recovering/resolving AEs will be followed until resolution, medically stabilized,
or 4 weeks after the study completion/termination visit, whichever comes first.”
Purpose for Change: Administrative, correction.
18. Section 12.3, Untoward Medical Occurrences
Description of Change: Text describing untoward medical occurances was
updated: “Untoward medical occurrences that occur before the first exposure to
M923 and are not related to study procedures are not considered AEs
(according to the definition of AE, see Section 12.1). However, each serious
untoward medical occurrence that is experienced before the first M923 exposure
(ie, from the time of signed informed consent up to but not including the first
M923 exposure) and is not related to study procedures will be described on the
AE CRF and on the SAER Form. These events will not be considered as SAEs
and will not be included in the analysis of SAEs. For the purposes of this study,
each non-serious untoward medical occurrence experienced by a subject
undergoing Screening study-related procedure(s) before the first M923 exposure
will be recorded on the AE CRF (see Section 12.1); these events will not be
included in the analysis of AEs. Serious untoward medical occurrences reported
before the first administration of M923 (ie, from the time of signed informed
consent up to but not including the first administration of M923) will be reported
as an SAE.”
Purpose for Change: Administrative, updated for clarity and consistency.
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19. Section 12.1.1, Definitions; Section 12.5, Medical, Medication, and Non-drug
Therapy History; Section 12.7.3.1, Assessment of Abnormal Laboratory Values
Description of Change: HAV, HEV and B19 virology assessments are not
planned for this study and were therefore removed.
Purpose for Change: Administrative, correction.
20. Section 13.4.2, Datasets and Analysis Cohorts
Description of Change: The text describing the number of instructions in the self-
injection assessment checklist was corrected: “Similarly, the number and
proportion of subjects who successfully completed all 14 instructions will be
summarized, along with 95% CI for the proportion using Wilson’s score method.”
Purpose for Change: Administrative, correction.
21. Section 16.4, Data Monitoring Committee
Description of Change: The text describing the reason for not establishing a DMC
was updated “Subjects are on IP which is the same dosage and form as the
product that is already licensed; however, the device that delivers the IP is
different from the licensed product.”
Purpose for Change: Administrative, updated for clarity.
22. Section 20.2, Schedule of Study Procedures and Assessments; throughout the
document
Description of Change: The following changes were made to Table 2, Schedule of
Study Procedures and Amendments: home-dosing visits were added at Weeks 6,
10, 16, 20, and 22; concomitant therapy assessments were added at Screening and
Weeks 0, 2, 4, 8, and 14; 28 joint counts were removed at Weeks 8, 14, and 18;
vital sign assessments were added at screening and Weeks 0, 2, 4, 12, 24, and 28;
AE monitoring assessments were added at Screening and Weeks 0, 2, 4, 8, and
14; pregnancy testing was removed at Weeks 8, and 18; IP injection at home was
added at Weeks 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24; the heading “IP injection”
was split into two separate rows: “IP injection at home” (Weeks 6, 8, 10, 14, 16,
18, 20, and 22) and “IP injection at office” (Weeks 0, 2, 4, 12, and 24/EDV); the
heading “Drug dispensing” was changed to “Drug dispensing for at home
dosing”; visit numbers were updated in the table footnote.
Purpose for Change: Administrative, updated for clarity.

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23.
Purpose for Change: Administrative, correction.
24. Investigator Acknowledgement Form
Description of Change: The investigator acknowledgement form for the
Coordinating Investigator was deleted.
Purpose for Change: Administrative, a form is required for the Principal
Investigator only.
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INVESTIGATOR ACKNOWLEDGEMENT
PRODUCT: M923
STUDY TITLE: An open-label single-arm multicenter study to evaluate usability of 
a subcutaneous autoinjector for a proposed adalimumab biosimilar (M923) in 
subjects with moderate to severe rheumatoid arthritis
PROTOCOL IDENTIFIER: 911502
CLINICAL TRIAL PHASE 3
AMENDMENT 1: 2016 AUG 26
Replaces: Original: 2016 JAN 29
ALL VERSIONS: 
Amendment 1: 2016 AUG 26
Original: 2016 JAN 29
OTHER ID(s)
NCT Number: NCT02722044
IND NUMBER: 115119
By signing below, the Investigator acknowledges that he/she has read and understands 
this protocol, and will comply with the requirements for obtaining informed consent from 
all study subjects prior to initiating any protocol-specific procedures, obtaining written 
initial and ongoing EC(s) protocol review and approval, understands and abides by the 
requirements for maintenance of source documentation, and provides assurance that this 
study will be conducted according to all requirements as defined in this protocol, Clinical 
Trial Agreement, ICH GCP guidelines, and all applicable national and local regulatory 
requirements.
Signature of Principal Investigator
Date
Print Name of Principal Investigator