A Phase 3 Randomized, Double-blind, Multicenter Study to Evaluate Efficacy, Safety, and Immunogenicity of an Adalimumab Biosimilar (M923) and Humira® in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis
Phase: PHASE3
Conditions: Chronic Plaque Psoriasis, Psoriasis
Sponsor: Momenta Pharmaceuticals, Inc.

VERSION: 2014 DEC 02
.
CLINICAL STUDY PROTOCOL
PRODUCT: M923
STUDY TITLE: A Phase 3 Randomized, Double-blind, Multicenter Study to 
Evaluate Efficacy, Safety, and Immunogenicity of M923 (a Proposed Adalimumab 
Biosimilar) and Humira® in Subjects with Moderate to Severe Chronic Plaque-type 
Psoriasis
STUDY SHORT TITLE: Phase 3 Study of M923 and Humira® in Subjects with 
Chronic Plaque-type Psoriasis
PROTOCOL IDENTIFIER: 911401
CLINICAL TRIAL PHASE 3
AMENDMENT 3 (Global): 2016 AUG 04
Replaces: Amendment 2: 2015 OCT 08
ALL VERSIONS: 
Amendment 3: 2016 AUG 04
Amendment 2: 2015 OCT 08
Amendment 1: 2015 JUL 27
Original: 2015 MAY 13
OTHER ID(s)
EudraCT Number: 2015-001751-76
NCT Number: NCT02581345
IND NUMBER: 115119
Study Sponsor(s):
Baxalta US Inc.
One Baxter Way
Westlake Village, CA  91362
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.
Medical monitors:
!
, MD
Associate Medical Director, Quintiles
Ing. Butty 275 Piso 9 y 10C1001AFA
Buenos Aires, Argentina
Office: 
Mobile:
!
, MD, MPH&HM
Medical Director, Quintiles
Sofia Tower, Fl.7
103, Aleksandar Stamboliyski Blvd
1303 Sofia, Bulgaria
Office: 
Mobile:
Fax: 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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.
Questions pertaining to an SAE should be directed to:
QLS_M923@quintiles.com
ALL SAEs ARE TO BE REPORTED ON THE ELECTRONIC CASE REPORT 
FORM (eCRF) AND TRANSMITTED TO THE SPONSOR WITHIN 24 HOURS 
AFTER BECOMING AWARE OF THE EVENT
See eCRF for contact information. 
Further details are also available in the study team roster.
For definitions and information on the assessment of these events, refer to the following:

Adverse events (AE), Section 12.1

SAE, Section 12.1.1.1

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(s) of Active Ingredient(s)
Adalimumab
CLINICAL CONDITION(S)/INDICATION(S)
Moderate to Severe Plaque Psoriasis
PROTOCOL ID
911401
PROTOCOL TITLE
A Phase 3 Randomized, Double-blind, Multicenter Study to Evaluate 
Efficacy, Safety, and Immunogenicity of M923 (a Proposed 
Adalimumab Biosimilar) and Humira® in Subjects with Moderate to 
Severe Chronic Plaque-type Psoriasis
Short Title
Phase 3 Study of M923 and Humira® in Subjects with Chronic Plaque-
type Psoriasis
STUDY PHASE
Phase 3
PLANNED STUDY PERIOD
Initiation
2015 AUG
Primary Completion
2017 FEB
Study Completion
2017 MAY
Duration
Approximately 86 weeks
STUDY OBJECTIVES AND PURPOSE
Study Purpose
The purpose of the study is to evaluate efficacy, safety, and immunogenicity of M923 (a proposed
adalimumab biosimilar) and a non-US-approved comparator (EU-approved Humira®) referred to as the 
Reference Protein Product (EU RPP) in subjects with moderate to severe chronic plaque-type psoriasis.
Primary Objective
Demonstrate equivalence in measures of efficacy between M923 (test) and EU RPP in subjects with 
moderate to severe chronic plaque-type psoriasis
Secondary Objective(s)
1. Evaluate the continued efficacy, safety, immunogenicity, and tolerability of M923 compared with EU
RPP
2. Evaluate the transition from EU RPP to M923 based on safety and immunogenicity compared with
continuous use of EU RPP
3. Evaluate drug concentrations over time

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STUDY DESIGN
Study Type/ Classification/ 
Discipline
Bioequivalence, Efficacy, Pharmacokinetic, Safety, Immunogenicity
Control Type
Concurrent (Active)
Study Indication Type
Treatment
Intervention model
Parallel
Blinding/Masking
Double-Blind
Study Design
This study is a Phase 3, controlled, randomized, double-blind, 
multicenter study to evaluate efficacy, safety, and immunogenicity of 
M923 (a proposed adalimumab biosimilar) versus EU RPP in 
516 randomized subjects with moderate to severe chronic plaque-type 
psoriasis to yield 490 subjects (in 2 arms) completing through Week 16.
Arm A:
M923 from Weeks 0 to 48 (last dose at Week 47; n = 258 subjects)
Arm B: 
Reference Protein Product from Weeks 0 to 15 (last dose at Week 15);
then randomized again at Week 16 into Arms B1 and B2:
Arm B1: Continues EU RPP from Weeks 17 through 48 (last dose at 
Week 47; n = up to 129 subjects)
Arm B2: Transition to M923 at Week 17, then to EU RPP at 
Week 25; and then to M923 at Week 37 (last dose at 
Week 47; n = up to 129 subjects)
Subjects who complete the treatment period will have a safety follow-
up visit at Week 52.
Planned Duration of Subject 
Participation
Approximately 56 weeks: 4-week screening period, 48-week treatment 
period, and 4-week safety follow-up period 
Primary Outcome Measure
Proportion of subjects with Psoriasis Area and Severity Index 75% improvement (PASI75) response at 
Week 16 with M923 vs EU RPP
Secondary Outcome Measures
Efficacy
1. Proportion of subjects with response by static Physician Global Assessment (sPGA) of clear or almost
clear (6-point scale) at Week 16 in subjects treated with M923 vs EU RPP
2. PASI50, PASI75, PASI90, and sPGA response rates over time in subjects treated with M923 or
EU RPP
3. Absolute PASI score over time in subjects treated with M923 and EU RPP
4. Health-related quality of life during treatment with M923 and EU RPP based on the Dermatology Life
Quality Index (DLQI) and the EuroQoL 5-Dimension Health Status Questionnaire (EQ-5D-5L)

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Safety
1. Clinical safety and tolerability of M923 compared with EU RPP as assessed by vital signs, clinical
laboratory results, electrocardiograms (ECGs), and adverse events (AEs) (including serious AEs
[SAEs], withdrawal from the study because of an AE, discontinuation of study-specific therapy
because of an AE, and injection site reactions)
2. Clinical safety and tolerability of the transitions between EU RPP and M923 (occurring twice in
arm B2) compared with continuous use of EU RPP (arm B1) – See Figure 1
Pharmacokinetics and Immunogenicity
1. Exposure to M923 and EU RPP assessed as serum levels collected periodically throughout the
treatment period
2. Immunogenicity of M923 and EU RPP assessed as proportion experiencing seroconversion, titer of
anti-drug antibody (ADA) levels over time, and neutralizing ADA
3. Immunogenicity, as evidenced by the presence of ADAs, following the transition from EU RPP to
M923 compared with continuous use of EU RPP assessed as proportion of subjects experiencing
seroconversion; titer of ADA levels over time; and neutralizing ADA over time.
INVESTIGATIONAL PRODUCT(S), DOSE, AND MODE OF ADMINISTRATION
Active Product
M923, a proposed adalimumab biosimilar
Dosage form: 40 mg (0.8 mL) prefilled syringe for injection
Dosage frequency: 80 mg at Week 0 and then 40 mg every 2 weeks (Q2W) 
starting at Week 1
Mode of Administration: subcutaneous (SC)
Comparator
Non-US-approved comparator (EU-approved Humira®) referred to as the 
EU Reference Protein Product
Dosage form: 40 mg (0.8 mL) prefilled syringe for injection
Dosage frequency: 80 mg at Week 0 and then 40 mg Q2W starting at Week 1
Mode of Administration: SC
SUBJECT SELECTION
Targeted Accrual
516 subjects planned for randomization 
572 subjects actually randomized
Number of 
Groups/Arms/Cohorts
258 subjects planned to be randomly assigned to Arm A and 258 subjects
randomly assigned to Arm B. 
At Week 16, subjects in Arm B planned to be randomly assigned again to Arms 
B1 and B2 (up to 129 subjects each)
Inclusion Criteria
1.
Subjects must be ≥ 18 years old at the time of screening
2.
Must be able to understand and communicate with the investigator and comply with the
requirements of the study (including administration of SC injections at home) and must give a
written, signed, and dated informed consent before any study-related activity. Where relevant, a
legal representative will also sign the informed study consent according to local laws and
regulations

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3.
Chronic plaque-type psoriasis diagnosed for at least 6 months before screening
4.
Stable plaque-type psoriasis, defined as no significant change in lesional area or severity, for a
period of 2 months or more before screening
5.
All countries except Canada: History of receipt of or candidate for systemic therapy or
phototherapy with active plaque-like psoriasis despite topical therapy.
Canada only: History of receipt of or candidate for systemic therapy with active plaque-like
psoriasis despite topical therapy.
Canada only: History of phototherapy treatment that was ineffective or phototherapy judged by
the treating physician to be inappropriate for the subject
6.
Moderate to severe psoriasis at screening and baseline (Visit 2), defined as:
a.
PASI score ≥ 12
b.
sPGA score ≥ 3 (based on a scale of 0 to 5)
c.
Body Surface Area (BSA) affected by plaque-type psoriasis ≥ 10%
7.
Must be willing and able to self-administer SC injections or have a caregiver available to
administer injections
8.
Male subjects must either abstain from sexual intercourse or 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 investigational product (IP) until
completion of study procedures. Alternatively, male subjects may have been vasectomized, with
confirmation of sterility.
9.
Female subjects must have a negative pregnancy test at screening and baseline and must not be
lactating. Female subjects must also meet one of the conditions below for the entire duration of the
study:
a.
Abstain from sexual intercourse
b.
Use a method of contraception, as described for female partners in Inclusion Criterion 8,
and have their male partner use a condom until 5 months after the last administration of
the IP
c.
Be of non-childbearing potential, confirmed at screening by fulfilling 1 of the following
criteria:
i.
Postmenopausal, defined as amenorrhea for at least 12 months following cessation
of all exogenous hormonal treatments and with follicle-stimulating hormone levels
drawn during screening within the laboratory-defined postmenopausal range or
postmenopausal with amenorrhea for at least 24 months and on hormonal
replacement therapy
ii.
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

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Exclusion Criteria
1.
Presence of forms of psoriasis other than chronic plaque-type (eg, pustular, erythrodermic, or
guttate psoriasis)
2.
History of or current drug-induced psoriasis (eg, from beta-blockers or lithium)
3.
Presence of other skin conditions, including skin infections, which would interfere with
assessment of psoriasis
4.
Presence of chronic or ongoing medical conditions other than psoriasis for which systemic
corticosteroids were used in the last year prior to screening, eg, asthma
5.
Presence of other inflammatory conditions other than psoriasis or psoriatic arthritis, eg,
rheumatoid arthritis, gout, or inflammatory bowel disease
6.
Subject must have no major deviations regarding concomitant medication, such as prior use of
systemic tumor necrosis factor (TNF) inhibitor therapy, investigational or licensed (ie, other
investigational biosimilar TNF inhibitor therapy exposure is not permitted), or 2 or more non-
TNF biologic therapies required concomitantly
7.
Ongoing use of prohibited psoriasis treatments (eg, prohibited topical corticosteroids, systemic
corticosteroids, ultraviolet (UV)-therapy including excessive sun exposure, immunosuppressant
therapy, including methotrexate); washout periods detailed in the Medications and Non-Drug
Therapies section of the protocol must be followed
8.
Ongoing use of other non-psoriasis prohibited treatments; washout periods detailed in the
Medications and Non-Drug Therapies section of the protocol must be followed
9.
All other prior non-psoriasis concomitant treatments must be on a stable dose for at least 4 weeks
before baseline
10. Laboratory abnormalities at screening deemed clinically significant by the investigator and/or:
a.
Hemoglobin < 8 g/dL for women or 8.5 g/dL for men
b.
White blood cell count < 3.5 x 109/L
c.
Platelet count < 120 x 109/L
d.
Aspartate transaminase or alanine transaminase > 1.5 times the upper limit of normal
e.
Creatinine > 1.5 mg/dL if < 65 years old, or > upper limit of normal if ≥ 65 years old
11. 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 or sponsor pose an unacceptable safety risk
12. History of latex allergy
13. History of or current signs or symptoms or diagnosis of a demyelinating disorder
14. History of or current Class III or IV New York Heart Association congestive heart failure
15. History or current signs, symptoms, or diagnosis of lymphoproliferative disorders, lymphoma,
leukemia, myeloproliferative disorders, or multiple myeloma
16. Current 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; no
more than 3 lifetime basal cell and squamous cell carcinomas permitted

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17. Chronic infections, recurrent infections (3 or more of the same infection requiring anti-infective
treatment in any rolling 12 month period); any recent infection requiring hospitalization or any
infection requiring parenteral anti-infective therapy within 30 days or oral infective therapies
within 14 days of baseline (Visit 2); 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, coccidiomycosis, histoplasmosis, toxoplasmosis)
18. History of or presence of human immunodeficiency virus (HIV), or Hepatitis B (HBV) or C virus
(HCV)
19. History of active tuberculosis (TB) or untreated or inadequately treated latent TB. Subjects must
have a negative QuantiFERON, T-SPOT, or purified protein derivative (PPD) test, and a
radiograph or comparable imaging with negative finding for TB or other similar infections at the
Screening visit or within 3 months prior to Screening visit
20. Subject has been exposed to an IP within 30 days prior to enrollment or is scheduled to
participate in another clinical study involving an IP or investigational device during the course of
this study
21. Subject is a family member or employee of the investigator or site staff or study team
STATISTICAL ANALYSIS
Sample Size Calculation
1.
Primary analysis: Test equivalence of M923 compared with EU RPP using the PASI75 response
rate at 16 weeks, 
2.
3.
516 subjects randomized (258 in Arm A and 258 in Arm B)
Equivalence Margin Justification:
The treatment effect versus placebo, based on PASI75 at 16 weeks from a Phase 3 study (REVEAL 1), was
estimated to be 0.647 (lower bound of 2-sided 95% confidence interval 0.460).
The treatment effect versus placebo, based on PASI75 at 16 weeks from the other pivotal Phase 3 study 
(CHAMPION 2), was estimated to be 0.64 (lower bound of 2-sided 95% confidence interval 0.597).
Margin for US: 
An 18% equivalence margin was selected based on observed variation in response rates in adalimumab’s 
Phase 2 3 vs Phase 3 studies at 12 weeks, and on the statistical (M1) margins in the Phase 3 studies at 
16 weeks. Based on the meta-analysis of the REVEAL 1 and CHAMPION 2 studies, the 95% confidence 
bound for the difference in proportions of PASI75 is 0.5975 to 0.6744.  The acceptable margins (M1) 
statistically from the Phase 3 studies were 0.298 at 16 weeks. The proposed margin of 18% preserves 70% 
of the treatment effect, and is well within both the inter-trial variation in response rates and the M1 from 
Phase 3 and comprises a conservative margin for assessment of equivalence. 
CCI
CCI
CCI

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Margin for EU: 
A 15% equivalence margin was selected based on observed variation in response rates in adalimumab’s 
Phase 2 3 vs Phase 3 studies at 12 weeks, and on the statistical (M1) margins in the Phase 3 studies 
at 16 weeks. Based on the meta-analysis of the REVEAL 1 and CHAMPION 2 studies, the 95% confidence 
bound for the difference in proportions of PASI75 is 0.5975 to 0.6744.  The acceptable margins (M1) 
statistically from the Phase 3 studies were 0.298 at 16 weeks. The proposed margin of 15% preserves 
75% of the treatment effect, and is well within both the inter-trial variation in response rates and the M1 
from Phase 3 and comprises a conservative margin for assessment of equivalence.
Planned Statistical Analysis
Primary Objective: The PASI75 response rate will be described at Week 16 for subjects on M923 (Arm A) 
vs EU RPP (Arm B).
Secondary Objective: The sPGA response rate will be described at Week 16 for subjects on M923 (Arm A) 
vs EU RPP (Arm B). The treatment arms (Arm A and Arm B, as well as Arm A to Arm B1) will be 
compared using descriptive statistics for PASI50, PASI75, PASI90, and sPGA response rates over time.
Safety Objective: Assess safety.

All treatment-emergent adverse events will be summarized by System Organ Class and Preferred
Term and by treatment arm

The clinical safety and tolerability of the transition from EU RPP to M923 as compared with
continuous use of EU RPP with regard to AEs will be evaluated

Physical examination, vital signs, laboratory parameters, and ECGs will be presented by treatment
group for each visit

The clinical safety and tolerability of the transition from EU RPP to M923 as compared with
continuous use of EU RPP will be evaluated using the descriptive statistics provided over time
Pharmacokinetics and immunogenicity: Assess pharmacokinetics and immunogenicity by time point.

The serum levels will be summarized by treatment arm at each scheduled collection. Summaries
will be further stratified by ADA formation. The within-subject variability in trough
concentrations over time (from Week 17 to Week 41) will be determined for each subject and then
compared between treatment arms

Transition from EU RPP to M923 as compared with continuous use of EU RPP with regard to PK
will be evaluated using the descriptive statistics at each schedule time point and statistical
comparison of within-subject variability A summary of the number and percent of subjects testing
positive for ADA or neutralizing antibodies before the dose of M923 or EU RPP and at scheduled
postdose assessments will be presented by treatment arm. The time to seroconversion will be
summarized

The number and percentage of subjects who had at least one ADA-positive result will be provided
by treatment arm

Immunogenicity following the transition from EU RPP to M923 as compared with continuous use
of EU RPP will be evaluated with the number and percentage of subjects who had at least once
ADA-positive by treatment arm and by treatment period

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Response Rate Justification: 
Adalimumab response rates were 71.0% (n = 578/814) and 79.6% (n = 86/108) in 2 previous pivotal 
psoriasis studies. Based on a meta-analysis, the estimated treatment effect was 63.6% (95% confidence 
interval of 59.8% - 67.4%), which was used as the basis for sample size calculation.
Primary Analysis
The methods of analysis for the primary outcome measure will be done on the per protocol (PP) population.
The PASI75 response rate will be described at Week 16 for subjects on M923 (Arm A) vs EU RPP
(Arm B). The Non-Responder Imputation (NRI) method will be used to handle missing data.
For the FDA, all equivalence comparisons will be made using 90% confidence intervals and an equivalence 
margin of 18%. For the EMA, all equivalence comparisons will be made using 95% confidence intervals 
and an equivalence margin of 15%.
A confidence interval for differences between M923 and EU RPP will be calculated using the stratified 
Newcombe confidence interval. 
The null hypothesis of differences in PASI75 proportions of at least 15% for EMA and 18% for FDA will 
be rejected if the 95% confidence interval for EMA and 90% confidence interval for FDA for the difference 
in PASI75 is wholly contained within the equivalence region; in this case, equivalence will be declared.
The primary analysis will be repeated on the intent-to-treat (ITT) population as a sensitivity analysis.
 
An administrative interim database lock will occur at Week 25 to perform the primary analysis, as well as
safety, PK and immunogenicity analysis over this time period. The purpose of the interim database lock is 
to provide an analysis of the primary endpoint data to regulatory agencies before the completion of the 
study. No trial-related decisions will be made based on the interim analysis. The interim analysis will be 
executed by an unblinded team, as appropriate, distinct from the study team. The study team will remain 
blinded until final database lock.
CCI

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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 ........................................................................................... 12
5. LIST OF ABBREVIATIONS .................................................................................... 16
6. BACKGROUND INFORMATION .......................................................................... 18
6.1 Description of Investigational Product ............................................................... 18
6.2 Clinical Condition/Indication .............................................................................. 19
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................................................................................................ 20
6.6 Compliance Statement.......................................................................................... 20
7. STUDY PURPOSE AND OBJECTIVES ................................................................. 20
7.1 Study Purpose ....................................................................................................... 20
7.2 Primary Objective................................................................................................. 20
7.3 Secondary Objectives ........................................................................................... 20
8. STUDY DESIGN......................................................................................................... 21
8.1 Brief Summary...................................................................................................... 21
8.2 Study Design.......................................................................................................... 21
8.3 Duration of Study Period(s) and Subject Participation .................................... 21
8.4 Outcome Measures ............................................................................................... 22
8.4.1 Primary Outcome Measure .......................................................................... 22
8.4.2 Secondary Outcome Measures ..................................................................... 22
8.4.2.1 Efficacy .................................................................................................... 22
8.4.2.2 Safety........................................................................................................ 22
8.4.2.3 Pharmacokinetics and Immunogenicity ............................................... 22
8.5 Randomization and Blinding............................................................................... 23
8.6 Study Stopping Rules............................................................................................ 23
8.7 Investigational Product(s).................................................................................... 24

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8.7.1 Packaging, Labeling, and Storage................................................................ 24
8.7.2 Administration ............................................................................................... 25
8.7.2.1 Injection training .................................................................................... 25
8.7.3 Description of Treatment.............................................................................. 25
8.7.4 Investigational Product Accountability ....................................................... 26
8.8 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 .......................................................................................... 32
10.1 Informed Consent and Enrollment ................................................................... 32
10.2 Subject Identification Code................................................................................ 32
10.3 Screening and Study Visits................................................................................. 32
10.3.1 Screening and Baseline Assessments.......................................................... 32
10.3.2 Treatment Visits........................................................................................... 34
10.3.3 Study Completion/Termination.................................................................. 36
10.3.4 Safety Follow-up .......................................................................................... 36
10.4 Medications and Non-Drug Therapies.............................................................. 37
10.5 Subject Diary....................................................................................................... 39
10.6 Subject Completion/Discontinuation ................................................................ 39
10.7 Procedures for Monitoring Subject Compliance............................................. 40
11. ASSESSMENT OF EFFICACY, IMMUNOGENICITY, AND
PHARMACOKINETICS........................................................................................... 41
11.1 Primary Efficacy Assessment ............................................................................ 41
11.2 Secondary Efficacy Assessments ....................................................................... 41
11.2.1 Static Physician Global Assessment........................................................... 41
11.2.2 Psoriasis Area and Severity Index.............................................................. 41
11.2.3 Body Surface Area....................................................................................... 42
11.2.4 Patient-reported Outcomes – Dermatology Life Quality Index (DLQI) 
and EuroQoL 5-Dimension Health Status Questionnaire......................... 42
11.3 Pharmacokinetics Assessments.......................................................................... 42
11.4 Immunogenicity Assessments ............................................................................ 43
12. ASSESSMENT OF SAFETY................................................................................... 44
12.1 Adverse Events.................................................................................................... 44
12.1.1 Definitions..................................................................................................... 44
12.1.1.1 Serious Adverse Events........................................................................ 44
12.1.1.2 Non-Serious Adverse Events................................................................ 45

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12.1.1.3 Unexpected Adverse Events................................................................. 45
12.1.1.4 Preexisting Diseases.............................................................................. 45
12.1.2 Assessment of Adverse Events.................................................................... 45
12.1.2.1 Severity .................................................................................................. 46
12.1.2.2 Causality................................................................................................ 47
12.2 Urgent Safety Measures ..................................................................................... 48
12.3 Untoward Medical Occurrences........................................................................ 49
12.4 Non-Medical Complaints ................................................................................... 49
12.5 Medical, Medication, and Non-Drug Therapy History................................... 49
12.6 Physical Examinations........................................................................................ 50
12.7 Clinical Laboratory Parameters........................................................................ 51
12.7.1 Hematology and Clinical Chemistry.......................................................... 51
12.7.2 Urinalysis...................................................................................................... 51
12.7.3 Assessment of Laboratory Values .............................................................. 51
12.7.3.1 Assessment of Abnormal Laboratory Values..................................... 51
12.8 Vital Signs............................................................................................................ 52
12.9 Electrocardiograms ............................................................................................ 52
12.10 Injection Site Evaluations ................................................................................ 52
13. STATISTICS............................................................................................................. 54
13.1 Sample Size and Power Calculations ................................................................ 54
13.1.1 Sample Size Calculation.............................................................................. 54
13.2 Populations and Analysis Cohorts..................................................................... 55
13.3 Handling of Missing, Unused, and Spurious Data........................................... 56
13.4 Methods of Analysis............................................................................................ 56
13.4.1 Disposition and Withdrawals...................................................................... 57
13.4.2 Demographic and other Baseline Characteristics .................................... 57
13.4.3 Primary Outcome Measure......................................................................... 57
13.4.4 Secondary Outcome Measures ................................................................... 58
13.4.4.1 Efficacy .................................................................................................. 58
13.4.4.2 Safety...................................................................................................... 58
13.4.4.3 Pharmacokinetics and Immunogenicity ............................................. 59
13.5 Planned Interim Analysis of the Study ............................................................. 60
14. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .................................... 61
15. QUALITY CONTROL AND QUALITY ASSURANCE...................................... 62
15.1 Investigator’s Responsibility.............................................................................. 62
15.1.1 Final Clinical Study Report........................................................................ 62
15.2 Training ............................................................................................................... 62
15.3 Monitoring........................................................................................................... 62
15.4 Auditing ............................................................................................................... 62
15.5 Non-Compliance with the Protocol ................................................................... 63

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15.6 Laboratory and Reader Standardization ......................................................... 63
16. ETHICS ..................................................................................................................... 64
16.1 Subject Privacy ................................................................................................... 64
16.2 Ethics Committee and Regulatory Authorities................................................ 64
16.3 Informed Consent ............................................................................................... 64
16.4 Data Monitoring Committee.............................................................................. 65
17. DATA HANDLING AND RECORD KEEPING................................................... 66
17.1 Confidentiality Policy ......................................................................................... 66
17.2 Study Documentation and Case Report Forms ............................................... 66
17.3 Document and Data Retention........................................................................... 66
18. FINANCING AND INSURANCE........................................................................... 67
19. PUBLICATION POLICY........................................................................................ 67
20. SUPPLEMENTS....................................................................................................... 68
20.1 Study 911401 Schematic..................................................................................... 68
20.2 Schedule of Study Procedures and Assessments.............................................. 69
21. REFERENCES.......................................................................................................... 74
22. SUMMARY OF CHANGES.................................................................................... 76
INVESTIGATOR ACKNOWLEDGEMENT.............................................................. 82
Tables
Table 1 Schedule of Study Procedures and Assessments................................................ 69
Table 2 Laboratory Parameters........................................................................................ 72
Table 3 Injection Site Reaction Grading Scheme............................................................ 73
Figures
Figure 1 Study Design for Baxalta Clinical Study 911401.............................................. 68

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5. LIST OF ABBREVIATIONS
Abbreviation
Definition
ADA
anti-drug antibody
ADCC
antibody-dependent cell-mediated cytotoxicity
AE
adverse event
BSA
body surface area
BTL
bilateral tubal ligation
CDC
complement dependent cytotoxicity
CV
coefficient of variation
DLQI
Dermatology Life Quality Index 
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EQ-5D-5L
EuroQoL 5-Dimension Health Status Questionnaire
ETV
end of treatment visit
EU
European Union
EU RPP
Reference Protein Product, the non-US-approved comparator (EU-approved Humira)
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
HBV
Hepatitis B virus
HCV
Hepatitis C virus
HIV
human immunodeficiency virus 
IB
Investigator's Brochure
ICF
Informed Consent Form
ICH
International Council for Harmonisation
IgG1
immunoglobulin G subclass 1
IP
investigational product
IRT
Interactive Response Technology
ITT
intent-to-treat population
mBOCF
modified baseline observation carried forward
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed models for repeated measures
MTX
methotrexate
NMC 
Non-medical complaint

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Abbreviation
Definition
NRI
non-responder imputation
PA
posterior-anterior
PASI
Psoriasis Area and Severity Index
PASI50
Psoriasis Area and Severity Index 50% improvement
PASI75
Psoriasis Area and Severity Index 75% improvement
PASI90
Psoriasis Area and Severity Index 90% improvement
PK
pharmacokinetics
PP
per protocol population
PPD
purified protein derivative
PUVA
psoralens and long-wave ultraviolet radiation
Q2W
every 2 weeks
QTcF
QT interval corrected for heart rate using Fridericia’s equation
QT
a measure of the time between the start of the Q wave and the end of the T wave in the 
heart's electrical cycle
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
Subcutaneous
SIC
subject identification code
sPGA
static Physician Global Assessment 
TB
Tuberculosis
TEAE
treatment-emergent adverse event
TNF
tumor necrosis factor
US
United States
US RP
Humira approved for use in the US; ie, the US-licensed Reference Product
UV
ultraviolet

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6. BACKGROUND INFORMATION
6.1 Description of Investigational Product
M923 is a proposed adalimumab biosimilar. HUMIRA® (hereafter referred to as Humira)
is the United States (US)-licensed reference product and contains adalimumab as the 
active substance. Adalimumab is a recombinant human immunoglobulin G subclass 1 
(IgG1) monoclonal antibody specific for human tumor necrosis factor–alpha (TNF)-
alpha. Unlike etanercept, adalimumab does not bind to TNF–beta.
Humira is licensed for use in the US and European Union (EU); Humira approved in the 
EU, which is the Reference Protein Product (EU RPP) in this study, is not approved for 
use in the US and hence is considered an investigational new drug. Hereafter, Humira 
licensed in the US is referred to as the US Reference Product (US RP), and the 
non-US-approved comparator (EU-approved Humira) is referred to as the EU RPP.
M923 injection is a preservative-free, sterile solution for subcutaneous (SC) 
administration and is provided as single-use, 1.0 mL prefilled glass syringes that deliver 
40 mg (0.8 mL) of M923. M923 is produced by recombinant deoxyribonucleic acid
technology in a Chinese hamster ovary mammalian cell expression system and is purified 
by a process that includes specific viral inactivation and removal steps. The amino acid 
sequences of M923 and adalimumab are identical. The M923 formulation has a different 
buffer composition than the EU RPP and the US RP; however, the solution characteristics 
(pH, osmolality) of M923 are found to be within pre-specified acceptance criteria to those
of the EU RPP and are expected to exhibit corresponding physiologic effects. There are 
no new components in the M923 buffer.
The M923 dose selected for this study is based on the recommended dose of US RP and 
EU RPP for adult patients with active chronic plaque psoriasis, ie, an initial dose of 
80 mg administered SC, followed by 40 mg SC given every other week starting 1 week 
after the initial dose.4 The safety profile of M923 is anticipated to correspond to the EU 
RPP. Investigators should carefully monitor for all adverse events (AEs), including AEs 
not described as associated with the EU RPP. The pharmacokinetic (PK) profile of M923 
is currently being evaluated in an ongoing PK Phase 1 clinical study; results are not yet 
available.

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6.2 Clinical Condition/Indication
The EU RPP is indicated for the treatment of moderate to severe chronic plaque psoriasis 
in adult patients who failed to respond to or who have a contraindication to, or are 
intolerant to other systemic therapy including cyclosporine, methotrexate (MTX), or 
phototherapy (psoralens and long-wave ultraviolet radiation [PUVA]).4
The medical need for a biosimilar to the EU RPP (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 rheumatoid 
arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, 
Crohn’s disease, ulcerative colitis, and plaque psoriasis.
Provided that comparability of M923 to the EU RPP is demonstrated in all aspects of 
safety and efficacy, then the medical need for this product is also established.
6.3 Population to Be Studied
The study population will include 516 subjects with moderate to severe chronic plaque-
type psoriasis. Adult (≥ 18 years) male and female subjects will be considered to be 
eligible provided that they satisfy all of the inclusion criteria listed in Section 9.1 and 
none of the exclusion criteria listed in Section 9.2.
6.4 Findings from Nonclinical and Clinical Studies
Multiple lots of the US RP and EU RPP have been extensively characterized in 
nonclinical pharmacology, PK, and immunogenicity studies and compared with the 
investigational M923 proposed adalimumab biosimilar product.  The results of these 
comparisons showed that the biological activities of M923 corresponded to the 
comparators (both US RP and EU RPP). Specifically, the results were within the 
acceptance range for M923, EU RPP, and US RP for binding to soluble human TNF-α, 
the human Fcγ receptor, C1q complex, and the human neonatal Fc receptor; activity in 
the antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent 
cytotoxicity (CDC) assays; potency in the L929 mouse fibroblast cell line assay; PK and 
in vitro immunogenicity. A Phase 1 PK study with M923 in healthy volunteers is 
currently ongoing.

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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 overdosage considerations that have been described for Humira (both the 
EU RPP and the US RP) apply to M923 (see Appendix A of the Investigator’s Brochure 
[IB] for M923). However, investigators should carefully monitor for all AEs, including 
AEs not described as associated with the EU RPP and the US RP.
6.6 Compliance Statement
This study will be conducted in accordance with this protocol, the International Council
on Harmonisation Guideline for Good Clinical Practice E6 (ICH GCP, April 1996), 
Title 21 of the US Code of Federal Regulations, the EU Directives 2001/20/EC and 
2005/28/EC, and the Declaration of Helsinki and applicable national and local regulatory 
requirements.
7. STUDY PURPOSE AND OBJECTIVES
7.1 Study Purpose
The purpose of the study is to evaluate efficacy, safety, and immunogenicity of M923 
(a proposed adalimumab biosimilar) and a non-US-approved comparator (EU-approved
Humira®) referred to as the Reference Protein Product (EU RPP) in subjects with 
moderate to severe chronic plaque-type psoriasis.
7.2 Primary Objective
The primary objective of the study is to demonstrate equivalence in measures of efficacy 
between M923 (test) and EU RPP (reference) in subjects with moderate to severe chronic 
plaque-type psoriasis.
7.3 Secondary Objectives
The secondary objectives of the study are to:
1. Evaluate the continued efficacy, safety, immunogenicity, and tolerability of M923
compared with EU RPP
2. Evaluate the transition from EU RPP to M923 based on safety and
immunogenicity compared with continuous use of EU RPP
3. Evaluate concentrations over time

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8. STUDY DESIGN
8.1 Brief Summary
This study is a Phase 3, active-controlled, randomized, double-blind, multicenter study to 
determine the clinical equivalence of M923 and EU RPP in a total of 516 randomized 
subjects (258 subjects in the M923 group and up to 129 subjects in each of 2 EU RPP
crossover groups) with moderate to severe chronic plaque-type psoriasis.
8.2 Study Design
The 2 treatment arms will include:

Arm A: M923 from Weeks 0 to 48 (last dose at Week 47)

Arm B: EU RPP from Weeks 0 to 16 (last dose at Week 15); then randomized
again at Week 16 into Arms B1 and B2:
Arm B1: Continues EU RPP from Weeks 17 through 48 (last dose at
Week 47; n = up to 129 subjects)
Arm B2: Transition to M923 at Week 17; then to EU RPP at Week 25;
and to M923 at Week 37 (last dose at Week 47; n = up to 129 subjects)
Subjects who complete the treatment period will have a safety follow-up visit at 
Week 52.
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 86 weeks from study initiation (ie, first subject 
enrolled) to study completion (ie, last subject last visit) The recruitment period was
expected to be 8 months (actual duration was 7 months).
The subject participation period is approximately 56 weeks (4-week screening period, 
48-week treatment period, and 4-week follow-up period) from enrollment to subject 
completion (ie, last study visit), unless prematurely discontinued.

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8.4 Outcome Measures
8.4.1 Primary Outcome Measure
The primary outcome measure is the Psoriasis Area and Severity Index 75% 
improvement (PASI75) response rate at Week 16 in subjects treated with M923 vs 
EU RPP.
8.4.2 Secondary Outcome Measures
8.4.2.1 Efficacy 
1. Proportion of subjects with response by static Physician Global Assessment
(sPGA) of clear or almost clear (6-point scale) at Week 16 in subjects treated with
M923 vs EU RPP
2. PASI50, PASI75, PASI90, and sPGA response rates over time in subjects treated
with M923 or EU RPP
3. Absolute PASI score over time in subjects treated with M923 and EU RPP
4. Health-related quality of life during treatment with M923 and EU RPP based on
the Dermatology Life Quality Index (DLQI) and the EuroQoL 5-Dimension
Health Status Questionnaire (EQ-5D-5L)
8.4.2.2 Safety
1. Clinical safety and tolerability of M923 compared with EU RPP as assessed by
vital signs, clinical laboratory results, electrocardiograms (ECGs), and AEs
(including serious AEs [SAEs], withdrawal from the study because of an AE,
discontinuation of study-specific therapy because of an AE, and injection site
reactions)
2. Clinical safety and tolerability of the transitions between EU RPP and M923
(occurring twice in arm B2) compared with continuous use of EU RPP (arm B1) –
See Figure 1.
8.4.2.3 Pharmacokinetics and Immunogenicity
1. Exposure to M923 and EU RPP assessed as serum levels collected periodically
throughout the treatment period
2. Immunogenicity of M923 and EU RPP assessed as proportion experiencing
seroconversion, titer of anti-drug antibody (ADA) levels over time, and
neutralizing ADA

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3. Immunogenicity, as evidenced by the presence of ADAs, following the transition
from EU RPP to M923 compared with continuous use of EU RPP assessed as
proportion of subjects experiencing seroconversion; titer of ADA levels over
time; and neutralizing ADA over time
8.5 Randomization and Blinding
This is a randomized, double-blind, active treatment clinical study. In order to 
minimize/avoid bias, subjects will be randomly assigned at the beginning of the 
study to 1 of 2 treatment regimens (M923 or EU RPP) at a ratio of 1:1, stratified 
by region (North America, Western Europe, and Eastern Europe/Asia). 
At Week 16, subjects who were randomly assigned to EU RPP at the screening visit will 
be randomly assigned again into 1 of 2 treatment regimens (continue EU RPP from 
Weeks 17 through 48; or transition between M923 and EU RPP approximately every 
12 weeks from Weeks 17 to 48) at a ratio of 1:1. Stratification will ensure balance of 
treatment assignment within region. The blocking scheme will be specified in the 
randomization specifications. Randomization will occur via an Interactive Response 
Technology (IRT) System until the targeted number of subjects in each treatment arm is 
achieved.
The investigational product (IP) blind shall not be broken by the investigator unless 
information concerning the IP is necessary for the medical treatment of the subject. In the 
event of a medical emergency, if possible, the medical monitor should be contacted 
before the IP blind is broken to discuss the need for unblinding.
For unblinding a subject’s data, the investigator can obtain the treatment assignment by 
utilizing the IRT System.
An administrative interim database lock will occur at Week 25 to perform the primary 
analysis, as well as safety, PK and immunogenicity analysis over this time interval. The 
interim analysis will be executed by an unblinded team distinct from the study team. The
study team will remain blinded, as appropriate, until final database lock.
8.6 Study Stopping Rules
This study will be stopped if 1 or more of the following criteria are met:
1. The sponsor or investigator, based on emerging data, considers there to be an
unfavorable risk-benefit
2. The sponsor or investigator considers continuation of the trial unjustifiable for
medical or ethical reasons

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3. Recruitment of sufficient number of subjects is considered to be impractical in the
required time frame (NB: recruitment requirements are met)
4. The sponsor decides to discontinue development of M923
5. An ethics committee and/or competent authority determines the trial should be
terminated
8.7 Investigational Product(s)
8.7.1 Packaging, Labeling, and Storage
The IPs for this study are EU RPP and M923, which are both clear, colorless solutions
essentially free from visible particles supplied in 40-mg (0.8 mL) prefilled syringes. 
 
 
M923 for injection will be supplied by Baxalta
or representative, and stored in compliance with Good Manufacturing Practice (GMP)
conditions and labeled in accordance with local regulations. The excipients for EU RPP
are sodium chloride, monobasic sodium phosphate dihydrate, dibasic sodium phosphate 
dihydrate, sodium citrate, citric acid, mannitol, polysorbate 80, and water for injection. 
Each EU RPP syringe will contain 0.86 mL to allow the entire labeled volume of 0.8 mL 
to be expelled from the syringe.
A sufficient quantity of 1.0 mL syringes (each syringe will contain 0.86 mL as described 
in Section 8.7.1) containing M923 (40 mg) or EU RPP (40 mg) will be supplied to each 
study site by Fisher Clinical Services. Fisher will package and label M923 and EU RPP, 
which will be released by a Qualified Person at Fisher to each study site.
Individual subject treatments will be dispensed at each study site in 1.0 mL syringes 
labeled in accordance with GMP Annex 13 requirements.
All study medication will be stored in the original container in a refrigerator at ºC
to
°C, protected from light, in a secure, temperature-controlled, locked environment 
with restricted access. The study medication will not be frozen.
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.
C
C
C
C
CCI

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8.7.2 Administration
M923 or EU RPP in prefilled syringes (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 (± 3 days) at the 
same time of day every 2 weeks. Directions for used materials will be provided.
8.7.2.1 Injection training
The study staff will train subjects (or a caregiver) on the SC injection procedure. This 
training should occur at the Baseline Visit. At the Baseline Visit, 2 prefilled syringes are 
required to be administered.  Site staff will show the subject or caregiver how to 
administer with the first syringe, and the subject (or caregiver) will demonstrate the 
injection technique by self-administering with the second syringe. The training and 
performance of self-injection will be documented in the subject’s source documents. 
The Visit at Week 1 may be used for additional training. It is expected that subjects (or 
caregiver) will self-administer from Week 1 forward. At visits where the subject is to 
self-inject at the clinic, site staff should observe the injection to ensure it is being 
performed correctly and to provide retraining as required. 
Subjects are to be instructed that used syringes must be placed in a safety container 
provided by the sponsor. This safety container should be returned to the investigational 
site for disposal. This training will be documented in the subject’s source documents.
8.7.3 Description of Treatment
Subjects will be administered 80 mg of M923 or EU RPP at Week 0 and then 40 mg 
every 2 weeks (Q2W) starting at Week 1 of the study. Self-injections should occur on the 
same day (± 3 days) each treatment week according to a predetermined randomization 
schedule with 2 arms indicated as follows:

Arm A: M923 from Weeks 0 to 48 (n = 258 subjects)

Arm B: EU RPP from Weeks 0 to 16 (last dose at Week 15); then randomized
again at Week 16 into Arms B1 and B2:
Arm B1: Continues EU RPP from Weeks 17 through 48 (last dose at
Week 47; n = up to 129 subjects)
Arm B2: Transition to M923 at Week 17; then to EU RPP at Week 25;
and to M923 at Week 37 (last dose at Week 47; n = up to 129 subjects)

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At Weeks 0, 1, 17, 19, 21, 25, 27, 37, and 39, injections will be administered in the clinic 
after all required assessments and blood sample collections have been completed. 
All other injections will be administered by the subjects or caregiver at home (but after 
assessments completed if a planned injection date coincides with a planned visit date
[Weeks 29, 33, 41, and 45]). When injection occurs in the clinic, subjects should be 
observed for 2 hours in the clinic post-injection at Weeks 0, 1, 17, 25, and 37; at 
Weeks 19, 21, 27, and 39, subjects should be observed for 30 minutes after injection.
At any time during the study, any of the IPs 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.
When injection occurs in the clinic, the investigator or a qualified designee will 
evaluate the current injection sites 30 minutes (± 10 minutes) after study drug 
administration in the clinic at Weeks 0, 1, 17, 19, 21, 25, 27, 37, and 39. 
They should also evaluate immediately prior injection site at each subsequent visit as 
applicable (Section 12.10). For injections given at home, injection site reactions will be 
recorded in the subject diary (Section 10.5). There will be no injection at Week 48 
(Visit 19), but injection site evaluation for previous injections will occur.
Any injection site reactions, regardless of causality, will be recorded on the AE electronic 
case report form (eCRF). Any concomitant medications, including those used to treat 
AE(s), will be recorded on the appropriate eCRF. 
8.7.4 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 kit number, date of manufacture or expiration date, amount received, and 
disposition. IP must be dispensed only at the study site or other suitable location, as 
applicable per study design. 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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8.8 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 
trial that are necessary for the reconstruction and evaluation of the trial. 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, and subject files including
records kept at the pharmacy, at the laboratories, and at medico-technical departments 
involved in the clinical study.
No data will be entered directly onto the eCRF.
For additional information on study documentation and eCRFs, 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 must be ≥18 years old at the time of screening
2. Must be able to understand and communicate with the investigator and comply
with the requirements of the study (including administration of SC injections at
home) and must give a written, signed, and dated informed consent before any
study-related activity. Where relevant, a legal representative will also sign the
informed study consent according to local laws and regulations
3. Chronic plaque-type psoriasis diagnosed for at least 6 months before screening
4. Stable plaque-type psoriasis, defined as no significant change in lesional area or
severity, for a period of 2 months or more before screening
5. All countries except Canada: History of receipt of or candidate for systemic
therapy or phototherapy with active plaque-like psoriasis despite topical therapy.
Canada only: History of receipt of or candidate for systemic therapy with active
plaque-like psoriasis despite topical therapy
Canada only: History of phototherapy treatment that was ineffective or
phototherapy judged by the treating physician to be inappropriate for the subject.
6. Moderate to severe psoriasis at screening and baseline (Visit 2), defined as:
a. PASI score ≥ 12
b. sPGA score ≥ 3 (based on a scale of 0 to 5)
c. Body Surface Area (BSA) affected by plaque-type psoriasis ≥10%
7. Must be willing and able to self-administer SC injections or have a caregiver
available to administer injections
8. Male subjects must either abstain from sexual intercourse or 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 completion of study procedures.
Alternatively, male subjects may have been vasectomized, with confirmation of
sterility.
9. Female subjects must have a negative pregnancy test at screening and baseline
and must not be lactating. Female subjects must also meet one of the conditions
below for the entire duration of the study:

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a. Abstain from sexual intercourse
b. Use a method of contraception, as described for female partners in Inclusion
Criterion 8, and have their male partner use a condom until 5 months after the
last administration of the IP
c. Be of non-childbearing potential, confirmed at screening by fulfilling 1 of the
following criteria:
i. Postmenopausal, defined as amenorrhea for at least 12 months following
cessation of all exogenous hormonal treatments and with follicle-
stimulating hormone levels drawn during screening within the laboratory-
defined postmenopausal range or postmenopausal with amenorrhea for at
least 24 months and on hormonal replacement therapy
ii. 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. Presence of forms of psoriasis other than chronic plaque-type (eg, pustular,
erythrodermic, or guttate psoriasis)
2. History of or current drug-induced psoriasis (eg, from beta-blockers or lithium).
3. Presence of other skin conditions, including skin infections, which would interfere
with assessment of psoriasis
4. Presence of chronic or ongoing medical conditions other than psoriasis for which
systemic corticosteroids were used in the last year prior to screening, eg, asthma
5. Presence of other inflammatory conditions other than psoriasis or psoriatic
arthritis, eg, rheumatoid arthritis, gout, or inflammatory bowel disease
6. Subject must have no major deviations regarding concomitant medication, such as
prior use of systemic TNF inhibitor therapy, investigational or licensed (ie, other
investigational biosimilar TNF inhibitor therapy exposure is not permitted), or 2
or more non-TNF biologic therapies required concomitantly
7. Ongoing use of prohibited psoriasis treatments (eg, prohibited topical
corticosteroids, systemic corticosteroids, ultraviolet (UV)-therapy including
excessive sun exposure, immunosuppressant therapy, including MTX); washout
periods detailed in Section 10.4 must be followed
8. Ongoing use of other non-psoriasis prohibited treatments; washout periods
detailed in Section 10.4 must be followed

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9. All other prior non-psoriasis concomitant treatments must be on a stable dose for
at least 4 weeks before baseline
10. Laboratory abnormalities at screening deemed clinically significant by the
investigator and/or:
a. Hemoglobin < 8 g/dL for women or 8.5 g/dL for men
b. White blood cell count < 3.5 x 109/L
c. Platelet count < 120 x 109/L
d. Aspartate transaminase or alanine transaminase > 1.5 times the upper limit of
normal
e. Creatinine > 1.5 mg/dL if < 65 years old, or > upper limit of normal if
≥65 years old
11. 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 or sponsor
pose an unacceptable safety risk
12. History of latex allergy
13. History of or current signs or symptoms or diagnosis of a demyelinating disorder
14. History of or current Class III or IV New York Heart Association congestive heart
failure
15. History or current signs, symptoms, or diagnosis of lymphoproliferative disorders,
lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma
16. Current 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; no more than 3 lifetime basal cell and squamous cell
carcinomas permitted
17. Chronic infections, recurrent infections (3 or more of the same infection requiring
anti-infective treatment in any rolling 12 month period); any recent infection
requiring hospitalization or any infection requiring parenteral anti-infective
therapy within 30 days or oral infective therapies within 14 days of baseline
(Visit 2); 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, coccidiomycosis, histoplasmosis, toxoplasmosis)
18. History of or presence of human immunodeficiency virus (HIV), or Hepatitis B
(HBV) or C virus (HCV)

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19. History of active tuberculosis (TB) or untreated or inadequately treated latent TB.
Subjects must have a negative QuantiFERON, T-SPOT or purified protein
derivative (PPD), and a radiograph or comparable imaging with negative finding
for TB or other similar infections at the Screening visit or within 3 months prior
to Screening visit
20. Subject has been exposed to an IP within 30 days prior to enrollment or is
scheduled to participate in another clinical study involving an IP or
investigational device during the course of this study
21. Subject is a family member or employee of the investigator or site staff or study
team
9.3 Withdrawal and Discontinuation
Any subject may voluntarily withdraw (ie, reduce the degree of participation in the study) 
consent for continued participation and data collection. The reason for withdrawal will be 
recorded on the End of Study eCRF. Assessments to be done at the termination visit 
(including in cases of withdrawal or discontinuation) are described in Section 10.6 and 
Section 20.2.
Discontinuation (ie, complete withdrawal from study participation) may be due to 
dropout (ie, active discontinuation by subject) or loss to follow-up (ie, discontinuation by 
subject without notice or action). 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 withdrawn from treatment or discontinued from further study 
participation for the following reasons:

Failure to achieve at least a PASI 50 response at Week 25

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

AEs/SAEs that in the investigator or sponsor opinion, poses 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, despite evidence of retraining of the subject. The subject will
be discontinued from further participation in the study

Participation in another clinical study involving an IP during the course of the
study

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10. STUDY PROCEDURES
10.1 Informed Consent and Enrollment
Any subject who provides informed consent (ie, signs and dates the informed consent 
form [ICF]) is considered enrolled in the study.
10.2 Subject Identification Code
 
 
 
 
 All study documents 
(eg, eCRFs, 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 the eCRFs, regardless of screening 
outcome. If a subject is re-screened with the approval of the medical advisor, the End of 
Study eCRF should be completed, and a new ICF, new SIC, and new eCRF are required 
for that subject.
The overall study design is illustrated in the Figure 1. Details on the procedures to be 
done at each study visit, including screening, can be found in Section 20.2. 
10.3.1 Screening and Baseline Assessments
After informed consent has been obtained, subjects will be screened for eligibility based 
on the inclusion and exclusion criteria defined in Section 9.1 and Section 9.2, 
respectively. Screening procedures must be done within 28 days of the baseline visit
(Visit 2; Week 0).
Screening assessments (Visit 1; Week -4 to baseline) include the following:
!
Eligibility evaluation (review of inclusion/exclusion criteria)
PPD

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
Relevant medical and surgical history and all medications according to the
instructions below:
o
Medications/therapies for psoriasis: 8 weeks prior to screening
o
Non-psoriatic medications/therapies: 4 weeks prior to screening
o
All prior biologic medications/therapies (including investigational
biologics)

Review of concomitant medications/non-drug therapies

TB screening

sPGA, PASI, BSA evaluation

Serology tests for HBV, HCV, and HIV-1/HIV-2

Complete physical examination (see Section 12.6)

12-lead ECG (see Section 12.9)

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and
measure body weight and height; see Section 12.8)

Clinical laboratory assessments (hematology and serum chemistry; see
Section 12.7.1)

Urinalysis (see Section 12.7.2)

Serum pregnancy test (female subjects of childbearing potential only)
At the baseline visit (Visit 2; Week 0), subject eligibility will be confirmed and the 
following baseline assessments done:

Patient-reported questionnaires: DLQI and EQ-5D-5L (to be completed prior to
any other assessments being done; see Section 11.2.4)

Eligibility evaluation reviewed (inclusion/exclusion criteria)

Review of concomitant medications/non-drug therapies

sPGA, PASI, BSA evaluation (see Section 11.2.1 and Section 11.2.2)

AE monitoring

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and
measure body weight)

Brief physical examination

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
12-lead ECG

PK and immunogenicity

Clinical laboratory assessments (hematology and serum chemistry)

Urinalysis

Urine pregnancy test (female subjects of childbearing potential only)
After all baseline assessments have been completed, subjects will be randomized and 
begin treatment with administration of their first dose of IP as below:

Randomization of eligible subjects to the following treatment arms:
Arm A: M923 from Weeks 0 to 48
Arm B: EU RPP from Weeks 0 to 16

Injection site training

Study drug injection (as directed by study site staff) and evaluation of self-
administration

Post-injection monitoring at 30 minutes (± 10 minutes) after injection and there
will be an observation period for a minimum of 2 hours post injection (see
Section 12.10)
10.3.2 Treatment Visits
During the double-blind treatment period (Weeks 1 to 48), subjects will return to study 
site according to the schedule presented in Table 1.
Subjects will self-administer 40 mg of M923 or EU RPP every 2 weeks (Q2W) starting at 
Week 1 of the study.
Prior to administration of IP, the following assessments will be done at all visits unless 
otherwise indicated:

Patient-reported questionnaires: DLQI and EQ-5D-5L (to be completed prior to
any other assessments being done [Weeks 16, 25, and 37])

Review of concomitant medications/non-drug therapies

AE monitoring

sPGA, PASI, BSA evaluation

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
Brief physical examination (Weeks 4, 8, 17, 19, 25, 27, 37, and 39; complete
physical examination at Week 16)

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and
measure body weight)

12-lead ECG (Weeks 16, 25, and 37)

PK and immunogenicity (Weeks 8, 16, 17, 21, 25, 29, 37, and 41)

Clinical laboratory assessments (hematology and serum chemistry; all visits,
except Weeks 12, 27, 33, 39, and 45)

Urinalysis (Weeks 4, 8, 16, 17, 19, 21, 25, and 37)

Urine pregnancy test (female subjects of childbearing potential only; all visits,
except Weeks 1, 19, 27, 39 and 45)

Study drug dispensing

Study drug injection in clinic by subject or caregiver (as directed by study site
staff)(Weeks 1, 17, 19, 21, 25, 27, 37, and 39)
Post-injection monitoring for 2 hours post-injection (clinic only;
Weeks 1, 17, 25, and 37)
Post-injection observation for 30 minutes post-injection (clinic only;
Weeks 19, 21, 27, and 39)

Study drug injection at home, but after assessments completed at clinic visit
(Weeks 29, 33, 41, and 45)

Study drug injection at home in-between clinic visits (Weeks 3, 5, 7, 9, 11, 13, 15,
23, 31, 35, 43, and 47)

Injection site evaluation either by clinical staff (at clinic visits) or by the subject
or caregiver (administration at home) per Section 12.10
At Week 16, subjects in Arm B will be randomly assigned again to a new treatment 
group:

Arm B1: Continues EU RPP from Weeks 17 through 48 (last dose at Week 47;
n = up to 129 subjects)

Arm B2: Transition to M923 at Week 17; then to EU RPP at Week 25; and to
M923 at Week 37 (last dose at Week 47; n = up to 129 subjects)

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10.3.3 Study Completion/Termination
At study completion (Week 48/end of treatment visit [ETV]), the following assessments 
will be done:

Patient-reported questionnaires: DLQI and EQ-5D-5L (should be completed prior
to any other assessments are done)

Review of concomitant medications/non-drug therapies

AE monitoring

sPGA, PASI, BSA evaluation

Complete physical examination

Vital signs (body temperature, pulse rate, blood pressure, respiratory rate, and
measure body weight)

12-lead ECG

PK and immunogenicity

Clinical laboratory assessments (hematology and serum chemistry)

Urinalysis

Urine pregnancy test (female subjects of childbearing potential only)

Injection site evaluation

Study drug return
10.3.4 Safety Follow-up
At the safety follow-up visit (Visit 20; Safety Follow-up, Week 52 ± 2 weeks), the 
following assessments will be performed:

Review of concomitant medications/non-drug therapies

AE monitoring

sPGA, PASI, BSA evaluation

Brief physical examination

Vital signs (body temperature, pulse rate, blood pressure, and respiratory rate and
measure body weight)

PK and immunogenicity

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
Clinical laboratory assessments (hematology and serum chemistry)

Urinalysis

Urine pregnancy test (female subjects of childbearing potential only)
The safety follow-up visit is done by subjects who completed the study treatment as per 
protocol requirements and those who have withdrawn from the study early. 
If the subject does not show up to the clinical visit, the site should try contacting the 
subject by phone for at least 8 weeks after the scheduled follow-up visit and obtain 
information regarding the occurrence of adverse events, treatments for psoriasis as well 
as other concomitant medications and pregnancy status. In case the subject is a female of 
childbearing potential, at Week 48 a urine dipstick pregnancy test should be provided.
Information collected after Week 52 visit will be collected only as source data and not 
included in the eCRF.
At the safety follow-up visit the investigator should consider the next therapy to prescribe 
to the subject off-study, in order to maintain clinical benefit.
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 psoriasis therapies. Subjects may take allowed
additional concomitant medication(s) as needed for medical management during this 
study. All medications taken 4 weeks prior to screening and concomitant medication use 
should be recorded in the appropriate eCRF. Exposure to all biologic medications at any 
time should be collected. 
The following medications and non-drug therapies are not permitted during the course of 
the study:

Medications:
Systemic TNF inhibitor therapy, or B-cell depleting therapy, including other
investigational biosimilar TNF inhibitors or B-cell depleting therapies, or 2 or
more non-TNF biologic therapies
Other biologic immunomodulating therapies such as ustekinumab or other
licensed or investigational biologics within 24 weeks prior to baseline
(Visit 2) and during the duration of the study. Prior exposure to more than
one such biologic immunomodulating therapy not permitted

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Systemic treatment with licensed or investigational immunosuppressive or
targeted agents such as, but not limited to, cyclosporine, tacrolimus, MTX,
azathioprine, 6-mercaptopurine, or hydroxyurea within 8 weeks prior to
baseline (Visit 2) and during the duration of the study; excepting apremilast,
tofacitinib within 4 weeks prior to baseline and during the duration of the
study
Systemic and topical retinoid or Vitamin D analog therapy within 4 weeks
prior to baseline and during the duration of the study. Up to 1000 IU/day
average dose of Vitamin D therapy is permitted if stable dose for 4 weeks
prior to screening and during the duration of the study
Topical calcineurin inhibitors, such as pimecrolimus, within 4 weeks prior to
baseline and during the duration of the study
Topical or systemic corticosteroids for treatment of psoriasis within 4 weeks
prior to baseline and during the duration of the study. Topical steroids of
weak potency (World Health Organization group VII) will be permitted for
use during the study, but must not be used within 24 hours of study visits.
Systemic corticosteroids used within the last year prior to screening for
conditions other than psoriasis are not permitted
Topical treatments containing acetylsalicylic acid, if used for psoriasis
Topical tar derivatives within 2 weeks prior to baseline and during the course
of the study
Phototherapy and photochemotherapy within 4 weeks prior to baseline and
during the course of the study. Subjects should be advised to avoid tanning
booths and excessive sun exposure, eg, sun bathing
Shampoos, moisturizers, and emollients that do not contain salicylic acid, tar,
corticosteroids, and vitamin D analogs are allowed but must not be used in
the 12 hours prior to study visits
All other prior non-psoriasis concomitant treatments must be on a stable dose
for at least 4 weeks prior to baseline
Injectable anti-infective therapy within 30 days, or oral infective therapies
within 14 days of baseline
Live/attenuated vaccination within 6 weeks prior to baseline and during the
duration of the study is not allowed
A subject who has taken any of these medications or received any of these non-drug 
therapies will be discontinued.

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10.5 Subject Diary
A paper subject diary will be provided to each subject at each visit to record the 
following information, as applicable according to Table 1:
1. Time, date, and location of IP administration; including whether the full dose was
administered and, if not, why the full dose was not administered (eg, device
malfunction)
2. IP administrator (self or caregiver)
3. AEs, including injection site reactions
Subjects and/or their legally authorized representatives will be trained on use of the diary. 
The diary will be provided in paper format and the subject should bring the completed 
diary to the site at each visit. The investigator will review the diary for completeness,
request missing information periodically and in a timely manner, photocopy the 
applicable pages, store them in the source documents until such time when the original 
subject diary is collected. Untoward events recorded in the diary will be reported as AEs 
according to the investigator’s discretion and clinical judgment.
During the treatment period, at Week 25, the subject diary may be collected and a new 
diary provided to the subject and retrieved at Week 48.
The subject diary will serve as a source record and remain at the study site once 
collected. Entries in the subject diary will be transferred into the eCRF. Any entry in the 
eCRF that does not correspond with an entry in the subject diary will be explained by the 
investigator in source documentation.
10.6 Subject Completion/Discontinuation
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 according with the protocol (with or without protocol deviations).
Reasons for completion/discontinuation will be reported on the 
Completion/Discontinuation eCRF, 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)

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
Physician decision (eg, pregnancy)

Progressive disease

Non-compliance with IP/protocol deviation(s), recovery, study terminated by
sponsor

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 eCRF. 
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 done at the termination visit (including in cases of withdraw or 
discontinuation) can be found in Table 1 and Table 2.
After the discontinuation visit, if the subject agrees, a follow-up visit performing the 
same assessments as the Week 52 visit should be conducted 5 weeks after last IP dose.
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 done 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 
or EU RPP.
Subjects receiving less than 18 doses (75% compliance) will be considered non-
compliant

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11. ASSESSMENT OF EFFICACY, IMMUNOGENICITY, AND
PHARMACOKINETICS
11.1 Primary Efficacy Assessment
The primary efficacy outcome measure is the proportion of subjects treated with M923 vs 
EU RPP who achieve a 75% reduction in PASI from Week 0 (baseline) to Week 16 of 
the treatment period. Psoriasis will be assessed using the PASI, which is a measure of the 
average redness, thickness, and scaliness of the lesions (each graded on a 0 to 4 scale, 
weighed by the area of involvement. PASI score will be recorded by the investigator/site 
staff at clinic visits as shown in the schedule in Table 1.
11.2 Secondary Efficacy Assessments
Secondary efficacy outcome measures consisting of response as measured by the sPGA, 
PASI scores over time, and health-related quality of life by the DLQI and the EQ-5D-5L
will be evaluated in subjects treated with M923 vs EU RPP as detailed in Section 11.2.1, 
Section 11.2.2, and Section 11.2.4.
11.2.1 Static Physician Global Assessment
The proportion of subjects with response by sPGA of clear or almost clear (6-point scale) 
at Week 16 in subjects treated with M923 vs EU RPP treatment will be assessed. In 
addition, the sPGA response rate of subjects treated with M923 vs EU RPP over time will 
be compared. 
The sPGA will be evaluated by a qualified investigator at the site. The sPGA is the 
physician’s determination of the subject’s psoriasis lesions overall at a given time point. 
The sPGA is recommended as an endpoint to use to assess efficacy in the treatment of 
psoriasis.5 Overall lesions are categorized by descriptions for induration, erythema, and 
scaling. For the analysis of responses, the subject’s psoriasis is assessed at a given time 
point on a 6 point scale in which 0 = cleared, 1 = minimal, 2 = mild, 3 = moderate, 
4 = severe, 5 = very severe. The sPGA evaluations will be recorded on the eCRF by the 
investigator/site staff at clinic visits as shown in the schedule in Table 1.
11.2.2 Psoriasis Area and Severity Index
A comparison of the proportion of subjects treated with M923 vs EU RPP who achieve 
50%, 75%, and 90% reductions in psoriasis severity over time, as well as the response of 
subjects treated with M923 and EU RPP over time based on the absolute PASI score, will 
be assessed. 

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The PASI will be evaluated by a qualified investigator at the site. The PASI combines 
assessments of the extent of body-surface involvement in 4 anatomical regions (head 
[10% of BSA], arms [20% of BSA], trunk [30% of BSA], and legs [40% of BSA]) and 
the severity of desquamation (scaling), erythema (redness), and induration (thickness) in 
each region, yielding an overall score of 0 for no disease to 72 for the most severe 
disease.6 Each of the body areas is scored by itself, and then the four scores are combined 
into the final PASI. For each body area, the percent of area of skin involved is estimated 
and then transformed into a score from 0 to 6: 0 = 0% of involved area, 1 = < 10% of 
involved area, 2 = 10% to 29% of involved area, 3 = 30% to 49% of involved area, 
4 = 50% to 69% of involved area, 5 = 70% to 89% of involved area, 6 = 90% to 100% of 
involved area. Severity parameters are measured on a five point scale in which 
0 = None, 1 = Slight, 2 = Moderate, 3 = Severe, 4 = Very Severe. The sum of all 
3 severity parameters is then calculated for each body area, multiplied by the area score 
for that area and multiplied by weight of respective section (0.1 for head, 0.2 for arms, 
0.3 for trunk and 0.4 for legs). Subjects achieving PASI 50, 75, 90, or 100 are defined as 
having an improvement of at least 50%, 75%, 90%, or 100%, respectively, in the PASI 
compared with baseline. Information required to calculate the PASI will be recorded on 
the eCRF by the investigator/site staff at clinic visits as shown in the schedule in Table 1.
11.2.3 Body Surface Area
The investigator will evaluate the percentage involvement of psoriasis on each subject’s 
BSA on a continuous scale from 0% = no involvement to 100% = full involvement, 
where 1% corresponds to the size of the subject’s handprint including the palm, fingers, 
and thumb.7
11.2.4 Patient-reported Outcomes – Dermatology Life Quality Index (DLQI) and 
EuroQoL 5-Dimension Health Status Questionnaire
Health-related quality of life during treatment with M923 and EU RPP will be evaluated 
by the DLQI and the EQ-5D-5L questionnaires. The assessments will be recorded on the 
eCRF by the investigator/site staff at clinic visits as shown in the schedule in Table 1.
11.3 Pharmacokinetics Assessments
Blood samples for analysis of serum M923 or EU RPP in terms of serum levels will be 
collected at the times shown in the schedule in Table 1. Samples should be obtained prior 
to administering study drug if an administration occurs at that visit and before any 
hematology/chemistry samples to be drawn at that visit. Samples will be collected and 
aliquotted into primary and back-up specimens. Back-up specimens should be stored at -
20 °C or -70 °C until shipment. Blood sample processing and handling details will be 
presented in a separate laboratory manual.

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Bioanalysis
Samples for determination of M923 or EU RPP concentrations in serum will be analyzed 
by Quintiles BioSciences, on behalf of Baxalta US Inc., using appropriate bioanalytical 
methods, which will be described in a separate bioanalytical report. All samples still 
within the known stability of the analytes of interest (ie, M923 or EU RPP) at time of 
receipt by the bioanalytical laboratory will be analyzed.
11.4 Immunogenicity Assessments
Blood samples for analysis of and ADA levels to M923 and EU RPP will be collected at 
the times shown in the schedule in Table 1. ADA analysis will be conducted using a 
screening assay based on M923 to identify potentially positive ADA samples. 
Subsequently, confirmatory assays based on EU RPP and M923 will be used to confirm 
the positive status of 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 and an iso-typing assay will be done. 
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.

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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.), disease (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.
12.1.1.1 Serious Adverse Events
A SAE is defined as an untoward medical occurrence that at any dose meets 1 or more of 
the following criteria:

Outcome is fatal/results in death

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

Requires inpatient hospitalization or results in prolongation of an existing
hospitalization – inpatient hospitalization refers to any inpatient admission,
regardless of length of stay
o
Hospitalizations occurring during the study and planned before subject
randomization will not be considered SAEs and should be clearly stated in
the subject’s medical history

Results in persistent or significant disability/incapacity (ie, a substantial
disruption of a person’s ability to conduct normal life functions)

Is a congenital anomaly/birth defect

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 1 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, hepatitis A virus,
HBV, HCV, hepatitis E virus, or parvovirus B19

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12.1.1.2 Non-Serious Adverse Events
A non-serious AE is an AE that does not meet the criteria of an SAE.
12.1.1.3 Unexpected Adverse Events
An unexpected AE is an AE whose nature, severity, specificity, or outcome is not 
consistent with the term, representation, or description used in the Reference Safety 
Information (eg, IB, package insert). “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 drug, but are not specifically mentioned as occurring 
with the particular drug under investigation.
For the purposes of this study, each unexpected AE reported by a subject undergoing 
study treatment or a study-related procedure will be recorded on the AE eCRF.
12.1.1.4 Preexisting Diseases
Preexisting 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 preexisting disease, the event must be described on 
the AE eCRF.
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 or EU RPP
treatment will be recorded on the AE eCRF; however, these events will not be considered 
as AEs and will not be included in the analysis of AEs.
Each treatment-emergent AE (non-serious AE or SAE) from the first M923 or EU RPP
treatment until study completion/discontinuation (Week 48) or 4 weeks following the last 
M923 or EU RPP treatment (for early termination subjects) will be described on the AE 
eCRF 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:

Seriousness as defined in Section 12.1.1.1

Severity as defined in Section 12.1.2.1

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
Causal relationship to IP exposure or study procedure 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 withdrawn, not applicable, or unknown) will also be recorded on the AE 
eCRF. Recovering/resolving AEs will be followed until resolution, medically stabilized, 
or 30 days 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.
Deviations from the protocol-specified dosage (including overdosing [any dose that is at 
least 20% higher than the highest explored dose level], underdosing [any dose that is 
lower than the intended explored dose level by 10%], abuse, and withdrawal [see 
Section 9.3]), 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 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 or EU RPP will be reported on a 
Pregnancy Form and followed-up at 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 SAE Form within 24 hours after 
awareness; no additional reporting on eCRFs is necessary.
A post-trial SAE report (SAER) form in paper will be used to report SAEs after a 
subject’s completion.
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:

Mild
The AE is a transient discomfort and does not interfere in a significant
manner with the subject’s normal functioning level

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The AE resolves spontaneously or may require minimal therapeutic
intervention

Moderate
The AE produces limited impairment of function and may require therapeutic
intervention
The AE produces no sequela/sequelae

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
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, dechallenge/rechallenge 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:

Not related (both circumstances must be met)
Is due to underlying or concurrent illness, complications, concurrent
treatments, or effects of concurrent drugs
Is not associated with the IP (ie, does not follow a reasonable temporal
relationship to the administration of IP or has a much more likely alternative
etiology)

Unlikely related (either 1 or both circumstances are met)
Has little or no temporal relationship to the IP
A more likely alternative etiology exists

Possibly related (both circumstances must be met)
Follows a reasonable temporal relationship to the administration of IP

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An alternative etiology is equally or less likely compared with the potential
relationship to the IP

Probably 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 (positive
rechallenge)
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 after 
IP administration, 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.
12.2 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 trial from immediate harm. 
Urgent safety measures may be taken by the sponsor or clinical investigator, and may 
include any of the following: 

Immediate change in study design or study procedures

Temporary or permanent halt of a given clinical trial or trials

Any other immediate action taken in order to protect clinical trial 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 is notified of the urgent measures taken in 
such cases according to local regulations.

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12.3 Untoward Medical Occurrences
Untoward medical occurrences occurring before the first exposure to M923 or EU RPP
are not considered AEs (according to the definition of AE, see Section 12.1). However,
each serious untoward medical occurrence reported before the first M923 or EU RPP
treatment (ie, from the time of signed informed consent up to but not including the first 
M923 or EU RPP treatment) will be described on the SAE Report.
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. NMCs include but are not limited to the following:

A failure of a product to exhibit its expected pharmacological activity and/or
design function, eg reconstitution difficulty

Missing components

Damage to the product or unit carton

A mislabeled product (eg, potential counterfeiting/tampering)

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 for 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, 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, throat, chest/respiratory, 
heart/cardiovascular, gastrointestinal/liver, gynecological/urogenital, 
musculoskeletal/extremities, skin, neurological/psychiatric, endocrine/metabolic, 
hematologic/lymphatic, allergies/drug sensitivities, past surgeries, substance abuse or any 
other diseases or disorders.
Subjects’ history of TB will be reviewed at screening; subjects with a negative history 
will proceed to QuantiFERON-TB Gold testing, T-SPOT, or PPD, and a radiograph or 
comparable imaging with negative finding for TB or other similar infections (PA, or PA 
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Subjects will be assessed for a history of or current diagnosis of active TB, or untreated 
latent TB infection (LTBI). Subjects may present documentation of results (PPD, 
T-SPOT, or QuantiFERON and radiograph or comparable imaging test) completed within 
3 months of the screening visit. If these results are unavailable, one of the following will 
be done at the screening visit: PPD (onsite), QuantiFERON (central lab), or T-SPOT 
(ELISPOT) test (onsite). History of or current diagnosis of active TB, or untreated latent 
TB infection (LTBI), is defined as a TB skin test with PPD as evidenced by induration 
≥5 mm; a positive QuantiFERON; or positive or borderline T-SPOT (ELISPOT).
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, and will 
be eligible for the study (minimum treatment period with a recognized and regionally 
appropriate regimen of 4-6 weeks prior to start of IP).
Clinically significant radiograph report per investigator opinion or evidence of active TB 
on radiograph will be documented. Radiograph must have been done within 3 months 
prior to the screening visit or during the screening period.
All medications taken and non-drug therapies received from enrollment until 
completion/termination will be recorded on the concomitant medications and non-drug 
therapies eCRFs.
12.6 Physical Examinations
At screening and subsequent study visits (as described in Table 1), a physical 
examination will be done on 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. Details regarding the procedures and tests to be 
conducted at the complete and brief physical exams are provided in the Schedule of 
Study Procedures and Assessments (Table 1). At screening, if an abnormal condition is 
detected, the condition will be described on the medical history eCRF. At study visits, if a 
new abnormal or worsened abnormal pre-existing condition is detected, the condition will 
be described on the AE eCRF. If the abnormal value was not deemed an AE because it 
was due to an error, due to a preexisting disease (described in Section 12.1.1.4), 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.

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12.7 Clinical Laboratory Parameters
12.7.1 Hematology and Clinical Chemistry
The hematology panel will consist of complete blood count (hemoglobin, hematocrit, 
erythrocytes [ie, red blood cell count], and leukocytes [ie, white blood cell count]) with 
differential (ie, basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelet 
counts, and mean cell volume.
The clinical chemistry panel will consist of sodium, potassium, chloride, bicarbonate, 
protein, albumin, ALT, AST, GGT, CPK, bilirubin, lactate dehydrogenase, C-reactive
protein, cholesterol, triglycerides, calcium, phosphate, uric acid, alkaline phosphatase, 
blood urea nitrogen, creatinine, and glucose.
Blood will be obtained for assessment of hematology and clinical chemistry parameters 
according to the schedule detailed in Table 1. A list of parameters to be assessed is 
included in Table 2.
Hematology and clinical chemistry assessments will be done on EDTA-anticoagulated 
whole blood and serum, respectively, at the central laboratory.
In addition, serum samples for pregnancy tests for females of childbearing potential will 
be done.
12.7.2 Urinalysis
Urine will be collected according to the schedule detailed in Table 1. A list of parameters 
to be assessed is included in Table 2.
12.7.3 Assessment of Laboratory Values
12.7.3.1 Assessment of Abnormal Laboratory Values
The investigator will assess each laboratory value. 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 eCRF), is a symptom or related to a previously 
recorded AE, is due to a pre-existing disease (described in Section 12.1.1.4), 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 
preexisting disease, due to a laboratory error, due to variation within the healthy
population, or due to another issue that will be specified). 

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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. 
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; 
screening visit only) and weight (lb or kg) will also be collected.
Vital signs will be measured at screening and prior to administration of M923 or EU 
RPP, at each study visit, and at study completion/termination. Blood pressure will be 
measured when subjects are in the supine position and after resting for at least 5 minutes.
Vital sign values are to be recorded on the eCRF. 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 eCRF).
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.
12.9 Electrocardiograms
A 12-lead ECG is done at study visits according to the schedule described in Table 1. The 
following parameters will be recorded in the eCRF: ventricular rate, PR interval, QRS 
duration, QT, and QT interval corrected for heart rate using Fridericia’s equation (QTcF). 
QTcF will be calculated as follows: QTcF = QT / (3√RR).
ECGs done at regular study visits will be interpreted locally.
12.10 Injection Site Evaluations
The current and prior site of SC injection of the study drug to the lower abdomen or thigh 
will be assessed for immediate local reactions 30 minutes (± 10 minutes) after injection.
In addition, there will be an observation period for a minimum of 2 hours post injection 
after administration of M923 or EU RPP onsite at Weeks 0, 1, 17, 25, and 37. For 
injections given at home, injection site reactions will be recorded in the subject diary as 
described in Section 10.5.

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Injection site evaluations will be made by clinical staff or by the subject or caregiver, 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 1, 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 3; 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 investigator’s judgment, based on the 
AE grading schemes presented in Section 12.1.2.1).

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13. STATISTICS
13.1 Sample Size and Power Calculations
13.1.1 Sample Size Calculation
Primary analysis: Test equivalence of M923 compared with EU RPP using the PASI75 
response rate at 16 weeks,
 
 
 A total of 516 subjects will be randomized (258 in Arm A and 258 in Arm B) 
Response Rate Justification: 
Adalimumab response rates were 71.0% (n = 578/814) and 79.6% (n = 86/108) in 
2 previous pivotal psoriasis studies. Based on a meta-analysis, the estimated treatment 
effect was 63.6% (95% confidence interval of 59.8% - 67.4%), which was used as the 
basis for sample size calculation.
Equivalence Margin Justification:
The treatment effect versus placebo, based on PASI75 at 16 weeks from a Phase 1 study 
(REVEAL 1), was estimated to be 0.647 (lower bound of 2-sided 95% confidence 
interval0.460).
The treatment effect versus placebo, based on PASI75 at 16 weeks from the other pivotal
Phase 3 study (CHAMPION 2), was estimated to be 0.64 (lower bound of 2-sided 95% 
confidence interval 0.597). 
Margin for USA:
An 18% equivalence margin was selected based on observed variation in response 
rates in adalimumab’s Phase 2 3 vs Phase 3 studies at 12 weeks, and on the statistical 
(M1) margins in the Phase 3 studies at 16 weeks. Based on the meta-analysis of the 
REVEAL and CHAMPION studies, the 95% confidence bound for the difference 
in proportions of PASI75 is 0.5975 to 0.6744.  The acceptable margins (M1) 
statistically from the Phase 3 studies were 0.298 at 16 weeks. The proposed margin of 
18% preserves 70% of the treatment effect, and is well within both the inter-trial 
variation in response rates and the M1 from Phase 3 and comprises a conservative 
margin for assessment of equivalence. 
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Margin for EU:
An 15% equivalence margin was selected based on observed variation in response rates 
in adalimumab’s Phase 2 3 vs Phase 3 studies at 12 weeks, and on the statistical (M1) 
margins in the Phase 3 studies at 16 weeks. Based on the meta-analysis of the REVEAL 1
and CHAMPION 2 studies, the 95% confidence bound for the difference in proportions of 
PASI75 is 0.5975 to 0.6744.  The acceptable margins (M1) statistically from the Phase 3 
studies were 0.298 at 16 weeks. The proposed margin of 15% preserves 75% of the 
treatment effect, and is well within both the inter-trial variation in response rates and the 
M1 from Phase 3 and comprises a conservative margin for assessment of equivalence. 
13.2 Populations and Analysis Cohorts
Intent-to-treat (ITT):
The ITT population will include all consenting subjects randomized to study treatment 
(Arm A or Arm B). Subjects will be assigned to treatment groups based on 
randomization.
Per-Protocol (PP):
The PP population is a subgroup of the ITT population which will include all subjects
who do not have any major protocol deviations and received at least 1 dose of study 
medication. 
Major protocol deviations will include, but are not limited to: deviation of 
inclusion/exclusion criteria, administration of prohibited medications and erroneous 
administration of study treatment. The criteria for grading protocol deviations will be 
established by the Quintiles Therapeutic Medical Advisor. Major protocol deviations will 
be determined on a case-by-case basis by the medical reviewer prior to database lock and 
unblinding. Subjects will be assigned to treatment groups based on randomization.
Safety:
The safety population will include all subjects who received at least 1 dose of study 
medication (M923 or EU RPP). Subjects will be assigned to treatment groups based on 
what they actually received.
Pharmacokinetics (PK):
The PK population will include all subjects who received at least 1 dose of study 
medication (M923 or EU RPP) and have at least 1 measured concentration at a scheduled 
PK time point after start of dosing. If any subjects are found to be noncompliant with 
respect to dosing or have incomplete data, a decision will be made on a case-by-case 
basis as to their inclusion in the analysis.

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13.3 Handling of Missing, Unused, and Spurious Data
Non-Responder Imputation (NRI) for Clinical Response: Subjects will be considered 
as non-responders for the NRI analysis if they do not meet the clinical response criteria 
for categorical responses (PASI50, PASI75, PASI90, sPGA) at a time point of interest 
(Week 16). All non-responders at Week 16, as well as all subjects who discontinue study 
treatment prior to Week 16 for any reason, will be defined as non-responders for the 
NRI analysis for all categorical PASI and sPGA analyses at the time point of interest.
Modified Baseline Observation Carried Forward (mBOCF): The continuous 
efficacy and health outcome variables will be based on a modified baseline observation 
carried forward (mBOCF) approach. For subjects who discontinue the study treatment 
due to AE, the baseline observation will be carried forward to the corresponding time 
point for evaluation. For subjects who discontinued the study treatment due to any 
other reason, the last non-missing observation before discontinuation will be carried 
forward to the corresponding time point for evaluation. Randomized subjects without
at least 1 post-baseline observation will not be included for evaluation with the exception 
of subjects who discontinued the study treatment due to AE.
Mixed Models for Repeated Measures (MMRM): As a supportive analysis, continuous 
endpoints will be imputed based on mixed-effects model repeated measures (MMRM) for 
the ITT population 8. Categorical endpoints derived from continuous measures will be 
derived from the imputed continuous measure. 
13.4 Methods of Analysis
In general, all efficacy, safety, PK, and immunogenicity variables will be summarized 
using descriptive statistics. Continuous variables will be summarized by sample size, 
mean, standard deviation, median, minimum, and maximum.  Categorical variables will 
be summarized in frequency tables (n, frequencies, and percentages).  Individual subject 
data will be presented in listings.
The study consists of a treatment period of 48 weeks and subsequent safety follow up. 
The analysis of primary outcome will use data from the first 16 weeks. 
The default significant level will be (5%); confidence intervals will be 95% and all tests 
will be 2-sided, unless otherwise specified in the description of the analyses. Details of 
the statistical analysis will be specified in the Statistical Analysis Plan (SAP), which will 
be finalized prior to treatment assignment unblinding. The SAP will contain the details of 
the missing data modeling, including model specification, the analysis of the secondary 
and pharmacokinetic endpoints, and the presentation of safety data.

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13.4.1 Disposition and Withdrawals
All subjects who provided informed consent will be accounted for in this study. Subject
disposition and withdrawals, and protocol deviations (including inclusion and exclusion 
criteria) will be presented for the ITT population.
13.4.2 Demographic and other Baseline Characteristics
Demographic data and other baseline characteristics will be described for the ITT and PP 
populations overall and by treatment arm. No statistical testing will be carried out for 
demographic or other baseline characteristics.
13.4.3 Primary Outcome Measure
The methods of analysis for the primary outcome measure (see Section 8.4) will be done
on the PP population.
The PASI75 response rate will be described at Week 16 for subjects on M923 (Arm A) vs 
EU RPP (Arm B). The NRI method (see Section 13.3) will be used to handle missing 
data.
For the FDA, all equivalence comparisons will be made using 90% confidence intervals 
and an equivalence margin of 18%. For the EMA, all equivalence comparisons will be 
made using 95% confidence intervals and an equivalence margin of 15%.
A confidence interval for differences between M923 and EU RPP will be calculated 
using the Newcombe confidence interval.9;10 The null hypothesis of differences in 
PASI75 proportions of at least 15% for EMA and 18% for FDA will be rejected if the 
95% confidence interval for EMA and 90% confidence interval for FDA for the 
difference in PASI75 is wholly contained within the equivalence region; in this case, 
equivalence will be declared.
The primary analysis will be repeated on the ITT population as a sensitivity analysis
using the NRI, mBOCF, and MMRM methods of imputation. The MMRM model will 
include baseline, treatment group (A, B1, or B2), region (North America, Western 
Europe, or Eastern Europe), and the treatment-by-visit interaction. An unstructured 
variance-covariance matrix will be estimated. If the procedure fails to converge then the 
treatment-by-visit term will be removed from the model. If the model still fails to 
converge, a heterogeneous Toeplitz structure will be used for the variance-covariance 
matrix. The Kenward-Roger method will be used for estimating degrees of freedom.11

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13.4.4 Secondary Outcome Measures 
13.4.4.1 Efficacy
The methods of analysis for the secondary efficacy outcome measures (see 
Section 8.4.2.1) will be done on the PP population and repeated on the ITT population.
The sPGA response rate will be described at Week 16 for subjects on M923 (Arm A) vs 
EU RPP (Arm B). 
The NRI method (see Section 13.3) will be used to handle missing data. A 95% 
confidence interval for differences between M923 and EU RPP will be calculated using 
the stratified Newcombe confidence interval.
The treatment arms (Arm A and Arms B1 and B2) will be compared using descriptive 
statistics for PASI50, PASI75, PASI90, and sPGA response rates over time. The NRI 
method (see Section 13.3) will be used to handle missing data.
13.4.4.2 Safety
The methods of analysis for the secondary safety outcome measures (see Section 8.4.2.2) 
will be done on the safety population.
AEs will be coded using Medical Dictionary for Regulatory Activities dictionary.
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Treatment-emergent adverse events (TEAEs) are defined as AEs that started or worsened 
in severity on or after the first dose of study medication.
All TEAEs (including SAEs, AEs related to study drug, AEs leading to discontinuation,
and injection site reactions) will be summarized by System Organ Class and Preferred 
Term and by treatment arm (Arm A and Arms B1 and B2). All AEs will be included in 
the listings (non-TEAEs and TEAEs).
The clinical safety and tolerability of the transition from EU RPP to M923 as compared 
with continuous use of EU RPP with regard to AEs will be evaluated with a summary of 
all TEAEs by treatment arm and by treatment period:

Period 1 from Week 0 to Week 16 (included)

Period 2 from Week 16 to Week 25 (included)

Period 3 from Week 25 to Week 37 (included)

Period 4 from Week 37 to Week 48 (included)

Follow-up
Physical examination, vital signs, laboratory parameters, and ECGs will be presented by 
treatment group for each visit. Descriptive statistics of value and change from baseline 
will be provided for vital signs and laboratory parameters. 
The clinical safety and tolerability of the transition from EU RPP to M923 as compared 
with continuous use of EU RPP with regard to all safety endpoints will be evaluated 
using the descriptive statistics provided over time.
13.4.4.3 Pharmacokinetics and Immunogenicity
The methods of analysis for the secondary PK outcome measures (see Section 8.4.2.3) 
will be done on the PK population.
The serum levels will be summarized by treatment arm at each scheduled collection. In 
addition to descriptive statistics described in Section 13.4, the geometric mean, 
corresponding 95% confidence interval, and the geometric coefficient of variation (CV) 
will also be presented. To evaluate whether of anti-adalimumab antibody formation will 
affect exposure, the summaries will be further stratified by ADA formation (subjects who 
did not form antibodies, subjects who formed ADAs, versus subjects who formed 
neutralizing ADAs). The within-subject variability (CV) in trough concentrations over 
time (from Week 17 to Week 41) will be determined for each subject, which will then be 
compared between treatment arms using an analysis of variance model with treatment as 
a fixed effect.

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The transition from EU RPP to M923 as compared with continuous use of EU RPP with 
regard to PK will be evaluated using the descriptive statistics at each schedule time point 
and statistical comparison of within-subject variability.
Pharmacokinetic data from the study may also be used for population 
PK/pharmacodynamic analyses. If done, a separate analysis plan will be prepared and 
results will be reported separately from the Clinical Study Report.  Population PK/PD 
analyses are not planned following the administrative interim database lock at Week 25.
The immunogenicity analysis will be done on the safety population.
Immunogenicity data (overall ADA results and titers, and neutralizing ADA results 
and isotype of ADA where applicable, and time to seroconversion) will be listed. 
A summary of the number and percent of subjects testing positive for ADA or 
neutralizing antibodies before the dose of M923 or EU RPP and at scheduled postdose 
assessments will be presented by treatment arm.  The time to seroconversion will be 
summarized by treatment arm using mean, median, standard deviation and range where 
appropriate. 
The number and percentage of subjects who had at least one ADA-positive result will be 
provided by treatment arm. Similar analysis may be done for subjects with predose ADA-
negative results and with at least one postdose ADA-positive results as appropriate.
The immunogenicity following the transition from EU RPP to M923 as compared with 
continuous use of EU RPP will be evaluated with the number and percentage of subjects
who had at least once ADA-positive by treatment arm and by treatment period (as 
defined in the Section 13.4.4.2).
13.5 Planned Interim Analysis of the Study
An administrative interim database lock will occur at Week 25 to perform the primary 
analysis on the first 516 randomized subjects. The purpose of the interim database lock is 
to provide an analysis of the primary endpoint, safety, PK and immunogenicity up 
through Week 25 to regulatory agencies before the completion of the study. No trial-
related decisions will be made based on the interim analysis. Since no trial-related 
decisions will be made based on this analysis, the Type I error rate is preserved and no 
multiplicity adjustment is needed. An interim clinical study report from the interim 
analysis week 25 (primary endpoint) will be to support regulatory submissions. 

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The interim analysis will be executed by an unblinded team distinct from the study team. 
The study team will remain blinded until final database lock. Data to be locked will 
include efficacy and safety up through Week 25 on the first 516 randomized subjects. 
The details of the interim analysis, including methodology to maintain the blind of the 
study team, will be discussed in a separate interim analysis plan.
The final analysis will include the total number of subjects (n=572) and a final clinical 
study report will be produced accordingly.
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 Study Agreement. 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 Clinical Study Agreement.

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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 regulatory requirements as described in the 
Clinical Study Agreement. 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 regulatory guidelines/requirements. 
The investigator will permit the study monitor to visit the study site at appropriate 
intervals, as described in the Clinical Study Agreement. 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 regulatory guidelines/requirements.

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The investigator will permit auditors to visit the study site, as described in the Clinical 
Study Agreement. Auditing processes specific to the study will be described in the 
auditing plan.
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 ethics committee 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 Clinical Study Agreement.
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 Clinical Study Agreement. 
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 subjects and/or their legally authorized representative must sign an ICF before 
entering into the study according to applicable 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 
regulatory requirements. Subjects or their legally authorized representative(s) will be 
allowed sufficient time to consider participation in the study. By signing the ICF, subjects
or their legally authorized representative(s) agree that they will complete all evaluations 
required by the study, unless they withdraw voluntarily or are terminated from the study 
for any reason.

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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 has 
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.
16.4 Data Monitoring Committee
A Data Monitoring Committee is not used for this study for the following reason:
Subjects are on IP which is the same dose as a product that is already licensed.
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 Clinical 
Study Agreement. 
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 8.8), 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, eCRFs, SAE reports, 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 done 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 eCRFs. The eCRFs will be provided in electronic form.
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 Clinical Study Agreement.

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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 Clinical Study 
Agreement.
19. PUBLICATION POLICY
The investigator will comply with the publication policy as described in the Clinical 
Study Agreement. 

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20. SUPPLEMENTS
20.1 Study 911401 Schematic
Figure 1
Study Design for Baxalta Clinical Study 911401
*Injections administered subcutaneously at Weeks 0 and 1, and then every 2 weeks in each arm. Last dose at Week 47.
# Subjects in Arm B are randomized again 1:1 at Week 16 into Arms B1 and B2.
D = Day; EU RPP = Reference Protein Product; N = number of subjects; PASI = Psoriasis Area and Severity Index.
Discontinue 
all subjects 
not achieving 
a PASI50
1:1 Randomization
Safety 
Follow-up
-
EU RPP
M923
EU RPP
             EU RPP
M923             M923    
M923
M923 (N = ~129)
EU RPP (N = ~129)
EU RPP, N = 258
M923, N = 258
Day -28 to -1 
Screening
Week 0 Baseline
Randomization 
1:1
Week 16
Primary endpoint
PASI75
Week 25
Major secondary endpoints
Interim data lock
          Week 37               Week 48
End of
Treatment
Week 52
End of 
Study
Double Blind Treatment Period*
Arm A
Arm B1
Arm B2

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20.2 Schedule of Study Procedures and Assessments
Table 1
Schedule of Study Procedures and Assessments
Phase
Screen
-ing
Double-Blind Period
Safety 
Follow-
ups
Week
-4 
to 0
0
1
4
8
12
16
17
19
21
25
27
29
33
37
39
41
45
48/
ETV
52
Study Day
-28 
to -1
1
8
29
57
85
113
120
134
148
176 190
204
232
260
274
288
316
337
365
Visitr
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Informed consent 
X
Medical history and prior 
medications (including 
prior therapy, psoriasis, and 
surgeries)
X
Inclusion/exclusion criteria 
X
Xa
Concomitant therapyb

Randomization
X
Xc
Tuberculosis screening
Xd
sPGA, PASI, BSAe
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQI and EQ-5D-5Lf
X
X
X
X
X
HIV, Hepatitis B and C 
viral testing
X
Adverse event monitoring

Physical exam
Xg
X
X
X
Xg
X
X
X
X
X
X
Xg
X
12-lead ECGh
X
X
X
X
X
X
Vital signsi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK and immunogenicityj
X
X
X
X
X
X
X
X
X
X
X
Hematology, chemistryk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy testl
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

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Table 1
Schedule of Study Procedures and Assessments
Phase
Screen
-ing
Double-Blind Period
Safety 
Follow-
ups
Week
-4 
to 0
0
1
4
8
12
16
17
19
21
25
27
29
33
37
39
41
45
48/
ETV
52
Study Day
-28 
to -1
1
8
29
57
85
113
120
134
148
176 190
204
232
260
274
288
316
337
365
Visitr
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Injection trainingm
X
Study drug injection onsiten
X
X
X
X
X
X
X
X
X
Post-injection monitoring 
onsiteo
X
X
X
X
X
X
X
X
X
Injection site evaluationp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study drug dispensing
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study drug return
X
Study diary 
dispensing/collectionq
X
X
X
AE = adverse event; BSA = body surface area; DLQI = Dermatology Life Quality Index; ECG = electrocardiogram; ETV = end of treatment visit; HIV = human 
immunodeficiency virus; EQ-5D-5L = EuroQoL-5 dimensions- 5 levels; PA: posterior-anterior, PASI = Psoriasis Area and Severity Index; PK = 
pharmacokinetics; PPD = purified protein derivative; sPGA = static Physician Global Assessment; TB = tuberculosis
a Inclusion/exclusion criteria to be reviewed before randomization. The screening visit needs to occur with enough time prior to randomization to ensure eligibility 
requirements for the screening visit are met.
b Concomitant therapy will include pharmacologic and nonpharmacologic therapies.
c Subjects in Arm B are randomized again at this visit.
d Subjects will receive testing if not received within previous 3 months and/or doesn’t have documented history of prior positive TB test result or active TB 
infection. Testing includes QuantiFERON, T-SPOT, or PPD and a radiograph or comparable imaging with negative finding for TB or other similar infections (PA 
or PA and lateral view).
e sPGA, PASI and BSA assessments should be conducted at screening and at baseline before randomization and study drug administration to ensure eligibility. 
f All subject-completed assessments (ie, patient-reported outcomes) should be completed before any other assessments are done. 
g Complete physical exam will be conducted at screening, Week 16, and 48.  All other physical exams will be brief and should include heart, lungs, abdomen and 
extremities and skin, and any other assessments required to evaluate AEs.
h ECG should be recorded before blood sampling.
i Vital signs should be taken before blood sampling.  Height will be measured at Visit 1 only.

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Table 1
Schedule of Study Procedures and Assessments
Phase
Screen
-ing
Double-Blind Period
Safety 
Follow-
ups
Week
-4 
to 0
0
1
4
8
12
16
17
19
21
25
27
29
33
37
39
41
45
48/
ETV
52
Study Day
-28 
to -1
1
8
29
57
85
113
120
134
148
176 190
204
232
260
274
288
316
337
365
Visitr
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
j PK and immunogenicity blood samples are to be collected in all subjects at these time points. Samples should be obtained prior to administering study drug if an 
administration occurs at that visit and before any hematology/chemistry samples to be drawn at that visit. 
k Blood samples will be taken before injection of study drug, 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. Serum test will be done at screening; all other assessments are done on urine.
m Self-injection training should be provided with the first injection, with subject or caregiver performing the second injection at the first visit.  Additional training 
can be provided with the Week 1 injection, if needed.  At all other visits where the injection occurs in clinic, the subject or caregiver should administer the 
injection and be observed to ensure correct administration.
n Study drug will be administered in clinic after all required assessments and blood sample collections have been completed at Weeks 0, 1, 17, 19, 21, 25, 27, 37, 
and 39. Injections will occur at home in-between clinic visits on Weeks 3, 5, 7, 9, 11, 13, 15, 23, 31, 35, 43 and 47.  At Weeks 29, 33, 41, and 45, the study drug 
injections will be completed at home after the assessments are completed at the clinic.  
o When injection occurs in the clinic, subjects should be observed for a minimum of 2 hours in the clinic after injection at Weeks 0, 1, 17, 25, and 37. Subjects
should be observed for 30 minutes after injection at Weeks 19, 21, 27, and 39. At Week 48, only return of study drug will occur.
p The investigator or a qualified designee will evaluate the current injection sites 30 minutes (± 10 minutes) after study drug administration in the clinic at Weeks 0, 
1, 17, 19, 21, 25, 27, 37, and 39. They should also evaluate any immediately prior injection site at each subsequent visit as applicable. For injections given at home, 
injection site reactions will be recorded in the subject diary. There will be no injection at Week 48 (Visit 19), but injection site evaluation for previous injections 
will occur.
q The subject should bring the diary at all visits between Weeks 1 and 48. The investigator will review the diary for completeness, request missing information 
periodically and in a timely manner, photocopy and store the applicable pages in the source documents until the original diary is collected. At Week 25, the subject 
diary will be collected by the investigator and a new one will be provided until Week 48.
r Visit windows are ±1 day at Visit 3, ±3 days for Visits 4-19 and ±2 weeks for Visit 20. Reference for visit windows/study day is scheduling based on Visit 
2/Baseline Visit.
s If the subject does not show up to the clinical visit, the site should try to contact the subject by phone for at least 8 weeks after the scheduled follow-up visit and 
obtain information regarding the occurrence of adverse events, psoriatic and concomitant treatments and pregnancy status. Discontinuing subjects will be invited to 
perform this visit 5 weeks after last IP dose.

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Table 2
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 transaminase 
Alanine transaminase 
Alkaline phosphatase 
Gamma glutamyl transferase 
Total bilirubin 
Lactate dehydrogenase 
Creatine kinase
C-reactive protein 
Cholesterol 
Triglycerides 
Total protein 
Sodium 
Potassium 
Chloride 
Bicarbonate
Urea 
Creatinine 
Albumin 
Calcium 
Phosphate 
Glucose 
Uric acid 
Urinalysis 
Leucocytes 
Protein 
Bilirubin 
Urobilinogen 
Glucose 
Ketones 
Blood 
pH 
Nitrite 
Specific gravity 
Urine microscopy 
To be done where clinically indicated
Viral serology
Hepatitis B surface antigen, anti-Hepatitis B surface 
antigen and anti-Hepatitis B core total (IgG and IgM)
Hepatitis C antibody 
Human immunodeficiency virus (HIV I and II) 
Tuberculosis (TB)
QuantiFERON®-TB Gold test
T-SPOT
Serum/urine pregnancy test
Beta human chorionic gonadotropin
Follicle-stimulating hormone
IgG = immunoglobulin G; IgM = immunoglobulin M. 

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Table 3
Injection Site Reaction Grading Scheme
Intensity Grading
Reaction
Absent
(0)
Milda
(1)
Moderatea
(2)
Severea
(3)
Potentially Life-threatening
(4)
Pain 
Absent 
Does not interfere with 
activity 
Repeated use of non-
narcotic pain reliever 
>24 hours or interferes 
with activity 
Any use of narcotic pain 
reliever or prevents daily 
activity 
Hospital visit (A and E) or 
hospitalization 
Tenderness 
Absent 
Mild discomfort to touch 
Discomfort with 
movement 
Significant discomfort at 
rest 
A and E visit or 
hospitalization 
Erythema/ redness 
Absent 
2.5 to 5.0 cm 
5.1 to 10.0 cm 
>10.0 cm 
Necrosis or exfoliative 
dermatitis 
Induration/ swelling 
Absent 
2.5 to 5.0 cm and does not 
interfere with activity 
5.1 to 10.0 cm or 
interferes with activity 
>10.0 cm or prevents 
daily activity 
Necrosis 
Otherb
Absent
Present
A and E = accident and emergency department; AE = adverse event. 
a Measurements refer to the reaction at the greatest single diameter. Measurements of less than 2.5 cm diameter for erythema or induration may be captured as 
mild per investigator discretion.
b Any other reactions such as bruising, itching or ulceration will be recorded as absent or present and will be recorded as AEs; AEs will be categorized according 
to the investigator’s judgment, using the guidance presented in Section 12.1.2

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21. REFERENCES
1. Cook, D. Medical Review Humira (adalimumab) Injection, Solution for
subcutaneous use. sBLA 125057/110, 80. 3-23-2007.  U.S. Food and Drug
Administration (FDA) and Center for Drug Evaluaton and Research (CDER).
2. Saurat JH, Stingl G, Dubertret L et al. Efficacy and safety results from the
randomized controlled comparative study of adalimumab vs. methotrexate vs.
placebo in patients with psoriasis (CHAMPION). Br.J.Dermatol. 2008;158:558-
566.
3. Gordon KB, Langley RG, Leonardi C et al. Clinical response to adalimumab
treatment in patients with moderate to severe psoriasis: Double-blind, randomized
controlled trial and open-label extension study. J.Am.Acad.Dermatol. 2006;55:598-
606.
4. Humira Summary of Product Characteristics.  2014.  European Medicines Agency
(EMEA).
Link to Publisher´s Site:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/
000481/human_med_000822.jsp&mid=WC0b01ac058001d124
5. Committe for Medicinal Products for Human Use. Guideline on clinical
investigation of medicinal products incidcated for the treatment of psoriasis.
CHMP/EWP/2454/02 corr, 18. 11-18-2014. London, European Medicines Agency
(EMEA). Link to Publisher´s Site:
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/200
9/09/WC500003329.pdf
6. Fredriksson T, Pettersson U. Severe psoriasis--oral therapy with a new retinoid.
Dermatologica. 1978;157:238-244.

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7. van Voorhees A, Feldman SR, Koo JYM, Lebwohl MG, Menter A. The Psoriasis
and Psoriatic Arthritis Pocket Guide: Treatment Algorithms and Management
Options. Portland, OR: National Psoriasis Foundation; 2009.
8. Mallinckrodt CH, Sanger TM, Dubé S et al. Assessing and interpreting treatment
effects in longitudinal clinical trials with missing data. Biol.Psychiatry
2003;53:754-760.
9. Yan X, Su XG. Stratified Wilson and Newcombe confidence intervals for multiple
binomial proportions. Stat.Biopharm.Res. 2010;2:329-335.
10. Kim Y, Won S. Adjusted proportion difference and confidence interval in stratified
randomized trials. Cary, NC: SAS Institute, Inc.; 2013:
11. Kenward MG, Roger JH. Small sample inference for fixed effects from restricted
maximum likelihood. Biometrics. 1997;53:983-997.

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22. SUMMARY OF CHANGES
Protocol 911401 Amendment 3 (Global) 2016 AUG 04
Replaces: Amendment 2: 2015 OCT 08
In this section, changes made in this amendment from the previous version of the
protocol, dated 2015 OCT 08, are described and their rationale is given.
1.
Throughout the document
Description of Change: Minor grammatical and/or administrative changes have
been made. 
Purpose for Change: To improve the readability and/or clarity of the protocol.
2.
Throughout the document
Description of Change: The following changes were applied to the PK sections of
the protocol:

Section 8.4.2.3: The outcome measure “Exposure to M923 and EU RPP
assessed as trough serum levels” was updated to “Exposure to M923 and
EU RPP assessed as serum levels”

Section 11.3: “Blood samples for analysis of serum M923 or EU RPP in
terms of trough serum levels will be collected at the times shown in the
schedule in Table 1” was changed to “Blood samples for analysis of serum
M923 or EU RPP in terms of serum levels will be collected at the times
shown in the schedule in Table 1”

Section 13.4.4.3:
o
“The trough serum levels will be summarized by treatment arm at
each scheduled collection” was changed to “The serum levels will
be summarized by treatment arm at each scheduled collection”
o
“To evaluate whether of anti-adalimumab antibody formation will
affect trough exposure…” was changed to “To evaluate whether of
anti-adalimumab antibody formation will affect exposure…”
Purpose for Change: Serum samples through Week 16 are collected at midpoint. 
For this reason, the term “trough” was removed in the aforementioned sections.
3.
Section 1.2 Study Organization
Description of Change: Inclusion of information from the study medical monitors
Purpose for Change: To identify the study medical monitors

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4.
Section 2 Serious Adverse Event Reporting
Description of Change: Contact for SAE questions changed to
“QLS_M923@quintiles.com”
Purpose for Change: This is the specific address for SAE processing, which was
considered the ideal destination for SAE reports and queries
5.
Section 7.2 Primary objective
Description of Change: Primary objective “to demonstrate equivalent efficacy
between M923 (test) and EU RPP (reference) in subjects with moderate to severe
chronic plaque-type psoriasis” was changed to “to demonstrate equivalence in
measures of efficacy between M923 (test) and EU RPP (reference) in subjects
with moderate to severe chronic plaque-type psoriasis”
Purpose for Change: To clarify the study objective
6.
Section 7.3 Secondary Objectives
Description of Change: Secondary objective “Evaluate the safety,
immunogenicity, and tolerability of M923 compared with EU RPP” was changed
to “Evaluate the continued efficacy, safety, immunogenicity, and tolerability of
M923 compared with EU RPP”
Purpose for Change: To clarify the study objective
7.
Section 7.3 Secondary Objectives
Description of Change: Secondary objective “Evaluate exposure of EU RPP and
M923” was changed to “Evaluate concentration summaries over time”
Purpose for Change: To clarify the study objective
8.
Section 8.2 Study Design
Description of Change: The following sentence was added “Subjects who
complete the treatment period will have a safety follow-up visit at Week 52”
Purpose for Change: To include a reference to the safety follow-up visit in this
Section
9.
Section 8.3 Duration of Study Period(s) and Subject Participation
Description of Change: The actual recruitment period that was observed in this
study was added
Purpose for Change: To reflect the actual recruitment period

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10. Section 8.4 Outcome measures
Description of Change: The following changes were applied

On safety outcome measures 1 and 2, the starting words “Evaluate the”
were removed

On PK outcome measure 1, the word “trough” was removed and it was
added that exposure would be assessed as serum levels “collected
periodically throughout the treatment period”

In PK outcome measure 3, it was reinforced that immunogenicity would
be assessed as evidenced by the presence of ADAs
Purpose for Change: To clarify the outcome measures and they will be measured
11. Section 8.8 Source data
Description of Change: It was added in the text that “no data will be entered
directly onto the eCRF”
Purpose for Change: To acknowledge that no source data will be entered directly
onto the eCRF
12. Section 9.1 Inclusion Criteria
Description of Change: the following changes were added

Minor typographical changes throughout the criteria

In inclusion criterion 1, the term “any age” was removed, as it was
incorrect

In inclusion criterion 9, bullet b, it was added that male partners should
use a condom “until 5 months after the last administration of IP”
Purpose for Change: To clarify a maximum period where male partners should 
use a condom
13. Section 9.2 Exclusion Criteria
Description of Change: the following changes were added

Minor typographical changes throughout the criteria

In exclusion criterion 6, it was added that the subject must have no major
deviations regarding concomitant medication

In exclusion criterion 8, the sentence “All other prior non-psoriasis
concomitant treatments must be on a stable dose for at least 4 weeks
before baseline (Visit 2)” was removed

In exclusion criterion 19, “x-ray” was replaced by “a radiograph or
comparable imaging with negative finding for TB or other similar
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Purpose for Change: For criterion 6, to clarify this criterion further. The sentence 
from exclusion criteria 8 was removed because it was reflected in exclusion 
criterion 9. For criterion 19, to clarify the type of imaging exam acceptable for 
this study.
14. Section 10.3.1 Screening and Baseline Assessments
Description of Change: the following instructions were added for screening
evaluation of relevant medical and surgical history and all medications:

Medications/therapies for psoriasis: 8 weeks prior to screening

Non-psoriatic medications/therapies: 4 weeks prior to screening

All prior biologic medications/therapies (including investigational
biologics)
Purpose for Change: To clarify the time periods for concomitant medication 
history data collection
15. Section 10.3.4 Safety follow-up
Description of Change: Inclusion of additional instructions for safety follow-up
visit, including eligibility to participate in this visit, time periods for clinical visits
and phone contacts and collection of information in the eCRF
Purpose for Change: To clarify the safety follow-up procedures and requirements
16. Section 10.4 Medications and Non-Drug Therapies
Description of Change: Inclusion of topical treatments containing acetylsalicylic
acid in the list of treatments not permitted during the course of the study
Purpose for Change: To clarify all non-permitted treatments
17. Section 10.5 Subject diary
Description of Change: The following was clarified in this Section

At each visit, the investigator will photocopy the applicable diary pages,
store them in the source documents until such time when the original
subject diary is collected

During the treatment period, at Week 25, the subject diary may be
collected and a new diary provided to the subject and retrieved at Week 48
Purpose for Change: To clarify how the study diary will be handled during the 
study

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18. Section 10.6 Subject Completion/Discontinuation
Description of Change: It was added that after the discontinuation visit, if the
subject agrees, a follow-up visit should be conducted 5 weeks after last IP dose.
Purpose for Change: To clarify that a follow-up visit may be conducted in
agreeing subjects who discontinue the study, for safety purposes
19. Section 10.7 Procedures for Monitoring Subject Compliance
Description of Change: Inclusion of criteria for minimum IP compliance in order
for subjects to be considered eligible for per protocol analysis
Purpose for Change: To clarify the IP compliance criteria
20. Section 11.3 Pharmacokinetics Assessments
Description of Change: Storage temperature of back-up specimens was updated
(to be stored at -20 ºC or -70 ºC)
Purpose for Change: To provide accurate acceptable storage temperatures
21. Section 12.1.1.1 Serious Adverse Events
Description of Change: In the SAE definition, it was clarified that hospitalizations
occurring during the study period but planned before subject inclusion will not be
considered SAEs
Purpose for Change: To clarify SAE definition
22. Section 12.5 Medical, Medication, and Non-Drug Therapy History
Description of Change: The following changes were carried out, along with other
typographical updates:

“x-ray” was replaced by “a radiograph or comparable imaging with
negative finding for TB or other similar infections”

A minimum treatment period for LTBI was clarified to be “with a
recognized and regionally appropriate regimen of 4-6 weeks prior to start
of IP”
Purpose for Change: To clarify the minimum LTBI treatment period and the 
acceptable imaging tests
23. Section 13.4.4.1 Efficacy
Description of Change: Formula updated
Purpose for Change: Typographical error in mathematical formula corrected

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24. Section 13.4.4.2 Safety
Description of Change: Periods defined for the analysis of AEs were re-defined.
Additionally the sentence “Frequency and percentages of changes between
normal and abnormal for physical examination and ECGs will be calculated” was
removed
Purpose for Change: To clarify and simplify the analysis
25. Section 13.4.4.3 Pharmacokinetics and Immunogenicity
Description of Change: the following changes were made, together with minor
typographical updates:

“Maximum likelihood estimator of the coefficient of variation” was
replaced by “the geometric coefficient variation”

The following sentence was added “population PK/PD analyses are not
planned following the administrative interim database lock at Week 25”

Purpose for Change: To clarify PK and immunogenicity analysis
26. Section 13.5 Planned Interim Analysis of the Study
Description of Change: It was clarified that the interim analysis would be done for
the first randomized subjects and would analyze primary endpoint data and PK up
through Week 25. It was also clarified that the final analysis would be carried out
in all subjects recruited (n=572)
Purpose for Change: To clarify interim and final analysis procedures
27. Section 20.2 Schedule of Study Procedures and Assessments
Description of Change: Table 1 was updated to include study diary dispensing and
returning procedures, as well as specifying drug returning procedures and reflect
the changes mentioned in the amendment
Purpose for Change: To improve clarity and coherence throughout the protocol
28. Section 20.2 Schedule of Study Procedures and Assessments
Description of Change: Table 2 was updated to include the following parameters:

Viral serology: Hepatitis B surface antigen, anti-Hepatitis B surface
antigen and anti-Hepatitis B core total (IgG and IgM)

Tuberculosis: T-SPOT
Purpose for Change: To clarify test parameters

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INVESTIGATOR ACKNOWLEDGEMENT
PRODUCT: M923
STUDY TITLE: A Phase 3 Randomized, Double-blind, Multicenter Study to 
Evaluate Efficacy, Safety, and Immunogenicity of M923 (a Proposed Adalimumab 
Biosimilar) and Humira® in Subjects with Moderate to Severe Chronic Plaque-type 
Psoriasis
PROTOCOL IDENTIFIER: 911401
CLINICAL TRIAL PHASE 3
AMENDMENT 3 (Global): 2016 AUG 04
Replaces: Amendment 2: 2015 OCT 08
ALL VERSIONS: 
Amendment 3: 2016 AUG 04
Amendment 2: 2015 OCT 08
Amendment 1: 2015 JUL 27
Original: 2015 MAY 13
OTHER ID(s)
EudraCT Number: 2015-001751-76
NCT Number: NCT02581345
IND NUMBER: 115119
By signing below, the investigator acknowledges that he/she has read and understands 
this protocol, and provides assurance that this study will be conducted according to all 
requirements as defined in this protocol, clinical study agreement, ICH GCP guidelines, 
and all applicable regulatory requirements.
Signature of Investigator
Date
Print Name and Title of Investigator
Signature of Sponsor Representative
Date
, MD, Vice President, Clinical Development
PPD