Conditions: Arthritis, Rheumatoid
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 311
Healthy volunteers: no

Brief summary:
This trial is designed to determine what effects the human body has on the investigational medicine, ABP 798, and what effects the body has on the investigational medicine after you have been given it, and if this is comparable to what is seen for the licensed medicine, rituximab, in patients with moderate or severe RA.

This study will also assess if the investigational medicine is safe and effective in treating moderate or severe RA compared to the licensed medicine.

Detailed description:

Arms:
arm 1: Participants received ABP 798 on days 1 and 15 (dose 1) and a second dose of ABP 798 at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart. arm 2: Participants received rituximab (United States \[US\] formulation) on days 1 and 15 (dose 1) and transitioned to receive ABP 798 at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart. arm 3: Participants received rituximab (European Union \[EU\] formulation) on days 1 and 15 (dose 1) and a second dose of rituximab (EU formulation) at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart.

Interventions: intervention 1: ABP 798 intervention 2: Rituximab (US) intervention 3: Rituximab (EU)
Intervention descriptions: intervention 1: Supplied as a 10 mg/mL liquid concentrate for intravenous (IV) administration. intervention 2: Supplied as a 10 mg/mL liquid concentrate for IV administration. intervention 3: Supplied as a 10 mg/mL liquid concentrate for IV administration.

Protocol document:
Prot_000.pdf: 
3URGXFW$%3
&OLQLFDO6WXG\3URWRFRO
'DWH0DUFK
3DJHRI
&RQILGHQWLDO

7,7/(3$*(
$5$1'20,=(''28%/(%/,1'678'<72&203$5(
3+$50$&2.,1(7,&6$1'3+$50$&2'<1$0,&6()),&$&<$1'
6$)(7<2)$%3:,7+5,78;,0$%,168%-(&76:,7+02'(5$7(
726(9(5(5+(80$72,'$57+5,7,6
7HVW'UXJ
$%3
3URWRFRO1XPEHU

(XGUD&7QXPEHU

6WXG\3KDVH

'DWHDQG9HUVLRQ
0DUFK9HUVLRQ
6SRQVRU
$PJHQ,QF
2QH$PJHQ&HQWHU'ULYH
7KRXVDQG2DNV&$86
&OLQLFDO5HVHDUFK2UJDQL]DWLRQ&52
35$
3DUN/DNH$YHQXH6XLWH
5DOHLJK1&86
0HGLFDO0RQLWRU0HGLFDO([SHUW
1RUWK$PHULFD
0'
35$
3KRQH
)$;
(XURSH
0'
3KRQH
)D[
6DIHW\&RQWDFW
1RUWK$PHULFD
3KRQH 
)D[

(PDLO &+26DIHW\#35$,QWOFRP
(XURSH
)$;
3KRQH
(PDLO &+26DIHW\#35$,QWOFRP
7KLVVWXG\ZLOOEHFRQGXFWHGLQFRPSOLDQFHZLWKWKHSURWRFRO*RRG&OLQLFDO3UDFWLFH
*&3DVVHWIRUWKLQWKH,QWHUQDWLRQDO&RXQFLOIRU+DUPRQLVDWLRQ,&+JXLGHOLQHVRQ
*&3,&+(DQGDSSOLFDEOHORFDOUHJXODWRU\UHTXLUHPHQWV
&21),'(17,$/
7KLVGRFXPHQWLVDFRQILGHQWLDOFRPPXQLFDWLRQRI$PJHQ,QF$FFHSWDQFHRIWKLVGRFXPHQWFRQVWLWXWHV
DJUHHPHQWE\WKHUHFLSLHQWWKDWQRXQSXEOLVKHGLQIRUPDWLRQFRQWDLQHGKHUHLQVKDOOEHSXEOLVKHGRU
GLVFORVHGZLWKRXWSULRUZULWWHQDSSURYDOH[FHSWWKDWWKLVGRFXPHQWPD\EHGLVFORVHGWRWKHDSSURSULDWH
,QVWLWXWLRQDO5HYLHZ%RDUGV,QGHSHQGHQW(WKLFV&RPPLWWHHVXQGHUWKHFRQGLWLRQWKDWWKH\NHHSLW
FRQILGHQWLDO
PPD
PPD
PPD
PPD
1&71XPEHU
7KLV1&7QXPEHUKDVEHHQDSSOLHGWRWKHGRFXPHQW
IRUSXUSRVHVRISRVWLQJRQFOLQLFDOWULDOVJRY


PPD
PPD
PPD
PPD


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 3 of 77 
Confidential 
 
Investigator 
I have read and agree to the protocol 20130108, entitled “A Randomized, Double-Blind 
Study to Compare Pharmacokinetics and Pharmacodynamics, Efficacy and Safety of ABP 
798 with Rituximab in Subjects with Moderate to Severe Rheumatoid Arthritis.” I am aware 
of my responsibilities as an Investigator under the guidelines of GCP, local regulations (as 
applicable) and the study protocol.  I agree to conduct the study according to these 
responsibilities and to appropriately direct and assist the staff under my control, who will 
be involved in the study. 
 
Clinical Site:  
 
 
 
Site Number: 
 
 
Site Principal Investigator: 
 
 
 
 
Print Name 
 
Title 
 
 
 
 
Signature 
 
Date 
 
 
Coordinating Investigator Signature: 
 
 
 
 
Print Name 
 
Title 
 
Institution/ Country 
 
 
 
Signature 
 
Date 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 4 of 77 
Confidential
2 
SYNOPSIS 
NAME OF SPONSOR:  Amgen 
PROTOCOL No.: 20130108 
NAME OF STUDY TREATMENT:  ABP 798
TITLE OF STUDY: A Randomized, Double-Blind Study to Compare Pharmacokinetics and 
Pharmacodynamics, Efficacy and Safety of ABP 798 with Rituximab in Subjects with Moderate to 
Severe Rheumatoid Arthritis 
STUDY CENTERS:  Approximately 80 sites in Europe and North America 
STUDY PERIOD:  Approximately 300 subjects will be randomized in a 
1:1:1 ratio to receive ABP 798 or rituximab (US) or rituximab (EU).  
The end of trial will be the date when the last subject has completed 
their last study assessment. 
PHASE OF 
DEVELOPMENT:  
Phase 1/3 
PLANNED STUDY DATES: 29 April 2016 to 28 February 2018.  The expected enrollment 
duration is 12 months, and each subject will participate for up to 52 weeks.  
OBJECTIVES:  
Primary Objective:  The primary objective for this study is to demonstrate pharmacokinetic (PK) 
similarity (as assessed principally by area under the serum concentration-time curve [AUC] from 
time 0 extrapolated to infinity [AUCinf] and the maximum observed serum concentration [Cmax] 
following the 2nd infusion of 1st dose) of ABP 798 following 2 intravenous (IV) infusions of 
1000 mg each, relative to that of 2 IV infusions of 1000 mg each of rituximab (US) and of 
rituximab (EU). 
Secondary Objective(s):  The secondary objectives are 

to demonstrate PK similarity between rituximab (US) and rituximab (EU) as
assessed by AUCinf and by Cmax after second infusion of the first dose

to assess the clinical efficacy of ABP 798 compared with rituximab

to assess the safety and immunogenicity of ABP 798 compared with rituximab.
STUDY DESIGN AND METHODOLOGY:  This is a randomized, double-blind, active-controlled 
3-arm study in adult subjects with moderate to severe rheumatoid arthritis (RA) who have had an 
inadequate response or intolerance to other disease-modifying anti-rheumatic drugs (DMARDs), 
which must include intolerance or inadequate response to one or more tumor necrosis factor 
(TNF) inhibitor therapies.  Approximately 300 subjects (100 per treatment group) will be enrolled.  
The subjects will be randomized to receive either ABP 798 1000 mg x 2 (treatment group A) 
infusions given 2 weeks apart, or rituximab (US) (treatment group B), or rituximab (EU) (treatment 
group C) 1000 mg x 2, given 2 weeks apart in a double-blinded fashion.  Randomization will be 
stratified by geographic region, seropositivity (rheumatoid factor [RF]-positive and/or cyclic 
citrullinated peptide [CCP]-positive vs. RF-negative, and CCP-negative), and number of prior 
biologic therapies used for RA (1 vs. > 1).   
An independent data monitoring committee (DMC) will evaluate the safety data throughout the 
study, including an initial safety analysis after the first 18 subjects have received the first dose 
(1000 mg x 2 infusions of either ABP 798 or rituximab [EU] or rituximab [US]). 
At week 24, the subjects in treatment groups A and C will continue with and receive the second 
dose of the same treatment, and the subjects in treatment group B will transition to treatment 
group A1 and receive ABP 798 1000 mg x 2 as their second dose.  Retreatment may occur 
earlier, ie, anytime from week 16 to week 24, in individual subjects, if necessary in the opinion of 
the Investigator. 
The end of study (EOS) will be at week 48 (or 24 weeks after the first infusion of the second dose 
for subjects retreated before week 24), and a final analysis will be performed when all subjects 
have completed or have had the opportunity to complete the week 48/EOS assessments.
STUDY POPULATION AND MAIN CRITERIA FOR INCLUSION/EXCLUSION:  
Subjects cannot be randomized before all inclusion criteria (including test results) are confirmed. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 5 of 77 
Confidential 
 
Inclusion Criteria:  
1. Subjects must sign an Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC)-approved informed consent form before any study specific 
procedures are preformed 
2. Men or women ≥ 18 and ≤ 80 years old 
3. Subjects must be diagnosed with RA as determined by meeting 2010 American 
College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 
classification criteria for RA 
4. Duration of RA of at least 6 months 
5. Active RA defined as ≥ 6 swollen joints and ≥ 6 tender joints (based on 66/68 joint 
count excluding distal interphalangeal joints) at screening and baseline and at least 
one of the following at screening:  
 
erythrocyte sedimentation rate (ESR) ≥ 28 mm/hr 
 
serum C-reactive protein (CRP) > 1.0 mg/dL 
6. Subjects have had an inadequate response or intolerance to other DMARDs (which 
must include intolerance or inadequate response to one or more TNF inhibitor 
therapies) 
7. Subjects must be taking methotrexate (MTX) for ≥ 12 consecutive weeks and be on a 
stable dose of MTX 7.5 to 25 mg/week for ≥ 8 weeks prior to receiving the 
investigational product (IP), and be willing to remain on a stable dose throughout the 
study 
8. Subjects on non-steroidal anti-inflammatory drugs (NSAIDs) or low potency 
analgesics such as tramadol, soma compounds, fioricet, fiorinal, should be on stable 
doses for ≥ 2 weeks prior to screening 
9. Subjects on oral corticosteroids, (≤ 10 mg prednisone or equivalent), should be on 
stable doses for ≥ 4 weeks prior to screening 
10. Subject has no known history of active tuberculosis 
11. Subject has a negative test for tuberculosis during screening defined as either: 
 
negative purified protein derivative (PPD) < 5 mm of induration at 48 to 
72 hours after test is placed) 
OR 
 
negative Quantiferon test 
12. Subjects with a positive PPD and a history of Bacillus Calmette-Guérin vaccination 
are allowed with a negative Quantiferon test 
13. Subjects with a positive PPD test (without a history of Bacillus Calmette-Guérin 
vaccination) or subjects with a positive or indeterminate Quantiferon test are allowed 
if they have all of the following:   
 
no symptoms per tuberculosis worksheet provided by the Sponsor, Amgen 
 
documented history of treatment with a TB prophylaxis regimen, with at least 
4 weeks of prophylaxis therapy completed at the time of screening.  If a 
subject has completed at least 4 weeks of prophylaxis therapy, and their 
regimen requires >4 weeks therapy, the subject must be deemed able and 
willing to complete the entire prophylaxis regimen in accordance with local 
guidance 
 
no known exposure to a case of active tuberculosis after most recent 
prophylaxis  
 
no evidence of active tuberculosis on chest radiograph within 3 months prior 
to the first dose of IP 
 
Exclusion Criteria: 
Rheumatoid arthritis related 
1. Class IV RA (Hochberg et al, 1992) according to ACR revised response criteria  
2. Felty’s syndrome (RA, splenomegaly, and granulocytopenia) 
3. History of prosthetic or native joint infection 
Other medical conditions 
4. Planned surgical intervention during the duration of the study 
5. Active infection or history of infections as follows:


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 6 of 77 
Confidential 
 
 
any active infection for which systemic anti-infectives were used within 4 
weeks prior to first dose of IP  
 
a serious infection, defined as requiring hospitalization or IV anti-infectives 
within 8 weeks prior to the first dose of IP  
 
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 
6. Known history of human immunodeficiency virus 
7. Hepatitis B surface antigen (HbsAg) or Hepatitis B core antibody (anti-HBc) positivity 
at screening (unless documentation of hepatitis B virus immunization) or Hepatitis C 
virus (HCV) antibody positivity at screening 
8. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, 
cardiovascular disease including severe heart failure (New York Heart Association 
[NYHA] class IV), or severe uncontrolled cardiac disease, renal disease, or liver 
disease  
9. Malignancy within 5 years EXCEPT treated and considered cured cutaneous 
squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal 
carcinoma 
10. History of neurologic symptoms suggestive of central nervous system demyelinating 
disease 
11. Major chronic inflammatory disease or connective tissue disease other than RA, with 
the exception of secondary Sjögren’s syndrome 
12. Concurrent medical condition that, in the opinion of the Investigator, could cause this 
study to be detrimental to the subject 
Laboratory abnormalities 
13. Laboratory abnormalities at screening, including any of the following: 
 
hemoglobin < 9 g/dL 
 
platelet count < 100,000/mm3 
 
white blood cell count < 3,000 cells/mm3 
 
aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 
≥ 2.0 x the upper limit of normal 
 
creatinine clearance < 50 mL/min (Cockroft-Gault formula) 
 
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. Any of the following within 28 days prior to first dose of IP: 
 
intra-articular (IA) hyaluronic acid injections 
 
IA, intramuscular (IM), or IV corticosteroids, including adrenocorticotropic 
hormone 
15. Non-biologic DMARDs, including Janus kinase inhibitors such as tofacitinib, other 
than MTX within 28 days prior to first dose of IP, except as below: 
 
leflunomide (unless an active washout with cholestyramine has been 
performed), cyclosporine, azathioprine, tacrolimus excluded within 3 months 
prior to first dose of IP  
 
use of IM or oral gold excluded within 6 months prior to first dose of IP  
 
cytotoxic agents such as cyclophosphamide, D-penicillamine excluded within 
6 months prior to first dose of IP  
 
received IV gamma-globulin or Prosorba column therapy excluded within 
3 months prior to first dose of IP 
16. Use of commercially available or investigational biologic therapies for RA as follows: 
 
anakinra, etanercept within 1 month prior to first dose of IP 
 
infliximab, abatacept, tocilizumab, golimumab, certolizumab, adalimumab 
within 3 months prior to first dose of IP 
 
other experimental or commercially available biologic therapies for RA within 
3 months or 5 half-lives (whichever is longer) prior to first dose of IP 
17. Live vaccines within 28 days prior to the first dose of IP


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 7 of 77 
Confidential 
 
18. Chronic use of high potency narcotic analgesics such as morphine or morphine 
derived medications, fentanyl, codeine, hydromorphone, levorphanol, meperidine, 
methadone, oxycodone or hydrocodone at screening 
19. Previous receipt of rituximab, a biosimilar of rituximab, or ocrelizumab  
20. Currently is enrolled in or has not yet completed at least 30 days or 5 half-lives 
(whichever is longer) since ending other investigational device or investigational drug, 
including vaccines, or subject is receiving other investigational agent(s) 
General 
21. For women:  pregnant or breast feeding, or planning to become pregnant while 
enrolled in the study and for 12 months after the last dose of IP 
22. Sexually active subjects and their partners who are of childbearing potential (ie, 
neither surgically sterile nor postmenopausal) and not agreeing to use adequate 
contraception (eg, true abstinence, sterilization, birth control pills, Depo-Provera 
injections, or contraceptive implants) while on study and for 12 months after the last 
dose of investigational product.   
23. Known sensitivity to mammalian cell derived drug products or hypersensitivity to the 
active substance or to any of the excipients of ABP 798 or rituximab 
24. Any physical or psychiatric disorder which, in the opinion of the Investigator, will 
prevent the subject from completing the study or interfere with the interpretation of 
the study results  
25. Any disorder that compromises the ability of the subject to give written informed 
consent and/or to comply with study procedures 
26. Active substance abuse, in the opinion of the Investigator (within 24 weeks of 
screening) 
NUMBER OF SUBJECTS:  Approximately 300 subjects will be randomized in a 1:1:1 ratio to 
receive ABP 798, rituximab (US), or rituximab (EU), stratified by geographic region, seropositivity 
(RF-positive and/or CCP-positive vs. RF-negative and CCP-negative) and number of prior 
biologic therapies used for RA (1 vs. > 1).  The sample size will provide > 90% power to 
demonstrate similarity on the primary PK endpoints, based on an assumption of between-subject 
variability (as measured by coefficient of variation) of 40%, true geometric mean ratio (GMR) of 1 
among ABP 798, rituximab (US), or rituximab (EU), a margin of (0.8, 1.25), and 15% dropout by 
week 24.  The PK similarity will be tested between ABP 798 versus rituximab (US) and ABP 798 
versus rituximab (EU), each with a significance level of 0.05.  The similarity between rituximab 
(US) and rituximab (EU) will be evaluated as well.
STUDY TREATMENT(S):  
Test Product, Dose and Mode of Administration: 
ABP 798 (Treatment A) 500 mg/mL given at 1000 mg IV x 2 infusions 2 weeks apart 
Reference Therapy, Dose and Mode of Administration: 
Rituximab (US) (Treatment B) or rituximab (EU) (Treatment C) 500 mg/mL given at 1000 mg IV x 
2 infusions 2 weeks apart 
DURATION OF TREATMENT:  Subjects will receive a first dose (2 infusions at days 1 and 15), 
followed by a second dose (2 infusions 2 weeks apart beginning at week 24 or earlier, ie, anytime 
from week 16 to week 24, in individual subjects, if necessary in the opinion of the Investigator), 
with assessment until week 48 (or 24 weeks after the first infusion of the second dose for subjects 
retreated before week 24), plus a screening period of up to 4 weeks, for a total of up to 52 weeks.  
A total of 2 doses will be administered during the study; each dose will consist of 2 infusions, 
2 weeks apart. 
STUDY EVALUATIONS:  
Primary Criteria:  
 
AUCinf, Cmax following the second infusion of the first dose 
Secondary Criteria: 
 
Percent of subjects with complete depletion in CD19+ cell count from day 1 to day 3 
 
Disease Activity Score (DAS)28-CRP change from baseline at week 24 
 
ACR20, ACR50 and ACR70   
 
AUC from time 0 on day 1 prior to the first infusion of the first dose to 14 days postdose 
(day 15) (AUC0-14 day), AUC from time 0 to week 12 (AUC0-12 wk), Cmax following the first 
infusion of the first dose 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 8 of 77 
Confidential 
 
Safety Criteria: 
 
Treatment-emergent adverse events (AEs) and serious adverse events (SAEs) 
 
Clinically significant changes in laboratory values and vital signs  
 
Incidence of antidrug antibodies 
STATISTICAL METHODS:  
The PK similarity will be demonstrated by comparing the 90% confidence interval (CI) for the 
GMR of test (ABP 798)-to-reference (rituximab [US] or rituximab [EU]) and rituximab [US] to 
rituximab [EU] for AUCinf and for Cmax following the second infusion of the first dose with the 
bounds of 0.8 to 1.25, where α=0.05.  PK parameters will be calculated using non-
compartmental methods.  Point estimates and CIs for the GMR will be estimated from an 
analysis of covariance model using the PK Analysis Set, consisting of all randomized subjects 
with an evaluable serum concentration-time profile.  
 
 
 
Clinical equivalence will be evaluated for DAS28-CRP at week 24 using the Full Analysis Set 
consisting of all randomized subjects.  If PK similarity is established between rituximab (US) 
and rituximab (EU), the 2 arms will be combined into a single reference arm for the 
primary assessment of clinical equivalence between ABP 798 and rituximab.  The results 
for ABP 798 vs. rituximab (EU) and ABP 798 vs. rituximab (US) will be provided for 
descriptive purposes. If PK similarity is not established, the ABP 798 arm will be 
compared to each of the individual rituximab arms separately to establish clinical 
equivalence of ABP 798 to the individual reference arms.   
 
With the planned sample size, there is 94% probability that the 90% CI of the difference 
between the ABP 798 arm and the pooled rituximab (rituximab[EU] and rituximab[US]) 
arm and 83% probability that the 90% CI of the difference between test (ABP 798) and 
reference (US-licensed rituximab or EU-authorized rituximab) in DAS28-CRP change from 
baseline at week 24 will fall into the equivalence margin of ± 0.6 (EULAR response criteria), 
assuming a standard deviation of 1.4 (Volkmann et al, 2010). DAS28-CRP at other timepoints 
and ACR20, 50 and 70 will be summarized descriptively.  
 
In addition, all categorical variables will be summarized using the number and percent of 
subjects falling into each category and all continuous variables will be summarized using mean, 
standard error or standard deviation, median, minimum, maximum, and number of subjects.  
Safety endpoints will be summarized descriptively as well, based on all randomized subjects 
who received at least one infusion of IP (ie, Safety Analysis Set). 
DATE AND VERSION: 20 March 2018; Version 4.0
 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 9 of 77 
Confidential
3 
TABLE OF CONTENTS 
1 
TITLE PAGE .................................................................................................. 1 
2 
SYNOPSIS ..................................................................................................... 4 
3 
TABLE OF CONTENTS ................................................................................. 9 
4 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................... 14 
5 
ETHICS ........................................................................................................ 17 
5.1 
Ethics Committee ....................................................................................... 17 
5.2 
Ethical Conduct of the Study .................................................................... 17 
5.3 
Subject Information and Consent ............................................................. 17 
6 
INTRODUCTION .......................................................................................... 19 
6.1 
Disease Review .......................................................................................... 19 
6.2 
Rituximab .................................................................................................... 19 
6.3 
Compound Review ..................................................................................... 20 
6.4 
Study Rationale .......................................................................................... 20 
7 
STUDY OBJECTIVES ................................................................................. 22 
7.1 
Primary Study Objective ............................................................................ 22 
7.2 
Secondary Study Objectives ..................................................................... 22 
8 
INVESTIGATIONAL PLAN .......................................................................... 23 
8.1 
Overall Study Design and Plan ................................................................. 23 
8.2 
Discussion of Study Design ...................................................................... 24 
8.3 
Study Duration ............................................................................................ 24 
8.4 
Study Population ........................................................................................ 25 
8.4.1 
Inclusion Criteria ........................................................................................... 25 
8.4.2 
Exclusion Criteria ......................................................................................... 26 
8.4.3 
Withdrawal and Replacement of Subjects .................................................... 28 
8.4.3.1 
Criteria for Subject Withdrawal ..................................................................... 28 
8.4.3.2 
Evaluations at Withdrawal ............................................................................ 28 
8.4.3.3 
Replacement of Subjects ............................................................................. 29 
8.5 
Treatment .................................................................................................... 29 
8.5.1 
Treatments Administered ............................................................................. 29 
8.5.2 
Study Treatment Formulation ....................................................................... 30 
8.5.2.1 
Study Drug ................................................................................................... 30 
8.5.2.2 
Comparator .................................................................................................. 30 
8.5.3 
Study Treatment Labeling and Packaging ................................................... 31 
8.5.4 
Blinding of Study Medication ........................................................................ 31 
8.5.5 
Study Treatment Storage and Accountability ............................................... 31 
8.5.5.1 
Study Treatment Storage ............................................................................. 31 
8.5.5.2 
Study Treatment Accountability .................................................................... 32 
8.5.6 
Dose Adjustments and Dose Escalation ...................................................... 32 
8.5.7 
Prior and Concomitant Therapy ................................................................... 32 
8.5.7.1 
Permitted Concomitant Treatments (Medications and Therapies) ............... 32 
8.5.7.2 
Prohibited Concomitant Medications ............................................................ 33 
8.5.7.3 
Rescue Medication ....................................................................................... 33 
8.5.7.4 
Prophylactic Treatment ................................................................................ 34 
8.5.7.5 
Other Concomitant Medications and Treatments ......................................... 34 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 10 of 77 
Confidential 
 
8.5.8 
Treatment Compliance ................................................................................. 34 
8.5.9 
Assignment to Treatment ............................................................................. 34 
8.5.10 
Unblinding Procedures ................................................................................. 35 
8.6 
Efficacy, Pharmacokinetic/Pharmacodynamic, and Safety Variables ... 35 
8.6.1 
Efficacy, Pharmacokinetic/Pharmacodynamic, and Safety Measurements 
Assessed ...................................................................................................... 35 
8.6.1.1 
Pharmacokinetic/Pharmacodynamic Endpoints ........................................... 35 
8.6.1.2 
Efficacy Measurements ................................................................................ 39 
8.6.1.2.1 
Efficacy Criteria ............................................................................................ 39 
8.6.1.3 
Safety Measurements .................................................................................. 39 
9 
STUDY EVALUATIONS BY VISIT .............................................................. 40 
9.1 
Screening .................................................................................................... 40 
9.1.1 
Screen Failures ............................................................................................ 40 
9.2 
Baseline (Day 1, first day of treatment, Week 0) ..................................... 41 
9.3 
Day 2 ............................................................................................................ 42 
9.4 
Day 3 ............................................................................................................ 42 
9.5 
Day 15 (Week 2) .......................................................................................... 42 
9.6 
Day 16 .......................................................................................................... 43 
9.7 
Day 17 .......................................................................................................... 43 
9.8 
Week 4 ( 2 days) ....................................................................................... 43 
9.9 
Week 8 ( 2 days) ....................................................................................... 43 
9.10 
Week 12 ( 2 days) ..................................................................................... 44 
9.11 
Week 24 ....................................................................................................... 44 
9.12 
Week 26 ....................................................................................................... 45 
9.13 
Week 30 ( 2 days) ..................................................................................... 45 
9.14 
Week 40 ( 3 days) ..................................................................................... 46 
9.15 
Week 48 (EOS) ............................................................................................ 46 
10 
METHODS OF ASSESSMENT .................................................................... 47 
10.1 
Rheumatoid Arthritis Assessments ......................................................... 47 
10.2 
Pregnancy Test ........................................................................................... 47 
10.3 
Physical Examination ................................................................................ 48 
10.4 
Vital Signs ................................................................................................... 48 
10.5 
Electrocardiogram ...................................................................................... 48 
10.6 
Tuberculosis Testing ................................................................................. 48 
10.7 
Chest Radiography .................................................................................... 49 
10.8 
Clinical Laboratory Testing ....................................................................... 49 
10.9 
Blood Samples for Pharmacokinetic Analysis ........................................ 50 
10.10 
Blood Samples for Pharmacodynamic Analysis ..................................... 50 
11 
SAFETY DATA COLLECTION, RECORDING, AND REPORTING ............ 51 
11.1 
Adverse Events .......................................................................................... 51 
11.1.1 
Definition of Adverse Events ........................................................................ 51 
11.1.2 
Reporting Procedures for Adverse Events ................................................... 51 
11.2 
Serious Adverse Events ............................................................................ 52 
11.2.1 
Definition of Serious Adverse Events ........................................................... 52 
11.2.2 
Reporting Procedures for Serious Adverse Events ...................................... 52 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 11 of 77 
Confidential
11.3 
Adverse Events of Special Interest .......................................................... 54 
11.4 
Pregnancy Reporting ................................................................................. 54 
12 
DATA MANAGEMENT AND STATISTICAL ANALYSIS ............................ 56 
12.1 
Data Management ....................................................................................... 56 
12.2 
Sample Size Estimation ............................................................................. 56 
12.3 
Statistical Analysis Plan ............................................................................ 56 
12.4 
Randomization ............................................................................................ 56 
12.5 
Analysis Populations ................................................................................. 57 
12.5.1 
Full Analysis Set ........................................................................................... 57 
12.5.2 
Per-protocol Set ........................................................................................... 57 
12.5.3 
Safety Analysis Set ...................................................................................... 57 
12.5.4 
Pharmacokinetic Analysis Set ...................................................................... 57 
12.5.5 
Per-protocol Pharmacokinetic Analysis Set ................................................. 57 
12.6 
Statistical Methods ..................................................................................... 58 
12.6.1 
Missing Data ................................................................................................. 58 
12.6.2 
Demographic and Baseline Data .................................................................. 58 
12.6.3 
Subject Disposition ....................................................................................... 58 
12.6.4 
Pharmacokinetics ......................................................................................... 59 
12.6.5 
Pharmacodynamics ...................................................................................... 59 
12.6.6 
Efficacy ......................................................................................................... 59 
12.6.7 
Safety ........................................................................................................... 60 
12.6.7.1 
Investigational Product Administration ......................................................... 61 
12.6.7.2 
Adverse Events ............................................................................................ 61 
12.6.7.3 
Immunogenicity ............................................................................................ 61 
12.6.7.4 
Concomitant Medications and Therapies ..................................................... 61 
12.6.7.5 
Clinical Laboratory Test ................................................................................ 61 
12.6.7.6 
Vital Signs and Physical Examinations ........................................................ 62 
12.6.8 
Interim Analysis ............................................................................................ 62 
12.6.9 
Data Monitoring Committee .......................................................................... 62 
13 
MONITORING PROCEDURES (QUALITY ASSURANCE) ......................... 63 
13.1 
Routine Monitoring .................................................................................... 63 
13.2 
Inspections and Auditing Procedures ...................................................... 63 
14 
STUDY MANAGEMENT AND MATERIALS ............................................... 65 
14.1 
Electronic Case Report Forms .................................................................. 65 
14.2 
Data Collection ........................................................................................... 65 
14.3 
Source Documents Maintenance .............................................................. 66 
14.4 
Record Maintenance .................................................................................. 66 
14.5 
Confidentiality ............................................................................................ 67 
15 
ADMINISTRATION PROCEDURES ............................................................ 68 
15.1 
Regulatory Approval .................................................................................. 68 
15.2 
Protocol Amendments ............................................................................... 68 
15.3 
Protocol Adherence and Deviations ......................................................... 69 
15.4 
Publication Policy ...................................................................................... 69 
15.5 
Clinical Study Report ................................................................................. 70 
15.6 
Contractual and Financial Details ............................................................. 70 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 12 of 77 
Confidential
15.7 
Compensation ............................................................................................ 70 
15.8 
Discontinuation of the Study .................................................................... 70 
15.9 
Study Center File Management ................................................................. 70 
16 
REFERENCE LIST ...................................................................................... 72 
17 
APPENDICES .............................................................................................. 74 
17.1 
Appendix 1: Elements of Informed Consent ............................................ 74 
17.2 
Appendix 2: American College of Rheumatology Revised Criteria for 
the Classification of Functional Capacity in RA ...................................... 75 
17.3 
Appendix 3: DAS28 and ACR Core Set Measurements .......................... 76 
17.4 
Appendix 4: Subjective Assessment Scales ........................................... 77 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 13 of 77 
Confidential
LIST OF TABLES 
Table 1.  Schedule of Assessments and Procedures ................................................ 36 
LIST OF FIGURES 
Figure 1.  Study Diagram .............................................................................................. 24 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 14 of 77 
Confidential
4 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Term 
Definition 
ACR 
American College of Rheumatology 
ACR20 
20% improvement in ACR core set measurements 
ACR50 
50% improvement in ACR core set measurements 
ACR70 
70% improvement in ACR core set measurements 
AE 
Adverse event  
ALT 
Alanine aminotransferase  
anti-HBc 
Hepatitis B core antibody 
AST 
Aspartate aminotransferase  
AUC 
Area under the serum concentration-time curve 
AUC0-14 day 
AUC from time 0 on day 1 prior to the first infusion of the 
first dose to 14 days postdose (day 15) 
AUC0-12wk 
AUC from time 0 on day 1 prior to the first infusion of the 
first dose to week 12  
AUCinf 
AUC from time 0 on day 1 prior to the first infusion of the 
first dose extrapolated to infinity 
CCP 
Cyclic citrullinated peptide 
CDC
Complement-mediated cytotoxicity
CFR 
Code of Federal Regulations 
CI
Confidence interval
Cmax 
Maximum observed serum concentration 
COX-2
Cyclooxygenase-2
CRO 
Clinical research organization 
CRP
C-reactive protein
CTCAE 
Common Terminology Criteria for Adverse Events  
DAS 
Disease Activity Score  
DMARD 
Disease-modifying antirheumatic drug 
DMC 
Data Monitoring Committee 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 15 of 77 
Confidential 
 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EOI 
End of infusion 
EOS 
End of study 
ESR 
Erythrocyte sedimentation rate 
EULAR 
European League Against Rheumatism  
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEE 
Generalized estimating equation 
GMR 
Geometric mean ratio 
HAQ-DI 
Health Assessment Questionnaire – Disability Index 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HCG 
Human chorionic gonadotrophin 
IA 
Intra-articular 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
Ig 
Immunoglobulin 
IL 
Interleukin 
IM 
Intramuscular  
IP 
Investigational Product 
IRB 
Institutional Review Board 
IV 
Intravenous 
IXRS 
Interactive voice and web response system 
λz 
Terminal elimination rate constant 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 16 of 77 
Confidential 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTX 
Methotrexate 
NSAID 
Non-steroidal anti-inflammatory drug 
NYHA 
New York Heart Association  
PD 
Pharmacodynamic(s) 
PIN 
Personal Identification Number 
PK 
Pharmacokinetic(s) 
PPD 
Purified protein derivative  
RA 
Rheumatoid arthritis 
RD 
Risk difference 
RF 
Rheumatoid factor 
rituximab (EU) 
European Medicines Agency EU-authorized rituximab 
rituximab (US) 
Food and Drug Administration US-licensed rituximab 
RR 
Risk ratio 
SAA 
Serum amyloid protein  
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous(ly) 
Scn 
Screening 
SUSAR 
Suspected unexpected serious adverse reactions 
t1/2 
Terminal elimination half-life 
tmax 
Time of Cmax 
TNF 
Tumor necrosis factor 
VAS 
Visual analogue scale 
WHO 
World Health Organization 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 17 of 77 
Confidential
5 
ETHICS 
5.1 
Ethics Committee 
This study will be conducted in compliance with Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) and International Council for Harmonisation 
(ICH) Good Clinical Practice (GCP) Guidelines - including Title 21 Part 56 of the US 
Code of Federal Regulations (CFR) relating to IRBs/IECs and GCP as described in the 
US Food and Drug Administration (FDA) CFR (21 CFR § 50, 56, 312) - in accordance 
with applicable ICH regulations regarding clinical safety data management (E2A, 
E2B[R3]), European Community directives 2001/20, 2001/83, 2003/94 and 2005/28 as 
enacted into local law, and with ICH guidelines regarding scientific integrity (E4, E8, E9, 
and E10).  In addition, this study will adhere to all local regulatory requirements, and 
requirements for data protection. 
Before initiating a trial/study, the Investigator/institution must have written and dated 
approval/favorable opinion from the IRB/IEC for the study protocol/amendment(s), 
written informed consent form (ICF), any consent form updates, subject recruitment 
procedures (eg, advertisements), and any written information to be provided to subjects 
and a statement from the IRB/IEC that they comply with GCP requirements.  The 
IRB/IEC approval must identify the protocol version as well as the documents reviewed. 
5.2 
Ethical Conduct of the Study 
This study will be conducted in accordance with the Note for Guidance on GCP (ICH 
Harmonised Tripartite Guideline E6 (R1); FDA CFR (21 CFR § 50, 56, 312)), the general 
principles indicated in the Declaration of Helsinki and all applicable regulatory 
requirements. 
5.3 
Subject Information and Consent 
The Investigator will explain the benefits and risks of participation in the study to each 
subject or the subject’s legally acceptable representative and obtain written informed 
consent.  Written informed consent must be obtained prior to the subject entering the 
study and before initiation of any study related procedure (including administration of 
investigational product).  
The Sponsor will provide a sample ICF, based on the elements of informed consent in 
Section 17.1.  The final, version dated, form must be agreed to by the Sponsor and the 
IRB/IEC and will contain all elements in the sample form, in language readily understood 
by the subject.  Each subject’s original consent form, personally signed and dated by the 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 18 of 77 
Confidential 
 
subject or by the subject’s legally acceptable representative, and by the person who 
conducted the informed consent discussion, will be retained by the Investigator.  The 
Investigator will supply all enrolled subjects with a copy of their signed ICF. 
The ICF may need to be revised during the study should important new information 
become available that may be relevant to the safety of the subject.  In this instance, 
approval should always be given by the IRB/IEC, and existing subjects informed of the 
changes and re-consented.  This is documented in the same way as previously 
described. 
The Investigator should, with the consent of the subject, inform the subject’s primary 
physician about the subject’s participation in the clinical study as needed. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 19 of 77 
Confidential
6 
INTRODUCTION 
6.1 
Disease Review 
Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology in 
which patients exhibit systemic features such as fatigue, low grade fever, weight loss, 
anemia, and increased systemic levels of acute phase reactants (eg, erythrocyte 
sedimentation rates [ESR] and C-reactive protein [CRP]; Aletaha et al, 2010).  Although 
the disease is systemic in nature, the primary target tissues are the synovial membrane, 
cartilage, and bone (McInnes et al, 2007), which exhibit uncontrolled synovium/pannus 
proliferation and excess fluid production, and ultimately undergo progressive destructive 
arthropathy (Aletaha et al, 2010; Choy et al, 2001).   
The pathologic processes in RA appear to be primarily driven by B cells, by autoantibody 
production, by antigen presentation to T cells, and by promoting inflammation through 
the activation of macrophages and dendritic cells (Tuscano and Sands, 2009).  
Targeting of B cells has become a major therapeutic approach in RA.  Therapeutic 
monoclonal antibodies have been developed with the aim of depleting B cells and 
reducing the RA disease process.  The depleting activity of B cell-targeted monoclonal 
antibodies largely relies on 2 Fc-dependent mechanisms: antibody-dependent cell-
mediated cytotoxicity and complement-mediated cytotoxicity (CDC).  The engagement of 
effector cells by therapeutic monoclonal antibodies involves the interaction of the 
monoclonal antibodies Fc with Fcγ receptors on the surface of natural killer cells, 
monocytes/macrophages, or neutrophils (Blüml et al, 2013).  
6.2 
Rituximab 
Rituximab (Rituxan®, MabThera®) is a genetically engineered chimeric murine/human 
monoclonal immunoglobulin (Ig) G1 kappa antibody directed against the B cell specific 
CD20 antigen.  In RA patients, treatment with rituximab induces depletion of peripheral 
B lymphocytes, with the majority of patients demonstrating near complete depletion 
(CD19 counts below the lower limit of quantification, 20 cells/μL) within 2 weeks after 
receiving the first dose.  Most patients showed peripheral B cell depletion for at least 
6 months.  A small proportion of patients (~4%) had prolonged peripheral B cell 
depletion lasting more than 3 years after a single course of treatment (Biogen Idec, 
2013).  
Total serum Ig levels, IgM, IgG, and IgA were reduced at 6 months with the greatest 
change observed in IgM.  In RA patients during repeated rituximab treatment, 23.3%, 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 20 of 77 
Confidential
5.5%, and 0.5% of patients experienced decreases in IgM, IgG, and IgA concentrations 
below the lower limit of normal, respectively, at any time after receiving rituximab.  The 
clinical consequences of decreases in Ig levels in RA patients are unclear (Biogen Idec, 
2013). 
Treatment with rituximab in patients with RA is associated with reduction of certain 
biologic markers of inflammation such as interleukin (IL)-6, CRP, serum amyloid protein 
(SAA), S100 A8/S100 A9 heterodimer complex (S100 A8/9), anti-cyclic citrullinated 
peptide (anti-CCP), and rheumatoid factor (RF; Biogen Idec, 2013). 
Rituximab is indicated, in combination with methotrexate (MTX), for the treatment of 
adult patients with moderately- to severely-active RA who have had an inadequate 
response to one or more tumor necrosis factor (TNF) antagonist therapies.  Rituximab is 
approved for use in other indications such as non-Hodgkin lymphoma, chronic 
lymphocytic leukemia, granulomatosis with polyangiitis, and microscopic polyangiitis 
(Biogen Idec, 2013).   
6.3 
Compound Review 
ABP 798 is being developed as a biosimilar candidate to Rituxan®, MabThera® 
(rituximab) for the treatment of RA and other indications.  The active ingredient of 
ABP 798 is an anti-CD20 monoclonal antibody which has the same amino acid 
sequence as rituximab.  ABP 798 has the same pharmaceutical form and dosage 
strength as FDA US-licensed rituximab [rituximab (US), Rituxan®] and European 
Medicines Agency EU-authorized rituximab [rituximab (EU), MabThera®]. 
Similarity of ABP 798 to rituximab has been shown using bioanalytical methods and pre-
clinical studies.  As outlined in the guideline on similar biological medicinal products 
containing monoclonal antibodies, applicants are expected to provide data on similarity 
of pharmacokinetics (PK)/pharmacodynamics (PD), safety and efficacy.   
Refer to the Investigator’s Brochure for additional information.   
6.4 
Study Rationale 
In the US, EU, and much of the world, laws, regulations, and guidances have been or 
are being put in place to increase availability of biological treatments by developing and 
licensing biosimilar products (CHMP/437/04 Rev 1; EMEA/CHMP/BWP/247713/2012; 
EMEA/CHMP/BMWP/42832/2005 Rev.1; US FDA 2012a; US FDA 2012b).  A biosimilar 
product, generally, is one that is highly similar to a licensed biologic reference product, 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 21 of 77 
Confidential 
 
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 
analytical and nonclinical similarity of ABP 798 and rituximab are summarized in the 
Investigator’s Brochure.  The current study is designed to demonstrate the PK similarity 
and that there is no clinically meaningful difference between ABP 798 and rituximab in 
terms of safety, efficacy, and immunogenicity. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 22 of 77 
Confidential
7 
STUDY OBJECTIVES  
7.1 
Primary Study Objective 
The primary objective for this study is to demonstrate PK similarity (as assessed 
principally by area under the serum concentration-time curve [AUC] from time 0 
extrapolated to infinity [AUCinf] and the maximum observed serum concentration [Cmax], 
following the 2nd infusion of 1st dose) of ABP 798 following 2 intravenous (IV) infusions of 
1000 mg each, relative to that of 2 IV infusions of 1000 mg each of rituximab (US) and of 
rituximab (EU). 
7.2 
Secondary Study Objectives 
The secondary objectives are  

to demonstrate PK similarity between rituximab (US) and rituximab (EU) as
assessed by AUCinf and by Cmax after second infusion of the first dose

to assess the clinical efficacy of ABP 798 compared with rituximab

to assess the safety and immunogenicity of ABP 798 compared with rituximab.


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 23 of 77 
Confidential 
 
8 
INVESTIGATIONAL PLAN 
8.1 
Overall Study Design and Plan 
This is a randomized, double-blind, active-controlled 3-arm study in adult subjects with 
moderate to severe RA who have had an inadequate response or intolerance to other 
disease-modifying anti-rheumatic drugs (DMARDs) (which must include intolerance or 
inadequate response to one or more TNF inhibitor therapies).  Approximately 
300 subjects (100 per treatment group) will be enrolled.  The subjects will be randomized 
to receive either 2 IV infusions of ABP 798, 1000 mg each, given 2 weeks apart 
(treatment group A), or 2 IV infusions of rituximab (US) 1000 mg each, given 2 weeks 
apart (treatment group B) or 2 IV infusions of rituximab (EU), 1000 mg each, given 2 
weeks apart (treatment group C), in a double-blinded fashion.  A total of 2 doses will be 
administered during the study; each dose consists of 2 infusions, 2 weeks apart. 
An independent data monitoring committee (DMC) will evaluate the safety data 
throughout the study, including an initial safety analysis after the first 18 subjects have 
been dosed (1000 mg x 2 infusions of either ABP 798 or rituximab [EU] or rituximab 
[US]).   
At week 24, the subjects in treatment groups A and C will continue with and receive the 
second dose of the same treatment, and the subjects in treatment group B will transition 
to become treatment group A1 and receive the second dose with ABP 798.  Retreatment 
may occur earlier, ie, anytime from week 16 to week 24 in individual subjects if 
necessary in the opinion of the Investigator. 
The end of study (EOS) will be at week 48 (or 24 weeks after the first infusion of the 
second dose for subjects retreated before week 24), and a final analysis will be 
performed when all subjects have completed or have had the opportunity to complete 
the week 48/EOS assessments.  Figure 1 is a summary of the study design. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 24 of 77 
Confidential 
 
Figure 1.  Study Diagram 
 
 
 
 
 
 
 
 
R 
 
 
 
 
 
 
A 
 
Treatment Group A
 
 
S 
 
N 
 
ABP 798 1000 mg x 2 (N=100)
 
 
C 
 
D 
 
 
 
Treatment Group A1* 
 
 
R 
 
O 
 
 
 
ABP 798 1000 mg x 2 (N=200) 
 
 
E 
 
M 
 
 
 
 
 
 
 
E 
 
I 
 
Treatment Group B
 
 
N 
 
Z 
 
Rituximab (US) 1000 mg x 2 (N=100)
 
 
I 
 
A 
 
 
 
N 
 
T 
 
 
 
 
 
 
 
G 
 
I 
 
 
 
 
 
 
 
 
 
O 
 
Treatment Group C 
 
Treatment Group C* 
 
 
 
 
N 
 
Rituximab (EU) 1000 mg x 2 (N=100)
Rituximab (EU) 1000 mg x 2 (N=100)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
End of Study week 48 
 
 
Up to 28 
days 
                                                  Week 16-24 
Final Analysis week 48 
 
* Retreatment will begin at week 24 or earlier, ie, anytime from week 16 to week 24 in individual subjects if 
necessary in the opinion of the Investigator. 
8.2 
Discussion of Study Design 
This study is randomized and double-blind to prevent bias in treatment allocation and in 
the subjective assessment of effect.   
8.3 
Study Duration 
Subjects will receive investigational product (IP) first dose (2 infusions at days 1 and 15), 
followed by a second dose (2 infusions 2 weeks apart beginning at week 24 or earlier, ie, 
anytime from week 16 to week 24 in individual subjects if necessary in the opinion of the 
Investigator) with assessment until week 48 (or 24 weeks after the first infusion of the 
second dose for subjects retreated before week 24), plus a screening period of up to 4 
weeks, for a total of up to 52 weeks.  A total of 2 doses will be administered during the 
study; each dose consists of 2 infusions, 2 weeks apart. 
Enrollment will continue until approximately 300 subjects have been randomized to 
treatment.  The end of trial will be the date when the last subject has completed their last 
study assessment. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 25 of 77 
Confidential 
 
8.4 
Study Population 
8.4.1 
Inclusion Criteria 
Subjects MUST satisfy all of the following entry criteria before they will be allowed to 
participate in the study: 
1. Subjects must sign an IRB/IEC-approved informed consent form before any 
study specific procedures are preformed 
2. Men or women ≥ 18 and ≤ 80 years old 
3. Subjects must be diagnosed with RA as determined by meeting 2010 American 
College of Rheumatology (ACR)/European League Against Rheumatism 
(EULAR) classification criteria for RA 
4. Duration of RA of at least 6 months 
5. Active RA defined as ≥ 6 swollen joints and ≥ 6 tender joints (based on 
66/68 joint count excluding distal interphalangeal joints) at screening and 
baseline and at least one of the following at screening:  
 
ESR ≥ 28 mm/hr 
 
serum CRP > 1.0 mg/dL 
6. Subjects have had an inadequate response or intolerance to other DMARDs 
(which must include intolerance or inadequate response to one or more TNF 
inhibitor therapies) 
7. Subjects must be taking MTX for ≥ 12 consecutive weeks and be on a stable 
dose of MTX 7.5 to 25 mg/week for ≥ 8 weeks prior to receiving the 
investigational product, and be willing to remain on a stable dose throughout the 
study 
8. Subjects on non-steroidal anti-inflammatory drugs (NSAIDs) or low potency 
analgesics such as tramadol, soma compounds, fioricet, fiorinal, should be on 
stable doses for ≥ 2 weeks prior to screening 
9. Subjects on oral corticosteroids, (≤ 10 mg prednisone or equivalent), should be 
on stable doses for ≥ 4 weeks prior to screening 
10. Subject has no known history of active tuberculosis 
11. Subject has a negative test for tuberculosis during screening defined as either: 
 
negative purified protein derivative (PPD) < 5 mm of induration at 48 to 
72 hours after test is placed) 
 
OR 
 
negative Quantiferon test 
12. Subjects with a positive PPD and a history of Bacillus Calmette-Guérin 
vaccination are allowed with a negative Quantiferon test 
13. Subjects with a positive PPD test (without a history of Bacillus Calmette-Guérin 
vaccination) or subjects with a positive or indeterminate Quantiferon test are 
allowed if they have all of the following:   
 
no symptoms per tuberculosis worksheet provided by the Sponsor, Amgen 
 
documented history of treatment with a TB prophylaxis regimen, with at least 
4 weeks of prophylaxis therapy completed at the time of screening.  If a 
subject has completed at least 4 weeks of prophylaxis therapy, and their 
regimen requires >4 weeks therapy, the subject must be deemed able and 
willing to complete the entire prophylaxis regimen in accordance with local 
guidance 
 
no known exposure to a case of active tuberculosis after most recent 
prophylaxis  


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 26 of 77 
Confidential 
 
 
no evidence of active tuberculosis on chest radiograph within 3 months prior 
to the first dose of investigational product  
 
8.4.2 
Exclusion Criteria 
If any of the following apply, the subject MUST NOT enter the study: 
Rheumatoid arthritis related 
1. Class IV RA (Hochberg et al, 1992) according to ACR revised response criteria 
(Section 17.2) 
2. Felty’s syndrome (RA, splenomegaly, and granulocytopenia) 
3. History of prosthetic or native joint infection 
Other medical conditions 
4. Planned surgical intervention during the duration of the study 
5. Active infection or history of infections as follows: 
 
any active infection for which systemic anti-infectives were used within 
4 weeks prior to first dose of investigational product  
 
a serious infection, defined as requiring hospitalization or IV anti-infectives 
within 8 weeks prior to the first dose of investigational product  
 
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 
6. Known history of human immunodeficiency virus 
7. Hepatitis B surface antigen (HbsAg) or Hepatitis B core antibody (anti-HBc) 
positivity at screening (unless documentation of hepatitis B virus immunization) 
or hepatitis C virus (HCV) antibody positivity at screening 
8. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, 
cardiovascular disease including severe heart failure (New York Heart 
Association [NYHA] class IV), or severe uncontrolled cardiac disease, renal 
disease, or liver disease  
9. Malignancy within 5 years EXCEPT treated and considered cured cutaneous 
squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast 
ductal carcinoma 
10. History of neurologic symptoms suggestive of central nervous system 
demyelinating disease 
11. Major chronic inflammatory disease or connective tissue disease other than RA, 
with the exception of secondary Sjögren’s syndrome 
12. Concurrent medical condition that, in the opinion of the Investigator, could cause 
this study to be detrimental to the subject 
Laboratory abnormalities 
13. Laboratory abnormalities at screening, including any of the following: 
 
hemoglobin < 9 g/dL 
 
platelet count < 100,000/mm3 
 
white blood cell count < 3,000 cells/mm3 
 
aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 
≥ 2.0 x the upper limit of normal 
 
creatinine clearance < 50 mL/min (Cockroft-Gault formula) 
 
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 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 27 of 77 
Confidential 
 
Washouts and non-permitted drugs 
14. Any of the following within 28 days prior to first dose of investigational product: 
 
intra-articular (IA) hyaluronic acid injections 
 
IA, intramuscular (IM), or IV corticosteroids, including adrenocorticotropic 
hormone 
15. Non-biologic DMARDs, including Janus kinase inhibitors such as tofacitinib, other 
than MTX within 28 days prior to first dose of investigational product, except as 
below: 
 
leflunomide (unless an active washout with cholestyramine has been 
performed), cyclosporine, azathioprine, tacrolimus excluded within 3 months 
prior to first dose of investigational product  
 
use of IM or oral gold excluded within 6 months prior to first dose of IP  
 
cytotoxic agents such as cyclophosphamide, D-penicillamine excluded within 
6 months prior to first dose of investigational product  
 
received IV gamma-globulin or Prosorba column therapy excluded within 
3 months prior to first dose of investigational product 
16. Use of commercially available or investigational biologic therapies for RA as 
follows: 
 
anakinra, etanercept within 1 month prior to first dose of IP 
 
infliximab, abatacept, tocilizumab, golimumab, certolizumab, adalimumab 
within 3 months prior to first dose of investigational product 
 
other experimental or commercially available biologic therapies for RA within 
3 months or 5 half-lives (whichever is longer) prior to first dose of 
investigational product 
17. Live vaccines within 28 days prior to the first dose of investigational product 
18. Chronic use of high potency narcotic analgesics such as morphine or morphine 
derived medications, fentanyl, codeine, hydromorphone, levorphanol, 
meperidine, methadone, oxycodone, or hydrocodone at screening 
19. Previous receipt of rituximab, a biosimilar of rituximab, or ocrelizumab  
20. Currently is enrolled in or has not yet completed at least 30 days or 5 half-lives 
(whichever is longer) since ending other investigational device or investigational 
drug, including vaccines, or subject is receiving other investigational agent(s) 
General 
21. For women:  pregnant or breast feeding, or planning to become pregnant while 
enrolled in the study and for 12 months after the last dose of investigational 
product 
22. Sexually active subjects and their partners who are of childbearing potential (ie, 
neither surgically sterile nor postmenopausal) and not agreeing to use adequate 
contraception (eg, true abstinence, sterilization, birth control pills, Depo-Provera 
injections, or contraceptive implants) while on study and for 12 months after the 
last dose of investigational product.   
23. Known sensitivity to mammalian cell derived drug products or hypersensitivity to 
the active substance or to any of the excipients of ABP 798 or rituximab 
24. Any physical or psychiatric disorder which, in the opinion of the Investigator, will 
prevent the subject from completing the study or interfere with the interpretation 
of the study results  
25. Any disorder that compromises the ability of the subject to give written informed 
consent and/or to comply with study procedures 
26. Active substance abuse, in the opinion of the Investigator (within 24 weeks of 
screening) 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 28 of 77 
Confidential 
 
8.4.3 
Withdrawal and Replacement of Subjects 
8.4.3.1 
Criteria for Subject Withdrawal 
Subjects have the right to withdraw from the study at any time and for any reason 
without prejudice to future medical care by the physician or at the institution. 
Subjects (or a legally acceptable representative) can decline to continue receiving 
investigational product and/or other protocol required therapies or procedures at any 
time during the study, but continue participating in the study.  If this occurs, the 
Investigator is to discuss with the subject the appropriate processes for discontinuation 
from investigational product or other protocol required therapies and must discuss with 
the subject the options for continuation of the Schedule of Assessments and Procedures 
(Table 1) and collection of data, including endpoints and AEs.  The Investigator must 
document the change to the Schedule of Assessments (Table 1) and the level of follow-
up that is agreed to by the subject (eg, in person, by telephone/mail, through 
family/friends, in correspondence/communication with other physicians, from review of 
the medical records).   
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.   
Reasons for removal from protocol-required investigational products or procedural 
assessments might include: 
 
subject request to end IP administration 
 
safety concern (eg, due to an AE, failure to follow contraception, and/or protocol 
requirements)  
 
pregnancy 
Reasons for removal of a subject from the study might include: 
 
withdrawal of consent from study 
 
lost to follow-up  
 
decision by Sponsor  
8.4.3.2 
Evaluations at Withdrawal 
For any subject who is withdrawn before completing all study visits, the Investigator 
should: 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 29 of 77 
Confidential 
 
 
Perform all the procedures scheduled for week 48/EOS.  The week 48/EOS 
assessments will be performed no later than 14 days after 
withdrawal/discontinuation (unless the subject withdraws consent to do so). 
 
Complete all appropriate electronic case report form (eCRF) screens, providing 
the date of and explanation for the subject’s withdrawal/discontinuation. 
 
When indicated, arrange for appropriate follow up and/or alternative medical 
care for the discontinued subject.  
If the subject fails to attend a scheduled termination visit, there will be at least 2 attempts 
to contact the subject via telephone and 2 written communications.  If these receive no 
reply, the subject will be considered lost to follow up. 
8.4.3.3 
Replacement of Subjects 
Subjects who are withdrawn will not be replaced.  However, sufficient subjects will be 
included to ensure the minimum sample size defined (see Section 12.2). 
8.5 
Treatment 
8.5.1 
Treatments Administered 
The Investigator must ensure that the investigational products will be used only in 
accordance with the protocol. 
Subjects will be randomly assigned at Baseline (day 1) to 1 of 3 treatment groups.  The 
first dose will be administered as follows: 
 
Treatment A:  ABP 798 1000 mg IV on study days 1 and 15  
 
Treatment B:  Rituximab (US) 1000 mg IV on study days 1 and 15  
 
Treatment C:  Rituximab (EU) 1000 mg IV on study days 1 and 15  
At week 24, the subjects in treatment groups A and C will continue with and receive the 
second dose with the same treatment (ABP 798 1000 mg x 2 and rituximab (EU) 
1000 mg x 2, respectively), and the subjects in treatment group B will transition to 
treatment group A1 and receive the second dose of ABP 798 1000 mg x 2.  Retreatment 
may occur earlier, ie, anytime from week 16 to week 24 in individual subjects, if 
necessary in the opinion of the Investigator.  The EOS will be at week 48 (or 24 weeks 
after the first infusion of the second dose for subjects retreated before week 24).  A total 
of 2 doses will be administered during the study; each dose will consist of 2 infusions. 
No dose reductions or changes will be allowed.   
ABP 798/rituximab will be administered after all other procedures are completed for each 
visit.  Investigational product will be administered only as an IV infusion by a healthcare 
professional with appropriate medical support to manage severe infusion reactions.  Do 


3URGXFW$%3
&OLQLFDO6WXG\3URWRFRO
'DWH0DUFK
3DJHRI
&RQILGHQWLDO

QRWDGPLQLVWHUDVDQ,9SXVKRUEROXV6XEMHFWVVKRXOGUHFHLYHSUHPHGLFDWLRQVEHIRUH
HDFKLQIXVLRQ
3UHPHGLFDWLRQVVKRXOGEHJLYHQDFFRUGLQJWRORFDOJXLGDQFHDQGWKHDSSURYHGSURGXFW
ODEHO7KHVHVKRXOGJHQHUDOO\LQFOXGHDFHWDPLQRSKHQDQGDQDQWLKLVWDPLQHDQG
PHWK\OSUHGQLVRQHPJ,9RUHTXLYDOHQWPLQXWHVEHIRUHHDFKLQIXVLRQ
,9LQIXVLRQVVKRXOGEHSHUIRUPHGDFFRUGLQJWRORFDOJXLGDQFHDQGWKHDSSURYHGSURGXFW
ODEHO5LWX[DQ3URGXFW,QVHUW0DE7KHUD3URGXFW,QVHUW
,QYHVWLJDWLRQDOSURGXFWLQIXVLRQUHDFWLRQVVKRXOGEHKDQGOHGDFFRUGLQJWRORFDOJXLGDQFH
DQGWKHDSSURYHGSURGXFWODEHO
$OOVXEMHFWVZLOOFRQWLQXHRQDVWDEOHGRVHRI07;PJZHHNRUDORUVXEFXWDQHRXV
>6&@IRUWKHGXUDWLRQRIWKHLUSDUWLFLSDWLRQLQWKHVWXG\DVSUHVFULEHGE\WKHWUHDWLQJ
SK\VLFLDQ:KHQSRVVLEOHWKHGRVHRI07;VKRXOGEHWDNHQRQWKHVDPHGD\RIWKH
ZHHN,QWKHHYHQWWKDWDVXEMHFWGHYHORSV07;UHODWHGVLGHHIIHFWVHJ
PXFRVLWLVVWRPDWLWLVDGRVHUHGXFWLRQRUFKDQJHRIURXWHVKRXOGEHFRQVLGHUHG

6WXG\7UHDWPHQW)RUPXODWLRQ

6WXG\'UXJ
$%3LVDJHQHWLFDOO\HQJLQHHUHGFKLPHULFPXULQHKXPDQPRQRFORQDO,J*NDSSD
DQWLERG\GLUHFWHGDJDLQVWWKH&'DQWLJHQ$%3KDVDQDSSUR[LPDWHPROHFXODU
ZHLJKWRIN'$%3LVSURGXFHGE\PDPPDOLDQFHOO&KLQHVH+DPVWHU2YDU\
VXVSHQVLRQFXOWXUHLQDQXWULHQWPHGLXP$%3LVDVWHULOHFOHDUSUHVHUYDWLYHIUHH
OLTXLGFRQFHQWUDWHIRU,9DGPLQLVWUDWLRQ$%3LVVXSSOLHGDWDFRQFHQWUDWLRQRI
PJP/LQHLWKHUPJP/RUPJP/VLQJOHXVHYLDOV2QO\
PJP/YLDOVZLOOEHXVHGLQWKLVVWXG\7KHSURGXFWLVIRUPXODWHGLQSRO\VRUEDWH

PJP/VRGLXPFLWUDWHGLK\GUDWH
PJP/VRGLXPFKORULGH
PJP/DQG
:DWHUIRU,QMHFWLRQ7KHS+LV

6LWHVZLOOSUHVFULEH07;DFFRUGLQJWRVWDQGDUGORFDOJXLGDQFH

&RPSDUDWRU
5LWX[LPDELVDJHQHWLFDOO\HQJLQHHUHGFKLPHULFPXULQHKXPDQPRQRFORQDO,J*NDSSD
DQWLERG\GLUHFWHGDJDLQVWWKH&'DQWLJHQKDYLQJDQDSSUR[LPDWHPROHFXODUZHLJKWRI
N'DQGELQGLQJDIILQLW\IRUWKH&'DQWLJHQRIDSSUR[LPDWHO\Q05LWX[LPDELV
SURGXFHGE\PDPPDOLDQFHOO&KLQHVH+DPVWHU2YDU\VXVSHQVLRQFXOWXUHLQDQXWULHQW
PHGLXPFRQWDLQLQJWKHDQWLELRWLFJHQWDPLFLQ%RWKULWX[LPDE86DQGULWX[LPDE(8
KDYHWKHVDPHSURGXFWIRUPXODWLRQRIDVWHULOHFOHDUFRORUOHVVSUHVHUYDWLYHIUHHOLTXLG
CC
I
CC
I
CCI
C
C
I


3URGXFW$%3
&OLQLFDO6WXG\3URWRFRO
'DWH0DUFK
3DJHRI
&RQILGHQWLDO

FRQFHQWUDWHIRU,9DGPLQLVWUDWLRQ5LWX[LPDE86DQGULWX[LPDE(8LVVXSSOLHGDWD
FRQFHQWUDWLRQRIPJP/LQHLWKHUPJP/RUPJP/VLQJOHXVHYLDOV
2QO\PJP/YLDOVZLOOEHXVHGLQWKLVVWXG\7KHSURGXFWLVIRUPXODWHGLQ
SRO\VRUEDWH
PJP/VRGLXPFLWUDWHGLK\GUDWH
PJP/VRGLXPFKORULGH
 PJP/DQGZDWHUIRULQMHFWLRQ7KHS+LV

5LWX[LPDE86DQGULWX[LPDE(8ZLOOEHSURYLGHGIURPFRPPHUFLDOVXSSOLHV

6WXG\7UHDWPHQW/DEHOLQJDQG3DFNDJLQJ
$PDQXDOFRQWDLQLQJGHWDLOHGLQIRUPDWLRQUHJDUGLQJWKHODEHOLQJSDFNDJLQJVWRUDJH
SUHSDUDWLRQDQGDGPLQLVWUDWLRQRIHDFKLQYHVWLJDWLRQDOSURGXFWHJLQYHVWLJDWLRQDO
SURGXFW>V@DQGFRPSDUDWRUSURGXFW>V@DQGEULHILQIRUPDWLRQDERXWRWKHUSURWRFROUHTXLUHG
WKHUDSLHVZLOOEHSURYLGHGVHSDUDWHO\LQWKH3KDUPDF\*XLGH

%OLQGLQJRI6WXG\0HGLFDWLRQ
6LQFHWKHLQYHVWLJDWLRQDOSURGXFWFRQWDLQHUVDUHGLIIHUHQWIRU$%3DQGULWX[LPDE
LQYHVWLJDWLRQDOSURGXFW$%3RUULWX[LPDEZLOOEHSUHSDUHGE\DQXQEOLQGHG
3KDUPDFLVWRUGHVLJQHHIRUDGPLQLVWUDWLRQWRWKHVXEMHFW7KHVXEMHFWVWKH6SRQVRU
$PJHQGHVLJQDWHG35$DQGRWKHUFOLQLFDOVLWHVWDIIZLOOEHEOLQGHGWRWKH
LQYHVWLJDWLRQDOSURGXFWDOORFDWLRQIRUHDFKVXEMHFW5DQGRPL]DWLRQGDWDZLOOEHNHSW
VWULFWO\FRQILGHQWLDOILOHGVHFXUHO\E\WKH6SRQVRURUGHVLJQHHDQGDFFHVVLEOHRQO\WR
DXWKRUL]HGSHUVRQVSHU6SRQVRURUGHVLJQHH¶VVWDQGDUGRSHUDWLQJSURFHGXUHV623V
XQWLOWKHWLPHRIXQEOLQGLQJ6HOHFW35$VWDIIHJFOLQLFDOUHVHDUFKDVVRFLDWHVZKRZLOO
QRWEHLQYROYHGLQWKHPRQLWRULQJRUWKHGDLO\RSHUDWLRQVRIWKHVWXG\ZLOOEHXQEOLQGHGWR
VXEMHFWLQYHVWLJDWLRQDOSURGXFWDOORFDWLRQLQRUGHUWRSHUIRUPLQYHVWLJDWLRQDOSURGXFW
DFFRXQWDELOLW\
)RUGHWDLOVRQWKHHPHUJHQF\SURFHGXUHIRUXQEOLQGLQJRILQGLYLGXDOVXEMHFWVVHH
6HFWLRQEHORZ
$WUDQGRPL]DWLRQUDQGRPL]DWLRQQXPEHUVZLOOEHDVVLJQHGWRHDFKVXEMHFWE\WKH
LQWHUDFWLYHYRLFHDQGZHEUHVSRQVHV\VWHP,;56

6WXG\7UHDWPHQW6WRUDJHDQG$FFRXQWDELOLW\
,WLVIRUELGGHQWRXVHLQYHVWLJDWLRQDOGUXJPDWHULDOIRUSXUSRVHVRWKHUWKDQWKRVHGHILQHG
LQWKLVSURWRFRO

6WXG\7UHDWPHQW6WRUDJH
,QYHVWLJDWLRQDOSURGXFWVKRXOGEHVWRUHGLQDVHFXUHOLPLWHGDFFHVVORFDWLRQ$%3
DQGULWX[LPDEVKRXOGEHVWRUHGSURWHFWHGIURPOLJKWDW &WR
&DQGDFFRUGLQJWRWKH
CC
I
C
C
I
CC
I
CCI
C
C
I
C
C
I


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 32 of 77 
Confidential 
 
storage and expiration information (where required) provided on the label that is affixed 
to the package containing the investigational product.  Do not freeze or shake. 
8.5.5.2 
Study Treatment Accountability 
All supplies of study medication will be accounted for in accordance with GCP.  There 
will be an investigational product accountability record and the pharmacist, or designee, 
should maintain accurate records of the disposition of all study medication supplies 
received during the study.  These records should include the amounts and dates that 
clinical drug supplies were received and destroyed/returned to Amgen or its designee.  If 
errors or damages in the clinical drug supply shipments occur, the Investigator should 
contact Amgen or its designee immediately.  Copies of the study medication 
accountability records will be provided by each Investigator for inclusion in the Trial 
Master File after database lock.  The study monitor will periodically check the supplies of 
study medication held by the Investigator or pharmacist to verify accountability of all 
medication used. 
The Investigator will administer the medication only to the identified subjects of this 
study, according to the procedures described in this study protocol.  After the end of the 
study, all unused medication and all medication containers should be destroyed or 
returned to Amgen or its designee, as appropriate, for destruction.  In either instance, 
complete documentation will be returned to the Sponsor. 
8.5.6 
Dose Adjustments and Dose Escalation 
There are no recommended dose reductions or escalations for the investigational 
products (ABP 798 or rituximab).   
All AEs should be reported in accordance with Section 11 of the protocol. 
8.5.7 
Prior and Concomitant Therapy 
8.5.7.1 
Permitted Concomitant Treatments (Medications and Therapies) 
The following concomitant medications are permitted: 
 
MTX as specified in Section 8.5.1.   
 
Oral corticosteroids at a dose of ≤ 10 mg prednisone, or equivalent, per day are 
permitted provided they are at a stable dose for at least 4 weeks prior to 
initiation of study treatment.  The dose of oral corticosteroids may be reduced 
according to local guidelines during the conduct of the study. 
If at any time a subject needs additional therapy (other than those specified in 
Section 8.5.7.3), including an increase in their MTX dose, to treat their RA, the 
Investigator should contact the Amgen Medical Monitor (or designee) to determine if the 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 33 of 77 
Confidential 
 
subject is eligible to remain on study treatment.  If the subject is no longer eligible to 
remain on study treatment, then the subject should undergo the assessments of the 
week 48/EOS visit before administration of any additional therapies.  The subject should 
be withdrawn from the study treatment. 
8.5.7.2 
Prohibited Concomitant Medications 
All of the following are prohibited at any time during the study: 
 
Non-biologic DMARDs (other than MTX; as per exclusion criteria) including 
tofacitinib 
 
Any biologic treatment for RA (eg, anakinra, soluble IL-1 type II receptor, 
etanercept, infliximab, abatacept, tocilizumab, golimumab, certolizumab, or 
adalimumab) 
 
Chronic minocycline or tetracycline (except use for ≤ 10 days to treat infection, 
or for nonarthritis indications, eg, acne), hydroxychloroquine, mycophenolate 
mofetil, or sulfasalazine 
 
Live and attenuated vaccinations are not allowed while subjects are enrolled in 
the study and receiving investigational product. 
 
Any experimental (biological or nonbiological) therapy (within or outside a clinical 
study). 
 
IA hyaluronic acid 
 
IA, IM, or IV corticosteroids including adrenocorticotropic hormone (except of 
use as pre-medication) 
8.5.7.3 
Rescue Medication 
The definition of rescue medication is any medication other than prohibited medication 
that is used to treat RA.  The use of rescue medication is allowed in this study under 
following conditions: 
 
Oral corticosteroids:  Maximum dose allowed is 10 mg prednisone (or 
equivalent) per day; dose can be decreased if needed, per Investigator’s clinical 
judgment. 
 
Acetaminophen, hydrocodone, codeine, tramadol, and/or propoxyphene may be 
used by the subject as rescue analgesics except at least 12 hours before a 
scheduled study efficacy evaluation (week 8, 12, 24, 40, and 48/EOS).  
 
NSAIDs/cyclooxygenase-2 (COX-2) Inhibitors:  If the subject enters the study 
taking an NSAID/COX-2 inhibitor, the dose of NSAIDs/COX-2 inhibitors can be 
reduced or discontinued during the study if necessary for safety reasons or 
standard of care.  In cases of flare, the dose of NSAIDs/COX-2 inhibitors can be 
temporarily increased as needed.  However, the subject must return to the 
maintenance dose (the dose at baseline) as soon as the flare resolves.  In 
subjects not taking an NSAID/COX-2 inhibitor, one such treatment may be 
added temporarily to treat a flare in RA.  It should be tapered and discontinued 
with resolution of flare.  In all cases, any dose regimen higher than baseline 
dose is not allowed at least 12 hours before the clinical efficacy assessments 
(week 8, 12, 24, 40, and 48/EOS). 


3URGXFW$%3
&OLQLFDO6WXG\3URWRFRO
'DWH0DUFK
3DJHRI
&RQILGHQWLDO
x
7RSLFDODQHVWKHWLFFUHDPVHJOLGRFDLQHSULORFDLQHFUHDPVDQGOLFHQVHG16$,'
FUHDPVDUHSHUPLWWHGH[FHSWZLWKLQKRXUVEHIRUHFOLQLFDOHIILFDF\
DVVHVVPHQWVZHHNDQG(26

3URSK\ODFWLF7UHDWPHQW
&HUWDLQ$(VDUHFRPPRQO\DVVRFLDWHGZLWK07;WUHDWPHQW,QRUGHUWRPLQLPL]H07;
WR[LFLW\VXEMHFWVPD\UHFHLYHDVWDEOHGRVHRIRUDOIRODWHRUIROLQLFDFLG7KLVFDQHLWKHU
EHJLYHQDVDVLQJOHGRVHRQDZHHNO\EDVLVRUDVDGLYLGHGZHHNO\GRVHDWWKH
,QYHVWLJDWRU
VGLVFUHWLRQ

2WKHU&RQFRPLWDQW0HGLFDWLRQVDQG7UHDWPHQWV
$Q\RWKHUWUHDWPHQWQRWH[SOLFLWO\H[FOXGHGZKLFKLVFRQVLGHUHGQHFHVVDU\IRUWKH
VXEMHFW¶VZHOIDUHPD\EHJLYHQDWWKHGLVFUHWLRQRIWKH,QYHVWLJDWRU$GPLQLVWUDWLRQRI
FRQFRPLWDQWPHGLFDWLRQVPXVWEHUHFRUGHG*HQHULFQDPHVIRUFRQFRPLWDQWPHGLFDWLRQ
VKRXOGEHXVHGLISRVVLEOH
$OOVXEMHFWVZKRGLVFRQWLQXHWKHVWXG\PHGLFDWLRQVKRXOGEHRIIHUHGDOWHUQDWLYH
WUHDWPHQWLIDSSOLFDEOH7UHDWPHQWVKRXOGEHJLYHQDFFRUGLQJWRQRUPDOFOLQLFDOSUDFWLFH
DIWHUDWHUPLQDWLRQYLVLWVHH6HFWLRQ

7UHDWPHQW&RPSOLDQFH
5HFRUGVRIVWXG\PHGLFDWLRQXVHGDQGLQWHUYDOVEHWZHHQYLVLWVZLOOEHNHSWGXULQJWKH
VWXG\'UXJDFFRXQWDELOLW\ZLOOEHQRWHGE\WKHILHOGPRQLWRUGXULQJVLWHYLVLWVDQGDWWKH
FRPSOHWLRQRIWKHVWXG\7KHVWXG\WUHDWPHQWVKRXOGEHGLVSHQVHGE\WKH,QYHVWLJDWRU
RUE\DTXDOLILHGLQGLYLGXDOXQGHUWKH,QYHVWLJDWRU¶VVXSHUYLVLRQ$QXSWRGDWHWUHDWPHQW
LQYHQWRU\GLVSHQVLQJUHFRUGPXVWEHPDLQWDLQHG

$VVLJQPHQWWR7UHDWPHQW
:KHQVXEMHFWVHQWHUWKHVFUHHQLQJSHULRGIRUWKHVWXG\WKH,QYHVWLJDWRURUGHVLJQHH
ZLOOFRQWDFWWKH,;56DQGUHFHLYHDXQLTXHGLJLWVXEMHFWLGHQWLILFDWLRQQXPEHUEHIRUH
DQ\VWXG\SURFHGXUHVDUHSHUIRUPHG7KLVQXPEHUZLOOEHXVHGWRLGHQWLI\WKHVXEMHFW
WKURXJKRXWWKHFOLQLFDOVWXG\DQGPXVWEHXVHGRQDOOVWXG\GRFXPHQWDWLRQUHODWHGWRWKDW
VXEMHFW
6LJQLQJRIWKH,&)HVWDEOLVKHVHQWU\LQWRWKH
VFUHHQLQJSHULRG
7KHVXEMHFWLGHQWLILFDWLRQQXPEHUPXVWUHPDLQFRQVWDQWWKURXJKRXWWKHHQWLUHFOLQLFDO
VWXG\LWPXVWQRWEHFKDQJHGDWWKHWLPHRIUHVFUHHQLQJHQUROOPHQWRUUDQGRPL]DWLRQ
PPD


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 35 of 77 
Confidential 
 
This number will not necessarily be the same as the randomization number assigned for 
the study. 
Upon completion of screening, the Investigator (or designee) will contact the IXRS to 
randomize the subject centrally to receive either ABP 798, rituximab (US), or rituximab 
(EU) in a 1:1:1 manner.  The randomization will be stratified by geographic region, 
seropositivity (RF positive and/or CCP-positive vs. RF-negative and CCP-negative), and 
number of prior biologic therapies used for RA (1 vs. >1).  
8.5.10 
Unblinding Procedures 
A subject’s treatment assignment should only be unblinded when knowledge of the 
treatment is essential for the further management of the subject on this study.  
Unblinding at the study site for any other reason will be considered a protocol deviation.  
The Investigator is strongly encouraged to contact the Amgen Medical Monitor (or 
designee) before unblinding any subject’s treatment assignment, but must do so within 
1 working day after the event. 
The identity of investigational product assigned to subject numbers or to individual boxes 
of investigational product will be available for emergency situations through the IXRS.  
Authorized site staff will be provided with a unique Personal Identification Number (PIN) 
to access the IXRS to obtain unblinding information.  This PIN is unique to the individual 
and must not be shared. 
8.6 
Efficacy, Pharmacokinetic/Pharmacodynamic, and Safety Variables 
8.6.1 
Efficacy, Pharmacokinetic/Pharmacodynamic, and Safety 
Measurements Assessed 
A schedule of procedures and assessments is presented in Table 1. 
8.6.1.1 
Pharmacokinetic/Pharmacodynamic Endpoints 
The primary PK endpoints will be AUCinf and Cmax following the second infusion of the 
first dose.  Additional PK endpoints will include AUC from time 0 on day 1 prior to the 
first infusion of the first dose to 14 days postdose (day 15) (AUC0-14 day), AUC from time 0 
on day 1 prior to the first infusion of the first dose to week 12 (AUC0-12 wk), and Cmax 
following the first infusion of the first dose.   
PD endpoints will include the percent of subjects with complete depletion in CD19+ cell 
count from days 1 to 3. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 36 of 77 
Confidential 
 
 
Table 1.  Schedule of Assessments and Procedures 
Study 
Visit/Day/Week 
D = Day; W = Week 
S 
c 
n 
BL/  
D1/ 
W0 
D1 
EOI 
D1
3 h 
D1
6 h 
D
2 
D
3 
D15/
W2 
D15
EOI 
D15
3 h 
D15
6 h 
D 
16 
D
17 
W
4 
W
8 
W
12 
W
24a
W
26 
W 
30 
W 
40 
W48/
EOSb 
Visit Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 2 days 
 
 
 2 
days 
± 3 
days 
 2 
days 
General Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
form 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical & medication 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
Vital signs 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
 
 
X 
X 
X 
 
X 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest radiography 
Xc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dosing of ABP 798/
rituximab 
a 
 
Xd 
 
 
 
 
 
Xd 
 
 
 
 
 
 
 
 
Xd 
Xd 
 
 
 
Concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Disease Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tender/swollen joint 
count 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
 
X 
X 
Subject and 
Investigator’s global 
health assessment
e 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
 
X 
X 
Pain VAS
e 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
 
X 
X 
HAQ-DI
e 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
 
X 
X 
Laboratory 
Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology (HBsAg, 
anti-HBc, HCV) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistry 
Xf 
X 
X 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
X 
 
X 
X 
Hematology 
X 
X 
X 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
X 
 
X 
X 
Page 1 of 2 
See footnotes on following page. 
 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 37 of 77 
Confidential 
 
 
Table 1.  Schedule of Assessments and Procedures 
Study 
Visit/Day/Week 
D = Day; W = Week 
S 
c 
n 
BL/  
D1/ 
W0 
D1 
EOI 
D1
3 h 
D1
6 h 
D
2 
D
3 
D15/
W2 
D15
EOI 
D15
3 h 
D15
6 h 
D 
16 
D
17 
W
4 
W
8 
W
12 
W
24a
W
26 
W 
30 
W 
40 
W48/
EOSb
Visit Window 
 
 
 
 
 
 
 
 
 
 
 
 
 
 2 days 
 
 
 2 
days 
 3 
days
 2 
days 
Laboratory 
Assessments (cont’d) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CRP 
Xg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
 
X 
X 
ESR 
Xg 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK sampling h 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Antidrug antibodies 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
CD19+ cell count 
 
X 
 
 
 
X 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
IgA, IgG, and IgM 
levels 
 
X 
 
 
 
Xi 
Xi 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
Urinalysis 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
Tuberculosis testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancyj 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
 
 
X 
X 
Anti-CCP 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rheumatoid factor 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 2 of 2 
AE = adverse event; BL = Baseline; CRP = C-Reactive Protein; EOI = End of Infusion; EOS = End of Study; ESR = Erythrocyte sedimentation rate; h = hour; HAQ-DI = 
Health Assessment Questionnaire – Disability Index; HBsAg = Hepatitis B surface antigen; Anti-HBc = Hepatitis B core antibody; HCV = Hepatitis C virus antibody; Ig = 
Immunoglobulin, PK = Pharmacokinetic; Scn = Screening; VAS = Visual analogue scale; Anti-CCP= Anti-cyclic citrullinated peptide antibody 
a The second dose will be administered at week 24 or earlier, ie, anytime from week 16 to week 24, in individual subjects, if necessary in the opinion of the 
Investigator.  For subjects who receive retreatment before week 24, all week 24 and post-week-24 assessments will be moved up to the corresponding time point 
after treatment (eg, week 26 will be 2 weeks after retreatment, week 30 will be 6 weeks after retreatment, etc.).  An infusion may be delayed up to 7 days to allow for 
recovery from infection. 
b Subjects early terminating study should perform week 48 procedures.  
c Historical radiograph performed within 3 months prior to first dose of IP may be used and does not need to be repeated at screening (section 10.7 for details) 
d ABP 798/rituximab dosing to be administered after all other procedures are completed for each visit.  
e Subjective assessments will be the first procedures performed at the visit. 
f Includes any other lab tests required only for screening.  Creatinine clearance calculation will be performed only at screening. 
g Either CRP or ESR is required at screening.  CRP will be performed by central lab and results will be blinded to study sites.  ESR will be performed by local 
laboratory. 
h PK sampling: day 1, predose, at EOI, and 3 and 6 hours postdose; day 2 (24 hours postdose); day 3 (48 hours postdose); day 15, predose, at EOI, and 3, 6, and 24 
hours postdose (day 16), and 48 hours postdose (day 17).  In addition, at week 4 (day 29), week 8 (day 57), week 12 (day 85), and predose week 24, week 26, and 
week 30, 48/EOS.  Blood sampling for PK analysis during each return visit, including the EOS visit, will occur per the scheduled time point with tolerance collection 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 38 of 77 
Confidential 
 
 
windows as follows:  Day 1 predose = within 1 hour prior to dosing; days 1 and 15 at EOI = infusion should be monitored to ensure collection of the PK sample within 
10 minutes after the end of the infusion; all other Day 1 sampling times = ± 10 minutes; days 2 and 3 = ± 3 hours; predose Day 15 = within 1 hour prior to dosing; all 
other Day 15 sampling time = ± 10 minutes; days 16 and 17 = ± 3 hours; week 4, 8 and 12 =  ± 2 days; predose at weeks 24 and 26 = within 1 hour prior to dosing; 
and weeks 30 and 48 = ± 2 days. 
i Only IgM required on Days 2 and 3. 
j Pregnancy test for females of child-bearing potential.  Serum pregnancy test will be done at screening by the central laboratory.  Urine pregnancy test performed 
locally at subsequent time points. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 39 of 77 
Confidential 
 
8.6.1.2 
Efficacy Measurements 
8.6.1.2.1 
Efficacy Criteria 
Efficacy is a secondary objective in this study.  The efficacy endpoint is Disease Activity 
Score (DAS) 28-CRP change from baseline at week 24.  The endpoint will also be 
assessed at weeks 8, 12, 40, and 48.   
In addition, ACR20 (20% improvement in ACR core set measurements), ACR50 (at least 
50% improvement compared to baseline) and ACR70 (at least 70% improvement 
compared to baseline) will also be assessed at weeks 8, 12, 24, 40, and 48.  
DAS28-CRP  
The DAS28-CRP is a continuous measure based on 28 DAS joints from the ACR 
(indicated with * in Section 17.3), the Subject's Global Health Assessment score (as 
assessed as a score of 0 to 100 transformed from the results on a 100-mm VAS scale), 
and CRP, as follows: 
DAS28-CRP = 0.56*(TJC28)0.5 + 0.28*(SJC28) 0.5 + 0.36*ln(CRP+1) + 0.014*GH + 0.96 
where TJC28 is the tender joint count of the 28 joints in the DAS, SJC28 is the 
28 swollen joint count, CRP is in mg/L, and GH is the Subject's Global Health 
Assessment in 0 to 100 scale (van Gestel et al, 1998).  
ACR 
Improvement compared to baseline is required for both swollen and tender joint counts 
(66/68 joint counts; Section 17.3), as well as for 3 out of the following 5 additional 
parameters:  
 
Subject's Global Health Assessment (on a 100-mm visual analogue scale [VAS]; 
Section 17.4) 
 
Investigator's Global Health Assessment (on a 100-mm VAS; Section 17.4) 
 
Subject's assessment of pain (on a 100-mm VAS; Section 17.4) 
 
Health Assessment Questionnaire – Disability Index (HAQ-DI; Section 17.4) 
 
CRP  
8.6.1.3 
Safety Measurements 
Safety endpoints include the following: 
 
treatment-emergent AEs and serious adverse events (SAEs) 
 
clinically significant changes in laboratory values and vital signs  
 
incidence of antidrug antibodies 
 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 40 of 77 
Confidential 
 
9 
STUDY EVALUATIONS BY VISIT 
After signing the informed consent, there are 15 visits, including a screening visit and 
visits on days 1, 2, 3, 15, 16, and 17 and weeks 4, 8, 12, 24, 26, 30, 40, and 48/EOS.  
After the first 18 subjects have received at least 1 dose of investigational product (ie, 
infusions on days 1 and 15) an initial safety analysis will be conducted by the DMC.   
9.1 
Screening 
After subjects have provided informed consent, the following assessments/procedures 
will be performed within the 28 day screening period: 
 
targeted medical history, including history of all prior treatments for RA within the 
past 3 years and any prior biologic therapies used for RA 
 
physical examination, including evaluation of body systems and height and 
weight 
 
vital signs (systolic and diastolic blood pressure, pulse, respiration rate, and 
temperature)  
 
standard 12-lead electrocardiogram (ECG) 
 
chest radiography (prior radiography or formal reports signed off by a radiologist 
within 3 months of first dose of investigational product is acceptable) 
 
screening joint assessments (DAS and ACR tender/swollen joint counts; 
Section 17.3)  
 
tuberculosis testing (PPD or Quantiferon test)  
 
clinical laboratory testing, including serology, serum chemistry, hematology, 
either CRP or ESR, anti-CCP, and rheumatoid factor.  
 
collection of samples for urinalysis 
 
serum pregnancy test for women of childbearing potential 
At the screening assessment, all concomitant medications from 3 months before the 
planned start of study treatment, all prior treatments for RA within the past 3 years and 
any prior biologic therapies used for RA will be recorded.  Any AEs occurring during the 
screening period will be recorded as medical history; any SAEs will be recorded using 
the eCRF.  SAEs will be reported as outlined in Section 11.2.2. 
Subjects will continue on their stable pre-study MTX regimen during the screening 
period. 
9.1.1 
Screen Failures 
Subjects determined to be screen failures will not be eligible for immediate participation 
and must be registered as a screen failure in IXRS.  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 re-screened up to 
2 times at the Investigator’s discretion (ie, a total of 3 screens including initial screening).  
The subject will retain the same subject ID number provided at the initial screening.  


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 41 of 77 
Confidential 
 
Subjects must be re-consented if more than 30 days have elapsed between date of 
initial informed consent and date of re-screen/randomization.  
9.2 
Baseline (Day 1, first day of treatment, Week 0) 
Day 1 will be defined as the first day of treatment.  After subjects are confirmed to meet 
the entry criteria (Section 8.4), the Investigator (or designee) will contact the IXRS to 
randomize the subject centrally to receive either ABP 798, rituximab (US), or rituximab 
(EU).  The following assessments/procedures will be performed before treatment: 
 
subjective assessments (Subject's Global Health Assessment, subject's 
assessment of pain, and HAQ-DI, Section 17.4); subjective assessments will be 
the first assessments performed at the visit 
 
physical examination, including evaluation of body systems  
 
vital signs (systolic and diastolic blood pressure, pulse, respiration rate, and 
temperature) 
 
baseline joint assessments (DAS and ACR tender/swollen joint counts; 
Section 17.3)  
 
Investigator's Global Health Assessment 
 
clinical laboratory testing, including serum chemistry, hematology, and CRP 
 
urinalysis and urine pregnancy test (for women of childbearing potential) 
 
collection of pretreatment PK samples (within 1 hour predose) and samples for 
pretreatment antidrug antibodies, CD19+ cell count, and IgA, IgG, and IgM 
levels 
Any changes in concomitant medications since the last assessment will be recorded.  
Any pretreatment AEs will be recorded as medical history; any pretreatment SAEs will 
be recorded using the eCRF.  SAEs will be reported as outlined in Section 11.2.2. 
After completion of pretreatment procedures, ABP 798, rituximab (US), or rituximab (EU) 
will be administered as an IV infusion in a double-blinded fashion.  Starting at the time of 
first treatment, all AEs, including increases in severity or frequency of pre-existing 
conditions, will be recorded in the eCRF.  
At the end of infusion (EOI), blood samples for serum chemistry and hematology will be 
drawn.  
At EOI and 3 and 6 hours after EOI, the following assessments will be performed: 
 
vital signs (systolic and diastolic blood pressure, pulse, respiration rate, and 
temperature)  
 
collection of PK samples (within 10 minutes after the end of the infusion, 
± 10 minutes at 3 and 6 hours) 
Subjects may leave the site after the 6-hour post-EOI assessment.  Subjects will 
continue on their stable MTX regimen.   


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 42 of 77 
Confidential 
 
9.3 
Day 2 
On day 2, approximately 24 hours after EOI, a PK sample (± 3 hours) and samples for 
CD19+ cell count and IgM levels will be collected.  Subjects will continue on their stable 
MTX regimen.   
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded.  SAEs will be reported as outlined in Section 11.2.2.   
9.4 
Day 3 
Two days (approximately 48 hours after EOI) after the first infusion, the subject will 
return to the study site for collection of samples PK (± 3 hours), CD19+ cell count, and 
IgM levels.   
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded.  SAEs will be reported as outlined in Section 11.2.2.   
9.5 
Day 15 (Week 2) 
Two weeks after the first infusion, the subject will return to the study site for the second 
infusion.  Subjects will remain at the site for 6 hours post-treatment for sample collection.  
The following assessments/procedures will be performed before the infusion on day 15: 
 
vital signs (systolic and diastolic blood pressure, pulse, respiration rate, and 
temperature) 
 
clinical laboratory testing, including serum chemistry and hematology 
 
urinalysis and urine pregnancy test (for women of childbearing potential) 
 
collection of pretreatment PK samples (within 1 hour predose) and samples for 
antidrug antibodies 
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded in the eCRF.  SAEs will be reported as outlined in Section 11.2.2. 
After completion of pretreatment procedures, ABP 798, rituximab (US), or rituximab (EU) 
will be administered as an IV infusion in a double-blinded fashion.   
At the EOI and 3 and 6 hours after EOI, the following assessments will be performed: 
 
vital signs (systolic and diastolic blood pressure, pulse, respiration rate, and 
temperature)  
 
collection of PK samples (within 10 minutes after the end of the infusion, 
± 10 minutes at 3 and 6 hours) 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 43 of 77 
Confidential 
 
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded in the eCRF.  SAEs will be reported as outlined in Section 11.2.2. 
Subjects may leave the site after the 6-hour post-EOI assessment. 
9.6 
Day 16 
On day 16, approximately 24 hours (± 3 hours) after completing the second infusion, a 
PK sample will be collected.  Subjects will continue on their stable MTX regimen.   
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded.  SAEs will be reported as outlined in Section 11.2.2.   
9.7 
Day 17 
On day 17, approximately 48 hours (± 3 hours) after the second infusion, the subject will 
return to the study site for collection of samples for serum chemistry, hematology, and 
PK.  
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded.  SAEs will be reported as outlined in Section 11.2.2.   
9.8 
Week 4 ( 2 days) 
Four weeks ( 2 days) after the first infusion, the subject will return to the study site.  The 
following assessments/procedures will be performed at week 4: 
 
collection of PK samples and samples for CD19+ cell count and IgA, IgG, and 
IgM levels 
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded in the eCRF.  SAEs will be reported as outlined in Section 11.2.2.   
9.9 
Week 8 ( 2 days) 
Eight weeks ( 2 days) after the first infusion, the subject will return to the study site.  
The following assessments/procedures will be performed at week 8: 
 
joint assessments (DAS and ACR tender/swollen joint counts; Section 17.3)  
 
subjective assessments (Subject's Global Health Assessment, subject's 
assessment of pain, and HAQ-DI, Section 17.4); subjective assessments will be 
the first assessments performed at the visit 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 44 of 77 
Confidential 
 
 
Investigator's Global Health Assessment 
 
clinical laboratory testing, including serum chemistry, hematology, and CRP 
 
collection of PK samples  
 
urine pregnancy test (for women of childbearing potential) 
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded in the eCRF.  SAEs will be reported as outlined in Section 11.2.2.   
9.10 Week 12 ( 2 days) 
Twelve weeks ( 2 days) after the first infusion, the subject will return to the study site for 
safety and efficacy assessment.  The following assessments/procedures will be 
performed at week 12: 
 
subjective assessments (Subject's Global Health Assessment, subject's 
assessment of pain, and HAQ-DI, Section 17.4); subjective assessments will be 
the first assessments performed at the visit 
 
joint assessments (DAS and ACR tender/swollen joint counts; Section 17.3)  
 
Investigator's Global Health Assessment 
 
clinical laboratory testing including CRP 
 
collection of PK samples 
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded in the eCRF.  SAEs will be reported as outlined in Section 11.2.2.   
9.11 Week 24  
Twenty-four weeks after the first infusion (or at the time of retreatment if required before 
week 24), the subject will return to the study site for assessment and treatment.  The 
following assessments/procedures will be performed before treatment at week 24: 
 
subjective assessments (Subject's Global Health Assessment, subject's 
assessment of pain, and HAQ-DI; Section 17.4); subjective assessments will be 
the first assessments performed at the visit 
 
physical examination, including evaluation of body systems 
 
vital signs (systolic and diastolic blood pressure, pulse, respiration rate, and 
temperature)  
 
joint assessments (DAS and ACR tender/swollen joint counts; Section 17.3)  
 
Investigator's Global Health Assessment 
 
clinical laboratory testing, including serum chemistry, hematology, and CRP 
 
urinalysis and urine pregnancy test (for women of childbearing potential) 
 
collection of pretreatment PK samples (within 1 hour predose) and samples for 
antidrug antibodies, CD19+ cell count, and IgA, IgG, and IgM levels 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 45 of 77 
Confidential 
 
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded in the eCRF.  SAEs will be reported as outlined in Section 11.2.2. 
After completion of pretreatment procedures, ABP 798 or rituximab (EU) will be 
administered as an IV infusion in a double-blinded fashion.  Subjects who had previously 
received rituximab (US) will be transitioned to ABP 798, but this change will be managed 
by the IXRS to maintain the blind.  Subjects will continue on their stable MTX regimen.   
9.12 Week 26  
Twenty-six weeks after the first infusion (or 2 weeks after initiation of retreatment if 
retreatment occurred before week 24), the subject will return to the study site for 
assessment and treatment.  The following assessments/procedures will be performed 
before treatment at week 26: 
 
vital signs (systolic and diastolic blood pressure, pulse, respiration rate, and 
temperature)  
 
clinical laboratory testing, including serum chemistry and hematology 
 
collection of pretreatment PK samples (within 1 hour predose) 
After completion of pretreatment procedures, ABP 798 or rituximab (EU) will be 
administered as an IV infusion in a double-blinded fashion.  Any changes in concomitant 
medications since the last assessment will be recorded.  All AEs, including increases in 
severity or frequency of pre-existing conditions, will be recorded in the eCRF and will be 
reported as outlined in Section 11.2.2.  Subjects will continue on their stable MTX 
regimen.   
9.13 Week 30 ( 2 days) 
Thirty weeks (± 2 days) after the first infusion (or 6 weeks after initiation of retreatment if 
retreatment occurred before week 24), the subject will return to the study site.  The 
following assessments/procedures will be performed at week 30: 
 
vital signs (systolic and diastolic blood pressure, pulse, respiration rate, and 
temperature)  
 
collection of PK samples and samples for antidrug antibodies  
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded in the eCRF.  SAEs will be reported as outlined in Section 11.2.2. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 46 of 77 
Confidential 
 
9.14 Week 40 ( 3 days)  
Forty weeks ( 3 days) after the first infusion (or 16 weeks after initiation of retreatment if 
retreatment occurred before week 24), the subject will return to the study site.  The 
following assessments/procedures will be performed at week 40: 
 
subjective assessments (Subject's Global Health Assessment, subject's 
assessment of pain, and HAQ-DI, Section 17.4); subjective assessments will be 
the first assessments performed at the visit 
 
joint assessments (DAS and ACR tender/swollen joint counts; Section 17.3)  
 
Investigator's Global Health Assessment 
 
clinical laboratory testing, including serum chemistry, hematology, and CRP 
 
urine pregnancy test (for women of childbearing potential) 
Any changes in concomitant medications since the last assessment will be recorded.  All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded in the eCRF.  SAEs will be reported as outlined in Section 11.2.2. 
9.15 Week 48 (EOS) 
Forty-eight weeks ( 2 days) after the first infusion (or 24 weeks after initiation of 
retreatment if retreatment occurred before week 24) or at the time of early 
discontinuation, the subject will return to the study site for a follow-up assessment.  The 
following assessments/procedures will be performed at week 48/EOS: 
 
subjective assessments (Subject's Global Health Assessment, subject's 
assessment of pain, and HAQ-DI; Section 17.4); subjective assessments will be 
the first assessments performed at the visit 
 
Investigator's Global Health Assessment 
 
physical examination, including evaluation of body systems 
 
vital signs (systolic and diastolic blood pressure, pulse, respiration rate, and 
temperature)  
 
joint assessments (DAS and ACR tender/swollen joint counts; Section 17.3)  
 
clinical laboratory testing, including serum chemistry, hematology, and CRP 
 
urinalysis and urine pregnancy (for women of childbearing potential) 
 
collection of PK samples (PK sample must be within 2 days of week 48) and 
samples for antidrug antibodies, CD19+ cell count, and IgA, IgG, and IgM levels 
Any changes in concomitant medications since the last assessment will be recorded. All 
AEs, including increases in severity or frequency of pre-existing conditions, will be 
recorded in the eCRF through the week 48/EOS visit.  SAEs will be reported as outlined 
in Section 11.2.2.  Any SAEs ongoing at week 48/EOS will be followed until they resolve 
or are considered chronic or stable. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 47 of 77 
Confidential 
 
10 
METHODS OF ASSESSMENT 
10.1 Rheumatoid Arthritis Assessments 
At each time point for RA assessments, the Subject's Global Health Assessment, 
subject's assessment of pain, and HAQ-DI (Section 17.4) will be completed.  These 
assessments should be the first assessments performed at the visits at which they are 
scheduled.   
At these same time points, joints will be assessed and classified as swollen/not swollen 
and tender/not tender by pressure and joint manipulation on physical examination.  Joint 
prosthesis, arthrodesis, or fused joints will not be assessed for swelling or tenderness.  
The joints to be assessed for swelling and tenderness are given in Section 17.3, 
including the 28 joint-count for DAS and the 66/68 joint set for ACR.  All joint 
assessments will be performed by an experienced joint evaluator.  The evaluator cannot 
be the treating physician and cannot interact with the subject on the study beyond the 
assessment of joints.  The evaluator should not discuss the subject’s clinical status, nor 
should the evaluator have access to subject medical records or eCRFs, including prior 
joint assessments.  The same evaluator should perform joint assessments across all 
time points for a subject where possible. 
For the screening and baseline joint counts, the distal interphalanges should be 
evaluated, but should not be included in the total joint count to determine eligibility. 
The Investigator's Global Health Assessment will also be completed at the times 
indicated in Table 1.  The independent joint assessor may not complete the 
Investigator’s Global Disease Assessment.  The physician completing the Investigator’s 
Global Disease Assessment will have access to the joint assessments.  The subject and 
physician must complete the global assessments independently from each other. 
10.2 Pregnancy Test 
Pregnancy will be determined by evaluation of -human chorionic gonadotrophin 
(-HCG) in serum at screening by central laboratory and in urine at subsequent time 
points locally for all women of childbearing potential.  Subjects who are pregnant are 
excluded from the study. 
The Investigator will inform the Sponsor immediately of any case of pregnancy and 
collect information on any female subject who becomes pregnant while participating in 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 48 of 77 
Confidential 
 
this study and in case of pregnancy among female partners of male subjects.  The 
subject will also be followed to determine the outcome of the pregnancy. 
10.3 Physical Examination  
Physical examinations will be performed by a physician and will include examination of 
the following:  general appearance, head, ears, eyes, nose, throat, neck, skin, 
cardiovascular system, respiratory system, abdominal system and nervous system.  For 
each body system an assessment of normal or abnormal will be recorded.  Clinically 
relevant changes from baseline will be reported as AEs. 
Body weight (kg) will be measured without shoes or jacket.  Height will be determined at 
screening. 
10.4 Vital Signs  
Systolic blood pressure and diastolic blood pressure will be measured on the same arm 
(preferentially on the left arm) after the subject has been in a supine/sitting position for 
5 minutes.  Pulse will be recorded simultaneously with blood pressure measurements.  
Respiration rate and temperature will also be recorded. 
During the study, measurement of vital signs may be repeated at the discretion of the 
Investigator for safety reasons.  Clinically relevant abnormal findings will be reported as 
AEs. 
10.5 Electrocardiogram 
Computerized 12-lead ECG recordings will be obtained after the subject has been 
supine for 5 minutes.  Each lead will be recorded for at least 3 to 5 beats at a speed of 
25 mm/sec paper speed and 10 mm/mV amplitude.  At a minimum, heart rate, P, PR, 
QRS, and QT will be recorded from the 12-lead ECG.  A copy of the ECGs will be 
retained on site.  For the purposes of screening, the Investigator or a designee will 
evaluate whether the ECG is normal or abnormal and whether it is clinically acceptable 
for inclusion, if abnormal.   
10.6 Tuberculosis Testing 
A tuberculosis test will be performed at screening by PPD or Quantiferon test.  PPD 
tests will be performed locally, and Quantiferon tests will be performed by the central or 
local laboratory.  Subjects with positive PPD/Quantiferon test may be eligible based on 
the Sponsor’s tuberculosis risk assessment worksheet and the other criteria listed in 
Inclusion Criterion 13. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 49 of 77 
Confidential 
 
10.7 Chest Radiography  
Chest radiography will be performed at screening as indicated in Table 1 and will include 
anterior/posterior or posterior/anterior and lateral views.  Chest x-ray performed at the 
site can be read by the Investigator.  A formal report, signed off by the Investigator, 
should be filed in subject’s medical records.  If the x-ray is performed off site, then formal 
reports signed off by a radiologist should be acceptable.  Historical films obtained, or 
formal reports signed off by a radiologist within the 3 months prior to receiving 
investigational product are acceptable for screening as well. 
10.8 Clinical Laboratory Testing 
Venous blood samples will be taken for clinical laboratory tests at the time points 
indicated in Table 1.  The following parameters will be determined: 
Serology:  HbsAg, anti-HBc, and HCV antibody 
Hematology:  Hemoglobin, hematocrit or packed cell volume, red blood cell count, 
mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, white blood 
cell count and differential, platelet count. 
Clinical chemistry:  Sodium, potassium, urea, creatinine, total protein, albumin, total 
bilirubin, AST, ALT, alkaline phosphatase, gamma glutamyl transferase, nonfasting 
glucose, phosphate, and uric acid.  Rheumatoid Factor and anti-CCP will be assessed at 
screening.  CRP will be assessed at the time points indicated in Table 1.  CRP results 
from the baseline visit and onwards will be blinded to study sites and not included in the 
central laboratory report to the site. 
Urinalysis (fresh urine):  pH, protein, glucose, bilirubin, blood. 
Immunology:  Blood samples for antidrug antibody assessments will be collected at the 
time points indicated in Table 1. 
The above clinical laboratory tests will be sent to and assessed at a central laboratory, 
except urine pregnancy, which will be assessed locally, and immunology, which will be 
sent to central laboratory and analyzed by Amgen or a designee.  Further details of the 
procedures to be followed for sample collection, storage, and shipment will be 
documented in a Laboratory Manual. 
Samples testing positive for binding antibodies will also be tested for neutralizing 
antibodies and may be further characterized for quantity/titer, isotype, affinity, and 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 50 of 77 
Confidential 
 
presence of immune complexes.  Additional blood samples may be obtained to rule out 
antidrug antibodies during the study. 
Additional and repeat laboratory safety testing may be performed at the discretion of the 
Investigator.  Any clinically relevant changes from baseline will be reported as AEs. 
IgA, IgG, and IgM levels will also be collected, as indicated in Table 1.  
10.9 Blood Samples for Pharmacokinetic Analysis  
During treatment, a series of serum samples will be taken according to Table 1.  The 
exact times of blood sampling will be recorded.  
Blood sampling for PK analysis during each return visit, including the EOS visit, will 
occur per the scheduled time point with tolerance collection windows as follows: 
 
predose day 1 = within 1 hour prior to dosing  
 
days 1 and 15 at EOI - infusion should be monitored to ensure collection of the 
PK sample within 10 minutes after the end of the infusion 
 
all other day 1 sampling times = ± 10 minutes 
 
days 2 and 3 = ± 3 hours 
 
predose day 15 = within 1 hour prior to dosing 
 
all other day 15 sampling time = ± 10 minutes 
 
days 16 and 17 = ± 3 hours 
 
weeks 4, 8, and 12 = ± 2 days 
 
predose at weeks 24 and 26 = within 1 hour prior to dosing 
 
weeks 30 and 48 = ± 2 days 
Details of the procedures to be followed for sample collection, storage, and shipment will 
be documented in the Laboratory Manual. 
10.10 Blood Samples for Pharmacodynamic Analysis 
Pharmacodynamic analyses will include CD19+ cell count.  Samples will be collected at 
the time points indicated in Table 1.   
Details of the procedures to be followed for sample collection, storage, and shipment will 
be documented in the Laboratory Manual. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 51 of 77 
Confidential 
 
11 SAFETY DATA COLLECTION, RECORDING, AND REPORTING 
11.1 Adverse Events 
11.1.1 
Definition of Adverse Events 
An AE is defined as any untoward medical occurrence in a clinical trial subject.  The 
event does not necessarily have a causal relationship with study treatment.  The 
Investigator is responsible for ensuring that any AEs observed by the Investigator or 
reported by the subject are recorded in the subject’s medical record as well as the 
eCRF.   
The definition of AEs includes worsening of a pre-existing medical condition.  Worsening 
indicates that the pre-existing medical condition (eg, diabetes, migraine headaches, 
gout) has increased in severity, frequency, and/or duration, and/or has an association 
with a significantly worse outcome.  In the case of worsening of a pre-existing condition, 
the start date of the event is the date when the first signs of worsening were observed.  
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 AE.   
11.1.2 
Reporting Procedures for Adverse Events 
The Investigator is responsible for ensuring that all AEs observed by the Investigator or 
reported by the subject that occur from the day of randomization until the week 48 visit 
(or through 28 days after the last dose of investigational product for subjects who 
discontinue study early) are reported using the applicable eCRF Adverse Event 
Summary page.  AEs observed by the Investigator or reported by the subject that occur 
after signing of informed consent but before randomization will be recorded.  
The Investigator must assign the following AE attributes: 
 
AE diagnosis or syndrome(s), if known (if not known, signs or symptoms) 
 
dates of onset and resolution 
 
severity  
 
assessment of relatedness to IP  
 
action taken 
AEs must be graded for severity according to the National Cancer Institute (US) 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm).   
The Investigator must assess whether the AE is possibly related to the investigational 
product.  This relationship is indicated by a “yes” or “no” response to the question:  “Is 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 52 of 77 
Confidential 
 
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 AEs.  However, laboratory value changes that require treatment or 
adjustment in current therapy are considered AEs.  Where applicable, clinical sequelae 
(not the laboratory abnormality) are to be recorded as the AE. 
The Investigator’s clinical judgment is used to determine whether a subject is to be 
removed from treatment due to an AE.  A subject, or subject’s legal guardian, can also 
voluntarily withdraw from treatment due to an AE.  If the subject withdraws consent, the 
subject is encouraged to undergo, at a minimum, an EOS assessment.   
11.2 Serious Adverse Events 
11.2.1 
Definition of Serious Adverse Events 
An SAE is defined as an AE that meets at least 1 of the following serious criteria: 
 
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 
An AE would meet the criterion of “requires hospitalization”, if the event necessitated an 
admission to a health care facility (eg, overnight stay).   
If an Investigator considers an event to be clinically important, but it does not meet any 
of the serious criteria, the event could be classified as a SAE under the criterion of “other 
medically important serious event.”  Examples of such events could include allergic 
bronchospasm, convulsions, blood dyscrasias, drug induced liver injury, or events that 
necessitate an emergency room visit, outpatient surgery, or urgent intervention. 
11.2.2 
Reporting Procedures for Serious Adverse Events 
The Investigator is responsible for ensuring that all SAEs observed by the Investigator or 
reported by the subject that occur after signing of the ICF through the week 48 visit (or 
28 days after the last dose of investigational product for subjects who discontinue early) 
are recorded in the subject’s medical record and are submitted to Amgen.   


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 53 of 77 
Confidential 
 
The SAE must be submitted to Amgen, or its designee, within 24 hours following the 
Investigator’s knowledge of the event via the applicable eCRF.   
If the electronic data capture (EDC) system is not functional, the SAE can be reported by 
faxing a completed paper SAE Fax Cover Sheet and SAE report form or by direct 
telephone communication with PRA Safety Risk Management at the numbers provided 
below.  The event must be updated electronically in EDC by the clinical site once the 
EDC function resumes. 
Fax information to Safety Risk Management/ PRA, for the attention of:  
PRA Drug Safety Center 
For Europe, Asia, and Pacific Region Clinical Sites: 
FAX:  +44 1792 525 720 
Phone:  +49.621.8782.154 
CHOSafety@praintl.com 
For North America, Latin America, and South America Clinical Sites: 
FAX:  1.888.772.6919 
Phone:  1.800.772.2215 
CHOSafety@praintl.com 
New information relating to a previously reported SAE must be submitted to Amgen, or 
its designee.  All new information for SAEs must be sent to Amgen, or its designee, 
within 24 hours following knowledge of the new information.  The Investigator may be 
asked to provide additional follow-up information, which may include a discharge 
summary or extracts from the medical record.  Information provided about the SAE must 
be consistent with that recorded on the applicable eCRF (eg, AE Summary eCRF). 
Elective hospitalizations are not considered SAEs.  If a subject is permanently withdrawn 
from protocol-required therapies because of a SAE, this information must be submitted 
to Amgen, or its designee. 
To comply with worldwide reporting regulations for SAEs, the treatment assignment of 
subjects who develop serious, unexpected, and related AEs may be unblinded by 
Amgen, or its designee, before submission to regulatory authorities.  Investigators will 
receive notification of related SAE reports sent to regulatory authorities in accordance 
with local requirements.   
Determination of expectedness for Amgen products will be based on the contents of the 
Investigator’s Brochure for investigational products and the regional prescribing 
information for products being studied for an approved use.  Expectedness assessments 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 54 of 77 
Confidential 
 
are to be made for all investigational products (Amgen and non-Amgen) using the 
appropriate reference safety information per local regulatory reporting requirements.  
Suspected unexpected serious adverse reactions (SUSARs) reported for subjects 
receiving a non-Amgen investigational products are to be expedited according to local 
requirements.  
Amgen, or its designee, reports SAEs and/or SUSARs as required to regulatory 
authorities, Investigators/institutions, and IRBs/IECs in compliance with all reporting 
requirements according to local regulations and GCPs.  
The Investigator is to notify the appropriate IRB/IEC of SAEs occurring at the site and 
other AE reports received from Amgen, in accordance with local procedures and 
statutes. 
After the protocol-required reporting period defined above, the Investigator does not 
need to actively monitor subjects for SAEs.  However, if the Investigator becomes aware 
of an SAE after this protocol-required reporting period, the Investigator will report the 
event to Amgen within 24 hours following the Investigator’s knowledge of the event.  
SAEs reported outside of the protocol-required reporting period will be captured within 
the safety database as clinical trial cases for the purposes of expedited reporting.   
11.3 Adverse Events of Special Interest 
AEs of Special Interest for ABP 798/rituximab will be defined in the Statistical Analysis 
Plan (SAP) and analyzed from the clinical database.  There are no expedited reporting 
requirements for AEs of Special Interest (other than those that meet other reporting 
requirements). 
11.4 Pregnancy Reporting 
Pregnancy in itself is not regarded as an AE unless there is a suspicion that an 
investigational product may have interfered with the effectiveness of a contraceptive 
medication.  However, the outcome of all pregnancies (spontaneous miscarriage, 
elective termination, normal birth, or congenital abnormality) must be followed up and 
documented even if the subject was discontinued from the study. 
All reports of congenital abnormalities/birth defects are SAEs.  Spontaneous 
miscarriages should also be reported and handled as SAEs.  Elective abortions without 
complications should not be handled as AEs.  All outcomes of pregnancy must be 
reported to Amgen, or its designee. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 55 of 77 
Confidential 
 
Pregnancies among female partners of male subjects will also be reported and followed 
for outcome. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 56 of 77 
Confidential 
 
12 
DATA MANAGEMENT AND STATISTICAL ANALYSIS 
The data management and statistical analysis of this study will be performed by an 
external clinical research organization (CRO) PRA. 
12.1 Data Management 
Previous and concomitant medications will be coded using the latest available World 
Health Organization (WHO) Drug Reference Dictionary.  Coexistent diseases and AEs 
will be coded using MedDRA (Medical Dictionary for Regulatory Activities). 
When the database has been declared to be complete and accurate, it will be locked. 
12.2 Sample Size Estimation 
Approximately 300 subjects will be randomized in a 1:1:1 ratio to receive ABP 798, 
rituximab (US), or rituximab (EU), stratified by geographic region, seropositivity 
(RF-positive and/or CCP-positive vs. RF-negative and CCP-negative), and number of 
prior biologic therapies used for RA (1 vs. > 1).  The sample size will provide > 90% 
power to demonstrate similarity on the primary PK endpoints based on an assumption of 
between-subject variability (as measured by coefficient of variation) of 40%, true 
geometric mean ratio (GMR) of 1 among ABP 798, rituximab (US), or rituximab (EU), a 
margin of (0.8, 1.25) and 15% dropout by week 24.  The PK similarity will be tested 
between ABP 798 versus rituximab (US) and ABP 798 versus rituximab (EU), each with 
a significance level of 0.05.  The similarity between rituximab (US) and rituximab (EU) 
will be evaluated as well. 
12.3 Statistical Analysis Plan 
A SAP will be written and finalized prior to any lock of the study database.  The SAP will 
provide a detailed description of the statistical methods and expand on the details 
provided in the protocol.  Additional analyses may be added.  Table, listing, and figure 
shells will also be included. 
12.4 Randomization 
Randomization will be performed by an IXRS.  The randomization schedule will be 
prepared by a statistician not involved in the conduct of the study.  Randomization will be 
stratified by geographic region, seropositivity (RF-positive and/or CCP-positive vs. RF-
negative and CCP-negative), and number of prior biologic therapies used for RA (1 vs. 
> 1).   


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 57 of 77 
Confidential 
 
12.5 Analysis Populations 
The analysis for the PK endpoints will be based on the PK Analysis Set.  Sensitivity 
analysis for the PK endpoints will be based on the per-protocol PK Analysis Set.  The 
primary analysis for the PD endpoint and efficacy endpoints will be performed using the 
Full Analysis Set (FAS).  The Per-protocol Analysis Set will be used for sensitivity 
analyses of the key efficacy endpoints.  The analysis of safety endpoints will be based 
on the Safety Analysis Set. 
12.5.1 
Full Analysis Set  
The FAS includes all subjects randomized in the study.  It will be analyzed according to 
randomized treatment group (regardless of actual treatment received).  
12.5.2 
Per-protocol Set 
The Per-protocol Analysis Set includes all subjects randomized in the study who have 
completed the week 24 disease assessment and did not experience a protocol deviation 
that affects their evaluation of the secondary objectives of the study to assess clinical 
efficacy.  It will be analyzed according to actual treatment received.  The protocol 
deviations that affect evaluation of efficacy endpoints will be determined based on a 
blinded data review prior to database lock. 
12.5.3 
Safety Analysis Set  
The Safety Analysis Set includes all randomized subjects who received at least 1 
infusion of investigational product.  It will be analyzed according to actual treatment 
received.  
12.5.4 
Pharmacokinetic Analysis Set  
The PK Analysis Set includes all randomized subjects who received the full 
protocol-specified dose on Day 1 and had an evaluable serum concentration-time 
profile.  It will be analyzed according to actual treatment received.  
12.5.5 
Per-protocol Pharmacokinetic Analysis Set  
The Per-protocol PK Analysis Set consists of a subset of subjects in the PK Analysis Set 
who do not experience a protocol deviation that affects their evaluation.  It will be 
analyzed according to actual treatment received.  The protocol deviations that affect 
evaluation of PK endpoints will be determined based on a blinded data review prior to 
database lock. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 58 of 77 
Confidential 
 
12.6 Statistical Methods 
The final analysis will be performed after all subjects have completed or have had 
the opportunity to complete the week 48/EOS assessment. Secondary analyses of 
long-term effects and safety will be performed after all subjects have had the opportunity 
to complete the week 48/EOS assessment. 
All categorical variables will be summarized using the number and percent of subjects 
falling into each category and all continuous variables will be summarized using mean, 
standard error or standard deviation, median, minimum, maximum, and number of 
subjects with observations.  Safety endpoints will be summarized descriptively.  
Subgroup analyses (by age, race, sex, and stratification factors as appropriate) will be 
presented if deemed necessary.  
The PK similarity for each primary PK endpoint will be tested between ABP 798 versus 
rituximab (US) and ABP 798 versus rituximab (EU), each with a significance level of 
0.05.   
12.6.1 
Missing Data 
Imputation rules will be presented in the SAP before unblinding of the study for the final 
analysis.   
12.6.2 
Demographic and Baseline Data 
The following demographic and baseline characteristics will be summarized:  age (in 
years, at time of signing informed consent), race, gender, ethnicity, height, and weight.  
Disease history and baseline disease characteristics will also be summarized. 
12.6.3 
Subject Disposition 
The following information will be summarized for subject disposition and accountability: 
 
number of subjects randomized will be tabulated by country, center, and 
stratification factor  
 
subject disposition (including number of subjects who were screened, 
randomized, treated with ABP 798/rituximab [US]/rituximab [EU], completed 
treatment, discontinued treatment with reason for discontinuation, completed 
study, and discontinued study with reason for discontinuation) 
 
summaries of analysis populations with reason for exclusion 
 
important protocol deviations 
 
number and percent of subjects on study at each visit  
 
randomization list of subjects and their actual versus randomized treatment 
group 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 59 of 77 
Confidential 
 
12.6.4 
Pharmacokinetics 
The PK similarity will be demonstrated by comparing the 90% confidence interval (CI) for 
the GMR of test (ABP 798)-to-reference (US-licensed rituximab or EU-authorized 
rituximab) and rituximab [US] to rituximab [EU] for AUCinf and for Cmax following the 
second infusion of the first dose with the bounds of 0.8 to 1.25, where =0.05.  PK 
parameters will be calculated using non-compartmental methods.  Point estimates and 
CIs for the GMR will be estimated from an analysis of covariance model using the PK 
Analysis Set. 
Other PK endpoints, AUC0-14 day after first infusion, AUC0-12 wk after the first and second 
infusions of the first dose and Cmax after the first infusion of the first dose, will be 
analyzed using the same methods as stated above.  Additional PK parameters including 
the time of Cmax (tmax), terminal elimination half-life (t1/2), and the terminal elimination rate 
constant (λz) will be summarized descriptively. 
12.6.5 
Pharmacodynamics 
The PD similarity will be evaluated descriptively by calculating the 90% CI of complete 
CD19+ cell depletion rate difference between test-to-reference.  The 95% CI will also be 
provided.  The point estimate and CIs for rate difference will be estimated using a 
generalized linear model (specifically, a log-binomial regression model) with relevant 
baseline values and stratification factors as covariates using the FAS. 
12.6.6 
Efficacy 
Clinical equivalence will be evaluated for DAS28-CRP at week 24 using the FAS 
consisting of all randomized subjects. If PK similarity is established between 
rituximab (US) and rituximab (EU), the 2 arms will be combined into a single 
reference arm for the primary assessment of clinical equivalence between ABP 
798 and rituximab.  The results for ABP 798 vs. rituximab (EU) and ABP 798 vs. 
rituximab (US) will be provided for descriptive purposes. If PK similarity is not 
established, the ABP 798 arm will be compared to each of the individual rituximab 
arms separately to  stablish clinical equivalence of ABP 798 to the individual 
reference arms. The 95% CI for both the difference between ABP 798 and US-licensed 
rituximab or EU-authorized rituximab in DAS28-CRP change from baseline will also be 
provided. 
With the planned sample size, there is 94% probability that the 90% CI of the 
difference between the ABP 798 arm and the pooled rituximab (rituximab [EU] and 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 60 of 77 
Confidential 
 
rituximab [US]) arm and 83% probability that the 90% CI of the difference between test 
(ABP 798) and reference (US-licensed rituximab or EU-authorized rituximab) in 
DAS28-CRP change from baseline at week 24 will fall into the equivalence margin of ± 
0.6 (EULAR response criteria), assuming a standard deviation of 1.4 (Volkmann et al, 
2010).  DAS28-CRP at other timepoints and ACR 20, 50 and 70 will be summarized 
descriptively.   
In addition, 90% and 95% CI for the risk ratio (RR) and risk difference (RD) of ACR20, 
ACR50 and ACR70 at week 24 between ABP 798 and rituximab (pooled US-licensed 
and EU-authorized rituximab, US-licensed rituximab or EU-authorized rituximab) will 
also be provided and the outcome is descriptive.  The CIs for the difference of DAS28-
CRP change from baseline between the ABP 798 and rituximab arms will be estimated 
using repeated-measures analysis.  Data from all assessed time points through week 24 
visit will be included in the analysis.  Besides stratification variables, visit (week), 
treatment, and treatment-by-visit interaction will be included in the model, with visit as a 
categorical variable.  The CIs for RR and RD of ACR20/50/70 between ABP 798 and 
rituximab arms will be estimated based on a repeated measures analysis where data 
from all assessed time points through week 24 visit are included.  Besides stratification 
variables, visit week (as a categorical variable), treatment, and treatment-by-visit 
interaction will be included in the generalized estimating equation (GEE) model.   
Other endpoints, RR and RD of ACR 20/50/70 at weeks 8, 12, 40, and 48, and RR and 
RD of ACR50 and ACR70 at weeks 8, 12, 40, and 48 will be summarized descriptively 
by treatment.  In addition, the difference of DAS28-CRP change from baseline between 
the ABP 798 and rituximab arms will be summarized descriptively by treatment at weeks 
8, 12, 40, and 48. 
12.6.7 
Safety 
All safety analyses will be performed using the Safety Analysis Set based on subject’s 
actual treatment received.  Safety analysis will include analyses of AEs, clinical 
laboratory tests, vital signs, ECGs, and antidrug antibodies.  In general, summaries will 
be provided separately for day 1 up to the 1st infusion of the 2nd dose of investigational 
product by actual treatment groups, for the entire study by treatment groups defined by 
first dose, and for the day of the 1st infusion of the 2nd dose of investigational product up 
to the week 48/EOS visit with subjects grouped as receiving ABP 798 for both 1st and 2nd 
doses, receiving rituximab (US) for the 1st dose and ABP 798 for the 2nd dose, and 
receiving rituximab (EU) for both 1st and 2nd doses, unless otherwise specified.  


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 61 of 77 
Confidential 
 
12.6.7.1 
Investigational Product Administration 
For the investigational product (ABP 798, rituximab [US], or rituximab [EU]), summary 
statistics will be provided for the total number of doses.   
12.6.7.2 
Adverse Events 
Safety analyses will focus on treatment-emergent AEs.  Treatment-emergent events are 
those that begin or increase in severity or frequency at or after the time of first treatment 
up to the week 48/EOS visit (or within 28 days following the last dose of study treatment 
if subject discontinues study early).  All treatment-emergent AEs will be summarized by 
treatment arm and according to the MedDRA system organ class (SOC) and preferred 
term.  Summaries will be provided for the incidence of all treatment-emergent AEs and 
by severity and relatedness to investigational product.  Additional summaries will be 
presented for SAEs. 
All AE data will be listed by subject, and a separate listing will include all SAEs, including 
any deaths on study. 
AEs of special interest (Section 11.3) will be summarized separately.   
The exposure adjusted subject incidence rates of adverse events throughout the study 
may be tabulated for selected categories of adverse events. 
12.6.7.3 
Immunogenicity 
The number and percentage of subjects developing antidrug antibodies and those 
developing neutralizing antibodies will be tabulated separately for day 1 to the 1st 
infusion of the 2nd dose of investigational product by actual treatment groups, and for 
day 1 of first infusion of second dose to 4 weeks after the 2nd infusion of the 2nd dose and 
for the entire study by treatment groups defined by first dose.  
12.6.7.4 
Concomitant Medications and Therapies 
Concomitant medications will be coded by WHODRUG and will be summarized by 
treatment group with number and percentage of subjects receiving each category of 
medication. 
12.6.7.5 
Clinical Laboratory Test 
Clinical laboratory test results and change from baseline will be summarized by time 
point.  In addition, shift tables, from baseline to the worst on-study laboratory toxicity 
based on CTCAE v4 grading, will be presented. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 62 of 77 
Confidential 
 
12.6.7.6 
Vital Signs and Physical Examinations 
Vital sign data (observed and change from baseline) will be summarized using 
descriptive statistics by time point and treatment.   
Abnormal findings from physical examinations will be listed by subject and assessed for 
clinical significance, which will be included in the AE listings and summaries. 
12.6.8 
Interim Analysis 
No formal interim analysis is planned for this study. 
12.6.9 
Data Monitoring Committee 
A DMC external to Amgen and PRA will be formed with members consisting of 
individuals chosen for their expertise in rheumatology.  Members of the DMC will include 
at a minimum, physicians external to Amgen and PRA, and appropriate statistical 
representation external to Amgen and PRA.  The primary role of this independent DMC 
will be to monitor safety data.  
The DMC will review unblinded safety data at regular intervals, as outlined in the DMC 
charter (approximately twice yearly; the start date will depend on subject accrual rates). 
In addition, the DMC will conduct an initial safety analysis after the first 18 subjects have 
received at least 1 dose of investigational product (ie, infusions on days 1 and 15) of 
either ABP 798, rituximab (US) or rituximab (EU).   
The DMC will communicate major safety concerns and recommendations regarding 
study modification or termination to Amgen management at any time during the conduct 
of the study.  
Records of all meetings will be archived.  Selected Amgen, or its designee, staff may 
serve as liaisons to the external DMC, but will not be voting members and will not be 
unblinded to the results.  Details regarding the DMC will be provided in the DMC charter. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 63 of 77 
Confidential 
 
13 
MONITORING PROCEDURES (QUALITY ASSURANCE) 
Amgen has ethical, legal, and scientific obligations to conduct this study in accordance 
with established research principles and ICH GCP guidelines.  As such, in order to fulfill 
these obligations and to maintain current of study progress, Amgen monitors, or 
Amgen’s designees, will visit the investigative sites during study conduct, in addition to 
maintaining telephone and written communication.  On-site visits, telephone calls, and 
regular inspection of the eCRFs will be conducted in order to assess subject enrollment, 
compliance with protocol procedures, completeness and accuracy of data entered on the 
eCRFs, verification of eCRF data against original source documents, and occurrence of 
AEs.  The Investigator must provide the monitor with full access to all source and study 
documents. 
13.1 Routine Monitoring 
Amgen, or its designee, assigned monitors will conduct regular site visits to the 
investigational facilities for the purpose of monitoring various aspects of the study.  The 
Investigator must agree to Amgen, or its designee, authorized personnel having direct 
access to the clinical (or associated) files and clinical study supplies (dispensing and 
storage areas) for all study subjects considered for study entry for the purpose of 
verifying entries made in the eCRF, and assist with their activities, if requested.  
Adequate time and space for monitoring visits should be made available by the 
Investigator. 
The site must complete the eCRFs in a timely manner and on an ongoing basis to allow 
regular review by the study monitor. 
Whenever a subject name is revealed on a document that is to be collected for the 
Sponsor, the name must be blacked out permanently by the site personnel, leaving the 
initials visible, and must be annotated with the subject number as identification. 
13.2 Inspections and Auditing Procedures 
Amgen, or its designee, may conduct audits at the investigative sites, including, but not 
limited to, drug supply, presence of required documents, the informed consent process, 
and comparison of eCRFs with source documents.  All medical records (progress notes) 
must be available for audit.  The Investigator agrees to participate with audits conducted 
at a convenient time in a reasonable manner. 
Government regulatory authorities may also inspect the Investigator during or after the 
study.  The Investigator or designee should contact Amgen, or its designee, immediately 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 64 of 77 
Confidential 
 
if this occurs.  He/she must cooperate fully with regulatory authorities or other audits 
conducted at a convenient time in a reasonable manner. 
The purpose of an audit is to assess whether ethics, regulatory and quality requirements 
are fulfilled. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 65 of 77 
Confidential 
 
14 
STUDY MANAGEMENT AND MATERIALS 
14.1 Electronic Case Report Forms 
An eCRF will be used to store and transmit subject information.  The file structure and 
format for the eCRF will be provided by the Sponsor or their representative and should 
be handled in accordance with the instructions provided. 
The eCRF must be reviewed and electronically signed and dated by the Investigator. 
Access to the eCRF will be strictly password protected and limited to personnel directly 
participating in the study.  Data should be entered into the eCRF completely by 
examining personnel or the appropriate site staff.  The eCRF 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 eCRFs and computers that store them must be accessible to study 
monitors and other regulatory auditors. 
14.2 Data Collection 
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 will contain: 
 
the date of the visit and the corresponding day or visit in the study schedule (eg, 
screening, day 1, week 2, etc). 
 
general condition and status remarks by the subject, including any significant 
medical findings.  The severity, frequency, duration, and resolution of any 
reported AE, and the Investigator's assessment as to whether or not the 
reported AE is investigational product-related. 
 
changes in concomitant medications or dosages. 
 
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 via telephone or other means that provides 
significant clinical information will also be documented in the medical record (progress 
notes), as described above.  
Information from the medical records (progress notes) and other source documents will 
be promptly transcribed to the appropriate section of the eCRF. 
Changes to information in the medical record (progress notes), CRF, and other source 
documents will be initialed and dated on the day the change is made by the Investigator 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 66 of 77 
Confidential 
 
or designee.  If the reason for the change is not apparent, a brief explanation for the 
change will be written adjacent to the change. 
14.3 Source Documents Maintenance 
Source documents contain the results of original observations and activities of a clinical 
investigation.  Source documents include, but are not limited to, medical records 
(progress notes), computer printouts, screening logs and recorded data from automated 
instruments.  
All source documents from this study will be maintained by the Investigator and made 
available for inspection by authorized persons.  The original signed informed consent for 
each subject shall be filed with records kept by the Investigator and a copy shall be 
given to the subject. 
14.4 Record Maintenance 
All data derived from the study will remain the property of Amgen Inc. 
Records must be retained in accordance with the current ICH Guidelines on GCP.  All 
essential study documents including records of subjects, source documents, eCRFs and 
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 the investigational products.  However, 
essential documents may be retained for a longer period if required by the applicable 
regulatory requirements or by agreement with the Sponsor.   
The Investigator shall take responsibility for maintaining adequate and accurate hard 
copy source documents of all observations and data generated during this study.  Such 
documentation is subject to inspection by the Sponsor, its representatives, and 
regulatory authorities. 
If an Investigator moves, withdraws from an investigation, 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. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 67 of 77 
Confidential 
 
14.5 Confidentiality 
All information obtained during the conduct of the study with respect to the subject’s 
state of health will be regarded as confidential.  For disclosure of any such information, 
an agreement will be obtained in writing.  
The Investigator must ensure that each subject’s anonymity is maintained.  On eCRFs 
and other documents submitted to the Sponsor or the CRO, subjects must not be 
identified by name.  Instead, subjects will only be known by the unique subject number 
allocated to them in order to ensure confidentiality on all study documentation.  Subjects 
will retain this unique number throughout the study.  The Investigator will keep a 
separate log of these codes. 
In order to comply with government regulatory guidelines and to ensure subject safety, it 
may be necessary for the Sponsor and its representative, the CRO personnel, the local 
research review board, or the US FDA to review subjects’ medical records as they relate 
to this study.  Only the subject’s unique number on the eCRFs will identify him/her, but 
their full names may be made known to a drug regulatory authority or other authorized 
government or health care officials, if necessary, and to personnel designated by the 
Sponsor. 
Documents that are not for submission to the Sponsor or the CRO (eg, consent forms) 
will be maintained by the Investigator in strict confidence, except to the extent necessary 
to allow monitoring by the Sponsor and the CRO, and auditing by regulatory authorities.  
No documents identifying subjects by name will leave the investigative site and subject 
identity will remain confidential in all publications related to the study. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 68 of 77 
Confidential 
 
15 
ADMINISTRATION PROCEDURES 
15.1 Regulatory Approval 
Amgen Inc., or their appointed agents, will be responsible for ensuring that appropriate 
regulatory authority approvals are obtained, according to local country requirements. 
No subject may enter the study until this approval has been obtained.  A copy of the 
approval (where one is provided as requested, according to local country requirements) 
will be provided to the Investigator and to the IRB(s)/IEC(s). 
15.2 Protocol Amendments 
In accordance with ICH Topic E 6 (R1) Guideline for GCP the Investigator should not 
implement any deviation from or changes of the protocol without agreement by the 
Sponsor and documented approval from the IRB/IECs of a protocol amendment, except 
where necessary to eliminate an immediate hazard(s) to study subjects, or when the 
change(s) involves only logistical or administrative aspects of the study (eg, change in 
monitor[s], change of telephone number[s]).  
Any change to the protocol must be handled as a protocol amendment.  Any potential 
amendment must be approved by the Sponsor.  A written amendment must be 
submitted to the appropriate regulatory authorities and to the IRB/IECs assuming this 
responsibility.  The Investigator must await IRB/IEC approval of protocol amendments 
before implementing the changes, except where necessary to eliminate apparent 
immediate hazard to subjects.  In these cases, the IRB/IEC must be notified within 
5 days of the change. 
All amendments to the protocol must be approved in writing by both the appropriate 
regulatory authorities and the IRB/IEC, except for administrative amendments, which 
require notification but not written approval.  Once approved, the protocol amendment 
will be distributed to all recipients of the original protocol, with instructions to append the 
amendment to the protocol. 
If, in the judgment of the local IRB/IEC, the Investigator and/or Sponsor, the protocol 
amendment alters the study design or procedures and/or increases the potential risk to 
the subject, the currently approved written ICF will require modification.  The modified 
ICF must also be reviewed and approved by the Sponsor, appropriate regulatory 
authorities, and the IRB/IEC.  In such cases, repeat informed consent must be obtained 
from subjects enrolled in the study before participation continues. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 69 of 77 
Confidential 
 
15.3 Protocol Adherence and Deviations 
The protocol must be read thoroughly, and the instructions must be followed.  However, 
exceptions will be made in emergency situations when the protection, safety, and 
well-being of the subject requires immediate intervention based on the judgment of the 
Investigator or (a) responsible, appropriately trained, and credentialed professional(s) 
designated by the Investigator as a sub-investigator.  
In the event of a significant protocol deviation due to an emergency, accident, or error, 
the Investigator or designee must contact the Medical Monitor at the earliest possible 
time by telephone.  This allows for an early joint decision to be made as to whether or 
not the subject should continue in the study.  The Investigator, Sponsor, and Medical 
Monitor will document this decision. 
15.4 Publication Policy 
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), 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; 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 are 
to meet conditions 1, 2, 3, and 4. 
 
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 are to 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 are to qualify for authorship, and all those 
who qualify are to be listed. 
 
Each author is to 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 between the institution, Investigator, and Amgen will detail the procedures 
for, and timing of, Amgen’s review of publications. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 70 of 77 
Confidential 
 
15.5 Clinical Study Report 
A final clinical study report will be prepared according to the ICH guideline on Structure 
and Contents of Clinical Study Reports.  A final clinical study report will be prepared 
regardless of whether the study is completed or prematurely terminated.    
15.6 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.  Financial Disclosure Statements will be completed only as required by local 
regulations. 
15.7 Compensation 
Any arrangements for compensation to subjects for injury or illness that arises in the 
study are described in the Compensation for Injury section of the Informed Consent that 
is available as a separate document. 
15.8 Discontinuation of the Study 
This study may be terminated by Amgen at any time.  In terminating the study, Amgen, 
the CRO (PRA) and the Investigator will ensure that adequate consideration is given to 
protection of the subjects’ interests.  Amgen will not provide ABP 798 or rituximab after 
termination of the trial or upon discontinuation of the study for the subject. 
15.9 Study Center File Management 
The Investigator is responsible for assuring that the Study Center File is maintained.  
The Study Center File will contain, but not be limited to, the information listed below: 
1. Investigator’s Brochure 
2. Current, signed version of the protocol and any previous versions of the protocol 
3. Protocol amendments (if applicable) 
4. Operations Manual (if applicable) 
5. Current ICF (blank) and any previous versions of the ICF 
6. Curricula Vitae of Investigator(s) and sub-investigator(s) and photocopy of their 
respective license(s) where required by law; Original US FDA Form 1572 (for all 
studies conducted under US Investigational New Drug [IND] regulations), signed 
by all Principal Investigators.  The names of any sub-investigators must appear 
on this form.  Investigators must also complete all regulatory documentation as 
required the ICH GCP and by local or national regulations 
7. Documentation of IRB/IEC approval of the protocol, the ICF, any protocol 
amendments, and any ICF revisions 
8. All correspondence between the Investigator, IRB/IEC, and the Sponsor/CRO 
relating to study conduct 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 71 of 77 
Confidential 
 
9. Lab certification(s) 
10. Monitoring log 
11. Investigational product invoices 
12. Signature list of all staff completing eCRFs 
13. Signature list of all staff completing drug accountability summaries 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 72 of 77 
Confidential 
 
16 
REFERENCE LIST 
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO III, et al. 2010 
rheumatoid arthritis classification criteria: an American College of 
Rheumatology/European League Against Rheumatism collaborative initiative. 
Arthritis Rheum. 2010;62: 2569–81. 
Biogen Idec, Inc. and Genentech, Inc.  Rituxan® (rituximab) Injection for Intravenous 
Infusion.  Package Insert.  September 2013. 
Blüml S, McKeever K, Ettinger R, et al.  B-cell targeted therapeutics in clinical 
development.  Arth Res Ther.  2013;15(Suppl 1):S4-S25. 
CHMP/437/04 Rev 1(draft).  Guideline on similar biological medicinal products.   
Choy EH, Panayi GS.  Cytokine pathways and joint inflammation in rheumatoid 
arthritis.  N Engl J Med. 2001;344(12):907-16. 
Cohen SB, Emery P, Greenwald MW, et al.  Rituximab for rheumatoid arthritis 
refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, 
double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety 
at twenty-four weeks.  Arthritis Rheum. 2006 Sep;54(9):2793-806. 
EMEA/CHMP/BWP/247713/2012 (Rev1)(draft).  Guideline on similar biological 
medicinal products containing biotechnology-derived proteins as active substance:  
quality issues.  
EMEA/CHMP/BMWP/42832/2005 Rev.1.(draft).  Guideline on similar biological 
medicinal products containing Biotechnology-derived proteins as active substance:  
Non-clinical and clinical issues.   
Hochberg MC, Rowland WC, Dwosh I, et aI. The American College of Rheumatology 
1991 Revised Criteria for the Classification of Global Functional Status in 
Rheumatoid Arthritis. Arthritis & Rheumatism. 1992;35(5):498-502. 
McInnes IB, Schett G.  Cytokines in the pathogenesis of rheumatoid arthritis.  Nat 
Rev Immunol. 2007;7(6):429-42. 
Roche Pharma AG.  MabThera® (rituximab) Injection for Intravenous Infusion.  
Package Insert.  May 2016. 
Tuscano JM, Sands J.  B cell reductive therapy with rituximab in the treatment of 
rheumatoid arthritis.  Biologics:  Target & Therapy.  2009;3:225-32. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 73 of 77 
Confidential 
 
US FDA.  Guidance for Industry:  Scientific considerations in demonstrating 
biosimilarity to a reference product.  February 2012a, US FDA (draft). 
US FDA.  Guidance for Industry:  Quality considerations in demonstrating 
biosimilarity to a reference protein product.  February 2012b, US FDA (draft). 
van Gestel AM, Haagsma CJ, van Riel PL.  Validation of rheumatoid arthritis 
improvement criteria that include simplified joint counts.  Arthritis Rheum. 1998 
Oct;41(10):1845-50. 
Volkmann ER, Agrawal H, Maranian P, Furst DE.  Rituximab for rheumatoid arthritis: 
A meta-analysis and systematic review.  Clin Med Insights: Therapeutics 2010:2 
749-760. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 74 of 77 
Confidential 
 
17 
APPENDICES 
17.1 Appendix 1: Elements of Informed Consent 
ELEMENTS OF INFORMED CONSENT 
Both the informed consent discussion and the written ICF and any other written 
information to be provided to subjects should include explanations of the following: 
 
 
That the study involves research. 
 
The purpose of the study. 
 
The study treatment(s) and the probability for random assignment to each 
treatment. 
 
The study procedures to be followed including all invasive procedures. 
 
The subject’s responsibilities. 
 
Those aspects of the study that are experimental. 
 
The reasonably foreseeable risks or inconveniences to the subject and, when 
applicable, to an embryo, fetus, or nursing infant. 
 
The reasonably expected benefits.  When there is no intended clinical benefit to 
the subject, the subject should be made aware of this. 
 
The alternative procedure(s) or course(s) of treatment that may be available to 
the subject, and their important potential benefits and risks. 
 
The compensation and/or treatment available to the subject in the event of 
study-related injury. 
 
The anticipated prorated payment, if any, to the subject for participating in the 
study. 
 
The anticipated expenses, if any, to the subject for participating in the study. 
 
That the subject’s participation in the study is voluntary and that the subject may 
refuse to participate or withdraw from the study, at any time, without penalty or 
loss of benefits to which the subject is otherwise entitled. 
 
That the monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) 
will be granted direct access to the subject’s original medical records for 
verification of clinical study procedures and/or data, without violating the 
confidentiality of the subject, to the extent permitted by the applicable laws and 
regulations and that, by signing a written ICF, the subject or the subject’s legally 
acceptable representative is authorizing such access. 
 
That records identifying the subject will be kept confidential and, to the extent 
permitted by the applicable laws and/or regulations, will not be made publicly 
available.  If the results of the study are published, the subject’s identity will 
remain confidential. 
 
That the subject or the subject’s legally acceptable representative will be 
informed in a timely manner if information becomes available that may be 
relevant to the subject’s willingness to continue participation in the study. 
 
The person(s) to contact for further information regarding the study and the 
rights of study subjects, and whom to contact in the event of study-related injury. 
 
The foreseeable circumstances and/or reasons under which the subject’s 
participation in the study may be terminated. 
 
The expected duration of the subject’s participation in the study. 
 
The approximate number of subjects involved in the study. 
 
 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 75 of 77 
Confidential 
 
17.2 Appendix 2: American College of Rheumatology Revised Criteria for 
the Classification of Functional Capacity in RA 
American College of Rheumatology revised criteria for classification of functional status 
in rheumatoid arthritis a 
Class I 
Completely able to perform usual activities of daily living (self-care, 
vocational, and avocational) 
Class II 
Able to perform usual self-care and vocational activities, but limited in 
avocational activities 
Class III 
Able to perform usual self-care activities, but limited in vocational and 
avocational activities 
Class IV 
Limited in ability to perform usual self-care, vocational, and avocational 
activities 
a 
Usual self-care activities include dressing, feeding, bathing, grooming, and toileting.  
Avocational (recreational and/or leisure) and vocational (work, school, homemaking) 
activities are patient-desired and age- and sex-specific. 
Hochberg MC, Rowland WC, Dwosh I, et aI. The American College of Rheumatology 
1991 Revised Criteria for the Classification of Global Functional Status in Rheumatoid 
Arthritis. Arthritis & Rheumatism. 1992;35(5):498-502. 
 
 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 76 of 77 
Confidential 
 
17.3 Appendix 3: DAS28 and ACR Core Set Measurements 
DAS28 Core Set Measurements: 
 
tender joint count 
 
swollen joint count 
 
Subject's Global Health Assessment 
 
CRP  
ACR Core Set Measurements: 
 
tender joint count 
 
swollen joint count 
 
Subject's Global Health Assessment 
 
Investigator's Global Health Assessment 
 
Subject's assessment of pain 
 
Health Assessment Questionnaire – Disability Index (HAQ-DI) 
 
CRP  
Joints to be Assessed for Swelling and Tenderness 
The joints to be assessed for tenderness (68 joints) and swelling (66 joints) consist of 
the following: 
 
temporomandibular joint 
 
sternoclavicular joint 
 
acromioclavicular joint 
 
shoulders* 
 
elbows* 
 
wrists* 
 
interphalangeal on digit 1* 
 
distal interphalangeal joints on digits 2 - 5 
 
proximal interphalangeal joints on digits 2 - 5* 
 
metacarpophalangeal joints on digits 1 - 5* 
 
hips (tenderness only) 
 
knees* 
 
ankles 
 
metatarsals 
 
interphalangeal joints on toes 1 - 5 
 
metatarsophalangeal joints on toes 1 - 5 
Joints assessed for swelling are the same, with the exception of the hips, which are 
excluded. 
* The 28 joints used to calculate the DAS28.


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 77 of 77 
Confidential 
 
 
17.4 Appendix 4: Subjective Assessment Scales 
Subject's Assessment of Disease Related Pain: 
The subject's assessment of their current level of pain on a 100-mm VAS.  The left-hand 
extreme of the line should be described as "no pain at all" and the right-hand extreme as 
"worst pain imaginable." 
Subject's Global Health Assessment: 
The subject's overall assessment of their disease activity in the past week on a 100-mm 
VAS. The left-hand extreme of the scale will be described as "no RA activity at all" 
(symptom-free and no arthritis symptoms) and the right-hand extreme as "worst RA 
activity imaginable" (maximum arthritis disease activity). 
Investigator's Global Health Assessment: 
The Investigator's assessment of the subject's current disease activity on a 100-mm 
VAS. The left-hand extreme of the scale will be described as "no activity at all" 
(symptom-free and no arthritis symptoms) and the right-hand extreme as "worst activity 
imaginable" (maximum arthritis disease activity). 
Health Assessment Questionnaire-Disability Index 
The HAQ-DI is a questionnaire on which subjects are asked to rate their level of difficulty 
on daily activities (dressing and grooming, arising, eating, and walking) and personal 
abilities (hygiene, reach, grip, and activity), as well as their use of aids, devices, or help 
from another person for these activities and disabilities. 
 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 1 of 7 
 
Confidential 
 
 
A RANDOMIZED, DOUBLE-BLIND STUDY TO COMPARE 
PHARMACOKINETICS AND PHARMACODYNAMICS, EFFICACY AND 
SAFETY OF ABP 798 WITH RITUXIMAB IN SUBJECTS WITH MODERATE 
TO SEVERE RHEUMATOID ARTHRITIS 
 
SUMMARY OF CHANGES 
 
Test Drug: 
ABP 798 
Protocol Number: 
20130108 
EudraCT number:  2013-005543-90 
Study Phase:  
1/3 
 
 
Date and Version: 
20 March 2018, 4.0 
 
Sponsor: 
 
Amgen Inc. 
One Amgen Center Drive 
Thousand Oaks, CA 91320 US 
 
Clinical Research Organization (CRO): 
 
PRA Health Sciences 
4130 ParkLake Avenue 
Raleigh, NC 27612 US 
 
 
 
 
 
This study will be conducted in compliance with the protocol, Good Clinical Practice 
(GCP) as set forth in the International Conference on Harmonisation (ICH) guidelines on 
GCP (ICH E6), and applicable local regulatory requirements. 
 
 
CONFIDENTIAL 
This document is a confidential communication of Amgen, Inc. Acceptance of this document constitutes 
agreement by the recipient that no unpublished information contained herein shall be published or 
disclosed without prior written approval, except that this document may be disclosed to the appropriate 
Institutional Review Board(s)/Independent Ethics Committee(s) under the condition that they keep it 
confidential. 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 2 of 7 
 
Confidential 
 
 
Rationale: 
This amendment is issued to make the following changes: 
 
Update the Table of Contents to reflect the correct title of Appendix 3. 
Delete the primary analysis as the revised regulatory filing strategy nullifies the 
 need for it. 
Clarify the ACR improvement description. 
Added a secondary objective to demonstrate the PK similarity of rituximab (US) a 
rituximab (EU). 
Update the sample size estimation and statistical methods language to clarify the 
efficacy analysis. 
Clarify the efficacy measurements, procedures, and remove redundancies as needed. 
Specify the statistical approach for the efficacy evaluation. 
Update to clarify the dosing requirement for inclusion in the PK analysis population 
   
 
 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 3 of 7 
 
Confidential 
 
 
Summary of Changes 
Any changes in the synopsis that also appear in the body of the protocol will appear only 
once in this summary of changes document, under the section number.  Additions are in 
bold and deletions are in strikethrough. 
Section 2, Synopsis, Objectives 
Section 7.2, Secondary Objectives 
Add:  
• 
to demonstrate PK similarity between rituximab (US) and rituximab (EU) as 
assessed by AUCinf and by Cmax after second infusion of the first dose 
Section 2, Synopsis, Study Design and Methodology 
Section 8.1, Overall Study Design and Plan 
Remove: 
The primary analysis will be conducted when all subjects have completed or have had 
the opportunity to complete the week 30 assessments. 
Section 2, Synopsis, Study Evaluations, Secondary Criteria 
Add: 
• 
ACR20, ACR50 and ACR70   
 
Section 2, Synopsis, Statistical Methods 
Replace: 
The PK similarity will be demonstrated by comparing the 90% confidence interval (CI) for 
the GMR of test (ABP 798)-to-reference (rituximab [US] or rituximab [EU]) for AUCinf and 
Cmax following the second infusion of the first dose with the bounds of 0.8 to 1.25, where 
α=0.05. 
Clinical equivalence will be evaluated for DAS28-CRP at week 24 using the Full Analysis 
Set consisting of all randomized subjects.  With the planned sample size, there is 83% 
probability that the 90% CI of the difference between test (ABP 798) and reference 
(rituximab [US] or rituximab [EU]) in DAS28-CRP change from baseline will fall into the 
equivalence margin of ± 0.6 (EULAR response criteria), assuming a standard deviation 
of 1.4 (Volkmann, 2012). The 95% CI for both the difference between ABP 798 and US-
licensed rituximab or EU authorized rituximab in DAS28 CRP change from baseline will 
also be provided. 
With: 
The PK similarity will be demonstrated by comparing the 90% confidence interval (CI) for 
the GMR of test (ABP 798)-to-reference (rituximab [US] or rituximab [EU]) and 
rituximab [US] to rituximab [EU] for AUCinf and for Cmax following the second infusion 
of the first dose with the bounds of 0.8 to 1.25, where α=0.05.   
Clinical equivalence will be evaluated for DAS28-CRP at week 24 using the Full Analysis 
Set consisting of all randomized subjects. If PK similarity is established between 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 4 of 7 
 
Confidential 
 
 
rituximab (US) and rituximab (EU), the 2 arms will be combined into a single 
reference arm for the primary assessment of clinical equivalence between ABP 
798 and rituximab.  The results for ABP 798 vs. rituximab (EU) and ABP 798 vs. 
rituximab (US) will be provided for descriptive purposes. If PK similarity is not 
established, the ABP 798 arm will be compared to each of the individual rituximab 
arms separately to establish clinical equivalence of ABP 798 to the individual 
reference arms.   
With the planned sample size, there is 94% probability that the 90% CI of the 
difference between the ABP 798 arm and the pooled rituximab (rituximab[EU] and 
rituximab[US]) arm and 83% probability that the 90% CI of the difference between test 
(ABP 798) and reference (US-licensed rituximab or EU-authorized rituximab) in 
DAS28-CRP change from baseline at week 24 will fall into the equivalence margin of ± 
0.6 (EULAR response criteria), assuming a standard deviation of 1.4 (Volkmann et al, 
2010). DAS28-CRP at other timepoints and ACR20, 50 and 70 will be summarized 
descriptively.   
Section 8.6.1.2.1, Efficacy Criteria 
Replace:  
ACR20 
To achieve ACR20 response, at least 20% improvement compared to baseline is 
required for both swollen and tender joint counts (66/68 joint counts; Section Error! 
Reference source not found.), as well as for 3 out of the following 5 additional 
parameters:  
 
With: 
 
ACR 
 
Improvement compared to baseline is required for both swollen and tender joint counts 
(66/68 joint counts; Section Error! Reference source not found.), as well as for 3 out 
of the following 5 additional parameters:  
 
Section 12.5.4, Pharmacokinetic Analysis Set 
Replace: 
 
The PK Analysis Set includes all randomized subjects who received at least 1 infusion of 
investigational product and had an evaluable serum concentration-time profile.  It will be 
analyzed according to actual treatment received. 
 
 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 5 of 7 
 
Confidential 
 
 
With: 
The PK Analysis Set includes all randomized subjects who received the full 
protocol-specified dose on Day 1 and had an evaluable serum concentration-time 
profile.  It will be analyzed according to actual treatment received. 
 
 
Section 12.6, Statistical Methods 
Replace: 
 
The primary analysis will be performed after all subjects have completed or have had the 
opportunity to complete the week 30 assessments.  Secondary analyses of long-term 
effects and safety will be performed after all subjects have had the opportunity to 
complete the week 48/EOS assessment. 
With: 
The final analysis will be performed after all subjects have completed or have had 
the opportunity to complete the week 48/EOS assessment. Secondary analyses of 
long-term effects and safety will be performed after all subjects have had the opportunity 
to complete the week 48/EOS assessment. 
Section 12.6.1, Missing Data 
Replace: 
Imputation rules will be presented in the SAP before unblinding of the study for the 
primary analysis. 
With: 
Imputation rules will be presented in the SAP before unblinding of the study for the final 
analysis. 
Section 12.6.4, Pharmacokinetics  
Replace:  
 
The PK similarity will be demonstrated by comparing the 90% confidence interval (CI) for 
the GMR of test (ABP 798)-to-reference (US-licensed rituximab or EU-authorized 
rituximab) for AUCinf and for AUCinf after first and second infusions and Cmax after second 
infusion of the first dose with the bounds of 0.8 to 1.25, where =0.05.   
 
With: 
The PK similarity will be demonstrated by comparing the 90% confidence interval (CI) for 
the GMR of test (ABP 798)-to-reference (rituximab [US] or rituximab [EU]) and 
rituximab [US] to rituximab [EU] for AUCinf and for Cmax following the second 
infusion of the first dose with the bounds of 0.8 to 1.25, where α=0.05. 
 
Section 12.6.6, Efficacy 
Replace: 
 
Clinical equivalence will be evaluated for DAS28-CRP at week 24 using the FAS 
consisting of all randomized subjects. With the planned sample size, there is 83% 
probability that the 90% CI of the difference between test (ABP 798) and reference (US 
licensed rituximab or EU-authorized rituximab) in DAS28-CRP change from baseline will 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 6 of 7 
 
Confidential 
 
 
fall into the equivalence margin of ± 0.6 (EULAR response criteria), assuming a standard 
deviation of 1.4 (Volkmann et al, 2010). The 95% CI for both the difference between 
ABP 798 and US-licensed rituximab or EU-authorized rituximab in DAS28-CRP change 
from baseline will also be provided.  In addition, 90% and 95% CI for the risk ratio (RR) 
and risk difference (RD) of ACR20 at week 24 between ABP 798 and US licensed 
rituximab or EU-authorized rituximab will also be provided, and the outcome is 
descriptive. The CIS for the difference of DAS28-CRP change from baseline between 
the ABP 798 and rituximab arms will be estimated using repeated-measures analysis. 
Data from all assessed time points through week 24 visit will be included in the analysis.  
Besides stratification variables, visit (week), treatment, and treatment-by-visit interaction 
will be included in the model, with visit as a categorical variable.  The CIs for RR and RD 
of ACR20 between ABP 798 and rituximab arms will be estimated based on a repeated 
measures analysis where data from all assessed time points through week 24 visit are 
included.  Besides stratification variables, visit week (as a categorical variable), 
treatment, and treatment-by-visit interaction will be included in the generalized 
estimating equation (GEE) model.  Other endpoints, RR and RD of ACR20 at weeks 8, 
12, 40, and 48, and RR and RD of ACR50 and ACR70 at weeks 8, 12, 24, 40, and 48 
will be summarized descriptively by treatment. In addition, the difference of DAS28-CRP 
change from baseline between the ABP 798 and rituximab arms will be summarized 
descriptively by treatment at weeks 8, 12, 40, and 48. 
 
With: 
Clinical equivalence will be evaluated for DAS28-CRP at week 24 using the FAS 
consisting of all randomized subjects.  If PK similarity is established between 
rituximab (US) and rituximab (EU), the 2 arms will be combined into a single 
reference arm for the primary assessment of clinical equivalence between ABP 
798 and rituximab.  The results for ABP 798 vs. rituximab (EU) and ABP 798 vs. 
rituximab (US) will be provided for descriptive purposes. If PK similarity is not 
established, the ABP 798 arm will be compared to each of the individual rituximab 
arms separately to  stablish clinical equivalence of ABP 798 to the individual 
reference arms. The 95% CI for both the difference between ABP 798 and US-licensed 
rituximab or EU-authorized rituximab in DAS28-CRP change from baseline will also be 
provided. 
 
With the planned sample size, there is 94% probability that the 90% CI of the 
difference between the ABP 798 arm and the pooled rituximab (rituximab [EU] and 
rituximab [US]) arm and 83% probability that the 90% CI of the difference between test 
(ABP 798) and reference (US-licensed rituximab or EU authorized rituximab) in DAS28 
CRP change from baseline at week 24 will fall into the equivalence margin of ± 0.6 
(EULAR response criteria), assuming a standard deviation of 1.4 (Volkmann et al, 2010).  
DAS28-CRP at other timepoints and ACR20, 50 and 70 will be summarized 
descriptively. 
 
In addition, 90% and 95% CI for the risk ratio (RR) and risk difference (RD) of ACR20, 
ACR50 and ACR70 at week 24 between ABP 798 and rituximab (pooled US-licensed 
and EU-authorized rituximab,  US-licensed rituximab or EU-authorized rituximab) will 
also be provided and the outcome is descriptive.   
 


Product: ABP 798 
Clinical Study Protocol: 20130108 
Date: 20 March 2018 
Page 7 of 7 
 
Confidential 
 
 
Other endpoints, RR and RD of ACR20/50/70 at weeks 8, 12, 40, and 48, and RR and 
RD of ACR50 and ACR70 at weeks 8, 12, 40, and 48 will be summarized descriptively 
by treatment. 
 
Section 3: Table of Contents Appendix 3 Title 
Replace:  
 
ACR Core Set Measurements 
 
With:  
DAS28 and ACR Core Set Measurements 
 
 
 


3URGXFW$%3
&OLQLFDO6WXG\3URWRFRO
'DWH2FWREHU
3DJHRI
&RQILGHQWLDO
$5$1'20,=(''28%/(%/,1'678'<72&203$5(
3+$50$&2.,1(7,&6$1'3+$50$&2'<1$0,&6()),&$&<$1'
6$)(7<2)$%3:,7+5,78;,0$%,168%-(&76:,7+02'(5$7(
726(9(5(5+(80$72,'$57+5,7,6

6800$5<2)&+$1*(6

7HVW'UXJ
$%3
3URWRFRO1XPEHU

(XGUD&7QXPEHU
6WXG\3KDVH



'DWHDQG9HUVLRQ
 2FWREHU 9HUVLRQ


6SRQVRU
$PJHQ,QF
2QH$PJHQ&HQWHU'ULYH
7KRXVDQG2DNV&$86

&OLQLFDO5HVHDUFK2UJDQL]DWLRQ&52
35$+HDOWK6FLHQFHV
3DUN/DNH$YHQXH6XLWH
5DOHLJK1&86


&21),'(17,$/
3DJHRI


Product: ABP 798
Clinical Study Protocol: 20130108
Date: 16 October 2017
Page 2 of 5
Confidential
Rationale:
This amendment is issued to make the following changes:

To make minor, non-substantive grammatical and typographic corrections
(changes not detailed in this summary)

To adjust the language regarding study treatment accountability logs to indicate a 
single log as opposed to logs for each subject

To remove ACR20 from secondary efficacy endpoints

To correct multiplicity adjustments and error rates for statistical analysis of 
pharmacokinetic variables

To add the DAS28 core set measurements to Appendix 2
Page 79 of 82


Product: ABP 798
Clinical Study Protocol: 20130108
Date: 01 December 2016
Page 1 of 21
Confidential
A RANDOMIZED, DOUBLE-BLIND STUDY TO COMPARE 
PHARMACOKINETICS AND PHARMACODYNAMICS, EFFICACY AND 
SAFETY OF ABP 798 WITH RITUXIMAB IN SUBJECTS WITH MODERATE 
TO SEVERE RHEUMATOID ARTHRITIS
SUMMARY OF CHANGES
Test Drug:
ABP 798
Protocol Number:
20130108
EudraCT number:
2013-005543-90
Study Phase:
1/3
Date and Version:
01 December 2016; Version 2.0
Sponsor:
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799 US
Clinical Research Organization (CRO):
PRA 
4130 ParkLake Avenue, Suite 400
Raleigh, NC 27612 US
CONFIDENTIAL


Product: ABP 798
Clinical Study Protocol: 20130108
Date: 01 December 2016
Page 2 of 21
Confidential
Rationale:
This amendment is issued to make the following changes:

To make minor, non-substantive grammatical and typographic corrections
(changes not detailed in this summary)

To update Medical Monitor contact information

To update International Council for Harmonisation (ICH) terminology

To update pharmacokinetics terminology for consistency with the Statistical 
Analysis Plan

To clarify the end of study period

To clarify the end of trial date

To modify the Inclusion Criteria as follows:
1. To specify subjects must have had intolerance or an inadequate response 
to one or more TNF inhibitor therapies
2. To specify that subjects must have completed at least 4 weeks of a TB 
prophylaxis regimen prior to enrollment

To modify the Exclusion Criteria as follows:
1. To allow subjects with a positive hepatitis B surface antigen or hepatitis B 
core antibody result to enroll provided documentation of hepatitis B virus 
immunization is provided
2. To add adalimumab to the list of biologic therapies not allowed within 3 
months prior to first dose of investigational product
3. To add ocrelizumab to the list of prohibited prior treatments

To change terminology from “local practice” to “local guidance” to ensure 
investigators follow general treatment guidelines

To add citations for the administration of investigational product intravenously

To add visits to the list of rescue medication administration guidelines

To specify the format of unique subject identifiers

To specify randomization stratification in regards to prior biologic therapies used 
to treat rheumatoid arthritis

To clarify the day pharmacokinetic sampling timeframes

To specify and clarify visit windows

To specify that creatinine clearance will only be assessed at screening

To clarify that C-reactive protein results will be blinded to study sites

To correct terminology related to visual analog scales


Product: ABP 798
Clinical Study Protocol: 20130108
Date: 01 December 2016
Page 3 of 21
Confidential

To specify the timeframe for performing screening assessments and procedures

To clarify treatment versus infusion terminology

To add that differential was added to hematology tests

To add additional pharmacokinetic parameters as outlined in the Statistical 
Analysis Plan

SAP_001.pdf: 
1&71XPEHU
7KLV1&7QXPEHUKDVEHHQDSSOLHGWRWKHGRFXPHQW
IRUSXUSRVHVRISRVWLQJRQFOLQLFDOWULDOVJRY
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


Amgen Proprietary - Confidential
Sponsor:  Amgen Inc.
Statistical Analysis Plan           
Protocol No:  20130108
10-December-2018/ Version 2.0 
 Page 2 of 73 
TABLE OF CONTENTS 
Approvals ............................................................................................................................1 
Table of Contents ...............................................................................................................2 
1.
Introduction ................................................................................................................6
2.
Study Objectives .........................................................................................................6
2.1 
Primary Objectives ............................................................................................... 6 
2.2 
Secondary Objectives ........................................................................................... 6 
3.
Study Design................................................................................................................6
3.1 
Sample Size Considerations ................................................................................. 8 
3.2 
Randomization ..................................................................................................... 9 
4.
Study Variables and Covariates ................................................................................9
4.1 
Primary Variable .................................................................................................. 9 
4.2 
Secondary Variables ............................................................................................. 9 
Pharmacokinetic ...............................................................................................9 
Efficacy ..........................................................................................................10 
Pharmacodynamic ..........................................................................................10 
Safety .............................................................................................................10 
4.3 
Predetermined Covariates and Prognostic Factors ............................................. 10 
5.
Definitions .................................................................................................................11
5.1 
General ............................................................................................................... 11 
Actual Treatment Received ........................................................................................11 
Baseline ......................................................................................................................12 
Binding and Neutralizing ADA status During First Dose Period ..............................12 
Change from Baseline ................................................................................................12 
Completed Study ........................................................................................................12 
Concomitant and Prior Medication ............................................................................13 
Duration of IP Exposure .............................................................................................13 
Early Retreatment .......................................................................................................13 
End of Study Date ......................................................................................................13 
First Dose Date ...........................................................................................................13 
Infusion delay .............................................................................................................13 
Infusion missed ...........................................................................................................13 
Last Dose Date ...........................................................................................................13 
Percent Improvement from Baseline ..........................................................................14 
RA Disease Duration ..................................................................................................14 
Seropositivity ..............................................................................................................14 
Study Day 1 ................................................................................................................14 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 3 of 73 
Study Day ...................................................................................................................14 
Study Randomization .................................................................................................15 
Study Visit ..................................................................................................................15 
For PK analyses: .................................................................................................... 15 
For efficacy analyses: ............................................................................................ 16 
For safety (Hematology and chemistry) analyses: ................................................. 17 
For CD19+, IgA, IgM and IgG analysis: ............................................................... 17 
For vital signs analyses: ......................................................................................... 17 
For ADA analyses: ................................................................................................. 18 
5.2 
Pharmacokinetic ................................................................................................. 18 
5.3 
Efficacy .............................................................................................................. 20 
ACR20/50/70 ..............................................................................................................20 
DAS28-CRP ...............................................................................................................20 
DAS28-CRP Remission .............................................................................................21 
Health Assessment Questionnaire – Disability Index (HAQ-DI) ..............................21 
Hybrid ACR Response ...............................................................................................21 
Swollen Joint Count ...................................................................................................21 
Tender Joint Count .....................................................................................................21 
5.4 
Safety .................................................................................................................. 22 
Adverse Event of Interest (AEOI) ..............................................................................22 
Exposure Adjusted Incidence Rate (EAIR) for Adverse Events and Adverse Event of 
Interest 22 
Subject Incidence Rate ...............................................................................................23 
Treatment-emergent Adverse Event ...........................................................................23 
5.5 
PHARMACODYNAMICS ................................................................................ 23 
Complete depletion of CD19+ cell count ...................................................................23 
Duration of CD19+ B-cell complete depletion ..........................................................23 
6. 
Analysis Sets ..............................................................................................................23 
6.1 
Full Analysis Set ................................................................................................ 23 
6.2 
Per-protocol Analysis Set ................................................................................... 24 
6.3 
Safety Analysis Set............................................................................................. 24 
6.4 
Pharmacokinetic Concentration Analysis Set .................................................... 24 
6.5 
Pharmacokinetic Parameter Analysis Set ........................................................... 24 
6.6 
Per-protocol Pharmacokinetic Parameter Analysis Set ...................................... 24 
6.7 
Anti-drug Antibody Analysis Set ....................................................................... 25 
7. 
Interim Analyses .......................................................................................................25 
8. 
Data Review ..............................................................................................................25 
8.1 
Data Handling and Transfer ............................................................................... 25 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 4 of 73 
8.2 
Data Screening ................................................................................................... 26 
9. 
Statistical Methods ...................................................................................................26 
9.1 
Subject Disposition ............................................................................................ 26 
9.2 
Protocol Deviations ............................................................................................ 27 
9.3 
Treatments .......................................................................................................... 27 
 
Extent of IP Exposure ....................................................................................27 
 
Prior and Concomitant Medications ..............................................................27 
9.4 
Demographic and Baseline Characteristics ........................................................ 28 
9.5 
Pharmacokinetic analyses .................................................................................. 29 
 
Pharmacokinetic Concentrations ...................................................................29 
 
Pharmacokinetic Parameters ..........................................................................29 
Primary Statistical Analysis ................................................................................... 30 
Sensitivity Analyses ............................................................................................... 30 
9.6 
Pharmacodynamics Analyses ............................................................................. 31 
 
CD19 ..............................................................................................................31 
 
IgA, IgG and IgM ..........................................................................................31 
9.7 
Efficacy Analyses ............................................................................................... 31 
 
DAS28-CRP ...................................................................................................32 
Primary StatisTical Analysis ................................................................................. 32 
Sensitivity Analyses ............................................................................................... 33 
 
ACR 20/50/70 ................................................................................................34 
 
Hybrid ACR ...................................................................................................35 
 
Methods for Handling Dropouts and Missing Data for Efficacy ...................36 
 
Multiplicity ....................................................................................................37 
 
Pooling of Sites ..............................................................................................37 
9.8 
Safety Analyses .................................................................................................. 37 
 
Adverse Events ..............................................................................................37 
 
Deaths and Serious Adverse Events ..............................................................38 
 
Laboratory Data .............................................................................................39 
 
Vital Signs and Physical Examination ...........................................................39 
 
Immunogenicity .............................................................................................40 
 
Methods for Handling Missing Data for Safety .............................................40 
9.9 
Exploratory Analyses ......................................................................................... 41 
 
DAS28-CRP Individual Components ............................................................41 
 
ACR Individual Components .........................................................................41 
10. 
CHANGE FROM PROTOCOL SPECIFIED ANALYSIS ..............................41 
11. 
Validation ..............................................................................................................42 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 5 of 73 
12. 
References ..............................................................................................................42 
Appendix 1 
Glossary of Abbreviations .....................................................................43 
Appendix 2 
Method for missing individual components of ACR calculation .......46 
Appendix 3 
Method for Missing individual joint assessments................................47 
Appendix 4 
HAQ-DI Scoring Algortihm ..................................................................49 
Appendix 5  List of Events of Interest and the Associated SMQ and EOI Searching 
Strategies ...........................................................................................................................50 
Appendix 6 
List of Post-Text Tables, Figures, Listings, and Supportive SAS 
Output Appendices ..........................................................................................................52 
Appendix 7 
Shells for Post-Text Tables, Figures, and Listings ..............................73 
 
 
 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 6 of 73 
1. INTRODUCTION 
This statistical analysis plan (SAP) describes the statistical methods to be used during the 
reporting and analyses of data collected under Amgen Inc. Protocol 20130108, titled “A 
Randomized, Double-Blind Study to Compare Pharmacokinetics and Pharmacodynamics, 
Efficacy and Safety of ABP 798 with Rituximab in Subjects with Moderate to Severe 
Rheumatoid Arthritis.” 
This SAP should be read in conjunction with the study protocol and electronic Case 
Report Forms (eCRFs). This version of the plan has been developed using the protocol 
version 4.0 dated 20 March 2018 and eCRFs version 5.0 dated 17 November 2016. Any 
further changes to the protocol or eCRFs may necessitate updates to the SAP. 
The SAP is to be developed in two stages. The purpose is to “finalize” a SAP in order to 
start programming earlier in the process. Versions of the SAP up to initial sponsor 
approval will be known as SAP1. Changes following approval of SAP1will be tracked in 
the SAP Change Log and a final version of the SAP, known as SAP2, will be issued for 
Amgen’s approval prior to unblinding for the final analysis.   
2. STUDY OBJECTIVES 
2.1 PRIMARY OBJECTIVES 
The primary objective for this study is to demonstrate pharmacokinetic (PK) similarity 
(as assessed principally by area under the serum concentration-time curve [AUC] from 
time 0 extrapolated to infinity [AUCinf] and the maximum observed serum concentration 
[Cmax], following the 2nd infusion of the 1st dose) of ABP 798 following 2 intravenous 
(IV) infusions of 1000 mg each, relative to that of 2 IV infusions of 1000 mg each of 
rituximab (US) and of rituximab (EU). 
2.2 SECONDARY OBJECTIVES 
The secondary objectives are: 
 to demonstrate PK similarity between rituximab (US) and rituximab (EU) as 
assessed by AUCinf and by Cmax after second infusion of the first dose 
 to assess the clinical efficacy of ABP 798 compared with rituximab 
 to assess the safety and immunogenicity of ABP 798 compared with rituximab. 
3. STUDY DESIGN 
This is a randomized, double-blind, active-controlled 3-arm study in adult subjects with 
moderate to severe Rheumatoid Arthritis (RA) who have an inadequate response or 
intolerance to other disease-modifying anti-rheumatic drugs (DMARDs), which must 
include intolerance or inadequate response to one or more tumor necrosis factor (TNF) 
inhibitor therapies. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 7 of 73 
Approximately 300 subjects (100 per treatment group) will be enrolled. The subjects will 
be randomized to receive either 2 IV infusions of ABP 798, 1000 mg each, given 2 weeks 
apart (treatment group A), or 2 IV infusions of rituximab (US) 1000 mg each, given 2 
weeks apart (treatment group B) or 2 IV infusions of rituximab (EU), 1000 mg each, 
given 2 weeks apart (treatment group C) in a double blind fashion. A total of 2 doses will 
be administered during the study; each dose consists of 2 infusions, 2 weeks apart. 
An independent data monitoring committee (DMC) will evaluate the safety data 
throughout the study, including an initial safety analysis after the first 18 subjects have 
received the first dose (1000 mg x 2 infusions of either ABP 798 or rituximab (EU) or 
rituximab (US)). 
At week 24, the subjects in treatment groups A and C will continue with and receive the 
second dose of the same treatment, and the subjects in treatment group B will transition 
to treatment group A1 and receive ABP 798 1000 mg x 2 as their second dose. 
Retreatment may occur earlier, i.e., anytime from week 16 to week 24, in individual 
subjects, if necessary in the opinion of the Investigator.  
The end of study (EOS) will be at week 48 (or 24 weeks after the first infusion of second 
dose for subjects retreated before week 24), and a final analysis will be performed when 
all subjects have completed or have had the opportunity to complete the week 48/EOS 
assessments.  
See Figure 1 below for a summary of the study design. 
 
 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 8 of 73 
 
Figure 1 
Study Diagram 
 
 
 
 
 
 
 
 
R 
 
 
 
 
 
 
A 
 
Treatment Group A 
 
 
 
 
 
S 
 
N 
 
ABP 798 1000 mg x 2 (N=100) 
 
 
 
 
 
C 
 
D 
 
 
 
 
 
 
R 
E 
 
O 
M 
 
 
 
Treatment Group A1* 
ABP 798 1000 mg x 2 (N=200) 
 
 
E 
 
I 
 
 
 
 
 
 
 
N 
 
Z 
 
Treatment Group B 
 
 
 
 
 
I 
N 
 
A 
T 
 
Rituximab (US) 1000 mg x 2 (N=100) 
 
 
 
 
 
G 
 
I 
 
 
 
 
 
 
 
 
 
O 
 
 
 
 
 
 
 
 
 
N 
 
 
 
 
 
 
 
 
 
 
 
Treatment Group C 
 
Treatment Group C* 
 
 
 
 
 
 
Rituximab (EU) 1000 mg x 2 (N=100) 
 
Rituximab (EU) 1000 mg x 2 (N=100) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
End of Study week 48 
 
 
Up to 28 days 
                                                  Week 16-24 
Final Analysis week 48 
 
 
* Retreatment will begin at week 24 or earlier, i.e., anytime from week 16 to week 24 in 
individual subjects if necessary in the opinion of the Investigator. 
3.1 SAMPLE SIZE CONSIDERATIONS 
Approximately 300 subjects will be randomized in a 1:1:1 ratio to receive ABP 798, 
rituximab (US), or rituximab (EU), stratified by geographic region (North America, 
Eastern Europe, and Western Europe), seropositivity (rheumatoid factor (RF)-positive 
and/or anti-cyclic citrullinated peptide (CCP)-positive vs. RF-negative and CCP-
negative), and number of prior biologic therapies used for RA (1 vs. >1). The sample size 
will provide > 90% power to demonstrate similarity on the primary PK endpoints based 
on an assumption of between-subject variability (as measured by coefficient of variation) 
of 40%, true geometric mean ratio (GMR) of 1 among ABP 798, rituximab (US), or 
rituximab (EU), a margin of (0.8, 1.25) and 15% dropout by week 24. PK similarity will 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 9 of 73 
be tested between ABP 798 versus rituximab (US) and ABP 798 versus rituximab (EU), 
each with a significance level of 0.05. The similarity between rituximab (US) and 
rituximab (EU) will be evaluated as well. 
With the planned sample size, there is 94% probability that the 90% CI of the difference 
between the ABP 798 arm and the pooled rituximab (rituximab [EU] and rituximab [US]) 
arm and 83% probability that the 90% CI of the difference between test (ABP 798) and 
reference (rituximab [EU] or rituximab [US]) in DAS28-CRP change from baseline at 
week 24 will fall into the equivalence margin of ± 0.6 (EULAR response criteria), 
assuming a standard deviation of 1.4 (Volkmann et al, 2010) and true mean difference of 
0.   
3.2 RANDOMIZATION 
Approximately 300 subjects will be randomized in a 1:1:1 ratio to receive either ABP 
798, rituximab (US), or rituximab (EU) via an Interactive Voice or Web Response System 
(IXRS), stratified by geographic region (North America, Eastern Europe, and Western 
Europe), seropositivity (RF-positive and/or CCP-positive vs. RF-negative and CCP-
negative), and number of prior biologic therapies used for RA (1 vs. >1). 
Assignment to the treatment arms will be based on a computer-generated randomization 
schedule created before the start of the study. The randomization schedule will be 
prepared by a statistician not involved in the conduct of the study.   
A third party vendor, 
, will be responsible for generating 
the randomization scheme and managing the randomization activities of this study. 
 678'<9$5,$%/(6$1'&29$5,$7(6
4.1 PRIMARY VARIABLE 
x The primary PK endpoints are the AUCinf and Cmax following the 2nd infusion of 
1st dose. 
4.2 SECONDARY VARIABLES 
 3KDUPDFRNLQHWLF
The secondary PK endpoints will include: 
x AUC from time 0 on day 1 prior to the 1st infusion of the 1st dose to 14 days 
postdose (AUC0-14 day) 
x AUC from time 0 on day 1 prior to the 1st infusion of the 1st dose to week 12 
(AUC0-12 wk) 
x Cmax following the 1st infusion of the 1st dose. 
PPD


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 10 of 73 
 
Additional PK endpoints including the time of Cmax (tmax), last measurable serum 
concentration after the second infusion up to week 12 (Clast),terminal elimination 
half-life (t1/2), the terminal elimination rate constant (λz), clearance (CL), mean 
residence time (MRT), percent of AUC extrapolation (%AUCextrap), and AUC0-12 
wk/AUCinf. 
 Efficacy 
The efficacy endpoints include: 
Primary efficacy endpoint: 
 
Disease activity score (DAS) 28-CRP change from baseline at week 24. 
Secondary efficacy endpoints: 
 
DAS 28-CRP change from baseline at week 8, 12, 40 and 48. 
 ACR20, ACR50  and ACR70  at weeks 8, 12, 24, 40 and 48.  
 Hybrid ACR at weeks 8, 12, 24, 40 and 48. 
 Pharmacodynamic  
Pharmacodynamic (PD) endpoints will include the percent of subjects with complete 
depletion in CD19+ cell count from day 1 to day 3 and duration of CD19+ B-cell 
complete depletion. 
 Safety 
Safety endpoints include the following: 
 Treatment-emergent adverse events (TEAE) and serious adverse events (SAE). 
 Clinically significant changes in laboratory values. 
 Changes in vital signs. 
 Incidence of anti-drug antibodies. 
4.3 PREDETERMINED COVARIATES AND PROGNOSTIC FACTORS 
For the PK analyses, geographic region and weight will be used as covariates in the 
model for the primary statistical analysis. The following covariates may be used for 
further exploration in subgroups: 
 Negative binding anti-drug antibodies (ADA) during first dose period 
 Negative neutralizing ADA during first dose period  
For efficacy analyses, unless stated otherwise, the following stratification factors will be 
included as covariates in the model or be used to examine treatment effect in subgroups: 
 Geographic region (North America vs. Eastern Europe vs. Western Europe)  


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 11 of 73 
 Seropositivity (RF-positive and/or CCP-positive vs. RF-negative and CCP-
negative) 
 Prior biologic use for RA (1 vs >1) 
In case the analysis model doesn’t converge,  the strata with least number of subjects may 
be combined to address the convergence issues. 
In addition, the following covariates may be used for further exploration in subgroups or 
as covariates: 
 Age Group (<65 years vs ≥65 years) 
 Race (Caucasian vs Non-Caucasian) 
 Gender 
 Binding ADA status during first dose period (negative vs positive)  
 Neutralizing ADA status during first dose period (negative vs positive)  
 Oral Corticosteroid use at baseline (Yes vs No) 
Additional baseline demographic and disease characteristics in Section 9.4 may also be 
considered as covariates in the model for assessing DAS28-CRP change from baseline at 
week 24. 
Analyses that are intended to evaluate the treatment effect and include stratification 
variables as covariates in the model will be based on the eCRF 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). 
For subgroup analyses where the subgroup factor is a stratification variable, an analysis 
similar to the primary statistical analysis (except the inclusion of the subgroup factor) 
should be done for each subgroup defined by the eCRF values of the subgroup factor. 
 
 
5. DEFINITIONS 
5.1 GENERAL 
Actual Treatment Received 
The actual treatment received is the investigational product (IP) treatment the subject 
actually received, regardless of what the subject was randomized to. In cases where a 
subject received more than 1 IP during a dose, the actual treatment received for that dose 
will be based on the first IP infusion of the dose the subject received. The actual 
treatment received for the entire study will be based on the combination of the actual 
treatment received for the first infusion of the two doses. In cases where a subject 
received only the 1st dose of IP, the actual treatment received for the entire study will be 
determined by the actual treatment of the 1st IP dose and the intended treatment of the 2nd 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 12 of 73 
dose per protocol. The actual treatment for the study will be unplanned if the sequence of 
the actual treatment of each dose are not described in the protocol.  
Specifically, by design for each subject, 2 doses will be administered during the study 
where each dose consists of 2 infusions, and each infusion consists of 2 boxes. In the 
cases where a subject receives mismatched boxes (differing IP) among the 2 possible 
boxes within an infusion, if either box is ABP 798 then the actual treatment for the 
infusion will be ABP 798.    
Baseline 
For the endpoint of interest, the baseline is defined as the last non-missing assessment 
taken prior to the first infusion of the first dose of study IP. In cases where baseline 
assessments are taken on the same day as the first infusion of 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. For subjects 
who are randomized but not dosed after the randomization, the baseline is defined as the 
last non-missing assessment prior to or on the date of randomization. 
For the ADA analysis following the 1st infusion of the 2nd dose, the baseline is defined as 
last non-missing assessment prior to the 1st infusion of the 2nd dose.  
Binding and Neutralizing ADA status During First Dose Period 
Subjects will be considered to have negative binding ADA status during first dose period 
if subjects had negative binding ADA  
 from baseline up to 1st infusion of 2nd dose for subjects who received 2nd dose, or  
 from baseline up to week 24 (day 175) or EOS (whichever is earlier) for subjects 
who didn’t receive 2nd dose.  
Subjects will be considered to have positive binding ADA status during first dose period 
if subjects had positive binding ADA status at any time point  
 up to the 1st infusion of the 2nd dose for subjects who received 2nd dose, or  
 up to week 24 (day 175) or EOS (whichever is earlier) for subjects who didn’t 
receive 2nd dose. 
The same definition applies to subjects’ neutralizing ADA status. Subjects with a binding 
negative or no result at baseline and at least one post baseline will be included in this 
derivation.   
Change from Baseline 
Change from baseline is defined as (value at post-baseline visit – value at baseline). 
Completed Study 
A subject is considered to have completed the study if they indicated they completed 
study on the EOS eCRF. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 13 of 73 
Concomitant and Prior Medication 
Prior medications are defined as medications with a stop date prior to the first infusion of 
the first dose of study IP. Concomitant medications are defined as any medications 
ongoing at the start of IP treatment or with a start date on or after the first dose date.  
Duration of IP Exposure 
For subjects who received 2nd dose of IP, the duration of IP exposure will be derived as 
min (EOS date, analysis data cutoff date) minus date of first IP exposure + 1 day. 
For subjects who didn’t receive 2nd dose of IP, the duration of IP exposure will be derived 
as min (EOS date, week 24 [day 175], analysis data cutoff date) minus date of first IP 
exposure + 1 day. 
Early Retreatment 
If 1st infusion of 2nd dose is administered prior to Study Day 162, subjects are considered 
as receiving early retreatment. 
End of Study Date  
EOS date is the date recorded on the End of Study page of the eCRF for a randomized 
subject. 
First Dose Date  
The date on which a subject is administered the first infusion of first dose of study IP. 
This date is also referred to as Study Day 1. 
Infusion delay 
If an IP administration form for a visit is entered with an infusion administered of NONE 
and a reason for delay/not administered, and also there is infusion information entered on 
a subsequent IP form, that subject is considered having an infusion delay.  
There is one exception. If the second infusion of the 1st dose is delayed for such a large 
extended period that it falls at week 16 or after, the infusion will be entered in the week 
24 folder. In this case, the Day 15 IP infusion will be considered missing instead of 
delayed.  
Infusion missed  
When a subject with an IP administration form entering an infusion administered of 
NONE and a reason for delay/not administered but there is no subsequent IP form with 
infusion information, the subject is considered to have missed an infusion at that visit.  
In addition, if the second infusion of the 1st dose is delayed for such a large extended 
period that it falls at week 16 or after, the infusion will be entered in the week 24 folder. 
In this case, the Day 15 IP infusion will be considered missing.  
Last Dose Date  
The date on which a subject is administered the last infusion of the last dose of study IP. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 14 of 73 
Percent Improvement from Baseline 
For endpoints where higher scores indicate greater severity, the percent improvement 
from baseline is: (value at baseline – value at post-baseline visit) X 100 / (value at 
baseline). 
For endpoints where lower scores indicate greater severity, the percent improvement 
from baseline is: (value at post-baseline visit – value at baseline) X 100 / (value at 
baseline). 
If the baseline value is 0 and the post-baseline value is also 0, then the percent 
improvement from baseline is set to 0. If the baseline value is 0 and the post-baseline 
value is non-zero, then the percent improvement from baseline is set to “missing” (or ‘.’). 
RA Disease Duration 
The RA disease duration is the number of years from the date of diagnosis of RA to the 
date of randomization, which will be derived based on the table below. No imputation 
will be done for disease diagnosis date, but to avoid a disease duration of zero, 1 month 
(or 1/12 years) may be added. 
 
Table 1 Calculation of the Duration of RA 
Observed 
portion  
Missing 
portion 
Formula to Calculate Duration  
Year, Month, 
Day 
 
(Date of Randomization – Date of RA Diagnosis + 
1)/365.25 
Year, Month  
Day  
[Year(Date of Randomization)-Year(Date of RA 
Diagnosis)]+ [Month(Date of Randomization)-
Month(Date of RA Diagnosis)]/12* 
Year 
Month, 
Day 
[Year(Date of Randomization)-Year(Date of RA 
Diagnosis)] *
*If the duration equals 0, add 1 month or 1/12 years. 
 
Seropositivity 
For seropositivity summary at baseline, a normal or negative baseline result for RF would 
be <12 IU/mL and for CCP3 would be <20 Units based on the laboratory assay maker’s 
guidance. 
Study Day 1 
Study Day 1 is defined as the first day of IP administration. For subjects who are 
randomized but not dosed after the randomization, study day 1 is defined as the date of 
randomization.  
Study Day 
Study day is defined as the number of days from Study Day 1. 
 Before Study Day 1: 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 15 of 73 
Study Day = (Date of Interest – Date of Study Day 1) 
 On or After Study Day 1: 
Study Day = (Date of Interest – Date of Study Day 1) + 1 
Therefore the day prior to Study Day 1 is -1.  
Study Randomization  
Study randomization is defined as when subject receives a random treatment allocation 
via the IXRS system. 
Study Visit  
Since the actual visit for a subject may not exactly coincide with their scheduled visit 
date, the actual visit date is mapped to the study analysis visit as follows. Note that the 
following analytical visit windows for statistical analysis are different from the ones 
defined in Section 18.0 of the IXRS Business Requirement. The actual visit date is 
allowed to fall within specified interval of the target day. 
In general, 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 latest visit with non-missing data will be considered for analysis. For Week 24, 
only actual visits that occur before or on same date as first infusion of second dose should 
be considered.  
The rules above for selecting a visit from multiple ones within the same visit window are 
not applicable to retest values of lab data. If the lab measurement is a retest, the retest 
value will be chosen. 
 
PK concentration will be summarized by the scheduled sample visit in the protocol. For 
PK concentration collected in the unscheduled visits or in the early discontinuation study 
visit, the associated scheduled sample visit is defined as below. If multiple records are 
assigned to the same visit, the one closest to the reference date/time will be selected into 
the summary. 
 
FOR PK ANALYSES: 
Scheduled Sample 
Visit 
Window Mapping 
Day 1 Pre-dose 
Prior to the 1st IP infusion of 1st dose start time but on the 
same day 
Day 1 End of infusion 
within 10 minutes of 1st infusion of 1st dose stop date/time
Day 1 3 hours 
 3 hr ± 10 minutes after 1st IP infusion of 1st dose stop 
date/time
Day 1 6 hours 
6 hours ± 10 minutes after 1st IP infusion of 1st dose stop 
date/time


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 16 of 73 
Day 2 24 hours post-
dose 
24 hr ± 3 hours after 1st IP infusion of 1st dose stop 
date/time
Day 3 48 hours post-
dose 
48 hr ± 3 hours  after 1st IP infusion of 1st dose stop 
date/time
Day 15 Pre-dose 
Prior to the 2nd IP infusion of 1st dose start time but on the 
same day 
Day 15 End of infusion within 10 minutes of 2nd infusion of 1st dose stop date/time
Day 15 3 hours 
3hr ± 10 minutes after 2nd IP infusion of 1st dose stop 
date/time
Day 15 6 hours 
 6hr ± 10 minutes after 2nd IP infusion of 1st dose stop 
date/time
Day 16 24 hours post-
dose 
24 hr ± 3 hours after 2nd IP infusion of 1st dose stop 
date/time
Day 17 48 hours post-
dose 
48hr ± 3 hours after 2nd IP infusion of 1st dose stop 
date/time
Week 4 
2 wks (14 days) ± 2 days after the 2nd infusion of 1st dose 
stop date
Week 8 
6 wks (14 days)  ± 2 days after the 2nd infusion of 1st dose 
stop date
Week 12 
10 wks (14 days)  ± 2 days after the 2nd infusion of 1st dose 
stop date
Week 24 Pre-dose 
Prior to the 1st IP infusion of 2nd dose start time but on the 
same day
Week 26 Pre-dose 
Prior to the 2nd IP infusion of 2nd dose start time but on the 
same day 
Week 30 
4 wks (28 days) ± 2 days from the 2nd infusion of 2nd dose 
stop date
Week 48 
22 wks (154 days) ± 2 days from the 2nd infusion of 2nd 
dose stop date
 
 
FOR EFFICACY ANALYSES: 
Study Analysis Visit  
Target Day 
Study Day
Interval (days)
Baseline  
1 
≤1 
NA  
Week 8  
57 
2 – 70
69 
Week 12  
85 
71 – 105
42  
Week 24  
169 
106 – 210 
98 
Week 40  
281
211– 308
98 
Week 48  
337
≥309
NA 
 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 17 of 73 
FOR SAFETY (HEMATOLOGY AND CHEMISTRY) ANALYSES: 
Study Analysis 
Visita 
Target Day  
Study Day  
Interval (days) 
Baselineb  
1 
≤1 
NA  
Week 2  
15 
2 – 16
15 
Day 17 
17
17
1 
Week 4  
29 
18 – 42 
25  
Week 8  
57 
43 – 105
70 
Week 24 
169
106 – 175
63 
Week 26 
183
176 – 196
21 
Week 30 
211
197 – 245
49 
Week 40 
281
246 – 308
63 
Week 48 
337
≥309
NA 
a Laboratory parameters will only be included at the visits where it is scheduled for 
assessment in the output tables. 
b If a subject has lab measurements on the same day as the first infusion date of first dose 
but at a time after the first infusion of first dose is administered, the lab measurements will 
not be defined as baseline, but as Week 2 measurements.
 
 
FOR CD19+, IGA, IGM AND IGG ANALYSIS: 
Study Analysis 
Visita  
Target Day 
Study Day  
Interval (days) 
Baselineb 
1 
≤1 
NA  
Day 2 
2
2
1 
Day 3 
3
3
1 
Week 4 
29
15 – 42
28 
Week 24 
169
106 – 210
98 
Week 48  
337
≥309
NA  
                      a IgG and IgA will not be collected at Day 2 and Day 3 
b If a subject has measurements on the same day as the first infusion date of first dose but at a time    
after the first infusion of first dose is administered, the measurements will not be defined as 
baseline, but as Day 2 measurement. 
 
FOR VITAL SIGNS ANALYSES: 
Study Analysis 
Visita  
Target 
Day 
Study Dayb  
Interval 
(days) 
Baseline
NA
Day 1 prior to infusion
NA  
Day 1 end of 
infusion (EOI) 
NA 
Day 1 after infusion 
NA 
Day 1 3 hours 
NA
Day 1 3 hours after EOI
NA 
Day 1 6 hours 
NA
Day 1 6 hours after EOI
NA 
Week 2 
NA
Day 15 prior to infusion
14  


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 18 of 73 
Day 15 EOI 
NA
Day 15 after infusion
NA 
Day 15 3 hours 
NA
Day 15 3 hours after EOI 
NA 
Day 15 6 hours 
NA
Day 15 6 hours after EOI 
NA 
Week 24 
169
106 – 175
63 
Week 26 
183
176 – 196
21 
Week 30 
211
197 – 245
49 
Week 48 
337
≥309
NA 
aIf a visit date with multiple records, the highest value per parameter will be selected for analysis. 
bDay 1 and Day 15 visit/timepoint are directly associated with infusion date/time. 
 
FOR ADA ANALYSES: 
Study Analysis 
Visit  
Target Day 
Study Day  
Interval (days) 
Baselinea 
1  
≤1 
NA  
Week 2 
15  
2 – 16
15  
Week 24 
169 
106 – 175
63 
Week 30 
211 
197 – 245
49 
Week 48 
337 
≥309
NA 
a If a subject has ADA assessments on the same day as the first infusion date of first dose but at a 
time after the first infusion of first dose is administered, the ADA assessments will not be defined as 
baseline, but as Week 2 assessments. 
5.2 PHARMACOKINETIC 
Pharmacokinetic parameters will be calculated from serum concentration-time data using 
noncompartmental analysis (NCA) methods using Phoenix WinNonLin® Version 6.4 or 
higher (Pharsight Corp, St. Louis, MO). The following PK parameters will be reported 
for serum rituximab and ABP 798, using actual elapsed sampling times: 
 
Variable 
 
Definition 
Cmax1 
Maximum observed serum concentration following Dose 1 
Infusion 1 
 
            Cmax2 
Maximum observed serum concentration following Dose 1 
Infusion 2 
tmax1 
 
 
Time to which the maximum serum concentration was  
observed following Dose 1 Infusion 1 
 
tmax2 
 
 
Time to which the maximum serum concentration was  
observed following Dose 1 Infusion 2 
 
TLST1 
Time of last quantifiable concentration following Dose 1 
Infusion 1 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 19 of 73 
CLST1 
Last quantifiable concentration following Dose 1 Infusion 1 
over first 14 days postdose (day 15) 
AUC0-14 day 
Area under the serum concentration-time curve from time 0 
on day 1 prior to the first infusion of the first dose to last 
quantifiable concentration associated with Dose 1 Infusion 
1 over the first 14 days postdose (day 15) 
TLST2 
Time of last quantifiable concentration associated with 
Dose 1 Infusion 2 
CLST2 
Last quantifiable concentration after Dose 1 Infusion 2 
AUC0-12 wk 
Area under the serum concentration-time curve from time 0 
on day 1 prior to the first infusion of the first dose to last 
quantifiable concentration over  12-week profile 
AUCinf 
Area under the serum concentration-time curve from time 0 
on day 1 prior to the first infusion of the first dose 
extrapolated to infinity; calculated as AUClast + CLST2/λz, 
where AUClast is the AUC from time 0 to the last 
quantifiable concentration up to week 12 (i.e. AUC0-12 wk) 
t1/2 
Terminal elimination half-life determined from time 0 to 
Week 12 profile; calculated as ln(2)/ λz 
λz 
Terminal elimination rate constant 
 
CL 
Clearance 
AUMC 
Area under the first moment curve 
MRT 
Mean residence time; calculated as AUMCinf/AUCinf – TI 
/2, where TI represents infusion duration and AUMCinf is 
the area under the moment curve from the time of first 
dosing extrapolated to infinity. 
AUC0-12 wk/AUCinf 
calculated as AUC0-12 wk/AUCinf 
AUC%extrap 
Percent of AUC extrapolated to infinity in AUCinf 
Following administration, Cmax. tmax, CLST and TLST will be obtained directly from the 
experimental observations. If multiple maxima occur at equal concentrations after an 
infusion, the first temporal value will be used. 
AUC0-14 day, AUC0-12 wk  and AUCinf will be estimated using the linear trapezoidal rule. 
Values of AUC0-14 day and Cmax associated with Dose 1 Infusion 2 will be listed but 
excluded from descriptive statistics and statistical analysis if the time of the last 
concentration following Dose 1 Infusion 1 is outside ± 2 day window around Day 15. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 20 of 73 
Values of AUC0-12 wk will be listed but excluded from descriptive statistics and statistical 
analysis if the time of the last concentration following Dose 1 Infusion 2 is outside ± 2 
week window around Week 12. 
The terminal half-life, t1/2, where determined, will be calculated as ln(2)/ λz. The number 
of data points included in the regression will be determined by visual inspection, but a 
minimum of three data points in the terminal phase, excluding Cmax, will be required to 
estimate λz. λz values (and consequently t1/2 and AUCinf values) will be considered 
unreliable estimates if the time period over which an individual λz was required is less 
than twice the resultant t1/2 or the adjusted coefficient of determination ’Rsq’ is less than 
or equal to 0.8. Additional exclusions of PK parameters, if any, will be described in the 
CSR.  
5.3 EFFICACY 
ACR20/50/70 
The ACR composite score evaluates clinical improvement relative to an initial 
assessment for clinical trials in subjects with RA. 
The ACR20 response is defined as at least 20% improvement compared to baseline for 
both swollen and tender joint counts (66/68 joint counts), as well as for at least 3 out of 
the following 5 additional parameters:  
 Subject's Global Health Assessment  
 Investigator's Global Health Assessment  
 Subject's assessment of pain  
 Health Assessment Questionnaire Disability Index (HAQ-DI) 
 C-Reactive Protein (CRP)  
ACR50 and ACR70 are defined in a similar fashion to ACR20 but require at least 50 and 
70 percent improvement respectively. Method for handling missing data is described in 
the appendice 2.  
DAS28-CRP 
The DAS28-CRP is a composite measure of disease activity in RA. It is a continuous 
measure based on 28 DAS joints from the ACR, the Subject's Global Health Assessment 
score, and CRP, as follows: 
 
DAS28-CRP = 0.56*(TJC28)0.5 + 0.28*(SJC28) 0.5 + 0.36*ln(CRP+1) + 0.014*SGH + 
0.96 
where TJC28 is the tender joint count of the 28 joints in the DAS, SJC28 is the swollen 
joint count of the 28 joints in the DAS, CRP is in mg/L, and SGH is the Subject's Global 
Health Assessment in 0 to 100 scale.  
If the CRP is at a non-detectable level, then replace it with the minimum detectable level. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 21 of 73 
DAS28-CRP Remission 
A subject will be considered to have achieved DAS28-CRP remission if the subject has a 
DAS28-CRP score less than 2.6.  
Health Assessment Questionnaire – Disability Index (HAQ-DI) 
The HAQ-DI score is defined as the average of the scores from eight sub-domains 
(dressing / grooming, arising, eating, walking, hygiene, reach, grip, and activities). The 
detailed score algorithm is described in Appendix 4. 
Hybrid ACR Response 
Hybrid ACR response is a continuous score of the mean improvement in the core set 
measures combining the ACR20, ACR50, and ACR70 response rates.   
The hybrid ACR can be calculated when all 7 components are available following the 
table below (American College of Rheumatology Committee to Reevaluate Improvement 
Criteria, 2007): 
 
  
Mean % change in all 7 core set measures 
ACR Status 
<20 
>=20, <50 
>=50, <70 
>=70 
Not ACR20 
Mean % 
change 
19.99 
19.99 
19.99 
ACR20 but not ACR50 
20 
Mean % 
change 
49.99 
49.99 
ACR50 but not ACR70 
50 
50 
Mean % 
change 
69.99 
ACR70 
70 
70 
70 
Mean % 
change 
 
If a core set measure worsens by > 100% , the percentage change will be limited to 
100%.   
Swollen Joint Count 
The swollen joint count will be the number of joints that are assessed as swollen among 
the 66 joints specified in Section 17.3 of the protocol and the corresponding Joint 
Assessment CRF page. Method for handling missing joint assessments (including those 
due to artificial/fused joint or intra-articular corticosteroid injection) is defined in 
Appendix 3.  
Tender Joint Count 
The tender joint count will be the number of joints that are assessed as Pain/Tenderness 
among the 68 joints specified in Section 17.3 of the protocol and the corresponding Joint 
Assessment CRF page.  Method for handling missing joint assessments (including those 
due to artificial/fused joint or intra-articular corticosteroid injection) is defined in 
Appendix 3. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 22 of 73 
5.4 SAFETY 
Adverse Event of Interest (AEOI) 
An AEOI is defined as a noteworthy  TEAE 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 AEOIs for this study will include:  
 infusion reactions including hypersensitivity, 
 cardiac disorders,  
 serious infections,  
 progressive multifocal leukoencephalopathy, 
 hematological reactions,  
 hepatitis B reaction, 
 opportunistic infections 
 hypogammaglobulinemia. 
 severe mucocutaneous reactions, 
 gastrointestinal perforation 
Events of interest were identified using the latest versions of pre-specified Standardised 
MeDRA query (SMQ) where available. If no SMQ is available for use as a search tool 
for a given EOI (eg. Infusion reactions), a customized search strategy developed at 
Amgen or medical review will be used where SMQ is not available. Appendix 5 provides 
the search strategy used to retrieve the events of interest. The preferred terms used in the 
searches are stored in a central PRA server location for analyses. 
Exposure Adjusted Incidence Rate (EAIR) for Adverse Events and Adverse Event 
of Interest 
The exposure adjusted incidence rate is defined as the number of subjects with a 
particular AE divided by the total exposure-time among subjects in the respective 
treatment group at risk of an initial occurrence of the event. Specifically,  
Exposure Adjusted Incidence Rate = 
௡
்ൌ
௡
∑௧௜, 
where n is the number of subjects with events, ti is a subject’s exposure time under a 
given unit and T is the total exposure time under a given time unit of the subjects in the 
group. If a subject has multiple events, the ti is the time from the first dose date of the 
respective treatment to the onset of the first event. For those subjects who crossed over 
from one IP treatment during the 1st dose to another IP treatment during the 2nd dose, the 
exposure time following each of the doses will be counted in the respective treatment 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 23 of 73 
group. For a subject with no event, the ti is set to the total exposure time duration of IP 
exposure (as defined in Section 5.1) for that subject. 
Subject Incidence Rate 
For adverse event summaries, subject incidence rate for a given event is defined as the 
number of subjects with at least 1 reported occurrence of the event divided by the number 
of subjects that received the given treatment or total subjects for the total column. For 
subjects with multiple occurrences of the same event, the event will only be counted once 
per subject. 
Treatment-emergent Adverse Event 
A treatment-emergent AE (TEAE) is defined as an AE that begins or increases in severity 
or frequency at or after the first study IP administration through EOS. If the AE starts on 
the same day as the first dose of IP, then the flag indicating whether the AE started prior 
to the first dose on the adverse event CRF page will be used. 
5.5 PHARMACODYNAMICS  
Complete depletion of CD19+ cell count 
Complete depletion of CD19+ cell count at any post-dose time is defined as CD19+ cell 
counts < 20 cell/uL (0.02 x10^9 cell/L). Subjects with missing CD19+ cell count at 
baseline or subjects with CD19+ cell count < 20 cell/uL at baseline will be excluded from 
the derivation of complete depletion of CD19+ cell count.  
Duration of CD19+ B-cell complete depletion 
This variable will be defined only for subjects who had a CD19+ B-cell complete 
depletion for at least one post-dose time. It is defined as time from the first incidence of 
complete depletion of CD19+ cell count to when CD 19+ cell count first increases to 
>=20 cell/uL. Subjects whose CD 19+ cell count doesn’t increase to >=20 cell/uL will be 
censored at the last CD19 assessment date. 
6. ANALYSIS SETS 
The primary statistical analysis for the PK endpoints will be based on the PK parameter 
analysis set. Sensitivity analysis for the PK endpoints will be based on the per-protocol 
(PP) PK parameter analysis set. The primary statistical analysis for the PD endpoint and 
efficacy endpoints will be performed using the full analysis set (FAS). The Per-protocol 
analysis set will be used for sensitivity analyses of the key efficacy endpoints. The 
analysis of safety endpoints will be based on the safety analysis set. The immunogenicity 
analysis will be based on anti-drug antibody analysis set.   
6.1 FULL ANALYSIS SET 
The FAS includes all subjects randomized in the study, with treatment assignment based 
on treatment the subject is randomized to (regardless of actual treatment received).  


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 24 of 73 
6.2 PER-PROTOCOL ANALYSIS SET 
The per-protocol (PP) analysis set includes all randomized subjects who have had two 
full infusions for the 1st dose (drug compliance of 90%-110%), have completed the week 
24 disease assessment (complete DAS28-CRP assessment in the week 24 window of day 
106-210 and before the 1st infusion of the 2nd dose), and did not experience a protocol 
deviation up to week 24 that affects their evaluation for the secondary objectives of the 
study to assess clinical efficacy. The protocol deviations that affect evaluation of the 
secondary objectives will be determined based on a blinded data review prior to database 
lock. Analyses for the per-protocol analysis set will be based on actual treatment 
received. 
6.3 SAFETY ANALYSIS SET 
The safety analysis set includes all randomized subjects who received at least 1 infusion 
of IP, with treatment assignment based on actual treatment received.  
6.4 PHARMACOKINETIC CONCENTRATION ANALYSIS SET 
The PK concentration analysis set is defined as the subset of subjects in the safety 
analysis set who received the full protocol-specified dose on Day 1 and had at least one 
evaluable serum concentration (including results below the quantifiable limit) of ABP 
798 or rituximab. Pharmacokinetic concentration data from subjects will be analyzed 
according to the actual treatment received. Subjects to be excluded from the PK 
concentration analysis set will be determined based on a blinded data review prior to 
database lock. 
6.5 PHARMACOKINETIC PARAMETER ANALYSIS SET 
The PK parameter analysis set is defined as the subset of subjects in the safety analysis 
set who received the full protocol-specified dose on Day 1 and had an evaluable ABP 798 
or rituximab serum concentration time profile. The PK parameter analysis set will be 
used for the primary statistical analysis of PK endpoints. Pharmacokinetic parameter data 
from subjects will be analyzed according to the actual treatment received. Subjects to be 
excluded from the PK parameter analysis set will be determined based on a blinded data 
review prior to database lock. 
6.6 PER-PROTOCOL PHARMACOKINETIC PARAMETER 
ANALYSIS SET 
The per-protocol PK parameter analysis set consists of a subset of subjects in the PK 
parameter analysis set who do not experience an important protocol deviation that affects 
their PK evaluation. It will be analyzed according to actual treatment received. The 
important protocol deviations that affect evaluation of PK endpoints will be determined 
based on a blinded data review prior to database lock. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 25 of 73 
6.7 ANTI-DRUG ANTIBODY ANALYSIS SET 
Anti-drug antibody analysis set is defined as the subset of subjects in the safety analysis 
set who had at least 1 evaluable antibody test. Immunogenicity data from subjects will be 
analyzed according to the actual treatment received. 
7. INTERIM ANALYSES 
No interim analyses are planned for this study.  
A Data Monitoring Committee (DMC) external to Amgen and PRA will be formed with 
members consisting of individuals chosen for their expertise in inflammatory disorders. 
Members of the DMC will include, at a minimum, physicians external to Amgen and 
PRA, and appropriate statistical representation external to Amgen and PRA. The primary 
role of this independent DMC will be to monitor safety data.  
The DMC will review unblinded safety data at regular intervals, as outlined in the DMC 
charter (approximately twice yearly; the start date will depend on subject accrual rates). 
The DMC will also review an initial safety analysis after the first 18 subjects have 
received the first dose.  
In addition, the DMC will communicate major safety concerns and recommendations 
regarding study modification or termination to Amgen management at any time during 
the conduct of the study.  
Details regarding the DMC will be provided in the DMC charter and DMC analysis plan.  
8. DATA REVIEW 
8.1 DATA HANDLING AND TRANSFER 
Data will be entered 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 1.3, 
Implementation Guide version v3.1.3) conventions. Analysis datasets will be created 
using SAS® and following CDISC Analysis Data Model (ADaM, version 2.1, 
Implementation Guide 1.0) standards. 
Medical history and AEs will be coded using the current version of MedDRA at the time 
of the 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). 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 analysis. 
Additional details can be found in the PRA Data Management Plan for this study. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 26 of 73 
8.2 DATA SCREENING 
Beyond the data screening built into the PRA Data Management Plan, the PRA 
programming of analysis datasets and tables, figures and listings (TFLs) provides 
additional data screening as described below.  
Review of a post-freeze dry run of TFLs allows for further data screening prior to final 
database lock for the entire study. This dry run will be discussed with the sponsor in data 
review meetings to identify any final data issues and seek corrections prior to the final 
database lock for the entire study. The PRA statistician and the sponsor must approve 
database lock. 
9. STATISTICAL METHODS 
All statistical analyses will be performed using SAS® (Version 9.4 or higher). 
The final analysis will be performed after all subjects have completed or have had the 
opportunity to complete the week 48/EOS assessment.  
Unless otherwise specified, descriptive data summaries will be tabulated by treatment for 
all endpoints. Categorical data will be summarized using number of subjects (n), 
frequency and percentages of subjects falling into each category, with the denominator 
for percentages being the number of subjects in the study population for each treatment 
group, unless otherwise noted. Percentages will be rounded to one decimal place. 
Confidence intervals will be provided where specified. 
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, median, Q1, and Q3 will be presented to one decimal place 
greater than the original data, standard deviation will be to 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. Confience intervals will be provided where specified.  
For any of the summaries that are to be done by visit, the derived analytical study visit as 
defined in section 5.1 will be used for analysis unless otherwise noted.  
9.1 SUBJECT DISPOSITION 
The following information will be summarized for subject disposition and accountability: 
 Number of subjects randomized will be tabulated by region, country and center 
based on the FAS. 
 Number of subjects randomized will be tabulated by stratification factors based 
on the FAS. 
 Subject disposition (including number randomized, treated with 
ABP 798/rituximab (US)/rituximab (EU), completed treatment, discontinued 
treatment with reason of discontinuation, completed study, and discontinued study 
with reason of discontinuation) using each of the analysis sets defined in Section 
6. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 27 of 73 
 Summaries of analysis sets with reason for exclusion for all screened subjects. 
 
Randomization list of subjects and their actual versus randomized treatment group 
for all randomized subjects. 
9.2 PROTOCOL DEVIATIONS  
Protocol deviation (PD) data will be entered into the Clinical Trials Management System 
(CTMS). The study team will conduct on-going reviews of the PD data from CTMS. The 
per-protocol analysis set and per protocol PK parameter analysis set must be finalized at 
the post-freeze data review meeting (or earlier), prior to the database lock.  
Based on the PD data entered into CTMS, a summary of important PDs will be tabulated 
using number and percentage of subjects with important PD by deviation type and 
randomized treatment arm. A listing of subjects with important PDs will be provided 
(with a flag indicating whether the deviation leads to exclusion from the per-protocol and 
per-protocol pharmacokinetic analysis sets). A summary table and listing of eligibility 
criteria deviations will also be tabulated showing the violations of the inclusion/exclusion 
criteria for each subject.  
9.3 TREATMENTS 
 Extent of IP Exposure 
For the IP (ABP 798, rituximab (US) or rituximab (EU)), summary statistics will be 
provided for the total number of doses administered, total dose received, total duration of 
IP exposure, number of subjects with four full infusions and number of subjects with at 
least one partial infusion (including missed infusion), number of subjects with at least one 
infusion delay, number of subjects with at least one infusion missed, and number of 
subjects with at least one infusion interruption by treatment group. An IP administration 
summary will also be provided by the reported visit for each dosing/infusion instance, 
with summaries of the number of subjects receiving a full or partial infusion, infusion 
delay, infusion missed and infusion interruption as well as reasons, and reasons for 
ending IP by treatment group.  The percentages for the IP administration summary will 
be based on the number of subjects with the given visit. The analysis will be performed 
using the safety analysis set according to the actual treatment received. 
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. 
 Prior and Concomitant Medications 
Prior and concomitant medications will be coded by WHO-DD and will be summarized 
by preferred name and treatment group. The prior medications and concomitant 
medications will be summarized by treatment groups. The analysis will be performed 
using the safety analysis set according to the actual treatment received. 
The number and percentage of subjects using each medication will be displayed by 
treatment arm. Subjects taking more than one medication in the same preferred name will 
be counted once for the number of subjects taking that preferred name.  


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 28 of 73 
9.4 DEMOGRAPHIC AND BASELINE CHARACTERISTICS 
The following demographics and baseline characteristics will be summarized by 
treatment for each of the analysis sets defined in Section 6.  
 age (in years, at time of signing informed consent) and age category (<65 vs ≥65),  
 race,  
 sex,  
 ethnicity,  
 height,  
 weight,  
 body mass index (BMI),  
 BSA, 
 geographic region (North America, Eastern Europe, and Western Europe),  
 Number of prior biologic use for RA (1 vs. >1), 
 Number of prior biologic use for RA (1, 2, 3, etc.), 
 seropositivity (RF-positive and/or CCP-positive vs. RF-negative and CCP-
negative), 
 Duration of RA (in years) and duration of RA category (<5, ≥5 years), 
 DAS28-CRP,  
 swollen joint count(66 and 28 counts) 
 tender joint count, (68 and 28 counts) 
 subject's global health assessment,  
 investigator's global health assessment,  
 subject's assessment of disease-related pain,  
 HAQ-DI,  
 CRP,  
 use of oral corticosteroid at baseline (Yes/No),  
 use of non-steroidal anti-inflammatory drug (NSAID) at baseline (Yes/No), 
 baseline methotrexate dose. 
Medical conditions at screening and the status of the medical condition at randomization 
(continuing versus resolved) will be summarized by SOC and PT and tabulated by 
treatment groups ABP 798/ABP 798, rituximab (US)/ABP 798, rituximab 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 29 of 73 
(EU)/rituximab (EU) and total. The analysis will be performed using the safety analysis 
set according to the actual treatment received. 
9.5 PHARMACOKINETIC ANALYSES 
 Pharmacokinetic Concentrations 
Serum rituximab and ABP 798 concentrations will be summarized descriptively by 
treatment and nominal sampling time point for the PK concentration analysis set. The 
following descriptive statistics will be calculated at each of the sampling times: 
arithmetic mean (mean), coefficient of variation (CV), SD, Q1, Q3, Geometric mean, 
Geometric CV, minimum, median, maximum and the number of measurements. For 
calculation of summary concentrations, values below the quantifiable limit (BQL) will be 
set to zero. 
In the event that a subject does not receive the full protocol-specified infusion, 
subsequent PK samples may be considered not evaluable and excluded from the 
descriptive statistics and mean concentration-time profiles. In addition, if samples are 
collected with a substantial deviation from nominal time that impacts the presentation of 
PK data, they will be excluded from the PK concentration vs nominal time profile. The 
samples excluded from the PK concentration analysis  will be determined based on a 
blinded data review prior to unblinding for the final analysis. 
Individual and mean (±SD) serum concentration-time profiles of rituximab and ABP 798 
will be presented graphically using nominal time by treatment on a semi-logarithmic and 
a linear scale.  
 Pharmacokinetic Parameters 
PK parameters for ABP 798 and rituximab will be estimated using noncompartmental 
analysis methods with Phoenix WinNonlin® Version 6.4 or higher (Pharsight Corp., St. 
Louis, MO). 
In the event that a subject does not receive the full protocol-specified infusion, 
subsequent PK samples may be considered not evaluable and thus certain PK parameters 
may not be reportable. In addition, if the full protocol-specified dose was given but there 
was a long dose interruption or unusually long infusion duration that was deemed to 
impact PK, the PK profile may be considered not evaluable. The subject exclusion from 
the PK parameter analysis set will be determined based on a blinded data review prior to 
unblinding for the final analysis. Any such exclusion will be clearly listed in the CSR 
along with justification for exclusion.  
Pharmacokinetic parameters will be listed by subject and summarized descriptively by 
treatment for the PK parameter analysis set. The following descriptive statistics will be 
provided: n, arithmetic mean, SD, Q1, Q3, minimum, median and maximum. Only n, 
median, Q1, Q3, minimum and maximum will be reported for tmax. In addition, geometric 
mean, and geometric CV will be calculated for AUCinf, AUC0-14 day, AUC0-12 wk, Cmax , 
CLST2 , t1/2,  λz , CL, MRT, AUC%extrap and AUClast/AUCinf. 
The serum PK parameters will be estimated from the individual concentration data for all 
subjects in the PK parameter analysis set. In estimating the PK parameters, BQL values at 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 30 of 73 
the beginning of the profile will be set to zero. BQL values that occur after the first 
quantifiable point will be considered missing. Actual sampling times will be used in all 
computations.  
35,0$5<67$7,67,&$/$1$/<6,6
The PK similarity will be demonstrated by comparing the 90% CI for the GMR of test 
(ABP 798)-to-reference (US-licensed rituximab or EU-authorized rituximab) and 
rituximab [US] to rituximab [EU] for AUCinf  and for Cmax following the second infusion 
of the first dose with the bounds of 0.8 to 1.25. Point estimates and CIs for the GMR will 
be estimated from an analysis of covariance model using the PK parameter analysis set.  
For AUCinf and Cmax after second infusion of the first dose, the point estimates and 90% 
CIs for the GMR for will be estimated using an analysis of covariance model adjusted for 
weight and geographic region. A sample SAS code for PROC MIXED is displayed 
below: 
 
The geometric least square means for each treatment will be presented. The ratios of the 
geometric means for the comparison of the test treatment to the reference treatment will 
be obtained by exponentiating the difference of the means on the natural log scale. The 
CIs will be obtained by exponentiating the CI for the difference between the means on 
the log scale. Plots of the ratio of geometric means and 90% CI will be displayed. 
Additionally, the similarity between PK endpoints of rituximab (US) and rituximab (EU) 
will be evaluated as well. The GMRs and 90% CIs will be generated for other PK 
endpoints: AUC0-14 day, AUC0-12 wk , and Cmax after the first infusion of the first dose by 
using the same methods as stated above.  
6(16,7,9,7<$1$/<6(6
A sensitivity analysis of all PK parameters will be analyzed similarly to the primary 
statistical analysis using the PP PK parameter analysis set. 
In addition, the following sensitivity analyses will be performed on the PK parameter 
analysis set: 
x The point estimates and CIs for the GMR will be estimated using a model similar 
to the primary statistical analysis model but excluding all covariates.  
x The point estimates and CIs for the GMR will be estimated using the primary 
statistical analysis model for the subgroups of subjects with negative binding 
ADA status and negative neutralizing ADA status during first dose period.  
 
CCI


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 31 of 73 
9.6 PHARMACODYNAMICS ANALYSES 
All pharmacodynamics analyses will be performed using the FAS according to 
randomized treatment.  
 &'
The pharmacodynamics similarity will be evaluated descriptively for the difference in 
percent of subjects with complete CD19+ cell depletion between test (ABP 798) and 
reference (US-licensed rituximab or EU-authorized rituximab) from day 1 to day 3. 
Subjects with baseline value less than 20 cell/uL or missing will not be evaluable for 
CD19+ depletion analyses. The point estimate, the 90% CI  and the 95% CI will be 
provided for rate difference and will be estimated using a generalized linear model 
(specifically, a log-binomial regression model) with stratification factors as covariates. A 
sample SAS code for PROC GENMOD is displayed below: 
Note: The contrasts in the estimate statement may need to be changed depending on the 
order of the treatments.  
Descriptive statistics for CD19+ counts as well as change from baseline will be provided 
at day 2 and day 3.  
In addition, for duration of CD19 complete depletion,  KM estimates and 90% CIs will be 
calculated by randomized treatment group for event time quartiles.   
 ,J$,J*DQG,J0
The total IgA, IgG and IgM levels as well as change from baseline will be summarized 
descriptively by treatment and visit. 
9.7 EFFICACY ANALYSES 
All efficacy analysis will be performed using the FAS based on subject’s randomized 
treatment. Sensitivity analysis of DAS28 at week 24 will also be performed using the 
per-protocol analysis set based on the actual treatment the subject received.  
Analyses will be performed for two different time periods:  
1. From day 1 until week 24 (efficacy analysis visit weeks 8, 12 and 24), only 
including results prior to 1st infusion of 2nd dose. Subjects who had the 1st 
infusion of 2nd dose prior to week 24 will have their efficacy endpoints data 
censored at the timing of 1st infusion of 2nd dose. For example, if disease 
CCI


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 32 of 73 
assessment is done at day 1 of week 16 and 1st infusion of 2nd dose is done on 
the same day, then the disease assessment on day 1 of week 16 will be 
included in modeling, but any disease assessment after that day will not be 
included. 
2. Day 1 through EOS (efficacy analysis visit weeks 8, 12, 24, 40 and 48).  
Analyses will be performed separately for all subjects and the subgroup of 
subjects who received the 1st infusion of the 2nd dose at week 24 (i.e., 
excluding early retreatment subjects as defined in section 5.1).  
 
If PK similarity is established between rituximab (US) and rituximab (EU), the 2 arms 
will be combined into a single reference arm for the primary assessment of clinical 
equivalence of DAS28-CRP change from baseline at week 24 between ABP 798 and 
rituximab. The results for ABP 798 vs. rituximab (EU) and ABP 798 vs. rituximab (US) 
will be provided for descriptive purposes. If PK similarity is not established, the ABP 798 
arm will be compared to each of the individual rituximab arms separately to establish 
clinical equivalence of ABP 798 to the individual reference arms. 
The pooling of the reference arms for ACR20/50/70 and hybrid ACR analyses will be 
conducted similarly.  
 DAS28-CRP 
PRIMARY STATISTICAL ANALYSIS 
DAS28-CRP at Week 24  
The analyses will be performed on the FAS based on the day 1 through week 24 time 
period described above, with observed data. Subjects with missing baseline DAS28-CRP 
will not be included in the analysis since no change from baseline can be calculated.  
Analyses will assess the hypothesis that there are no clinically meaningful differences 
between ABP 798 and rituximab arms in DAS28-CRP change from baseline at week 24. 
This primary efficacy endpoint  will be tested by comparing the 2-sided 90% CI of the 
change from baseline at week 24 of DAS28-CRP between ABP 798 and rituximab arms 
with an equivalence margin of (-0.6, 0.6).  
To evaluate treatment differences across time points at which DAS28-CRP was assessed, 
repeated-measures analysis will be utilized for the day 1 through week 24 time period 
described above. Data from all assessed postbaseline time points will be included in the 
analysis. Besides stratification variables, baseline DAS28-CRP value, visit (week), 
treatment, and treatment-by-visit interaction will be included in the models, with visit as 
a categorical variable. The adjusted mean with 95% CI for each arm and 90% and 95% 
CIs for the mean difference will be constructed for mean difference of DAS28-CRP 
change from baseline between ABP 798 and rituximab arms at each time point.   
The mixed model repeated measures analysis will be implemented using PROC MIXED 
in SAS. Because the time points at which measurements occur are not equally spaced (8, 
12, and 24 weeks) and because measurements over time are expected to be correlated, 
with correlation coefficients being greater for time points that are closer together, a 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 33 of 73 
spatial covariance structure denoted SP(POW) in SAS will be used. However, before 
implementing this structure, its appropriateness will be checked by choosing the smaller 
Akaike’s information criterion when comparing the SP(POW) covariance structure with 
unstructured covariance structure. Example code for PROC MIXED with three treatment 
groups is displayed below: 
Note: The contrasts in the lsmestimate statement may need to be changed depending on 
the order of the treatments. Only the individual arm comparison SAS code is presented.  
 
'$6&53DW2WKHU7LPH3RLQWV
For time period from Day 1 to EOS, the treatment difference and its confidence intervals 
will be estimated using an ANCOVA model with baseline DAS28-CRP measurement 
and stratification factors as covariates at each visit window. A sample SAS code for 
ANCOVA model using PROC MIXED is displayed below: 
Note: The contrasts in the estimate statement may need to be changed depending on the 
order of the treatments. Only the individual arm comparison SAS code is presented. 
6(16,7,9,7<$1$/<6(6
To assess the robustness of the DAS28-CRP at week 24 results, the repeated measures 
analysis described above will be repeated using the PP analysis set based on the day 1 
through week 24 time period described above. In addition, DAS28-CRP change from 
CCI
CCI


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 34 of 73 
baseline at week 24 will be analyzed using ANCOVA adjusting for stratification factors 
and baseline DAS28-CRP results. 
A sensitivity analysis will also be done to explore the impact of the baseline covariates in 
section 9.4 on  DAS28-CRP at week 24 in addition to the stratification factors. A 
stepwise model selection (with <0.25 p-value to enter the model and <0.1 to stay in the 
model) will be fit using PROC GLM and will be used to determine if any of the 
covariates have significant impact on the outcome variable. The final repeated measures 
model will be fit using PROC MIXED and will maintain treatment, the stratification 
factors, baseline DAS28-CRP, visit and visit by treatment regardless and the covariates 
identified by the stepwise model and the same covariance structure selected in the 
primary statistical analysis regardless. This additional exploration will be performed on 
the FAS based on the day 1 through week 24 time period described above.  
Additional sensitivity analysis considering the drop-out and missing value will be 
described in the section 9.7.4.  
In addition, for each subgroup (described in section 4.4) the DAS28-CRP at week 24 will 
also be examined in the subgroups. These additional explorations will be performed on 
the FAS based on the day 1 through week 24 time period described above by using the 
repeated measures analysis with the same covariance structure chosen in the primary 
statistical analysis. The 90% CI and 95% CIs of difference in mean change from baseline 
of DAS28-CRP will be displayed.  
The DAS28-CRP change from baseline will be plotted by treatment and visit for the FAS 
with adjusted mean and 95% CI. 
 $&5
The analyses of ACR20/50/70 are descriptive. The RR of ACR20/50/70 at week 8, week 
12 and week 24 (refers to the analysis visit) will be analyzed based on the day 1 through 
week 24 time period using a repeated measures analysis, where data are included as 
observed for both FAS and PP, unless otherwise specified. Besides stratification 
variables, visit week (as a categorical variable), treatment, and treatment-by-visit 
interaction will be included in the generalized estimating equation (GEE) model 
assuming a log link and an AR (1) correlation structure. Both 90% CI and 95% CI will be 
provided.  
A sample SAS code for PROC GENMOD with the repeated statement is displayed 
below: 
CCI


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 35 of 73 
 
Note: The contrasts in the estimate statement may need to be changed depending on the 
order of the treatments. Only the individual arm comparison SAS code is presented. 
The risk difference (RD) of ACR20 at week 8, week 12 and week 24 between ABP 798 
and rituximab arms and corresponding 90% and 95% CIs will be displayed based on a 
GEE model similar to the above model with the link function changed to ‘link=identity’ 
and without the exponential transformation option under LSMESTIMATE and 
LSMEANS statement.  
From Day 1 to EOS, the RR of ACR20/50/70  between ABP 798 and rituximab arms and 
their corresponding CIs will be estimated at each visit (weeks 8, 12, 24, 40 and 48) using 
generalized linear model (specifically, a log-binomial regression model) adjusted for the 
stratification factors as covariates with observed data. A sample SAS code for PROC 
GENMOD is displayed below: 
Note: The contrasts in the estimate statement may need to be changed depending on the 
order of the treatments. Only the individual arm comparison SAS code is presented. 
The RD of ACR20 between ABP and rituximab arms and their corresponding CIs will be 
obtained, based on a similar generalized linear model with link function changed to 
‘link=identity’ and without the exponential transformation option under LSMESTIMATE 
and LSMEANS statements. 
The adjusted percent of subjects achieving ACR20/50/70 will be plotted by treatment and 
week for the FAS accordingly. 
 +\EULG$&5
The analyses of hybrid ACR are descriptive. The mean difference of hybrid ACR score at 
week 8, week 12 and week 24 (refers to the analysis visit) will be analyzed using a 
repeated measures analysis described in section 9.7.1.  From Day 1 to EOS, the mean 
difference and its confidence intervals will be estimated using an ANOVA model with 
stratification factors as covariates at each visit window. A similar sample SAS code for it 
is displayed in section 9.7.1.  
CCI
CCI


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 36 of 73 
 0HWKRGVIRU+DQGOLQJ'URSRXWVDQG0LVVLQJ'DWDIRU(IILFDF\
For ACR, the determination of ACR20/50/70 response will be based on the data available 
at each visit (refer to Appendix 2 for handling missing ACR individual components), 
taking into account prorated tenderness and swollenness of joints.  
For the primary DAS28-CRP analysis, the primary repeated measures model will be fit to 
the observed data. The rate of missing DAS28-CRP at week 24 will be tabulated with 
reasons, such as missing baseline, incomplete week 24 assessment (missing up to 3 of 4 
components), outside of the defined week 24 analysis time frame, missing week 24 
component assessments (missing all 4 components), and discontinued from the study 
early prior to week 24 (day 210). 
Tipping point analyses will be performed for the efficacy endpoints of DAS28-CRP 
change from baseline at week 24 based on ANCOVA model  using FAS analysis set to 
explore the sensitivity of results to violations in assumptions about the missing data (i.e., 
to various missing not-at-random assumptions). Assumptions (tipping point) under which 
the 90% CI no longer rules out unacceptable differences in efficacy as determined by 
DAS28-CRP change from baseline at week 24 between ABP 798 and reference 
(Rituximab (US) and Rituximab (EU)) will be identified.  
In this analysis, all the observed data will be included as non-missing, regardless of 
adherence to treatment or use of prohibited medication. The analysis will be performed 
using a general three-step approach: 
(1) Multiple imputation will be done using PROC MI to generate multiple (e.g., 10) 
imputed datasets by imputing missing data assuming monotone missing pattern and that 
subjects with missing data have, on average, worse or better efficacy compared to those 
who have values. The mean difference between the (unobserved) missing values and 
observed values (refer to as shift) can vary independently for the different treatment 
groups. For this analysis, the shifts for Rituximab(EU) and Rituximab(US) are assumed 
to be the same. 
(2) Each of these imputed datasets (which contains identical values of non-missing data 
but different values imputed for missing data) is analyzed using standard SAS procedure, 
e.g., PROC GLM, PROC GENMOD, etc. 
(3) Results from all imputed datasets are then combined together for overall inference 
using PROC MIANALYZE.  
For DAS28-CRP change from baseline at week 24, seven equally spaced shifts (-0.9 to 
0.9 by 0.3) for the DAS28-CRP change from baseline for subjects with missing data will 
be explored.  A sample SAS code for given shifts is given as follows: 
CCI


Amgen Proprietary - Confidential
Sponsor:  Amgen Inc.
Statistical Analysis Plan           
Protocol No:  20130108
10-December-2018/ Version 2.0 
 Page 37 of 73 
Note: Only the individual arm comparison SAS code is presented. 
0XOWLSOLFLW\
No multiplicity adjustment will be done for efficacy endpoints.  
3RROLQJRI6LWHV
All sites will be pooled together for all analyses. 
9.8 SAFETY ANALYSES 
All safety analyses will be performed on the Safety analysis set based on subject’s actual 
treatment received. In general, summaries will be provided separately for (1) day 1 to 1st 
infusion of the 2nd dose of IP (exclusive) for subjects who received 2nd dose or to week 
24 (day 175) or EOS (whichever is earlier) for subjects who didn’t receive 2nd dose and 
(2) entire study, unless otherwise specified. 
$GYHUVH(YHQWV
All reported AEs will be coded to the appropriate SOC and PT according to the most 
current version of MedDRA, and the severity of each AE will be graded by the 
investigator per CTCAE v4.03 criteria.  
Only TEAE will be tabulated.  
Subject incidence of the following AEs will be tabulated by treatment groups and by 
SOC, PT, and maximum severity grade per CTCAE v4.03: 
x
treatment-emergent AEs
Subject incidence of the following AEs will be tabulated by treatment groups and by 
SOC and PT: 
CCI


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 38 of 73 
 treatment-emergent AEs  
Subject incidence of the following AEs will be tabulated by preferred term in descending 
order of frequency in the ABP798 column: 
 treatment-emergent AEs  
 grade 3 or higher treatment-emergent AEs  
 treatment-emergent AEs leading to discontinuation of IP/study 
 treatment-emergent AEs leading to infusion delay/infusion not given 
 treatment-emergent AEOIs 
For treatment-emergent AEOIs, the point estimate and 95% CI for RD of the subject 
incidence between ABP and the reference product are provided. 
 
Exposure adjusted subject incidence rate (EAIR) of the following AEs will be tabulated 
by preferred term in descending order of frequency in the ABP798 column for the entire 
study: 
 treatment-emergent AEs 
 treatment-emergent AEOIs 
The point estimate and 95% CI for RR of the EAIR between ABP and the reference 
product are also provided.  
AEs leading to discontinuation of IP/study are those with an action taken with 
Investigational Medicinal Product of “dose discontinued” or those with other action taken 
of “discontinued from study”. If subjects have an AE for action taken with Investigational 
Medicinal Product of “dose delayed/not administered” checked, that AE leads to the 
infusion delay/infusion not given. If an AE leads to multiple actions taken with IP, only 
the last action will be captured in the eCRF. 
Counting of AEs will be by subject, and subjects will be counted only once within each 
SOC or PT. 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.  
An overall summary table of treatment-emergent AEOIs will be displayed, providing the 
number and percent of subjects that are within each AEOI category. In addition, infusion 
reaction EOIs will also be summarized by PT and maximum CTCAE grade and also by 
infusion and PT.  
A subject listing of AEs leading to discontinuation of IP/ study will be provided.  
 Deaths and Serious Adverse Events 
Subject incidence of the following will be tabulated by SOC, PT and maximum severity 
grade per CTCAT V4.03:  
 serious treatment-emergent AEs  


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 39 of 73 
Subject incidence of the following will be tabulated by preferred term in descending 
order of frequency of the ABP798 arm: 
 serious treatment-emergent AEs  
 treatment-emergent fatal AEs  
A subject listing of SAEs and AEs with fatal outcome will be also provided. 
 Laboratory Data 
Laboratory test results are reported in International System of Units (SI) units. 
Laboratory values and change from baseline will be summarized using descriptive 
statistics at each analysis visit by treatment. Shift tables of the worst on-study laboratory 
toxicity based on CTCAE v4.03 grading relative to baseline will be presented by 
treatment group. The shift tables will take into account all post-baseline (schedule and 
unscheduled) laboratory results for determination of worst on-study laboratory toxicity 
within the two summary timeframes listed previously. For labs with toxicity grading in 
two directions, for toxicity due to decreased value, the maximum grade is corresponding 
to the minimum post-baseline value. For toxicity due to increase value, the maximum 
grade is corresponding to the maximum post-baseline value. In addition, subject 
incidence tables and listings of grade ≥ 3 laboratory toxicities will be provided based on 
all post-baseline (scheduled and unscheduled) laboratory results for each of the two 
reporting periods. Standard ranges will be used for the laboratory analysis. 
Lab assessments will be grouped for summary as follows: 
 Hematology – white blood cell parameters: white blood cell count and differential 
 Hematology – red blood cell parameters: hemoglobin, packed cell volume or 
hematocrit, red blood cell count, mean corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration 
 Hematology – other parameters: platelets 
 Serum chemistry – hepatobiliary parameters: alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, gamma 
glutamyl transferase 
 Serum chemistry – general chemistry: sodium, potassium, albumin, total protein, 
non-fasting glucose 
 Serum chemistry – renal function tests: urea, creatinine 
 Vital Signs and Physical Examination 
Observed and change from baseline in vital signs will be summarized by parameter and 
treatment. Descriptive statistics will be shown for baseline, each post-baseline time point 
up to EOS, and the change from baseline to each post-baseline time point. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 40 of 73 
 Immunogenicity 
The number and percentage of subjects developing binding and neutralizing ADA will be 
tabulated by treatment . 
Pre-existing antibody incidence and developing antibody incidence will be summarized. 
Pre-existing antibody is defined as a positive antibody result at baseline (see Section 5.1 
for definition of baseline). Developing antibody incidence is defined as a negative or no 
binding antibody result at baseline and a positive antibody result at a post-baseline time 
point. A transient antibody result is defined as a positive post-baseline result with a 
negative result at the subject’s last time point tested within the study period.  
In addition, the frequency and percent of subjects with positive binding or neutralizing 
ADA results will be tabulated by visit and treatment. 
 Methods for Handling Missing Data for Safety 
Missing safety 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:  
Table 2. Imputation Rules for Partial or Missing Start Dates 
Start Date 
Stop Date
Complete: 
yyyymmdd 
Partial: yyyymm 
Partial: yyyy 
Missing 
<1st 
dose 
≥1st 
dose
<1st 
dose 
yyyym
m
≥1st 
dose 
yyyymm
<1st 
dose 
yyyy
≥1st 
dose 
yyyy
Partial
: 
yyyym
m 
= 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 
≠ 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: 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 41 of 73 
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. 
9.9 EXPLORATORY ANALYSES 
 DAS28-CRP Individual Components 
The DAS28-CRP individual components of swollen (28) and tender joint counts (28), 
subject’s global health assessment,  and CRP will be summarized as change from 
baseline descriptively by treatment and visit using the FAS as observed.  
 ACR Individual Components 
The ACR individual components of swollen (66) and tender joint counts (68), subject’s 
global health assessment, investigator’s global assessment, subject’s assessment of 
disease-related pain, HAQ-DI and CRP will be summarized descriptively by treatment 
and visit using the FAS as observed.  
10. CHANGE FROM PROTOCOL SPECIFIED ANALYSIS 
Druing the development of this document, pharmacokinetic concentration analysis set 
was defined in the SAP to better describe the analysis population criteria which will be 
the population set in the PK serum concentration TFLs.  Additionally, the definition of 
per protocol and per protocol pharmacokinetic parameter analysis sets were modified to 
include “important protocol deviation” instead of “protocol deviation” to properly reflect 
the population included in this analysis set.    


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 42 of 73 
Furthemore, per protocol analysis set criteria also includes the condition of 2 full infusion 
of the first dose, meaning that the drug compliance of 90%-110% of the first dose, 
additionally to ensure this analysis set follows the protocol requirements.  
 
11. VALIDATION 
The programming (including quality control) of the analysis datasets and TFLs will be 
conducted under PRA's standard processes PRS 050 and documented accordingly. The 
entire set of TFL will be checked for completeness and consistency prior to its delivery to 
the client by the lead statistician and a senior level statistician, or above, who is not a 
member of the project team. 
The PRA validation process is repeated any time TFL are redelivered using different 
data. Execution of this validation process is documented through the study Table of 
Programs that is provided to the client at study conclusion. 
12. REFERENCES 
Ke C, Wang J, Zhang C, Jiang Q, Snapinn S. On errors in stratified randomization. 
Statistics in Biopharmaceutical Research 2017; 9 (2): 225-33. 
Volkmann ER, Agrawal H, Maranian P, Furst DE. Rituximab for rheumatoid arthritis: A 
meta-analysis and systematic review. Clin Med Insights: Therapeutics 2010:2 749-760. 
American College of Rheumatology Committee to Reevaluate Improvement Criteria, 
2007, A 286 Proposed Revision to the ACR20: The Hybrid Measure of American 
College of Rheumatology Response, Arthritis Rheum., Mar 15;57(2):193-202 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 43 of 73 
APPENDIX 1 
GLOSSARY OF ABBREVIATIONS 
Glossary of Abbreviations: 
ACR 
American College of Rheumatology 
ACR20 
20% Improvement in ACR Core Set Measurements 
ACR50 
50% Improvement in ACR Core Set Measurements 
ACR70 
70% Improvement in ACR Core Set Measurements 
ADA 
Anti-drug Antibody 
ADaM 
Analysis Data Model 
AEOI 
Adverse Event of Interest 
AE 
Adverse Event 
ALT 
Alanine Aminotranferase 
AST 
Aspartate Aminotransferase 
AUC 
Area Under the Curve 
BMI 
Body Mass Index 
BQL 
Below Quantifiable Limit 
CCP 
Anti-cyclic Citrullinated Peptide 
CDAI 
Clinical Disease Activity Index 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CL 
clearance 
Clast 
Last measurable Concentration 
Cmax 
Maximum Concentration 
CRP 
C-reactive Protein 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTMS 
Clinical Trial Management System 
CV 
Coefficient of Variation 
DAS 
Disease Activity Score 
DMARDs 
Disease-modifying Anti-rheumatic Drugs 
DMC 
Data Monitoring Committee 
eCRF 
Electronic Case Report Form 
EOI 
End of Infusion 
EOS 
End of Study 
EULAR 
European League Against Rheumatism 
FAS 
Full Analysis Set 
GEE 
Generalized Estimating Equation 
GH 
General Health 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 44 of 73 
GMR 
Geometric Mean Ratio 
HAQ-DI 
Health Assessment Questionnaire Disability Index 
IP 
Investigational Product 
IPD 
Important protocol deviation 
IXRS 
Interactive Voice or Web Response System 
IV 
Intravenous 
KM 
Kaplan-meier 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRT 
mean residence time 
NCA 
Noncompartmental techniques 
NCI-US 
National Cancer Institute 
NSAID 
Non-steroidal Anti-inflammatory Drug 
PD 
Pharmacodynamic 
PD 
Protocol Deviations 
PK 
Pharmacokinetic 
PP 
Per Protocol 
PT 
Preferred Term 
Q1 
25th Percentile 
Q3 
75th Percentile 
RA 
Rheumatoid Arthritis 
RD 
Risk Difference 
RF 
Rheumatoid Factor 
RR 
Risk Ratio 
SAP 
Statistical Analysis Plan 
SAE 
Serious Adverse Event 
SDAI 
Simplified Disease Activity Index score 
SDTM 
Standard Data Tabulation Model 
SI 
International System of Units 
SJC28 
Swollen Joint Count (28 Joints) 
SMQ 
Standardised MedDRA Query 
SOC 
System Organ Class 
t1/2 
Terminal elimination half-life 
TEAE 
Treatment-emergent Adverse Event 
TFL 
Tables, Figures, and Listings 
Tmax 
Time to which the maximum serum concentration was observed 
TJC28 
Tender Joint Count (28 Joints) 
TNF 
Tumor Necrosis Factor 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 45 of 73 
VAS 
Visual Analog Scale 
WHO-DD 
World Health Organization Drug Dictionary 
λz 
Terminal elimination rate constant 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 46 of 73 
APPENDIX 2 METHOD FOR MISSING INDIVIDUAL 
COMPONENTS OF ACR CALCULATION  
In the case of some ACR components are missing, the ACR composite scores will be 
based on the non-missing components. If a subject’s non-missing components are not 
sufficient to identify ACR composite score, then that subject will be considered as 
missing ACR response. The corresponding algorithm is listed below (using ACR 20 as an 
example): 
 If both Tender or Swollen Joint Counts are improved at least 20%, and   
o If three or more of the other five ACR components are improved at least 20%, the 
subject is an ACR 20 responder; 
o If three or more of the other five ACR components are not improved at least 20%, 
the subject is an ACR 20 non-responder; 
o If none of the above, the ACR response for the subject cannot be determined due 
to missing data and is therefore coded as missing. 
 If either swollen or tender joint counts is not improved at least 20%, the subject is an 
     ACR non-responder 
 If either swollen or tender joint counts is missing and the other improved at least 
20%,  
      and 
o If three or more of the other five ACR components are not improved at least 20%, 
the subject is an ACR 20 non-responder; 
o Otherwise, the ACR response for the subject cannot be determined due to missing 
data and is therefore coded as missing 
 
 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 47 of 73 
 
APPENDIX 3 METHOD FOR MISSING INDIVIDUAL JOINT 
ASSESSMENTS  
A Pain/Tenderness or Swollen Joints may be coded as follows: 
 
Joint 
Codes: 
00   = None 
01   = Positive 
08   = Permanently inevaluable because of replaced, fused joint 
09   = Not evaluated because of intra-articular corticosteroid injection 
77   = Not Done 
The missing individual joint assessments due to artificial/fused joint, intra-articular 
corticosteroid injection or not done for other reason are imputed as the followings:  
For Joint Codes = 08,  
 At Screening: Code as missing at current visit only 
 At Baseline: Exclude the joint from the total joint counts for baseline and all 
subsequent visits.  
 Post-Baseline (If a joint is coded as 08 at a post-baseline visit but not at baseline): 
Code as “01” (failed) beginning with the current visit and all visits subsequent to 
the current visit. 
For Joint Codes = 09,  
 At Screening: Code as “01” (failed) at current visit only 
 At Baseline: Code as “01” (failed) for baseline and all subsequent visits.  
 Post-Baseline: Code as “01” (failed) beginning with the current visit and all visits 
subsequent to the current visit.   
For Joint Codes = 77,  
 At Baseline: Code as missing and exclude the joint from the total joint counts for 
baseline. 
 Post-baseline: Code as missing and exclude the joint from the total joint counts 
for the current visit. 
If there are joints being excluded after above imputation, the Tender or Swollen Joint 
Counts will be prorated based on the algorithm described below. 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 48 of 73 
Prorated Joint Counts 
If at least half but not all joints are evaluable (14 joints for the DAS28 joint counts, 34/33 
for the 68/66 joint counts), then the observed prorated Tender or Swollen Joint Counts 
will be calculated.   The prorated scores will be adjusted based upon the number of 
evaluable joints: the counted score will be multiplied by 28, 66, or 68 as applicable and 
divided by the number of joints evaluated.  Otherwise, the Tender or Swollen Joint 
Counts is missing.  
For example, if only 25 of the 28 DAS joints are assessed at a visit and 10 of those 25 are 
pain/tenderness and 8 of those 25 are swollen, the prorated joint counts are: 
 
Tender Joint Counts: 10/25*28 = 11.20 
 
Swollen Joint Counts: 8/25*28 = 8.96 
That is, the values of 11.20 and 8.96 will be used in calculating the percent improvement, 
not the values of 10 and 8. 
 
 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 49 of 73 
APPENDIX 4 HAQ-DI SCORING ALGORTIHM  
All language versions will use the following scoring system. 
 There are four possible responses for each sub-category item, or component, within a 
category: 
         0 = without ANY difficulty  
     2 = with MUCH difficulty  
         1 = with SOME difficulty  
     3 = UNABLE to do  
 Step 1: Calculate the maximum score for each of the 8 categories (7 of the categories 
are listed in the table below. The eighth category “Activities” is not listed in the table 
due to lack of questions regarding use of aids or device). At least one question in each 
category needs to be answered to compute the maximum score. 
 If an aid or device is used or help from another person is needed, set the score for 
the associated category to the maximum score between 2 and the score in step 1. 
 
Sub-domain 
Aids or devices 
Dressing&Grooming Devices used for dressing (button hook, zipper pull, long-handled 
shoe horn, etc.) 
Arising 
Special or built up chair 
Eating 
Built up or special utensils 
Walking 
Cane, Walker, Crutches, Wheelchair 
Hygiene 
Raised toilet seat, Bathtub seat, Bathtub bar, Long-handled 
appliances in bathroom 
Reach 
Long-handled appliances for reach 
Grip 
Jar opener (for jars previously opened) 
 
If no more than 2 categories have missing scores, then the disability score is the mean of 
the non-missing category scores.  Otherwise, the disability score is set to missing. 
 
 
 
 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 50 of 73 
APPENDIX 5  LIST OF EVENTS OF INTEREST AND THE 
ASSOCIATED SMQ AND EOI SEARCHING STRATEGIES  
Event of 
Interest 
Category of EOI query
(SMQ, Amgen query, 
or SOC) 
Search  
Strategy 
Additional 
Medical Review 
of the SMQ or 
SOC dataset for  
confirmation of 
the EOI 
Infusion reactions 
including 
Hypersensitivity 
Infusion reactions  
(Amgen query) 
Broad*- TEAE with start 
date same as, or one day 
after, IP administration 
date  
No 
Hypersensitivity (SMQ) 
Broad- TEAE with start 
date same as, or one day 
after, IP administration 
date 
No 
Cardiac disorders 
Cardiac disorders (SOC) 
 
No 
Serious infections 
Infections and Infestations 
(SOC)  
CTCAE grade >=3 or the 
serious TEAE 
No 
Progressive 
multifocal 
leukoencephalopa
thy 
Progressive multifocal 
leukoencephalopathy 
(Amgen query) 
Broad 
Yes 
Hematological 
reactions 
Hematopoietic cytopenia 
(SMQ) 
Broad  
No 
Hepatitis B 
reactivation 
Hepatitis B Infection 
(Amgen query) 
Broad 
Yes 
Opportunistic 
infections 
Infections and infestations 
(SOC) 
 
Yes 
Hypogammaglob
ulinemia 
Immune  mediated events 
associated  with oncologic 
immune therapies (Amgen 
query) 
Broad  
Yes 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 51 of 73 
Severe 
mucocutaneous 
reactions 
Severe cutaneous adverse 
reactions (SMQ) 
CTCAE grade >=3 or the 
serious TEAE, Broad 
search  
No 
Gastrointestinal 
perforation 
Gastrointestinal 
perforation(SMQ) 
Narrow 
No 
*Broad search strategy includes both narrow scope terms and broad scope terms. 
 
 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 52 of 73 
 
APPENDIX 6 LIST OF POST-TEXT TABLES, FIGURES, 
LISTINGS, AND SUPPORTIVE SAS OUTPUT APPENDICES 
Table 
Number 
Table Title 
14.1 
Disposition and Analyzed Dataset Tables 
Table 14.1.1  
Subject Analysis Sets by Treatment (All Screened Subjects) 
Table 14-
1.2.1. 
Randomization by Region, Country and Center (Full Analysis Set) 
Table 14-
1.2.2. 
Randomization by Stratification Factors (Full Analysis Set) 
Table 14-
1.3.1. 
Subject Study Disposition by Treatment (Full Analysis Set) 
Table 14-
1.3.2. 
Subject Study Disposition by Treatment (Safety Analysis Set) 
Table 14-
1.3.3. 
Subject Study Disposition by Treatment (Pharmacokinetic 
Concentration Analysis Set) 
Table 14-
1.3.4. 
Subject Study Disposition by Treatment (Pharmacokinetic Parameter 
Analysis Set) 
Table 14-
1.3.5. 
Subject Study Disposition by Treatment (Per Protocol Analysis Set) 
Table 14-
1.3.6. 
Subject Study Disposition by Treatment (Per Protocol 
Pharmacokinetic Parameter Analysis Set) 
Table 14-
1.3.7. 
Subject Study Disposition by Treatment (Anti-drug Antibody 
Analysis Set) 
14.2 
Demographic and Baseline Characteristics Data Tables 
Table 14-2.1. 
Demographic and Baseline Characteristics by Treatment (Full 
Analysis Set) 
Table 14-2.2. 
Demographic and Baseline Characteristics by Treatment (Safety 
Analysis Set) 
Table 14-2.3. 
Demographic and Baseline Characteristics by Treatment 
(Pharmacokinetic Concentration Analysis Set) 
Table 14-2.4. 
Demographic and Baseline Characteristics by Treatment 
(Pharmacokinetic Parameter Analysis Set) 
Table 14-2.5. 
Demographic and Baseline Characteristics by Treatment (Per 
Protocol Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 53 of 73 
Table 14-2.6. 
Demographic and Baseline Characteristics by Treatment (Per 
Protocol Pharmacokinetic Parameter Analysis Set) 
Table 14-2.7. 
Demographic and Baseline Characteristics by Treatment (Anti-drug 
Antibody Analysis Set) 
Table 14-
2.8.1. 
Resolved Medical Conditions at Randomization by System Organ 
Class, Preferred Term, and Treatment (Safety Analysis Set) 
Table 14-
2.8.2. 
Unresolved Medical Conditions at Randomization by System Organ 
Class, Preferred Term, and Treatment (Safety Analysis Set) 
Table 14-2.9. 
Prior Medications by Preferred Name and Treatment (Safety Analysis 
Set) 
14.3 
Measures of Treatment Compliance Data Tables 
Table 14-3.1. 
Inclusion/Exclusion Criteria Protocol Deviations (Full Analysis Set) 
Table 14-3.2. 
Important Protocol Deviations  (Full Analysis Set) 
Table 14-3.3. 
Concomitant Medications by Preferred Name and Treatment (Safety 
Analysis Set) 
14.4 
Efficacy Data Tables 
Table 14-4.1.1. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline at Week 24 – Primary Analysis (Full Analysis Set) 
Table 14-4.1.2. 
Analysis of DAS28-CRP Change From Baseline at Week 24 – 
Sensitivity Analysis (Full Analysis Set) 
Table 14-4.1.3.1. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Visit – Day 1 Through Week 24 (Full Analysis Set) 
Table 14-4.1.3.2. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Visit – Day 1 Through Week 24 (Per Protocol  
Analysis Set) 
Table 14-4.1.4.1. 
Analysis of DAS28-CRP Change From Baseline by Visit – Day 1 
Through End of Study (Full Analysis Set) 
Table 14-4.1.4.2. 
Analysis of DAS28-CRP Change From Baseline by Visit – Day 1 
Through End of Study (Full Analysis Set – Subgroup who 
received the 1st infusion of the 2nd dose at week 24 ) 
Table 14-4.1.5. 
Summary for Reason of Missing DAS28-CRP Change from 
Baseline Results at Week 24 (Full Analysis Set) 
Table 14-4.1.6. 
Tipping Point Analysis Results for Mean Difference of DAS28-
CRP Change From Baseline at Week 24 for ABP 798 vs 
Rituximab with 90% Confidence Interval (Full Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 54 of 73 
Table 14-4.1.7. 
Repeated Measures Analysis with Additional Selective Covariates 
for DAS28-CRP Change From Baseline at Week 24  (Full 
Analysis Set) 
Table 14-4.2.1. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Age Subgroup - Day 1 Through Week 24 (Full 
Analysis Set) 
Table 14-4.2.2. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Race Subgroup – Day 1 Through Week 24 (Full 
Analysis Set) 
Table 14-4.2.3. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Gender Subgroup – Day 1 Through  Week 24 (Full 
Analysis Set) 
Table 14-4.2.5. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Binding Anti-drug Antibodies Status Subgroup – Day 
1 Through Week 24 (Full Analysis Set) 
Table 14-4.2.6. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Neutralizing Anti-drug Antibodies Status Subgroup – 
Day 1 Through Week 24 (Full Analysis Set) 
Table 14-4.2.7. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Baseline Oral Corticosteroid Use Subgroup – Day 1 
Through Week 24 (Full Analysis Set) 
Table 14-4.3.1. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Geographic Region Subgroup – Day 1 Through Week 
24 (Full Analysis Set) 
Table 14-4.3.2. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Seropositivity Subgroup – Day 1 Through Week 24 
(Full Analysis Set) 
Table 14-4.3.3. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline by Prior Biologics Use Subgroup – Day 1 Through Week 
24 (Full Analysis Set) 
 
 
 
 
Table 14-4.5.1.1 
Repeated Measures Analysis of ACR20 by Visit – Day 1 Through 
Week 24 (Full Analysis Set) 
Table 14-4.5.1.2 
Repeated Measures Analysis of ACR20 by Visit – Day 1 Through 
Week 24 (Per Protocol Analysis Set) 
Table 14-4.5.2.1. 
Analysis of ACR20 by Visit – Day 1 Through End of Study (Full 
Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 55 of 73 
Table 14-4.5.2.2. 
Analysis of ACR20 by Visit – Day 1 Through End of Study (Full 
Analysis Set – Subgroup who received the 1st infusion of the 2nd 
dose at week 24) 
Table 14-4.5.3.1 
Repeated Measures Analysis of Hybrid ACR by Visit – Day 1 
Through Week 24 (Full Analysis Set) 
Table 14-4.5.3.2 
Repeated Measures Analysis of Hybrid ACR by Visit – Day 1 
Through Week 24 (Per Protocol Analysis Set) 
Table 14-4.5.3.3. 
Analysis of Hybrid ACR by Visit – Day 1 Through End of Study 
(Full Analysis Set) 
Table 14-4.5.3.4. 
Analysis of Hybrid ACR by Visit – Day 1 Through End of Study 
(Full Analysis Set – Subgroup who received the 1st infusion of the 
2nd dose at week 24) 
Table 14-4.6.1. 
Repeated Measures Analysis of ACR50 by Visit – Day 1 Through 
Week 24 (Full Analysis Set) 
Table 14-4.6.2.1. 
Analysis of ACR50 by Visit – Day 1 Through End of Study (Full 
Analysis Set) 
Table 14-4.6.2.2. 
Analysis of ACR50 by Visit – Day 1 Through End of Study (Full 
Analysis Set – Subgroup who received the 1st infusion of the 2nd 
dose at week 24) 
Table 14-4.7.1. 
Repeated Measures Analysis of ACR70 by Visit – Day 1 Through 
Week 24 (Full Analysis Set) 
Table 14-4.7.2.1. 
Analysis of ACR70 by Visit – Day 1 Through End of Study (Full 
Analysis Set) 
Table 14-4.7.2.2. 
Analysis of ACR70 by Visit – Day 1 Through End of Study (Full 
Analysis Set– Subgroup who received the 1st infusion of the 2nd 
dose at week 24 ) 
Table 14-4.8.1. 
Summary of Swollen Joint Counts by Visit (Full Analysis Set) 
Table 14-4.8.2. 
Summary of Tender Joint Counts by Visit (Full Analysis Set) 
Table 14-4.8.3. 
Summary of Subject’s Global Health Assessment by Visit (Full 
Analysis Set) 
Table 14-4.8.4. 
Summary of Investigator’s Global Health Assessment by Visit 
(Full Analysis Set) 
Table 14-4.8.5. 
Summary of Subject’s Assessment of Disease-related Pain by 
Visit (Full Analysis Set) 
Table 14-4.8.6. 
Summary of HAQ-DI Total Score by Visit (Full Analysis Set) 
Table 14-4.8.7. 
Summary of CRP by Visit (Full Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 56 of 73 
Table 14-4.8.8. 
Summary of Swollen Joint Counts by Visit – DAS28-CRP 
Component (Full Analysis Set) 
Table 14-4.8.9. 
Summary of Tender Joint Counts by Visit – DAS28-CRP 
Component (Full Analysis Set) 
Table 14-4.8.10. 
Summary of Subject’s Global Health Assessment by Visit – 
DAS28-CRP Component (Full Analysis Set) 
Table 14-4.8.11. 
Summary of CRP by Visit – DAS28-CRP Component (Full 
Analysis Set) 
Table 14-4.10.1.1. Repeated Measures Analysis of DAS28-CRP Change From 
Baseline at Week 24 Comparing ABP 798 with Pooled Rituximab 
(Full Analysis Set) 
Table 14-4.10.1.2. Analysis of DAS28-CRP Change From Baseline (ANCOVA) at 
Week 24 Comparing ABP 798 with Pooled Rituximab (Full 
Analysis Set) 
Table 14-
4.10.1.3.1. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline Comparing ABP 798 with Pooled Rituximab by Visit – 
Day 1 ThroughWeek 24 (Full Analysis Set) 
Table 14-
4.10.1.3.2. 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline Comparing ABP 798 with Pooled Rituximab by Visit – 
Day 1 Through Week 24 (Per Protocol  Analysis Set) 
Table 14-
4.10.1.4.1. 
Analysis of DAS28-CRP Change From Baseline (ANCOVA) 
Comparing ABP 798 with Pooled Rituximab by Visit – Day 1 
Through End of Study (Full Analysis Set) 
Table 14-
4.10.1.4.2. 
Analysis of DAS28-CRP Change From Baseline (ANCOVA) 
Comparing ABP 798 with Pooled Rituximab by Visit – Day 1 
Through End of Study (Per Protocol Set) 
Table 14-4.10.1.6. Tipping Point Analysis Results for Mean Difference of DAS28-
CRP Change From Baseline at Week 24 for ABP 798 vs Pooled 
Rituximab with 90% Confidence Interval (Full Analysis Set) 
Table 14-4.10.1.7. Repeated Measures Analysis with Additional Selective Covariates 
for DAS28-CRP Change From Baseline at Week 24 Comparing 
ABP 798 with Pooled Rituximab (Full Analysis Set) 
Table 14-4.10.5.1 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline Comparing ABP 798 with Pooled Rituximab by Age 
Subgroup - Day 1 Through Week 24 (Full Analysis Set) 
Table 14-4.10.5.2 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline Comparing ABP 798 with Pooled Rituximab by Race 
Subgroup – Day 1 Through Week 24 (Full Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 57 of 73 
Table 14-4.10.5.3 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline Comparing ABP 798 with Pooled Rituximab by Gender 
Subgroup – Day 1 Through  Week 24 (Full Analysis Set) 
Table 14-4.10.5.5 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline Comparing ABP 798 with Pooled Rituximab by Binding 
Anti-drug Antibodies Status Subgroup – Day 1 Through Week 24 
(Full Analysis Set) 
Table 14-4.10.5.6 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline Comparing ABP 798 with Pooled Rituximab by 
Neutralizing Anti-drug Antibodies Status Subgroup – Day 1 
Through Week 24 (Full Analysis Set) 
Table 14-4.10.5.7 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline  Comparing ABP 798 with Pooled Rituximab by 
Baseline Oral Corticosteroid Use Subgroup – Day 1 Through 
Week 24 (Full Analysis Set) 
Table 14-4.10.6.1 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline  Comparing ABP 798 with Pooled Rituximab by 
Geographic Region Subgroup – Day 1 Through Week 24 (Full 
Analysis Set) 
Table 14-4.10.6.2 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline Comparing ABP 798 with Pooled Rituximab by 
Seropositivity Subgroup – Day 1 Through Week 24 (Full Analysis 
Set) 
Table 14-4.10.6.3 
Repeated Measures Analysis of DAS28-CRP Change From 
Baseline Comparing ABP 798 with Pooled Rituximab by Prior 
Biologics Use Subgroup – Day 1 Through Week 24 (Full Analysis 
Set) 
Table 14-
4.11.5.1.1 
Repeated Measures Analysis of ACR20 Comparing ABP 798 with 
Pooled Rituximab by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 
Table 14-
4.11.5.1.2 
Repeated Measures Analysis of ACR20 Comparing ABP 798 with 
Pooled Rituximab by Visit – Day 1 Through Week 24 (Per 
Protocol Analysis Set) 
Table 14-4.12.1.1 
Repeated Measures Analysis of Hybrid ACR Comparing ABP 798 
with Pooled Rituximab by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 
Table 14-4.12.1.2 
Repeated Measures Analysis of Hybrid ACR Comparing ABP 798 
with Pooled Rituximab by Visit – Day 1 Through Week 24 (Per 
Protocol Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 58 of 73 
Table 14-4.13.1 
Repeated Measures Analysis of ACR 50 Comparing ABP 798 
with Pooled Rituximab by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 
Table 14-4.14.1 
Repeated Measures Analysis of ACR 70 Comparing ABP 798 
with Pooled Rituximab by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 
Figure 14-4.10. 
Mean DAS28-CRP Change from Baseline – Day 1 Through Week 
24 (Full Analysis Set) 
Figure 14-4.11.1. 
Percent of Subjects Achieving ACR20 Response – Day 1 Through 
End of Study (Full Analysis Set) 
Figure 14-4.11.2. 
Percent of Subjects Achieving ACR50 Response – Day 1 Through 
End of Study (Full Analysis Set) 
Figure 14-4.11.3. 
Percent of Subjects Achieving ACR70 Response – Day 1 Through 
End of Study (Full Analysis Set) 
Figure 14-4.11.4. 
Mean Hybrid ACR – Day 1 Through End of Study (Full Analysis 
Set) 
Figure 14-4.11. 
ACR Response at Week 24 (Full Analysis Set) 
Figure 14-4.12. 
Mean DAS28-CRP Change from Baseline with Pooled Rituximab 
– Day 1 Through Week 24 (Full Analysis Set) 
Figure 14-4.13.1. 
Percent of Subjects Achieving ACR20 Response with Pooled 
Rituximab – Day 1 Through Week 24 (Full Analysis Set) 
Figure 14-4.13.2. 
Percent of Subjects Achieving ACR50 Response with Pooled 
Rituximab – Day 1 Through Week 24 (Full Analysis Set) 
Figure 14-4.13.3. 
Percent of Subjects Achieving ACR70 Response with Pooled 
Rituximab – Day 1 Through Week 24 (Full Analysis Set) 
Figure 14-4.13.4. 
Mean Hybrid ACR with Pooled Rituximab – Day 1 Through 
Week 24 (Full Analysis Set) 
14.5 
Extent of Exposure Tables 
Table 14-5.1. 
Investigational Product Exposure Summary by Treatment (Safety 
Analysis Set) 
Table 14-5.2. 
Investigational Product Administration by  Visit and Treatment 
(Safety Analysis Set) 
14.6 
Adverse Events Data Tables 
Table 14-6.1.1. 
Overall Summary of Treatment-emergent Adverse Events by 
Treatment – Day 1 Until  1st Infusion of 2nd Dose (Safety 
Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 59 of 73 
Table 14-6.1.2. 
Overall Summary of Treatment-emergent Adverse Events by 
Treatment –Day 1 Through End of Study (Safety Analysis Set) 
Table 14-6.2.1.1. 
Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term, and Treatment – Day 1 Until  1st Infusion of 2nd 
Dose  (Safety Analysis Set) 
Table 14-6.2.1.2. 
Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term, and Treatment – Day 1 Through End of Study  
(Safety Analysis Set) 
Table 14-6.2.2.1. 
Treatment-emergent Adverse Events by Preferred Term and 
Treatment – Day 1 Until  1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-6.2.2.2. 
Treatment-emergent Adverse Events by Preferred Term and 
Treatment – Day 1 Through End of Study (Safety Analysis Set) 
Table 14-6.2.2.3. 
Treatment-emergent Adverse Events by Age Subgroup, Preferred 
Term and Treatment – Day 1 Until 1st Infusion of 2nd Dose 
(Safety Analysis Set) 
Table 14-6.2.2.4. 
Treatment-emergent Adverse Events by Age Subgroup, Preferred 
Term and Treatment – Day 1 Through End of Study (Safety 
Analysis Set) 
Table 14-6.2.3.1. 
Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term, Maximum CTCAE Grade, and Treatment – Day 1 
Until 1st Infusion of 2nd Dose (Safety Analysis Set) 
Table 14-6.2.3.2. 
Treatment-emergent Adverse Events by System Organ Class, 
Preferred Term, Maximum CTCAE Grade, and Treatment – Day 1 
Through End of Study  (Safety Analysis Set) 
Table 14-6.2.4.1. 
Grade ≥3 Treatment-emergent Adverse Events by Preferred Term 
and Treatment - Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-6.2.4.2. 
Grade ≥3 Treatment-emergent Adverse Events by Preferred Term 
and Treatment – Day 1 Through End of Study (Safety Analysis 
Set) 
Table 14-6.3.1.1. 
Treatment-emergent Adverse Events Leading to Discontinuation 
of IP/Study by Preferred Term and Treatment – Day 1 Until 1st 
Infusion of 2nd Dose (Safety Analysis Set) 
Table 14-6.3.1.2. 
Treatment-emergent Adverse Events Leading to Discontinuation 
of IP/Study by Preferred Term and Treatment – Day 1 Through 
End of Study (Safety Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 60 of 73 
Table 14-6.3.1.3. 
Treatment-emergent Adverse Events Leading to Infusion 
Delay/Infusion Not Given by Preferred Term and Treatment – 
Day 1 Until 1st Infusion of 2nd Dose (Safety Analysis Set) 
Table 14-6.3.1.4. 
Treatment-emergent Adverse Events Leading to Infusion 
Delay/Infusion Not Given by Preferred Term and Treatment – 
Day 1 Through End of Study (Safety Analysis Set) 
Table 14-6.4.1.1. 
Treatment-emergent Adverse Events with Fatal Outcome by 
Preferred Term and Treatment – Day 1 Until 1st Infusion of 2nd 
Dose (Safety Analysis Set) 
Table 14-6.4.1.2. 
Treatment-emergent Adverse Events with Fatal Outcome by 
Preferred Term and Treatment – Day 1 Through End of Study  
(Safety Analysis Set) 
Table 14-6.4.2.1. 
Serious Treatment-emergent Adverse Events by System Organ 
Class, Preferred Term, Maximum CTCAE Grade and Treatment – 
Day 1 Until 1st Infusion of 2nd Dose (Safety Analysis Set) 
Table 14-6.4.2.2. 
Serious Treatment-emergent Adverse Events by System Organ 
Class, Preferred Term, Maximum CTCAE Grade and Treatment – 
Day 1 Through End of Study  (Safety Analysis Set) 
Table 14-6.4.3.1. 
Serious Treatment-emergent Adverse Events by Preferred Term 
and Treatment – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-6.4.3.2. 
Serious Treatment-emergent Adverse Events by Preferred Term 
and Treatment – Day 1 Through End of Study (Safety Analysis 
Set) 
Table 14-6.5.1.1. 
Overall Events of Interest Treatment-emergent Adverse Events by 
Treatment – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-6.5.1.2. 
Overall Events of Interest Treatment-emergent Adverse Events by 
Treatment – Day 1 Through End of Study (Safety Analysis Set) 
Table 14-
6.6.1.1.1. 
Infusion Reactions Including Hypersensitivity Treatment-
emergent Adverse Events by Preferred Term – Day 1 Until 1st 
Infusion of 2nd Dose (Safety Analysis Set) 
Table 14-
6.6.1.1.2. 
Infusion Reactions Including Hypersensitivity Treatment-
emergent Adverse Events by Preferred Term – Day 1 Through 
End of Study (Safety Analysis Set) 
Table 14-
6.6.1.2.1. 
Cardiac Disorders Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 61 of 73 
Table 14-
6.6.1.2.2. 
Cardiac Disorders Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Through End of Study (Safety Analysis 
Set) 
Table 14-
6.6.1.3.1. 
Serious Infections Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-
6.6.1.3.2. 
Serious Infections Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Through End of Study (Safety Analysis 
Set) 
Table 14-
6.6.1.4.1. 
Progressive Multifocal Leukoencephalopathy Treatment-emergent 
Adverse Events by Preferred Term – Day 1 Until 1st Infusion of 
2nd Dose (Safety Analysis Set) 
Table 14-
6.6.1.4.2. 
Progressive Multifocal Leukoencephalopathy Treatment-emergent 
Adverse Events by Preferred Term – Day 1 Through End of Study 
(Safety Analysis Set) 
Table 14-
6.6.1.5.1. 
Hematological Reactions Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-
6.6.1.5.2. 
Hematological Reactions Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Through End of Study (Safety Analysis 
Set) 
Table 14-
6.6.1.6.1. 
Hepatitis B Reactions Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-
6.6.1.6.2. 
Hepatitis B Reactions Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Through End of Study (Safety Analysis 
Set) 
Table 14-
6.6.1.7.1. 
Opportunistic infections Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-
6.6.1.7.2. 
Opportunistic infections Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Through End of Study (Safety Analysis 
Set) 
Table 14-
6.6.1.8.1. 
Hypogammaglobulinemia Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-
6.6.1.8.2. 
Hypogammaglobulinemia Treatment-emergent Adverse Events by 
Preferred Term – Day 1 Through End of Study (Safety Analysis 
Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 62 of 73 
Table 14-
6.6.1.9.1. 
Severe Mucocutaneous Reactions Treatment-emergent Adverse 
Events by Preferred Term – Day 1 Until 1st Infusion of 2nd Dose 
(Safety Analysis Set) 
Table 14-
6.6.1.9.2. 
Severe Mucocutaneous Reactions Treatment-emergent Adverse 
Events by Preferred Term – Day 1 Through End of Study (Safety 
Analysis Set) 
Table 14-
6.6.1.10.1. 
Gastrointestinal Perforation Treatment-emergent Adverse Events 
by Preferred Term – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-
6.6.1.10.2. 
Gastrointestinal Perforation Treatment-emergent Adverse Events 
by Preferred Term – Day 1 Through End of Study (Safety 
Analysis Set) 
Table 14-
6.6.2.1.1. 
Infusion Reactions Including Hypersensitivity Treatment-
emergent Adverse Events by Preferred Term, Maximum CTCAE 
Grade, and Treatment – Day 1 Until 1st Infusion of 2nd Dose  
(Safety Analysis Set) 
Table 14-
6.6.2.1.2. 
Infusion Reactions Including Hypersensitivity Treatment-
emergent Adverse Events by Preferred Term, Maximum CTCAE, 
and Treatment – Day 1 Through End of Study (Safety Analysis 
Set) 
Table 14-
6.6.2.2.1. 
Infusion Reactions Including Hypersensitivity Treatment-
emergent Adverse Events of Interest (EOI) by Infusion, Preferred 
Term, and Treatment – Day 1 Through End of Study (Safety 
Analysis Set) 
Table 14-6.7.1. 
Exposure Adjusted Incidence Rate for Treatment-emergent 
Adverse Events by Preferred Term and Treatment - Day 1 
Through End of Study (Safety Analysis Set) 
Table 14-6.7.2. 
Exposure Adjusted Incidence Rate for Treatment-emergent 
Adverse Events of Interest by Treatment – Day 1 Through End of 
Study  (Safety Analysis Set) 
14.7 
Clinical Laboratory Tables 
Table 14-7.1.1.  
Hematology Results by Visit and Treatment – White Blood Cell 
Parameters (Safety Analysis Set) 
Table 14-7.1.2.  
Hematology Results by Visit and Treatment – Red Blood Cell 
Parameters (Safety Analysis Set) 
Table 14-7.1.3.  
Hematology Results by Visit and Treatment – Other Parameters 
(Safety Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 63 of 73 
Table 14-7.1.4.1.  
Shift Summary of Hematology Results by Maximum Post-
baseline CTCAE Grade and Treatment – Day 1 Until 1st Infusion 
of 2nd Dose (Safety Analysis Set) 
Table 14-7.1.4.2.  
Shift Summary of Hematology Results by Maximum Post-
baseline CTCAE Grade and Treatment – Day 1 Through Entire 
Study (Safety Analysis Set) 
Table 14-7.1.5.1. 
Incidence of Grade ≥3 Post-baseline Hematology Result by 
Treatment – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-7.1.5.2. 
Incidence of Grade ≥3 Post-baseline Hematology Result by 
Treatment – Day 1 Through End of Study (Safety Analysis Set) 
Table 14-7.2.1. 
Serum Chemistry Results by Visit and Treatment – Hepatobiliary 
Parameters (Safety Analysis Set) 
Table 14-7.2.2. 
Serum Chemistry Results by Visit and Treatment – General 
Chemistry (Safety Analysis Set) 
Table 14-7.2.3. 
Serum Chemistry Results by Visit and Treatment – Renal 
Function Tests (Safety Analysis Set) 
Table 14-7.2.4.1. 
Shift Summary of Serum Chemistry Results by Maximum Post-
baseline CTCAE Grade and Treatment – Day 1 Until 1st Infusion 
of 2nd Dose (Safety Analysis Set) 
Table 14-7.2.4.2. 
Shift Summary of Serum Chemistry Results by Maximum Post-
baseline CTCAE Grade and Treatment – Day 1 Through End of 
Study (Safety Analysis Set) 
Table 14-7.2.5.1. 
Incidence of Grade ≥3 Post-baseline Chemistry Result by 
Treatment – Day 1 Until 1st Infusion of 2nd Dose (Safety 
Analysis Set) 
Table 14-7.2.5.2. 
Incidence of Grade ≥3 Post-baseline Chemistry Result by 
Treatment – Day 1 Through End of Study (Safety Analysis Set) 
14.8 
Other Safety Endpoints Data Tables 
Table 14-8.1. 
Vital Sign Results by Visit and Treatment (Safety Analysis Set) 
14.9 
Pharmacokinetics Data Table 
Table 14-9.1.1. 
Summary of ABP 798 Serum Concentrations (ug/mL)  (PK 
Concentration Analysis Set) 
Table 14-9.1.2. 
Summary of Rituximab (US) Serum Concentrations (ug/mL) 
(Through Week 24) and ABP 798 Serum Concentration (Week 26 
Through End of Study)   (PK Concentration Analysis Set) 
Table 14-9.1.3. 
Summary of Rituximab (EU) Serum Concentrations (ug/mL)  (PK 
Concentration Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 64 of 73 
Figure 14-9.4.1. 
Mean (+/-SD) Serum Concentrations Over Time by Treatment - 
Through Week 12 (PK Concentration Analysis Set) 
Figure 14-9.4.5. 
Boxplot of Trough ABP 798 Serum Concentration - Week 24 
Through End of Study (PK Concentration  Analysis Set) 
Figure 14-9.4.6.1. 
Individual ABP 798 Concentration (Linear)-Time Profiles for 
Subjects in the ABP798/ABP798 Arm - Through Week 12 (PK 
Concentration Analysis Set) 
Figure 14-9.4.7.1 
Individual ABP 798 Concentration (Linear)-Time Profiles for 
Subjects in the Rituximab (US)/ABP798 Arm - Through Week 12 
(PK Concentration Analysis Set) 
Figure 14-9.4.8.1 
Individual Rituximab (EU) Concentration (Linear) - Time Profiles 
for Subjects in the Rituximab (EU)/Rituximab (EU) Arm - 
Through Week 12 (PK Concentration Analysis Set) 
Figure 14-9.4.9 
Ratio of Geometric Means and 90% Confidence Intervals of PK 
Parameters  (PK Parameter Analysis Set) 
 
 
 
 
 
 
Table 14-9.2.9. 
Summary of ABP 798 PK Parameters  (PK Parameter Analysis 
Set) 
Table 14-9.2.10. 
Summary of Rituximab (US) PK Parameters  (PK Parameter 
Analysis Set) 
Table 14-9.2.11. 
Summary of Rituximab (EU) PK Parameters  (PK Parameter 
Analysis Set) 
Table 14-9.3.1.1. 
Summary of Statistical Assessment of PK Parameters  (PK 
Parameter Analysis Set) 
Table 14-9.3.1.2. 
Summary of Statistical Assessment of PK Parameters for Negative 
Binding ADA Status Subgroup (PK Parameter Analysis Set) 
Table 14-9.3.1.3. 
Summary of Statistical Assessment of PK Parameters for Negative 
Neutralizing ADA Status Subgroup (PK Parameter Analysis Set) 
Table 14-9.3.1.4. 
Summary of Statistical Assessment of PK Parameters without 
Covariates  (PK Parameter Analysis Set) 
Table 14-9.3.2. 
Summary of Statistical Assessment of PK Parameters  (Per 
Protocol PK Parameter Analysis Set) 
14.10 
Immunogenicity Data Table 
Table 14-10.1.1.   
Anti-drug Antibodies Summary Results by Treatment- Day 1 
Until 1st Infusion of the 2nd Dose (ADA Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 65 of 73 
Table 14-10.1.2.   
Anti-drug Antibodies Summary Results by Treatment- Entire 
Study (ADA Analysis Set) 
14.11 
Pharmacodynamics 
Table 14-11.1.1.  
Pharmacodynamics Results by Visit (Full Analysis Set) 
Table 14-11.2.   
Analysis of CD19+ Complete Depletion by Visit (Full Analysis 
Set) 
Table 14-11.3.   
Duration of CD19+ Complete Depletion (Full Analysis Set) 
16.1 
Study Information Listings 
Listing 16-1.6.1.   
Listing of Unique Manufacturing Lot Numbers 
Listing 16-1.6.2.   
Listing of Subjects Receiving Investigational Product – Subject 
Listing of Manufacturing Lot Numbers (Safety Analysis Set) 
Listing 16-1.7.   
Randomization Assignments (All Randomized Subjects) 
16.2 
Subject Data Listings 
Listing 16-2.1.1.   
Subject Listing of Disposition (All Randomized Subjects) 
Listing 16-2.1.2. 
Subject Listing of Screen Failures (All Screened Subjects) 
Listing 16-2.2.   
Important Protocol Deviations  (Full Analysis Set) 
Listing 16-2.3.   
Inclusion/Exclusion Criteria Protocol Deviations  (Full Analysis 
Set) 
Listing 16-2.4.   
Deviation/Exclusion From Analysis Populations (All Randomized 
Subjects) 
Listing 16-2.5. 
Investigational Product Administration (Safety Analysis Set) 
Listing 16-2.6.1. 
Blood Sampling Times and Serum ABP 798 and Rituximab 
Concentration Data  (PK Concentration Analysis Set) 
Listing 16-
2.6.2.1.1 
Individual PK Parameters from PK Analysis of ABP 798 (PK 
Parameter Analysis Set) 
Listing 16-
2.6.2.2.1   
Individual PK Parameters from PK Analysis of Rituximab (US) 
(PK Parameter Analysis Set) 
Listing 16-
2.6.2.3.1   
Individual PK Parameters from PK Analysis of Rituximab (EU) 
(PK Parameter Analysis Set) 
Listing 16-2.7.1.   
Subjects Who Experienced Treatment-emergent Adverse Events 
Leading to Discontinuation of Study IP/Study (Safety Analysis 
Set) 
Listing 16-2.7.2.   
Subjects with Treatment-emergent Adverse Events with Fatal 
Outcome (Safety Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 66 of 73 
Listing 16-2.7.3.   
Subjects Who Experienced Serious Treatment-emergent Adverse 
Events (Safety Analysis Set) 
Listing 16-2.8.1.   
Subjects Who Experienced a Grade ≥3 Hematology Result (Safety 
Analysis Set) 
Listing 16-2.8.2.   
Subjects Who Experienced a Grade≥3 Serum Chemistry Result 
(Safety Analysis Set) 
Listing 16-2.8.3.   
Subject Binding and Neutralizing Antibody Classification – 
Through Entire Study (ADA Analysis Set) 
Listing 16-2-8.4. 
On-study Procedure (Safety Analysis Set) 
 
 
SUPPORTIVE SAS OUTPUT APPENDICES 
Appendix 1 
Statistical Output of Table 14-4.1.1: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline at Week 24 
– Primary Analysis (Full Analysis Set) 
Appendix 2 
Statistical Output of Table 14-4.1.2: Analysis of DAS28-
CRP Change From Baseline at Week 24 – Sensitivity 
Analysis (Full Analysis Set) 
Appendix 3 
Statistical Output of Table 14-4.1.3.1: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by Visit – 
Day 1 Through Week 24 (Full Analysis Set) 
Appendix 4 
Statistical Output of Table 14-4.1.3.2: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by Visit – 
Day 1 Through Week 24 (Per Protocol  Analysis Set) 
Appendix 5 
Statistical Output of Table 14-4.1.4.1: Analysis of DAS28-
CRP Change From Baseline by Visit – Day 1 Through End 
of Study (Full Analysis Set) 
Appendix 6 
Statistical Output of Table 14-4.1.4.2: Analysis of DAS28-
CRP Change From Baseline by Visit – Day 1 Through End 
of Study (Full Analysis Set – Subgroup who received the 1st 
infusion of the 2nd dose at week 24 ) 
Appendix 7 
Statistical Output of Table 14-4.1.6: Tipping Point Analysis 
Results for Mean Difference of DAS28-CRP Change From 
Baseline at Week 24 for ABP 798 vs Rituximab with 90% 
Confidence Interval (Full Analysis Set) 
Appendix 8 
Statistical Output of Table 14-4.1.7:  Repeated Measures 
Analysis with Additional Selective Covariates for DAS28-
CRP Change From Baseline at Week 24  (Full Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 67 of 73 
Appendix 9 
Statistical Output of Table 14-4.2.1: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by Age 
Subgroup - Day 1 Through Week 24 (Full Analysis Set) 
Appendix 10 
Statistical Output of Table 14-4.2.2: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by Race 
Subgroup – Day 1 Through Week 24 (Full Analysis Set) 
Appendix 11 
Statistical Output of Table 14-4.2.3: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by Gender 
Subgroup – Day 1 Through  Week 24 (Full Analysis Set) 
Appendix 12 
Statistical Output of Table 14-4.2.5: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by Binding 
Anti-drug Antibodies Status Subgroup – Day 1 Through 
Week 24 (Full Analysis Set) 
Appendix 13 
Statistical Output of Table 14-4.2.6: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by 
Neutralizing Anti-drug Antibodies Status Subgroup – Day 1 
Through Week 24 (Full Analysis Set) 
Appendix 14 
Statistical Output of Table 14-4.2.7: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by Baseline 
Oral Corticosteroid Use Subgroup – Day 1 Through Week 
24 (Full Analysis Set) 
Appendix 15 
Statistical Output of Table 14-4.3.1: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by 
Geographic Region Subgroup – Day 1 Through Week 24 
(Full Analysis Set) 
Appendix 16 
Statistical Output of Table 14-4.3.2: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by 
Seropositivity Subgroup – Day 1 Through Week 24 (Full 
Analysis Set) 
Appendix 17 
Statistical Output of Table 14-4.3.3: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline by Prior 
Biologics Use Subgroup – Day 1 Through Week 24 (Full 
Analysis Set) 
Appendix 18 
Statistical Output of Table 14-4.5.1.1: Repeated Measures 
Analysis of ACR20 by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 
Appendix 19 
Statistical Output of Table 14-4.5.1.2: Repeated Measures 
Analysis of ACR20 by Visit – Day 1 Through Week 24 (Per 
Protocol Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 68 of 73 
Appendix 20 
Statistical Output of Table 14-4.5.2.1: Analysis of ACR20 
by Visit – Day 1 Through End of Study (Full Analysis Set) 
Appendix 21 
Statistical Output of Table 14-4.5.2.2: Analysis of ACR20 
by Visit – Day 1 Through End of Study (Full Analysis Set – 
Subgroup who received the 1st infusion of the 2nd dose at 
week 24) 
Appendix 22 
Statistical Output of Table 14-4.5.3.1: Repeated Measures 
Analysis of Hybrid ACR by Visit – Day 1 Through Week 24 
(Full Analysis Set) 
Appendix 23 
Statistical Output of Table 14-4.5.3.2: Repeated Measures 
Analysis of Hybrid ACR by Visit – Day 1 Through Week 24 
(Per Protocol Set) 
Appendix 24 
Statistical Output of Table 14-4.5.3.3: Analysis of Hybrid 
ACR by Visit – Day 1 Through End of Study (Full Analysis 
Set) 
Appendix 25 
Statistical Output of Table 14-4.5.3.4: Analysis of Hybrid 
ACR by Visit – Day 1 Through End of Study (Full Analysis 
Set – Subgroup who received the 1st infusion of the 2nd 
dose at week 24) 
Appendix 26 
Statistical Output of Table 14-4.6.1: Repeated Measures 
Analysis of ACR50 by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 
Appendix 27 
Statistical Output of Table 14-4.6.2.1: Analysis of ACR50 
by Visit – Day 1 Through End of Study (Full Analysis Set) 
Appendix 28 
Statistical Output of Table 14-4.6.2.2: Analysis of ACR50 
by Visit – Day 1 Through End of Study (Full Analysis Set – 
Subgroup who received the 1st infusion of the 2nd dose at 
week 24) 
Appendix 29 
Statistical Output of Table 14-4.7.1: Repeated Measures 
Analysis of ACR70 by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 
Appendix 30 
Statistical Output of Table 14-4.7.2.1: Analysis of ACR70 
by Visit – Day 1 Through End of Study (Full Analysis Set) 
Appendix 31 
Statistical Output of Table 14-4.7.2.2: Analysis of ACR70 
by Visit – Day 1 Through End of Study (Full Analysis Set– 
Subgroup who received the 1st infusion of the 2nd dose at 
week 24 ) 
Appendix 32 
Statistical Output of Table 14-4.10.1.1: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline at Week 24 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 69 of 73 
Comparing ABP 798 with Pooled Rituximab (Full Analysis 
Set) 
Appendix 33 
Statistical Output of Table 14-4.10.1.2: Analysis of DAS28-
CRP Change From Baseline (ANCOVA) at Week 24 
Comparing ABP 798 with Pooled Rituximab (Full Analysis 
Set) 
Appendix 34 
Statistical Output of Table 14-4.10.1.3.1: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline Comparing 
ABP 798 with Pooled Rituximab by Visit – Day 1 
ThroughWeek 24 (Full Analysis Set) 
Appendix 35 
Statistical Output of Table 14-4.10.1.3.2: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline Comparing 
ABP 798 with Pooled Rituximab by Visit – Day 1 Through 
Week 24 (Per Protocol  Analysis Set) 
Appendix 36 
Statistical Output of Table 14-4.10.1.4.1: Analysis of 
DAS28-CRP Change From Baseline (ANCOVA) 
Comparing ABP 798 with Pooled Rituximab by Visit – Day 
1 Through End of Study (Full Analysis Set) 
Appendix 37 
Statistical Output of Table 14-4.10.1.4.2: Analysis of 
DAS28-CRP Change From Baseline (ANCOVA) 
Comparing ABP 798 with Pooled Rituximab by Visit – Day 
1 Through End of Study (Per Protocol Set) 
Appendix 38 
Statistical Output of Table 14-4.10.1.6: Tipping Point 
Analysis Results for Mean Difference of DAS28-CRP 
Change From Baseline at Week 24 for ABP 798 vs Pooled 
Rituximab with 90% Confidence Interval (Full Analysis Set) 
Appendix 39 
Statistical Output of Table 14-4.10.1.7: Repeated Measures 
Analysis with Additional Selective Covariates for DAS28-
CRP Change From Baseline at Week 24 Comparing ABP 
798 with Pooled Rituximab (Full Analysis Set) 
Appendix 40 
Statistical Output of Table 14-4.10.5.1: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline Comparing 
ABP 798 with Pooled Rituximab by Age Subgroup - Day 1 
Through Week 24 (Full Analysis Set) 
Appendix 41 
Statistical Output of Table 14-4.10.5.2: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline Comparing 
ABP 798 with Pooled Rituximab by Race Subgroup – Day 1 
Through Week 24 (Full Analysis Set) 
Appendix 42 
Statistical Output of Table 14-4.10.5.3: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline Comparing 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 70 of 73 
ABP 798 with Pooled Rituximab by Gender Subgroup – Day 
1 Through  Week 24 (Full Analysis Set) 
Appendix 43 
Statistical Output of Table 14-4.10.5.5: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline Comparing 
ABP 798 with Pooled Rituximab by Binding Anti-drug 
Antibodies Status Subgroup – Day 1 Through Week 24 (Full 
Analysis Set) 
Appendix 44 
Statistical Output of Table 14-4.10.5.6: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline Comparing 
ABP 798 with Pooled Rituximab by Neutralizing Anti-drug 
Antibodies Status Subgroup – Day 1 Through Week 24 (Full 
Analysis Set) 
Appendix 45 
Statistical Output of Table 14-4.10.5.7: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline  Comparing 
ABP 798 with Pooled Rituximab by Baseline Oral 
Corticosteroid Use Subgroup – Day 1 Through Week 24 
(Full Analysis Set) 
Appendix 46 
Statistical Output of Table 14-4.10.6.1: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline  Comparing 
ABP 798 with Pooled Rituximab by Geographic Region 
Subgroup – Day 1 Through Week 24 (Full Analysis Set) 
Appendix 47 
Statistical Output of Table 14-4.10.6.2: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline Comparing 
ABP 798 with Pooled Rituximab by Seropositivity Subgroup 
– Day 1 Through Week 24 (Full Analysis Set) 
Appendix 48 
Statistical Output of Table 14-4.10.6.3: Repeated Measures 
Analysis of DAS28-CRP Change From Baseline Comparing 
ABP 798 with Pooled Rituximab by Prior Biologics Use 
Subgroup – Day 1 Through Week 24 (Full Analysis Set) 
Appendix 49 
Statistical Output of Table 14-4.11.5.1.1: Repeated Measures 
Analysis of ACR20 Comparing ABP 798 with Pooled 
Rituximab by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 
Appendix 50 
Statistical Output of Table 14-4.11.5.1.2: Repeated Measures 
Analysis of ACR20 Comparing ABP 798 with Pooled 
Rituximab by Visit – Day 1 Through Week 24 (Per Protocol 
Analysis Set) 
Appendix 51 
Statistical Output of Table 14-4.12.1.1: Repeated Measures 
Analysis of Hybrid ACR Comparing ABP 798 with Pooled 
Rituximab by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 71 of 73 
Appendix 52 
Statistical Output of Table 14-4.12.1.2: Repeated Measures 
Analysis of Hybrid ACR Comparing ABP 798 with Pooled 
Rituximab by Visit – Day 1 Through Week 24 (Per Protocol 
Analysis Set) 
Appendix 53 
Statistical Output of Table 14-4.13.1: Repeated Measures 
Analysis of ACR50 Comparing ABP 798 with Pooled 
Rituximab by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 
Appendix 54 
Statistical Output of Table 14-4.14.1: Repeated Measures 
Analysis of ACR70 Comparing ABP 798 with Pooled 
Rituximab by Visit – Day 1 Through Week 24 (Full 
Analysis Set) 
Appendix 55 
Statistical Output of Table 14-6.5.1.1: Overall Events of 
Interest Treatment-emergent Adverse Events by Treatment – 
Day 1 Until 1st Infusion of 2nd Dose (Safety Analysis Set) 
Appendix 56 
Statistical Output of Table 14-6.7.1: Exposure Adjusted 
Incidence Rate for Treatment-emergent Adverse Events by 
Preferred Term and Treatment - Day 1 Through End of 
Study (Safety Analysis Set) 
Appendix 57 
Statistical Output of Table 14-6.7.2: Exposure Adjusted 
Incidence Rate for Treatment-emergent Adverse Events of 
Interest by Treatment – Day 1 Through End of Study  
(Safety Analysis Set) 
Appendix 58 
Statistical Output of Table 14-9.3.1.1: Summary of 
Statistical Assessment of PK Parameters  (PK Parameter 
Analysis Set) 
Appendix 59 
Statistical Output of Table 14-9.3.1.2:  Summary of 
Statistical Assessment of PK Parameters for Negative 
Binding ADA Status Subgroup (PK Parameter Analysis Set) 
Appendix 60 
Statistical Output of Table 14-9.3.1.3: Summary of 
Statistical Assessment of PK Parameters for Negative 
Neutralizing ADA Status Subgroup (PK Parameter Analysis 
Set) 
Appendix 61 
Statistical Output of Table 14-9.3.1.4: Summary of 
Statistical Assessment of PK Parameters without Covariates  
(PK Parameter Analysis Set) 
Appendix 62 
Statistical Output of Table 14-9.3.2: Summary of Statistical 
Assessment of PK Parameters  (Per Protocol PK Parameter 
Analysis Set) 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 72 of 73 
Appendix 63 
Statistical Output of Table 14-11.2: Analysis of CD19+ 
Complete Depletion by Visit (Full Analysis Set) 
Appendix 64 
Statistical Output of Table 14-11.3: Duration of CD19+ 
Complete Depletion (Full Analysis Set) 
 
 
 
 
 


Amgen Proprietary - Confidential 
            
Sponsor:  Amgen Inc.                                                                   Statistical Analysis Plan           
Protocol No:  20130108                                                     10-December-2018/ Version 2.0 
 Page 73 of 73 
APPENDIX 7 SHELLS FOR POST-TEXT TABLES, FIGURES, AND 
LISTINGS 
See associated TFL shell document.