Clinical trial NCT04761627
Conditions: Psoriasis
Keywords: Psoriasis Biosimilar Psoriasis area and severity index Ustekinumab Skin Diseases Dermatologic Agents Papulosquamous
Sponsor: Amgen
Start date: 2021-03-24; Completion date: 2023-02-28
Enrollment: 494 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the study is to evaluate pharmacokinetic similarity, efficacy, safety and immunogenicity of multiple switches between ustekinumab and ABP 654 compared with continued use of ustekinumab in participants with moderate to severe plaque psoriasis.

Detailed description:
This is a multi-center study and will enroll approximately 480 participants.

After eligibility confirmation, all participants will be randomized in a 1:1 ratio into 2 treatment arms: continued use of ustekinumab or multiple switches between ustekinumab and ABP 654 at Week 28. The randomization will be stratified by prior biologic use for psoriasis (yes versus \[vs\] no) at baseline (Week 0), geographic region, and baseline (Week 0) body weight.

All participants will receive an initial 3 doses of ustekinumab on Day 1 (Week 0), Week 4 and Week 16. At Week 28, participants will be randomized to continue on ustekinumab or switching between ABP 654 and ustekinumab every 12 weeks.

At Week 28, efficacy assessments will be conducted including evaluation of Psoriasis and Area Severity Index (PASI). Participants who do not achieve PASI 50 response or better improvement at Week 28 will be considered as run-in failures and will not be randomized at Week 28; these participants will complete End of Study procedures at Week 28. The run-in period will occur from Day 1 until randomization at Week 28. Those unable to complete the Week 28 visit or did not have a PASI assessment completed at Week 28 will be discontinued from the study.

The total duration of study participation for each participant will be 68 weeks, with up to 4 weeks for screening and 64 weeks after the first investigational product administration.

Arms: arm 1: Participants will receive subcutaneous injection of ustekinumab up to Week 52. arm 2: Participants will initially receive injection of ustekinumab up to Week 16. Thereafter, starting from Week 28, participants will switch between ABP 654 and ustekinumab every 12 weeks up to Week 52.
Interventions: intervention 1: Ustekinumab intervention 2: ABP 654
Intervention descriptions: intervention 1: Participants will receive subcutaneous (SC) injection of ustekinumab. intervention 2: Participants will receive SC injection of ABP 654.

Protocol documents:
Prot_002.pdf: 
Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 1 of 88 
Title Page 
Protocol Title: 
A Multicenter, Randomized, Double-blinded 
Study Evaluating the Pharmacokinetics, Efficacy 
and Safety of Multiple Switches Between 
Ustekinumab and ABP 654 Compared With 
Continued Use of Ustekinumab in Subjects with 
Moderate to Severe Plaque Psoriasis 
Short Title: 
A Study to Investigate Interchangeability of 
ABP 654 for the Treatment of Subjects with 
Moderate to Severe Plaque Psoriasis 
Compound: 
ABP 654 
Indication: 
Moderate to Severe Plaque Psoriasis 
Study Sponsor: 
Amgen Inc. 
One Amgen Center Drive 
Thousand Oaks 
CA 91320-1799, US 
Protocol Number: 
20200417 
Study Phase: 
Phase 3 
Regulatory Agency Identifying 
Number: 
IND: 139331 
EudraCT: 2020-005205-42 
Approval Date: 
Final 2.0, 02 June 2021 
NCT Number: NCT04761627
This NCT number has been applied to the document
for purposes of posting on Clinicaltrials.gov


Protocol Signature Page - Sponsor Signatory: 
This protocol has been reviewed and approved by the representative(s) listed below. Any 
modification of the protocol must be agreed upon by the sponsor and the investigator and must 
be documented in writing. 
Amgen Inc. representative(s): 
Print Name 
___ _ 
Signature 
Title 
Date (DD MMM YYYY)
Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 2 of 88 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 3 of 88 
Protocol Signature Page – Contract Research Organization 
This protocol has been reviewed and approved by the representative(s) listed below.  Any 
modification of the protocol must be agreed upon by the sponsor and the investigator and must 
be documented in writing. 
Contract research organization representative(s): 
Print Name 
Title 
Signature 
Date (DD MMM YYYY) 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 4 of 88 
 
Protocol Signature Page – Investigator 
I have read this protocol, which has been agreed to by Amgen Inc. and given approval/favorable 
opinion by the Institutional Review Board/Independent Ethics Committee, and I agree that it 
contains all necessary details for my staff and I to conduct this study as described.  I will provide 
copies of the protocol and any amendments to all study personnel under my supervision and 
provide access to all information provided by Amgen Inc. or their specified designees.  I will 
discuss the material with the study personnel to ensure that they are fully informed about the 
study. 
I understand that information contained in or pertaining to this protocol is confidential and should 
not be disclosed, other than to those directly involved in the execution or the ethical review of 
the study, without written authorization from Amgen Inc.  It is, however, permissible to provide 
information to a subject in order to obtain consent. 
I agree to conduct this study according to this protocol and to comply with its requirements, 
subject to ethical and safety considerations and guidelines, and to conduct the study in 
accordance with the general guidelines indicated in the Declaration of Helsinki, International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 
guidelines on Good Clinical Practice (GCP), and applicable national or regional regulatory 
requirements. 
I agree to comply with the procedures described for data recording and reporting and to permit 
monitoring and auditing by Amgen Inc. and inspection by the appropriate regulatory authorities. 
I agree to make my subjects’ study records available to Amgen Inc. personnel, their 
representatives and relevant regulatory authorities in order to verify data that I have entered into 
the case report forms.  I will retain the study-related essential documents until Amgen Inc. 
indicates that they are no longer needed.  I am aware of my responsibilities as an investigator 
as provided by Amgen Inc. 
I agree to ensure that Financial Disclosure Statements will be completed by me (including, if 
applicable, my spouse [or legal partner] and dependent children) and my sub-investigators 
(including, if applicable, their spouses [or legal partners] and dependent children) at the start of 
the study and for up to 1 year after the study is completed, if there are changes that affect my 
financial disclosure status. 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 5 of 88 
 
I understand that Amgen Inc. may decide to suspend or prematurely terminate the study at any 
time for whatever reason; such a decision will be communicated to me in writing.  Conversely, 
should I decide to withdraw from execution of the study, I will communicate my intention 
immediately in writing to Amgen Inc. 
Investigator: 
 
Print Name 
 
Title 
Institution 
 
 
Signature 
 
Date (DD MMM YYYY) 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 6 of 88 
 
Protocol Amendment Summary of Changes 
Document History 
Document 
Version 
Date 
Substantial Amendment 1 
Final 2.0 
02 June 2021 
Original Protocol 
Final 1.0 
19 November 2020 
 
Substantial Amendment 1 (02 June 2021) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the EU. 
Overall Rationale for the Amendment: 
Section 
Description of Change 
Brief Rationale 
1.1 Synopsis 
1.2 Study Schema 
5 
Study Population 
9.3 Sample Size 
Determination 
Change of sample size from 
352 enrolled subjects to 480 enrolled 
subjects. 
Adjustment of sample size to maintain 
sufficient power on primary objective to 
align with Food and Drug Administration 
recommended margin (0.8, 1.25). 
1.1 Synopsis 
2.1 Study Rationale 
3 
Objectives and 
Endpoints 
4.2 Scientific Rationale for 
Study Design 
9.2 Statistical Hypotheses 
Update verbiage of bioequivalence and 
pharmacokinetic equivalence to 
similarity and pharmacokinetic 
similarity. 
To provide clarity using the appropriate 
terminology for a proposed biosimilar 
product. 
1.1 Synopsis 
9.2 Statistical Hypotheses 
9.3 Sample Size 
Determination 
Update of bioequivalence margin from 
(0.77, 1.3) to (0.8, 1.25). 
To follow Food and Drug Administration 
recommended bioequivalence margin. 
1.1 Synopsis 
9.5 Planned Analyses 
Change in method for handling missing 
values for the Psoriasis Area and 
Severity Index endpoint from last 
observation carried forward method to 
multiple imputation method. 
To follow Food and Drug Administration 
recommendation. 
1.3 Schedule of 
Assessments 
Include pharmacokinetic and antidrug 
antibody samples at week 4. 
To follow Food and Drug Administration 
recommendation. 
Update to Table 1-2: Clarification of 
tolerance windows for pharmacokinetic 
sample collection times. 
To provide better clarity on expected 
sample collection times. 
1.3 Schedule of 
Assessments 
5.2 Exclusion Criteria 
8.2 Safety Assessments 
Include human immunodeficiency virus 
serology at screening and 
electrocardiogram at baseline and 
weeks 16, 28, 40, and 52. 
To follow Food and Drug Administration 
recommendation. 
5.1 Inclusion Criteria 
Update to inclusion criterion 3: removed 
additional mention of baseline Psoriasis 
Area and Severity Index. 
Removal of duplicative wording. 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 7 of 88 
 
Section 
Description of Change 
Brief Rationale 
5.2 Exclusion Criteria 
Update of exclusion criterion 23: update 
to specify female subject should not get 
pregnant for at least 5 months after the 
last dose of investigational product. 
To ensure consistency of contraception 
language and pregnancy criteria 
throughout the protocol. 
9.5 Planned Analyses 
Include electrocardiogram data analysis 
descriptive summary for the number of 
abnormal electrocardiograms. 
To follow Food and Drug Administration 
recommendation. 
Clarify that the concomitant medication 
for Run-in Treated Set is for Run-in 
Period. 
To align with language in the Statistical 
Analysis Plan. 
Throughout protocol 
Minor formatting and grammatical 
revisions. 
To ensure correction of typographical 
errors and inconsistencies. 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 8 of 88 
 
Table of Contents 
 
Protocol Amendment Summary of Changes .............................................................................. 6 
Table of Contents ....................................................................................................................... 8 
1 
Protocol Summary ..............................................................................................................12 
1.1 
Synopsis .........................................................................................................................12 
1.2 
Schema ..........................................................................................................................18 
1.3 
Schedule of Assessments ...............................................................................................19 
2 
Introduction .........................................................................................................................21 
2.1 
Study Rationale...............................................................................................................21 
2.2 
Background .....................................................................................................................22 
2.3 
Benefit/Risk Assessment ................................................................................................24 
2.3.1 
Overall Benefit: Risk Conclusion .................................................................................24 
3 
Objectives and Endpoints ...................................................................................................25 
4 
Study Design ......................................................................................................................26 
4.1 
Overall Design ................................................................................................................26 
4.2 
Scientific Rationale for Study Design ..............................................................................26 
4.2.1 
Subject Input into Design ............................................................................................27 
4.3 
Justification for Dose .......................................................................................................27 
4.4 
End of Study Definition....................................................................................................27 
5 
Study Population .................................................................................................................27 
5.1 
Inclusion Criteria .............................................................................................................28 
5.2 
Exclusion Criteria ............................................................................................................29 
5.3 
Subject Enrollment ..........................................................................................................31 
5.4 
Lifestyle Considerations ..................................................................................................32 
5.4.1 
Meals and Dietary Restrictions ....................................................................................32 
5.4.2 
Caffeine, Alcohol, and Tobacco ...................................................................................32 
5.4.3 
Activity ........................................................................................................................32 
5.4.4 
Coronavirus Disease 2019 Considerations ..................................................................32 
5.5 
Screen Failures ...............................................................................................................33 
6 
Investigational Product ........................................................................................................33 
6.1 
Investigational Product(s) Administered ..........................................................................34 
6.1.1 
ABP 654 Dosage Form ...............................................................................................34 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 9 of 88 
 
6.1.2 
Ustekinumab Dosage Form .........................................................................................35 
6.2 
Preparation, Handling, Storage, and Accountability ........................................................35 
6.3 
Investigational Product Complaints .................................................................................36 
6.4 
Measures to Minimize Bias: Blinding and Randomization ...............................................36 
6.4.1 
Blinding .......................................................................................................................36 
6.4.2 
Randomization ............................................................................................................37 
6.5 
Investigational Product Compliance ................................................................................38 
6.6 
Concomitant Therapy ......................................................................................................38 
6.6.1 
Prohibited Treatments .................................................................................................38 
6.6.2 
Prior and Concomitant Therapy ...................................................................................38 
6.7 
Dose Modification ...........................................................................................................39 
6.8 
Intervention After the End of the Study ............................................................................40 
7 
Discontinuation of Investigational Product and Subject Discontinuation ..............................40 
7.1 
Discontinuation of Investigational Product .......................................................................40 
7.2 
Subject Discontinuation/Withdrawal from the Study ........................................................41 
7.3 
Loss of Subjects to Follow-Up .........................................................................................42 
8 
Study Assessments and Procedures ...................................................................................43 
8.1 
Efficacy Assessments .....................................................................................................44 
8.1.1 
Psoriasis Area and Severity Index ...............................................................................44 
8.1.2 
Static Physical Global Assessment .............................................................................45 
8.1.3 
Affected Body Surface Area ........................................................................................45 
8.2 
Safety Assessments .......................................................................................................45 
8.2.1 
Physical Examinations ................................................................................................45 
8.2.2 
Vital Signs ...................................................................................................................45 
8.2.3 
Twelve-lead Electrocardiogram ...................................................................................46 
8.2.4 
Tuberculosis Testing ...................................................................................................46 
8.2.5 
Chest Radiography .....................................................................................................46 
8.2.6 
Clinical Safety Laboratory Assessments .....................................................................46 
8.3 
Adverse Events and Serious Adverse Events .................................................................48 
8.3.1 
Definitions ...................................................................................................................48 
8.3.2 
Assessments of Adverse Events .................................................................................52 
8.3.3 
Causality .....................................................................................................................52 
8.3.4 
Documenting and Reporting of Adverse Events ..........................................................53 
8.3.5 
Pregnancy ...................................................................................................................57 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 10 of 88 
 
8.3.6 
Events of Interest ........................................................................................................57 
8.4 
Treatment of Overdose ...................................................................................................58 
8.5 
Pharmacokinetics ............................................................................................................58 
8.6 
Pharmacodynamics ........................................................................................................58 
8.7 
Genetics .........................................................................................................................58 
8.8 
Biomarkers ......................................................................................................................58 
8.9 
Immunogenicity Assessments .........................................................................................58 
9 
Statistical Considerations ....................................................................................................60 
9.1 
General Considerations ..................................................................................................60 
9.2 
Statistical Hypotheses .....................................................................................................60 
9.3 
Sample Size Determination .............................................................................................61 
9.4 
Populations for Analysis ..................................................................................................61 
9.5 
Planned Analyses ...........................................................................................................62 
9.5.1 
Primary Endpoints .......................................................................................................62 
9.5.2 
Secondary Endpoint(s) ................................................................................................62 
9.5.3 
Safety Endpoints .........................................................................................................63 
9.5.4 
Other Analyses ...........................................................................................................64 
9.5.5 
Demographic and Baseline Characteristics .................................................................65 
9.5.6 
Exposure to Investigational Product ............................................................................65 
9.5.7 
Exposure to Prior and Concomitant Medication ...........................................................65 
9.5.8 
Subgroup Analyses and Covariates ............................................................................66 
9.6 
Interim Analyses .............................................................................................................66 
10 Supporting Documentation and Operational Considerations ...............................................67 
10.1 Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ............................67 
10.1.1 
Regulatory and Ethical Considerations ........................................................................67 
10.1.2 
Informed Consent Process ..........................................................................................68 
10.1.3 
Data Monitoring Committee .........................................................................................70 
10.1.4 
Financing and Insurance .............................................................................................70 
10.1.5 
Data and Records Management ..................................................................................71 
10.1.6 
Publication Policy ........................................................................................................75 
10.1.7 
Auditing and Monitoring ...............................................................................................76 
10.1.8 
Data Protection ...........................................................................................................78 
10.1.9 
Protocol Approval and Amendment .............................................................................78 
10.1.10 Study and Site Start and Closure ................................................................................78 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 11 of 88 
10.2 Appendix 2: Contraceptive Guidance and Collection of Pregnancy Information ..............79 
10.3 Appendix 3: Static Physician’s Global Assessment Scale ...............................................85 
10.4 Appendix 4: Abbreviations and Trademarks ....................................................................86 
11 References .........................................................................................................................88 
List of Figures 
Figure 1–1. 
Study Schema ...................................................................................................18 
List of Tables 
Table 1-1. 
Schedule of Assessments ..................................................................................19 
Table 1-2. 
Tolerance Windows for Pharmacokinetic Endpoint Sample Collection ...............20 
Table 3-1. 
Objectives and Endpoints ..................................................................................25 
Table 4-1. 
Investigational Product Groups ..........................................................................26 
Table 6-1. 
Investigational Product(s) Administered .............................................................34 
Table 8-1. 
Protocol-required Safety Laboratory Assessments .............................................48 
Table 9-1. 
Populations for Analysis .....................................................................................61 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 12 of 88 
 
1 Protocol Summary 
1.1 Synopsis 
Protocol Title: A Multicenter, Randomized, Double-blinded Study Evaluating the 
Pharmacokinetics, Efficacy and Safety of Multiple Switches Between Ustekinumab and 
ABP 654 Compared With Continued Use of Ustekinumab in Subjects with Moderate to Severe 
Plaque Psoriasis 
Sponsor Protocol No.: 20200417 
Study Phase: Phase 3 
Sponsor: Amgen Inc. 
Rationale: 
The current study is designed to investigate the pharmacokinetics similarity, efficacy, safety and 
immunogenicity of multiple switches between ustekinumab and ABP 654 compared with 
continued use of ustekinumab in subjects with moderate to severe plaque psoriasis. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary Objective: 
Primary Endpoints: 
• 
To demonstrate similarity of pharmacokinetics in 
subjects with multiple switches between 
ustekinumab and ABP 654 compared to subjects 
receiving continued use of ustekinumab 
Pharmacokinetic parameters: 
• 
AUCtau between week 52 and week 64 
• 
Cmax between week 52 and week 64 
Secondary Objective: 
Secondary Endpoints: 
• 
To assess the efficacy, safety and immunogenicity 
in subjects with multiple switches between 
ABP 654 and ustekinumab compared with subjects 
receiving continued use of ustekinumab 
Pharmacokinetic-related Endpoints: 
• 
tmax between week 52 and week 64 
• 
Ctrough,ss between week 28 and week 52 
Efficacy-related Endpoints: 
• 
PASI percent improvement from baseline (day 1) to 
week 64 
• 
PASI 75 response at week 64 
• 
PASI 100 response at week 64 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 13 of 88 
 
Objectives 
Endpoints 
Safety-related Endpoints: 
• 
Treatment-emergent adverse events and serious 
adverse events, post randomization 
• 
Events of interest, post randomization 
• 
Incidence of antidrug antibodies, post 
randomization 
AUCtau: area under the curve from time 0 over the dosing interval; Cmax: maximum concentration; Ctrough,ss: trough 
concentration at steady state; PASI: Psoriasis Area and Severity Index; tmax: time of maximum concentration 
 
Overall Design: 
This is a randomized, double-blinded, phase 3 study in adult subjects with moderate to severe 
plaque psoriasis. 
The total duration of study participation for each subject will be 68 weeks, with up to 4 weeks for 
screening and 64 weeks after the first investigational product administration. 
Subjects will receive an initial 3 doses of ustekinumab on day 1 (week 0), week 4 and week 16.  
From week 28, subjects in the continued-use group will stay on ustekinumab and subjects in the 
switching group will switch between ABP 654 and ustekinumab every 12 weeks. 
At week 28, efficacy assessments will be conducted including evaluation of Psoriasis and Area 
Severity Index (PASI). 
Subjects who do not achieve a PASI 50 response or better improvement at week 28 are 
considered as run-in failures and will not be randomized at week 28; these subjects will 
complete End of Study procedures at week 28.  The run-in period will occur from day 1 until 
randomization at week 28.  Those unable to complete the week 28 visit or did not have a PASI 
assessment completed at week 28 will be discontinued from the study.  All enrolled subjects not 
randomized at week 28 will be considered run-in failures and the run-in failure reason will be 
documented. 
Disclosure Statement: This is a parallel group, treatment study with 2 arms that are both 
subject and investigator blinded. 
Number of Arms: 
Continued-use group 
Switching group 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 14 of 88 
 
Number of Subjects: 
Approximately 480 subjects will be enrolled to receive ustekinumab during the run-in period.  
Subjects with prior biologic use for psoriasis will be capped at 50% of the total enrolled subjects.  
This sample size will ensure approximately 310 randomized subjects at week 28 after the run-in 
period, considering 35% run-in failures.  Randomization will be in a 1:1 ratio to the 
continued-use group or the switching group.  The randomization will be stratified by prior 
biologic use for psoriasis (yes versus no) at baseline (week 0), geographic region, and body 
weight at baseline (week 0).  The number of subjects enrolled may be adjusted during the study 
with the actual run-in failure rate seen to ensure approximately 310 randomized subjects at 
week 28.  Subjects already enrolled will be allowed to be randomized at week 28.  The sample 
size of 310 randomized subjects will provide 90% power to demonstrate similarity of the primary 
PK endpoints based on the Two One Sided Tests at a 0.05 significance level, assuming a 
between-subject variability (as measured by coefficient of variation) of 55% for ABP 654 and 
ustekinumab, a true geometric mean ratio (GMR) of 1 between ABP 654 and ustekinumab, a 
similarity margin of (0.8, 1.25), and 25% drop-outs after randomization through week 64 
(including subjects who discontinue the study prior to week 52 and those reaching week 52 but 
do not have evaluable primary PK endpoints between weeks 52 and 64). 
Intervention Groups and Duration: 
The total duration of study participation for each subject will be 68 weeks, with up to 4 weeks for 
screening, and for 64 weeks after the first administration of ustekinumab. 
Dose regimens:  Continued use of ustekinumab (ustekinumab 45 mg or 90 mg, subcutaneous 
[SC] injection) and switching group (ustekinumab and ABP 654 45 mg or 90 mg, SC injection). 
Reference Group 
Continued-use Group 
Continued use of ustekinumab administered by subcutaneous injection using a 
blinded prefilled syringe at a dose of 45 mg (baseline body weight ≤ 100 kg) or 
90 mg (baseline body weight > 100 kg) at day 1, week 4, and week 16. 
Subsequent dosing will be done at the same dose every 12 weeks at weeks 28, 
40, and 52. 
Test Group 
Switching Group 
Switching group with ustekinumab administered by subcutaneous injection using 
a blinded prefilled syringe at a dose of 45 mg (baseline body weight ≤ 100 kg) or 
90 mg (baseline body weight > 100 kg) at day 1, week 4 and week 16. 
Subject will then be switched to ABP 654 at week 28, back to ustekinumab at 
week 40, and again to ABP 654 at week 52. 
 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 15 of 88 
 
Sites and Regions: 
This study is planned to be conducted globally at sites including but not limited to North America 
and Europe. 
Data Monitoring Committee: For details on the Data Monitoring Committee, refer to 
Section 10.1.3, Appendix 1. 
Statistical Analysis: 
The primary analysis of the primary PK endpoints, AUCtau and Cmax, between weeks 52 and 64 
will be performed based on the PK Parameter Analysis Set (consisting of all subjects who are 
randomized and receive all 3 doses of the assigned investigational product between weeks 28 
and 52 and who have an evaluable ABP 654 or ustekinumab serum concentration-time profile 
between weeks 52 and 64), according to the actual treatment groups (switching group versus 
continued-use group).  The point estimates and 90% confidence intervals (CIs) for the GMRs 
between ABP 654 and ustekinumab for AUCtau and Cmax between weeks 52 and 64 will be 
estimated using an analysis of covariance (ANCOVA) model adjusting for stratification factors.  
Prior to statistical modeling, the PK parameters will be logarithmically-transformed (natural log).  
Point estimates and 90% CIs for the mean difference in logarithmic PK parameters will be 
estimated from the ANCOVA model, which will then be transformed back to the original scale to 
obtain the point estimates and 90% CIs for GMR.  AUCtau and Cmax of ABP 654 and 
ustekinumab between weeks 52 and 64 will be listed by subject and summarized descriptively 
by treatment group.  A sensitivity analysis of the primary PK endpoints will be conducted on the 
Per-protocol PK Parameter Analysis Set (consisting of all subjects from the PK Parameter 
Analysis Set who do not have an important protocol deviation that could affect the primary PK 
endpoints).  To support a demonstration of interchangeability, the 90% CI of GMRs of ABP 654 
versus ustekinumab for AUCtau and Cmax from the primary analysis should fall within the 
pre-specified similarity margin. 
The analyses of the secondary PK endpoints of tmax between weeks 52 and 64 and Ctrough,ss 
between weeks 28 and 52 will be based on the PK Parameter Analysis Set according to the 
actual treatment groups (switching group versus continued-use group); tmax will be summarized 
descriptively by treatment group and Ctrough,ss between weeks 28 and 52 will be summarized 
descriptively by visit and treatment group.  The point estimates and 90% CIs for GMR for 
Ctrough,ss between the two treatment groups will be estimated using an ANCOVA model adjusting 
for stratification factors. 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 16 of 88 
 
The analysis of the secondary efficacy endpoints will be based on the Per-protocol Efficacy 
Analysis Set (consisting of all subjects who are randomized and receive all 3 doses of the 
assigned investigational product between weeks 28 and 52 and who have not experienced an 
important protocol deviation that may affect the evaluation of the efficacy endpoints) according 
to the actual treatment groups (switching group versus continued-use group).  The point 
estimate and 90% CI of the mean difference in PASI percent improvement from day 1 at 
week 64 will be estimated from an ANCOVA model adjusting for the baseline PASI value and 
the stratification factors.  The point estimate and 90% CI of the risk difference in PASI 75 
response rate and PASI 100 response rate at week 64 will be estimated from a generalized 
linear model with an identity link adjusting for the stratification factors.  Missing data will be 
imputed by multiple imputation method for PASI percent improvement from day 1 at week 64 
and by non-responder imputation for PASI 75 response rate and PASI 100 response rate at 
week 64.  In addition, the PASI percent improvement from day 1 at weeks 28, 40, and 52 and 
the PASI 75 and PASI 100 response rates at weeks 28, 40, and 52 will be summarized 
descriptively by treatment group. 
All reported adverse events will be categorized by system organ class and preferred term 
according to the Medical Dictionary for Regulatory Activities (MedDRA, latest version at the time 
of final analysis) dictionary and graded by Common Terminology Criteria for Adverse Events, 
version 4.03.  Safety analyses of the safety endpoints will be performed based on the Safety 
Analysis Set (consisting of all subjects who are randomized and receive any investigational 
product post randomization) according to the actual treatment groups (switching group versus 
continued-use group).  Treatment-emergent adverse events post randomization are defined as 
adverse events that start or worsen on or after the first dose of investigational product post 
randomization and prior to the End of Study.  The numbers and percentages of subjects 
reporting treatment-emergent adverse events, serious adverse events and events of interests 
will be tabulated by treatment group.  The number and percent of subjects developing binding or 
neutralizing antidrug antibody (ADA) in the subset of Safety Analysis Set who have never tested 
positive (ie, tested negative or no results) prior to the first dose of investigational product post 
randomization and have at least one ADA result post randomization will be tabulated 
descriptively by treatment group and by visit. 
In addition, safety analyses prior to randomization will be performed based on the Run-in 
Treated Set (consisting of all enrolled subjects treated with at least 1 dose of ustekinumab 
during the run-in period).  The number and percentage of subjects reporting treatment-emergent 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 17 of 88 
 
adverse events, serious adverse events and events of interest while receiving ustekinumab 
during the run-in period will be summarized.  The number and percentage of subjects 
developing binding or neutralizing ADAs for ustekinumab during the run-in period will be 
summarized.


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1.2 Schema 
Figure 1–1.  Study Schema 
 
≤ 28 days 
Screening 
Day 1 
Week 28 
 
Week 64 
 
 
 
 
 
Run-in Period 
 
Interchangeability 
 
 
 
Pharmacokinetic Endpoint 
week 52 to week 64 
(8 pharmacokinetic visits) 
PASI: Psoriasis Area and Severity Index 
Subjects with ≤ 100 kg will receive 45 mg of investigational product and subjects with > 100 kg will receive 90 mg of investigational product. 
At week 28, run-in failures (eg, subjects achieving PASI improvement < 50%) will not be randomized and will complete an End of Study visit at week 28.  The 
run-in period will occur from day 1 until prior to randomization at week 28. 
Subjects achieving PASI improvement ≥ 50% will be randomized at week 28 (1:1) to continue ustekinumab or the switching group, at the same 45 mg or 90 mg 
dose stratified by geographic region, prior biologic use for psoriasis at baseline (week 0, “yes” versus “no”) and body weight at baseline (week 0, ≤ 100 kg and 
> 100 kg). 
S
C
R
E
E
N
I
N
G
E
N
R
O
L
L
M
E
N
T
Ustekinumab
Day 1, Week 4,
Week 16
N = 480
R
A
N
D
O
M
I
Z
A
T
I
O
N
Ustekinumab
Every 12 weeks
Weeks 28, 40 and 52
ABP 654
Week 28
Ustekinumab
Week 40
ABP 654
Week 52
E
N
D
O
F
S
T
U
D
Y


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1.3 Schedule of Assessments 
Table 1-1.  Schedule of Assessments 
 
Screening 
Baseline 
Study Visits 
(Week ± 5 days)f 
Pharmacokinetic Endpoint Assessments 
Post Actual Week 52 Dose Date 
End of 
Studyd 
Study Visit 
 
 28 days 
day 1/ 
week 0 
4 
16 
28 
40 
52 
2d 
7d 
10d 
2w 
4w 
8w 
12w post 
week 52 
(week 64g) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/Medication History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Height 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Body Weight 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
X 
Adverse Events 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Efficacy Assessments 
PASI/sPGA/Affected BSA 
X 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
X 
Laboratory Assessments 
Tuberculosis Testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tuberculosis Worksheet 
Xb 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-ray 
Xc 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy Test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology (HBsAg, HCV, HIV) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Urine Pregnancy Test 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
X 
Hematology 
X 
X 
 
 
X 
 
X 
 
 
 
 
 
 
X 
Chemistry 
X 
X 
 
 
X 
 
X 
 
 
 
 
 
 
X 
Urinalysis 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Pharmacokinetics 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Antidrug Antibodies 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
X 


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Screening 
Baseline 
Study Visits 
(Week ± 5 days)f 
Pharmacokinetic Endpoint Assessments 
Post Actual Week 52 Dose Date 
End of 
Studyd 
Study Visit 
 
 28 days 
day 1/ 
week 0 
4 
16 
28 
40 
52 
2d 
7d 
10d 
2w 
4w 
8w 
12w post 
week 52 
(week 64g) 
Investigational Product 
Randomization 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Investigational Product 
Administratione 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
BSA: body surface area; ECG: electrocardiogram; HBsAg: hepatitis B surface antigen; HCV: hepatitis C virus antibody; HIV: human immunodeficiency virus; 
PASI: Psoriasis Area and Severity Index; PPD: purified protein derivative; sPGA: static Physician’s Global Assessment 
aReport serious adverse events that occur after signing informed consent form.  Nonserious adverse events are reported as medical history prior to enrollment. 
bOnly for subjects with a positive tuberculosis test (ie, positive PPD or positive or indeterminate Quantiferon®/T-spot® ) 
cPrior radiography or formal reports signed off by a radiologist within 3 months of screening is acceptable. 
dSubjects who missed week 28 visit or terminated early from the study should complete all procedures scheduled for week 64 within 28 days after 
withdrawal/discontinuation if possible.  Subjects not achieving PASI 50 at week 28 will not be randomized and will complete End of Study procedures at week 28. 
eABP 654/ ustekinumab will be administered after all other procedures are completed for each dosing visit.  Pharmacokinetic and antidrug antibody blood draws 
must be done prior to dosing at the visits where pharmacokinetic and antidrug antibody blood draws and investigational product administration occur. 
fDosing should be delayed if subject has a serious infection (up to 5 days).  Refer to Section 6.7 for details. 
gFor subjects completing the study, the End of Study visit should be conducted 12 weeks post actual week 52 dose date.  If the subject is adhering to protocol 
schedule, this visit will be completed at week 64. 
Table 1-2.  Tolerance Windows for Pharmacokinetic Endpoint Sample Collection 
Study Visit 
Tolerance Windowsa 
Week 52 predose 
Within 1 hour prior to week 52 investigational product administration 
2 days post week 52 dose 
 5 hours 
7 days post week 52 dose 
 5 hours 
10 days post week 52 dose 
 24 hours 
2 weeks post week 52 dose 
 24 hours 
4 weeks post week 52 dose 
 48 hours 
8 weeks post week 52 dose 
 72 hours 
12 weeks post week 52 dose (End of Study Visit) 
 72 hours 
aThe week 52 visit should be performed 52 weeks from day 1, with a window of ± 5 days.  Subsequent visits are done in relation to the actual week 52 
investigational product dose date (eg, for the 2 days post week 52 dose timepoint, the pharmacokinetic sample should be collected 2 days after the actual week 52 
dose, with a collection window of ± 5 hours). 


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2 Introduction 
ABP 654 is a biosimilar candidate to ustekinumab (Stelara®) which is an interleukin 12 (IL-12) 
and IL-23 antagonist. 
The term “investigational product” throughout the protocol, refers to ABP 654 or ustekinumab. 
2.1 Study Rationale 
Amgen Inc. is developing ABP 654 as a biosimilar candidate to ustekinumab.  The current study 
is designed to investigate the pharmacokinetic (PK) similarity, efficacy, safety, and 
immunogenicity of multiple switches between ustekinumab and ABP 654 compared with 
continued use of ustekinumab in subjects with moderate to severe plaque psoriasis.  This study 
is being conducted to support a demonstration of interchangeability of ABP 654 and 
ustekinumab as defined by the United States (US) Biologic Price Competition and Innovation 
Act of 2009 (BPCI Act).  An interchangeable biosimilar is defined as a biosimilar that can be 
expected to produce the same clinical result as the reference product in any given patient and 
the risk in terms of safety or diminished efficacy of switching between use of the biosimilar and 
the reference product is not greater than the risk of using the reference product without such 
switch (BPCI Act). 
ABP 654 and ustekinumab belong to the pharmacologic class of IL-12 and IL-23 antagonists.  
The mechanism of action across indications involves the ustekinumab protein molecule binding 
with specificity to the p40 protein subunit used by both the IL-12 and IL-23 cytokines.  This 
binding disrupts IL-12 and IL-23 mediated signaling and cytokine cascades by disrupting the 
interaction of these cytokines with a shared cell surface receptor chain, IL-12 receptor subunit 
beta 1 (IL-12Rβ). 
In the US, ustekinumab is approved for subcutaneous (SC) administration in the treatment of 
patients 6 years or older with moderate to severe plaque psoriasis who are candidates for 
phototherapy or systemic therapy, and active psoriatic arthritis in adults alone or in combination 
with methotrexate, as well as maintenance dosing for adult patients with moderate to severe 
active Crohn’s disease and moderate to severe active ulcerative colitis; ustekinumab is also 
approved for intravenous (IV) administration in the initial treatment of moderate to severe active 
Crohn’s disease in adults and moderate to severe active ulcerative colitis in adults (Stelara® 
United States Prescribing Information [USPI], July 2020).  In the European Union (EU), 
ustekinumab is approved for SC administration in the treatment of patients 6 years or older with 


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moderate to severe plaque psoriasis, and active psoriatic arthritis in adults (Stelara® Summary 
of Product Characteristics [SmPC], February 2020). 
A biosimilar product, generally, is one that is highly similar to a licensed biologic reference 
product, and there are no clinically meaningful differences between the biosimilar and reference 
products in terms of safety, purity, and potency.  Biosimilarity is demonstrated by the totality of 
the evidence, including quality, nonclinical, and clinical evidence.  The quality and nonclinical 
data for ABP 654 and ustekinumab are summarized in the Investigator’s Brochure. 
2.2 Background 
ABP 654 is designed to have an identical amino acid sequence and the same biological and 
functional characteristics as ustekinumab.  ABP 654 has the same dosage form (solution for 
injection), product strengths, and formulation as ustekinumab (US and EU). 
The totality of evidence available from an ongoing analytical program suggests that ABP 654 is 
analytically similar to ustekinumab with respect to its physicochemical properties and biological 
activities, except for minor differences expected from cell line changes; these minor differences 
are not expected to be clinically meaningful.  ABP 654 and ustekinumab (US and EU) have 
similar in vitro binding to IL-23, IL-12, and neonatal fragment crystallizable receptor (FcRn), 
similar inhibition of IL-23 and IL-12, and similar binding kinetics and affinity to IL-23 and IL-12.  
Effector functions (antibody-dependent cell-mediated cytotoxicity [ADCC] and 
complement-dependent cytotoxicity [CDC]) towards cells expressing IL-12 and/or IL-23 
receptors are not expected to occur with ABP 654 and ustekinumab.  The lack of ADCC was 
confirmed when ABP 654 and ustekinumab were tested for effector functions using human IL-12 
expressing U937 cells.  Lack of CDC activity is currently being investigated. 
As of the date of this protocol, ABP 654 has not been approved as a biosimilar to ustekinumab; 
however, based on the analytical similarity of ABP 654 and ustekinumab established to date, 
clinical experience with ustekinumab is deemed relevant to predicting the effects of ABP 654 in 
humans and is summarized in the following paragraphs.  Additionally, ABP 654 is being used in 
2 ongoing clinical studies.  Study 20190230 is being conducted to evaluate the single-dose PK, 
safety, tolerability, and immunogenicity of ABP 654 (90 mg SC injection) compared to 
ustekinumab (US and EU) in healthy subjects.  Study 20190232 is being conducted to 
demonstrate that there is no clinically meaningful difference between ABP 654 and ustekinumab 


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Page 23 of 88 
 
in terms of PK, efficacy, safety, and immunogenicity in adult subjects with moderate to severe 
plaque psoriasis. 
Ustekinumab has been investigated in a number of clinical studies and for a number of different 
indications.  In healthy subjects, the median time of maximum concentration (tmax) value 
following a single SC administration of 90 mg of ustekinumab was comparable to subjects with 
psoriasis.  The maximum concentration (Cmax) and area under the curve (AUC) in healthy 
subjects were higher than values seen in subjects with psoriasis.  This is likely attributed to 
differing pharmacokinetic sampling schedules between the 2 studies, differences in body weight 
between the 2 populations, or increased IL-12/IL-23 binding target concentrations in subjects 
with psoriasis.  In healthy subjects following a single 90 mg SC dose, the apparent volume of 
distribution was 90.2 mL/kg and the terminal half-life (t½) was 22.1 days with an apparent 
systemic clearance of 3.1 mL/day/kg (BLA 125261 Clinical Pharmacology and 
Biopharmaceutics Review, 2009). 
In subjects with plaque psoriasis, exposure increased in an approximately dose proportional 
manner after a single SC administration at doses range from 0.27 mg/kg to 2.7 mg/kg.  Serum 
concentrations of ustekinumab were higher in the group receiving the 90 mg dose, as opposed 
to the 45 mg dose.  However, when comparing the difference among the 2 groups, dose 
proportionality was also shown.  Assessment of intrinsic factors including body weight, age, and 
sex were performed.  When given the same dose of ustekinumab, subjects that weighed 
> 100 kg had lower median serum ustekinumab concentrations compared with those subjects 
weighing ≤ 100 kg.  Subgroup analysis showed that age, sex, and race had no effects on clinical 
response (Stelara® USPI, July 2020; BLA 125261 Clinical Pharmacology and Biopharmaceutics 
Review, 2009). 
The clinical efficacy and safety information for ustekinumab as described in the product labeling 
(Stelara® USPI, July 2020; Stelara® SmPC, February 2020) are considered relevant to 
predicting the effects of ABP 654 in humans.  When ustekinumab was administered to subjects 
with plaque psoriasis in clinical studies, subjects had a reduction in disease as measured by 
Psoriasis Area and Severity Index (PASI) score (≥ 75% improvement in PASI [PASI 75]) from 
baseline to week 12 and treatment success (cleared or minimal) on the Physician’s Global 
Assessment (PGA) as compared with the placebo arm.  Adverse events reflected in the 
warnings and precautions section of the product labeling for ustekinumab that may be serious 
include bacterial, fungal, and viral infections including tuberculosis, malignancies, 


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Page 24 of 88 
 
hypersensitivity reactions, posterior reversible encephalopathy syndrome, noninfectious 
pneumonia and serious dermatological conditions (eg, erythrodermic psoriasis, exfoliative 
dermatitis, hypersensitivity vasculitis). 
A detailed description of the chemistry, pharmacology, efficacy, and safety of ABP 654 is 
provided in the Investigator’s Brochure. 
2.3 Benefit/Risk Assessment 
ABP 654 is expected to be biosimilar to ustekinumab.  The risks and benefits of ABP 654 are 
therefore expected to be the same as those of ustekinumab, as specified in the product labeling; 
therefore, there are no anticipated risks for switching between ABP 654 and ustekinumab.  All 
subjects in this study will receive an active treatment.  More detailed information about the 
expected benefits, risks, and reasonably expected adverse events of ABP 654 can be found in 
the Investigator’s Brochure. 
A risk assessment will be performed on an ongoing basis to evaluate the potential impact of 
coronavirus disease 2019 (COVID-19) on subjects.  Risk mitigation measures, including 
COVID-19 related precautions and procedures (including severe acute respiratory syndrome 
coronavirus 2 [SARS-CoV-2] testing/screening) will be implemented based on the prevailing 
situation during study conduct, at the investigator’s discretion and in accordance with local and 
institutional guidelines, as applicable. 
2.3.1 Overall Benefit: Risk Conclusion 
Considering the measures taken to minimize risk to subjects participating in this study, the 
potential risks identified in association with ABP 654, as well as switching between ABP 654 
and ustekinumab, are justified by the anticipated benefits to subjects with moderate to severe 
plaque psoriasis. 


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3 Objectives and Endpoints 
Table 3-1.  Objectives and Endpoints 
Objectives 
Endpoints 
Primary Objective: 
Primary Endpoints: 
• 
To demonstrate similarity of pharmacokinetics in 
subjects with multiple switches between 
ustekinumab and ABP 654 compared to subjects 
receiving continued use of ustekinumab 
Pharmacokinetic parameters: 
• 
AUCtau between week 52 and week 64 
• 
Cmax between week 52 and week 64 
Secondary Objective: 
Secondary Endpoints: 
• 
To assess the efficacy, safety and immunogenicity 
in subjects with multiple switches between 
ABP 654 and ustekinumab compared with subjects 
receiving continued use of ustekinumab 
Pharmacokinetic-related Endpoints: 
• 
tmax between week 52 and week 64 
• 
Ctrough,ss between week 28 and week 52 
Efficacy-related Endpoints: 
• 
PASI percent improvement from baseline (day 1) to 
week 64 
• 
PASI 75 response at week 64 
• 
PASI 100 response at week 64 
Safety-related Endpoints: 
• 
Treatment-emergent adverse events and serious 
adverse events, post randomization 
• 
Events of interest, post randomization 
• 
Incidence of antidrug antibodies, post 
randomization 
AUCtau: area under the curve from time 0 over the dosing interval; Cmax: maximum concentration; Ctrough,ss: trough 
concentration at steady state; PASI: Psoriasis Area and Severity Index; tmax: time of maximum concentration 
 


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4 Study Design 
4.1 Overall Design 
This is a randomized, double-blinded, phase 3 study in adult subjects with moderate to severe 
plaque psoriasis.  This study is planned to be conducted globally at study centers including but 
not limited to North America and Europe. 
The total duration of study participation for each subject will be 68 weeks, with up to 4 weeks for 
screening and 64 weeks after the first investigational product administration. 
Table 4-1.  Investigational Product Groups 
Reference Group 
Continued-use Group 
Continued use of ustekinumab administered by subcutaneous injection using a 
blinded prefilled syringe at a dose of 45 mg (baseline body weight ≤ 100 kg) or 
90 mg (baseline body weight > 100 kg) at day 1, week 4, and week 16. 
Subsequent dosing will be done at the same dose every 12 weeks at weeks 28, 
40, and 52. 
Test Group 
Switching Group 
Switching group with ustekinumab administered by subcutaneous injection using 
a blinded prefilled syringe at a dose of 45 mg (baseline body weight ≤ 100 kg) or 
90 mg (baseline body weight > 100 kg) at day 1, week 4 and week 16. 
Subject will then be switched to ABP 654 at week 28, back to ustekinumab at 
week 40, and again to ABP 654 at week 52. 
 
Subjects will receive an initial 3 doses of ustekinumab on day 1 (week 0), week 4 and week 16.  
From week 28, subjects in the continued-use group will stay on ustekinumab and subjects in the 
switching group will switch between ABP 654 and ustekinumab every 12 weeks. 
At week 28, efficacy assessments will be conducted including evaluation of PASI. 
Subjects who do not achieve a PASI 50 response or better improvement at week 28 are 
considered as run-in failures and will not be randomized at week 28; these subjects will 
complete End of Study (EOS) procedures at week 28.  The run-in period will occur from day 1 
until prior to randomization at week 28.  Those unable to complete the week 28 visit or did not 
have a PASI assessment completed at week 28 will be discontinued from the study.  All enrolled 
subjects not randomized at week 28 will be considered run-in failures and the run-in failure 
reason will be documented. 
4.2 Scientific Rationale for Study Design 
ABP 654 is being developed globally as a biosimilar to the reference product ustekinumab.  
Additionally, ABP 654 is being developed as an interchangeable biosimilar with ustekinumab, as 


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Final 2.0 Date: 02 June 2021 
Page 27 of 88 
 
defined by US regulations.  Accordingly, the continued-use group administered with only 
ustekinumab was chosen as the control group.  Analytical similarity data available to date 
support the conclusion that ABP 654 is analytically similar to ustekinumab. 
The current study is designed to investigate the pharmacokinetic similarity, efficacy, safety and 
immunogenicity of multiple switches between ustekinumab and ABP 654 compared with 
continued use of ustekinumab in subjects with moderate to severe plaque psoriasis. 
4.2.1 Subject Input into Design 
Not applicable. 
4.3 Justification for Dose 
The dose (45 mg or 90 mg, which is based on body weight) is the approved psoriasis dosing 
regimen for ustekinumab (US and EU) for which ABP 654 is being tested for interchangeability.  
See Section 6.7 for dose modifications. 
4.4 End of Study Definition 
A subject is considered to have completed the study if he/she has completed all phases of the 
study including an EOS visit or the last scheduled procedure shown in the Schedule of 
Assessments (Table 1-1). 
The end of the study is defined as the date of the last visit of the last subject in the study or last 
scheduled procedure shown in the Schedule of Assessments (Table 1-1) for the last subject in 
the study globally. 
5 Study Population 
The study population will consist of subjects with moderate to severe plaque psoriasis.  Subjects 
(or legally acceptable representative) must be able to provide written consent and subjects must 
meet all the inclusion criteria and none of the exclusion criteria. 
Approximately 480 subjects will be enrolled.  Randomization will be stratified based on 
geographic region, prior biologic use for psoriasis (“yes” versus “no”) at baseline (week 0), and 
baseline body weight.  Subjects with prior biologic use for psoriasis will be capped at 50% of the 
total enrolled subjects. 


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The number of subjects enrolled may be adjusted during the study with the actual run-in failure 
rate seen to ensure approximately 310 randomized subjects at week 28. 
5.1 Inclusion Criteria 
Subjects cannot be enrolled before all the inclusion criteria (including test results) are confirmed.  
Subjects are eligible to be included in the study only if all of the following criteria apply: 
1. Subject is male or female and is ≥ 18 and ≤ 75 years of age inclusive, at the time of 
enrollment. 
2. Subject has stable moderate to severe plaque psoriasis for at least 6 months (eg, no 
morphology changes or significant flares of disease activity in the opinion of the 
investigator). 
3. Subject has a score of PASI ≥ 12, involvement of ≥ 10% body surface area (BSA) and static 
Physician Global Assessment (sPGA) ≥ 3 at screening and at baseline. 
4. Subject is a candidate for phototherapy or systemic therapy. 
5. Subject has previous failure, inadequate response, intolerance, or contraindication to at 
least 1 conventional antipsoriatic systemic therapy (eg, methotrexate, cyclosporine, psoralen 
plus ultraviolet light [PUVA]). 
6. Female subject (except if at least 2 years postmenopausal or surgically sterile): a negative 
serum pregnancy test during screening and a negative urine pregnancy test at baseline. 
7. Subject or legally acceptable representative is capable of giving signed Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC) informed consent. 
8. Subject has no known history of latent or active tuberculosis.  Subject must meet any 1 of 
the following 3 criteria: 
1. Subject has a negative test for tuberculosis during screening, defined as either: 
o Negative purified protein derivative (PPD); < 5 mm of induration at 48 hours to 
72 hours after test is placed, or 
o Negative Quantiferon®/T-spot® test. 
2. Subject with a positive PPD test and a history of Bacillus Calmette-Guérin (BCG) 
vaccination is allowed with a negative Quantiferon/T-spot test 
3. Subject with a positive PPD test (without a history of BCG vaccination) or subject with a 
positive or indeterminate Quantiferon/T-spot test is allowed if he/she has all of the 
following: 
o No symptoms per tuberculosis worksheet provided by the sponsor, Amgen Inc. 


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o Documented history of adequate prophylaxis initiation prior to receiving 
investigational product in accordance with local recommendations 
o No known exposure to a case of active tuberculosis after most recent prophylaxis 
o No evidence of active tuberculosis on chest radiograph within 3 months prior to the 
first dose of investigational product 
5.2 Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
Skin Disease Related Conditions 
1. Subject has erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication 
induced psoriasis, or other skin conditions at the time of screening (eg, eczema) that would 
interfere with evaluations of the effect of investigational product of psoriasis. 
Other Medical Conditions 
2. Subject has a planned surgical intervention during the duration of the study. 
3. Subject has an active infection or history of infections, as follows: 
a. Any active infection for which systemic anti-infectives were used within 28 days prior to 
enrollment 
b. A serious infection, defined as requiring hospitalization or IV anti-infectives within 
8 weeks prior to enrollment 
c. Recurrent or chronic infections or other active infection that, in the opinion of the 
investigator, might cause this study to be detrimental to the subject 
4. Subject has known history or tests positive of human immunodeficiency virus (HIV) at 
screening. 
5. Subject has hepatitis B surface antigen or hepatitis C virus antibody positivity at screening. 
6. Subject has uncontrolled, clinically significant systemic disease, such as uncontrolled 
diabetes mellitus, cardiovascular disease, renal disease, liver disease, or hypertension. 
7. Subject has known malignancy within the previous 5 years (except treated or considered 
cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast 
ductal carcinoma). 
8. Subject has active neurological disease, such as multiple sclerosis, Guillain Barre 
syndrome, optic neuritis, transverse myelitis, or history of neurologic symptoms suggestive 
of central nervous system demyelinating disease. 


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9. Subject has a mean QT internal or abnormal long QT syndrome corrected using Fridericia’s 
formula (QTcF) of > 450 msec (for male subject) or > 470 msec (for female subject) at 
baseline that, in the opinion of the investigator, is abnormal or clinically significant.  If the 
mean QTcF exceeds the limits above, 1 additional triplicate electrocardiogram (ECG) may 
be taken. 
10. Subject has moderate to severe heart failure (New York Heart Associate class III/IV). 
11. Subject has known hypersensitivity to the investigational product or to any of the excipients. 
12. Subject has any concurrent medical condition that, in the opinion of the investigator, could 
cause this study to be detrimental to the subject. 
Laboratory Abnormalities 
13. Subject has laboratory abnormalities at screening, including any of the following: 
a. Hemoglobin < 9 g/dL 
b. Platelet count < 100,000/mm3 
c. White blood cell count < 3,000 cells/mm3 
d. Aspartate aminotransferase and/or alanine aminotransferase ≥ 2.0 × the upper limit of 
normal 
e. Creatinine clearance < 50 mL/min (Cockcroft Gault formula) 
f. Any other laboratory abnormality which, in the opinion of the investigator, will prevent the 
subject from completing the study or will interfere with the interpretation of the study 
results 
Washouts and Non-permitted Drugs 
14. Subject has had previous treatment with any agent specifically targeting IL-12 or IL-23 within 
1 year prior to enrollment. 
15. Subject has received biologic treatment for psoriasis within the previous month or 5 drug 
half-lives (whichever is longer) prior to enrollment. 
16. Subject has received any investigational agents within the previous month or 5 half-lives 
(whichever is longer) prior to enrollment. 
17. Subject has received non-biologic systemic psoriasis therapy within 4 weeks prior to 
enrollment (including, but not limited to, oral retinoids, methotrexate, cyclosporine, 
systemically administered calcineurin inhibitors, azathioprine, thioguanine, hydroxyurea, 
fumarates, mycophenolate mofetil, Janus kinase inhibitors, or oral or parenteral 
corticosteroids including intramuscular or intraarticular administration, exception: ophthalmic, 
otic, nasal, or inhaled corticosteroids within recommended doses is permitted). 


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18. Subject has received ultraviolet A phototherapy (with or without psoralen) or excimer laser 
within 4 weeks prior to enrollment, or ultraviolet B phototherapy within 2 weeks prior to 
enrollment. 
19. Subject has received topical psoriasis treatment within 2 weeks prior to enrollment 
(exception: upper mid-strength to least potent [class III to VII] topical steroids permitted on 
the palms, soles, face, and intertriginous areas; bland emollients [without urea or α- or 
β-hydroxy acids]). 
20. Subject has received live viral or live bacterial vaccination within 2 weeks prior to enrollment. 
21. Subject has received BCG vaccination within 1 year prior to enrollment. 
22. Subject has received other investigational procedures within 4 weeks prior to enrollment and 
during the course of the study. 
General 
23. Subject has active substance abuse within 24 weeks prior to enrollment. 
24. Female subject is pregnant or breastfeeding or planning to become pregnant while 
participating in the study and for at least 5 months after the last dose of investigational 
product. 
25. Sexually active subjects and their partners who are of childbearing potential (ie, neither 
surgically nor postmenopausal) and not agreeing to use adequate contraception (eg, true 
abstinence, sterilization, birth control pills, Depo-Provera injections, or contraceptive 
implants) while participating in the study and for 5 months after the last dose of 
investigational product.  Male subjects must agree not to donate sperm during the study and 
for 5 months following after last dose of investigational product or until the scheduled EOS 
visit (whichever is longer). 
26. Subject is not likely to comply with all required study procedures (eg, Clinical Outcome 
Assessments) to the best of the subject and investigator knowledge. 
27. Subject has any physical or psychiatric disorder that, in the opinion of the investigator, may 
compromise the ability of the subject to give informed consent and/or to comply with all the 
required study procedures. 
5.3 Subject Enrollment 
Before subjects begin participation in any study-specific activities/procedures, Amgen requires a 
copy of the site’s written IRB/IEC approval of the protocol, informed consent form (ICF), and all 
other subject information and/or recruitment material. 
The subject or legally acceptable representative must personally sign and date the IRB/IEC and 
Amgen approved ICF before commencement of study-specific procedures. 


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A subject is considered enrolled when the investigator decides that the subject has met all 
eligibility criteria and has been enrolled in the Interactive Web/Voice Response System (IXRS).  
The investigator is to document this eligibility decision and date in the subject’s medical record. 
Each subject will have a unique subject identification number obtained from the IXRS.  This will 
be assigned at screening.  The unique 11-digit subject identification number will be assigned in 
sequential order for each site in the format “417XXXXX###,” where “417XXXXX” refers to the 
site number and “###” refers to the sequential subject ordering as each subject at a site is 
entered into the IXRS (eg, 41712345001).  This number will be used to identify the subject 
throughout the clinical study and must be used on all study documentation related to that 
subject.  The investigator will keep a record (the subject screening log) that includes limited 
information (such as date of screening) about the potential candidates for subjects who entered 
screening. 
If a subject withdraws from study participation, his/her unique identification number(s) cannot be 
re-used for another subject. 
The subject identification number must remain constant throughout the entire clinical study; it 
must not be changed after initial assignment, including if a subject is rescreened.  This number 
will not necessarily be the same as the randomization number assigned for the study. 
5.4 Lifestyle Considerations 
5.4.1 Meals and Dietary Restrictions 
Not applicable. 
5.4.2 Caffeine, Alcohol, and Tobacco 
Not applicable. 
5.4.3 Activity 
Not applicable. 
5.4.4 Coronavirus Disease 2019 Considerations 
Study centers and subjects will follow local and institutional guidelines, as applicable, for the 
prevention of COVID-19 infection.  In the event that a subject experiences any signs/symptoms 
of COVID-19, the subject should promptly notify the investigator. 


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5.5 Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently enrolled to the study.  A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure subjects to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities.  
Minimal information includes demography, reason for screen failure (eg, eligibility requirements 
failed), and any serious adverse events. 
If a subject has not met all eligibility criteria at the end of the screening period, the subject will 
be registered as a screen failure.  Individuals who do not meet the criteria for participation in this 
study (screen failure) may be rescreened.  Rescreened subjects should be assigned the same 
subject identification number as for the initial screening.  Laboratory assessments used to 
determine subject eligibility may be repeated during the screening period before the subject is 
considered a screen failure.  Screen failed subjects may be rescreened up to 2 times at the 
investigator’s discretion (ie, a total of 3 screens including initial screening).  If screening 
procedures cannot be completed within 28 days before day 1, the subject will be considered a 
screen failure but may be eligible for rescreening.  These subjects can be rescreened under the 
same ICF if rescreening and enrollment occurs within 30 days of initial consent date.  If it is 
longer than 30 days from the initial consent date, the subject will need to be re-consented and 
all screening procedures need to be repeated. 
6 Investigational Product 
Investigational product is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study subject according to the 
study protocol. 
The investigator must ensure that the investigational product will be used only in accordance 
with the protocol.  Study treatments and investigational product are described in Table 6-1. 


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6.1 Investigational Product(s) Administered 
Table 6-1. 
Investigational Product(s) Administered 
Intervention Name 
ABP 654 
Ustekinumab 
Type 
Biologic 
Biologic 
Dosage Formulation 
Liquid suspension 
Liquid suspension 
Unit Dose Strength(s) 
45 mg/0.5 mL solution in a single dose 
prefilled syringe for subjects with 
baseline body weight ≤ 100 kg 
or 
90 mg/1.0 mL solution in a single dose 
prefilled syringe for subjects with 
baseline body weight > 100 kg 
45 mg/0.5 mL solution in a single dose 
prefilled syringe for subjects with 
baseline body weight ≤ 100 kg 
or 
90 mg/1.0 mL solution in a single dose 
prefilled syringe for subjects with 
baseline body weight > 100 kg 
Dosage Level(s) 
Dose based on baseline body weight: 
•
45 mg (≤ 100 kg)
•
90 mg (> 100 kg)
Dose based on baseline body weight: 
•
45 mg (≤ 100 kg)
•
90 mg (> 100 kg)
Route of Administration 
Subcutaneous injection 
Subcutaneous injection 
Use 
Experimental 
Active comparator 
IMP and NIMP 
IMP 
IMP 
Sourcing 
Provided centrally by the sponsor 
Provided centrally by the sponsor 
Dosing Instructions 
Subjects in the switching group will be 
administered ABP 654 at week 28 and 
again at week 52. 
Subjects in the switching group will be 
administered ustekinumab on day 1, 
week 4, week 16 and week 40. 
Subjects in the continued-use group 
will be administered ustekinumab on 
day 1, week 4, week 16 and every 
12 weeks at week 28, week 40 and 
week 52. 
Packaging and Labeling 
Investigational product will be provided 
in a prefilled syringe.  Each prefilled 
syringe will be labeled as required per 
country requirement. 
Investigational product will be provided 
in a prefilled syringe.  Each prefilled 
syringe will be labeled as required per 
country requirement. 
IMP: investigational medicinal product; NIMP: non-investigational medicinal product 
6.1.1 ABP 654 Dosage Form 
ABP 654 is a recombinant fully human IgGκ monoclonal antibody produced by recombinant 
DNA technology and is produced in a glyco-engineered Chinese hamster ovary cell line.  
ABP 654 is purified by processes that include specific viral inactivation and filtration steps.  
ABP 654 and ustekinumab have the same amino acid sequence. 
ABP 654 is supplied as a sterile, single-dose, preservative-free solution for SC injection and is 
supplied in a prefilled syringe (PFS) containing 45 mg/0.5 mL ABP 654 or 90 mg/1.0 mL 
ABP 654. 


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Each 0.5 mL PFS delivers 45 mg ABP 654, L-histidine and L-histidine monohydrochloride 
monohydrate, polysorbate 80, and sucrose.  Each 1 mL PFS delivers 90 mg ABP 654, 
L-Histidine and L-Histidine monohydrochloride monohydrate, polysorbate 80, and sucrose.  See 
the Investigator’s Brochure for additional details. 
6.1.2 Ustekinumab Dosage Form 
Ustekinumab is a recombinant fully human IgGκ monoclonal antibody produced by recombinant 
DNA technology, and is produced by a Sp2/0 cell line. 
Ustekinumab is supplied in 45 mg/0.5 mL and 90 mg/1.0 mL single use PFS. 
Each single-dose PFS delivers 45 mg or 90 mg ustekinumab, L-Histidine, L-Histidine 
monohydrochloride monohydrate, polysorbate 80, and sucrose. 
6.2 Preparation, Handling, Storage, and Accountability 
Investigational product should be stored protected from light and according to the storage and 
expiration information provided on the label (where required) that is affixed to the package 
containing the investigational product.  The PFS should be stored in a secured refrigerator 
(2°to 8°C) and monitored (manual or automated) in accordance with the labeled storage 
conditions and country-specific regulations, with access limited to the investigator and 
authorized site staff.  Investigational product should not be frozen.  The investigator or designee 
must maintain documentation to confirm appropriate temperature conditions have been 
maintained during transit and storage at site for all investigational product received and any 
discrepancies are reported and resolved before use of the investigational product. 
The PFS should be checked for cracks or damage that may occur during transport.  Damaged 
product should not be administered and should be returned to Amgen or its designee. 
Detailed information regarding the labeling, packaging, storage, preparation, and administration 
of each investigational product is to be provided separately in the Pharmacy Manual. 
All supplies of investigational product will be accounted for in accordance with GCP guidelines.  
The investigator, pharmacist, or designee should maintain accurate records of the disposition of 
all investigational product supplies received during the study.  These records should include the 
amounts and dates clinical drug supplies were received and returned to Amgen or its designee.  
If errors or damages in the clinical drug supply shipments occur, the investigator should contact 


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Amgen or its designee immediately.  Copies of the investigational product accountability records 
will be provided by each investigator for inclusion in the Trial Master File (TMF).  The clinical 
research associate (CRA) will periodically check the supplies of investigational product held by 
the investigator or pharmacist to verify accountability of all medication used. 
The investigator will administer investigational product only to the identified subjects of this 
study, according to the procedures described in this study protocol.  After the end of study, all 
unused investigational product and all investigational product containers should be destroyed 
on-site (if approved by the sponsor or designee) or returned to Amgen or its designee for 
destruction.  In either instance, complete documentation will be returned to the sponsor or 
designee.  Further guidance and information for the final disposition of unused investigational 
product are provided in the Pharmacy Manual. 
The investigational product resupply will be managed by the IXRS. 
6.3 Investigational Product Complaints 
An investigational product complaint is any written, electronic, or oral communication that 
alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a drug(s) or device(s) after it is released for distribution to market or clinic by 
either Amgen or by distributors and partners for whom Amgen manufactures the material. 
Any investigational product complaint(s) associated with ABP 654 or ustekinumab supplied by 
Amgen are to be reported according to the instructions provided in the Pharmacy Manual.  Any 
investigational product complaints associated with an adverse event are to be reported as per 
adverse event reporting guidelines. 
6.4 Measures to Minimize Bias: Blinding and Randomization 
6.4.1 Blinding 
The study is double-blinded; therefore, the investigators, study personnel (with the exception of 
the Data Monitoring Committee (DMC), and unblinded Parexel staff supporting DMC activities 
and randomization list activities) and the study subjects will remain blinded to treatment 
allocation. 
Randomization data will be kept strictly confidential, accessible only to authorized staff and the 
DMC until the time of unblinding.  Authorized staff includes the randomization statistician, who 


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will store the master randomization list in a secure system, an unblinded statistician, and 
unblinded programmers, who will provide the DMC with unblinded data for review, as and when 
required, in accordance with the procedures described in the DMC Charter.  All authorized 
unblinded staff must be documented. 
ABP 654 and ustekinumab will be coded and labeled in a manner that protects blinding. 
Unblinding is only allowed in the case of an emergency, when knowledge of the investigational 
product is essential for the clinical management of the subject.  The investigator must make 
every effort to contact the sponsor or designee’s medical monitor prior to breaking the blind and 
must contact the sponsor or designee within 1 working day after the event, without revealing to 
the sponsor (or clinical research organization [CRO]) the results of the code break, except to the 
designated global  safety representative. 
Emergency unblinding will be organized through the IXRS.  The investigator must record the 
date of unblinding and the reason.  All unblinding must be adequately documented. 
If a serious adverse event is reported, the designated global safety representative may unblind 
the treatment assignment for the individual subject through IXRS in order to meet regulatory 
reporting requirements.  Authorized staff will be provided with a unique Personal Identification 
Number (PIN) to access the IXRS to obtain blinding information.  The PIN is unique to the 
individual and must not be shared. 
6.4.2 Randomization 
The site will contact the IXRS at week 28 (subjects with PASI 50 or better improvement) to 
receive a unique subject randomization number in order to randomize the subject centrally to 
either the switching group or continued-use group in a 1:1 manner.  Randomization will be 
stratified according to the following factors: prior biologic use for psoriasis (“yes” versus “no”), 
baseline body weight (≤ 100 kg versus > 100 kg) at baseline (week 0), and geographic region.  
All enrolled subjects not randomized at week 28 will be considered run-in failures and the run-in 
failure reason will be documented. 
In the event of a quality assurance (QA) audit, the auditor(s) will be allowed access to unblinded 
investigational product records to verify that randomization/dispensing has been done 
accurately. 


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6.5 Investigational Product Compliance 
Records of investigational product used and intervals between visits will be kept during the 
study.  Drug accountability will be noted by the CRA during site visits and at the completion of 
the study.  The study treatment should be dispensed by the investigator, or by a qualified 
individual under the investigator’s supervision.  An up-to-date treatment inventory/dispensing 
record must be maintained. 
6.6 Concomitant Therapy 
6.6.1 Prohibited Treatments 
• 
Nonstudy use of ustekinumab, or therapies that target IL-12 or IL-23, are prohibited 
(exclusion criterion 14). 
• 
Any biologic treatment for psoriasis, or any experimental (biological or nonbiological) 
therapy (within or outside of a clinical study), except for investigational product, for subjects 
are prohibited (exclusion criteria 15 and 16). 
• 
Treatments (exclusion criterion 17) which include nonbiologic systemic psoriasis therapy 
(including but not limited to oral retinoids, methotrexate, cyclosporine, systemically 
administered calcineurin inhibitors, azathioprine, thioguanine, hydroxyurea, fumarates, 
mycophenolate mofetil, Janus kinase inhibitors, or oral or parenteral corticosteroids 
including intramuscular or intraarticular administration [exception: ophthalmic, otic, nasal, or 
inhaled corticosteroids within recommended doses is permitted]). 
• 
Any other nonstudy treatment for psoriasis, including UVA or UVB phototherapy and 
excimer laser (exclusion criterion 18) and topical therapies for psoriasis (except for those 
specifically allowed, exclusion criterion 19) are prohibited. 
• 
Live viral or live bacterial vaccination (exclusion criterion 20).  The investigational product 
should be withheld for at least 15 weeks before vaccination and only resumed at least 
2 weeks after vaccination. 
6.6.2 Prior and Concomitant Therapy 
Prohibited treatments are described in Section 6.6.1. 
Any other treatment (not explicitly excluded) which is considered necessary for the subject’s 
welfare may be given at the discretion of the investigator.  Allowed treatments include: 


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• 
Bland moisturizers/emollients (without urea or α- or β-hydroxy acids) are allowed, as 
needed, during the study 
• 
Upper mid-strength to least potent (class III to VII) topical steroids are permitted only on the 
palms, soles, face, and intertriginous areas 
• 
Otic, nasal, ophthalmic, or inhaled corticosteroids are not considered “systemic 
immunomodulating treatments” and are allowed during the study. 
At screening, prior medication history will be documented. 
Any vaccine or medication (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the subject is receiving at the time of enrollment or receives 
during the study must be recorded. 
The medical monitor should be contacted if there are any questions regarding prior or 
concomitant therapy. 
All subjects who discontinue investigational product should be offered alternative treatment, if 
applicable.  Treatment should be given according to normal clinical practice after the EOS visit. 
6.7 Dose Modification 
There are no dose modifications for investigational products (ABP 654 or ustekinumab) in this 
study.  The ABP 654/ustekinumab dose will be based on the subject’s baseline body weight and 
will remain the same throughout the study.  Dosing will not be corrected on the basis of body 
weight at current visit. 
If the subject presents with a serious infection at the dosing visit(s), the administration of 
investigational product may be delayed (up to 5 days); and subjects with serious infections need 
to be monitored closely and investigational product should not be administered until the infection 
resolves. 
In the case of delayed or missed dose for any reason, subsequent doses should be 
administered according to the original schedule (ie, at the planned timepoint relative to first 
dose) investigational product dose(s). 
Any toxicities associated or possibly associated with investigational product treatment should be 
managed according to standard medical practice.  A summary of expected adverse drug 
reactions is provided in the Investigator’s Brochure.  Ustekinumab has a terminal half-life of 


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approximately 28.1 days, therefore discontinuation results in slow elimination over several 
months and will have no immediate effect. 
If unmanageable toxicity due to investigational product occurs at any time during the study, 
treatment with the investigational product should be discontinued. 
6.8 Intervention After the End of the Study 
After completing dosing with investigational product at week 52 and the EOS visit at week 64, 
subjects will have completed the study.  ABP 654 or ustekinumab will not be provided for post 
study use. 
7 Discontinuation of Investigational Product and Subject 
Discontinuation 
Subjects have the right to withdraw from treatment with investigational product, protocol 
procedures, or the study completely at any time and for any reason without prejudice to their 
future medical care by the physician or at the institution. 
7.1 Discontinuation of Investigational Product 
Subjects (or a legally acceptable representative) can decline to continue receiving 
investigational product or procedures at any time during the study but continue participation in 
the study.  If this occurs, the investigator is to discuss with the subject the appropriate 
processes for discontinuation from investigational product and must discuss with the subject the 
possibilities for continuation of the Schedule of Assessments (Table 1-1) including different 
options of follow-up (eg, in person, by phone/mail, through family/friends, in 
correspondence/communication with other treating physicians, from the review of medical 
records) and collection of data, including adverse events, and must document this decision in 
the subject’s medical records.  Subjects who have discontinued investigational product and/or 
other protocol-required therapies or procedures should not be automatically removed from the 
study.  Whenever safe and feasible, it is recommended that these subjects remain in the study 
to ensure safety surveillance and/or collection of efficacy data, where possible.  Reasons for 


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early removal from protocol-required investigational product(s) or procedural assessments may 
include: 
• 
Decision by sponsor 
• 
Lost to follow-up 
• 
Death 
• 
Adverse event 
• 
Subject request 
• 
Protocol deviation 
• 
Noncompliance 
• 
Pregnancy 
7.2 Subject Discontinuation/Withdrawal from the Study 
Participation in the study is strictly voluntary.  Subjects have the right to withdraw from the study 
by his/her own request at any time and for any reason without any reprisal, and without 
prejudice to future medical care by the physician or institution. 
Subjects who do not achieve a PASI 50 response or better improvement at week 28 will not be 
randomized and will complete EOS procedures at week 28.  Those unable to complete the 
week 28 visit or did not have a PASI assessment completed at week 28 will be discontinued 
from the study.  The run-in period will occur from day 1 until randomization at week 28.  All 
enrolled subjects not randomized at week 28 will be considered run-in failures and the run-in 
failure reason will be documented.  Subjects terminating early from the study should complete 
all procedures scheduled for EOS visit (ie, week 64) within 28 days after 
withdrawal/discontinuation if possible. 
Withdrawal of consent for a study means that the subject does not wish to receive further 
protocol-required therapies or procedures, and the subject does not wish to or is unable to 
continue further study participation.  Subject data up to withdrawal of consent will be included in 
the analysis of the study, and where permitted, publicly available data can be included after 
withdrawal of consent.  The investigator is to discuss with the subject appropriate procedures for 
withdrawal from the study and must document the subject’s decision to withdraw in the subject’s 
medical records.  If the subject withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a withdrawal of consent.  
If a subject withdraws from the study, he/she may request destruction of any samples taken and 


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not tested, and the investigator must document this in the study center study records and notify 
the sponsor or designee.  Although a subject is not obliged to give his/her reason(s) for 
withdrawing prematurely from a study, the investigator should make a reasonable effort to 
ascertain the reason(s), while fully respecting the subject's rights.  Subjects who are withdrawn 
will not be replaced.  Subjects who prematurely discontinue from the study cannot subsequently 
rejoin the study. 
A subject may be discontinued from the study at any time at the discretion of the investigator for 
safety, behavioral, or administrative reasons, including, but not limited to: 
• 
Requirement for alternative therapy or alternative dosing schedule per the investigator’s 
determination 
• 
The subject develops a malignancy (exception: subjects may be allowed to continue if they 
develop no more than 2 non-melanoma skin cancers during the study) 
• 
Adverse events or serious adverse events 
• 
Any laboratory abnormalities that in the judgment of the investigator, taking into 
consideration the subject’s overall status, prevents the subject from continuing participation 
in the study 
• 
Any other reason relating to the subject's safety or integrity of the study data 
• 
Noncompliance with study procedures 
• 
Withdrawal of consent from the study 
• 
Lost to follow-up 
• 
Decision by sponsor/investigator 
• 
Death 
Refer to the Schedule of Assessments (Table 1-1) for data to be collected at the time of study 
discontinuation and evaluations that need to be completed. 
If a subject withdraws or is discontinued from the study, the CRA will be informed immediately. 
7.3 Loss of Subjects to Follow-Up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 


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The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• 
The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible (and within the visit window, where one is defined) and counsel the subject on the 
importance of maintaining the assigned visit schedule and ascertain whether or not the 
subject wishes to and/or should continue in the study. 
• 
In cases in which the subject is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the subject (where possible, 3 telephone calls and, 
if necessary, a certified letter to the subject’s last known mailing address or local equivalent 
methods).  These contact attempts should be documented in the subject’s medical record. 
• 
If the subject continues to be unreachable, he/she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 
8 Study Assessments and Procedures 
Study procedures and their timing are summarized in the Schedule of Assessments (Table 1-1).  
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence 
or awareness to determine if the subject should continue or discontinue investigational product. 
Adherence to the study design requirements, including those specified in the Schedule of 
Assessments, is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria.  The investigator will maintain a screening log to record details of all 
subjects screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
Procedures conducted as part of the subject’s routine clinical management and obtained before 
signing of the ICF may be utilized for screening or baseline purposes provided the procedures 
met the protocol-specified criteria and were performed within the time frame defined in the 
Schedule of Assessments (Table 1-1). 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. 


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Investigational product will be administered after all other procedures are completed for each 
dosing visit. 
Informed Consent 
Informed consent must be documented according to Section 10.1.2, Appendix 1. 
Eligibility Criteria 
All inclusion and exclusion criteria will be reviewed by the investigator or designee to ensure 
that the subject qualifies for the study. 
Medical History 
A medical history will be obtained by the investigator or qualified designee.  The medical history 
will collect all active conditions and any prior conditions that the investigator considers to be 
clinically relevant. 
Prior and Concomitant Medications Review 
The investigator or qualified designee will review prior medication use and record prior 
medications taken by the subject. 
The investigator or qualified designee will record medication, if any, taken by the subject during 
the study through the last visit. 
Demographic Data 
Demographic data, including (where permitted), date of birth/age, sex, race, and ethnicity will be 
documented. 
8.1 Efficacy Assessments 
8.1.1 Psoriasis Area and Severity Index 
The PASI is a measure of the average redness (erythema), thickness (induration), and 
scaliness (scaling), each graded on a 0 to 4 scale of the lesions, weighted by the area of 
involvement (Feldman and Krueger, 2005).  All assessments for a given subject should be 
made by the same observer, wherever possible. 


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8.1.2 Static Physical Global Assessment 
The sPGA is a 6-point scale (0 to 5) used to measure the severity of disease (induration, 
scaling, and erythema, Section 10.3, Appendix 3).  The sPGA should be completed by the same 
assessor performing the PASI assessments.  All assessments for a given subject should be 
made by the same observer, whenever possible. 
8.1.3 Affected Body Surface Area 
The percent of affected BSA affected is estimated by assuming that the subject’s palm, 
excluding the fingers and thumb, represents roughly 1% of the body’s surface (Chandran, 
2009).  At any given visit, BSA should be performed by the same assessor performing PASI 
assessment.  Because of interobserver variability in estimated BSA, all assessments for a given 
subject should be made by the same observer, whenever possible. 
8.2 Safety Assessments 
8.2.1 Physical Examinations 
Physical examination findings will be recorded and performed by a physician. 
Clinically significant abnormal changes from baseline will be reported as adverse events. 
Body weight (kg) and height will be measured with the subject dressed in light clothing, without 
shoes or jacket.  Body weight and height will be determined at screening.  The baseline body 
weight will be measured at baseline. 
Investigators should pay special attention to clinical signs related to previous serious illnesses.  
Any new abnormalities or worsening of existing abnormalities should be reported as adverse 
events, as appropriate (Section 8.3). 
8.2.2 Vital Signs 
Vital signs will be measured after the subject has been resting for 5 minutes and will include 
systolic and diastolic blood pressure, pulse, respiratory rate, and temperature. 
Systolic and diastolic blood pressure will be measured on the same arm. 
Respiratory rate and temperature will also be recorded. 


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During the study, the measurement of vital signs may be repeated at the discretion of the 
investigator for safety reasons.  Clinically relevant abnormal findings should be reported as 
adverse events. 
8.2.3 Twelve-lead Electrocardiogram 
Routine 12-lead ECGs will be taken as indicated in the Schedule of Assessments (Table 1-1).  
A routine 12-lead ECG will be taken after the subject has been resting in the supine position for 
at least 5 minutes.  12-lead ECGs will be taken in triplicate with approximately 1-minute intervals 
and all 3 ECGs will be completed within 5 minutes. 
The investigator will use the study site’s system to review, sign and date the ECG after 
recording to ensure subject safety.  The time of the ECG, the interval measurements (measured 
automatically using the same lead whenever possible), as well as an overall conclusion, will be 
documented.  This overall outcome will be recorded as normal, abnormal not clinically 
significant, or abnormal clinically significant. 
Per time point, the ECGs will be stored electronically and reviewed in a timely manner by the 
investigator. 
8.2.4 Tuberculosis Testing 
A tuberculosis test will be performed at screening by PPD or Quantiferon/T-spot test.  PPD tests 
will be performed locally, and Quantiferon/T-spot tests will be performed by the local or central 
laboratory.  Subjects with positive PPD or positive or indeterminate Quantiferon/T-spot test may 
be eligible based on the sponsor’s tuberculosis assessment worksheet and the other criteria 
listed in inclusion criterion 8. 
8.2.5 Chest Radiography 
Chest radiography will include anterior/posterior or posterior/anterior and lateral views.  
Historical films or formal reports signed off by a radiologist obtained in the 3 months prior to 
screening are acceptable. 
8.2.6 Clinical Safety Laboratory Assessments 
Refer to the list of clinical laboratory tests (Table 8-1) to be performed and to the Schedule of 
Assessments (Table 1-1) for the timing and frequency. 


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Urine pregnancy tests will be performed locally.  PPD and Quantiferon/T-spot tests will be 
performed by the local or central laboratory as described in the Schedule of Assessments 
(Table 1-1).  All other laboratory assessments will be performed by a central laboratory.  Blood 
and urine samples will be collected at the times indicated in the Schedule of Assessments 
(Table 1-1).  At visits when investigational product is administered, clinical laboratory samples 
will be collected before investigational product administration.  Venous blood samples will be 
taken for hematology and biochemistry testing at visits specified in the Schedule of 
Assessments (Table 1-1). 
Refer to the investigator Laboratory Manual for details regarding the collection, processing, and 
shipping of the blood and urine samples. 
Any blood samples (eg, PK, immunogenicity) collected according to the Schedule of 
Assessments (Table 1-1) can be analyzed for any of the tests outlined in the protocol and for 
any tests necessary to minimize risks to study subjects.  This includes testing to ensure 
analytical methods produce reliable and valid data throughout the course of the study.  This can 
also include, but is not limited to, investigation of unexpected results, incurred sample 
reanalysis, and analyses for method transfer and comparability. 
Additional and repeat laboratory safety testing may be performed at the discretion of the 
investigator. 
The investigator (or designee) must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the adverse event section of 
the case report form (CRF).  The laboratory reports must be filed with the source documents.  
Clinically relevant abnormal laboratory findings are those which are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 
subject's condition. 


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Table 8-1. 
Protocol-required Safety Laboratory Assessments 
Laboratory Assessments 
Parameters 
Hematology 
Absolute neutrophil count 
Hematocrit 
Hemoglobin 
Platelet count 
RBC count 
WBC count (total) 
WBC count (differential) 
Clinical Chemistry 
Blood urea nitrogen 
Potassium 
Total bilirubin 
Creatinine 
Sodium 
Total protein 
Albumin 
Glucose (random) 
Alkaline phosphatase 
AST 
ALT 
gamma-glutamyl transferase 
Routine Urinalysis 
pH, specific gravity, creatinine, glucose, bilirubin, blood, and protein 
Other Screening Tests 
FSH and estradiol (as needed in non-WOCBP only) at screening 
Serum hCG pregnancy test (as needed for WOCBP) at screening 
Serology (HbsAg, HCV, and HIV) at screening 
TB1 testing (including a TB worksheet and chest X-ray) at screening 
12-lead electrocardiogram
Urine pregnancy tests
Creatinine clearance
Immunology (ADA antibody)
ADA: antidrug antibody; ALT: alanine aminotransferase; AST: aspartate aminotransferase; FSH: follicle-stimulating 
hormone; HbsAG: hepatitis B surface antigen; hCG: human chorionic gonadotropin; HCV: hepatitis C virus; 
HIV: human immunodeficiency virus; RBC: red blood cell; TB: tuberculosis; WBC: white blood cell; WOCBP: women 
of childbearing potential 
1.
Quantiferon®/T-spot® or purified protein derivative testing.
8.3 Adverse Events and Serious Adverse Events 
8.3.1 Definitions 
8.3.1.1 Adverse Events 
An adverse event is any untoward medical occurrence in a clinical trial subject.  The event does 
not necessarily have a causal relationship with the investigational product.  An adverse event 
can therefore be an unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally associated with the use of a treatment, 
combination product, medical device, or procedure.  The investigator is responsible for ensuring 
that any adverse events observed by the investigator or reported by the subject are recorded in 
the subject’s medical record as well as the electronic case report form (eCRF). 


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8.3.1.1.1 Events Meeting the Adverse Event Definition 
Events that meet the adverse event definition: 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (e.g., ECG, radiological scans, vital signs measurements), including 
those that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the investigator (e.g., not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after investigational product administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either investigational 
product or a concomitant medication.  Overdose per se will not be reported as an adverse 
event/serious adverse event unless it is an intentional overdose taken with possible 
suicidal/self-harming intent.  Such overdoses should be reported regardless of sequelae.  In 
case of overdosage, it is recommended that the subject be monitored for any signs or 
symptoms of adverse reactions or effects and appropriate symptomatic treatment be 
instituted immediately. 
• 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be reported 
as an adverse event or serious adverse event.  Such instances will be captured in the 
efficacy assessments.  However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as adverse events or serious adverse events if they 
fulfill the definition of an adverse event or serious adverse event. 
8.3.1.1.2 Events NOT Meeting the Adverse Event Definition 
Events not meeting the adverse event definition include: 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads to 
the procedure is the adverse event. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital [inpatient hospitalization for less than 24 hours]). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 


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• 
A pre-existing condition that has not worsened during the study or involves an intervention 
such as elective cosmetic surgery or a medical procedure while on study is not considered 
an adverse event. 
8.3.1.2 Serious Adverse Event 
A serious adverse event is defined as any untoward medical occurrence that meets at least 1 of 
the following serious criteria: 
• 
Results in death (fatal) 
• 
Life-threatening (places the subject at immediate risk of death) 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability/incapacity 
• 
Congenital anomaly/birth defect 
• 
Other medically important serious event 
Definitions 
Life-threatening: The term “life-threatening” in the definition of “seriousness” refers to an event 
in which the subject was at risk of death at the time of the event.  It does not refer to an event, 
which hypothetically might have caused death, if it were more severe.  For example, 
drug-induced hepatitis that resolved without evidence of hepatic failure would not be considered 
life-threatening even though drug-induced hepatitis can be fatal.  It does not include an adverse 
event or suspected adverse reaction that, had it occurred in a more severe form, might have 
caused death. 
Hospitalization: In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient setting.  
Complications that occur during hospitalization are an adverse event.  If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event is serious.  When in doubt as to 
whether “hospitalization” occurred or was necessary, the adverse event should be considered 
serious.  Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an adverse event. 
Disability/incapacity: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions.  This definition is not intended to include experiences of relatively 


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minor medical significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 
Other medically important serious event: Medical or scientific judgment is to be exercised in 
deciding whether serious adverse event reporting is appropriate in other situations such as 
important medical events that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the subject or may require medical or surgical intervention to 
prevent 1 of the other outcomes listed in the above definition.  These events are typically to be 
considered serious. 
Examples of such events include invasive or malignant cancers, 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 dependency or drug abuse. 
8.3.1.3 Clinical Laboratory Abnormalities and Other Abnormal 
Assessments 
The investigator is responsible for reviewing all laboratory test results, including review of 
laboratory test results prior to subject enrollment and reviewing subsequent laboratory test 
results throughout the study.  The investigator will determine whether an abnormal value in an 
individual study subject represents a clinically significant change from the subject’s baseline 
values.  Laboratory abnormalities without clinical significance (based on the investigator’s 
judgment) should not be recorded as adverse events or serious adverse events.  However, 
laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis abnormalities) that 
require medical or surgical intervention or lead to investigational product interruption, 
modification, or discontinuation must be recorded as an adverse event or serious adverse 
event, as applicable.  Where applicable, clinical sequelae (not the laboratory abnormality) are to 
be recorded as the adverse event.  In addition, laboratory or other abnormal assessments 
(eg, vital signs) that are associated with signs and/or symptoms must be recorded as an 
adverse event or serious adverse event if they meet the definition of an adverse event or 
serious adverse event as described in Section 8.3.1.  If the laboratory abnormality is part of a 
syndrome, record the syndrome or diagnosis (eg, anemia), not the laboratory result 
(eg, decreased hemoglobin). 


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8.3.2 Assessments of Adverse Events 
8.3.2.1 Severity 
The investigator will make an assessment of severity for each adverse event and serious 
adverse event reported during the study.  The assessment of severity will be based on Common 
Terminology Criteria for Adverse Events (CTCAE, version 4.03): 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
8.3.3 Causality 
The investigator is obligated to assess the relationship between investigational product and 
each occurrence of each adverse event or serious adverse event. 
Relatedness means that there are facts or reasons to support a relationship between 
investigational product and the event. 
The investigator will use clinical judgment to determine the relationship. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study treatment administration will be 
considered and investigated. 
The investigator will also consult the Investigator’s Brochure in his/her assessment. 
For each adverse event or serious adverse event, the investigator must document in the 
medical notes that he/she has reviewed the adverse event or serious adverse event and has 
provided an assessment of causality. 
There may be situations in which a serious adverse event has occurred and the investigator has 
minimal information to include in the initial report.  However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the serious adverse event data. 
The investigator may change his/her opinion of causality in light of follow-up information and 
send a serious adverse event follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 


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8.3.4 Documenting and Reporting of Adverse Events 
The investigator is responsible for ensuring that all adverse events observed by the investigator 
or reported by the subject that occur from the time of enrollment through the EOS visit are 
recorded in subject’s medical records as well as the applicable CRF Adverse Event Summary 
page.  The adverse event grading scale to be used for this study will be CTCAE version 4.03, as 
described in Section 8.3.2.1. 
The investigator must assign the following adverse event attributes: 
• 
Adverse event diagnosis or syndrome(s), if known (if not known, signs or symptoms) 
• 
Dates of onset and resolution 
• 
Severity (National Cancer Institute CTCAE version 4.03) 
• 
Assessment of relatedness to investigational product, other protocol-required therapies or 
devices 
• 
Action taken 
The investigator must assess whether the adverse event is possibly related to the 
investigational product.  This relationship is indicated by a “yes” or “no” response to the 
question: “Is there a reasonable possibility that the event may have been caused by the 
investigational product?”  The investigator is responsible for reviewing laboratory test results 
and determining whether an abnormal value in an individual study subject represents a clinically 
significant change from the subject’s baseline values.  In general, abnormal laboratory findings 
without clinical significance (based on the investigator’s judgment) are not to be recorded as 
adverse events.  However, laboratory value changes that require treatment or adjustment in 
current therapy are considered adverse events.  Where applicable, clinical sequelae (not the 
laboratory abnormality) are to be recorded as the adverse event. 
The investigator’s clinical judgment is used to determine whether a subject is to be removed 
from treatment due to an adverse event.  A subject, or subject’s legal representative, can also 
voluntarily withdraw from treatment due to an adverse event.  If the subject withdraws consent, 
the subject is encouraged to undergo, at a minimum, an EOS assessment. 
It is the investigator’s responsibility to review all documentation (eg, hospital notes, laboratory 
reports, and diagnostic reports) related to an adverse event.  Wherever possible, the 
investigator’s diagnosis, not the individual signs and symptoms, will be documented as the 
adverse event. 


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It is not acceptable for the investigator to send photocopies of the subject’s medical records to 
sponsor or responsible CRO in lieu of completion of the CRF page. 
If specifically requested, the investigator may need to provide additional follow-up information, 
such as discharge summaries, medical records, or extracts from the medical records.  In this 
case, all subject identifiers, with the exception of the subject number, will be blinded on the 
copies of the medical records before submission to the sponsor or responsible CRO. 
Investigators are not obligated to actively seek adverse events or serious adverse events after 
the subject’s conclusion of study participation.  However, if the investigator learns of any serious 
adverse event, including death, at any time after a subject has been discharged from the study, 
and he/she considers the event to be reasonably related to the investigational product or study 
participation, the investigator must promptly notify the sponsor. 
8.3.4.1 Reporting of Serious Adverse Events 
The investigator is responsible for ensuring that all serious adverse events observed by the 
investigator or reported by the subject that occur after signing of the ICF through the EOS visit 
are reported using the applicable CRF Adverse Event Summary page or via the paper serious 
adverse event report form for serious adverse events occurring during screening for subjects 
not enrolled. 
All serious adverse events must be documented, recorded and transmitted to Amgen, or its 
designee, within 24 hours following the investigator’s knowledge of the event. 
The investigator will submit any updated serious adverse event data to the sponsor or designee 
within 24 hours of it being available. 
The criteria for grade 4 in the CTCAE (version 4.03) grading scale differs from the regulatory 
criteria for serious adverse events.  It is left to the investigator’s judgment to report these 
grade 4 abnormalities as serious adverse events. 
If the electronic data capture (EDC) system is not functional, the serious adverse event can be 
reported by faxing a completed paper Serious Adverse Event Form or by direct telephone 
communication with Parexel at the numbers provided below.  The event must be updated 
electronically in the EDC system by the clinical study center once the EDC function resumes. 


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Global reporting of serious adverse events: 
• 
Phone (Safety line): +1 (781) 434-5010 
• 
NorthAmerica_Medical@parexel.com 
After the study is completed at a given center, the EDC system will be taken off-line to prevent 
the entry of new data or changes to existing data.  If a center receives a report of a new serious 
adverse event from a study subject or receives updated data on a previously reported serious 
adverse event after the EDC has been taken off-line, then the center can report this information 
on a paper Serious Adverse Event Form. 
8.3.4.2 Regulatory Reporting Requirements for Serious Adverse 
Events 
If a subject is permanently withdrawn from protocol-required therapies because of a serious 
adverse event, this information must be submitted to Amgen, or its designee. 
Prompt notification by the investigator to the sponsor (or designee) of serious adverse events is 
essential so that legal obligations and ethical responsibilities towards the safety of subjects and 
the safety of a study treatment under clinical investigation are met. 
The sponsor (or designee) has a legal responsibility to notify both the local regulatory authority 
and other regulatory agencies about the safety of a study treatment under clinical investigation. 
The sponsor (or designee) will comply with country-specific regulatory requirements relating to 
safety reporting to the regulatory authority, IRBs/IECs, and investigators. 
Individual safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and sponsor (or designee) policy and forwarded to 
investigators as necessary. 
An investigator who receives an individual safety report describing a serious adverse event or 
other specific safety information (eg, summary or listing of serious adverse events) from the 
sponsor (or designee) will file it along with the Investigator’s Brochure and will notify the 
IRB/IEC, if appropriate according to local requirements. 
To comply with worldwide reporting regulations for serious adverse events, the treatment 
assignment of subjects who develop serious, unexpected, and related adverse events may be 
unblinded by Amgen or designee before submission to regulatory authorities.  Aggregate 


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analyses may also be unblinded by the Safety Assessment Team, as appropriate. Investigators 
will receive notification of related serious adverse events reports sent to regulatory authorities in 
accordance with local requirements. 
8.3.4.3 Reporting of Serious Adverse Event After the 
Protocol-required Reporting Period 
There is no requirement to monitor study subjects for serious adverse events following the 
protocol-required reporting period or after the EOS.  However, these serious adverse events 
can be reported to Amgen.  Per local requirements in some countries, investigators are required 
to report serious adverse events that they become aware of after the EOS.  If serious adverse 
events are reported, the investigator is to report them to Amgen within 24 hours following the 
investigator’s knowledge of the event. 
Serious adverse events reported outside of the protocol-required reporting period will be 
captured within the safety database as clinical study cases and handled accordingly based on 
relationship to investigational product. 
8.3.4.4 Method of Detecting Adverse Events and Serious Adverse 
Events 
Care will be taken not to introduce bias when detecting adverse events and/or serious adverse 
events.  Open-ended and nonleading verbal questioning of the subject is the preferred method 
to inquire about adverse event occurrence. 
8.3.4.5 Adverse Event and Serious Adverse Event Follow-up 
During the study the adverse events and serious adverse events should be followed proactively 
by the investigator at subsequent visits/contact.  All adverse events and serious adverse events 
will be followed until resolution, stabilization, until the event is otherwise explained, or until the 
subject is lost to follow-up.  At the time the subject’s study participation ends, all ongoing 
adverse events and serious adverse events should be evaluated for resolution.  All new or 
updated information for previously reported serious adverse events must be sent to Amgen 
within 24 hours following knowledge of the new information and will be recorded in the originally 
completed Adverse Event CRF.  If specifically requested, the investigator may need to provide 
additional follow-up information, such as discharge summaries, medical records, or extracts 


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from the medical records.  Information provided about the serious adverse event must be 
consistent with that recorded on the Adverse Event CRF. 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Amgen to elucidate 
the nature and/or causality of the adverse event and serious adverse event as fully as possible.  
This may include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
If a subject is permanently withdrawn from protocol-required therapies because of a serious 
adverse event, this information must be submitted to Amgen.  If a subject dies during 
participation in the study, the investigator will provide Amgen with a copy of any post-mortem 
findings including histopathology if available. 
Events of interest are described in Section 8.3.6.  Formal pre-specified evaluations for events of 
interest are not planned at this time. 
8.3.5 Pregnancy 
Details of all pregnancies and/or lactation in female subjects and female partners of male 
subjects that occur after the start of study treatment and until 5 months after the last 
investigational product injection will be documented. 
If a pregnancy is reported, the investigator is to inform Amgen within 24 hours of learning of the 
pregnancy and/or lactation and is to follow the procedures outlined in Section 10.2, Appendix 2.  
Amgen or its designee will follow-up with the investigator regarding additional information that 
may be requested. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered serious adverse events. 
Further details regarding pregnancy and lactation are provided in Section 10.2, Appendix 2.  
Pregnancy is not an adverse event unless there is suspicion of investigational product 
interference with effectiveness of contraceptive measures. 
8.3.6 Events of Interest 
Events of interest for ABP 654/ustekinumab will be defined in the Statistical Analysis Plan (SAP) 
and will be reviewed on an ongoing basis as part of this study.  There are no additional 


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expedited reporting requirements for events of interest, beyond what is defined for any adverse 
event report that qualifies to be expedited as part of regulatory reporting rules for investigational 
product. 
8.4 Treatment of Overdose 
Single doses up to 6 mg/kg have been administered intravenously in Stelara clinical studies 
without dose-limiting toxicity.  In case of overdose, it is recommended that the subject be 
monitored for any signs or symptoms of adverse reactions and appropriate symptomatic 
treatment be instituted immediately. 
8.5 Pharmacokinetics 
Serum samples will be collected for measurement of serum concentrations of investigational 
product as specified in the Schedule of Assessments (Table 1-1).  Instructions for the collection, 
handling, storage and shipment of biological samples will be provided in the Laboratory Manual.  
Blood samples for PK testing will be collected from all subjects.  Samples should be taken prior 
to administration of investigational product (predose) on dosing visits. 
The actual date and time (24-hour clock time) of each sample will be recorded. 
Samples collected for analyses of investigational product serum concentration may also be 
used to evaluate safety or efficacy aspects that address concerns arising during or after the 
study. 
8.6 Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.7 Genetics 
Genetics are not evaluated in this study. 
8.8 Biomarkers 
Biomarkers are not evaluated in this study. 
8.9 Immunogenicity Assessments 
Antibodies (binding and neutralizing) to investigational product will be evaluated in serum 
samples collected from all subjects.  Additionally, serum samples should also be collected at the 


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final visit from subjects who discontinued investigational product or were withdrawn from the 
study.  These samples will be tested by the sponsor or sponsor’s designee.  Samples should be 
taken prior to administration of investigational product (predose) on dosing visits.  Samples 
tested positive for binding antibodies will also be further assessed for neutralizing antibodies.  
Additional blood samples may be obtained to rule out antidrug antibodies (ADAs) during the 
study. 
The detection and characterization of anti-drug antibodies will be performed using a validated 
assay method by the sponsor or under the supervision of the sponsor. 


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9 Statistical Considerations 
9.1 General Considerations 
All personnel involved with the analysis of the study will remain blinded until database lock.  
Analysis will be performed using SAS® version 9.4 or higher (SAS Institute, Cary, NC, US) by 
the sponsor or its representatives. 
The SAP will be developed and finalized prior to the unblinding for the final analysis.  The SAP 
will provide a detailed description of the statistical methods and expand on the details provided 
in the protocol. 
All data post randomization will be presented by treatment group (switching group versus 
continued-use group).  Data during the run-in period, where all subjects are receiving 
ustekinumab, will be presented.  Descriptive statistics (number of observations, mean, standard 
deviation, median, minimum, and maximum) will be provided for continuous variable, and 
counts and percentages will be presented for categorical variables.  Confidence intervals (Cis) 
and other inferential statistics may also be provided. 
In general, baseline will be defined as the last non-missing measurement/procedure before or 
on the date of first administration of investigational product. 
9.2 Statistical Hypotheses 
The analysis of the primary PK endpoints will test the following hypotheses for each endpoint: 
Null Hypothesis (H0): The geometric means ratio (GMR) between ABP 654 and ustekinumab is 
outside a similarity margin of (0.8, 1.25), 
versus 
Alternative Hypothesis (HA): The GMR between ABP 654 and ustekinumab is within a similarity 
margin of (0.8, 1.25). 
To support a demonstration of interchangeability, the 90% CI of GMRs of ABP 654 versus 
ustekinumab for AUCtau and Cmax from the primary analysis should fall within the pre-specified 
similarity margin. 


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9.3 Sample Size Determination 
Approximately 480 subjects will be enrolled to receive ustekinumab during the run-in period.  
Subjects with prior biologic use for psoriasis will be capped at 50% of the total enrolled subjects. 
This sample size will ensure approximately 310 randomized subjects at week 28 after the run-in 
period, considering 35% run-in failures.  Randomization will be in a 1:1 ratio to the 
continued-use group or the switching group.  The randomization will be stratified by prior 
biologic use for psoriasis (yes versus no) at baseline (week 0), geographic region, and body 
weight at baseline (week 0).  The number of subjects enrolled may be adjusted during the study 
with the actual run-in failure rate seen to ensure approximately 310 randomized subjects at 
week 28.  Subjects already enrolled will be allowed to be randomized at week 28.  The sample 
size of 310 randomized subjects will provide 90% power to demonstrate similarity of the primary 
PK endpoints based on the Two One Sided Tests at a 0.05 significance level, assuming a 
between-subject variability (as measured by coefficient of variation) of 55% for ABP 654 and 
ustekinumab, a true GMR of 1 between ABP 654 and ustekinumab, and a similarity margin of 
(0.8, 1.25), and 25% drop-outs after randomization through week 64 (including subjects who 
discontinue the study prior to week 52 and those reaching week 52 but do not have evaluable 
primary PK endpoints between weeks 52 and 64). 
9.4 Populations for Analysis 
For purposes of analysis, the following analysis sets are defined in Table 9-1.  The Full Analysis 
Set will be analyzed according to the treatment that the subject is randomized to (regardless of 
actual treatment received).  For all other analysis sets, subjects will be analyzed according to 
the investigational product they actually received.  A precise definition of “as actually received” 
will be added in the SAP. 
Table 9-1. 
Populations for Analysis 
Population (Analysis Set) 
Description 
Run-in Treated Set 
The Run-in Treated Set consists of all enrolled subjects treated with at least 
1 dose of ustekinumab during the run-in period. 
Full Analysis Set 
The Full Analysis Set consists of all randomized subjects (randomization 
occurs at week 28). 
Safety Analysis Set 
The Safety Analysis Set consists of all randomized subjects who received at 
least 1 dose of investigational product post randomization. 
PK Concentration Analysis Set 
The PK Concentration Analysis Set which will include all randomized subjects 
who received at least 1 dose of investigational product post randomization and 
have at least 1 reported serum concentration of ABP 654 or ustekinumab. 


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Population (Analysis Set) 
Description 
PK Parameter Analysis Set 
The PK Parameter Analysis Set consists of all randomized subjects who 
receive all 3 doses of the assigned investigational product between weeks 28 
and 52 and who have an evaluable ABP 654 or ustekinumab serum 
concentration-time profile between weeks 52 and 64. 
Per-protocol PK Parameter 
Analysis Set 
The Per-protocol PK Parameter Analysis Set consists of all subjects in the PK 
Parameter Set who do not have an important protocol deviation that could 
affect the primary PK endpoints. 
Per-protocol Efficacy Analysis 
Set 
The Per-protocol Efficacy Analysis Set consists of all subjects who are 
randomized and receive all 3 doses of the assigned investigational product 
between weeks 28 and 52 and who have not experienced an important 
protocol deviation that may affect the evaluation of the efficacy endpoints. 
ICF: informed consent form; PASI: Psoriasis Area and Severity Index; PK: pharmacokinetic(s); SAP: statistical 
analysis plan 
9.5 Planned Analyses 
9.5.1 Primary Endpoints 
9.5.1.1 Primary Pharmacokinetic Endpoints 
The primary analysis of the primary PK endpoints, AUCtau and Cmax, between weeks 52 and 64 
will be performed based on the PK Parameter Analysis Set according to the actual treatment 
groups (switching group versus continued-use group).  The point estimates and 90% Cis for the 
GMRs between ABP 654 and ustekinumab for AUCtau and Cmax between weeks 52 and 64 will 
be estimated using an analysis of covariance (ANCOVA) model adjusting for stratification 
factors.  Prior to statistical modeling, the PK parameters will be logarithmically-transformed 
(natural log).  Point estimates and 90% Cis for the mean difference in logarithmic PK 
parameters will be estimated from the ANCOVA model, which will then be transformed back to 
the original scale to obtain the point estimates and 90% Cis for GMR. 
AUCtau and Cmax of ABP 654 and ustekinumab between weeks 52 and 64 will be listed by 
subject and summarized descriptively by treatment group. 
A sensitivity analysis of the primary PK endpoints will be conducted on the Per-protocol PK 
Parameter Analysis Set. 
9.5.2 Secondary Endpoint(s) 
9.5.2.1 Secondary Pharmacokinetic Endpoints 
The analyses of the secondary PK endpoints of tmax between weeks 52 and 64 and Ctrough,ss 
between weeks 28 and 52 will be based on the PK Parameter Analysis Set according to the 


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actual treatment groups (switching group versus continued-use group); tmax will be summarized 
descriptively by treatment group and Ctrough,ss between weeks 28 and 52 will be summarized 
descriptively by visit and treatment group.  The point estimates and 90% Cis for GMR for 
Ctrough,ss between the two treatment groups will be estimated using an ANCOVA model adjusting 
for stratification factors. 
Mean serum concentration-time data post randomization will be presented graphically using PK 
Concentration Analysis Set. 
9.5.2.2 Secondary Efficacy Endpoints 
The analysis of the secondary efficacy endpoints will be based on the Per-protocol Efficacy 
Analysis Set according to the actual treatment groups (switching group versus continued-use 
group).  A sensitivity analysis will be conducted using observed data based on the Full Analysis 
Set according to randomized treatment groups. 
PASI 75 and PASI 100 are defined as at least 75% and 100% improvement from baseline in 
PASI, respectively. 
The point estimate and 90% CI of the mean difference in PASI percent improvement from day 1 
at week 64 will be estimated from an ANCOVA model adjusting for the baseline PASI value and 
the stratification factors. 
The point estimate and 90% CI of the risk difference in PASI 75 response rate and PASI 100 
response rate at week 64 will be estimated from a generalized linear model with an identity link 
adjusting for the stratification factors. 
Missing data will be imputed by multiple imputation method for PASI percent improvement from 
day 1 at week 64 and by non-responder imputation for PASI 75 response rate and PASI 100 
response rate at week 64. 
9.5.3 Safety Endpoints 
All reported adverse events will be categorized by system organ class and preferred term 
according to the Medical Dictionary for Regulatory Activities (MedDRA, latest version at the time 
of final analysis) dictionary and graded by CTCAE, version 4.03. 
Safety analyses of the safety endpoints will be performed based on the Safety Analysis Set 
according to the actual treatment groups (switching group versus continued-use group).  


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Treatment-emergent adverse events post randomization are defined as adverse events that 
start or worsen on or after the first dose of investigational product post randomization and prior 
to the EOS.  The numbers and percentages of subjects reporting treatment-emergent adverse 
events, serious adverse events and events of interests will be tabulated by treatment group.  
The number and percent of subjects developing binding or neutralizing ADA in the subset of 
Safety Analysis Set who have never tested positive (ie, tested negative or no results) prior to the 
first dose of investigational product post randomization and have at least one ADA result post 
randomization will be tabulated descriptively by treatment group and by visit. 
Laboratory data (hematology, serum chemistry, and urinalysis) will be converted to Système 
International units for reporting purposes.  Absolute values and changes from week 28 for 
laboratory data post randomization will be summarized descriptively by treatment group and 
visit. 
For vital signs post randomization, absolute values and changes from week 28 will be 
summarized descriptively by treatment group and visit. 
The number of abnormal ECG assessments will be summarized by visit for baseline and for the 
post-randomization period using SAS® version 9.4 or higher.  Associated listing detailing the 
abnormality will be generated for SAS® version 9.4 or higher. 
Physical examination values post randomization will be summarized descriptively by treatment 
group and by visit. 
9.5.4 Other Analyses 
9.5.4.1 Efficacy 
The analyses of the other efficacy endpoints in this section will be based on the Per-protocol 
Efficacy Analysis Set. 
The PASI percent improvement from day 1 at weeks 28, 40, and 52 and the PASI 75 and 
PASI 100 response rates at weeks 28, 40, and 52 will be summarized descriptively by treatment 
group. 
BSA absolute values and changes from baseline will be summarized descriptively by visit and 
actual treatment group; the change from baseline in BSA at week 64 will be analyzed in a 
similar manner as the PASI percent improvement from baseline at week 64. 


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sPGA scores will be summarized descriptively by visit and treatment group.  sPGA response 
(0/1) will also be summarized descriptively by visit and actual treatment group; the sPGA 
response (0/1) at week 64 will be analyzed similarly as the PASI 75 and PASI 100 response 
rates at week 64. 
9.5.4.2 Analyses for the Run-in Period 
All analyses for the run-in period will be based on the Run-in Treated Set. 
Available serum concentrations over time will be summarized descriptively for each scheduled 
visit during the run-in period. 
Treatment emergent adverse events during the run-in are defined as adverse events that start 
or worsen on or after the first dose of investigational product and prior to the first dose post 
randomization or EOS for run-in failures. 
The numbers and percentages of subjects reporting treatment-emergent adverse events, 
serious adverse events and events of interest while receiving ustekinumab during the run-in 
period will be summarized. 
The number and percentage of subjects developing binding or neutralizing ADAs for 
ustekinumab during the run-in period will be summarized. 
9.5.5 Demographic and Baseline Characteristics 
Demographic characteristics (including age, sex, ethnicity, and race) and baseline 
characteristics (including height, body weight, body mass index, and disease characteristics) will 
be presented for the ustekinumab arm for the Run-in Treated Set and by treatment group 
descriptively for the other analysis sets defined in Section 9.4. 
9.5.6 Exposure to Investigational Product 
Exposure to ABP 654/ustekinumab will be summarized descriptively for the ustekinumab arm 
for the Run-in Treated Set and for each treatment group in the Safety Analysis Set for the run-in 
period and post randomization period, respectively. 
9.5.7 Exposure to Prior and Concomitant Medication 
Prior and concomitant medications will be coded using the latest available World Health 
Organization Drug Dictionary.  For the run-in period concomitant medication will be summarized 


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descriptively for the Run-in Treated Set.  For the Safety Analysis Set, concomitant medications 
during the run-in period and during the post randomization period will be summarized 
separately. 
9.5.8 Subgroup Analyses and Covariates 
The stratification factors (prior biologic use for psoriasis [“yes” versus “no”] at baseline [week 0], 
geographic region, and body weight at baseline [week 0]) will be included as covariates in the 
statistical models for the PK and efficacy analyses.  Subgroup analyses will be conducted for 
PK parameter endpoints for ADA negative subgroups. 
Full details of the subgroup analyses and covariates will be pre-specified in the SAP. 
9.6 Interim Analyses 
No interim analysis is planned for this study. 


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10 Supporting Documentation and Operational Considerations 
10.1 Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1 Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines 
o Note for Guidance on International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Harmonised 
Tripartite Guideline E6 (R1)/Integrated Addendum E6 (R2); US Food and Drug 
Administration (FDA) Code of Federal Regulations (CFR) (Title 21 Parts 50, 56, 312), 
requirements for the conduct of clinical studies as provided in the EU 
Directive 2001/20/EC, and all applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, any ICF updates, Investigator’s Brochure, 
subject-facing recruitment materials (eg, advertisements) and other relevant documents to 
be provided to subjects (if applicable) must be submitted to an IRB/IEC by the investigator 
and reviewed and approved by the IRB/IEC before the study is initiated. 
• 
A copy of the written approval of the protocol and ICF must be received by Amgen or 
designee before recruitment of subjects into the study and shipment of Amgen 
investigational product.  Amgen may amend the protocol at any time.  The IRB/IEC 
approval(s) must identify the protocol version as well as the documents reviewed. 
• 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study subjects. 
• 
The investigator will be responsible for the following: 
o Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 


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o Notifying the IRB/IEC of serious adverse events or other significant safety findings, 
including adverse drug reactions that are both serious and expected, as required by 
IRB/IEC procedures 
o Providing oversight of the conduct of the study at the study center and adherence to the 
requirements of all applicable regulations 
o Promptly reporting deviations from, or changes to, the protocol to eliminate immediate 
hazards to the study subjects 
o Obtaining annual IRB/IEC approval/renewal throughout the duration of the study.  
Copies of the investigator’s reports and the IRB/IEC continuance of approval must be 
sent to Amgen or designee 
o Overall conduct of the study at the site and adherence to requirements of 21 CFR, ICH 
GCP guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations 
10.1.2 Informed Consent Process 
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirement(s) and should adhere to GCP and to the ethical principles that 
have their origin in the Declaration of Helsinki.  Prior to the beginning of the study, the 
investigator should have the IRB/IEC’s written approval/favorable opinion of the written ICF and 
any other written information to be provided to subjects. 
• 
The investigator or his/her representative will explain the purpose and nature of the study as 
well as possible adverse effects to the subject or his/her legally acceptable representative 
and answer all questions regarding the study. 
• 
Subjects must be informed that their participation is voluntary, and consent can be 
withdrawn at any point. 
• 
Subject data up to withdrawal of consent will be included in the analysis of the study, and 
where permitted, publicly available data can be included after withdrawal of consent. 
• 
Subjects or their legally acceptable representative will be required to sign a statement of 
informed consent that meets the requirements of US FDA CFR Title 21 Part 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
requirements where applicable, and the IRB/IEC or study center. 


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• 
Prior to a subject’s participation in the study, the written ICF should be signed and 
personally dated by the subject or by the subject’s legally acceptable representative, and by 
the person who conducted the informed consent discussion. 
• 
The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled to the study and the date the written consent was obtained.  
Subject withdrawal of consent or discontinuation from study, study treatment, and/or 
procedures must also be documented in the subject’s medical records. 
• 
The original copy of the signed ICF will be retained at the study center. 
• 
A copy of the ICF and any other written information must be provided to the subject or the 
subject’s legally acceptable representative. 
• 
If a protocol amendment is required, the ICF may need to be revised to reflect the changes 
to the protocol. 
• 
If the ICF is revised, the revised ICF must have received the IRB/IEC’s approval/favorable 
opinion in advance of its use.  Subjects must be informed of the changes to the ICF and 
must re-consent to the most current version during their participation in the study.  The 
subject or the subject’s legally acceptable representative should be informed in a timely 
manner if new information becomes available that may be relevant to the subject’s 
willingness to continue participation in the study.  The communication of this information 
should be documented. 
• 
The investigator is also responsible for asking the subject if the subject has a primary care 
physician and if the subject agrees to have his/her primary care physician informed of the 
subject’s participation in the clinical study unless it is a local requirement.  If the subject 
agrees to such notification, the investigator is to inform the subject’s primary care physician 
of the subject’s participation in the clinical study.  If the subject does not have a primary care 
physician and the investigator will be acting in that capacity, the investigator is to document 
such in the subject’s medical record. 
If a subject is unable to read or if a legally acceptable representative is unable to read, an 
impartial witness should be present during the entire informed consent discussion.  The witness 
should sign and personally date the ICF after: 
• 
The written ICF and any other written information to be provided to subjects is read and 
explained to the subject or to the subject’s legally acceptable representative 
• 
The subject or the subject’s legally acceptable representative has orally consented to the 
subject’s participation in the study 


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• 
The subject or the subject’s legally acceptable representative has signed and personally 
dated the ICF, if they are capable of doing so 
By signing the ICF, the witness attests that the information in the ICF and any other written 
information was accurately explained to, and apparently understood by, the subject or the 
subject’s legally acceptable representative, and that informed consent was freely given by the 
subject or the subject’s legally acceptable representative. 
10.1.3 Data Monitoring Committee 
For details on the DMC, refer to DMC Charter.  The DMC will evaluate unblinded safety data 
throughout the study and convene approximately every 6 months after the first subject is 
enrolled to review safety data and issue recommendations.  The DMC’s constitution and the 
details of their roles and responsibilities are described in the DMC Charter. 
A DMC will be formed with members consisting of individuals external to Amgen and the CRO 
chosen for their expertise in plaque psoriasis.  Members of the DMC will include, at a minimum, 
physicians and statistician(s).  The primary role of this independent DMC will be to monitor 
safety data. 
In addition, the DMC will communicate any major safety concerns and recommendations 
regarding study modification or termination to Amgen senior management at any time during the 
conduct of the study. 
Records of DMC meetings will be maintained by the CRO in a restricted, unblinded location for 
the duration of the study.  Meeting records will be transferred and stored in the study TMF at the 
conclusion of the study.  Selected Amgen, or its designee, staff may serve as liaisons with the 
DMC, but will not be voting members.  Personnel at Amgen or its designee involved in 
preparation or review of DMC unblinded materials will not be otherwise involved in the study. 
10.1.4 Financing and Insurance 
10.1.4.1 Contractual and Financial Details 
The investigator (and/or, as appropriate, the hospital administrative representative) and Amgen, 
or its designee, will sign a clinical study agreement prior to the start of the study, outlining 
overall Amgen, or its designee, and investigator responsibilities in relation to the study. 


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10.1.4.2 Insurance, Indemnity, and Compensation 
The sponsor will take out reasonable third-party liability insurance cover in accordance with all 
legal requirements.  The civil liability of the investigator, the persons instructed by him or her 
and the hospital, practice, or institute in which they are employed and the liability of the sponsor 
with respect to financial loss due to personal injury and other damage that may arise as a result 
of the carrying out of this study are governed by the applicable law. 
The sponsor will arrange for subjects participating in this study to be insured against financial 
loss due to personal injury caused by the pharmaceutical products being tested or by medical 
steps taken in the course of the study. 
10.1.4.3 Financial Disclosure 
Investigators and sub-investigators will provide the sponsor or designee with sufficient, accurate 
financial information in accordance with local regulations to allow the sponsor to submit 
complete and accurate financial certification or disclosure statements to the appropriate 
regulatory authorities.  Investigators are responsible for providing information on financial 
interests during the course of the study and for 1 year after completion of the study. 
10.1.5 Data and Records Management 
All clinical study information should be recorded, handled, and stored in a way that allows its 
accurate reporting, interpretation, and verification.  This principle applies to all records 
referenced in this protocol, irrespective of the type of media used. 
A CRF will be used to store and transmit subject information.  The CRF must be reviewed and 
electronically signed and dated by the investigator on an ongoing basis throughout the study.  
The investigator is responsible for verifying that the data entries are accurate and correct by 
signing the CRF. 
Access to the CRF will be strictly password protected and limited to personnel directly 
participating in the study.  Data should be entered into the CRF completely by authorized site 
personnel (eg, investigators and the study coordinator).  The CRF must be completed as soon 
as possible after any subject evaluation or communication.  If data are to be changed due to 
erroneous input or other reason, an electronic audit trail will track these changes.  The CRFs 
and computers that store them must be accessible to CRAs and other regulatory auditors. 


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During each study visit, a physician participating in the study will maintain progress notes in the 
subject’s medical records to document all significant observations.  At a minimum, these notes 
are to contain: 
• 
The date of the visit and the corresponding day or visit in the study schedule 
• 
General condition and status remarks by the subject, including any significant medical 
findings.  The severity, frequency, duration, and resolution of any reported adverse event, 
and the investigator’s assessment as to whether or not the reported adverse event is related 
to investigational product 
• 
Changes (including dosages) in concomitant medications/therapies (including 
over-the-counter medications and vitamins or dietary supplements) or procedures 
• 
A general reference to the procedures completed 
• 
The signature or initials of all physicians making an entry in the medical record (progress 
notes) 
In addition, any contact with the subject by telephone or other means that provides significant 
clinical information is to also be documented in the medical record (progress notes), as 
described above. 
Information from the medical records (progress notes) and other source documents is to be 
promptly entered into the appropriate section of the CRF. 
Changes to information in the medical record (progress notes) and other source documents are 
to be initialed and dated on the day the change is made by the investigator (or designee).  If the 
reason for the change is not apparent, a brief explanation for the change is to be written 
adjacent to the change.  Changes to the CRF will be electronically tracked. 
10.1.5.1 Source Documentation 
Source documents contain the results of original observations and activities of a clinical 
investigation.  They are the original records in which raw data are first recorded.  Source 
documents include, but are not limited to, medical records (progress notes), computer printouts, 
screening logs, completed scales, and recorded data from automated instruments. 
The investigator/site personnel should maintain adequate and accurate source documents and 
study records that include all pertinent observations on each of the study center’s study 
subjects.  Source data should be attributable, legible, contemporaneous, original, accurate, and 


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complete.  Changes to source data should be traceable, should not obscure the original entry, 
and should be explained if necessary (eg, through an audit trail). 
All source documents from this study are to be maintained by the investigator and made 
available for inspection by authorized persons.  The investigator will provide direct access to 
source documents/data for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspections.  They will be carried out giving due consideration to data protection and medical 
confidentiality.  The sponsor should verify that each subject has consented, in writing, to direct 
access to his/her original medical records for study-related monitoring, audit, IRB/IEC review, 
and regulatory inspection. 
During the study, a CRA will review protocol compliance, compare CRF entries and individual 
subject’s medical records, assess drug accountability, and ensure that the study is being 
conducted according to pertinent regulatory requirements. 
10.1.5.2 Case Report Form 
The file structure and format for the CRF will be provided by the sponsor or its representative 
and should be handled in accordance with the instructions provided. 
Data will be entered/loaded into a validated electronic database using a clinical data 
management system.  Computerized data cleaning checks will be used in addition to manual 
review to check for discrepancies and to ensure consistency of the data. 
If corrections are needed, the responsible monitor or data manager will raise a query in the EDC 
application.  The appropriate staff at the study site will answer queries sent to the investigator.  
The name of the staff member responding to the query, and time and date stamp will be 
captured to provide an audit trail. 
The specific procedures to be used for data entry and query resolution using the EDC 
system/eCRF will be provided to study sites in a training manual.  In addition, site personnel will 
receive training on the EDC system/eCRF. 
10.1.5.3 Study Files and Record Retention 
All data derived from the study will remain the property of the sponsor.  The sponsor assumes 
accountability for actions delegated to other individuals, eg, the CRO. 


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Records must be retained in accordance with the current ICH Guidelines on GCP.  All essential 
study documents, including records of subjects, source documents, CRFs, and the 
investigational product inventory, must be kept on file. 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region, or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of ABP 654.  However, essential documents may be 
retained for a longer period if required by the applicable regulatory requirements or by 
agreement with the sponsor.  The sponsor is responsible for informing the investigator when 
these documents need no longer be retained. 
If an investigator moves, withdraws from a study, or retires, the responsibility for maintaining the 
records may be transferred to another person who will accept responsibility.  Notice of transfer 
must be made to and agreed by the sponsor. 
Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, depending on 
the study.  Also, current medical records must be available. 
The study start date is the date on which the first subject is enrolled to the study.  The End of 
Study date is defined as the date when the last subject across all centers is assessed or 
receives an intervention for evaluation in the study (ie, last subject visit) or has withdrawn 
prematurely, as applicable. 
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor.  Study sites will typically be closed upon study 
completion.  A study site is considered closed when all required documents and study supplies 
have been collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 


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Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the sponsor’s procedures, or GCP guidelines 
• 
Inadequate recruitment of subjects by the investigator 
• 
Discontinuation of further investigational product development 
10.1.6 Publication Policy 
This study will be registered on ClinicalTrials.gov in accordance with applicable laws and 
publication policy and may also be registered on other publicly accessible websites, as 
necessary.  The results of the study will be posted for public disclosure within 12 months of 
study completion. 
The sponsor or designee is responsible for preparing and providing the appropriate regulatory 
authorities with the clinical study report (CSR) according to the applicable regulatory 
requirements.  The sponsor should ensure that the CSR meets the standards of the ICH 
Guideline for Structure and Content of CSRs (ICH E3). 
To coordinate dissemination of data from this study, Amgen may facilitate the formation of a 
publication committee consisting of several investigators and appropriate Amgen staff.  The 
criteria described below are to be met for every publication. 
Authorship of any publications resulting from this study will be determined on the basis of the 
Uniform Requirement for Manuscripts Submitted to Biomedical Journals International 
Committee of Medical Journal Editors’ (ICMJE) Recommendations for the Conduct of Reporting, 
Editing, and Publications of Scholarly Work in Medical Journals, which states: Authorship credit 
is to be based on: 
1. Substantial contributions to conception and design, acquisition of data, or analysis and 
interpretation of data; 
2. Drafting the article or revising it critically for important intellectual content; 
3. Final approval of the version to be published; and 
4. Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved. 
Authors need to meet conditions 1, 2, 3, and 4. 


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When a large, multicenter group has conducted the work, the group is to identify the individuals 
who accept direct responsibility for the manuscript.  These individuals must fully meet the 
criteria for authorship defined above.  Acquisition of funding, collection of data, or general 
supervision of the research group, alone, does not justify authorship.  All persons designated as 
authors must qualify for authorship, and all those who qualify are to be listed.  Each author must 
have participated sufficiently in the work to take public responsibility for appropriate portions of 
the content.  All publications (eg, manuscripts, abstracts, oral/slide presentations, book 
chapters) based on this study must be submitted to Amgen for review.  The Clinical Trial 
Agreement among the institution, investigator, and Amgen will detail the procedures for, and 
timing of, Amgen’s review of publications. 
10.1.7 Auditing and Monitoring 
Sponsor-assigned CRAs will conduct regular center visits to the investigational facilities for the 
purpose of monitoring various aspects of the study, such as assessing subject recruitment, 
compliance with protocol procedures, completeness and accuracy of data entered into the 
CRFs, verification of CRF data against original source documents, occurrence of adverse 
events and the safety and rights of subjects are being protected, and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements.  The investigator must agree to sponsor-
authorized personnel having direct access to the clinical (or associated) files and clinical study 
supplies (dispensing and storage areas) to ensure compliance with applicable regulations, and 
the investigator will assist with the sponsor’s monitoring activities. 
Quality control will occur at each stage of data handling to ensure that all data are reliable and 
have been processed correctly.  The sponsor should ensure oversight of any study-related 
duties and functions carried out on its behalf, including study-related duties and functions that 
are subcontracted to another party by the sponsor’s contracted CRO(s). 
The CRFs should be completed in a timely manner and on an ongoing basis to allow regular 
review by the CRA.  Details describing the strategy, responsibilities, and requirements of the 
study monitoring are provided in the Study Monitoring Plan. 
The purpose of an audit is to assess whether ethics, regulatory, and quality requirements are 
being fulfilled.  The sponsor or its representative may conduct audits at the investigative centers 
including, but not limited to, drug supply, presence of required documents, the informed consent 


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process, and comparison of CRFs with source documents.  Government regulatory authorities 
may also inspect the investigator during or after the study. 
The investigator (or designee) should contact the sponsor/CRO immediately if this occurs.  All 
medical records (progress notes) must be available for audit.  The investigator must agree to 
participate with audits conducted at a convenient time in a reasonable manner 
10.1.7.1 Risk and Quality Tolerance Limits 
Perceived risks and quality tolerance limits (QTLs) will be identified and documented before the 
start of the study. 
The sponsor and CRO will review risk control measures periodically to ascertain whether the 
implemented quality management activities remain effective and relevant.  The quality 
management approach and any important deviations from the predefined QTLs (and remedial 
actions adopted) will be described in the CSR. 
10.1.7.2 Protocol Adherence and Deviations 
The investigator and site personnel should conduct the study in compliance with the protocol 
and should use continuous vigilance to identify and report protocol deviations. 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures defined in the protocol that may be on the part of the investigator, site personnel, or 
the subject. 
Important protocol deviations are a subset of protocol deviations that may significantly impact 
the completeness, accuracy, and/or reliability of the study data or that may significantly affect a 
subject’s rights, safety, or well-being.  For example, important protocol deviations may include 
randomizing subjects in violation of key eligibility criteria designed to ensure a specific subject 
population or failing to collect data necessary to interpret primary endpoints, as this may 
compromise the scientific value of the study. 
The investigator should not implement any deviation from the protocol without agreement from 
the sponsor and prior review and approval from the IRB/IEC of an amendment, except where 
necessary to eliminate an immediate hazard to a study subject.  In the event of an important 
protocol deviation, the investigator will discuss the deviation with the sponsor’s medical monitor 


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and will come to an agreement as to whether the subject should be withdrawn from the study 
due to the important protocol deviation. 
10.1.8 Data Protection 
Subjects will be assigned a unique identifier by the sponsor.  Any subject records or datasets 
that are transferred to the sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred. 
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  The level of disclosure must also be 
explained to the subject. 
The subject must be informed that his/her medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.9 Protocol Approval and Amendment 
Protocol modifications, except those intended to reduce immediate risk to study subjects, may 
be made only by the sponsor. 
Any permanent change to the protocol must be handled as a protocol amendment.  The written 
amendment must be submitted to the IRB/IEC, and the investigator must await approval before 
implementing the changes.  The sponsor or designee will submit protocol amendments to the 
appropriate regulatory authorities for approval. 
The current version of the ICF will require similar modification if the IRB/IEC, investigator, and/or 
sponsor, judge the amendment to the protocol to substantially change the study design and/or 
increase the potential risk to the subject and/or impact the subject’s involvement as a study 
subject.  In such cases, the ICF will be renewed for enrolled subjects before their continued 
participation in the study. 
10.1.10 
Study and Site Start and Closure 
The study start date is the date on which the first subject is enrolled to the study.  The End of 
Study date is defined as the date when the last subject across all centers is assessed or 
receives an intervention for evaluation in the study (ie, last subject visit) or has withdrawn 
prematurely, as applicable. 


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The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will typically be closed 
upon study completion.  A study site is considered closed when all required documents and 
study supplies have been collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the sponsor’s procedures, or GCP guidelines 
• 
Inadequate recruitment of subjects by the investigator 
• 
Discontinuation of further investigational product development 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by 
the applicable regulatory requirements.  The investigator shall promptly inform the subject and 
should assure appropriate subject follow-up. 
10.2 Appendix 2: Contraceptive Guidance and Collection of 
Pregnancy Information 
Study-specific contraception requirements for males and females of childbearing potential are 
outlined in Section 5.2. 
Male and female subjects of childbearing potential must receive pregnancy prevention 
counseling and be advised of the risk to the fetus if they become pregnant or father a child 
during treatment and for 5 months after the last dose of protocol-required therapies. 
Additional medications given during the study may alter the contraceptive requirements.  These 
additional medications may require female subjects to use highly effective methods of 
contraception and/or for an increased length of time.  In addition, male subjects may also be 
required to use contraception.  The investigator must discuss these contraceptive changes with 
the subject. 


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Page 80 of 88 
 
Definitions 
Woman of Childbearing Potential 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before first dose of investigational product, additional evaluation should be 
considered. 
Women in the following categories are not considered women of childbearing potential 
(WOCBP): 
1. Premenarchal 
2. Premenopausal female with one of the following: 
1. Documented hysterectomy 
2. Documented bilateral salpingectomy 
3. Documented bilateral oophorectomy 
NOTE: Documentation can come from the site personnel’s review of the subject’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
4. A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause 
o A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be 
used to confirm a postmenopausal state in women not using hormonal contraception 
or hormonal replacement therapy (HRT).  However, in the absence of 12 months of 
amenorrhea, a single FSH measurement > 40 IU/L is required. 
o Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-estrogen hormonal highly effective contraception methods if they wish 
to continue their HRT during the study.  Otherwise, they must discontinue HRT to 
allow confirmation of postmenopausal status before study enrollment. 


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Contraception Guidance 
Male Subjects: 
Male subjects with female partners of childbearing potential are eligible to participate if the 
agree to ONE of the following during the protocol-defined time frame in Section 5.2: 
• 
Sexual abstinence (defined as refraining from heterosexual intercourse during the entire 
period of risk associated with protocol-required therapies; the reliability of sexual abstinence 
must be evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the subject) 
• 
Use a condom during treatment and for an additional 5 months after the last dose of 
investigational product 
• 
The female partner should consider using an acceptable method of effective contraception 
such as: hormonal, intrauterine device, intrauterine hormonal-releasing system, female 
barrier method (diaphragm, cap, sponge [a female condom is not an option because there is 
a risk of tearing when both partners use a condom]) 
Note: If the male’s sole female partner is of nonchildbearing potential or has had a bilateral tubal 
ligation/occlusion, he is not required to use additional forms of contraception during the study 
Female Subjects: 
Female subjects of childbearing potential are eligible to participate if they agree to use a highly 
effective method of contraception consistently and correctly as described in the table below and 
as described in Section 5.2. 
Highly Effective Contraceptive Methods That Are User Dependent1 
Failure rate of < 1% per year when used consistently and correctly. 
Combined (estrogen- and progestin-containing) hormonal contraception associated with inhibition of ovulation2 
1. 
Oral 
2. 
Intravaginal 
3. 
Transdermal 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Injectable 


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Highly Effective Contraceptive Methods That Are User Independent1 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation2 
• 
Intrauterine device 
• 
Intrauterine hormone-releasing system 
• 
Bilateral tubal occlusion 
Vasectomized Partner 
A vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual 
partner of the women of childbearing potential and the absence of sperm has been confirmed.  If not, an additional 
highly effective method of contraception should be used. 
Sexual Abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse 
during the entire period of risk associated with the investigational product.  The reliability of sexual abstinence needs 
to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the subject. 
1. 
Typical use failure rates may differ from those when used consistently and correctly.  Use should be consistent 
with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. 
2. 
Hormonal contraception may be susceptible to interaction with the investigational product, which may reduce the 
efficacy of the contraceptive method.  In this case, two highly effective methods of contraception should be 
utilized during the intervention period and for at least 5 months after the last dose of investigational product or 
until the scheduled End of Study visit (whichever is later). 
 
Pregnancy Testing 
• 
WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive serum pregnancy test. 
• 
Additional pregnancy testing should be performed at intervals as per the Schedule of 
Assessments (Table 1-1), and as required locally. 
• 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. 
• 
Pregnancy testing, with a sensitivity of 5 mIU/mL will be performed will be performed. 
Collection of Pregnancy Information: 
Male Subjects With Partners Who Become Pregnant 
• 
In the event a male subject fathers a child during treatment, and for an additional 5 months 
after the last dose of investigational product, the information will be recorded on the 
Pregnancy Notification Form.  The form must be submitted to Amgen or its designee within 
24 hours of the center’s awareness of the pregnancy (Note: Sites are not required to provide 
any information on the Pregnancy Notification Form that violates the country or regions local 
privacy laws). 


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• 
The investigator will attempt to obtain a signed authorization for release of pregnancy and 
infant health information directly from the pregnant female partner to obtain additional 
pregnancy information. 
• 
After obtaining the female partner’s signed authorization for release of pregnancy and infant 
health information, the investigator will collect pregnancy outcome and infant health 
information on the pregnant partner and her baby and complete the pregnancy 
questionnaires.  This information will be forwarded to Amgen or its designee. 
• 
Generally, infant follow-up will be conducted up to 12 months after the birth of the child (if 
applicable). 
• 
Any termination of the pregnancy will be reported to Amgen or its designee regardless of 
fetal status (presence or absence of anomalies) or indication for procedure. 
Female Subjects Who Become Pregnant 
• 
The investigator will collect pregnancy information on any female subject who becomes 
pregnant while taking protocol-required therapies through 5 months after the last dose of 
investigational product. 
• 
Information will be recorded on the Pregnancy Notification Form.  The form must be 
submitted to Amgen or its designee within 24 hours of learning of a subject’s pregnancy 
(Note: Sites are not required to provide any information on the Pregnancy Notification Form 
that violates the country or regions local privacy laws). 
• 
After obtaining the female subject’s signed authorization for release of pregnancy and infant 
health information, the investigator will collect pregnancy and infant health information and 
complete the pregnancy questionnaire for any female subject who becomes pregnant while 
taking protocol-required therapies through 5 months after the last dose of investigational 
product.  This information will be forwarded to Amgen or its designee.  Generally, infant 
follow-up will be conducted up to 12 months after the birth of the child (if applicable). 
• 
Any termination of the pregnancy will be reported to Amgen or its designee regardless of 
fetal status (presence or absence of anomalies) or indication for procedure. 
• 
While pregnancy itself is not considered to be an adverse event or serious adverse event, 
any pregnancy complication or report of a congenital anomaly or developmental delay, fetal 
death, or suspected adverse reactions in the neonate will be reported as an adverse event 
or serious adverse event.  Note that an elective termination with no information on a fetal 
congenital malformation or maternal complication is generally not considered an adverse 
event, but still must be reported to Amgen or its designee as a pregnancy exposure case. 


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• 
If the outcome of the pregnancy meets a criterion for immediate classification as a serious 
adverse event (eg. Female subject experiences a spontaneous abortion, stillbirth, or 
neonatal death or there is a fetal or neonatal congenital anomaly) the investigator will report 
the event as a serious adverse event. 
• 
Any serious adverse event occurring as a result of a poststudy pregnancy which is 
considered reasonably related to the study treatment by the investigator, will be reported to 
Amgen or its designee.  While the investigator is not obligated to actively seek this 
information in former study subjects, he or she may learn of a serious adverse event through 
spontaneous reporting. 
• 
Any female subject who becomes pregnant while participating will discontinue study 
treatment. 
Collection of Lactation Information 
• 
Investigator will collect lactation information on any female subject who breastfeeds while 
taking protocol-required therapies through 5 months after the last dose of investigational 
product. 
• 
Information will be recorded on the Lactation Notification Form and submitted to Amgen or 
its designee within 24 hours of the investigator’s knowledge of event. 
• 
Study treatment will be discontinued if female subject breastfeeds during the study as 
described in exclusion criterion 24 (Section 5.2). 
• 
With the female subjects signed authorization for release of mother and infant health 
information, the investigator will collect mother and infant health information and complete 
the lactation questionnaire on any female subject who breastfeeds while taking 
protocol-required therapies through 5 months after discontinuing protocol-required 
therapies. 


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10.3 Appendix 3: Static Physician’s Global Assessment Scale 
Below is the sPGA scale that will be used in this study. 
Score 
Category 
Category Description 
0 
Clear 
• 
Plaque elevation = 0 (no elevation over normal skin) 
• 
Scaling = 0 (no scale) 
• 
Erythema = no evidence, hyperpigmentation may be present 
1 
Almost Clear 
• 
Plaque elevation = ± (possible but difficult to ascertain whether there is a slight 
elevation above normal skin) 
• 
Scaling = ± (surface dryness with some white coloration) 
• 
Erythema = light red coloration 
2 
Mild 
• 
Plaque elevation = slight (slight but definite elevation, typically edges are 
indistinct or sloped) 
• 
Scaling =fine (fine scale partially or mostly covering lesions) 
• 
Erythema = light red coloration 
3 
Moderate 
• 
Plaque elevation = moderate (moderate elevation with rough or sloped edges) 
• 
Scaling = coarser (coarse scale covering most or all of the lesions) 
• 
Erythema = moderate (definite red coloration) 
4 
Severe 
• 
Plaque elevation = marked (marked elevation typically with hard or sharp edges) 
• 
Scaling = coarse (coarse, non-tenacious scale predominates covering most or all 
of the lesions) 
• 
Erythema = severe (very bright red coloration) 
5 
Very Severe 
• 
Plaque elevation = very marked (very marked elevation typically with hard sharp 
edges) 
• 
Scaling = very coarse (coarse, thick tenacious scale over most of the lesions, 
rough surface) 
• 
Erythema = very severe (extreme red coloration, dusky to deep red coloration) 
 


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10.4 Appendix 4: Abbreviations and Trademarks 
ADA 
antidrug antibody 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
ANCOVA 
analysis of covariance 
AUC 
area under the curve 
AUCtau 
area under the curve from time 0 over the dosing interval 
BCG 
Bacillus Calmette-Guérin 
BSA 
body surface area 
CFR 
Code of Federal Regulations 
CDC 
complement-dependent cytotoxicity 
CI 
confidence interval 
Cmax 
maximum concentration 
COVID-19 
coronavirus disease 2019 
CRA 
clinical research associate 
CRF 
case report form 
CRO 
contract research organization 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough,ss 
trough concentration at steady state 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOS 
End of Study 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
FAS 
full analysis set 
FcRn 
neonatal fragment crystallizable receptor 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GMR 
geometric mean ratio 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 


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Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 87 of 88 
 
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Independent Ethics Committee 
IL 
interleukin 
IL-12Rβ 
IL-12 receptor subunit beta 1 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IV 
intravenous 
IXRS 
Interactive Web/Voice Response System 
MedDRA 
Medical Dictionary for Regulatory Activities 
PASI 
Psoriasis Area and Severity Index 
PFS 
prefilled syringe 
PGA 
Physician’s Global Assessment 
PIN 
personal identification number 
PK 
pharmacokinetic(s) 
PPD 
purified protein derivative 
PPS 
per-protocol analysis set 
QA 
quality assurance 
QTcF 
QT interval corrected using Fridericia’s formula 
QTL 
quality tolerance limit 
SAP 
statistical analysis plan 
SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 
SC 
subcutaneous 
SmPC 
Summary of Product Characteristics 
SOP 
standard operating procedure 
sPGA 
static Physician’s Global Assessment 
SUSAR 
suspected unexpected serious adverse reaction 
t½ 
terminal half-life 
tmax 
time of maximum concentration 
TMF 
Trial Master File 
US 
United States 
USPI 
United States Prescribing Information 
WOCBP 
woman of childbearing potential 
 


Product: ABP 654 
Clinical Study Protocol: 20200417 
Final 2.0 Date: 02 June 2021 
Page 88 of 88 
 
11 References 
Amgen Inc. ABP 654 – Investigator’s Brochure (Version 1-0). 21 July 2020. 
BLA 125261 Clinical Pharmacology and Biopharmaceutics Review, 2009. 
Chandran V, Gottlieb A, Cook RJ, Duffin KC, Garg A, Helliwell P, et al. International Multicenter 
Psoriasis and Psoriatic Arthritis Reliability Trial for the Assessment of Skin, Joints, Nails, and 
Dactylitis. Arthritis Rhem. 2009;61(9):1235-1242. doi: 10.1002/art.24562 
Feldman SR, Krueger GG. Psoriasis Assessment Tools in Clinical Trials. Ann Rheum Dis. 
2005;64 suppl 2(Suppl2):ii65-ii68;discussion ii69-ii73. doi 10.1136/ard.2004.031237 
Stelara® Summary of Product Characteristics [SmPC], February 2020. 
Stelara® United States Prescribing Information [USPI], July 2020. 

SAP_003.pdf: 
Product:  ABP 654  
Protocol Number:  20200417 
Date:  24 Apr 2023 
Page 1 of 39 
CONFIDENTIAL  
 
 
Statistical Analysis Plan 
Protocol Title: 
A Multicenter, Randomized, Double blinded Study 
Evaluating the Pharmacokinetics, Efficacy and Safety of 
Multiple Switches Between Ustekinumab and ABP 654 
Compared With Continued Use of Ustekinumab in 
Subjects with Moderate to Severe Plaque Psoriasis 
 
Short Protocol Title: 
A Study to Investigate Interchangeability of ABP 654 for 
the Treatment of Subjects with Moderate to Severe 
Plaque Psoriasis 
Protocol Number: 
20200417 
NCT Number: 
NCT04761627 
Authors: 
Sponsor: 
Amgen Inc. 
One Amgen Center Drive 
Thousand Oaks 
CA 91320 1799, US 
 
SAP Date: 
Document Version 
Date 
Current (v3.0) 
24 Apr 2023 
 
 
 


Product:  ABP 654  
Protocol Number:  20200417 
Date:  24 Apr 2023 
Page 2 of 39 
CONFIDENTIAL  
 
 
Version Number 
Date 
(DDMMMYYYY) 
Summary of Changes,  
including rationale for changes 
Original (v2.0) 
17 June 2021 
Compared to v1.0, 18Dec2020: 
 
Updated similarity margin and 
associated sample size to follow 
FDA’s suggestion  
 
 
Added PK and ADA assessment 
samples at Week 4 per protocol 
amendment 
 
 
Changed missing data handling from 
LOCF to MI to follow FDA’s 
suggestion 
 
 
Added footnote for clarification that 
laboratory parameters will only be 
included at the visits where it is 
scheduled for assessment in the 
output tables. 
 
 
Added clarification that actual 
treatment is to be used for RTS  
 
 
Added COVID 19 related analyses 
and analysis tables.  
 
 
Added additional analysis for sPGA 
combined score of 4/5 to follow FDA’s 
suggestion 
 
 
Added Medical History by System 
Organ Class and Preferred Term for 
not resolved findings for the Run-in 
Period in SAP 
 
 
Updated the descriptive summary of 
Tmax such that only median, min and 
max will be presented to align with 
standard shell 
 
 
Changed the figure for Ctrough,ss   from 
Mean +/- SD plot using RTS to box 
plots using RTS  
 
 
Added analysis of TEAE Leading to 
Dose delayed / not administered of IP 


Product:  ABP 654  
Protocol Number:  20200417 
Date:  24 Apr 2023 
Page 3 of 39 
CONFIDENTIAL  
 
 
Version Number 
Date 
(DDMMMYYYY) 
Summary of Changes,  
including rationale for changes 
by PT for the Post-randomization 
Period 
 
 
Added ECG analyses to align with 
protocol amendment 
 
 
The Category of EOI query (SOC, 
SMQ / Amgen query) for the EOI 
Reversible posterior 
leukoencephalopathy syndrome is 
updated to Reversible posterior 
leukoencephalopathy syndrome 
(Amgen query) from Posterior 
reversible encephalopathy 
syndrome/reversible posterior 
leukoencephalopathy syndrome 
(Amgen query)  
 
 
Serious depression including 
suicidality EOI scope is updated to 
broad.  
 
 
Additional minor wording clarifications 
or corrections were made throughout 
the document. 
v3.0 
15 Feb 2023 
Compared to v2.0, 17June2021: 
 
Added ECG summary tables by visit 
and treatment arm and an ECG shift 
table of the worst post randomization 
ECG results (normal, abnormal & non 
clinically significant (NCS), and 
abnormal & clinically significant (CS)) 
relative to randomization at Week 28 
for the Post randomization Period per 
Protocol Amendment 2.0 section 
9.5.3. 
 
Added ECG visits to the Study 
Analysis Visit table. 
 
Added a footnote to clarify the upper 
bound for analysis window of Week 
28 for Efficacy, Vital, Safety Lab, ADA 
& PK in the Study Analysis Visit table. 
 
In TEAE summary, “TEAE leading to 
dose delayed / not administered” is 
changed to “TEAE leading to dose 
delayed” for being consistent with the 
CRF. 


Product:  ABP 654  
Protocol Number:  20200417 
Date:  24 Apr 2023 
Page 4 of 39 
CONFIDENTIAL  
 
 
Version Number 
Date 
(DDMMMYYYY) 
Summary of Changes,  
including rationale for changes 
 
Changed the method for estimating 
the point estimate and 90% CI of the 
risk difference in PASI 75 response 
rate and PASI 100 response rate at 
Week 64 and sPGA response at 
Week 64 from generalized linear 
model with an identity link to the 
stratified Newcombe confidence limits 
in Section 9.6.2.1. This change 
addresses the potential non-
convergence issue from the 
generalized linear model. 
 
Updated the definition of the PK 
Concentration Analysis Set in Section 
6.3 to clarify that PK samples on or 
after randomization date should be 
included. 
 
Added PK summary statistic reporting 
precision in Section 9.1. 
 
Removed four categorical parameters 
(glucose, bilirubin, blood, and protein) 
from urinalysis in Section 9.7.2.  That 
level of detail for urinalysis results is 
not critical in this program/study and 
any clinically relevant abnormal 
finding was also captured as Adverse 
Event. 
 
Added the PK trough concentration at 
Week 28 as a covariate to the 
ANCOVA models for AUCtau, Cmax and 
Ctrough,ss (at Week 40 and Week 52) in 
Sections 9.5.1.1 and 9.5.2 to adjust 
for the baseline PK trough 
concentration.  
 
Changed the denominator for 
calculating “Developing antibody 
incidence during the Post-
randomization Period” to “the number 
of subjects in the Safety Analysis Set 
who have antibody negative or no 
result prior to the first dose of post-
randomization IP” in Section 9.7.6, in 
order to exclude subjects with 
antibody positive at baseline or 
developing antibody during the Run-in 
Period from the denominator. 
 


Product:  ABP 654  
Protocol Number:  20200417 
Date:  24 Apr 2023 
Page 5 of 39 
CONFIDENTIAL  
 
 
Table of Contents 
1. 
Introduction ........................................................................................................... 10 
2. 
Objectives, Endpoints and Hypotheses ................................................................. 10 
2.1 
Objectives and Endpoints .......................................................................... 10 
2.2 
Hypotheses and/or Estimations ................................................................. 11 
3. 
Study Overview .................................................................................................... 11 
3.1 
Study Design ............................................................................................. 11 
3.2 
Sample Size .............................................................................................. 12 
3.3 
Adaptive Design ........................................................................................ 12 
4. 
Covariates and Subgroups ................................................................................... 12 
4.1 
Planned Covariates ................................................................................... 12 
4.2 
Subgroups ................................................................................................. 13 
5. 
Definitions ............................................................................................................. 13 
5.1 
General ..................................................................................................... 13 
5.2 
Pharmacokinetic........................................................................................ 18 
5.3 
Efficacy ..................................................................................................... 19 
5.4 
Safety ........................................................................................................ 20 
6. 
Analysis Sets ........................................................................................................ 21 
6.1 
Full Analysis Set........................................................................................ 21 
6.2 
Safety Analysis Set ................................................................................... 22 
6.3 
PK Analysis Sets ....................................................................................... 22 
6.4 
Health-related Quality-of-Life or Health Economics Analyses 
Set(s) ........................................................................................................ 22 
6.5 
Per-protocol Efficacy Analysis Set ............................................................. 22 
6.6 
Interim Analyses Set(s) ............................................................................. 23 
6.7 
Study-specific Analysis Set ....................................................................... 23 
7. 
Planned Analyses ................................................................................................. 23 
7.1 
Interim Analysis and Early Stopping Guidelines ........................................ 23 
7.2 
Primary Analysis ....................................................................................... 23 
7.3 
Final Analysis ............................................................................................ 23 
8. 
Data Screening and Acceptance ........................................................................... 23 
8.1 
General Principles ..................................................................................... 23 
8.2 
Data Handling and Electronic Transfer of Data ......................................... 23 
8.3 
Handling of Missing, Below LLOQ and Incomplete Data ........................... 24 
8.4 
Detection of Bias ....................................................................................... 25 
8.5 
Outliers ..................................................................................................... 25 
8.6 
Distributional Characteristics ..................................................................... 26 
8.7 
Validation of Statistical Analyses ............................................................... 26 


Product:  ABP 654  
Protocol Number:  20200417 
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Page 6 of 39 
CONFIDENTIAL  
 
 
9. 
Statistical Methods of Analysis.............................................................................. 26 
9.1 
General Considerations ............................................................................. 26 
9.2 
Subject Accountability ............................................................................... 27 
9.3 
Important Protocol Deviations and COVID-19 Related Protocol 
Deviations ................................................................................................. 28 
9.4 
Demographic and Baseline Characteristics ............................................... 28 
9.5 
PK Analyses .............................................................................................. 29 
9.5.1 
Analyses of Primary PK Endpoint(s) .......................................... 29 
9.5.1.1 
Primary Analysis ..................................................... 29 
9.5.1.2 
Secondary Analyses................................................ 30 
9.5.2 
Analyses of Secondary PK Endpoints ....................................... 30 
9.5.3 
Analyses of Other PK Endpoint(s) ............................................. 30 
9.5.4 
Subgroup Analyses ................................................................... 31 
9.6 
Efficacy Analyses ...................................................................................... 31 
9.6.1 
Analyses of Primary Efficacy Endpoint(s) .................................. 31 
9.6.2 
Analyses of Secondary Efficacy Endpoint(s).............................. 31 
9.6.2.1 
Primary Analysis ..................................................... 31 
9.6.2.2 
Secondary Analyses................................................ 32 
9.6.3 
Analyses of Other Efficacy Endpoint(s) ...................................... 33 
9.7 
Safety Analyses ........................................................................................ 33 
9.7.1 
Adverse Events ......................................................................... 33 
9.7.2 
Laboratory Test Results ............................................................ 34 
9.7.3 
Vital Signs ................................................................................. 35 
9.7.4 
Physical Measurements ............................................................ 35 
9.7.5 
Electrocardiogram ..................................................................... 35 
9.7.6 
Antibody Formation ................................................................... 36 
9.7.7 
Exposure to Investigational Product .......................................... 36 
9.7.8 
Exposure to Non-investigational Product ................................... 36 
9.7.9 
Exposure to Other Protocol-required Therapy ........................... 36 
9.7.10 
Exposure to Concomitant Medication ........................................ 36 
10. 
Changes From Protocol-specified Analyses.......................................................... 37 
11. 
Literature Citations / References ........................................................................... 37 
12. 
Prioritization of Analyses....................................................................................... 37 
13. 
Data Not Covered by This Plan............................................................................. 37 
14. 
Appendices ........................................................................................................... 38 
 


Product:  ABP 654  
Protocol Number:  20200417 
Date:  24 Apr 2023 
Page 7 of 39 
CONFIDENTIAL  
 
 
 
List of Appendices 
Appendix A.  List of Events of Interest and the Associated SMQ and EOI 
Searching Strategies .............................................................................. 39 
 


Product:  ABP 654  
Protocol Number:  20200417 
Date:  24 Apr 2023 
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List of Abbreviations and Definition of Terms 
 
Abbreviation 
Explanation 
ADA 
antidrug antibody 
ADaM 
Analysis Data Model 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
AUCtau 
area under the curve from time 0 over the dosing interval 
AUCtau extrap 
area under the curve from time 0 over the dosing interval 
extrapolated 
BMI 
body mass index 
BSA 
body surface area 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
confidence interval 
Cmax 
maximum concentration 
CRF 
case report form 
CS 
Clinically significant 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough,ss 
trough concentration at steady state 
DMC 
Data Monitoring Committee 
EOI 
events of interest 
EOS 
end-of-study 
FAS 
Full Analysis Set 
GMR 
geometric mean ratio 
IP 
investigational product 
IXRS 
Interactive Web/Voice Response System 
LLOQ 
lower limit of quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
multiple imputation 
NCS 
Non Clinically Significant 
NRI 
non responder imputation 
PASI 
Psoriasis Area and Severity Index 
PK 
pharmacokinetic(s) 


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PT 
preferred term 
Q1 
25th percentile 
Q3 
75th percentile 
RTS 
Run-in Treated Set 
SAP 
statistical analysis plan 
SDTM 
Standard Data Tabulation Model 
sPGA 
Static Physician’s Global Assessment 
SAS 
Safety Analyses Set 
SOC 
system organ class 
TEAE 
treatment-emergent adverse events 
TFL 
table, figure, listing 
tmax 
time of maximum concentration 
t1/2 
terminal elimination half life 
WBC 
white blood cell 
z 
terminal elimination rate constant 
 


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1. 
Introduction 
The purpose of this Statistical Analysis Plan (SAP) is to provide details of the statistical 
analyses that have been outlined within the protocol for study 20200417, ABP 654, 02 
June 2021 V2.0.  The scope of this plan includes the final analysis that is planned and 
will be executed by Parexel International, the designated contract research organization.    
2. 
Objectives, Endpoints and Hypotheses 
2.1 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
To demonstrate pharmacokinetic 
similarity in subjects with multiple 
switches between ustekinumab and 
ABP 654 compared to subjects 
receiving continued use of 
ustekinumab 
Primary pharmacokinetic parameters: 
 
AUCtau between Week 52 and Week 
64 
 
Cmax between Week 52 and Week 64 
 
Secondary 
To assess the efficacy, safety and 
immunogenicity in subjects with 
multiple switches between ABP 654 
and ustekinumab compared with 
subjects receiving continued use of 
ustekinumab 
Secondary pharmacokinetic parameters: 
 
tmax between Week 52 and Week 64 
 
Ctrough,ss between Week 28 and Week 
52 
 
Efficacy related parameters: 
 
Psoriasis Area and Severity Index 
(PASI) percent improvement from 
baseline (day 1) at Week 64 
 
PASI 75 response at Week 64 
 
PASI 100 response at Week 64 
 
Safety related parameters: 
 
Treatment-emergent adverse events 
(TEAEs) and serious adverse events 
(SAEs), post randomization 
 
Treatment-emergent events of interest 
(EOIs), post randomization 
 
Immunogenicity-related Endpoints: 
 
Incidence of antidrug antibodies, post 
randomization 


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2.2 
Hypotheses and/or Estimations 
The analyses of the primary pharmacokinetic(s) (PK) endpoints will test the following 
hypotheses for each endpoint: 
Null Hypothesis (H0): The geometric means ratio (GMR) between ABP 654 and 
ustekinumab is outside a similarity margin of (0.8, 1.25), 
versus 
Alternative Hypothesis (Ha): The GMR between ABP 654 and ustekinumab is within a 
similarity margin of (0.8, 1.25). 
To establish interchangeability, both 90% confidence intervals (CIs) of GMR of ABP 654 
versus ustekinumab for AUCtau and Cmax from the primary analysis must fall within the 
above similarity margin. 
3. 
Study Overview 
3.1 
Study Design 
This is a randomized, double-blinded, phase 3 study in adult subjects with moderate to 
severe plaque psoriasis.  This study is planned to be conducted globally at study centers 
including but not limited to North America and Europe. 
The total duration of study participation for each subject will be 68 weeks, with up to 
4 weeks for screening and 64 weeks after the first investigational product administration. 
Subjects will receive an initial 3 doses of ustekinumab on day 1 (Week 0), Week 4 and 
Week 16.  From Week 28, subjects in the continued use group will stay on ustekinumab 
and subjects in the switching group will switch between ABP 654 and ustekinumab every 
12 weeks. 
At Week 28, efficacy assessments will be conducted including evaluation of PASI. 
Subjects who do not achieve a PASI 50 response or better improvement at Week 28 are 
considered as run-in failures and will not be randomized at Week 28; these subjects will 
complete End of Study (EOS) procedures at Week 28.  The Run-in Period will occur 
from day 1 until prior to randomization at Week 28.  Those unable to complete the 
Week 28 visit or did not have a PASI assessment completed at Week 28 will be 
discontinued from the study.  All enrolled subjects not randomized at Week 28 will be 
considered run-in failures and the run-in failure reason will be documented. 


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3.2 
Sample Size 
Approximately 480 subjects will be enrolled to receive ustekinumab during the Run-in 
Period.  Subjects with prior biologic use for psoriasis will be capped at 50% of the total 
enrolled subjects.  This sample size will ensure approximately 310 subjects will be 
randomized at Week 28 after the Run-in Period, considering 35% run-in failures, in a 1:1 
ratio to the continued use group or the switching group.  The randomization will be 
stratified by prior biologic use for psoriasis (yes versus no) at baseline (Week 0), 
geographic region, and body weight group at baseline (Week 0).  The number of 
subjects enrolled may be adjusted during the study with the actual run-in failure rate 
seen to ensure approximately 310 subjects will be randomized at Week 28.  Subjects 
already enrolled will be allowed to be randomized at Week 28.  The sample size of 310 
enrolled subjects will provide 90% power to demonstrate similarity of the primary PK 
endpoints based on the Two One-Sided Tests at a 0.05 significance level, assuming a 
between-subject variability (as measured by coefficient of variation) of 55% for ABP 654 
and ustekinumab, a true GMR of 1 between ABP 654 and ustekinumab, and a similarity 
margin of (0.8, 1.25), and 25% drop outs after randomization through Week 64 (including 
subjects who discontinue the study prior to Week 52 and those reaching Week 52 but do 
not have evaluable primary PK endpoints between weeks 52 and 64). 
3.3 
Adaptive Design 
None. 
4. 
Covariates and Subgroups 
4.1 
Planned Covariates 
Unless stated otherwise, stratification factors (prior biologic use for psoriasis at baseline, 
geographic region, and body weight group at baseline) will be included as covariates in 
models for PK and efficacy endpoints. For continuous efficacy endpoints (e.g. PASI 
percent improvement from baseline, Body Surface Area (BSA) change from baseline), 
the relevant baseline scores will also be included as covariates in models. 
Covariate values may be discordant if collected via case report form (CRF) and 
Interactive Web/Voice Response System (IXRS). Analyses that are intended to evaluate 
the treatment effect and include stratification variables as covariates in the model will be 
based on the CRF stratification values, regardless of the subject’s IXRS stratification 
values, to provide unbiased estimates of the effects of treatment and stratification 
variables without loss of efficiency (Ke et al, 2017). Analyses using the stratified 
Cochran-Mantel-Haenszel method will be based on the IXRS stratification values.  


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4.2 
Subgroups 
Subgroup analyses will be conducted for the primary PK parameter endpoints for the 
binding antidrug antibody (ADA) negative subgroup (see definition in Section 5.1). 
5. 
Definitions 
5.1 
General 
Actual Treatment Received During Run-in Period 
If a subject received any dose of ABP 654 during the Run-in Period, the actual treatment 
for the subject is defined as ABP 654. Otherwise, the actual treatment for the subject is 
defined as ustekinumab. 
Actual Treatment Received During Post-randomization Period 
For subjects randomized to switching group or continued use group and received all 
assigned treatments, the actual treatment received is defined as the switching group or 
the continued use group. Otherwise, the actual treatment received by a subject is 
defined as the actual treatment sequence (including missed doses, if any) received by 
the subject. 
Baseline 
Unless stated otherwise, the baseline of the study is defined as the last non-missing 
assessment taken prior to the first dose of investigational product (IP) a subject received 
(see definition of first dose date). In cases where baseline assessments are taken on the 
same day as the first dose of IP, and either no times are reported or the IP and 
assessment times are the same, it will be assumed that these assessments are taken 
prior to IP being administered. 
Binding ADA Negative Subgroup   
Defined as subjects in the subset of Safety Analysis Set (SAS) who have never tested 
positive (i.e. tested negative or no results) prior to the first dose of post-randomization 
IP, have at least one ADA result post randomization, and all available post-
randomization ADA results are negative. 
Change from Baseline 
Change from baseline is defined as (value at post-baseline visit – value at baseline). 


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Concomitant and Prior Medication 
Prior medications are defined as medications with a stop date prior to first dose of IP the 
subject received (see definition of first dose date). Concomitant medications are defined 
as any medications ongoing at the start of IP treatment for the subject or with a start 
date on or after the first dose date, through end of study date. 
End of Study (EOS) Date  
The EOS date is the date recorded on the End of Study page of the CRF. 
First Dose Date  
It is defined as the date the subject received the first dose of IP. 
Last Dose Date  
It is defined as the date the subject received the last dose of IP. 
First Post-randomization Dose Date  
It is defined as the date the subject received the first post-randomization dose of IP. 
Multiple Imputation (MI) 
A method of imputation which takes into consideration the uncertainty of the missing 
data by creating several different plausible imputed data sets and appropriately 
combining analysis results obtained from each of the imputed datasets.   
Non-Responder Imputation (NRI)  
A method of imputation where a subject with missing post-baseline binary response data 
will be imputed as a non-responder, regardless of the reasons for missing data. 
Study Analysis Visit 
If more than one actual visit (including the unscheduled visits) falls within the same 
defined window, the visit closest to the target day with non-missing data will be 
considered for analysis. If two actual visit dates are at the same distance from the target 
day, the later visit with non-missing data will be considered for analysis. 
For Efficacy, Vital, Safety Lab and PK 
Study 
Analysis Visit 
 
Target 
Day 
Study 
Day 
Interval 
(days) 
 
Endpoint  
Efficacyb
c 
Vital 
Signbc 
Safet
y 
Lababc 
PKb
c 
ECG
bc 
Baseline 
1 
<=1 
NA 
X 
X 
X 
X 
X 


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Study 
Analysis Visit 
 
Target 
Day 
Study 
Day 
Interval 
(days) 
 
Endpoint  
Efficacyb
c 
Vital 
Signbc 
Safet
y 
Lababc 
PKb
c 
ECG
bc 
Week 4 
29 
2-70 
69 
 
X 
 
X 
 
Week 16 
113 
71-154 
84 
 
X 
 
X 
X 
Week 28 
197 
155-238 
84 
X 
X 
X 
X 
X 
Week 40 
281 
239-322 
84 
X 
X 
 
X 
X 
Week 52 
365 
323-406 
84 
X 
X 
X 
X 
X 
Week 64 
449 
>=407 
NA 
X 
X 
X 
X  
 
a. Laboratory parameters will only be included at the visits where it is scheduled for 
assessment in the output tables. 
b. If only assessment dates of efficacy, vital, safety laboratory, and PK are available 
and the assessment date is on the same day of first dose of IP at week 0 or week 
28 respectively, the measurement is treated as baseline or pre the first IP dose 
post-randomization assessment. 
c. If both assessment date and time are available for efficacy, vital sign,  safety 
laboratory, PK or ECG measurements, the measurements either (1) are on the 
same day as the first dose date at Week 0 or Week 28, but the assessment time is 
after the first dose of IP at Week 0 or Week 28, respectively, or (2) fall within the 
Week 28 window and are after the first post-randomization IP, the measurements 


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will not be defined as baseline or Week 28, but will be included in consideration for 
the next visit, Week 4 or Week 40 measurements, respectively.  
PK concentrations between Week 52 – Week 64 are summarized by nominal study visit 
per the following table: 
Tolerance Windows for Pharmacokinetic Endpoint Sample Collection 
Study Visit 
Tolerance Windowsa 
Week 52 predose 
Within 1 hour prior to Week 52 
investigational product administration 
2 days post Week 52 dose 
 ±5 hours 
7 days post Week 52 dose 
 ±5 hours 
10 days post Week 52 dose 
 ±24 hours 
2 weeks post Week 52 dose 
 ±24 hours 
4 weeks post Week 52 dose 
 ±48 hours 
8 weeks post Week 52 dose 
 ±72 hours 
12 weeks post Week 52 dose (End of 
Study Visit) 
 ±72 hours 
aThe Week 52 visit should be performed 52 weeks from day 1, with a window of 
± 5 days.  Subsequent visits are done in relation to the actual Week 52 investigational 
product dose date (e.g., for the 2 days post Week 52 dose timepoint, the 
pharmacokinetic sample should be collected 2 days after the actual Week 52 dose, with 
a collection window of ± 5 hours). 
 
For ADA 
Study Analysis Visit 
 
Target Day 
Study Day 
Baselineab 
1 
<=1 
By Week 4 
29 
<=70 
By Week 16 
113 
<=154 
By Week 28ab 
197 
<=238 
By Week 40 
281 
<=322 
By Week 52 
365 
<=406 
By Week 64 
449 
<=EOS Visit Date 
a. If a subject has ADA measurements on the same day as the first dose date at Week 0 or 
Week 28 but the administered time is after the first dose of IP at Week 0 or Week 28, 
respectively, the ADA measurements will not be defined as baseline or Week 28, but will 
be included in consideration for Week 4 or Week 40 measurements, respectively.  


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b. If only an assessment date of ADA is available and the assessment date is on the same 
day of first dose of IP at Week 0 or Week 28, respectively, the measurement is treated as 
baseline or pre first IP dose post-randomization assessment. 
 
Study Day  
Study day is defined as the number of days from Study Day 1. 
Before Study Day 1: Study Day = (Date of assessment – Date of Study Day 1) 
On or After Study Day 1: Study Day = (Date of assessment – Date of Study Day 1) +1 
Therefore, the day prior to Study Day 1 is -1.  
Study Day 1 
Study day 1 is defined as the first day of IP the subject received (see definition of first 
dose date).  
Study Period 
The following definitions will be used for PK and safety analyses. 
Run-in Period 
It is defined as the time period from the first dose of IP the subject received (see 
definition of first dose date for the subject) to prior to first post-randomization dose for 
subjects who are randomized and treated post-randomization, or to the EOS visit for 
subjects not randomized or for subjects who were randomized but not treated post-
randomization. 
Post-randomization Period 
For subjects who are randomized and treated post-randomization, it is defined as the 
time period from the first post-randomization dose to the EOS visit.   
Study Randomization 
Study randomization is defined as when subject receives a random treatment allocation 
via the IXRS system. 
Total IP Exposure Duration 
The total IP exposure duration for a subject (in weeks) for each study period (Run-in 
Period and Post-randomization Period) will be derived as: (the period end date – the 
period start date +1)/7. The Run-in Period end date for the subjects who are 


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randomized and treated post-randomization is the date of the first IP post 
randomization -1.  
5.2 
Pharmacokinetic  
Pharmacokinetic parameters will be calculated from the serum concentration-time data 
using noncompartmental methods (Phoenix WinNonlin, version 8.2 or higher, Pharsight 
Corp, St. Louis, MO) and actual sampling times. The following PK parameters will be 
reported: 
Variable 
Definition 
AUCtau 
area under the curve from time 0 (Week 52) over the dosing 
interval up to Week 64 using the observed values 
Cmax 
Maximum observed serum concentration obtained directly from the 
experimental observations. If multiple maxima occur at equal 
concentrations, the first temporal value will be taken. 
tmax 
Time at which the maximum serum concentration was observed 
obtained directly from the experimental observations 
Ctrough,ss 
trough concentration at steady state obtained directly from the 
experimental observations 
 
If data allows, the following PK parameters will also be derived: 
Variable 
Definition 
z 
Terminal elimination rate constant 
t1/2 
Terminal elimination half-life; calculated as ln(2)/z 
AUCtau extrap 
area under the curve from time 0 (Week 52) over the dosing 
interval extrapolated to Week 64 
 
The AUCtau is the sum of areas up to the time tau and will be calculated using the linear 
trapezoidal rule. Actual time post dose for the observed value between weeks 52 and 64 
will be used as time for AUCtau and no extrapolation will be applied. In the event of below 
the lower limit of quantification (LLOQ) at the end of the profile, the time of the last 
quantifiable sample will be used. Individual AUCtau will be flagged and excluded from 


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summary statistics and statistical testing if less than 2 post tmax concentration values are 
reported or above LLOQ.  
The z will be estimated by linear regression of concentration versus time data 
presented in a log-linear scale. Only those data points that are judged to describe the 
terminal log-linear decline will be used in the regression. A minimum number of three 
data points in the terminal phase will be used in calculating z with the line of regression 
starting at any post tmax data point (Cmax will not be part of the regression slope).  
The interval used to determine z should be equal or greater than 2-fold the estimated 
t1/2.    Otherwise, the derived z and t1/2 will be flagged.  
For the estimation of AUCtau extrap, extrapolation will be considered acceptable if the 
following conditions are satisfied: 
 
Extrapolation is <20% of the total area 
 
z and t1/2 are correctly estimated based on above criteria 
 
Terminal phase regression R2 adjusted > 0.8 
Any individual AUCtau extrap not meeting the above criteria will be flagged.  
The derived PK parameters (i.e. z, t1/2 and AUCtau extrap) will be included in the listing of 
individual PK parameters. No summaries statistics and statistical testing will be 
conducted for these derived parameters.  
5.3 
Efficacy 
Body Surface Area (BSA) affected by psoriasis 
The percent of BSA affected by psoriasis (%BSA) is estimated by assuming that the 
subject’s palm, excluding the fingers and thumb, represents roughly 1% of the body’s 
surface (Chandran, 2009). At any given visit, BSA should be performed by the same 
assessor performing PASI assessment. Because of interobserver variability in estimated 
BSA, all assessments for a given subject should be made by the same observer 
whenever possible. 
PASI 
The PASI is a measure of the average redness (erythema), thickness (induration), and 
scaliness (scaling; each graded on a 0–4 scale of the lesions, weighted by the area of 
involvement (Feldman and Krueger, 2005). PASI combines the assessment of the 


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severity of lesions and the area affected into a single score in the range 0 (no disease) 
to 72 (maximal disease). 
PASI Percent Improvement from Baseline 
PASI percent improvement from baseline is defined as 100 × (value at baseline – value 
at post-baseline visit) / value at baseline. A percent improvement will not be calculated if 
the baseline value is missing. A positive value will be considered PASI improvement. 
Hence, PASI percent improvement will be in a positive direction while PASI percent 
worsening will be in a negative direction. 
PASI Response 
PASI Response is defined as a subject meeting or surpassing a pre-specified threshold 
for percent improvement in PASI score compared to the baseline PASI score. An 
improvement of at least 75% qualifies a subject as being a PASI 75 responder, and an 
improvement of 100% qualifies a subject as being a PASI 100 responder. 
Static Physician’s Global Assessment (sPGA) 
The sPGA is a 6-point scale (0-5) used to measure the severity of disease (induration, 
scaling, and erythema). The sPGA should be completed by the same assessor 
performing the PASI assessments. All assessments for a given subject should be made 
by the same observer whenever possible. 
sPGA Response 
An sPGA response is defined as a subject meeting sPGA assessment values of 0 
(Clear) or 1 (Almost Clear). 
5.4 
Safety 
Adverse Events Leading to Discontinuation from IP/Study 
AEs leading to discontinuation from IP/study are those with an action taken with IP 
indicating “drug withdrawn” or Other action taken of “study discontinued”.  
Event of Interest (EOI)  
An EOI is defined as a noteworthy event for a particular product or class of products that 
a sponsor may wish to monitor carefully. It could be serious or non-serious and could 
include events that might be potential precursors or prodromes for more serious medical 
conditions in susceptible individuals (Council for International Organizations of Medical 
Sciences [CIOMS] VI, 2005). The EOIs for this study will include: 


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 
Serious systemic hypersensitivity reactions 
 
Facial palsy 
 
Pustular psoriasis 
 
Erythrodermic psoriasis 
 
Serious infections (including mycobacterial and salmonella infections) 
 
Malignancy 
 
Cardiovascular events 
 
Reversible posterior leukoencephalopathy syndrome 
 
Serious depression including suicidality 
 
Venous thromboembolism 
The detailed search strategies for the EOIs are included in Appendix A. 
Treatment-emergent Adverse Event 
Treatment emergent adverse events (TEAEs) during the Run-in Period are defined as 
adverse events that start on or after the first dose of IP and prior to the first dose post 
randomization for randomized and treated subjects, or EOS for run-in failures or for 
subjects who were randomized but not treated post-randomization. 
TEAEs during the post randomization period are defined as adverse events that start on 
or after the first dose of IP post-randomization and prior to the EOS. 
If the adverse event starts on the same day as the first dose of IP, then the flag 
indicating whether the adverse event started prior to the first dose on the adverse event 
CRF page will be used to determine whether this is a TEAE during the Run-in Period. 
For randomized and treated subjects, an adverse event that starts on the same day as 
the first post-randomization dose will be considered as a TEAE post-randomization. 
6. 
Analysis Sets 
6.1 
Full Analysis Set 
The Full Analysis Set (FAS) consists of all randomized subjects. This analysis set will be 
used for sensitivity analyses of efficacy endpoints and will be analyzed according to 
randomized treatment group.  


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6.2 
Safety Analysis Set 
The Safety Analysis Set (SAS) consists of all randomized subjects who received at least 
1 dose of IP post randomization. This analysis set will be used for analyses of the safety 
endpoints during the post randomization period according to actual treatment received. 
6.3 
PK Analysis Sets 
PK Concentration Analysis Set 
The PK Concentration Analysis Set will include all randomized subjects who received at 
least 1 dose of IP post randomization and have at least 1 reported serum concentration 
of ABP 654 or ustekinumab on or after the day of randomization. This analysis set will be 
used for analyses of PK concentrations during the post randomization period according 
to actual treatment received. 
PK Parameter Analysis Set 
The PK Parameter Analysis Set will include all randomized subjects who receive all 
3 doses of the assigned IP between weeks 28 and 52 and who have an evaluable 
ABP 654 or ustekinumab serum concentration time profile between weeks 52 and 64. 
This analysis set will be used for the primary analysis of the primary and secondary PK 
endpoints and will be analyzed according to actual treatment received. 
Per-protocol PK Parameter Analysis Set  
The Per-protocol PK Parameter Analysis Set will include all subjects in the PK 
Parameter Analysis Set who do not have an important protocol deviation during the 
study that could affect the primary PK endpoints. This analysis set will be used for a 
sensitivity analysis of the primary PK endpoints and will be analyzed according to actual 
treatment received. 
6.4 
Health-related Quality-of-Life or Health Economics Analyses Set(s) 
None. 
6.5 
Per-protocol Efficacy Analysis Set 
The Per-protocol Efficacy Analysis Set consists of all subjects who are randomized and 
receive all 3 doses of the assigned IP between weeks 28 and 52 and who have not 
experienced an important protocol deviation during the study that may affect the 
evaluation of the efficacy endpoints. This analysis set will be used for primary analysis of 
the secondary efficacy endpoints and will be analyzed according to actual treatment 
received. 


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6.6 
Interim Analyses Set(s) 
None. 
6.7 
Study-specific Analysis Set 
Run-in Treated Set 
The Run-in Treated Set (RTS) consists of all enrolled subjects treated with at least 1 
dose of IP during the Run-in Period. This analysis set will be used for all analyses for the 
Run-in Period based on actual treatment. 
7. 
Planned Analyses 
7.1 
Interim Analysis and Early Stopping Guidelines 
None. 
7.2 
Primary Analysis 
None. 
7.3 
Final Analysis 
The final analysis for the study will be performed after all subjects reach Week 64 or 
terminate early. 
8. 
Data Screening and Acceptance 
8.1 
General Principles 
The objective of the data screening is to assess the quantity, quality, and statistical 
characteristics of the data relative to the requirements of the planned analyses. 
Data screening process will be documented in a data management plan by Parexel and 
agreed by Amgen.  In addition to the data screening built into the Parexel Data 
Management Plan, the programming of analysis datasets, tables, figures and listings 
(TFL) provides additional data screening.  
When the database has been declared to be complete and accurate, the database will 
be locked.  Database lock will follow the standard operating procedure(s) at Parexel. 
8.2 
Data Handling and Electronic Transfer of Data 
Clinical data will be entered in RAVE database and exported as SAS® version 9.4 or 
higher datasets. Converted datasets will be created using SAS® and following standard 
Clinical Data Interchange Standards Consortium Standard Data Tabulation Model 
(CDISC SDTM, version 1.4, Implementation Guide version v3.2) conventions.  Analysis 
datasets will be created using SAS® and following CDISC Analysis Data Model (ADaM, 
version 2.1, Implementation Guide 1.1) standards. 


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Medical history and AEs will be coded using the current version of Medical Dictionary for 
Regulatory Activities (MedDRA) at the time of the final analysis to assign a system organ 
class (SOC) and preferred term (PT) to each event. Adverse events and abnormal 
laboratory results considered as AEs are assigned a toxicity grade according to National 
Cancer Institute (NCI-US) Common Terminology Criteria for Adverse Events (CTCAE) 
version 4.03. Prior and concomitant medications will be coded using the current version 
of the World Health Organization Drug Dictionary (WHO-DD) at the time of the final 
analysis. 
8.3 
Handling of Missing, Below LLOQ and Incomplete Data 
Missing PK concentration data and endpoints will not be imputed. 
For the purpose of calculating AUCtau, concentrations that are below the LLOQ after tmax 
will be excluded; values less than the LLOQ that are encountered prior to tmax will be set 
to zero and included. Individual AUCtau will be flagged if less than 2 post tmax 
concentration values are reported or if less than 2 post tmax concentration values are 
above LLOQ. 
For summary statistics and linear plots for the PK concentrations, concentration values 
< LLOQ will be set to zero. For log-linear plots, concentration values below LLOQ will not 
be displayed. 
The handling of missing values for efficacy endpoints are detailed in Section 9.6.  
Missing safety and ADA endpoints will not be imputed. 
Imputation for Partial or Missing Dates 
If dates are missing or incomplete for an AE (including deaths) or concomitant 
medication, the following algorithm will be used for imputation:  
Start Date 
Stop Date 
Complete: 
yyyymmdd 
Partial: yyyymm 
Partial: yyyy 
Missing 
<1st 
dose 
≥1st 
dose 
<1st dose 
yyyymm 
≥1st dose 
yyyymm 
<1st dose 
yyyy 
≥1st dose 
yyyy 
Partial: 
yyyymm 
= 1st dose 
yyyymm 
2 
1 
n/a 
1 
n/a 
1 
1 
≠ 1st dose 
yyyymm 
2 
2 
2 
2 
2 
2 
Partial: 
yyyy 
= 1st dose 
yyyy 
3 
1 
3 
1 
n/a 
1 
1 


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≠ 1st dose 
yyyy 
3 
3 
3 
3 
3 
Missing 
4 
1 
4 
1 
4 
1 
1 
 
1 = Impute as the date of first dose 
2 = Impute as the first of the month 
3 = Impute as January 1 of the year 
4 = Impute as January 1 of the stop year 
Note: If the start date imputation leads to a start date that is after the stop date, then 
there is a data error and do not impute the start date. 
Imputation rules for partial or missing stop dates: 
1. Initial imputation 
a. For partial stop date “mmyyyy”, impute the last of the month. 
b. For partial stop date “yyyy”, impute December 31 of the year. 
c. For completely missing stop date, do not impute. 
2. If the stop date imputation leads to a stop date that is after the death date, 
then impute the stop date as the death date. 
3. If the stop date imputation leads to a stop date that is before the start date, 
then there is a data error and do not impute the stop date. 
 
 
Imputation rules for partial or missing death dates: 
1. If death year and month are available but day is missing: 
a. If “mmyyyy” for last contact date = “mmyyyy” for death date, set death 
date to the day after the last contact date. 
b. If “mmyyyy” for last contact date < “mmyyyy” for death date, set death 
date to the first day of the death month. 
c. If “mmyyyy” for last contact date > “mmyyyy” for death date, data error 
and do not impute. 
2. If both month and day are missing for death date or a death date is totally 
missing, set death date to the day after the last contact date. 
 
The imputed dates will be used to assess whether AEs should be considered as 
treatment-emergent and if medications should be included in the safety summaries as 
prior or concomitant, however the original, partial dates will be included in data listings. 
 
8.4 
Detection of Bias 
None. 
8.5 
Outliers 
Individual ABP 654 and ustekinumab serum concentration-time points, if considered 
anomalous, may be excluded from the analysis if due to a protocol deviation at the 


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discretion of the pharmacokineticist following a review of the available documentation 
(bioanalytical report, clinical report, etc.). Any such exclusion will be documented and 
clearly outlined in the clinical study report (CSR).  
Entire individual PK profile for a subject may be excluded following review of the 
available documentation. Any such exclusion will be clearly listed in the CSR along with 
justification for exclusion.  
8.6 
Distributional Characteristics 
None. 
8.7 
Validation of Statistical Analyses 
All report outputs will be produced/all statistical analyses will be performed using SAS® 
version 9.4 or a higher version in a secure and validated environment. 
Programs will be developed and maintained and output will be verified in accordance 
with current standard operating procedures at Parexel. The validation process is 
repeated any time TFLs are re-delivered with different data. Execution of this validation 
process is documented throughout the study. The entire set of TFLs will be checked for 
completeness, accuracy prior to its delivery to Amgen. 
9. 
Statistical Methods of Analysis 
9.1 
General Considerations 
All statistical analyses will be performed using SAS® (Version 9.4 or higher). 
Unless otherwise specified, descriptive data summaries will be tabulated by treatment 
for all endpoints. Categorical data will be summarized using number of subjects, 
frequency and percentages of subjects falling into each category, with the denominator 
for percentages being the number of subjects in the analysis sets for each treatment 
group, unless otherwise noted. Percentages will be rounded to one decimal place except 
for 100%, which will have no decimal place. 
All continuous variables will be summarized using mean, standard deviation, median, 
minimum, maximum, 25th percentile (Q1), 75th percentile (Q3), and number of subjects 
with observations. The mean, geometric mean, median, Q1, and Q3 will be presented 
to one decimal place greater than the original data, standard deviation will be two 
decimal places greater than the original data, and the minimum and maximum will have 
the same number of decimal places as the original data.  
For PK endpoints, additional precision rules are as follow: 


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Pharmacokinetic serum concentrations will be reported in ng/ml and will follow 
the general conventions for summary statistics. 
Pharmacokinetic parameters with units of ng/ml or h*ng/ml will be converted to 
ug/ml or h*ug/ml with 1 decimal place. 
Summary Statistics  
Reporting Precision  
CV%/geometric CV% 
1 d.p. 
Geometric LS mean 
2 d.p. 
Geometric LS mean ratios 
4 d.p. 
CI 
Same number of decimal places as the 
associated statistic 
 d.p.= decimal place(s) 
 
Confidence intervals may also be provided (when specified). 
 
For any of the summaries that are to be done by visit, the derived analysis study visit as 
defined in Section 5.1 will be used for analysis unless otherwise noted. 
9.2 
Subject Accountability 
The following information will be summarized for subject disposition and accountability 
for each of the analysis sets defined in Section 6, unless stated otherwise: 
 
Number of subjects enrolled in the RTS and number of subjects randomized in 
the FAS by region, country, and site 
 
Subject disposition including 
o Number of subjects in the RTS who discontinued treatment with reason of 
discontinuation, discontinued treatment with reason of discontinuation 
related to COVID-19, completed the Run-in Period and who failed the 
Run-in Period (i.e., run-in failures) with reason for run-in failures and 
reason for run-in failures related to COVID-19 for the Run-in Period;   
o Number of subjects who were randomized, who were treated with IP, 
completed treatment, discontinued treatment with reason of 
discontinuation, discontinued treatment with reason of discontinuation 
related to COVID-19, completed study, and discontinued study with 
reason of discontinuation and discontinued study with reason related to 
COVID-19 for the Post-randomization Period 


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 
Summary of analysis sets with reasons for exclusion from each analysis set (for 
all screened subjects) 
 
Randomization list for the FAS 
 
List of discontinued subjects from IP and/or study in the RTS for the Run-in 
Period and in the FAS for the Post-randomization Period 
9.3 
Important Protocol Deviations and COVID-19 Related Protocol 
Deviations 
Important Protocol Deviations (IPDs) data will be identified and recorded. The study 
team will conduct on-going reviews of the IPD data throughout the study and the 
resulting set of subjects to be included in the Per-protocol (PP) PK and efficacy analysis 
sets. The PP analysis sets must be finalized prior to database lock of the final analysis. 
For the Post-randomization Period, a summary of incidence of IPDs will be based on 
FAS and tabulated using number and percentage of subjects by deviation type (including 
COVID-19 related) and randomized treatment group. A listing of subjects with IPDs will 
be provided (with a flag indicating whether the deviation leads to exclusion from the PP 
PK or efficacy analysis sets and a flag indicating whether an IPD is COVID-19 related) 
based on FAS.  
For the Run-in Period, a summary of incidence of IPDs will be based on RTS and 
tabulated using number and percentage of subjects by deviation type (including COVID-
19 related). A listing of subjects with IPDs (with a flag indicating whether an IPD is 
COVID-19 related) will be provided based on RTS. 
All COVID-19 related protocol deviations (PDs) will be summarized by COVID-19 related 
deviation type for the FAS for the Post-randomization Period and RTS for Run-in Period. 
A listing of subjects with COVID-19 related PDs will be provided for the FAS for the Post-
randomization Period and RTS for Run-in Period. 
 
9.4 
Demographic and Baseline Characteristics 
 
The following demographics and baseline characteristics will be summarized 
descriptively by treatment group for each of the analysis sets defined in Section 6. 
 
age (in years, at time of signing informed consent)  
 
race  


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 
sex  
 
ethnicity  
 
height  
 
weight  
 
body mass index (BMI)  
 
prior biologic use for psoriasis 
 
geographic region 
 
prior topical steroid use 6 months prior to the baseline  
 
disease duration (< 1 year vs. ≥ 1 year) 
 
baseline PASI 
 
baseline sPGA (in addition to the original scale, extra section for combined scale 
4 and 5 will also be added) 
 
baseline BSA 
 
Medical history by SOC and PT for not resolved findings will be summarized 
descriptively for RTS. 
 
9.5 
PK Analyses 
9.5.1 
Analyses of Primary PK Endpoint(s) 
9.5.1.1 
Primary Analysis  
The primary analysis of the primary PK endpoints, AUCtau and Cmax, between weeks 52 
and 64 will be performed based on the PK Parameter Analysis Set according to the 
actual treatment groups (switching group versus continued use group).   
The point estimates and 90% CIs for the GMRs between ABP 654 and ustekinumab for 
AUCtau and Cmax between weeks 52 and 64 will be estimated using an analysis of 
covariance (ANCOVA) model adjusting for stratification factors and PK trough 
concentration at Week 28.  Prior to statistical testing, the PK parameters will be 
logarithmically transformed (natural log).  Point estimates and 90% CIs for the mean 
difference in logarithmic PK parameters will be estimated using the ANCOVA model, 
which will then be transformed back to the original scale to obtain the point estimates 
and 90% CIs for GMR. To establish interchangeability, the 90% CIs of GMR of ABP 654 
vs ustekinumab for AUCtau and Cmax from the primary analysis should fall within the 
prespecified similarity margin (0.8, 1.25). 


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9.5.1.2 
Secondary Analyses 
AUCtau and Cmax of ABP 654 and ustekinumab between weeks 52 and 64 will be listed 
by subject and summarized descriptively by treatment group using PK Parameter 
Analysis Set. 
To assess the robustness of the primary analysis result, the ANCOVA analysis 
described above will be repeated using the Per-protocol PK Parameter Analysis Set.  
9.5.2 
Analyses of Secondary PK Endpoints 
The analyses of the secondary PK endpoints of tmax between weeks 52 and 64 and 
Ctrough,ss between weeks 28 and 52 will be based on the PK Parameter Analysis Set 
according to the actual treatment groups. The median, min and max of tmax will be 
summarized descriptively by the treatment group. Ctrough,ss between weeks 28 and 52 will 
be summarized descriptively by visit and treatment group.  The point estimates and 90% 
CIs for GMR for Ctrough,ss at Week 28 between the two treatment groups will be estimated 
using an ANCOVA model adjusting for stratification factors. The point estimates and 
90% CIs for GMR for Ctrough,ss at Week 40 and Week 52 between the two treatment 
groups will be estimated using an ANCOVA model adjusting for stratification 
factors and PK trough concentration at Week 28.  
In addition, Ctrough,ss between weeks 28 and 52 will be summarized descriptively by visit 
and treatment group in the PK Concentration Analysis Set. Boxplots of Ctrough,ss between 
weeks 28 and 52 will also be generated for the PK Concentration Analysis Set by actual 
treatment group. 
9.5.3 
Analyses of Other PK Endpoint(s) 
PK concentrations during the Run-in Period will be summarized descriptively by visit 
based on the RTS. Boxplots for trough concentrations during Run-in Period will be 
presented using the RTS. 
PK concentrations between weeks 52 and 64 will be summarized descriptively by 
nominal visit and actual treatment group based on the PK Concentration Analysis Set.  
Individual and mean (+/- STD) serum concentration time-profiles between weeks 52 and 
64 by actual treatment group will be presented graphically on semi-logarithmic and linear 
scales using the PK Concentration Analysis Set. 


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9.5.4 
Subgroup Analyses 
The primary PK endpoints will be summarized and compared within the binding ADA 
negative subgroup in the PK Parameter Analysis Set using similar methods described in 
Section 9.5.1.  
9.6 
Efficacy Analyses 
9.6.1 
Analyses of Primary Efficacy Endpoint(s) 
None. 
9.6.2 
Analyses of Secondary Efficacy Endpoint(s) 
9.6.2.1 
Primary Analysis  
The primary analysis for PASI percent improvement from day 1 at Week 64 will be 
performed based on the Per-protocol Efficacy Analysis Set according to the actual 
treatment groups with missing PASI score at post-baseline visits including Week 64 
imputed by MI. The MI method will use the treatment allocation, the stratification factors 
and PASI assessment collected in previous visits to inform the plausible values to be 
imputed for missing Week 64 PASI values and will involve the following 3 or 4 steps, 
depending on the actual missing pattern observed in the data. 
(1) If the missing pattern for PASI scores at weeks 40, 52 and 64 is not monotone, 
PROC MI with the MCMC option for imputing missing data will be used to impute 
data with sporadic missing values to create 20 data sets having monotone 
missing pattern. A sample code for this step is provided below: 
PROC MI data=dataset seed=xxxx out =Datastep1 
NIMPUTE = 20 MINIMUM = 0  MAXIMUM =72; 
MCMC CHAIN= MULTIPLE IMPUTE=MONOTONE; 
VAR treatment <stratification variables> PASIbase PASIw40 PASIw52 PASIw64; 
RUN; 
This sample code requires the treatment and the stratification variables to be 
binary and to be coded using numeric values. The data should also have no 
missing values for treatment variable, stratification variables and PASI baseline 
assessment. 
(2) For each data set with monotone missing pattern generated in the step 1, PROC 
MI with regression option will be used to generate 20 complete data sets, 
providing 400 complete data sets. A sample code for this step is provided below: 


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PROC MI data=Datastep1 seed = xxxxx out=yyyy 
NIMPUTE =20 MINIMUM =0 MAXIMUM=72; 
CLASS treatment <stratification variables>; 
MONOTONE METHOD = REG; 
VAR treatment <stratification variables> PASIbase PASIw40 PASIw52 PASIw64; 
BY imputedsetinstep1; 
RUN; 
If there is no sporadic missing PASI scores, i.e., the actual PASI data for weeks 
40, 52 and 64 has monotone missing pattern, step (1) is skipped. In this case 50 
complete data sets will be created using regression method. 
(3) For each imputed data set, the PASI percent improvement from day 1 at 
Week 64 will be derived and the mean difference between the treatment groups 
in PASI percent improvement from day 1 at Week 64 will be estimated from an 
ANCOVA model adjusting for the baseline PASI value and the stratification 
factors. 
(4) Results of these ANCOVA analysis from all the imputed data sets are combined 
using PROC MIANALYZE, generating an overall mean treatment difference 
estimate and associated standard error and 90% CI. 
For the primary analysis of PASI 75 and PASI 100, missing PASI scores at Week 64 will 
be imputed by NRI.  Using this imputation method, the point estimate and 90% CI of the 
risk difference in PASI 75 response rate and PASI 100 response rate at Week 64 will be 
estimated from the Mantel-Haenszel method for the point estimate, and the stratified 
Newcombe confidence limits for the 90% CI, adjusting for the IXRS stratification factors.  
These methods deviated from the method indicated in the protocol version 2.0, in order 
to resolve the possible convergent issue met when using generalized linear model with 
identify link function.  
9.6.2.2 
Secondary Analyses 
These endpoints will also be summarized descriptively by actual treatment group based 
on Per-protocol Efficacy Analysis Set using observed data. 
Additional sensitivity analysis will be conducted for PASI percent improvement from day 
1 at week 64 by fitting the same ANCOVA model (i.e., adjusting for the baseline PASI 


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value and the stratification factors) using observed data for the FAS and according to 
randomized treatment groups and for the Per-protocol Efficacy Analysis Set according to 
the actual treatment groups. 
9.6.3 
Analyses of Other Efficacy Endpoint(s) 
The analyses of the other efficacy endpoints in this section will be based on the Per-
protocol Efficacy Analysis Set by actual treatment group. 
The PASI percent improvement from day 1 at weeks 28, 40, and 52 and the PASI 75 
and PASI 100 response rates at weeks 28, 40, and 52 will be summarized descriptively 
by treatment group based on observed data. 
BSA absolute values and changes from baseline will be summarized descriptively by 
visit (at weeks 28, 40, 52, and 64) and treatment group using observed data.  In addition, 
the adjusted mean difference in change from baseline in BSA at Week 64 will be 
estimated from an ANCOVA model adjusting for the baseline BSA value and the 
stratification factors after applying MI as described in Section 9.6.2.1.  
sPGA scores will be summarized descriptively by visit (at weeks 28, 40, 52, and 64) and 
treatment group. sPGA response (0/1) will also be summarized descriptively by visit and 
treatment group using observed data.   The point estimate and 90% CI of the risk 
difference in sPGA response (0/1) response rate at Week 64 will use same analysis 
method to PASI 75 response described in Section 9.6.2.1. 
9.7 
Safety Analyses 
Safety analyses of the safety endpoints during the post randomization period and the 
Run-in Period will be performed based on the SAS and RTS, respectively, according to 
actual treatment received.  
9.7.1 
Adverse Events 
For summary of AEs, the following summaries, (a) through (n), will be provided for the 
post randomization period. In addition, summaries (a), (e), (f), (k) without risk difference, 
(m), and (n) will be provided for the Run-in Period.  
(a) overall summary of TEAEs 
(b) TEAEs by PT 
(c) TEAEs by SOC and PT 
(d) TEAEs by SOC, PT, and maximum severity grade 
(e) treatment-emergent SAEs by PT 


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(f) treatment-emergent SAEs by SOC and PT 
(g) grade 3 or higher TEAEs by PT 
(h) TEAEs leading to discontinuation from IP/study by PT 
(i) fatal TEAEs by PT 
(j) treatment-emergent EOIs by PT 
(k) overall summary of treatment-emergent EOIs with risk difference 
(l) TEAEs leading to dose delayed of IP by PT 
(m) Treatment Emergent COVID-19 Adverse Events by Preferred Term  
(n)  Treatment Emergent SAEs occurring on or after presumed start date of 
COVID-19 infection by PT 
Counting of AEs will be by subject, and subjects will be counted only once within each 
SOC or PT by study period. For tables categorized by severity, subjects with multiple 
events within a particular SOC or preferred term will be counted under the category of 
their most severe event with that SOC or preferred term.  
AEs tabulated by preferred term will be presented in descending order of frequency of 
the switching group for the post Randomization period or the ustekinumab subjects for 
the Run-in Period. 
The risk difference and 95% CI of each EOI in post randomization period will be 
calculated on the SAS using Wald asymptotic confidence limits or exact confidence 
limits (Farrington-Manning score) if the number of subjects for any treatment group is 
less than 25.  
A listing of treatment-emergent SAEs and treatment-emergent SAEs occurring on or 
after presumed start date of COVID-19 infection will be provided for the post 
randomization period and the Run-in Period separately. 
9.7.2 
Laboratory Test Results 
Laboratory data (hematology, serum chemistry, and urinalysis) will be converted to Système 
International units for reporting and processing purposes.   
For the Post-randomization Period, absolute values and changes from baseline by visit will be 
presented descriptively. In addition, shift tables of the maximum post randomization laboratory 
toxicity based on CTCAE grading relative to randomization at Week 28 will be presented. The 
shift tables will consider all post-randomization (schedule and unscheduled) laboratory results in 
the determination of the maximum post randomization laboratory toxicity. Furthermore, 


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subject incidence tables of grade ≥ 3 laboratory toxicities will be provided. Standard ranges will 
be used for the laboratory analysis. 
For the Run-in Period, absolute values and changes from baseline by visit will be presented 
descriptively. 
Lab assessments will be grouped for summary as follows: 
Hematology:  hemoglobin, hematocrit, red blood cells, platelets, total white blood cell (WBC) 
count, differential WBC count, and absolute neutrophil count. 
Biochemistry:  albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), creatinine, gamma-glutamyl transferase, glucose(random), 
potassium, sodium, total protein, blood urea nitrogen and total bilirubin. 
Urinalysis:  pH, specific gravity, and creatinine. 
9.7.3 
Vital Signs 
Observed and change from baseline for each vital sign parameter will be summarized 
descriptively by visit for the Post-randomization Period.  
9.7.4 
Physical Measurements 
None. 
9.7.5 
Electrocardiogram 
For the Run-in Period, for patients in the Run-in Treated Set, their ECG 
assessments will be summarized by visit and treatment arm. The by visit summary 
will include the number and percentage of patients that have an assessment value 
of normal, abnormal & non clinically significant (NCS), and abnormal & clinically 
significant (CS).   
Similarly, for the Post-randomization Period, for patients in the Safety Analysis 
Set, ECG assessment will be summarized by visit and treatment arm.  
In addition, for patients in the Safety Analysis Set, shift tables of the worst post 
randomization ECG results (normal, abnormal & non clinically significant (NCS), 
abnormal & clinically significant (CS) and missing) relative to randomization at 
Week 28 will be presented. The shift tables will consider all post-randomization 
(schedule and unscheduled) ECG results in the determination of the worst post 
randomization assessment. 


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9.7.6 
Antibody Formation 
The number and percent of subjects developing binding or neutralizing ADA will be 
tabulated descriptively by treatment group and visit in the SAS for the post 
randomization period and in the RTS for the Run-in Period. 
Developing antibody incidence during the Post-randomization Period is defined as the 
number of subjects in the SAS who have a positive result post randomization and have 
never tested positive (i.e., negative or no results) prior to the first dose of post 
randomization IP divided by the number of subjects in the SAS who have antibody 
negative or no result prior to the first dose of post-randomization IP. 
Developing antibody incidence during the Run-in Period is defined as the number of 
subjects in the RTS with a negative or no antibody result at baseline and a positive 
antibody result during the Run-in Period divided by the number of subjects in the RTS 
with at least one post baseline result during the Run-in Period. 
The incidence of transient antibody will also be summarized for each study period. A 
transient antibody result is defined as a positive result during a study period with a 
negative result at the subject’s last visit tested within the respective study period.  
9.7.7 
Exposure to Investigational Product 
Exposure to ABP 654/ustekinumab will be summarized descriptively by actual treatment 
group for the RTS for the Run-in Period and for the SAS for the Post-randomization 
Period, respectively. Summary statistics will be provided for the total number of doses 
administered, total dose received, subjects with at least one dose delay/not administered 
and reasons (including whether or not it is due to COVID-19 related reasons), subjects 
with at least one dose of IP missed due to COVID-19 related reasons, and total duration 
of IP exposure.  
A subject listing of each administered lot number(s) for IP and a listing of unique 
manufacturing lot numbers used in the study will be provided. 
9.7.8 
Exposure to Non-investigational Product  
None. 
9.7.9 
Exposure to Other Protocol-required Therapy 
None. 
9.7.10 
Exposure to Concomitant Medication 
Prior and concomitant medications will be coded using the latest available World Health 
Organization Drug Dictionary as of the time of the final analysis. 


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For the Run-in Period, concomitant medication use by PT is summarized descriptively 
for the RTS and for the SAS by actual treatment group. 
For the Post-randomization Period, concomitant medication use by PT is summarized 
descriptively by actual treatment group based on SAS. 
10. 
Changes From Protocol-specified Analyses 
The protocol specifies EOI of posterior reversible encephalopathy syndrome in Section 
2.2. The SMQ / AMQ search term for this EOI is reversible posterior 
leukoencephalopathy syndrome (RPLS). To keep consistent with the search term, the 
term RPLS is used in this SAP and will be used in the outputs to describe this EOI. 
The method for estimating the risk difference in PASI 75 response rate and PASI 
100 response rate at Week 64 has been changed from the protocol. The Mantel-
Haenszel method will be used for the point estimate, and the stratified Newcombe 
confidence limits will be used for the 90% CI, adjusting for the IXRS stratification 
factors.  These methods deviated from the method indicated in the protocol 
version 2.0, in order to resolve the possible convergent issue met when using 
generalized linear model with identify link function. 
11. 
Literature Citations / References 
Ke C, Wang J, Zhang C, Jiang Q, Snapinn S. On errors in stratified randomization. 
Statistics in Biopharmaceutical Research. 2017 Apr 3;9(2):225-33.  
Chandran V, Gottlieb A, Cook RJ, Duffin KC, Garg A, Helliwell P, Kavanaugh A, Krueger 
GG, Langley RG, Lynde C, McHugh N. International multicenter psoriasis and psoriatic 
arthritis reliability trial for the assessment of skin, joints, nails, and dactylitis. Arthritis 
Care & Research: Official Journal of the American College of Rheumatology. 2009 Sep 
15;61(9):1235-42. 
Feldman SR, Krueger GG. Psoriasis assessment tools in clinical trials. Annals of the 
rheumatic diseases. 2005 Mar 1;64(suppl 2):ii65-8. 
12. 
Prioritization of Analyses 
None. 
13. 
Data Not Covered by This Plan 
None. 


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14. 
Appendices 


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Appendix A.  List of Events of Interest and the Associated SMQ and EOI Searching 
Strategies 
 
Event of Interest 
Category of EOI query (SOC, SMQ 
/ Amgen query) 
Search Strategy 
Serious systemic 
hypersensitivity 
reactions 
Hypersensitivity (SMQ) 
Broad – CTCAE grade 
>=3 or the serious 
TEAE terms with cut-
off period up to 2 days 
after IP administration  
Facial palsy 
Facial paralysis 
PT 
Pustular psoriasis 
Pustular psoriasis 
PT 
Erythrodermic psoriasis 
Erythrodermic psoriasis 
PT 
Serious infections 
(including mycobacterial 
and salmonella 
infections) 
Infections and Infestations (SOC) 
CTCAE grade >=3 or 
the serious TEAE 
terms 
Malignancy 
Malignancies (SMQ) 
Narrow 
Cardiovascular events 
Cardiac disorders (SOC) 
SOC 
Reversible posterior 
leukoencephalopathy 
syndrome 
Reversible posterior 
leukoencephalopathy syndrome 
(Amgen query) 
Narrow 
Serious depression 
including suicidality 
Depression and suicide/self- injury 
(SMQ) 
CTCAE grade >=3 or 
the serious TEAE 
terms (broad) 
Venous 
thromboembolism 
Embolic and thrombotic events, 
venous (SMQ) 
Narrow