A Randomized, Double-blind, Parallel Group, Multicenter Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of SAIT101 Versus MabThera® Versus Rituxan® in Patients With Rheumatoid Arthritis (RA)
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Sponsor: Archigen Biotech Limited

Protocol Number: AGB 001 
 
 
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Clinical Study Protocol 
Protocol Title:  
A Randomized, Double-blind, Parallel Group, 
Multicenter Study to Compare the Pharmacokinetics, 
Pharmacodynamics, Safety, and Efficacy of SAIT101 
versus MabThera® versus Rituxan® in Patients with 
Rheumatoid Arthritis (RA). 
Protocol Number: 
AGB 001 
Date of Protocol: 
 
 
26APR2017 (Amendment 04) 
Product: 
SAIT101 
Clinical Trails Identifier: 
NCT02819726 
EudraCT No.: 
2014-005368-13 
Study Phase: 
I/III 
Sponsor: 
Archigen Biotech Limited 
1 Francis Crick Avenue                                       
Cambridge Biomedical Campus, Cambridge 
CB2 0AA, United Kingdom 
Sponsors Representatives: 
Kyoungsoo Ha, Head of Medical & 
Pharmacovigilance 
Leah Suh, Senior Director of Clinical Development 
 
16F Kamco Yangjae Tower 
262 Gangnam-daero, Gangnam-gu, Seoul, 
South Korea 
 
Confidentiality Statement 
This confidential information in this document is provided to you as an Investigator or 
consultant for review by you, your staff, and the applicable Institutional Review 
Board/Independent Ethics Committee.  Your acceptance of this document constitutes 
agreement that you will not disclose the information contained herein to others without 
written authorization from the Sponsor. 
 
 

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Signatures 
PROTOCOL TITLE: 
A Randomized, Double-blind, Parallel Group, 
Multicenter Study to Compare the Pharmacokinetics, 
Pharmacodynamics, Safety, and Efficacy of SAIT101 
versus MabThera® versus Rituxan® in Patients with 
Rheumatoid Arthritis (RA). 
PROTOCOL NO: 
 
AGB 001 
 
Signature of Sponsor’s authorized representative(s):  
 
 
--------------------------  
---------------------- 
--------------- 
Name  
 
 
Signature 
 
Date 
Head of Medical & Pharmacovigilance 
 
--------------------------  
---------------------- 
--------------- 
Name  
 
 
Signature 
 
Date 
Head of Clinical Development 
 
 
 

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SYNOPSIS 
Name of Sponsor/Company: 
Archigen Biotech Ltd 
 
Name of Finished Product: 
SAIT101 (proposed rituximab biosimilar) 
Name of Active Ingredient: 
Rituximab 
Title of Study:
 
 
A Randomized, Double-blind, Parallel Group, Multicenter Study to Compare the 
Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of SAIT101 versus 
MabThera® versus Rituxan® in Patients with Rheumatoid Arthritis (RA). 
Protocol 
No:
 
 
AGB001 
Phase: I/III 
Investigators: 
Approximately 70 Investigators 
Study 
centers:
 
 
Approximately 70 study centers globally 
Objectives: 
Primary Objective: 
The primary objective of the study is to compare the pharmacokinetics (PK) of SAIT101 (proposed 
rituximab biosimilar) versus rituximab licensed in the European Union (hereafter designated MabThera®, 
brand name in EU) versus rituximab licensed in the United States (hereafter designated Rituxan®, brand 
name in US) in patients with rheumatoid arthritis (RA). 
Secondary Objectives: 
The secondary objectives of the study are to compare the safety, additional PK, pharmacodynamics (PD), 
efficacy, tolerability, and immunogenicity of SAIT101 versus MabThera® versus Rituxan® in patients with 
rheumatoid arthritis (RA).   
Methodology: 
This is a multicenter, randomized, double-blind, parallel group study to compare the PK, PD, safety, 
efficacy, tolerability, and immunogenicity of SAIT101 versus MabThera® versus Rituxan® in patients with 
RA. This study consists of Part A up to 24 weeks followed by Part B up to Week 52 that also collects 
transition data in patients eligible for a second course of treatment.  
It is planned to randomize approximately 282 patients. 
The regular study duration per individual patient will be 52 weeks from the start date of the first course. 
Overview of Study Design 
Part A - First Course: Patients will be randomized in a 1:1:1 ratio to receive one course of SAIT101 
(n=94) versus Rituxan® (n=94) versus MabThera® (n=94). 
Part B - Second Course:  
Eligible patients in the SAIT101 arm will receive the second course of SAIT101 treatment at Week 24 and 
Week 26.  
Eligible patients in the MabThera® arm will receive the second course of MabThera® treatment at Week 
24 and Week 26.  
Eligible patients in the Rituxan® arm will be randomized in a 1:1 ratio to receive SAIT101 or Rituxan® 
treatment at Week 24 and Week 26. 
Study Population 
Patients with RA who have had an inadequate response to at least 3 months’ treatment (according to the 
approved treatment and dosage) or intolerance (at Investigator's discretion and/or experience of severe 
adverse event [AE] or toxicity such as infusion related reaction, hypersensitivity, anaphylaxis or severe 
toxicity) to anti-tumour necrosis factor (TNF) therapy. 
 

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Name of Sponsor/Company: 
Archigen Biotech Ltd 
 
Name of Finished Product: 
SAIT101 (proposed rituximab biosimilar) 
Name of Active Ingredient: 
Rituximab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening and Baseline 
All the Screening assessments should be performed within 30 days prior to randomization on Day 1 (Visit 
2, Baseline), except in patients who require prophylaxis of latent tuberculosis or a washout of current anti-
TNF medication or other biologic and non-biologic disease-modifying anti-rheumatic drug (DMARD) 
treatment (except methotrexate [MTX]).  For these patients the Screening Period may be extended to allow 
for the washout required, but will not exceed 60 days. In these patients all Screening assessments must be 
performed within 30 days prior to randomization with the exception of the informed consent and chest X-
ray. 
Treatment Regimen   
Each patient will receive first course which includes two intravenous (i.v.) 1,000 mg study drug infusions: 
one on Day 1 (Visit 2) and the second on Day 15 (Visit 5). Patients will receive an anti-pyretic and an 
anti-histamine, e.g., paracetamol and diphenhydramine or equivalent, 30 to 60 minutes before each 
infusion, plus 100 mg i.v. methylprednisone within 30 minutes prior to each infusion.  
Patients with an inadequate response (<50% improvement from Baseline in both the swollen and tender 
joint counts) at Week 24 (Visit 12), will be eligible to receive the second course of two 1,000 mg i.v. 
infusions (one at Week 24 and the second infusion at Week 26 [14 days later]) of study drug. 
On Day 1 and Day 15 (first and second infusions) blood PK samples and PD (CD19+ B-cell) samples will 
be collected before and 3 hours after the start of infusion and immediately (within 10 minutes) before and 
1 hour after the end of infusion, at 48 hours after the start of each infusion (Days 3 and 17). 
The PK/PD samples will also be taken at Weeks 4, 8, 12, 16, 20, and 24 to estimate elimination.  
Blood PD samples will be additionally collected simultaneously at Weeks 36 and 52. 
The main efficacy variable change from baseline in DAS28 (Disease Activity Score) will be evaluated on 
completion of 24 weeks of study assessments. 
• 
All patients will be followed up for up to 52 weeks from the start date of the first infusion. 
• 
Patients will attend the study center approximately every 12 weeks during Part B, from the start date 
of the second course of infusions. Patient who are not eligible for the second course of study treatment 
will also attend all visits until week 52. 
SAIT101 Arm (n = 94) 
MabThera® Arm 
Part A 
Part B 
SAIT101 Arm 
MabThera® Arm (n = 94) 
Rituxan® Arm (n = 94) 
Rituxan ® Arm 
Screening 
Week 24 
Week 52 
First course (2 doses) 
Second course (Possible 2 additional doses) 
End of Study 
SAIT101 Arm 

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Name of Sponsor/Company: 
Archigen Biotech Ltd 
 
Name of Finished Product: 
SAIT101 (proposed rituximab biosimilar) 
Name of Active Ingredient: 
Rituximab 
• 
To prevent missing data in important supportive efficacy and safety analysis, patients who 
discontinued study treatment, will also attend all visits until week 52. 
• 
Patients, Investigators, joint assessor and other study personnel (except pharmacist) will remain 
blinded to the treatments throughout the entire Treatment Period (52 weeks).  
• 
An interim analysis of 10 patients per arm (30 patients in total) of safety data collected up to Week 4 
and 20 patients per arm (60 patients in total) of safety data collected upto Week 12 are planned. 
• 
The study will be unblinded at Week 24 and an interim CSR will be prepared based on the 24-week 
data of all patients. The investigators and patients will remain blinded to treatment assignment 
during the post Week 24 follow-up period.  
• 
An independent Data Safety Monitoring Board (DSMB) will be assigned for this study. The DSMB 
will review available study data at pre-specified time points as outlined in the DSMB charter. 
• 
Investigators will be instructed to monitor the patients throughout the study to detect the first 
symptoms or neurological signs suggestive of progressive multifocal leukoencephalopathy (PML, i.e., 
cognitive or visual disorders, hemiparesis, confusion or behavior disorders). If the patients develop 
new neurological signs or symptoms they should be evaluated for PML. Neurological warning signs 
include: major changes in vision, unusual eye movements; loss of balance or coordination; and 
disorientation or confusion. Any patient who is suspected of developing PML will be discontinued 
from the study treatment and the AE will be followed closely, at the discretion of the Investigator. 
Number of patients: 
Approximately 282 patients will be randomized into the study, at 
approximately 70 investigative centers. 
Diagnosis and main criteria for 
inclusion: 
Male and female patients aged between 18 and 80 with severe RA 
who have had an inadequate response to at least 3 months’ treatment 
(according to the approved treatment and dosage) or intolerance (at 
Investigator's discretion and/or experience of intolerable adverse 
events or toxicity such as infusion related reaction, hypersensitivity, 
anaphylaxis or severe toxicity) to anti-TNF therapy (experience of 
severe adverse event or toxicity). 
Patients have to be on a stable weekly dose of MTX, 7.5 – 25 
mg/week at least 12 weeks, including the last 4 weeks prior to Day 
1 at a stable dose (lower doses of MTX <10 mg/week are only 
permitted if patients have documented evidence of intolerance to 
higher doses of MTX). 
Test product, and comparator, 
dose 
and 
mode 
of 
administration: 
1,000 mg (10 mg/mL) SAIT101 or Rituxan® or MabThera® for i.v. 
infusion. 
In Part A, each patient will receive one course of two 1,000 mg study 
drug infusions: one infusion on Day 1 and the second on Day 15.  
In Part B, patients with an inadequate response (<50% improvement 
from Baseline in swollen and tender joint counts at Week 24 [Visit 

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Name of Sponsor/Company: 
Archigen Biotech Ltd 
 
Name of Finished Product: 
SAIT101 (proposed rituximab biosimilar) 
Name of Active Ingredient: 
Rituximab 
12]) will be eligible for a further course of two 1,000 mg drug 
infusions: one infusion at Week 24 and the second one at Week 26: 
• Eligible patients in the SAIT101 arm will receive additional 
SAIT101 treatment at Week 24 and Week 26. 
• 
Eligible patients in the MabThera® arm will receive additional 
MabThera® treatment at Week 24 and Week 26. 
• Eligible patients in the Rituxan® arm will be randomized in a 1:1 
ratio to receive SAIT101 or Rituxan® treatment at Week 24 and 
Week 26. 
Method of administration: 
Patients will receive an anti-pyretic and an anti-histamine, e.g., 
paracetamol and diphenhydramine, or equivalent 30 to 60 minutes 
before each infusion, plus 100 mg i.v. methylprednisone at least 30 
minutes prior to each infusion. 
The Day 1 infusion rate (both first and second courses) of SAIT101 
or MabThera® or Rituxan® will be 50 mg/hour; after the first 30 
minutes, it can be escalated in 50 mg/hour increments every 30 
minutes, to a maximum of 400 mg/hour. If there has been no infusion 
related reaction on Day 1, the Day 15 infusion (both first and second 
courses) can be started at 100 mg/hour and increased by 100 mg/hour 
increments at 30 minute intervals, to a maximum of 400 mg/hour. 
Drug infusions will take place under the close supervision of an 
experienced physician, and in an environment where full 
resuscitation facilities are immediately available. 
Duration of study: 
Total study duration up to 52 weeks for each patient, including 
Baseline, Part A and Part B. 
Main criteria for evaluation: 
Pharmacokinetics 
Primary PK endpoints 
• 
Area under the concentration-time curve from time 0 (immediately predose on Day 1) to last 
quantifiable concentration (AUC0-t) 
• 
AUC from time 0 to infinity (AUC0-) 
• 
AUC from time 0 to Day 15 prior to infusion (AUC0-d15) 
• 
Maximum concentration (Cmax) after Day 15 infusion 
• 
Trough concentration (Ctrough) before the second infusion on Day 15 
Secondary PK endpoints 
• 
AUC from Week 2 to Week 24 (AUCw2-w24) 
• 
AUC from time 0 (immediately predose on Day 1) to Week 12 (AUC0-w12) 
• 
Time of maximum concentration (Tmax) post infusion on Day 15 
• 
Systemic clearance (CL) 
• 
Volume of distribution (VD) 
• 
Terminal half-life (t½) 

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Efficacy 
Main Efficacy endpoint 
• 
Change from Baseline in DAS28 at Week 24 
Other Efficacy endpoints 
• 
Change from Baseline in DAS28 at Weeks 8, 16, 36, and 52 
• 
ACR20 response rates at Weeks 8, 16, 24, 36, and 52 
• 
ACR50 response rate and ACR70 response rate at Weeks 8, 16, 24, 36, and 52 
• 
Individual components of the ACR improvement criteria on Day 1 and at Weeks 8, 16, 24, 36, and 52 
− 
Swollen and tender joint count (the 66/68 joint count system) 
− 
Patient’s assessment of pain (assessed on 1 to 100 mm Visual Analogue Scale [VAS]) 
− 
Physician’s global assessment of disease activity (assessed on 1 to 100 mm VAS) 
− 
Patient’s global assessment of disease activity (assessed on 1 to 100 mm VAS) 
− 
Patient’s assessment of disability (Health Assessment Questionnaire-Disability Index; HAQ-DI) 
− 
C-reactive protein level. 
• 
Change from Baseline in DAS28-CRP to Weeks 8, 16, 24, 36, and 52 
• 
Major clinical response (continuous ACR70 for at least 24 weeks) 
• 
Clinical remission (defined by SDAI <3.3) at Weeks 8, 16, 24, 36, and 52 
• 
Proportion of patients with European League Against Rheumatism (EULAR) response (good 
response, moderate response or no response) at Weeks 8 16, 24, 36, and 52 
Pharmacodynamics 
The CD19+ B cell count at the pre-infusion on Day 1 will be used as Baseline. The following PD 
variables will be calculated: 
• 
Depletion of CD19+ B cell count at Week 24 
• 
Time needed to B cell depletion 
• 
Duration of CD19+ B cell depletion 
• 
% CD19+ B-cell count vs. baseline at Week 24 
• 
AUC of CD19+ B-cell count change at Week 24 
• 
Change from Baseline in CD19+ B cell count during the study period 
• 
Change from Baseline in immunoglobulin (Ig) IgG, IgM, and IgA levels at Weeks 24 and 52 
• 
Change from Baseline in CRP levels at Weeks 8, 16, 24, 36, and 52 
Safety 
• 
Serious adverse events (SAEs), adverse events (AEs), adverse drug reactions (ADRs) 
• 
Vital signs 
• 
Clinical laboratory parameters including hematology, chemistry and urinalysis 
• 
Physical findings 
• 
Concomitant medication, incidence of rescue medication, where rescue medication is defined as the 
use of non-biologic DMARDs after Week 16 of the study 
• 
B cell recovery measured by a CD+19 B cell count after Week 24 
Immunogenicity (HACA and Neutralizing Antibody) 
• 
Incidence of human anti-chimeric antibodies (HACA) and neutralizing antibody at Day 1 predose and 
at Weeks 1, 2, 4, 12, 16, 24, 36, and 52 
Statistical methods:  
Pharmacokinetic Analyses 

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Name of Sponsor/Company: 
Archigen Biotech Ltd 
 
Name of Finished Product: 
SAIT101 (proposed rituximab biosimilar) 
Name of Active Ingredient: 
Rituximab 
The PK analysis will be performed on the PK Analysis Set. The PK parameters, AUC0-t, AUC0-, AUC0-
d15, Cmax after the second infusion on Day 15 and Ctrough before the second infusion on Day 15 will be 
considered the co-primary PK endpoints. All other PK endpoints will be regarded as secondary. 
The statistical analysis of the loge-transformed primary endpoints will be based on an analysis of variance 
model. The difference in least squares means between each of the three pairs (SAIT101 vs. MabThera®, 
SAIT101 vs. Rituxan®, and MabThera® vs. Rituxan® )  and the associated 90% confidence interval (CI) 
will be determined. Back transformation will provide the ratio of geometric means and 90% CI for this 
ratio. Equivalence will be concluded if the 90% CI for the ratio of geometric means of each of the three 
pairs for primary endpoints are completely contained within the acceptance interval of 0.8 to 1.25.  
Descriptive statistics (N, mean, standard deviation, coefficient of variation (CV), minimum, median, and 
maximum) will be used to summarize serum concentration data by treatment at each planned sampling 
time point. Concentrations that are below the lower limit of quantification will be assigned a value of 0 
for the purposes of computing descriptive statistics. Serum PK parameters calculated from the 
concentration-time data will also be summarized by treatment using descriptive statistics. 
Plots of the mean and individual serum rituximab concentrations over time for SAIT101 and MabThera® 
or Rituxan® will be provided following i.v. infusions.  
Pharmacodynamic Analyses 
Observed, change from Baseline, and percent change from Baseline in CD19+ B cell counts, depletion 
incidence for CD19+ B cell counts, time needed to B cell depletion, duration of CD19+ B cell depletion 
and IgG, IgM, IgA, CRP levels will be summarized using descriptive statistics.   
Efficacy Analyses 
The change from Baseline in DAS28 at Week 24 will be considered the main efficacy endpoint. 
Two-sided 95% CI for the difference between SAIT101 and MabThera® in DAS28 change from Baseline 
at Week 24 will be computed from an analysis of covariance using Baseline DAS28 as covariate and 
treatment as model factors. Equivalence will be concluded if the 95% CI for the mean difference for main 
endpoint is completely contained with the equivalence margin of -0.6 to 0.6. Both of the per protocol (PP) 
set and full analysis set (FAS) will be considered as the efficacy analysis population and no missing data 
will be imputed for the efficacy analyses in FAS. 
Continuous variables will be summarized using N, mean, standard deviation, minimum, median, and 
maximum. Categorical variables will be summarized using frequency counts and percentages. 
Safety Analyses 
All reported terms for AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). No statistical testing will be performed for AEs. For all AE and SAE tables, patients will be 
counted at most once for each Preferred Term (PT) and each System Organ Class (SOC). Adverse events 
will be summarized by the number and percentage of patients experiencing events by SOC, PT and 
severity. 
Changes in vital signs and clinical laboratory measurements will be summarized descriptively by visit. 
Other safety variables will be summarized and listed. 
Immunogenicity Analyses 
Incidence of HACA and neutralizing antibody and summary of counts of antibodies per patient at prior 
first dose on Day 1 and at Week 1, 2, 4, 12, 16, 24, 36 and 52 will be summarized overall and by treatment 
group.  
Interim Analysis 
Interim Analyses of 10 patients per group (30 patients in total) of safety data collected up to Week 4 and 
20 patients per group (60 patients in total) of safety data collected up to Week 12 are planned. 

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Name of Sponsor/Company: 
Archigen Biotech Ltd 
 
Name of Finished Product: 
SAIT101 (proposed rituximab biosimilar) 
Name of Active Ingredient: 
Rituximab 
The study will be unblinded at Week 24 and an interim CSR will be prepared based on the 24-week data 
of all patients. The investigators and patients will remain blinded to treatment assignment during the post 
Week 24 follow-up period.  
Sample Size 
A percentage co-efficient of variation (CV%) ranging from 26.3 to 37.3% for the five co-primary 
parameters is assumed for this study based on a recent study in RA patients treated with rituximab.  
When the evaluable sample size in each group is 84, a three group design will have 81% power to reject 
both the null hypothesis that the ratio of test to standard geometrics means is below 0.800, and the null 
hypothesis that the ratio of test to standard geometrics means is above 1.250 (i.e., that the test and standard 
are not equivalent), in favor of the alternative hypothesis, that the means of the two groups are equivalent, 
assuming that the expected ratio of means is 1.000, the CV% for the standard is 0.330, that data will be 
analyzed in the log scale using analysis of variance (ANOVA) and that each one sided test is made at the 
5% level. Each of the 15 hypotheses tests (five co-primary endpoints × three pairwise comparisons) are 
powered at 98% to 99.0% to yield 81% study-wide power. 
Approximately 282 patients (94 patients per group) will be randomized in order to yield a minimum of 
84 patients per group to account for a presumed 10% withdrawal.  
This 94 patients in SAIT101 group and MabThera® group will provide 96% probability of declaring the 
equivalence in FAS with each one sided test at the 2.5% level, accounting for a presumed 1.0 standard 
deviation of DAS28 from the REFLEX study, and the equivalence margin of -0.6 to 0.6 chosen as the half 
of a clinical meaningful improvement of 1.2 in DAS28. Considering 18% withdraw from the REFLEX 
study, approximately 77 patients per group will provide approximately 91% probability of declaring the 
equivalence in the PP set. 

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TABLE OF CONTENTS 
Signatures ....................................................................................................... 2 
SYNOPSIS ...................................................................................................... 3 
LIST OF IN-TEXT TABLES ..................................................................... 15 
LIST OF APPENDICES ............................................................................. 16 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .......... 17 
1 
INTRODUCTION .............................................................................. 21 
1.1 
Background .......................................................................................................21 
1.2 
Overview of SAIT101 .......................................................................................21 
1.3 
Comparator drug: Rituximab.............................................................................23 
1.3.1 
Clinical Pharmacokinetics of Rituximab ........................................................24 
1.3.2 
Clinical Data of Rituximab .............................................................................24 
2 
STUDY RATIONALE AND OBJECTIVES ................................... 25 
2.1 
Study Rationale .................................................................................................25 
2.2 
Study Objectives................................................................................................25 
2.2.1 
Primary Objective ...........................................................................................25 
2.2.2 
Secondary Objectives .....................................................................................25 
2.3 
Study Endpoints ................................................................................................25 
2.3.1 
Pharmacokinetics ............................................................................................25 
2.3.2 
Efficacy ...........................................................................................................26 
2.3.3 
Pharmacodynamics .........................................................................................27 
2.3.4 
Immunogenicity ..............................................................................................27 
2.3.5 
Safety ..............................................................................................................27 
3 
STUDY DESIGN ................................................................................ 29 
3.1 
Summary of Study Design ................................................................................29 
3.2 
Treatments .........................................................................................................31 
3.2.1 
Test Product and Comparator, Dose and Mode of Administration ................31 
3.2.2 
Study Drug Administration (Part A)...............................................................34 
3.2.3 
Study Drug Administration (Part B) ...............................................................35 
3.2.4 
Dosage Modification ......................................................................................35 
3.2.5 
Allowed Concomitant Medication ..................................................................36 

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3.2.6 
Rescue Therapy ..............................................................................................37 
3.2.7 
Management of Hepatitis Reactivation and Other Infections During 
Rituximab Therapy .........................................................................................37 
3.3 
Study Population ...............................................................................................38 
3.4 
Eligibility Criteria..............................................................................................38 
3.4.1 
Informed Consent ...........................................................................................38 
3.4.2 
Inclusion Criteria ............................................................................................38 
3.4.3 
Exclusion Criteria ...........................................................................................40 
3.4.4 
Patient Withdrawal .........................................................................................42 
3.5 
Measures to Minimize/Avoid Bias ....................................................................42 
3.5.1 
Blinding ..........................................................................................................42 
3.5.2 
Randomization ................................................................................................43 
3.5.3 
Unblinding Procedure .....................................................................................43 
3.5.4 
Unblinding for Interim Analysis .....................................................................44 
3.6 
Study Procedures ...............................................................................................44 
3.6.1 
Schedule of Assessments ................................................................................49 
3.6.1.1 
Screening Period .........................................................................................49 
3.6.1.2 
Study Drug Administration Part A ..............................................................51 
3.6.1.3 
Study Drug Administration Part B ..............................................................56 
3.6.2 
Efficacy Assessments .....................................................................................59 
3.6.2.1 
ACR and DAS28 Score ...............................................................................59 
3.6.2.1.1 
Joint Assessments ....................................................................................59 
3.6.2.1.2 
Patient’s Global Assessment of Disease Activity ...................................60 
3.6.2.1.3 
Physician’s Global Assessment of Disease Activity ...............................60 
3.6.2.1.4 
Patient’s Assessment of Disability ..........................................................60 
3.6.2.2 
Systemic Inflammation: CRP Level and ESR ............................................61 
3.6.3 
Pharmacokinetic and Pharmacodynamic Assessments ..................................61 
3.6.3.1 
Pharmacokinetic Assessments ....................................................................61 
3.6.3.2 
Pharmacodynamic Assessments .................................................................61 
3.6.4 
Immunogenicity Assessments ........................................................................62 
3.6.5 
Safety Assessments .........................................................................................62 
3.6.5.1 
Adverse Events............................................................................................62 
3.6.5.2 
Clinical Laboratory Assessments ................................................................62 

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3.6.5.3 
Physical Examination ..................................................................................63 
3.6.5.4 
Vital Signs ...................................................................................................63 
3.6.5.5 
Resting 12-lead ECG...................................................................................64 
3.6.5.6 
Pregnancy Test ............................................................................................64 
3.6.5.7 
Chest X-ray .................................................................................................64 
3.6.6 
End of Study ...................................................................................................64 
3.6.7 
Data Safety Monitoring Board ........................................................................65 
3.7 
Stopping Rules, Discontinuation Criteria, and Procedures ...............................65 
3.7.1 
Entire Study or Treatment Arms .....................................................................65 
3.7.2 
Individual Study Center ..................................................................................65 
3.7.3 
Individual Patient ............................................................................................65 
3.8 
Screen Failures ..................................................................................................67 
3.9 
Re-screening ......................................................................................................67 
3.10 
Definition of Completed Patients ......................................................................68 
3.11 
Definition of Patients Lost to Follow-up ...........................................................68 
3.12 
Treatment Compliance ......................................................................................68 
3.13 
Protocol Deviations ...........................................................................................69 
4 
RESTRICTIONS ................................................................................ 70 
4.1 
Measures Regarding Patients Being Treated or Scheduled for Treatment 
at another Department or Hospital ....................................................................70 
4.2 
Prohibited Medications/Therapies .....................................................................70 
4.3 
Concomitant Medications with Restrictions .....................................................71 
5 
REPORTING OF ADVERSE EVENTS .......................................... 74 
5.1 
Adverse Event (AE) ..........................................................................................74 
5.2 
Serious Adverse Events (SAE)..........................................................................74 
5.3 
Adverse Drug Reactions ....................................................................................75 
5.4 
Adverse Event of Special Interest (AESI) .........................................................75 
5.4.1 
Progressive Multifocal Leukoencephalopathy ...............................................75 
5.4.2 
Hepatitis Reactivation .....................................................................................76 
5.4.3 
Serious Infections ...........................................................................................76 
5.4.4 
Mucocutaneous Reactions ..............................................................................76 
5.4.5 
Infusion Reactions ..........................................................................................76 
5.4.6 
Anaphylaxis ....................................................................................................77 

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5.5 
Pregnancy ..........................................................................................................78 
5.6 
Overdose ............................................................................................................78 
5.7 
Changes in Clinical Laboratory Assessment Results ........................................79 
5.8 
Recording of Adverse Events ............................................................................79 
5.9 
Eliciting and Reporting Adverse Events ...........................................................81 
5.10 
Follow-up of Adverse Events ............................................................................81 
5.11 
Reporting of Serious Adverse Events to Regulatory Authorities and 
Investigators ......................................................................................................81 
6 
STATISTICS ....................................................................................... 82 
6.1 
Sample Size .......................................................................................................82 
6.2 
Statistical Methods ............................................................................................82 
6.2.1 
Analysis Sets ...................................................................................................83 
6.2.1.1 
Pharmacokinetic Analysis Set .....................................................................83 
6.2.1.2 
Safety Analysis Set .....................................................................................83 
6.2.1.3 
Full Analysis Set .........................................................................................83 
6.2.1.4 
Per Protocol Set ...........................................................................................83 
6.2.1.5 
Pharmacodynamic Analysis Set ..................................................................84 
6.2.2 
Patient Disposition ..........................................................................................84 
6.2.3 
Demographic and Baseline Characteristics Analysis .....................................84 
6.3 
Pharmacokinetic Analysis .................................................................................84 
6.4 
Efficacy Analysis ..............................................................................................85 
6.5 
Pharmacodynamic Analysis ..............................................................................86 
6.6 
Safety Analysis ..................................................................................................86 
6.6.1 
Adverse Events ...............................................................................................86 
6.6.2 
Clinical Laboratory Tests ...............................................................................87 
6.6.3 
Concomitant Medication ................................................................................88 
6.6.4 
Vital Signs, ECG Findings, and Physical Examination ..................................88 
6.6.5 
B Cell Recovery ..............................................................................................88 
6.7 
Immunogenicity Analysis..................................................................................89 
6.8 
Other Analysis ...................................................................................................89 
6.9 
Interim Analysis ................................................................................................89 
6.10 
Safety Review....................................................................................................89 
6.11 
Handling of Missing Values and Outliers .........................................................89 

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6.12 
Procedure for Reporting Deviations ..................................................................90 
7 
MANAGEMENT OF THE INVESTIGATIONAL 
MEDICINAL PRODUCT .................................................................. 91 
7.1 
Investigational Medicinal Product Identification ..............................................91 
7.2 
Packaging and Labeling ....................................................................................91 
7.3 
Storage ...............................................................................................................91 
7.4 
Preparation, Storage after Preparation and Administration ...............................92 
7.5 
Accountability ...................................................................................................92 
7.6 
Returns and Destruction ....................................................................................93 
8 
DATA HANDLING AND RECORD KEEPING ............................ 94 
8.1 
Source Documents .............................................................................................94 
8.2 
Data Collection ..................................................................................................94 
8.3 
File Management at the Study Center ...............................................................96 
8.4 
Records Retention at the Study Center..............................................................96 
9 
QUALITY CONTROL AND QUALITY ASSURANCE ............... 98 
9.1 
Monitoring .........................................................................................................98 
9.2 
Auditing .............................................................................................................98 
9.3 
Inspection ..........................................................................................................98 
10 
ETHICS AND RESPONSIBILITY .................................................. 99 
11 
CONFIDENTIALITY ...................................................................... 100 
12 
PUBLICATION POLICY ............................................................... 101 
13 
AMENDMENT POLICY ................................................................ 103 
14 
REFERENCES ................................................................................. 104 
15 
APPENDICES ................................................................................... 106 
 
 
 

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LIST OF IN-TEXT TABLES 
Table 1 
Recommended Infusion Rates .......................................................32 
Table 2 
Schedule of Assessments ...............................................................45 
Table 3 
Clinical Laboratory Assessments ...................................................63 
Table 4 
Prior Treatments Required to be Discontinued Prior to 
Baseline ..........................................................................................70 
Table 5 
List of Medications Permitted During the Study ...........................72 
Table 6 
Example of Washout Periods .........................................................73 
Table 7 
Clinical Criteria for Diagnosing Anaphylaxis ...............................77 
 
LIST OF IN-TEXT FIGURES 
Figure 1 
Study Design ..................................................................................30 
 

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LIST OF APPENDICES 
Appendix 1 
 
Signature of Investigator 
Appendix 2 
 
Investigator Responsibilities 
Appendix 3 
 
American College of Rheumatology 1987 Revised Criteria for the  
 
 
 
Classification of Acute Arthritis of Rheumatoid Arthritis 
Appendix 4 
Functional Class:  Classification of Global Functional Status in 
Rheumatoid Arthritis (as per ACR 1991 Revised Criteria) 
Appendix 5 
 
DAS28 and EULAR Response Criteria 
 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ACR 
American College of Rheumatology 
ACR20 
American College of Rheumatology 20% response criteria 
ACR50 
American College of Rheumatology 50% response criteria 
ACR70 
American College of Rheumatology 70% response criteria 
ADCC 
Antibody dependent cell-mediated cytotoxicity 
ADR 
Adverse drug reaction 
AE 
Adverse event 
AESI 
Adverse event of special interest 
AIDS 
Acquired immunodeficiency syndrome 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase 
ANC 
Absolute neutrophil count 
AST 
Aspartate aminotransferase 
ANCOVA 
Analysis of Covariance 
ANOVA 
Analysis of variance 
AUC(0-t) 
Area under the concentration-time curve from time 0 to the last quantifiable 
concentration 
AUC(0-d15) 
Area under the concentration-time curve from time 0 to Day 15 
AUC(0-∞) 
Area under the concentration-time curve from time 0 extrapolated to infinite 
time 
AUC(w2-w24) 
Area under the concentration-time curve from Week 2 to Week 24 
AUC(0-w12) 
Area under the concentration-time curve from time 0 to Week 12 
B cell 
B lymphocyte 
CCP 
Cyclic citrullinated peptide 
CD20 
Activated-glycosylated phosphoprotein expressed on the surface of all B cells 
CDC 
Complement-dependent cytotoxicity 
CHO 
Chinese hamster ovary 
CHOP 
Cyclophosphamide, doxorubicin, vincristine, prednisone 
CI  
Confidence interval 
CL 
Systemic clearance 
CLL 
Chronic lymphoid leukemia 
Cmax 
The maximum concentration after the Day 15 infusion 
Ctrough 
The lowest (trough) concentration before the Day 15 infusion 
COPD 
Chronic obstructive pulmonary disease 
CRO 
Contract research organization 
CRP 
C-reactive protein 

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CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTMS 
Clinical trial management system  
CV 
Coefficient of variation 
DAS 
Disease Activity Score  
DAS28 
Disease Activity Score based on a 28 joint count 
DMARD 
Disease-modifying anti-rheumatic drug 
DNA 
Deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic case report form 
ECG 
Electrocardiogram 
EDTA 
Ethylenediaminetetraacetic Acid 
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 
GFR 
Glomerular Filtration Rate 
GGT 
Gamma-glutamyl transpeptidase 
GLS 
Geometric Least Square 
HACA 
Human anti-chimeric antibodies 
HAQ-DI 
Health Assessment Questionnaire-Disability Index 
HbcAb 
Hepatitis B core antibody 
HbsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B Virus 
hCG 
Human Chorionic Gonadotropin 
HCV 
Hepatitis C Virus 
HIV 
Human immunodeficiency virus 
ICF 
Informed consent form 
ICH 
International Council for Harmonization 
ID 
Identification 
IEC 
Independent Ethics Committee 
Ig 
Immunoglobulin  
IL 
Interleukin 
IM 
Intramuscular 
i.v. 
Intravenous 

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IRB 
Institutional Review Board 
IUD 
Intrauterine device 
IXRS 
Interactive voice / web response system 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTX 
Methotrexate 
NCI 
National Cancer Institute 
NHL 
Non-Hodgkin’s lymphoma 
NSAIDs 
Non-steroidal anti-inflammatory drugs 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic(s) 
PE 
Polyethylene 
PEF 
Peak expiratory flow 
PK 
Pharmacokinetic(s) 
PML 
Progressive multifocal leukoencephalopathy 
PP 
Per Protocol 
PT 
Preferred Term 
PVC 
Polyvinyl chloride 
RA 
Rheumatoid arthritis 
RF 
Rheumatoid factor 
RNA 
Ribonucleic Acid  
SAE 
Serious adverse event 
SAF 
Safety analysis set 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SDAI 
Simple Disease Activity Index 
SOC 
System Organ Class 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TB 
Tuberculosis 
t½ 
Terminal half-life  
Tmax 
Time of maximum concentration  
TNF 
Tumour necrosis factor 
ULN 
Upper limit of normal 
US 
United States 
VAS 
Visual analogue scale 
VD 
Volume of distribution  

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WBC 
White blood cell 
WHO-DD 
World Health Organization-Drug Dictionary 
 

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1 
INTRODUCTION 
1.1 
Background 
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder characterized by 
inflammation in the synovium of joints, which is associated with progressive joint 
destruction, and depending on the severity, may be accompanied by systemic 
manifestations including lung disease, rheumatoid nodules, and effects on the 
cardiovascular system. If left untreated, RA may lead to severe functional disabilities, and 
therefore a considerable reduction in quality of life for the patient.1,2 The prevalence of RA 
is relatively constant in many populations, at 0.5 to 1%, but can vary with factors such as 
gender, race and smoking status.3 
B lymphocytes (B cells) are thought to contribute considerably to the pathogenesis of RA. 
B cells contribute to the formation of immune complexes and complement activation in 
affected joints as they are the primary source of rheumatoid factors (RFs) and anti-cyclic 
citrullinated peptide (anti-CCP) antibodies. They are highly efficient antigen-presenting 
cells and therefore contribute to the auto-immune response through downstream activation 
of T cells via co-stimulatory molecules. B cells respond to, and produce, chemokines and 
cytokines that promote lymphocyte infiltration into joints, formation of ectopic lymphoid 
structures, angiogenesis, and synovial hyperplasia that characterize the pathology observed 
in the rheumatoid joint.4  
Traditionally, RA has been treated with a combination of anti-inflammatory agents and 
disease-modifying anti-rheumatic drugs (DMARDs). While therapeutic options have 
improved with the introduction of biologic DMARDs, neutralizing cytokines such as tumor 
necrosis factor (TNF) and interleukin-1 (IL-1) which have been shown to both control signs 
and symptoms of joint inflammation and retard progression of joint destruction, targeting 
other mediators and pathways might improve the overall response rate. Although TNF- 
antagonists and other biologic therapies represent an important advance in the management 
of patients with RA, there remains a significant unmet medical need for effective novel 
therapies given the significant non-responder rates and well-documented systemic 
toxicities of the traditional treatments. 
1.2 
Overview of SAIT101 
SAIT101 is a proposed biosimilar product rituximab being developed by Archigen Biotech. 
Similar to rituximab, SAIT101 has 1,328 amino acids with an approximate molecular weight of 
145 kDa with a similar glycan profile to rituximab, and is a genetically engineered chimeric 

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human/mouse glycosylated monoclonal antibody specific to the human antigen CD20 
expressed on lymphocytes. SAIT101 consists of human IgG1 heavy and kappa light chain 
constant regions, and murine heavy and light chain variable regions, which is similar to 
rituximab.4,5,6,7 It is produced by Chinese hamster ovary (CHO) cell suspension culture and 
purified by various affinity and ion exchange chromatography steps that include specific viral 
inactivation and removal procedures. 
SAIT101 has been demonstrated to be similar to MabThera® (rituximab licensed in the 
European Union) and Rituxan® (rituximab licensed in the United States) in the extensive 
similarity studies using state-of-art techniques. Quality and in vitro characterization studies 
have been performed to date.  
An in vitro study confirmed that SAIT101 has similar pharmacological actions to rituximab, 
resulting from its binding to CD20-positive antigen. In vivo efficacy studies using murine 
xenograft models confirmed similar profiles of tumor suppression activity for SAIT101, 
MabThera® and Rituxan®. 
Pharmacokinetics (PK) and pharmacodynamics (PD) studies in cynomolgus monkeys have 
also shown similarity of PK/PD profiles between SAIT101 and rituximab. Furthermore, 
the single- and repeat-dose toxicity studies confirmed that SAIT101 did not show any 
toxicity at dose levels up to 10 times higher than the clinical dose (~10 mg/kg). The single-
dose toxicity, repeat-dose toxicity, toxicokinetics and immunogenicity profiles of SAIT101 
were similar to MabThera® and Rituxan®. 
Clinical Data of SAIT101 
The first clinical study with SAIT101 began in May 2011. S101-NKR-001 was a 
first-in-human Phase I study conducted in 14 centers in Korea aimed to compare and assess 
PK and PD profiles, and preliminary efficacy and safety of SAIT101 compared to 
MabThera®, after intravenous (i.v.) infusion of MabThera® or SAIT101. As of 
26 September 2011, a total of 24 diffuse large B cell lymphoma patients had been 
randomized to receive either SAIT101 (proposed rituximab biosimilar) or MabThera® 
(rituximab, Roche) in combination with the chemotherapy regimen, CHOP 
(cyclophosphamide, doxorubicin, vincristine, and prednisone). 
Kim et al reported that the ratio of geometric least square (GLS) mean (90% confidence 
interval, CI) of SAIT101 versus MabThera® were 0.92 (0.78 to 1.09) for AUClast and 0.93 
(0.78 to 1.13) for Cmax. The LS means change from baseline of B-cell (%) in SATI101 and 
MabThera® group were -7.7% and -8.0% respectively and the difference between two 
groups was 0.3% (90%CI, -0.9 to 1.4). The safety and efficacy profile of SAIT101 were 
not significantly different from MabThera®.9  

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1.3 
Comparator drug: Rituximab 
Rituximab is a genetically engineered recombinant chimeric human/murine antibody 
directed against the CD20 antigen. Following binding of CD20, rituximab triggers a 
cytotoxic immune response against CD20-positive cells. 
Rituximab was initially developed by IDEC Pharmaceuticals. Based on its safety and 
effectiveness in clinical studies, rituximab was approved under the trade name Rituxan® 
by the US Food and Drug Administration (FDA) in 1997 to treat B cell non-Hodgkin’s 
lymphomas (NHL) resistant to other chemotherapy regimens. Rituximab, in combination 
with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, 
is now a standard therapy in the initial treatment of diffuse large B cell lymphoma and 
many other B cell lymphomas. It has been approved as a therapeutic agent for patients with 
NHL, chronic lymphocytic leukemia (CLL) and RA.10, 11 
Rituxan® was co-developed and marketed in the US (under the brand name Rituxan®) by 
Biogen Idec and Genentech (now a part of Roche). It is marketed outside the US by Roche 
under the brand name MabThera®. 
Antigen CD20 is a hydrophobic transmembrane protein with a molecular weight of 
approximately 35 kDa located on pre-B and mature B lymphocytes. The antigen is 
expressed on more than 90% of B cell NHL, but is not found on hematopoietic system 
cells, pro-B cells, normal plasma cells, or other normal tissues. CD20 regulates early steps 
in the activation process for cell cycle initiation and differentiation, and possibly functions 
as a calcium ion channel. CD20 is not shed from the cell surface and does not internalize 
upon antibody binding. Free CD20 antigen is not found in the circulation. 
B cells are believed to play a role in the pathogenesis of RA and associated chronic 
synovitis. In this setting, B cells may be acting at multiple sites in the 
autoimmune/inflammatory process, including through production of RF and other 
autoantibodies, antigen presentation, T-cell activation and/or pro-inflammatory cytokine 
production. 
The Fab domain of rituximab binds to the CD20 antigen on B lymphocytes, and the Fc 
domain recruits immune effector functions to mediate B cell lysis. Possible mechanisms of 
cell lysis include complement-dependent cytotoxicity (CDC) and antibody-dependent cell-
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1.3.1 
Clinical Pharmacokinetics of Rituximab 
In one of the Phase IIa double blind studies conducted in RA patients to evaluate the PK 
of rituximab, it was found that the mean areas under the plasma concentration–time curves 
for rituximab were similar across treatment groups (rituximab alone, rituximab in 
combination with cyclophosphamide and rituximab in combination with methotrexate 
[MTX]). The mean terminal half-life (t1/2) of 19 to 22 days was observed in rituximab after 
the second infusion. Systemic clearance of rituximab was slow at 242, 226, and 221 mL/d 
in all 3 treatment groups. The volume of distribution (VD) of rituximab at steady state was 
low at 4.28 to 4.74 L and similar to normal plasma volume in all treatment groups. These 
data indicate that the PK characteristics of rituximab are not discernibly altered when it is 
administered in combination with either cyclophosphamide or MTX. This observation is 
supportive of the contention that rituximab does not require dose adjustments when 
administered with either cyclophosphamide or MTX.12 
1.3.2 
Clinical Data of Rituximab 
In one of the recent (2006) RA studies conducted in 520 patients to determine the efficacy 
and safety of rituximab along with MTX in patients with active RA who had an inadequate 
response to anti-tumor necrosis factor (anti-TNF) therapies, it was found that patients who 
received two 1,000 mg infusions of rituximab the Disease Activity Score (DAS) improved 
-1.9 when compared with MTX alone (-0.4%; p <0.0001 ) and met the American College 
of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at 
Week 24, 51% when compared with placebo (18%; p <0.0001).13, 14 
In another long-term safety study (2010), it was observed that rituximab was well tolerated 
over time and multiple courses. Overall, the findings indicated that there was no evidence 
of an increased safety risk or increased reporting rates of any types of AEs with prolonged 
exposure to rituximab.15 
 
 

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2 
STUDY RATIONALE AND OBJECTIVES 
2.1 
Study Rationale 
SAIT101, as a proposed biosimilar of rituximab in pharmaceutical form, strength and 
administration route, is expected to play an important role in the treatment of RA. The 
substitution of rituximab by SAIT101 is expected to provide similar efficacy, PK, PD, 
safety, tolerability, and immunogenicity in patients with RA. The dose selected for this 
study is based on the clinically effective dose of rituximab. 
This study is to evaluate similarity in terms of PK, PD, safety, efficacy, tolerability, and 
immunogenicity between SAIT101 and rituximab and also to provide a benefit and risk 
profile of SAIT101. 
This study will be conducted in compliance with the protocol, the International Council for 
Harmonization (ICH) guidelines, Good Clinical Practice (GCP) and with all applicable and 
current regulatory requirements. 
2.2 
Study Objectives 
2.2.1 
Primary Objective 
The primary objective of the study is to compare the PK of SAIT101 versus rituximab 
licensed in the European Union (hereafter designated MabThera®, brand name in EU) 
versus rituximab licensed in the United States (hereafter designated Rituxan®, brand name 
in US) in patients with RA. 
2.2.2 
Secondary Objectives 
The secondary objectives of the study are to compare the safety, additional PK, PD, 
efficacy, tolerability, and immunogenicity of SAIT101 versus MabThera® versus Rituxan® 
in patients with RA. 
2.3 
Study Endpoints 
2.3.1 
Pharmacokinetics 
Primary PK Endpoints 
• Area under the concentration-time curve from time 0 (immediately predose on Day 1) 
to last quantifiable concentration (AUC0-t) 
• AUC from time 0 (immediately predose on Day 1) to infinity (AUC0-) 

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• AUC from time 0 (immediately predose on Day 1) to Day 15 prior to infusion 
(AUC0-d15)  
• Maximum concentration (Cmax) after the second infusion on Day 15 
• Trough concentration (Ctrough) before the second infusion on Day 15 
Secondary PK Endpoints 
• AUC from Week 2 to Week 24 (AUCw2-w24) 
• AUC from time 0 (immediately predose on Day 1) to Week 12 (AUC0-w12) 
• Time of maximum concentration (Tmax) post infusion on Day 15 
• Systemic clearance (CL) 
• Volume of distribution (VD) 
• Terminal half-life (t½) 
2.3.2 
Efficacy 
Main Efficacy Endpoints 
• Change from Baseline in DAS28 at Week 24 
Other Efficacy Endpoints 
• Change from Baseline in DAS28 at Weeks 8, 16, 36, and 52 
• ACR20 response rates at Weeks 8, 16, 24, 36, and 52 
• ACR50 response rates and ACR70 response rates at Weeks 8, 16, 24, 36, and 52 
• Individual components of the ACR improvement criteria on Day 1 and at Weeks 8, 16, 
24, 36, and 52 
− Swollen and tender joint count (the 66/68 joint count system) 
− Patient’s assessment of pain (assessed on 1 to 100 mm Visual Analogue Scale 
[VAS]) 
− Physician’s global assessment of disease activity (assessed on 1 to 100 mm VAS) 

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− Patient’s global assessment of disease activity (assessed on 1 to 100 mm VAS) 
− Patient’s assessment of disability (Health Assessment Questionnaire-Disability 
Index [HAQ-DI]) 
− CRP level 
• Change from Baseline DAS28-CRP at Weeks 8, 16, 24, 36, and 52 
• Major clinical response (continuous ACR70 for at least 24 weeks) 
• Clinical remission (defined by SDAI < 3.3) at Weeks 8, 16, 24, 36, and 52 
• Proportion of patients with European League Against Rheumatism (EULAR) response 
(good response, moderate response or no response) at Weeks 8, 16, 24, 36, and 52 
2.3.3 
Pharmacodynamics 
• Depletion of CD19+ B cell count at Week 24 
• Time needed to B cell depletion 
• Duration of CD19+ B cell depletion 
• % CD19+ B-cell count vs. baseline at Week 24  
• AUC of CD19+ B-cell count change at Week 24 
• Change from Baseline in CD19+ B cell count during the study period  
• Change from Baseline in IgG, IgM, and IgA levels at Weeks 24 and 52 
• Change from Baseline in CRP levels at Weeks 8, 16, 24, 36, and 52 
2.3.4 
Immunogenicity 
• Incidence of HACA and neutralizing antibody at Day 1 predose and at Week 1, 2, 4, 
12, 16, 24, 36, and 52 
2.3.5 
Safety 
• SAEs, AEs, ADRs 
• Vital signs 

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• Clinical laboratory parameters including hematology, chemistry and urinalysis 
• Physical findings 
• Concomitant medication, incidence of rescue medication, where rescue medication is 
defined as the use of non biologic DMARDs after Week 16 of the study 
• B cell recovery measured by a CD19+ B cell count after Week 24 
 
 
 
 

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3 
STUDY DESIGN 
3.1 
Summary of Study Design 
This is a multicenter, randomized, double-blind, parallel group study to compare the PK, 
PD, safety, efficacy, tolerability, and immunogenicity of SAIT101 versus MabThera® 
versus Rituxan® in patients with RA. This study will take place globally across 
approximately 70 study centers in order to randomize approximately 282 patients. The 
study consists of Part A from baseline for PK and efficacy analysis, followed by Part B 
from Week 24 to 52 for safety follow-up that also collects transition data.  
Patients with RA who have had an inadequate response to at least 3 months’ treatment 
(according to the approved treatment and dosage) or intolerance (at Investigator's 
discretion and/or experience of severe adverse event [AE] or toxicity such as infusion 
related reaction, hypersensitivity, anaphylaxis or severe toxicity) to anti-TNF therapy. All 
the Screening assessments should be performed within 30 days prior to randomization on 
Day 1 (Visit 2, Baseline), except in patients who require prophylaxis of latent tuberculosis 
or a washout of current anti-TNF medication or other biologic and non-biologic DMARD 
treatment except MTX. For these patients the Screening period may be extended to allow 
for the washout required, but will not exceed 60 days. In these patients all Screening 
assessments must be performed within 30 days prior to randomization with the exception 
of the informed consent and chest X-ray (see Section 3.2.5). 
In Part A, patients will be randomized in a 1:1:1 ratio to receive one course of SAIT101 
(n=94) versus Rituxan® (n=94) versus MabThera® (n=94).  
At Week 24, patients will be evaluated for a second course of the infusion.   
In Part B, eligible patients in the SAIT101 arm will receive the second course of SAIT101 
treatment at Weeks 24 and 26. Eligible patients in the MabThera® arm will receive the 
second course of MabThera® treatment at Week 24 and 26. Eligible patients in the Rituxan® 
arm will be randomized in a 1:1 ratio to receive SAIT101 or Rituxan® treatment at Weeks 
24 and 26. Patients will be followed up for safety till Week 52. 
For each course of infusion, patients will receive two infusions of 1,000 mg (10 mg/mL) 
SAIT101 or Rituxan® or MabThera® for i.v. infusion for the treatment. 
Patients will continue to take their usual prescribed concomitant medications as allowed 
by the protocol. It is mandatory that doses of all RA medications (MTX, steroids and non-
steroidal anti-inflammatory drugs [NSAID]) taken during the first 24-week period must 

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remain stable (see Section 3.2.5). Patients will also receive an anti-pyretic and an 
anti-histamine, e.g., paracetamol and diphenhydramine or equivalent, 30 to 60 minutes 
before each infusion, plus 100 mg i.v. methylprednisone (or its equivalent) at least 30 
minutes prior to each infusion. 
The study design for individual patients is schematically detailed in Figure 1. 
At each visit, blood PK and PD samples should be taken at the same time of day as the start 
of the first infusion, within a window of ± 10 minutes of the determined time points of 
Days 1, 3, 8, 15, 17 and ± 3 hours at all other time points. All patients will be followed up 
for safety up to 52 weeks from the start date of the first infusion. 
 
 
 
 
 
 
 
 
 
 
Figure 1 
Study Design 
Standard arthritis assessments and safety assessments will be performed. A disease activity 
score based on a 28 joint count (DAS28) will be calculated by the study personnel at 
regularly scheduled visits. At least one experienced, independent joint assessor, blinded to 
other study assessments as well as the dosing regimen, will be identified at each study 
center to perform the swollen and tender joint counts. 
A provision is made for patients to initiate “rescue therapy” with the use of one 
non-biologic DMARD after Week 16 of the study (see Section 3.2.6).  
Patients with rheumatoid arthritis (<50% improvement from Baseline in both the swollen 
and tender joint counts) who have been followed up during Part A will be provided with 
SAIT101 Arm (n = 94) 
MabThera® Arm 
Part A 
Part B 
SAIT101 Arm 
MabThera® Arm (n = 94) 
Rituxan® Arm (n = 94) 
SAIT101 Arm 
Screening 
Week 24 
Week 52 
First course (2 doses) 
Second course (Possible 2 additional doses) 
Clinical Study Report 
Rituxan® Arm 

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additional treatment of study drug with two 1,000 mg i.v. infusions (at Week 24 and Week 
26 [14 days later]). Patients will attend the study center approximately every 12 weeks 
during Part B. Patient who are not eligible for the second course of study treatment will 
also attend all visits until week 52. 
Patients may return for unscheduled visits if their medical condition requires immediate 
attention.  
To prevent missing data in important supportive efficacy and safety analysis, patients who 
discontinued study treatment, will also attend all visits until week 52.  
The primary safety concerns associated with rituximab are progressive multifocal 
leukoencephalopathy (PML), anaphylactic reactions, hepatitis reactivation, and severe 
mucocutaneous reactions.  Patients will be monitored carefully for these during the study.  
Any patient who is suspected of developing PML, anaphylactic reactions, hepatitis 
reactivation, and severe mucocutaneous reactions will be discontinued from the study 
treatment and the AE will be followed closely, at the discretion of the Investigator. 
3.2 
Treatments 
3.2.1 
Test Product and Comparator, Dose and Mode of Administration 
SAIT101 is a sterile, clear to opalescent and colorless or a pale yellow, preservative-free 
solution for i.v. infusion. The formulation of SAIT101 is similar to MabThera® or 
Rituxan®.  
Each patient will be randomized on Day 1 to receive one of three possible treatments (study 
drug): 
• SAIT101: 1,000 mg (10 mg/mL)-Test product; 
• Rituxan®: 1,000 mg (10 mg/mL)-Comparator; 
• MabThera®: 1,000 mg (10 mg/mL)-Comparator. 
All patients received premedication with 100 mg i.v. methylprednisolone (or its 
equivalent), 
an 
antipyretic 
and 
an 
antihistaminic 
(e.g. 
acetaminophen 
and 
diphenhydramine) per the accepted infusion protocols for rituximab prior to study drug 
infusions to decrease incidence rate and severity of acute infusion-related reactions. 

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Since hypotension may occur during rituximab infusion, consideration should be given to 
withholding anti-hypertensive medications 12 hours prior to the infusion. 
The Day 1 infusion rate (both week 0 and week 24) of SAIT101 or MabThera® or Rituxan® 
will start at 50 mg/hour; after the first 30 minutes, it can be escalated in 50 mg/hour 
increments every 30 minutes, to a maximum of 400 mg/hour. If there has been no infusion 
related reaction on Day 1, the Day 15 infusion (both first and second courses) can be 
infused at 100 mg/hour and increased by 100 mg/hour increments at 30 minute intervals, 
to a maximum of 400 mg/hour. 
The recommended infusion rates are presented in Table 1. 
Table 1 
Recommended Infusion Rates 
Day 1 
infusion 
Total dose  
(mg) 
Time 
(minutes)*** 
Day 15 infusion 
Total dose 
(mg) 
Time 
(minutes)*** 
50 mg/h 
25 
0-30 
100 mg/h 
50 
0-30 
100 mg/h 
50 
31-60 
200 mg/h 
100 
31-60 
150 mg/h 
75 
61-90 
300 mg/h 
150 
61-90 
200 mg/h 
100 
91-120 
400 mg/h 
700 
91-196** 
250 mg/h 
125 
121-150 
- 
- 
- 
300 mg/h 
150 
151-180 
- 
- 
- 
350 mg/h 
175 
181-210 
- 
- 
- 
400 mg/h 
200 
211-240 
- 
- 
- 
400 mg/h 
100 
241-255* 
 
 
 
* Approximately at 255 minutes (4 hours 15 minutes) to complete the 1,000 mg total dose. 
** Approximately at 196 minutes (3 hours 16 minutes) to complete the 1,000 mg total dose. 
***Allowed window for infusion rate time: For each time point: ± 5 minutes (e.g. when start 50 mg/h for 
first course: 25~35 minutes can be allowed). 
In the event that a patient experiences an infusion-related reaction or an adverse drug 
reaction (ADR), the infusion rate should be reduced to half the rate (e.g., from 100 mg/hour 
to 50 mg/hour). Once the infusion-related reaction or ADR has resolved, the Investigator 
should wait an additional 30 minutes while delivering the infusion at the reduced rate. If 
tolerated, the rate may be increased to the next closest rate on the patient’s infusion 
schedule. Please refer to the following examples: 
(Example 1) An infusion-related reaction or an ADR at a rate of 50 mg/h → change rate 
to 25 mg/h → reaction resolved → additional 30 minutes at a rate of 25 mg/h → change 
back to 50 mg/h. 

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(Example 2) An infusion-related reaction or an ADR at a rate of 300 mg/h → change rate 
to 150 mg/h → reaction resolved → additional 30 minutes at a rate of 150 mg/h → change 
back to 200 mg/h. 
Drug infusions will take place under the close supervision of an experienced physician, 
and in an environment where full resuscitation facilities are immediately available. 
Although the study drug may be administered on an outpatient basis, patients may be 
hospitalized for observation at the discretion of the Investigator, and such instances of 
planned hospitalization will NOT be recorded as a serious adverse event (SAE).   
Any drugs that are used to manage hypersensitivity reactions or ADRs, including but not 
limited to epinephrine, antihistamine, and corticosteroid, should be immediately available 
in case of emergency. 
Attention should be given to the development of anaphylaxis during infusion of the study 
drug. When an anaphylactic reaction is suspected during infusion of the study drug: 
• Discontinue the study drug. 
• Apply a tourniquet close to the infusion site in order to slow systemic absorption of 
the study drug.  Do not block artery flow. 
• Perform appropriate airway management. 
• If required, administer antihistamine, epinephrine, or other drugs. 
• Closely monitor the patient and document the observations. 
Patients who experience a moderate to severe infusion-related reaction (fever, chills or 
hypotension), should have their infusion interrupted immediately and should receive 
aggressive symptomatic treatment, such as glucocorticoids, epinephrine, bronchodilators 
or oxygen, as per local practice. Depending on the severity of the infusion reaction and the 
required interventions, patients should either have their infusion temporarily interrupted or 
be discontinued from the study treatment. The infusion should not be restarted before all 
the symptoms have disappeared, and then it should be restarted at half the rate. If the patient 
tolerates the reduced rate for 30 minutes then the infusion rate may be increased to the next 
closest rate on the patient’s infusion schedule. If the subject does not tolerate the reduced 
rate for at least 30 minutes or, if the same severe (NCI-CTCAE Grade 3) infusion reaction 
occurs for a second time, the patient can be discontinued from the study treatment. 

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At the end of each infusion, the i.v. line is recommended to remain in place for at least 
1 hour to allow infusion of i.v. drugs if necessary. If no AE occurs during this time, the i.v. 
line may be removed. 
3.2.2 
Study Drug Administration (Part A) 
First Infusion (Day 1 of First Course) 
The first infusion rate of SAIT101 or MabThera® or Rituxan® will be 50 mg/hour; after the 
first 30 minutes, it can be escalated in 50 mg/hour increments every 30 minutes, to a 
maximum of 400 mg/hour (see Table 1). 
Second Infusion (Day 15 of First Course) 
Patients who experienced infusion-related reactions to the first infusion should receive 
study drug as per the initial infusion schedule, with the rate of infusion not exceeding half 
that associated with the prior reactions. If this reduced rate is tolerated for 30 minutes, then 
the infusion rate may be increased to the next closest rate following the infusion schedule. 
Patients who miss the allocated day (Day 15 ± 1 day) for the second infusion (the first 
infusion will be administered following randomization on Day 1) will be contacted and 
another visit arranged as soon as practically possible in order to administer study drug. 
Such cases will be considered protocol deviations (see Section 3.13). 
If a patient experiences a new infection or other AE between the Day 1 and Day 15 
infusions of any treatment, the Day 15 infusion should be delayed until the infection or AE 
has completely resolved and the Investigator considers it safe to resume treatment. A 
maximum delay of 15 days from the scheduled date of the second infusion is permitted. 
Patients who have a delay of >15 days in receiving the second infusion due to an AE or 
otherwise will be discontinued from the study treatment.  

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3.2.3 
Study Drug Administration (Part B) 
Patients with active rheumatoid arthritis (<50% improvement from Baseline in both the 
swollen and tender joint counts) who have been followed up during Part A will be provided 
with continued (or additional) treatment of rituximab.  
Before subsequent dose, absolute neutrophil count must be ≥1.5 × 109/L and platelet counts 
must be ≥75 × 109/L. If the Absolute Neutrophil Count (ANC) value and platelet count are 
marginally lower, re-testing at an unscheduled visit may be performed at the discretion of 
the Investigator within the 4-week period between Week 20 and Week 24. In case Visit 11 
is missed, all safety evaluations including ANC value and platelet count must be completed 
as an unscheduled visit for patient to be eligible for second course of infusion. 
Eligible patients in the SAIT101 arm will receive additional SAIT101 treatment at Week 24 
and Week 26. Eligible patients in the MabThera® arm will receive additional MabThera® 
treatment at Week 24 and Week 26. Eligible patients in the Rituxan® arm will be 
randomized in a 1:1 ratio to receive SAIT101 or Rituxan® treatment at Week 24 and Week 
26. 
Patients who develop an infusion reaction during the second course of treatment should be 
managed as described in Section 3.2.1. 
Patient who are not eligible for the second course of study drug will also attend all visits 
after Week 24. 
3.2.4 
Dosage Modification 
Dose modification of rituximab is not permitted during this study. In the event of an 
infusion-related reaction, the rate of infusion may be adjusted (see Section 3.2.1). Patients 
who experience a life-threatening event, as considered by the Investigator, during an 
infusion of study drug should have their infusion stopped and no further infusions should 
be administered. 

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3.2.5 
Allowed Concomitant Medication 
It is mandatory that all doses of all RA medications (MTX, steroids and NSAIDs) taken 
during the first 24-week period (Part A) must remain stable. 
Patients will continue to take their usual prescribed concomitant medications as allowed 
by the protocol, including MTX (7.5 to 25 mg/week) and folic or folinic acid, from their 
usual source, according to local standards and availability.  
All patients should also continue to receive if there is any background oral corticosteroids 
(≤10 mg/day prednisone or equivalent) or NSAIDs. During the 4 weeks (for oral 
corticosteroids) or 3 weeks (for NSAIDs) prior to Day 1, the doses must remain stable.   
If clinically required for safety reasons, modifications to doses of MTX, corticosteroids 
and NSAIDs will be allowed. The Investigator must use the procedures outlined below in 
making modifications to these medications and document all changes and the reason for 
the changes should be documented in the patient’s electronic case report form (eCRF). 
Methotrexate: Dose of MTX should remain stable throughout the study. Reductions for 
MTX dose or a change of route of administration may be performed after visit at Week 24 
for safety reasons only.  
Lower doses of MTX (<10 mg/week) are only permitted if patients have a documented 
evidence of intolerance to higher doses of MTX. 
If dose reduction is a result of intolerance, such intolerance must be recorded as an AE and 
the dose modification recorded in the eCRF. 
Oral corticosteroids: If receiving current treatment with oral corticosteroids (other than 
intra-articular or parenteral corticosteroids), the dose must not exceed 10 mg/day 
prednisone or equivalent. The dose should remain stable from 4 weeks prior to 
randomization throughout the study. From Visit 12 at Week 24, reductions in these 
treatments will be allowed only for safety reasons. Increases in corticosteroids for treatment 
of RA are not allowed over the study period and should be avoided. To treat non-RA 
conditions, increased doses of oral corticosteroids, up to 40 mg of prednisone daily (or 

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equivalent), for 2 weeks or less will be permitted. The corticosteroid dose should be tapered 
down to the previous level as rapidly as medically possible.  
NSAIDs: Patients may be treated with NSAIDs, up to the maximum recommended dose, 
(including cyclooxygenase-2 inhibitors) throughout the study. The choice and doses of 
NSAIDs used to treat patients are at the discretion of the Investigator. Patients on NSAIDs 
at Screening should continue at a stable dose from 3 weeks prior to randomization 
throughout the study. The dose and type of NSAID may be changed after Visit 12 at Week 
24 of the study. Aspirin may be taken to reduce cardiovascular risk, but should not exceed 
350 mg/day. NSAIDs or other analgesics for treatment of conditions other than RA may 
be used for short periods not exceeding 7 days. 
3.2.6 
Rescue Therapy 
From Week 16, patients who have less than a 20% improvement in both tender and swollen 
joint counts compared to Baseline (<ACR20) may receive “rescue” treatment with one 
non-biologic DMARD. The patient will be discontinued from the study treatment and the 
choice of DMARD is at the discretion of the Investigator, but could be hydroxychloroquine 
or sulfasalazine. Patients receiving “rescue” medication attend all visits until week 52. 
The following medications are not permitted for use as “rescue” treatment: azathioprine, 
mycophenolate mofetil, cyclophosphamide, cyclosporine or any biologic agent. Any 
patient requiring medication mentioned above, should be discontinued from study 
treatment but will attend all visits until week 52. 
3.2.7 
Management of Hepatitis Reactivation and Other Infections 
During Rituximab Therapy 
Patients with HBV DNA >20 IU/ml are ineligible as per exclusion criteria. Patients who 
show evidence of prior hepatitis B infection may participate in the study following 
consultation with a hepatitis expert regarding monitoring and use of HBV antiviral therapy, 
and provided that they agree to undergo monthly PCR HBV DNA testing during treatment 
and to receive treatment as indicated. During the study, a HBV re-test will be performed 
monthly including Day 1, Weeks 4, 8, 12, 16, 20, 24, 36, 52, or unscheduled visit if 
required. 

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Patients will receive HBV antiviral prophylaxis therapy and be monitored as recommended 
by hepatitis experts. HBV reactivation has been reported up to 24 months following 
completion of rituximab therapy. If a patient develops reactivation of HBV or any other 
significant infections while on rituximab, the Investigator should immediately discontinue 
study drug, consult with hepatitis experts, and institute appropriate treatment. For details 
and management of other infections, refer to the current marketed rituximab prescribing 
information.6, 7 
3.3 
Study Population 
Patients with RA who have had an inadequate response (at least 3 months’ treatment 
according to the approved treatment and dosage of each TNF inhibitor) or intolerance (at 
Investigator’s discretion and/or experience of intolerable AE such as infusion related 
reaction, hypersensitivity, anaphylaxis or severe toxicity) to one or more anti-TNF 
therapies.  
3.4 
Eligibility Criteria 
3.4.1 
Informed Consent 
Patients must have the ability and willingness to provide written informed consent, prior 
to any study-specific procedures, and to comply with the requirements of the protocol. 
3.4.2 
Inclusion Criteria 
Patients are required to meet the following inclusion criteria:  
1 
Male or female outpatient, between 18 and 80 years of age at Screening. 
2. 
Severe RA defined as: 
• 
Diagnosis of RA according to the revised (1987) ACR criteria for the classification of RA for at 
least 3 months prior to screening visit (see Appendix 3). 
• 
And ≥6 swollen joints and ≥6 tender/painful joints (from the 66/68 joint count system). 
• 
And C-reactive protein (CRP) ≥1.0 mg/dL or an ESR ≥28 mm/hour at Screening.  
• 
And positive RF (≥20 units/mL) or anti-CCP antibodies (≥10 units/mL) at Screening. 
3. 
Patients with severe RA who have had an inadequate response to at least 3 months’ treatment (according 
to the approved treatment and dosage) or intolerance (at Investigator's discretion and/or experience of 
intolerable AE or toxicity such as infusion related reaction, hypersensitivity, anaphylaxis or severe 
toxicity) to anti-TNF therapy (experience of severe AE or toxicity). 

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4. 
Current treatment for RA on an outpatient basis: 
• 
Receiving MTX 7.5 - 25mg/week (oral or parenteral) for at least 12 weeks, including the last 4 
weeks prior to Day 1 at a stable dose, via the same route of administration, dose, and formulation. 
Patients receiving a lower dose of MTX (<10 mg/week), stable for 4 weeks prior to Day 1, should 
be doing so as a result of a documented evidence of intolerance to higher doses of MTX. 
• 
Leflunomide must be withdrawn at least 12 weeks prior to Day 1 or a minimum of 4 weeks prior to 
Day 1 if after 11 days of standard cholestyramine washout. 
• 
All DMARDs different from MTX and leflunomide must be withdrawn at least 4 ~ 8 weeks as 
described in Table 4 prior to Day 1. 
• 
If receiving current treatment with oral corticosteroids, the dose must not exceed 10 mg/day 
prednisone or equivalent. During the 4 weeks prior to Day 1 the dose must be stable.  
• 
The most recent IM/intra-articular steroid injection should be 6 weeks prior to Day 1.  
• 
If receiving current treatment with NSAIDs at the time of Screening, the patient must remain on a 
stable dose for at least 3 weeks prior to Day 1.  
• 
Patients are willing to receive oral folic or folinic acid or equivalent during the entire study 
(mandatory co-medication for MTX treatment), according to local standards and availability. 
5 
Men and women of childbearing potential must use highly effective methods of contraception during the 
course of the treatment period and for at least 12 months after the last infusion of study drug.  A man or 
women is of childbearing potential if, in the opinion of the investigator, he or she is biologically capable 
of having children and is sexually active.  Examples of highly effective contraception include:  
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition 
of ovulation 1: 
– oral 
– intravaginal 
– transdermal 
• progestogen-only hormonal contraception associated with inhibition of ovulation 1: 
– oral 
– injectable 
– implantable 2 
• intrauterine device (IUD) 2 
• intrauterine hormone-releasing system (IUS) 2 
• bilateral tubal occlusion 2 
• vasectomised partner 2,3 
• sexual abstinence 4 
1 Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the 
efficacy of the contraception method. 
2 Contraception methods that in the context of this guidance are considered to have low user 
dependency. 
3 Vasectomised partner is a highly effective birth control method provided that partner is the sole 
sexual partner of the study participant and that the vasectomised partner has received medical 
assessment of the surgical success. 
4 In the context of this guidance sexual abstinence is considered a highly effective method only if 
defined as refraining from heterosexual intercourse during the entire period of risk associated with the 

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study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration 
of the clinical trial and the preferred and usual lifestyle of the subject. 
6 
Female patients of childbearing potential must have a negative serum pregnancy test at Screening 
(Visit 1) and a negative urine pregnancy test at each applicable visit thereafter. Females will be 
considered to be of non-childbearing potential if they fulfill one of the following criteria at Screening: 
• Postmenopausal defined as amenorrheic for at least 12 months following cessation of all exogenous 
treatments 
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or 
bilateral salpingectomy but not tubal ligation 
3.4.3 
Exclusion Criteria 
Patients will be excluded if they meet any of the following exclusion criteria: 
1 
Females who are pregnant, breastfeeding, or planning a pregnancy during the Treatment Period of and 
12 months after the last infusion of study drug. 
2 
Class IV as per the Classification of Global Functional Status in Rheumatoid Arthritis (as per ACR 1991 
Revised Criteria) (see Appendix 4) or wheelchair/bed-bound. 
3 
History of or current inflammatory joint disease other than RA (including but not limited to gout, reactive 
arthritis, psoriatic arthritis, seronegative spondyloarthropathy or Lyme disease).  
4 
History of or current systemic autoimmune disorder (including but not limited to systemic lupus 
erythematosus, inflammatory bowel disease, pulmonary fibrosis, Felty syndrome, scleroderma, 
inflammatory myopathy, fibromyalgia, juvenile idiopathic arthritis, mixed connective tissue disease, 
vasculitis or other overlap syndrome), with the exception of the secondary Sjögren's syndrome. 
5 
Primary or secondary immunodeficiency (history of, or currently active), including known history of 
human immunodeficiency virus (HIV) infection or positive test at screening. 
6 
History of opportunistic infection.  
7 
History of deep space/tissue infection (e.g., fasciitis, abscess, osteomyelitis) and infected prosthetic joint. 
8 
Active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection 
requiring hospitalization or treatment with i.v. anti-infective agents within 4 weeks prior to Screening or 
oral anti-infective agents within 2 weeks prior to Screening or use of antibiotic therapy three or more 
times in the last six months prior to Screening 
9 
Positive serological test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or 
hepatitis C serology. 
• 
Patients with a negative HBsAg and positive HBcAb must have a hepatitis B virus (HBV) 
deoxyribonucleic acid (DNA) level <20 IU/mL (or 112 copies/mL) by polymerase chain reaction 
(PCR). These HBV patients must be willing to undergo monthly PCR HBV DNA testing during 
treatment and may participate following consultation with a hepatitis expert regarding monitoring 
and use of HBV antiviral therapy, and provided they agree to receive treatment as indicated. An 
HBV re-test will be performed monthly including Day 1, Weeks 4, 8, 12, 16, 20, 24, 36, 52, and 
unscheduled visit if required. 
• 
Patients with a positive test because of HBV vaccine may be included (i.e., anti-HBs+ and anti 
HBc–). 
• 
Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV 
ribonucleic acid (RNA). 
10 
Confirmed current active tuberculosis (TB).  
• 
Patients with latent TB as determined by positive QuantiFERON-TB test may be enrolled if such 
patients have written confirmation from health care provider (e.g., Pulmonologist or Infection 

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Specialist) of adequate prophylaxis before or within the screening period and no evidence of 
tuberculosis on a chest X-ray performed within 3 months from Day 1. 
• 
Screening period can be extended to 60 days for prophylaxis of latent TB. 
• 
QuantiFERON-TB test can be re-tested, if inconclusive. 
11 
Any significant cardiac disease (e.g., coronary artery disease with unstable angina, coronary heart failure 
New York Heart Association Class III and IV, familial long QT syndrome, uncontrolled cardiac disease).  
12 
History of moderate to severe chronic obstructive pulmonary disease (COPD) and/or history of severe 
COPD exacerbation(s) within the last 12 months of Screening. 
13 
Vaccination with live or attenuated vaccines within 6 weeks prior to first dose of study drug or planned 
administration during study participation or within 4 weeks following last dose of study drug. Treatment 
with IV Gamma Globulin or the Prosorba® Column within 6 months prior to Day 1. 
14 
History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of 
hypersensitivity to any component of the study drug including known hypersensitivity or allergy to a 
murine product. 
15 
Hypogammaglobulinemia at screening (IgG <600 mg/dL). 
16 
Patients with hemoglobin <8.5 g/dL, ANC <1,500 cells/µL or platelet count <75,000 cells/µL at 
Screening. If a patient has findings marginally below this limit, re-testing is allowed, at the Investigator’s 
discretion, within the 30 day period between Visit 1 and Visit 2. 
17 
• 
Creatinine clearance < 50 mL/min (Cockroft-Gault formula) 
• 
Liver function:  Total bilirubin >2.0 mg/dL (>34 µmol/L) except for patients with Gilbert’s 
Syndrome or hemolysis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >3 
× upper limit of normal (ULN). Patients with total bilirubin >2.0 mg/dL possibly due to Gilbert’s 
Syndrome should have a direct bilirubin checked. If the direct bilirubin is normal and medical history 
is suggestive/positive for Gilbert’s Syndrome, the patient successfully meets the criteria.  
The AST and ALT may be repeated once within the Screening period if the initial result exceeds this 
limit, and the lesser value accepted if it meets this criterion. 
18 
History of cancer within the last 5 years prior to Screening, treated with anti-cancer chemotherapy, 
including solid tumors and hematologic malignancies and carcinoma in situ (except basal cell and 
squamous cell carcinomas of the skin or carcinoma in situ of the cervix uteri that have been excised and 
cured). 
19 
Major surgical procedure within 4 weeks prior to or planned within 24 weeks of Day 1, with the exception 
of surgical procedures for dental prosthesis. 
20 
Previous treatment with a B cell modulating or B cell depletion therapy, such as, but not limited to 
rituximab, belimumab, atacicept, tabalumab, ocrelizumab, ofatumumab, obinutuzumab, epratuzumab and 
other experimental treatments. 
21 
Injectable corticosteroids within 6 weeks prior to Day 1. 
22 
Participation in a previous clinical study within 4 weeks of Screening or having received treatment with 
a drug that has not received regulatory approval for any indication within a minimum of 5 half-lives prior 
to Day 1. 
23 
Patients who, based on the Investigator’s judgment, have a clinically significant or unstable medical or 
surgical condition that may preclude safe and complete study participation. Conditions may also include 
cardiovascular, vascular, pulmonary, hepatic, renal, endocrine or neurological conditions as determined 
by medical history, physical examination, laboratory tests or electrocardiogram (ECG). 
24 
Patients who, in the judgment of the Investigator, are likely to be non-compliant or uncooperative during 
the study. 
25 
History of substance abuse (alcohol or drug). 

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26 
History of demyelinating disorders (such as multiple sclerosis or Guillain-Barré syndrome).  
27 
Patients at risk of PML: 
• 
Patients with immune deficiency such as transplant patients on immunosuppressive medications 
• 
Patients receiving certain kinds of chemotherapy 
• 
Patients receiving natalizumab (Tysabri®) for multiple sclerosis 
• 
Patients with psoriasis on longer term efalizumab (Raptiva®) or patients with acquired 
immunodeficiency syndrome (AIDS) 
 
3.4.4 
Patient Withdrawal 
All patients are free to withdraw from participation in the study at any time, for any reason, 
specified or unspecified, and without prejudice to further treatment. If the withdrawn 
patients meet the PK data set, then those patients can be included in the PK analysis.  
Patients will be withdrawn from the study in the following circumstances: 
• The patient withdraws consent to contribute additional outcome information or is lost 
to follow-up despite reasonable efforts to make contact with the patient  
Adverse events will be followed up as detailed in Section 5.10. Investigators are 
encouraged to discuss the patient’s case with the Sponsor physician or representative to 
agree upon appropriate action. 
3.5 
Measures to Minimize/Avoid Bias 
The treatment groups will be blinded to minimize any bias that could be introduced by 
knowledge of the treatment by either Investigator or patient, which is especially important 
given that many of the efficacy and safety measures are subjective. Potential bias will be 
further minimized by identifying at least one experienced, blinded, joint assessor at each 
study center who will be independent of the rest of the study team. This person will perform 
the swollen and tender joint counts without access to any other study-related outcomes. 
The parallel group design takes into account the progressive nature of RA. 
3.5.1 
Blinding 
This will be a double-blind study. Patients, Investigators, the joint assessor and other site 
personnel will remain blinded throughout the entire Study Period except for the study 
pharmacist or designee. The study will be unblinded at week 24 to facilitate the primary 
analysis although investigators and patients remain blinded to treatment assignment during 
the post week 24 follow-up period. 

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The interactive voice / web response system (IXRS) will be used to manage randomization 
to treatment groups in a blinded manner. This includes maintaining the blind for those 
patients who are eligible to receive a further course of study drug. 
To ensure blinding of the treatments, the SAIT101, Rituxan® and MabThera® should only 
be managed by the pharmacist or designee from the time of reception till the time the 
prepared infusion is dispensed to the blind study team. 
The SAIT101, Rituxan® and MabThera® solutions will be provided in a blinded manner to 
the blinded Investigator’s team. Patients will receive the i.v. drug infusions in the same 
manner regardless of the treatment group they are randomized to. All details will be 
provided in the Pharmacy Manual. 
3.5.2 
Randomization 
Patients will be assigned a unique patient number at Screening. The patient number will be 
used to register the patient using the IXRS and the patient will then be randomized (in a 
1:1:1 ratio) to either SAIT101, Rituxan® or MabThera®.  
Eligible patients in the SAIT101 arm will receive the second course of SAIT101 treatment 
at Weeks 24 and 26. Eligible patients in the MabThera® arm will receive the second course 
of MabThera® treatment at Weeks 24 and 26. Eligible patients in the Rituxan® arm will be 
randomized in a 1:1 ratio to receive SAIT101 or Rituxan® treatment at Weeks 24 and 26. 
This randomization will occur according to a computer-generated randomization scheme. 
This will randomize patients at study level. If patients are withdrawn the patient number 
will not be re-used.  
At the time of study drug infusion the Investigator or designee will contact the IXRS and 
a Medication ID will be provided. These codes will indicate which vials should be allocated 
to the patient. Further details on using the IXRS system are presented in the IXRS manual. 
3.5.3 
Unblinding Procedure 
The IXRS will be used to break the blind and details on how to do this are provided in the 
IXRS manual. Investigators are strongly discouraged from requesting that the blind be 
broken for an individual patient, unless there is a patient safety issue that requires 
unblinding and would change patient management. If the blind is broken, it may be broken 
only for the patient in question and the patient must be discontinued from the study 
treatment. If time permits, before requesting that the blind be broken for an individual 
patient, the Investigator should discuss the situation with the Sponsor or designee via phone 
or e-mail. The Sponsor or designee must be notified immediately if a patient and/or 
Investigator is unblinded during the course of the study along with the reason for breaking 

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the blind. Pertinent information regarding the circumstances of unblinding of a patient’s 
treatment code must be documented in the patient’s source documents and IXRS. This 
includes who performed the unblinding, the patient(s) affected, the reason for the 
unblinding, the date of the unblinding and the relevant study drug information. The 
Investigator should ensure that the appropriate measurements are taken at the study center 
to maintain the blinding of the study. 
3.5.4 
Unblinding for Interim Analysis 
An interim analysis of 10 patients per arm (30 patients in total) of safety data collected up 
to Week 4 and 20 patients per arm (60 patients in total) of safety data collected up to 
Week 12 are planned. Safety data will be handled by unblinded study team in CRO for 
interim analysis (see Section 6.9). The study will be unblinded at Week 24 and an interim 
CSR will be prepared based on the 24-week data of all patients. The investigators and 
patients will remain blinded to treatment assignment during the post Week 24 follow-up 
period.  
For review purposes, the DSMB members will be unblinded to treatment assignment (see 
Section 3.6.7). 
3.6 
Study Procedures 
A schedule of assessments is provided in Table 2. 

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Table 2 
Schedule of Assessments 
 
Screeninga 
Part A 
Part B 
EOSk 
Un- 
Scheduled
k 
Week 
Baselineb 
0 1 
2 
2 
4 
8 
12 
16 
20 
24j 
26 
36 
52 
Visit 
1 
2  
3 4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
Day (± window in days) 
-30 (within    
-60)a 
1 
3 8 
15 
±1 
17 
±1 
29 
±3 
57 
±3 
85 
±3 
113 
±3 
141 
±3 
169 
±3 
183 
±3 
253 
±7 
365 
±7 
Assessments 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/surgical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationd 
X 
X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Neurological examinatione  
X 
X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsf 
X 
X 
 
 
X 
 
 
 
 
 
 
X 
X 
 
X 
X 
Chest X-rayg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xs 
Resting 12-ECGh 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
AEs/Serious AEs/ADRs 
 
X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior/concomitant medication 
X 
X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine or serum pregnancy testi 
X 
X 
 
 
X 
 
 
 
 
 
 
X 
X 
 
X 
X 
Study drug 
 
Contact IXRS 
X 
X 
 
 
X 
 
 
 
 
 
 
Xl 
Xl 
 
X 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Drug infusionm 
 
X 
 
 
X 
 
 
 
 
 
 
X 
X 
 
 
 

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Screeninga 
Part A 
Part B 
EOSk 
Un- 
Scheduled
k 
Week 
Baselineb 
0 1 
2 
2 
4 
8 
12 
16 
20 
24j 
26 
36 
52 
Visit 
1 
2  
3 4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
Day (± window in days) 
-30 (within    
-60)a 
1 
3 8 
15 
±1 
17 
±1 
29 
±3 
57 
±3 
85 
±3 
113 
±3 
141 
±3 
169 
±3 
183 
±3 
253 
±7 
365 
±7 
Efficacy assessments 
 
HAQ-DI, including Patient’s 
pain VASn 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
 
Patient Global Assessment 
VASn 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
 
Physician Global Assessment 
VAS 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
 
Swollen and tender joint countso 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
 
Laboratory assessments 
 
Virology screeningp  
X 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
QuantiFERON®-TB Goldq  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
IgG, IgM, IgA  
Xr 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
 
CRP / ESR 
X 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
 
RF  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Clinical chemistry, hematology 
and urinalysis 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
PK samplings 
 
X 
X X X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
PD (CD19+ B-cell) samplings 
 
X 
X X X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Immunogenicity samplingt 
 
X 
 
X X 
 
X 
 
X 
X 
 
X 
 
X 
X 
 

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ADR: Adverse drug reaction; AE: Adverse event; CRP: C-reactive protein; DNA: Deoxyribonucleic acid; ECG: Electrocardiogram; EOS: End-of-Study; ESR: 
Erythrocyte sedimentation rate; HACA: Human anti-chimeric antibody; HAQ-DI: Health Assessment Questionnaire-Disability Index; HBV: Hepatitis B virus; 
HbcAb: Hepatitis B core antibody; HBsAg: Hepatitis B surface antigen; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; Ig: Immunoglobulin; IXRS: 
Interactive voice/web response system; PCR: Polymerase chain reaction; PK: Pharmacokinetic; PD: Pharmacodynamic; PML: Progressive multifocal 
leukoencephalopathy; RF: Rheumatoid factor; SAE: Serious adverse event; TB: Tuberculosis; TNF: Tumor necrosis factor; VAS: Visual analogue scale. 
 
a 
The total time period for Screening is not to exceed 30 days. However, in case a washout of currently used anti-TNF medication or DMARDs is required or 
prophylaxis of latent TB is required, the Screening may be extended to allow for this washout, but is not to exceed 60 days. (Refer to Table 6 for examples of 
washout periods.) 
b 
Prior to Visit 2, Baseline, patients will be discontinued from their current anti-TNF medication or other biologic and non-biologic DMARDs, except MTX. 
c 
Exclusion criteria to be re-checked at admission to the study center. 
d 
The physical examination should include assessment of general appearance, skin, head, neck, throat, lymph nodes, thyroid, abdomen, and cardiovascular, 
neurological, musculoskeletal/extremities, and respiratory systems. Body weight will be measured. Height will be measured at Screening only. 
e 
Neurological examination for signs and symptoms of PML. 
f 
Blood pressure measurement can be performed prior to drug infusion. To be measured after the patient has been in a sitting/lying down position for at least 5 
minutes.  During all infusions of study drug, vital signs will be assessed at the following time points:  pre-infusion (within 10 minutes prior to the start of the 
infusion); at the start of infusion (within 30 minutes after the start of the infusion); and at the end of infusion (within 10 minutes from the end of the infusion).  
Additional readings may be taken at the discretion of the Investigator in the event of an infusion-related reaction. 
g 
Posterior-anterior and lateral chest X-rays (or chest radiographs in accordance with local requirements) should be obtained and reviewed by the Investigator 
or designee. If chest radiographs taken within the past 3 months show no clinically significant abnormality, and there are no signs or symptoms suggestive of 
pulmonary disease that would exclude the patient from the study, then a chest radiograph does not need to be repeated. Chest X-rays may be repeated at any 
time during the study for suspected TB or chest infection. 
h 
Patients should rest for at least 5 minutes in a supine position before ECG evaluation. 
i 
In women of childbearing potential; serum pregnancy test (central laboratory) at Screening and EOS. Urine pregnancy test prior to each dose (first and second 
courses of treatment). 
j 
All patients except withdrawn patients will continue to attend visits until Week 52 regardless of the second course infusion to obtain PK / PD, safety, efficacy, 
and immunogenicity data. 
k 
Unscheduled visits should be scheduled as per Investigator discretion. Tests will be performed as per Investigator’s discretion. 
l 
Study drug is required to be dispensed at Week 24 and Week 26, based on ANC value and platelet count at Week 20 and both the swollen and tender joint 
counts assessed at Week 24. If the ANC value and platelet count are marginally lower, re-testing at an unscheduled visit may be performed at the discretion 
of the Investigator within the 4-week period between Week 20 and Week 24. In case Visit 11 is missed, all safety evaluations including ANC value and platelet 
count must be completed as an unscheduled visit for patient to be eligible for second course of infusion. 

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m 
SAIT101 or Rituxan® or MabThera® for intravenous infusion. On Days 1 and 15, each patient will receive one course of two 1,000 mg (10 mg/mL) drug 
infusions. Patients who, at Week 24, have a <50% improvement from Baseline in both the swollen and tender joint counts will be eligible for a further course 
of two 1,000 mg drug infusions. Eligible patients in the SAIT101 arm will receive the second course of SAIT101 treatment at Week 24 and Week 26. Eligible 
patients in the MabThera® arm will receive the second course MabThera® treatment at Week 24 and Week 26. Eligible patients in the Rituxan® arm will be 
randomized in a 1:1 ratio to receive SAIT101 or Rituxan® treatment at Week 24 and Week 26. 
n 
Questionnaires must be completed in the study center by the patient or patient’s representative (in case patient is unable to read and/or write) based on the 
patient’s verbal answers. 
o 
Joint assessor(s) will be independent to the rest of the study team. 
p 
To be performed by the central laboratory.  Screening performed to confirm negative serology for HIV, HBV and HCV.  Patients with negative HBsAg and 
positive HBcAb must have a HBV DNA level <20 IU/mL (or 112 copies/mL) by PCR test.  These HBV patients must be willing to undergo PCR HBV DNA 
testing during treatment and may participate following consultation with a hepatitis expert regarding monitoring and use of HBV antiviral therapy, and provided 
they agree to receive treatment as indicated.  An HBV re-test will be performed monthly including Day 1, Weeks 4, 8, 12, 16, 20, 24, 36,52, early EOS or 
unscheduled visit, if required. Patients who are confirmed positive and those who have active infections will be excluded from the participation in the study. 
q 
QuantiFERON Gold test is conducted at Screening. If TB is suspected at any time during the study, chest X-ray and/or QuantiFERON Gold test should be 
performed (Central Laboratory) 
r 
To determine presence of hypogammaglobulinemia (IgG <600mg/dL), which is an exclusion criterion. 
s 
On Day 1 and Day 15 (first and second infusions) blood PK and PD (CD19+ B-cell) samples will be collected before and 3 hours after the start of infusion 
and immediately (within 10 minutes) before and 1 hour after the end of infusion, at 48 hours after the start of infusion (Days 3 and 17, in case of 2nd 
infusion at Day 16, the following PK sampling should be on Day 18). The PK and PD samples will also be taken (at the same time of the day first infusion 
started) at Day 8 (Week 1), Days 29 (Week 4), 57 (Week 8), 85 (Week 12), 113 (Week 16), 141 (Week 20), 169 (Week 24). PD sampling will be additionally 
collected at D 253 (Week 36), and 365 (Week 52, EOS). Window of each sampling is ± 10 minutes of the determined time points of Days 1, 3, 8, 15 and 17 
and ± 3 hours at all other time points. 
t 
On Day 1, Day 15 (Week 2), and Week 24: immunogenicity sample will be collected before start of infusion. Wherever possible immunogenicity blood 
samples will be taken at the same time as blood is drawn for other analyses to limit repeated venipuncture. Immunogenicity sampling is also taken when 
patients show signs or symptoms of immune-response-related adverse events.  
 
 
 

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3.6.1 
Schedule of Assessments 
The sequence of assessments at each visit will be standardized as follows (at visits as 
required by the schedule of assessments): 
1. At Visit 1 (Screening): Obtaining of informed consent 
2. General assessments: Physical examination, Neurological examination, and Vital signs 
3. Efficacy assessments: Patient-reported assessments (patient pain VAS, global VAS, 
and HAQ-DI) 
4. Efficacy assessments: Investigator assessments (swollen and tender joint counts, 
physician’s global assessment of disease activity VAS, EULAR, DAS28) 
5. Laboratory/Safety assessments 
6. PK/PD/immunogenicity assessments, where applicable 
7. If applicable, pre-medication and study drug  
All assessments will be performed prior to administration of pre-medication, unless 
otherwise specified. 
Patient-reported data (pain VAS, global VAS, HAQ-DI) should be recorded by the patient 
on the relevant source documents. In special circumstances when the patient has difficulty 
writing or is unable to read, the study personnel or patient representative can record this 
data on behalf of the patient and based on responses provided by the patient verbally. The 
procedure followed must be documented clearly in the patient notes. 
3.6.1.1 
Screening Period 
Visit 1 (-30 days and not to exceed 60 days before Day 1) 
Patients must have the ability and willingness to provide written informed consent (prior 
to any study-specific procedures being performed) and to comply with the requirements of 
the protocol. All the Screening assessments should be performed within 30 days prior to 
randomization on Day 1 (Visit 2, Baseline). 
However, in patients who require a washout of current anti-TNF medication or other 
biologic and non-biologic DMARD treatment (except MTX) the Screening period may be 
extended to allow for the washout required, but will not exceed 60 days. In these patients 
all Screening assessments must be performed within 30 days prior to randomization with 
the exception of the informed consent and chest X-ray. 

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Once the patient has provided written informed consent and meets the inclusion and 
exclusion criteria (see Section 3.4), the study center will register the patient in the IXRS. 
The following must also be performed: 
• Document patient’s demographic information (including gender, date of birth and, 
when possible per local regulations, race), and medical and surgical history (including 
RA history; 
• Physical examination, including height (cm) and weight (kg); 
• Neurological examination (for signs and symptoms of PML); 
• Chest X-ray, unless taken within the previous 3 months; 
• Serum pregnancy test;  
• Vital signs;  
• Document previous and concomitant medications (including vaccination history); 
• Resting 12-lead ECG. 
The following safety/laboratory assessments will be performed: 
• QuantiFERON® TB- Gold test;  
• Serology (HBsAg and HBcAb, HBV DNA by PCR [<20 IU/mL or 112 copies/mL], 
anti-HCV, and HIV test), IgG, IgM, IgA, clinical chemistry, hematology, and 
urinalysis;  
• CRP, ESR; 
• RF. 

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3.6.1.2 
Study Drug Administration Part A 
Prior to Day 1, patients will be discontinued from their current anti-TNF medication, other 
biologic DMARDs or non-biologic DMARDs, except MTX. 
The following must be performed on Baseline (Day 1, Week 0): 
Review inclusion and exclusion criteria and confirm patient eligibility. If eligible, the 
following procedures should be performed: 
• Physical examination and vital signs; 
• Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs;  
• Urine pregnancy test for applicable female; 
• Randomization to one of the study drugs; 
• Contact IXRS. 
The following efficacy assessments will be performed: 
• Patient’s assessment: global VAS and HAQ-DI, including patient’s pain VAS; 
• Physician’s assessment: global VAS; 
• Joint assessment. Each of the 66/68 joints will be evaluated for tenderness and 
swelling. 
The following laboratory assessments will be performed: 
• Clinical chemistry, hematology, urinalysis and HBV DNA only when negative 
HBsAg and positive HbcAb at screening; 
• CRP, ESR; 
• PK and PD sample collection; 
• Immunogenicity. 

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The following must be also performed: 
• The first of the two infusions of the study drug, as per IXRS.  
The following must be performed on Day 3 (Week 0): 
• Physical / Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs;  
• PK and PD sample collection. 
The following must be performed on Day 8 (Week 1): 
• Physical / Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs;  
• PK and PD sample collection; 
• Immunogenicity. 
The following must be performed on Day 15 ± 1 day (Week 2): 
• Physical examination and vital signs; 
• Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs; 
• Urine pregnancy test for applicable female; 
• Contact IXRS; 
• The second of the two infusions of study drug, as per IXRS; 
• Clinical chemistry, hematology, urinalysis 
• PK and PD sample collection; 

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• Immunogenicity. 
The following must be performed on Day 17 ± 1 day (Week 2): 
• Physical / Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs;  
• PK and PD sample collection. 
The following must be performed on Day 29 ± 3 days (Week 4): 
• Physical / Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs.  
The following laboratory assessments will be performed: 
• Clinical chemistry, hematology, urinalysis and HBV DNA only when negative 
HBsAg and positive HbcAb at screening; 
• PK and PD sample collection; 
• Immunogenicity. 
The following must be performed on Day 57 ± 3 days (Week 8): 
• Physical / Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs. 
The following efficacy assessments will be performed: 
• Patient’s assessment: global VAS and HAQ-DI, including patient’s pain VAS; 
• Physician’s assessment: global VAS; 

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• Joint assessment. Each of the 66/68 joints will be evaluated for tenderness and 
swelling. 
The following laboratory assessments will be performed: 
• Clinical chemistry, hematology, urinalysis and HBV DNA only when negative 
HBsAg and positive HbcAb at screening; 
• IgG, IgM, IgA; 
• CRP, ESR; 
• PK and PD sample collection. 
The following must be performed on Day 85 ± 3 days (Week 12): 
• Physical / Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs. 
The following laboratory assessments will be performed: 
• Clinical chemistry, hematology, urinalysis and HBV DNA only when negative 
HBsAg and positive HbcAb at screening; 
• PK and PD sampling; 
• Immunogenicity. 
The following must be performed on Day 113 ± 3 days (Week 16): 
• Physical / Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs. 
The following efficacy assessments will be performed: 
• Patient’s assessment: global VAS and HAQ-DI, including patient’s pain VAS; 
• Physician’s assessment: global VAS; 

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• Joint assessment. Each of the 66/68 joints will be evaluated for tenderness and 
swelling. 
The following laboratory assessments will be performed: 
• Clinical chemistry, hematology, urinalysis and HBV DNA only when negative 
HBsAg and positive HbcAb at screening; 
• IgG, IgM, IgA; 
• CRP, ESR; 
• PK and PD sample collection; 
• Immunogenicity. 
The following must be performed on Day 141 ± 3 days (Week 20): 
• Physical / Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs. 
The following laboratory assessments will be performed: 
• Clinical chemistry, hematology, urinalysis and HBV DNA only when negative 
HBsAg and positive HbcAb at screening; 
• PK and PD sampling. 
To be eligible for the second course of treatment, patients must have an absolute neutrophil 
count (ANC) ≥1.5x103/µL and platelet counts ≥ 75 x 109/L observed at Week 20 (V11). If 
the ANC value and platelet count are marginally lower, re-testing at an unscheduled visit 
may be performed at the discretion of the Investigator within the 4-week period between 
Week 20 and Week 24. In case Visit 11 is missed, all safety evaluations including ANC 
value and platelet count must be completed as an unscheduled visit for patient to be eligible 
for second course of infusion. 
Following must be performed in the unscheduled visit in this case:  
• Neurological examination; 
• Physical examination and vital signs; 

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• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs; 
• Clinical chemistry, hematology, and urinalysis; 
3.6.1.3 
Study Drug Administration Part B 
Patients with an inadequate response (<50% improvement from Baseline in both the 
swollen and tender joint counts) at Week 24 (Visit 12), will be eligible to receive a further 
course of two 1,000 mg i.v. infusions, one infusion at Week 24 (Day 1 of second course) 
and the second infusion at Week 26 (14 days after first dose of second course).  
The following must be performed on Day 169 ± 3 days (Week 24, Day 1 of the Second 
course of infusion): 
Following must be performed:  
• Physical examination and vital signs; 
• Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs; 
• Urine pregnancy test for applicable females administered the second course of the 
study drug; 
The following efficacy assessments will be performed: 
• Patient’s assessment: global VAS and HAQ-DI, including patient’s pain VAS; 
• Physician’s assessment: global VAS; 
• Joint assessment. Each of the 66/68 joints will be evaluated for tenderness and 
swelling. 
The following laboratory assessments will be performed: 
• IgG, IgM, and IgA; 

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• Clinical chemistry, hematology, urinalysis and HBV DNA only when negative 
HBsAg and positive HbcAb at screening; 
• CRP, ESR; 
• PK and PD sampling; 
• Immunogenicity.  
The following must be also performed: 
• Contact IXRS; 
• Randomization; 
• The first of the two infusions of the study drug (see Section 3.2.1), as per IXRS for 
eligible patients only. 
The following must be performed on Day 183 ± 3 days (Week 26, Day 15 of the Second 
course of infusion): 
• Physical examination and vital signs 
• Neurological examination; 
• Documentation of concomitant medications; 
• Assessment of AEs/SAEs/ADRs; 
• Urine pregnancy test for applicable females administered the second course of the 
study drug; 
• Contact IXRS; 
• The second of the two infusions of study drug (see Section 3.2.1), as per IXRS, for 
eligible patients only.  
The following assessments will be performed on Day 253 ± 7 days (Week 36):  
• Physical / Neurological examination; 
• Document concomitant medications; 

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• Assessment of AEs/SAEs/ADRs. 
The following efficacy assessments will be performed: 
• Patient’s assessment: global VAS and HAQ-DI, including patient’s pain VAS; 
• Physician’s assessment: global VAS; 
• Joint assessment. Each of the 66/68 joints will be evaluated for tenderness and 
swelling. 
Laboratory assessments 
• Clinical chemistry, hematology, urinalysis and HBV DNA only when negative 
HBsAg and positive HbcAb at screening; 
• IgG, IgM, IgA; 
• CRP, ESR; 
• PD sampling; 
• Immunogenicity. 
End of Study Visit 
The following assessments will be performed on Day 365 ± 7 days (Week 52): 
• Physical examination and vital signs; 
• Neurological examination; 
• Document concomitant medications; 
• Resting 12-ECG; 
• Assessment of AEs/SAEs/ADRs; 
• Serum pregnancy test for applicable female; 
• Contact IXRS. 
The following efficacy assessments will be performed: 

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• Patient’s assessment: global VAS and HAQ-DI, including patient’s pain VAS; 
• Physician’s assessment: global VAS; 
• Joint assessment. Each of the 66/68 joints will be evaluated for tenderness and 
swelling. 
The following laboratory assessments will be performed: 
• Clinical chemistry, hematology, urinalysis and HBV DNA only when negative 
HBsAg and positive HbcAb at screening; 
• IgG, IgM, and IgA; 
• CRP, ESR; 
• PD sampling; 
• Immunogenicity.  
Unscheduled Visit Assessments 
Patients may attend the clinic for unscheduled visits at any time for additional safety 
monitoring at the discretion of the Investigator. 
3.6.2 
Efficacy Assessments 
3.6.2.1 
ACR and DAS28 Score 
The following assessments will be performed at the time points indicated in Table 2 for the 
purposes of calculating the ACR and DAS28 response scores. 
3.6.2.1.1 
Joint Assessments 
Wherever possible, the same person should perform the joint assessment throughout the 
study (i.e., for all patients at each study center). Independent joint assessors (require at least 
one or more if necessary) will be assigned at each study center. This person will be 
independent to the rest of the study team in order to minimize any bias that could be 
introduced as a result of the assessment. Standardized training will be provided and the 
training records filed.  
Each of the 66/68 joints will be evaluated for tenderness and swelling (prior to taking any 
required analgesic that day if possible). Immobilized or injected joints and prosthetic joints 
and joints which have undergone surgery within 1 year of the Screening visit will be 
excluded from the assessments.  

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The 66/68 Joint Count evaluates 66 joints for swelling and 68 joints for tenderness and 
pain with movement. Hip joints can be evaluated for tenderness only - but not for swelling. 
The 66/68 joint count includes the following joints: the temporomandibular; 
sternoclavicular; acromioclavicular; shoulder; elbow; wrist; metacarpophalangeal, 
proximal interphalangeal, and distal interphalangeal joints of the hands; hip; knee; ankle; 
tarsus; and the metatarsal phalangeal and proximal joints of the feet. 
3.6.2.1.2 
Patient’s Global Assessment of Disease Activity 
Patients will mark on a VAS their overall assessment of how their RA has affected them, 
rating how they are managing from 0 (very well) to 100 (very poor). This is equivalent to 
the General Health component of the DAS (see Appendix 5). 
Patients will sign and date the completed VAS. 
Patient-reported outcomes and physician-reported outcomes should be completed 
independently of each other (to avoid bias of the Investigator or the patient). 
3.6.2.1.3 
Physician’s Global Assessment of Disease Activity 
The physician’s assessment of the patient’s current disease activity will be documented on 
a VAS, ranging from ‘no disease activity’ (0) to ‘maximum disease activity’ (100) (see 
Appendix 5). Wherever possible, the same physician should perform the assessment for a 
given patient at every visit. 
The physician will sign and date the completed VAS. 
Physician-reported outcomes and patient-reported outcomes should be completed 
independently from each other (to avoid bias of the Investigator or the patient). 
3.6.2.1.4 
Patient’s Assessment of Disability 
If the patient is unable to read and/or write, the HAQ-DI can be completed by the patient’s 
representative based on the patient’s verbal responses. 
The patient’s ability to function in daily life will be assessed using the HAQ-DI 
questionnaire. This is a widely used patient self-report tool which assesses the degree of 
difficulty the patient has in accomplishing tasks in eight functional areas, over the previous 
week, taking into account any aids or help required. It consists of eight component sets: 
(1) dressing and grooming, (2) rising, (3) eating, (4) walking, (5) hygiene, (6) reach, 
(7) grip and (8) common daily activities (see Appendix 5). 

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The HAQ-DI questionnaire includes a pain VAS. Patients will mark on a VAS the current 
level of pain due to their RA, ranging from 0 (no pain) to 100 (severe pain) (see 
Appendix 5). 
Patients will sign and date the completed questionnaire. 
3.6.2.2 
Systemic Inflammation: CRP Level and ESR 
A blood sample for CRP assessment will be collected and analysis will be conducted by a 
suitably qualified central laboratory using validated methods. 
A whole blood sample (2 mL) will be collected for the erythrocyte sedimentation rate 
(ESR) value to be measured locally by Westergren method.  
3.6.3 
Pharmacokinetic and Pharmacodynamic Assessments 
3.6.3.1 
Pharmacokinetic Assessments 
Blood samples for the determination of concentrations of rituximab will be taken for each 
treatment at the times presented in the schedules of assessments (see Table 2). 
Individual venipunctures for each time point may be performed or an indwelling catheter 
may be used. The exact date/time of the blood sample collection will be recorded in the 
patient’s eCRF. 
The blood samples (approximately 5 mL) will be drawn in K2EDTA tubes and processed 
using instructions provided by designated central laboratory. Serum will be harvested in 
duplicate samples approximately 2.5 mL respectively including back-up sample.  
Determination of serum concentrations of rituximab will be performed by central 
laboratory using validated analytical methods. Detailed sample collection, labeling, 
storage, and shipment information will be described in the Laboratory Manual. 
3.6.3.2 
Pharmacodynamic Assessments 
Blood samples for the determination of CD19+ count will be taken for each treatment at 
the times presented in the schedules of assessments (see Table 2). The exact date/time of 
the blood sample collection will be recorded in the patient’s eCRF. 
The blood samples (approximately 5 mL) will be drawn and processed using instructions 
provided by the designated laboratory retained by the Sponsor.  

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The samples will be analyzed for CD19+ count by designated central laboratory using 
validated analytical methods. Detailed sample collection, labelling, storage, and shipment 
information will be described in the Laboratory Manual.  
3.6.4 
Immunogenicity Assessments 
Blood samples (approximately 5 to 8 mL) will be taken at the visits shown in (Table 2) to 
determine the incidence of HACA and neutralizing antibody (using validated analytical 
methods). 
Blood immunogenicity samples will be collected on Day 1 of First course (prior to the start 
of the first infusion), and on Weeks 1, 2, 4, 12, 16, 24, 36, and 52 with date and time of 
sampling accurately recorded. Wherever possible immunogenicity blood samples will be 
taken at the same time as blood is drawn for other analyses to limit repeated venipuncture. 
Additionally, immunogenicity should be assessed when patients show signs or symptoms 
of immune-response-related adverse events. 
Human anti-chimeric antibody will be detected in serum samples using validated 
analytical methods. Serum samples in which HACA are detected will be reflexed to a 
Neutralizing Antibody Assay to evaluate the effect of the HACA on the biological activity 
of rituximab. Full instructions for collection, labeling, storage, and shipment of samples 
are provided in the Laboratory Manual. 
3.6.5 
Safety Assessments 
All the safety assessments must be performed as provided in Table 2. 
3.6.5.1 
Adverse Events 
The details of the assessment of AEs are presented in Section 5. 
3.6.5.2 
Clinical Laboratory Assessments 
The list of clinical laboratory assessments is provided in Table 3. 

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Table 3 
Clinical Laboratory Assessments 
Hematology 
White blood cell count, red blood cell count, hemoglobin, platelets, absolute 
neutrophil count  
Clinical 
chemistry (serum) 
Creatinine, aspartate transaminase, alanine transaminase (ALT), lactate 
dehydrogenase, alkaline phosphatase (ALP), total bilirubin, cholesterol, calcium, 
glucose, gamma glutamyl transferase (GGT), phosphate, hCG 
Urinalysis 
Glucose, blood, protein, hCG 
Virology 
Hepatitis C virus antibodies, human immunodeficiency virus, hepatitis B surface 
antigen, and hepatitis B core antibody (total and immunoglobulin M), HBV DNA 
Other 
C-reactive protein, rheumatoid factor, erythrocyte sedimentation rate*, 
QuantiFERON-TB Gold 
* ESR estimation (Westergren method) and urine pregnancy test would be performed locally 
3.6.5.3 
Physical Examination 
A physical examination will be performed by the Investigator and recorded as ‘normal’ or 
‘abnormal’ with specified abnormalities at the visits indicated in Table 2. Any persisting 
abnormalities should be stated each time the examination is performed. Diagnosis of new 
abnormalities, or worsening of abnormalities, should be recorded as AEs if appropriate. 
Wherever possible, the same person should perform the physical examination throughout 
the study (i.e., for all patients at each study center). The physical examination should 
include assessment of general appearance, skin, head, neck, throat, lymph nodes, thyroid, 
abdomen, and cardiovascular, neurological, musculoskeletal/extremities, and respiratory 
systems. 
Body weight will also be measured. Height will be measured at Screening (Visit 1) only. 
3.6.5.4 
Vital Signs 
Vital signs (blood pressure, pulse rate, respiratory rate, and oral or tympanic body 
temperature) will be assessed at the visits indicated in Table 2. BP measurements should 
be performed after the patient has been in a sitting/lying down position for at least 
5 minutes 
During all infusions of the study drug, vital signs will be assessed at the following time 
points: 
1. Pre-infusion (within 10 minutes prior to the start of the infusion); 
2. Start of infusion (within 30 minutes after the start of the infusion); 
3. End of infusion (within 10 minutes after the end of the infusion). 

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Additional readings may be assessed at the discretion of the Investigator in the event of an 
infusion-related reaction. 
The Investigator must assess all vital signs findings at each visit. If the Investigator finds 
any clinically relevant abnormalities, these should be reported as AEs/SAEs as appropriate. 
3.6.5.5 
Resting 12-lead ECG 
Resting 12-lead ECG data will be collected at Screening (Visit 1) and EOS (see Table 2).  
Patients should rest for at least 5 minutes in a supine position before ECG evaluations. 
The original ECG traces and variables must be stored in the patients’ medical record as 
source data. The Investigator should evaluate the ECG from a clinical perspective and the 
result (whether the ECG result is normal or abnormal) should be recorded on the ECG 
tracing and on the appropriate section of the eCRF. 
3.6.5.6 
Pregnancy Test 
A serum pregnancy test will be performed at Screening and EOS. Urine pregnancy tests 
will be performed at the different time points indicated in Table 2 to rule out pregnancy in 
patients of childbearing potential. If a pregnancy test was performed within 4 weeks prior 
to the relevant time point, it need not be repeated.  
3.6.5.7 
Chest X-ray 
Posterior-anterior and lateral chest X-rays (or chest radiographs in accordance with local 
requirements) should be obtained at Screening and reviewed by the Investigator or 
designee. At Screening, if chest radiographs taken within the past 3 months show no 
clinically significant abnormality, and there are no signs or symptoms suggestive of 
pulmonary disease that would exclude the patient from the study, then a chest radiograph 
does not need to be repeated. 
3.6.6 
End of Study 
All patients will be followed up for up to 52 weeks from the start date of the first course of 
study drug. The patients who discontinue the study treatment attend all visits until Week 
52 in order to address any safety concerns, to record the concomitant medications, and to 
measure drug level, CD19+ B cell count immunogenicity and efficacy (if applicable). 

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3.6.7 
Data Safety Monitoring Board 
An independent Data Safety Monitoring Board (DSMB) will be assigned for this study. 
The DSMB will review available study data at pre-specified time points as outlined in the 
DSMB charter. The details of the DSMB roles and responsibilities and details of the review 
process will be outlined in the DSMB Charter. 
3.7 
Stopping Rules, Discontinuation Criteria, and Procedures 
3.7.1 
Entire Study or Treatment Arms 
If the Sponsor decides to terminate or suspend the study for safety or unanticipated other 
reasons, the Sponsor will promptly notify the Investigators, Sub-investigators, Institutional 
Review Boards/Independent Ethics Committees (IRBs/IECs), and Regulatory Authorities 
as required by the applicable regulatory requirements. 
3.7.2 
Individual Study Center 
The Sponsor, IRB/IEC and/or Regulatory Authorities have the right to close an individual 
study center at any time. In case of premature termination of an individual study center, 
the Sponsor, Investigator, participating study patients, IRB/EC and Regulatory Authorities 
should be informed as described in ICH-GCP and according to other applicable regulatory 
requirements. 
Prior to closure of the study center, the Investigator or institution must assure appropriate 
therapy and follow-up for the patients. 
The Sponsor may decide to close an individual study center prematurely for the following 
reasons: 
• Lack of enrollment; 
• Non-compliance with the requirements of the study protocol; 
• Non-compliance with ICH-GCP and/or other applicable regulatory requirements. 
3.7.3 
Individual Patient 
If a patient discontinues the study treatment prematurely, the reason given must be fully 
evaluated and recorded appropriately in the source documents and the patient’s eCRF. If 
the patient is discontinued from study treatment because of an AE, that AE should be 
indicated as the reason for discontinuation. 

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The Investigator can discontinue treatment of a patient at any time if medically necessary. 
In addition, patients meeting the patient discontinuation criteria must be discontinued from 
the study treatment.  
Patients will be discontinued from the study treatment in the following circumstances: 
• A patient who does not meet the enrolment criteria is inadvertently randomized, that 
patient must be discontinued from study treatment and the Sponsor or Clinical 
Research Organization (CRO) must be contacted. 
• The Investigator decides that the patient should be discontinued from study treatment. 
If this decision is made because of an intolerable AE or a clinically significant 
laboratory value, the study drug is to be discontinued and appropriate measures are to 
be taken. The Sponsor or designee is to be notified immediately. 
• Patient non-compliance, defined as refusal or inability to adhere to the study schedule 
or procedures (see Section 3.12). 
• Treatment with a prohibited concomitant medication other than the use of appropriate 
medications for the treatment of AEs under the direction of the Sponsor and/or 
Investigator or Sub-investigator 
• Lack of efficacy. Subjects who lack efficacy can be included in the PK and efficacy 
analysis. Patients receiving rescue therapy prior to Week 24 would not be eligible for 
second course of infusion. 
• Patients who meet any of the following specific safety discontinuation criteria, 
however can be included for the PK analysis: 
− Patients who develop severe infusion-related reactions, especially severe dyspnea, 
bronchospasm or hypoxia, should have the infusion interrupted immediately to 
receive aggressive symptomatic treatment. In all patients, the infusion should not 
be restarted on the same day until complete resolution of all symptoms. At this time, 
the infusion may be initially resumed at the discretion of the Investigator at not 
more than one-half the previous rate. If the same ADRs occur for a second time, 
the infusion should be permanently discontinued. 
− Active TB 
− Invasive fungal infection or opportunistic infection including, but not limited to, 
listeriosis, legionellosis or pneumocystis.  
− Hepatitis B virus reactivation, in some cases resulting in fulminant hepatitis, or 
hepatic failure 

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− Any other AEs which, in the opinion of the Investigator or the Sponsor, could 
compromise the patient’s safety or well-being if they continue to participate in the 
study. 
− PML. Neurological warning signs include: major changes in vision, unusual eye 
movements; loss of balance or coordination; and disorientation or confusion 
− Cancer: any malignant lesion. Patients with basal cell and squamous cell 
carcinomas of the skin or carcinoma in situ of the cervix uteri that has been excised 
and cured, may be continued on the study at the discretion of the Investigator. 
− Pregnancy in a female participant 
− Patient lost to follow-up despite reasonable efforts to make contact with the patient 
− Patients who have a delay of >15 days in receiving the second infusion due to an 
AE or otherwise 
• 
Judgment by the Investigator or Sub-investigator that study treatment discontinuation 
is necessary for reasons other than those described above. 
To prevent missing data in important supportive efficacy and safety analysis, patients who 
discontinued study drug, will also attend all visits until week 52. 
3.8 
Screen Failures 
A screen failure patient is a patient who provided written informed consent (i.e., the patient 
signs an informed consent form [ICF]), but failed to meet all the inclusion criteria or who 
meets any of the exclusion criteria or withdraws consent prior to randomization. The reason 
for screen failure will be documented in the source documents. 
Patients are only allowed to be re-screened once and it should be performed in consultation 
with the Sponsor or representative. 
Laboratory tests if marginally abnormal may be repeated once at the discretion of the 
Investigator during the Screening period if the patient does not meet the criteria the first 
time. If the patient fails the laboratory criteria a second time, they will be considered a 
screen failure. Re-testing may only be done at the central laboratory except for ESR. 
3.9 
Re-screening 
Re-screening may be required if a patient has not met all the eligibility criteria. Patients are 
only allowed to be re-screened once and it should be performed in consultation with the 

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Sponsor or representative. Each patient must give written informed consent before re-
screening occurs. 
3.10 
Definition of Completed Patients 
In this study, patients who complete at least the first course of study drug in Part A and 
undergo the tests and assessments at Week 52 will be defined as study completers. 
3.11 
Definition of Patients Lost to Follow-up 
Lost to follow-up is defined as a patient who stops attending study visits and study 
personnel are unable to contact the patient. 
To prevent lost to follow-up, several approaches should be implemented to retain patients 
who fail to actively maintain contact with the investigator (e.g., telephone calls to friends 
or family members, emails, offers for transportation to the clinic, etc.). 
If a patient is lost to follow-up, every possible effort must be made by the study center 
personnel to contact the patient and determine the reason for withdrawal. The measures 
taken to follow up must be documented. 
3.12 
Treatment Compliance 
The administration (dose, frequency and dates) of all concomitant medications (including 
new medications taken during the study and investigational product) should be recorded in 
the appropriate sections of the eCRF from Visit 1. 
The infusion schedule consists of two 1,000 mg i.v. drug infusions of either SAIT101 or 
MabThera® or Rituxan® (the first on Day 1 and the second on Day 15) with the possibility 
of a further course of two 1,000 mg infusions (see Section 3.2.1). The study drugs will be 
administered at the study center. This should guarantee that full compliance was achieved, 
provided the patient attended the appropriate visits. Patients who miss the allocated day for 
the second of their two infusions will be contacted and another visit arranged as soon as 
practically possible in order to administer the missed dose of the study drug. 
The prescribed dosage, timing, and mode of administration of the study drug may not be 
changed. Any departures from the intended regimen must be recorded in the eCRF.  
Patients exhibiting poor compliance as assessed by attendance to appointments for their 
drug infusions should be counseled on the importance of good compliance to the study 
dosing regimen.  

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3.13 
Protocol Deviations 
This study is intended to be conducted as described in this protocol. In the event of a 
significant deviation from the protocol due to an emergency, accident, or mistake (e.g., 
violation of the informed consent process, study drug dispensing or patient dosing error, 
treatment assignment error, patient enrolled in violation of eligibility criteria or 
concomitant medication criteria), the Investigator or Sub-investigator must contact the 
Sponsor at the earliest possible time. This will allow an early joint decision regarding the 
patient’s continuation of study treatment. This decision will be documented by the 
Investigator and confirmed by the Sponsor.  
 
 

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4 
RESTRICTIONS 
4.1 
Measures Regarding Patients Being Treated or Scheduled for 
Treatment at another Department or Hospital 
When obtaining informed consent, the Investigator or Sub-investigator will confirm with 
the patient whether they are being treated or are scheduled for treatment at another 
department or hospital and note any drugs that they are using. If the patient is being treated 
by another physician (receiving treatment at another department or medical institution), the 
Investigator or Sub-investigator will contact the treating physician and inform them of the 
patient’s participation in the study and provide information on the study drug. In addition 
to obtaining and recording the information on the medications prescribed at the other 
department or hospital, the appropriateness of the patient’s study participation or 
continuation in the study will be decided. 
4.2 
Prohibited Medications/Therapies 
Prior treatments required to be discontinued prior to Baseline is summarized in Table 4. 
Table 4 
Prior Treatments Required to be Discontinued Prior to 
Baseline 
Treatment 
Restriction 
Leflunomide 
Not permitted. Must be withdrawn at least 12 weeks prior to the 
beginning of the Treatment Period or a minimum of 4 weeks 
prior Day 1 if after 11 days of standard cholestyramine washout 
Sulfasalazine 
Not permitted within 4 weeks prior to Day 1 
Hydroxychloroquine 
Not permitted within 8 weeks prior to Day 1 
Other non-biologic (conventional) 
DMARDs 
Not permitted within 4 weeks prior to Day 1 
Biologic DMARDs 
Not permitted within defined washout period prior to Day 1 
(see Table 6) 

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Treatment 
Restriction 
Intravenous or intramuscular 
corticosteroids 
Not permitted within 6 weeks prior to Day 1 
Intra-articular corticosteroids 
Not permitted within 6 weeks prior to Day 1 
Anti-infective agents 
Intravenous anti-infective agents within 4 weeks prior to 
Screening or oral anti-infective agents within 2 weeks prior to 
Screening are not permitted 
Live/attenuated vaccine 
Not permitted within 6 weeks prior to Day 1 or during the study 
Any drug that has not received 
regulatory approval for any indication 
Not permitted within 4 weeks or a minimum of 5 half-lives, 
whichever is longer, prior to Day 1 
Traditional herbal medicines (e.g., 
preparations containing derivatives of 
Tripterygium wilfordii Hook, 
Sinomenium acutum and Paeonia 
lactiflora) 
Any traditional herbal medicine which has RA as an 
indication in its label is not permitted 
Anti-cancer chemotherapy 
Not permitted within 5 years prior to Screening 
Surgical procedure 
Not permitted within 4 weeks prior to Day 1 
B cell modulating or B cell depletion 
therapies 
Treatment with such therapies, such as, but not limited to 
rituximab, belimumab, atacicept, tabalumab, ocrelizumab, 
ofatumumab, obinutuzumab, epratuzumab and other 
experimental treatments is not permitted prior to or during the 
study 
4.3 
Concomitant Medications with Restrictions 
Other medication that is considered necessary for the patient’s safety and well-being (e.g., 
as a result of an AE) may be given at the discretion of the Investigator. Investigators are 
encouraged to discuss the introduction of any restricted medications with the Sponsor 
physician or representative. Any concomitant medications should be recorded in the 
appropriate sections of the eCRF. 
The list of medications permitted during the study is presented in Table 5. 

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Table 5 
List of Medications Permitted During the Study 
Treatment 
Restriction 
Methotrexate 
Patients must be taking MTX at a dose of 7.5-25 mg/week (oral or 
parenteral) throughout the study and for at least 12 weeks prior to study 
entry. Patients receiving a lower dose of MTX (<10 mg/week) should be 
doing so as a result of a documented evidence of intolerance to higher doses 
of MTX. The dose and route of administration should remain stable from 4 
weeks prior to randomization and where possible, throughout the entire 
study period. 
Folic or folinic acid 
Patients must be taking oral folic or folinic acid or equivalent during the 
entire study (mandatory co-medication for MTX treatment), according to 
local standards and availability. The dosing regimen is at the Investigator’s 
discretion. 
Antipyretics 
Patients will receive an antipyretic, e.g., paracetamol or equivalent, 30 to 60 
minutes before each drug infusion. 
Antihistamines 
Patients will receive an antihistamine, e.g., diphenhydramine or equivalent, 
30 to 60 minutes before each drug infusion. 
Oral corticosteroids 
If receiving current treatment with oral corticosteroids at the time of 
Screening (≤10 mg/day prednisone or equivalent), the dose must remain 
stable during the 4 weeks prior to Day 1. Increases in corticosteroids for 
treatment of RA are not allowed over the study period and should be avoided 
(see Section 3.2.5). 
Reductions in the dose of corticosteroids will be allowed as clinically 
required only for safety reasons. 
Intravenous or 
intramuscular 
corticosteroids 
Use of i.v. or intramuscular corticosteroids for RA will be considered 
worsening of a patient’s condition from Baseline and should be recorded as 
an AE in the eCRF. 
The only exception will be the administration of 100 mg i.v. 
methylprednisone or equivalent within 30 minutes before each infusion as 
part of the study procedures. 
Intra-articular 
corticosteroids 
Injection of intra-articular steroids during the study period is discouraged, 
but may be used in a limited fashion. Joints injected within 8 weeks prior to 
Week 24 and Week 52 will cause the exclusion of the joint from the 
subsequent efficacy analysis and therefore should be avoided. No more than 
1 joint per 24-week period may be injected during the study period. No 
single injection should exceed 40 mg of triamcinolone (or equivalent) and 
the total dose of intra-articular corticosteroid may not exceed 80 mg of 
triamcinolone (or equivalent) during any 52-week period. 
Inhaled/topical/ophthalmic 
steroids 
Limited uses of these preparations are allowed during the study. 
NSAIDs 
Patients may be treated with NSAIDs, up to the maximum recommended 
dose, (including cyclooxygenase-2 inhibitors) throughout the study. The 
choice and doses of NSAIDs used to treat patients is at the discretion of the 
Investigator. Increases in the NSAID dose are not allowed over the study 
period and should be avoided. After Week 24, dose adjustments may be 
made only for safety reasons, and if absolutely required to treat disease 
flares, according to the Investigators’ normal practices. Dose adjustments in 
NSAIDs cannot be made within 24 hours of a study visit. Aspirin may be 
taken to reduce cardiovascular risk, not to exceed 350 mg/day. 

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Treatment 
Restriction 
Analgesics (other than 
NSAIDs) 
Analgesics up to the maximum recommended doses may be used for pain as 
required. However, patients should not take analgesics within 24 hours prior 
to a visit where clinical efficacy assessments are performed and recorded. 
Non-pharmacological 
treatments (e.g., physical 
therapy) 
Permitted freely. 
 
Example washout periods for prior medications are presented in Table 6. 
Table 6 
Example of Washout Periods 
Treatment 
Washout period 
Leflunomide 
12 weeks* 
Abatacept 
Adalimumab 
Certolizumab 
Infliximab 
Golimumab 
Tocilizumab 
Hydroxychloroquine 
Tofacitinib 
8 weeks 
8 weeks 
8 weeks 
8 weeks 
8 weeks 
8 weeks 
8 weeks 
8 weeks 
Etanercept 
Anakinra 
Sulfasalazine 
Azathioprine 
4 weeks 
4 weeks 
4 weeks 
4 weeks 
* At least 12 weeks or a minimum of 4 weeks prior to the beginning of Part A if after 11 days of standard 
cholestyramine washout. 
 
 

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5 
REPORTING OF ADVERSE EVENTS 
5.1 
Adverse Event (AE) 
An AE is defined as “any untoward medical occurrence in a patient or clinical investigation 
patient administered a pharmaceutical product and which does not necessarily have to have 
a causal relationship with this treatment.” 
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom, or disease temporally associated with the use 
of a medicinal product, whether or not considered related to the medicinal product. 
5.2 
Serious Adverse Events (SAE) 
A SAE is any untoward medical occurrence that: 
• results in death; 
• is life-threatening. The term “life-threatening event” refers to an event in which the 
patient was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe; 
• requires inpatient hospitalization or prolongation of existing hospitalization: Hospital 
admissions and/or surgical operations planned before or during a study are not 
considered AEs if the illness or disease existed before the subject was enrolled in the 
study, provided that it did not deteriorate in an unexpected way during the study.  
Hospitalizations required purely for the purposes of performing study procedures are 
not SAEs; 
• results in persistent or significant disability/incapacity; 
• is a congenital anomaly/birth defect, which includes ectopic pregnancy, spontaneous 
abortion, intrauterine fetal demise, or neonatal death.  In addition, infant death after 1 
month should be reported as a SAE when the investigator assesses the infant death as 
related or possibly related to exposure to investigational product; 
• any other medically or scientifically significant event that, although it may not be 
immediately life-threatening or result in death or hospitalization, endangers the 
patient or requires that appropriate measures be taken to avoid any of the events listed 
above (e.g., bronchospasm requiring intensive treatment, blood dyscrasia or 
convulsion not requiring hospitalization, drug dependency or abuse). 

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5.3 
Adverse Drug Reactions 
An adverse drug reaction (ADR) is defined as a noxious and unintended response to a 
medicinal product related to any dose. 
AEs which meet all of the following criteria:  
• 
Serious  
• 
Unexpected (i.e. is not consistent with the currently applicable Investigator Brochure 
list of AEs)  
• 
There is at least a reasonable possibility that there is a causal relationship between 
the event and the medicinal product  
will be classified as Suspected Unexpected Serious Adverse Reactions (SUSARs) and 
should be reported to the relevant ethics committee and to the relevant Health Authorities 
for expedited reporting in accordance with Directive 2001/20/EC or as per national 
regulatory requirements in participating countries. 
5.4 
Adverse Event of Special Interest (AESI) 
An AE of special interest (AESI) is one of scientific and medical interest specific to 
understanding of the study drug and may require close monitoring and rapid 
communication by the Investigator to the Sponsor and/or QuintilesIMS. An AESI may be 
serious or non-serious. The rapid reporting of AESIs allows ongoing surveillance of these 
events in order to characterize and understand them in association with the use of this study 
drug. All AESIs must be reported in an expedited manner similar to SAEs (i.e., non-serious 
AESIs also must follow serious timelines). 
The following will be considered AESIs in this study:  PML, hepatitis reactivation, 
mucocutaneous reactions, infusion reactions, anaphylactic reactions, and serious infections. 
5.4.1 
Progressive Multifocal Leukoencephalopathy 
The Investigator is required to monitor the patients throughout the study for any new or 
worsening neurological symptoms or signs that may be suggestive of PML. Typical 
symptoms are diverse, and include cognitive or visual disorders, hemiparesis, confusion, 
and behavioral disorders. If a patient develops new or worsening neurological signs or 
symptoms, he/she will be evaluated for PML. Neurological warning signs include:  
• Major changes in vision, unusual eye movements. 
• Loss of balance or coordination. 

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• Disorientation or confusion. 
If PML is suspected, further dosing must be suspended until PML has been excluded. 
Consultation with a neurologist should be considered as clinically indicated. If any doubt 
exists, further evaluation, including an MRI scan (preferably with contrast), cerebrospinal 
fluid testing for John Cunningham viral deoxyribonucleic acid (DNA), and repeat 
neurological assessments, should be considered. 
The Sponsor must be notified of any suspected PML cases within 24 hours of awareness 
according to the procedure outlined in the Site Manual. If any patient reports PML during 
the study, the patient must be discontinued from study treatment and followed up until 
resolution at the discretion of the Investigator. 
5.4.2 
Hepatitis Reactivation 
If a patient develops reactivation of HBV while on rituximab, the patient should be 
managed as outlined in Section 3.2.7. 
5.4.3 
Serious Infections 
Serious infections are defined as infections requiring i.v. antibiotics or meeting the 
definition of an SAE. 
5.4.4 
Mucocutaneous Reactions 
Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with 
rituximab. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, 
lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset 
of these reactions has been variable and includes reports with onset on the first day of 
rituximab exposure. Rituximab should be discontinued in patients who experience a severe 
mucocutaneous reaction. The safety of re-administration of rituximab to patients with 
severe mucocutaneous reactions has not been determined. 
5.4.5 
Infusion Reactions 
An acute onset infusion reaction generally occurs within 24 hours of infusion of the study 
drug. Rituximab can cause severe, including fatal, infusion reactions. Severe reactions 
typically occur during the first infusion with time to onset of 30 to 120 minutes. Rituximab-
induced infusion reactions and sequelae include urticaria, hypotension, angioedema, 
hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, 

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myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or 
death. 
Medical management (e.g., glucocorticoids, epinephrine, bronchodilators, or oxygen) for 
infusion reactions must be instituted as needed. Depending on the severity of the infusion 
reaction and the required interventions, rituximab may be temporarily or permanently 
discontinued. Resume infusion at a minimum 50% reduction in rate after symptoms have 
resolved. Closely monitor patients with pre-existing cardiac or pulmonary conditions. 
Infusion reactions should be reported in the eCRF as AEs, or SAEs if it meets the 
seriousness criteria, with the event term “infusion-related reaction”. The signs and 
symptoms of the infusion reaction should be described in the appropriate part of the eCRF. 
Please refer also to Section 5.4.6 (Anaphylaxis). 
5.4.6 
Anaphylaxis  
Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. 
Diagnostic criteria are outlined in Table 7.  
Table 7 
Clinical Criteria for Diagnosing Anaphylaxis  
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both 
(e.g., generalized hives, pruritus or flushing, swollen lips/tongue/uvula) 
AND AT LEAST ONE OF THE FOLLOWING 
a. 
Respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory 
flow (PEF), hypoxemia) 
b. 
Reduced blood pressure or associated symptoms of end-organ dysfunction (e.g., hypotonia 
[collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient 
(minutes to several hours): 
a. 
Involvement of the skin/mucosal tissue (e.g., generalized hives, itch/flush, swollen 
lips/tongue/uvula) 
b. 
Respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, reduced PEF, hypoxemia) 
c. 
Reduced blood pressure or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence) 
d. 
Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
3. Reduced blood pressure after exposure to known allergen for that patient (minutes to several hours): 
a. 
Infants and children: low systolic blood pressure (age specific) or greater than 30% decrease in 
systolic blood pressure 
b. 
Adults: systolic blood pressure of less than 90 mm Hg or greater than 30% decrease from that 
person’s baseline 
 
As with the treatment of any critically ill patient, the treatment of anaphylaxis begins with 
a rapid assessment and maintenance of airway, breathing, and circulation. When a patient 
fulfills any of the 3 criteria of anaphylaxis outlined above, the patient should receive 

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epinephrine immediately because epinephrine is the treatment of choice in anaphylaxis. 
There undoubtedly will be patients who present with symptoms not yet fulfilling the criteria 
of anaphylaxis yet in whom it would be appropriate to initiate therapy with epinephrine, 
such as a patient with a history of near-fatal anaphylaxis to peanut who ingested peanut 
and within minutes is experiencing urticaria and generalized flushing. Subsequent 
interventions are determined on the basis of the clinical course and response to epinephrine.  
Anaphylaxis should be reported in the eCRF as AE or SAE if it meets the seriousness 
criteria, with the event term “anaphylaxis”. The signs and symptoms of the anaphylaxis 
should be described in the appropriate part of the eCRF. 
5.5 
Pregnancy 
Any pregnancy in a female patient should be reported to the Sponsor from the time the 
patient signed the ICF until 12 months after the last infusion of study drug. Pregnancy 
reports should be submitted to the Sponsor within 24 hours of awareness of the 
pregnancy by the Investigator as per the reporting procedure outlined in the Site Manual. 
Pregnancy occurring in the partner of a male patient participating in the study should be 
reported to the Investigator and the Sponsor following the same procedure for pregnancy 
in the female patient. The partner should be counseled, the risks of continuing the 
pregnancy discussed, as well as the possible effects on the fetus. Monitoring of the 
pregnant female should continue until conclusion of the pregnancy. The pregnant partner 
will need to sign an Authorization for “Use and Disclosure of Pregnancy Health 
Information” (a sort of specific consent form) to allow for follow-up of her pregnancy. 
Although pregnancy is not an AE, all pregnancies must be followed until 6 to 8 weeks 
after the estimated date of delivery to determine their outcome. The pregnancy outcome 
will be notified to the Sponsor by submitting a follow-up pregnancy report form. If the 
outcome of the pregnancy meets the SAE criteria then the Investigator should report this 
case according to the SAE reporting process (Section 5.9). 
5.6 
Overdose 
An overdose of SAIT101 or MabThera® or Rituxan® is defined as an infusion of >1,000 
mg during a single infusion in this study. 
In case of overdose, the patient must be managed for any AE caused by overdose as per 
standard of care at the site or symptomatically and the case discussed with the Clinical 
Research Organization and Sponsor medical advisor for decision on treatment 
discontinuation of the patient.  

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When an overdose is reported during the course of the study, the patient should be 
monitored closely and evaluated by the Investigator to determine whether the patient 
experiences any AE or SAE as a result of the overdose. 
Overdoses will be reported as protocol deviations. If the overdose is associated with an 
AE/SAE, the site should follow the AE/SAE reporting procedures described in Section 5 
of this protocol and as per the eCRF completion guidelines. 
5.7 
Changes in Clinical Laboratory Assessment Results 
It is the responsibility of the Investigator or Sub-investigator to review the results of all 
laboratory tests as they become available. For each abnormal laboratory test result, the 
Investigator or Sub-investigator needs to ascertain if this is an abnormal (i.e., clinically 
significant) change from Baseline for that individual patient. This determination, 
however, does not necessarily need to be made the first time an abnormal value is 
observed. The Investigator or Sub-investigator may repeat the laboratory test or conduct 
additional tests to verify the results of the original clinical laboratory tests. If this 
laboratory value is determined by the Investigator or Sub-investigator to be a clinically 
significant change from Baseline for that patient, it is considered to be an AE. 
5.8 
Recording of Adverse Events 
Relationship 
The causal relationship of the study drug to all AEs occurring after the start of study drug 
infusion will be assessed as one of the following two categories. 
1. Unrelated (AE for which relationship to the study drug can be ruled out). A reasonable 
possibility of the AE occurring is considered highly unlikely for one of the following 
reasons: 
• Occurrence of the event can be expected based on the patient’s underlying disease, 
concurrent illness, or medical history. 
• Occurrence of the event can be expected based on the patient’s age, gender, or other 
characteristics. 
• There is no apparent temporal relationship between study drug infusion and 
occurrence of the event. Example: Occurrence of an AE after a considerable length 
of time has elapsed since completion or discontinuation of study drug infusion. 

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• A causal relationship is considered highly unlikely from the status of study drug 
infusion and the course of the event. Example: An AE that recovers without 
treatment while continuing study drug infusion (excluding cases in which the 
patient becomes accustomed to the condition through continued study drug 
infusion). 
• The event is considered to be the effect of a concomitant drug. 
• The event is considered to be incidental (accident, incidental symptom, etc). 
Example: Occurrence of a femoral fracture resulting from a traffic accident. 
• A causal relationship of study drug infusion can be medically ruled out for some 
other reason. 
2. Related (AE for which relationship to the study drug cannot be ruled out). A reasonable 
possibility of the AE occurring is considered likely for one of the following reasons: 
• Occurrence of the event can be expected from the pharmacological or toxicological 
action of the study drug. Examples: Occurrence of pancytopenia when an effect on 
the hematopoietic system has been observed in non-clinical studies, or occurrence 
of dehydration with a study drug that has a diuretic action.  
• The same event was previously observed in non-clinical studies or clinical studies. 
Example: Occurrence of an event that was observed at a high incidence in Phase I 
studies. 
• A temporal relationship between study drug infusion and occurrence of the event is 
suspected. Example: Occurrence of allergic dermatitis several days after the start of 
study drug infusion. 
• A causal relationship is suspected from the outcome of the event following 
discontinuation or dose reduction of the study drug. Example: Rapid recovery of 
nausea following discontinuation of study drug infusion. 
• A causal relationship of study drug infusion cannot be medically ruled out for some 
other reason. 
Severity 

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AEs will be graded on a 3-point scale. The intensity of an adverse experience is defined as 
follows. 
1 = Mild: Discomfort noticed, but no disruption to daily activity. 
2 = Moderate: Discomfort sufficient to reduce or affect normal daily activity. 
3 = Severe: Inability to work or perform normal daily activity. 
 
5.9 
Eliciting and Reporting Adverse Events 
After the patient has signed the ICF, but prior to initiation of study drug, only SAEs caused 
by a protocol-mandated procedure should be reported (e.g., SAEs related to invasive 
procedures such as biopsies). The Investigator or Sub-investigator will periodically assess 
patients for the occurrence of AEs and record AE information offered spontaneously by 
patients. To avoid bias in eliciting AEs, patients should be asked the following non-leading 
question:  "How have you felt since your last visit?"   
The QuintilesIMS must be notified of any SAEs within 24 hours of awareness according 
to the procedure outlined in the Site Manual. 
5.10 
Follow-up of Adverse Events 
Any AEs will be followed up to resolution. Resolution means that the patient has returned 
to a Baseline state of health or the Investigator does not expect any further improvement 
or worsening of the AE. 
5.11 
Reporting of Serious Adverse Events to Regulatory Authorities 
and Investigators 
Investigators will be notified by the Sponsor or QuintilesIMS of all SAEs that require 
prompt submission to their IRB or IEC.  Investigators should provide written 
documentation of IRB/IEC notification for each report to the Sponsor or QuintilesIMS.  
The Sponsor or QuintilesIMS will ensure that SAEs are reported to the appropriate 
regulatory authorities in accordance with the local regulations. 
All contact details and detail instructions for SAE reporting will be provided in the site 
manual, and SAE form completion instruction. 
 

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6 
STATISTICS 
6.1 
Sample Size 
The PK parameters reported from a recent study with rituximab in patients with RA 
revealed a percentage coefficient of variation (CV%) ranging from 26.3% for Cmax to 
37.3% for AUC0-∞.12 
When the evaluable sample size in each group is 84, a three group design will have 81% 
power to reject both the null hypothesis that the ratio of test to standard geometrics means 
is below 0.800, and the null hypothesis that the ratio of test to standard geometrics means 
is above 1.250 (i.e., that the test and standard are not equivalent), in favor of the 
alternative hypothesis, that the means of the two groups are equivalent, assuming that the 
expected ratio of means is 1.000, that data will be analyzed in the log scale using analysis 
of variance (ANOVA) and that each one sided test is made at the 5% level. Each of the 
15 hypotheses tests (five co-primary endpoints × three pairwise comparisons (i.e., 
SAIT101 vs. MabThera®, SAIT101 vs. Rituxan®, MabThera® vs. Rituxan®)) are powered 
at 98% to 99.0% to yield 81% study-wide power. 
Approximately 282 patients (94 patients per group) will be randomized in order to yield a 
minimum of 84 patients per group to account for a presumed 10% withdrawal. 
This 94 patients in SAIT101 group and MabThera® group will provide 96% probability of 
declaring the equivalence in FAS with each one sided test at the 2.5% level, accounting for 
a presumed 1.0 standard deviation of DAS28 from the REFLEX study13, 14, and the 
equivalence margin of -0.6 to 0.6 chosen as the half of a clinical meaningful improvement 
of 1.2 in DAS28.16 Considering 18% withdraw from the REFLEX study, approximately 77 
patients per group will provide approximately 91% probability of declaring the equivalence 
in the PP set with the same above assumption. 
6.2 
Statistical Methods 
Categorical variables will be summarized by the number and percentage of patients in each 
category. Continuous variables will be summarized using N, mean, standard deviation (SD), 
median, minimum, and maximum values. 
For all efficacy analyses, patients will be analyzed under the treatment they were 
randomized to, even if the treatment actually received differs from the treatment the patient 
was randomized to receive. For all safety analyses, patients will be analyzed under the 
treatment they actually received. 

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Generally, the Baseline value to be used in any change from Baseline 
listings/summaries/graphical presentations or as a covariate in a statistical analysis is 
defined as the latest available pre-randomization value. If necessary, detailed Baseline 
definitions of specific parameters or assessments will be defined in the statistical analysis 
plan (SAP). 
6.2.1 
Analysis Sets 
6.2.1.1 
Pharmacokinetic Analysis Set 
The PK analysis set will include all patients who receive both planned doses of SAIT101 
or MabThera® or Rituxan®, have a measured drug serum concentration and have no major 
protocol deviations or violations thought to significantly affect the PK of the drug. Reasons 
for excluding patients from the PK Analysis set will be specified in the statistical analysis 
plan. 
Major protocol deviations or violations thought to significantly affect the PK of the drug 
include (but not limited to) missing dose or incorrect dose, sampling date and time not 
available, sample processing errors that might render a subject’s bioanalytical data to be 
inaccurate etc. Subjects with these issues will be reported in the study report.  
6.2.1.2 
Safety Analysis Set 
The Safety Analysis Set (SAF) will consist of all randomized patients who received at least 
one dose of study drug. 
Safety Analysis Set will be used as the basis for all safety analyses. 
6.2.1.3 
Full Analysis Set 
The Full Analysis Set (FAS) will consist of all randomized patients in accordance with the 
intended treatment arm, regardless of the treatment actually received. 
6.2.1.4 
Per Protocol Set 
In this study, patients who complete at least the first course of study drug in Part A and 
continue study treatment up to Week 24 will be included in the PP set. A patient may be 
excluded from the PP set for, but not limited to, any of the following conditions: 
• Patient does not meet inclusion/exclusion criteria. 
• Infusion of wrong study drug occurred. 

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• Patient did not receive both infusions of study drug (Day 1 and Day 15). 
• Intake of disallowed concomitant medication, patient to evaluation of clinical 
relevance of the intake. 
6.2.1.5 
Pharmacodynamic Analysis Set 
The PD analysis set will include all patients who receive both planned doses of SAIT101 
or MabThera® or Rituxan®, have at least one measured CD19+ count at scheduled time 
point postdose and have no major protocol deviations or violations thought to significantly 
affect the PD of the drug. 
6.2.2 
Patient Disposition 
The number and percentage of patients who were screened, and were randomized will be 
presented. For the patients who left the study prior to randomization, a summary will be 
presented for the reasons of screen failure. For the patients who were randomized or 
re-randomized at Week 24, summaries will be presented for the number and percentage of 
patients who completed the study, discontinued study drug (by reason for treatment 
discontinuation), and withdrew early from the study (by reason for study withdrawal).  
6.2.3 
Demographic and Baseline Characteristics Analysis 
Patient demographics and Baseline characteristics will be summarized by treatment group 
for all randomized patients. Continuous variables (e.g., age, weight, height, disease 
duration, duration of MTX use, swollen and tender joint count, patient and physician global 
assessments VAS, patient pain assessment VAS) will be summarized with descriptive 
statistics (N, mean, SD, median, minimum, maximum). Qualitative variables (e.g., gender, 
race, ethnicity, number of previous DMARDs) will be summarized with counts and 
percentages.  
Relevant medical history and continuing medical conditions will be summarized by 
treatment group for all randomized patients.  
6.3 
Pharmacokinetic Analysis 
The PK analysis will be performed on the PK Analysis Set. The PK parameters, AUC0-t, 
AUC0-, AUC0-d15, Cmax after the second infusion on Day 15 and Ctrough before the second 
infusion on Day 15 will be considered the primary PK endpoints. All other PK endpoints 
will be regarded as secondary. 

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The statistical analysis of the loge-transformed primary endpoints will be based on an 
analysis of variance model. Covariates may be added to the planned analysis. The 
difference in least squares means between each of the three pairs (i.e., SAIT101 vs. 
MabThera®, SAIT101 vs. Rituxan®, MabThera®  vs. Rituxan®) and the associated 90% CI 
will be determined. Back transformation will provide the ratio of geometric means and 
90% CI for this ratio. Equivalence will be concluded if the 90% CI for the ratio of geometric 
means of each of the three pairs for each primary endpoint are completely contained within 
the acceptance interval of 0.8 to 1.25.  
Descriptive statistics (N, mean, SD, %CV, minimum, median, and maximum) will be used 
to summarize serum concentration data by treatment at each planned sampling time point. 
Concentrations that are below the lower limit of quantitation will be assigned a value of 0 
for the purposes of computing descriptive statistics. Serum PK parameters calculated from 
the concentration-time data will also be summarized by treatment using descriptive 
statistics (N, mean, SD, %CV, geometric mean, geometric %CV, minimum, median, 
maximum). 
Plots of the mean and individual serum rituximab concentrations over time for SAIT101 
and MabThera® and Rituxan® will be provided following i.v. infusions. 
6.4 
Efficacy Analysis 
The continuous efficacy endpoint will be analyzed using Analysis of Covariance 
(ANCOVA) using treatment (SAIT101 and MabThera®) as model factor and Baseline 
DAS28 as covariate. The Difference between SAIT101 and MabThera® in DAS28 change 
from Baseline at Week 24 and the associated two-sided 95% CI will be determined. 
Equivalence will be concluded if the 95% CI for the mean difference for main efficacy 
endpoint is completely contained with the equivalence margin of -0.6 to 0.6. Both of the 
per protocol (PP) set and full analysis set (FAS) will be considered as the efficacy analysis 
population and the equivalence will be concluded only if the analyses of both PP set and 
FAS meet the equivalence criteria defined above. No missing data will be imputed for the 
efficacy analyses in FAS. The possibility of a treatment-by-baseline interaction may be 
explored as exploratory analyses. In addition, sensitivity analyses will be performed to 
assess the effect of missing Week 24 data and detailed in the SAP. 
Binary endpoints will be analyzed as for the proportion of patients achieving an ACR20 
response at Week 24. Two-sided 95% CI for the difference between SAIT101 and 

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MabThera® in the proportion of patients achieving an ACR20 response at Week 24 will be 
computed using the Wilson score method.  
All statistical comparisons for the secondary efficacy variables will be made using two 
sided tests at the 0.05 significance level. The 95% CIs of the difference between SAIT101 
and MabThera® will be computed. 
All efficacy endpoints will be analyzed on the both PP set and FAS. 
6.5 
Pharmacodynamic Analysis 
A listing of PD blood sample collection times by individual, as well as derived sampling 
time deviations, will be provided. 
Area under the depletion-time curve of CD19+ B cells depletion from time 0 across  
24 weeks (AUC0-w24), depletion in CD19+ B cell count (defined as a CD19+ B cell count 
below 14/μL) will be descriptively compared between the test and comparator groups. 
Observed, change from Baseline, and percent change from Baseline in CD19+ B cell 
counts, and depletion of CD19+ B cell counts will be summarized using descriptive 
statistics. Baseline is defined as the CD19+ B cell count on Day 1 (immediately before the 
start of the first infusion). 
Observed change from Baseline in IgG, IgM, and IgA levels at Weeks 8, 16, 24, 36 and 52 
and observed change from Baseline in CRP levels at Weeks 8, 16, 24, 36, and 52 will be 
summarized using descriptive statistics. 
6.6 
Safety Analysis 
6.6.1 
Adverse Events 
All reported terms for AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). No statistical testing will be performed for AEs. Adverse events 
will be summarized by the number and percentage of patients experiencing events by 
System Organ Class (SOC), Preferred Term (PT) and severity. 
A listing of all ADRs will be presented. The listing will present SOC and PT of the ADR, 
severity, action taken, outcome, start and stop date of the ADR, study day of onset of the 
ADR, age, race, and gender. 
The incidence of AESI in the study will be summarized in the similar way as ADRs. 

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A listing will be presented for all AEs with an outcome of death. Narratives will be 
prepared for all patients who died.  
The incidence of all SAEs will be summarized by SOC and PT, if there are a sufficient 
number of SAEs to warrant such a presentation. A listing of all SAEs with an onset date 
prior to receiving study drug will also be presented. These listings will present SOC and 
PT of the SAE, severity, action taken, outcome, and relationship of the SAE to study drug, 
start and stop date of the SAE, study day of onset of the SAE, age, race, and gender.  
Narratives will be prepared for all patients with a SAE, including deaths. 
Narratives will be prepared for patients who permanently discontinued from study drug 
due to an AE. 
6.6.2 
Clinical Laboratory Tests 
Summary statistics will be presented for observed values of all hematology, chemistry, and 
urinalysis parameters at each visit with laboratory assessment and at End-of-Study, and 
also for changes from Baseline to each post-baseline visit with laboratory assessment and 
End-of-Study. 
Shifts (abnormal low, normal, and abnormal high) for changes from Baseline to each 
post-baseline visit with laboratory assessment and End-of-Study, based on normal ranges, 
will be presented for hematology, chemistry and urinalysis parameters. 
The incidence of laboratory abnormalities overall will also be presented. Where applicable, 
the incidence of abnormal values will be presented separately by whether the value is 
abnormally high or low. Patients will be counted at most once for a high or low abnormality 
for each laboratory parameter. 
Listings of all laboratory abnormalities will be presented (separately for hematology and 
blood chemistry parameters). Laboratory ranges used to identify abnormal results will be 
provided by the central laboratory. 
Listings of observed values of all hematology, chemistry, and urinalysis parameters, as 
well as pregnancy test results will be presented for all randomized patients. 

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6.6.3 
Concomitant Medication 
The incidence of concomitant medications will be summarized for the Safety Analysis Set 
by generic term coded with the World Health Organization-Drug Dictionary (WHO-DD) 
Enhanced, overall and by treatment group. 
To allow assessment of concomitant medication that might affect the efficacy outcomes, 
counts will be presented for each treatment group at each visit of patients receiving any 
rescue medication at that visit; counts of patients receiving any rescue medication will also 
be presented during the study. Rescue medication is defined as the use of non-biologic 
DMARDs, after Week 16 of the study. Time to first incidence of rescue medication after 
Week 16 of the study will be estimated for each treatment group and presented using 
Kaplan-Meier methods. Kaplan-Meier plots will also be presented. In addition, percentiles 
of time without rescue medication will be presented.  
6.6.4 
Vital Signs, ECG Findings, and Physical Examination 
Summary statistics will be presented for results at each visit with vital sign assessments 
and at End-of-Study, as well as for change from Baseline results to each visit with vital 
sign assessments and End-of-Study for systolic and diastolic blood pressure, and pulse rate. 
The overall incidence of vital sign abnormalities will also be presented. Patients will be 
counted at most once for an abnormality for each vital sign parameter. 
A listing of all vital sign abnormalities will be presented for the safety set. Criteria used to 
define abnormal vital sign results will be defined in the SAP. Shifts (abnormal low, normal, 
and abnormal high) for changes from Baseline to each post-baseline visit with vital sign 
assessments and End-of-Study, based on normal ranges, will be presented for vital sign 
parameters. 
A table and listing of any ECG abnormalities at Screening will be presented for the Safety 
Analysis Set. 
A listing of physical examination abnormalities will be presented for the Safety Analysis 
Set. 
6.6.5 
B Cell Recovery 
B cell recovery is defined as “peripheral B cell counts that have returned to Baseline values 
or the lower limit of normal, whichever is lower”. The incidence of B cell recovery and 
CD19+ B cell count per patient will be summarized at each visit after Week 24, overall and 

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by treatment group. The follow-up of patients will be up to Week 52 from the start date of 
the first course of treatment in order to monitor B cell recovery.  
6.7 
Immunogenicity Analysis 
Incidence of HACA and neutralizing antibody and summary of counts of antibodies per 
patient at prior first dose on Day 1 and at Week 1, 2, 4, 12, 16, 24, 36, and 52 will be 
summarized overall and by treatment group.  
6.8 
Other Analysis 
The exploratory subgroup analysis will be performed. The subgroups to be used for this 
analysis will be based on the results of analysis of PK, PD, efficacy, safety, 
immunogenicity and concomitant medication. 
6.9 
Interim Analysis 
Interim analysis of 10 patients per group (30 patients in total) of safety data collected up 
to Week 4 and 20 patients per group (60 patients in total) of safety data collected up to 
Week 12 are planned. Safety data will be handled by unblinded study team in CRO for 
interim analysis, and the safety report will be submitted to regulatory. The study will be 
unblinded at Week 24 and an interim CSR will be prepared based on the 24-week data of 
all patients. The investigators and patients will remain blinded to treatment assignment 
during the post Week 24 follow-up period.  
After review by DSMB, this analysis will be reported to health authorities upon request. 
6.10 
Safety Review 
An independent DSMB will be established to act in an advisory capacity to monitor patient 
data. The DSMB will review available study data at pre-specified time-points, as outlined 
in the DSMB charter. 
The details of the DSMB roles and responsibilities, the stopping rules for safety reasons 
and the logistics of the DSMB activities will be outlined in a DSMB charter. 
6.11 
Handling of Missing Values and Outliers 
No missing data will be imputed for the efficacy analyses in FAS. Treatment of missing 
values, and outliers, and methodology will be detailed in a separate SAP. 

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6.12 
Procedure for Reporting Deviations 
A protocol deviation is any change, divergence, or departure from the study design or 
procedure that is under the Investigator’s responsibility and oversight (as defined by 
regulations) without prior written IRB/IEC approval or favorable opinion of an appropriate 
amendment, and that does not have a major impact on the patient’s rights, safety, or well-
being, or on the integrity and authenticity of the study data. 
All deviations from the approved protocol must be documented and notified to the Sponsor 
or CRO at the earliest. The Investigator should not deviate from the protocol, except for 
patient safety reasons, in which case the deviation must be reported to the Sponsor or CRO 
immediately. The Sponsor will not assume any resulting responsibility or liability from 
unapproved deviations. The Investigator, according to applicable regulations and the IEC 
established procedures, will inform the IEC of protocol deviations. 
All instances where the requirements of the study protocol are not complied with will be 
captured in the clinical trial management system (CTMS) and the study monitor will 
prepare a Protocol Deviation/Violation Log. Corresponding patients may be discontinued 
from the study treatment at the discretion of the Sponsor/designee. Deviations from the 
study protocol should not be made other than as part of a protocol amendment. An 
amendment must be agreed upon by the Sponsor, but not implemented until written 
IRB/IEC approval is obtained, except where necessary to eliminate an immediate hazard 
to study patients or when the change(s) involves only logistical or administrative aspects. 
Protocol deviations/violations and the reason why they occurred will be documented in the 
clinical study report (CSR). 
 
 

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7 
 MANAGEMENT OF THE INVESTIGATIONAL MEDICINAL 
PRODUCT 
7.1 
Investigational Medicinal Product Identification 
SAIT101, Rituxan® and MabThera® will be provided in sterile, preservative-free, 
non-pyrogenic, single-use vials containing 500 mg of rituximab per 50 mL. Two vials will 
be used per infusion (1,000 mg per 100 mL) with each carton of study drug containing two 
50 mL vials of either SAIT101, Rituxan® or MabThera®.  
The SAIT101, Rituxan® and MabThera® vials will be different in size. Therefore, site staff 
managing medication preparation will be unblinded.  
7.2 
Packaging and Labeling 
Each carton and medication vial will be labelled with all the required information according 
to local regulations, including the Protocol Number (AGB001) and a unique identifier 
(Med ID) in a blinded manner. This will be programmed into the IXRS. At each infusion 
visit, the IXRS will assign the correct vial for the allocated treatment group and visit and 
the Med ID will be linked to an individual patient. The Med ID is assigned by the IXRS.  
Any used and unused product or waste material should be disposed of in accordance with 
local requirements, when certificates of destruction are available, or in case not possible, 
centrally as per Sponsor guidance. 
7.3 
Storage 
Study drugs will be stored in a secure area according to local regulations. Access should 
be strictly limited to unblinded study personnel (e.g., pharmacist). It is the responsibility 
of the Investigator, Sub-investigator, or authorized person to ensure that study drugs are 
only administered to study patients.  
All study drugs must be kept in a secure place under appropriate storage conditions. The 
medication vials must be stored in a refrigerator at a controlled temperature (2 to 8°C) and 
handled according to GCP. Vials should be kept in the outer carton in order to protect it 
from light. A temperature log must be kept, on which the storage temperature of the study 
drug is recorded at least once a day. The study drug, SAIT101, Rituxan® and MabThera®, 
must be kept strictly separate and in a different location than commercially available 
product at all times. Additional details regarding the storage and handling of the study 
drugs will be provided to the study centers. 

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7.4 
Preparation, Storage after Preparation and Administration 
Study drug preparation should be done using aseptic techniques. Sterile, non-pyrogenic, 
disposable containers, syringes, needles, stopcocks, and transfer tubing, etc., should be 
used during dosage preparation and infusion. 
An unblinded study team member should dilute the 2 vials of study drug (1,000 mg) 
assigned via IXRS to a calculated concentration of 1 to 4 mg/mL rituximab in a 250 mL, 
500 mL or 1,000 mL polyvinyl chloride (PVC) or polyethylene (PE) infusion bag 
containing either 0.9% sodium chloride or 5% glucose for injection. The unblinded study 
team member should clearly label the bag in a blinded manner with the study code and 
patient number and total dose of rituximab contained in the bag. 
The prepared infusion solutions of study drug are physically and chemically stable for 
24 hours at 2 to 8°C and subsequently 12 hours at room temperature. From a 
microbiological point of view, the prepared infusion solutions should be used immediately. 
If not used immediately, the prepared infusion solutions must be stored at 2 to 8°C for no 
longer than 24 hours. The prepared infusion solutions must be at room temperature prior 
to infusion. 
Infusion of the study drug should be performed according to the recommended infusion 
rates provided in Table 1. 
An infusion device capable of administering the study drug with rates varying from as low 
as 0.2 mL/minute up to 3.3 mL/minute would be suitable. This would be best achieved by 
a volumetric infusion pump. An in-line filter is not mandatory. 
More detailed instructions for study drug preparation, storage, and infusion will be 
provided in the Pharmacy Manual. 
7.5 
Accountability 
The unblinded study personnel (e.g., pharmacist) must maintain an inventory record of the 
study drug (including test or comparator drug) received, dispensed to blinded team and 
returned. The Investigator or delegate should maintain an inventory record of the study 
drug (including collection from pharmacy, infusion to the patient). Accountability assures 
the Regulatory Authorities and the Sponsor that the study drug will not be dispensed to any 
person who is not a patient under the terms and conditions set forth in this protocol. Records 
or logs must comply with applicable regulations and guidelines. 

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7.6 
Returns and Destruction 
Upon completion or termination of the study, all unused IMP may return to sponsor or may 
managed in accordance with the local regulation.. 
All study drug returned to the Sponsor must be accompanied by the appropriate 
documentation and be clearly identified by protocol number and study center number on 
the outermost shipping container. Returned supplies should be in the original containers 
(e.g., patient kits). The assigned study monitor should facilitate the return of unused and/or 
partially used study drug. 
If the study drug is authorized to be destroyed at the study center by the Sponsor, it is the 
Investigator’s responsibility to ensure that arrangements have been made for its disposal. 
Written authorization should be issued by the Sponsor, procedures for proper disposal 
should be established according to applicable regulations, guidelines and procedures, and 
appropriate records of the disposal should be documented and forwarded to the Sponsor. 

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8 
DATA HANDLING AND RECORD KEEPING 
8.1 
Source Documents 
Source documents are defined as the results of original observations and activities of a 
clinical investigation. Source documents will include, but are not limited to, medical 
records, electronic data, screening logs, and recorded data from automated instruments. All 
source documents pertaining to this study will be maintained by the study center or 
Investigators and, as defined in the ICF, made available for study-related monitoring, 
audits, IRB/IEC review and regulatory inspection by authorized persons. 
8.2 
Data Collection 
An eCRF will be created for all patients who provide consent to participate in the study. 
However, no data will be collected in case of screen failure. 
During each patient’s visit to the study center, the Investigator or Sub-investigator 
participating in the study will record source documents to document all significant 
observations. At a minimum, these records will contain: 
• Documentation of the informed consent process, including any revised consents; 
• The date of the visit and the corresponding Visit or Day in the study schedule; 
• General patient status remarks, including any significant medical findings i.e., the 
severity, frequency, duration, action taken, and outcome of any AEs and the 
Investigator's assessment of relationship to study drug must also be recorded; 
• Any changes in concomitant medications or dosages; 
• A general reference to the procedures completed;  
• The signature (or initials) and date of each Investigator (or Sub-investigator) who made 
an entry in the source document. 
In addition, any contact with the patient via telephone or other means that provides 
significant clinical information will also be documented in the source documents as 
described above. 
Information from the source documents will be LEGIBLY and promptly transcribed to 
eCRFs for transmission to the Sponsor. 

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1. Patient data entered directly into the database from the study center via a web browser 
will constitute the patient’s eCRF. 
2. An eCRF will be created for all patients who provide consent to participate in the 
study. However, no data will be collected in case of screen failure. 
3. Data generated within this clinical study will be handled according to the relevant SOPs 
of the data management and biostatistics departments of the Sponsor (or an appropriate 
company designated by the Sponsor to perform these activities). Patient data will be 
captured in an eCRF and reviewed by the monitor to check adherence to the protocol 
and to detect any data inconsistency or discrepancy. 
4. The Investigator or Sub-investigator will ensure that the clinical data are reported in 
the eCRF in accordance to the study protocol and eCRF completion guidelines created 
by Clinical and/or Data Management. 
5. Forms should be available during periodic visits by study monitors to enable review 
for completeness and acceptability. Any correction to the data entered into the eCRF 
must be carried out by the Investigator or study personnel. 
6. When data is entered into eCRFs from study centers, an automatic preliminary logical 
check will be applied. Additionally monitors and clinical data managers will review the 
eCRF for accuracy and can generate queries to the study personnel for resolution. The 
Investigator or Sub-investigator will make corrections as necessary. These changes 
may be made either on the initiative of the site personnel or in response to monitoring 
or data queries. Any changes to written data must be made using GCP corrections and 
any change to electronic data should be made in a system which can provide an audit 
trail.  
7. An audit trail history can be provided. All revisions made after the initial data entry is 
saved on the server, will be recorded within the system (date and time of revision, date 
and time of query, name of person making revision, name of person issuing query, pre- 
and post-revision data, reason for revision, etc.). 
8. After completion of all eCRF data revisions, and confirmation that the revision history 
and corrections of revision are correct and complete, the Investigator must provide 
his/her electronic signature in the relevant signature forms. Thereafter, eCRF in PDF 
files (CRF and audit trail) will be stored on CD-ROM or DVD-ROM and kept at the 
study center.  

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9. Coding: Medical/surgical history and underlying diseases and AEs will be coded using 
the Medical Dictionary for Regulatory Activities. Concomitant medications will be 
coded using the World Health Organization-Drug Dictionary Enhanced. The versions 
of coding dictionaries used will be stated in the study report. 
8.3 
File Management at the Study Center 
It is the responsibility of the Investigator to ensure that the study center file is maintained 
in accordance with Section 8 of the ICH-GCP Guideline and as required by applicable local 
regulations. The Investigator/institution should take measures to prevent accidental or 
premature destruction of these documents. 
8.4 
Records Retention at the Study Center 
Regulatory requirements for the archiving of records for this study necessitate that 
participating Investigators maintain detailed clinical data for the longest of the following 
periods: 
The Investigator must maintain essential study documents (protocol and protocol 
amendments, completed eCRFs, signed ICFs, relevant correspondence, and all other 
supporting documentation) 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 at least 2 years after the formal discontinuation of clinical 
development of the study drug. These documents should be retained for a longer period if 
required by the applicable regulatory requirements or the hospital, institution, or private 
practice in which the study is being conducted. Patient identification codes (patient names 
and corresponding study numbers) will be retained for this same period of time. These 
documents may be transferred to another responsible party, acceptable to the Sponsor, who 
agrees to abide by the retention policies. Written notification of transfer must be submitted 
to the Sponsor. The Investigator must contact the Sponsor prior to disposing of any study 
records.  
The Investigator must not dispose of any records relevant to this study without either 
written permission from the Sponsor or providing an opportunity for the Sponsor to collect 
such records. The Investigator shall take responsibility for maintaining adequate and 
accurate electronic or hard copy source documents of all observations and data generated 
during this study. Such documentation is patient to inspection by the Sponsor and relevant 
regulatory authorities. If the Investigator withdraws from the study (e.g., relocation, 
retirement), all study-related records should be transferred to a mutually agreed-upon 

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designee within a Sponsor-specified timeframe. Notice of such transfer will be given to the 
Sponsor in writing. 
 
 

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9 
QUALITY CONTROL AND QUALITY ASSURANCE  
9.1 
Monitoring 
The Sponsor has ethical, legal, and scientific obligations to follow this study carefully in a 
detailed and orderly manner in accordance with established research principles, the ICH-
GCP Guidelines, and applicable regulatory requirements and local laws. As part of a 
concerted effort to fulfill these obligations (maintain current personal knowledge of the 
progress of the study), the Sponsor's monitors will visit the study center during the study 
in addition to maintaining frequent telephone and written communication.  
9.2 
Auditing 
The Sponsor's Quality Management Unit (or representative) may conduct audits at the 
study centers. Audits will include, but are not limited to, study drug supply, presence of 
required documents, the informed consent process, and comparison of eCRFs with source 
documents. The Investigator agrees to participate in audits conducted at a reasonable time 
in a reasonable manner. 
9.3 
Inspection 
Regulatory authorities worldwide may inspect the study center during or after the study. 
The Investigator should contact the Sponsor immediately if this occurs, and must fully 
cooperate with the inspections conducted at a reasonable time in a reasonable manner. 

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ETHICS AND RESPONSIBILITY 
This study must be conducted in compliance with the ethical principles outlined in the 
Declaration of Helsinki, the ICH-GCP Guidelines, all applicable regulatory requirements, 
and the protocol. Each study center will seek approval by an IRB/IEC according to regional 
regulations. The IRB/IEC will investigate the ethical, scientific, and medical 
appropriateness of the study. Further, in preparing and handling eCRFs, the Investigator, 
Sub-investigator, and their study personnel must take measures to ensure adequate care in 
protecting patient privacy. To this end, patient numbers will be used to identify each patient. 

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CONFIDENTIALITY 
All information generated in this study must be considered highly confidential and must 
not be disclosed to any persons not directly concerned with the study without written prior 
permission from the Sponsor. Patient confidentiality requirements of the region(s) where 
the study is conducted must be met. However, authorized regulatory officials and Sponsor 
personnel (or their representatives) will be allowed full access to inspect and copy the 
records. All study drugs, patient bodily fluids, and/or other materials collected shall be used 
solely in accordance with this protocol, unless otherwise agreed to in writing by the 
Sponsor. 
Patients will be identified only unique patient numbers in the eCRFs. 
 

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PUBLICATION POLICY 
The Sponsor supports the efforts of health authorities to increase the transparency of 
medical research conducted in human patients and will register and maintain the 
information of clinical studies on a public registry program such as www.clinicaltrials.gov. 
The Sponsor is committed to the public disclosure of the results from clinical studies 
through posting on public clinical study data banks such as www.clinicalstudyresults.org. 
The results summary will be posted to the public clinical study data bank within one year 
after study completion, defined as the last patient’s last visit, whether or not the results are 
favorable to the study drug. For studies involving products whose development program is 
discontinued before approval, the Sponsor will post the results within one year after such 
discontinuation. The Sponsor will comply with the guidelines of regulatory authorities with 
regards to public registration and disclosure of clinical study data. 
The Sponsor has no objection to publication by the Investigator of any information 
collected or generated by the Investigator, whether or not the results are favorable to the 
study drug. However, to ensure against inadvertent disclosure of confidential information 
or unprotected inventions, the Investigator will provide the Sponsor an opportunity to 
review any proposed publication or other type of disclosure (poster presentation, invited 
speaker or guest lecturer presentation, etc.) before it is submitted or otherwise disclosed.  
If the study is part of a multi-center study, the Investigator agrees that the first publication 
is to be a joint publication covering all centers. Results from subsets should not be 
published in advance or without clear reference to the entire primary data. Authors will be 
the Sponsor, Coordinating Investigator and those who have made the most significant 
contribution to the overall success of the study. This contribution will be assessed, in part 
but not entirely, in terms of number of patients enrolled and will be reviewed at the end of 
the study by the Sponsor. In the event of any disagreement in the content of any publication, 
both the Investigator’s and the Sponsor’s opinion will be fairly and sufficiently represented 
in the publication.  
An external CRO or laboratory involved in the conduct of the study has no publication 
rights regarding the study. 
If the Investigator wishes to independently publish/present any results from the study, the 
draft manuscript, abstract or presentation must be submitted in writing to the Sponsor for 
comment at least 60 days prior to submission. Comments will be given within 60 days from 
receipt of the draft manuscript. The Investigator will comply with requests from the 
Sponsor to delete references to its confidential information (other than the study results) in 

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any paper, abstract or presentation. If any patent action is required to protect intellectual 
property rights, the Investigator agrees to withhold publication or presentation to allow 
sufficient time for the Sponsor. 
Publication of study results is also provided for in the Clinical Study Agreement between 
the Sponsor and the institution.  
 

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AMENDMENT POLICY 
The Investigator will not make any changes to this protocol without prior written consent 
from the Sponsor and subsequent approval by the IRB/IEC. Any permanent change to the 
protocol, whether it is an overall change or a change for specific study centers, must be 
handled as a protocol amendment. Any amendment to the protocol that appears indicated 
as the study progresses will be fully discussed by the Investigator(s) and the Sponsor. If 
agreement is reached regarding the need for an amendment, it will be written by the 
Sponsor. The written amendment must be submitted to the chairman of the IRB/IEC 
identified with this responsibility. Except for “administrative” or “non-substantial” 
amendments, Investigators must await IRB/IEC approval of protocol amendments before 
implementing the change(s). Administrative amendments are defined as amendments that 
have no effect on the safety of the research patients, scope of the investigation, conduct or 
management of the study, quality, the scientific value of the study, or the quality or safety 
of the study drug used in the study. A protocol change intended to eliminate an apparent 
immediate hazard to patients should be implemented immediately, and the IRB/IEC should 
be notified according to the provisions specified by each IRB/IEC. The Sponsor will ensure 
protocol amendments are submitted to the applicable regulatory agencies. 
When, in the judgment of the chairman of the IRB/IEC, the Investigators and/or the 
Sponsor, the amendment to the protocol substantially alters the study design and/or 
increases the potential risk to the patient, the currently approved written ICF will require 
similar modification. In such cases, repeat informed consent will be obtained from patients 
enrolled in the study before expecting continued participation. 

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14 
REFERENCES 
1. Ku IA, Imboden JB, Hsue PY, Ganz P. Rheumatoid arthritis: model of systemic 
inflammation driving atherosclerosis. Circ J, 2009; 73(6): 977-85. 
2. Scott DL. Early rheumatoid arthritis. Br Med Bull, 2007. 81-82: 97-114. 
3. Silman AJ, Pearson JE.  Epidemiology and genetics of rheumatoid arthritis. Arthritis 
Res, 2002; 4: 265-72. 
4. MabThera®: European Public Assessment Report – EMEA/H/C/259/II/0039, Variation, 
29/09/2006. 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Assessment_Report_-_Variation/human/000165/WC500025822.pdf. 
5. MabThera®: European Public Assessment Report – EMEA/H/C/000165/II/0065, 
Variation, 
25/10/2010.  
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Assessment_Report_-_Variation/human/000165/WC500099488.pdf. 
6. MabThera®: European Public Assessment Report – Summary of Product 
Characteristics, 
18/01/2011.  
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/000165/WC500025821.pdf. 
7. FDA label for Rituxan® (rituximab), revised 08/2014.  Retrieved Jan 30, 2015, from 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/103705s5432lbl.pdf 
8. Investigator’s Brochure.  SAIT101 (Rituximab). Archigen Biotech Ltd. Edition 
Number: 1.0 (draft).  Release date: Feb 2015.  
9. Kim WS, Kim SJ, Kang HJ, Kim JS, Choi CW, Lee SI, et al. Safety, Pharmacokinetic, 
Pharmacodynamic Profile and Efficacy of SAIT101, a Biosimilar Product of 
Rituximab in Patients with Diffuse Large B-Cell Lymphoma.  European Hematology 
Association 2012. Abstract 780-P 
10. Summary of product characteristics. EMA. (n.d.). Retrieved Jan 30, 2015 from 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/000165/WC500025821.pdf. 

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11. Rituxan® highlights of prescribing information. FDA. (2011, April 19). Retrieved Oct 
17, 
2011 
from 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103705s5311lbl.pdf. 
12. Ferdinand Breedveld, Sunil Agarwal, Ming Yin, Song Ren et al., Rituximab 
Pharmacokinetics in Patients With Rheumatoid Arthritis: B-Cell Levels Do Not 
Correlate With Clinical Response, The Journal of Clinical Pharmacology. 2007; 
47:1119-1128. 
13. Cohen SB1, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, 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; 
54: 2793-806 
14. Lopez-Olivo MA1, Amezaga Urruela M, McGahan L, Pollono EN, Suarez-Almazor 
ME. Rituximab for rheumatoid arthritis. Cochrane Database Syst Rev. 2015 Jan 20; 
1: CD007356. 
15. Vollenhoven RF, Emery P, Bingham CO.  Long-term safety of rituximab in rheumatoid 
arthritis: 9.5-year follow-up of the global clinical trial programme with a focus on 
adverse events of interest in RA patients; Ann Rheum Dis. 2013; 72: 1496-502.  
16. Pope JE, Haraoui B, Thorne JC, Vieira A, Poulin-Costello M, Keystone EC. The 
Canadian methotrexate and etanercept outcome study: a randomised trial of 
discontinuing versus continuing methotrexate after 6 months of etanercept and 
methotrexate therapy in rheumatoid arthritis. Ann Rheum Dis. 2014; 73: 2144-51. 
 
 
 
 

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15 
APPENDICES 

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Appendix 1 Signature of Investigator  
PROTOCOL TITLE:  A Randomized, Double-blind, Parallel Group, Multicenter 
Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of 
SAIT101 versus MabThera® versus Rituxan® in Patients with Rheumatoid Arthritis 
(RA). 
PROTOCOL NO: 
AGB001 
This protocol is a confidential communication of Archigen Biotech Ltd, I confirm that 
I have read this protocol, I understand it, and I will work according to this protocol. I 
will also work consistently with the ethical principles that have their origin in the 
Declaration of Helsinki and that are consistent with good clinical practices and the 
applicable laws and regulations. Acceptance of this document constitutes my agreement 
that no unpublished information contained herein will be published or disclosed without 
prior written approval from Archigen Biotech Ltd. 
Instructions to the Investigator:  Please SIGN and DATE this signature page. PRINT your name, title, 
and the name of the center in which the study will be conducted. Return the signed page to Archigen 
Biotech Ltd. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
Signature Principal Investigator:  
Printed Name: 
 
Date: 
 
Investigator Title: 
 
Name/Address  
 
and Contact Details:  
 
 
 
 
 
 

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Appendix 2 
Investigator Responsibilities 
Per Good Clinical Practices 21CFR312.53 
The Investigator: 
• Will conduct the study in accordance with the relevant, current protocol and will 
only make changes in the protocol after notifying the Sponsor, except when 
necessary to protect the safety, the rights, or welfare of patients; 
• Will comply with all requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements; 
• Will personally conduct or supervise the described investigation; 
• Will inform any potential patients that the drugs are being used for 
investigational purposes and will ensure that the requirements relating to 
obtaining informed consent and IRB/IEC review and approval are met; 
• Will report to the Sponsor adverse experiences that occur in the course of the 
investigation in accordance with 21CFR312.64; 
• Has read and understands the information in the Investigator’s Brochure, 
including the potential risks and side effects of the drug; and 
• Will ensure that all associates, colleagues, and employees assisting in the 
conduct of the study are informed about their obligations in meeting the above 
commitments. 
Per Good Clinical Practices 21CFR312.60 
General Responsibilities of Investigators: 
An Investigator is responsible for ensuring that an investigation is conducted according 
to the signed Investigator’s statement, the investigational plan, and applicable 
regulations; for protecting the rights, safety, and welfare of patients under the 
Investigator’s care; and for the control of drugs under investigation. An Investigator 
shall, in accordance with the provisions of part 50, obtain the informed consent of each 
human patient to whom the drug is administered. 

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Obligations of the Investigator 
The Investigator shall: 
• Obtain IEC/IRB approval to conduct the clinical study and report to the IEC/IRB 
as required. The IEC/IRB must assume continued responsibility for the study 
and review the research on at least an annual basis. 
• Maintain a file of all communications with the IEC/IRB. 
• If in the US, complete, sign, and return to CRO a Form FDA 1572 including a 
current CV for the Principal Investigator and Sub-investigator(s), if listed. 
• Conduct the study in strict adherence to the protocol. 
• Supervise the use of the investigational product as outlined in the protocol. The 
investigational product may only be provided by study personnel under the 
supervision of the Investigator. 
• Store the investigational product in a secure and locked area with limited access. 
The storage and custody of the investigational product are the responsibilities of 
the Investigator. 
• Maintain adequate records of the receipt and disposition of all investigational 
products (including dates, quantities and use by study patients). 
• Inform each patient of the risks and benefits of participating in the study and 
obtain a properly signed, dated and witnessed (if applicable) ICF for each patient 
before he or she begins any study-related procedures. 
• Document all adverse events on the medical records and the eCRFs; document 
all SAEs on the SAE form and immediately notify Sponsor or CRO within 24 
hours of awareness. 
• Report all SAEs to the IEC/IRB, as per IEC/IRB requirements. 
• Maintain a master log of all patients screened for the study and establish a 
system to alert study personnel of scheduled Follow-up visits; provide study 
personnel with a system for contacting study patients who do not return for 
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• Document and maintain accurate eCRFs for all patients. As required, sign forms 
ascertaining the accuracy of data recorded. Storage and custody of all study-
related records are the responsibility of the Investigator. 
• Retain the copies of the eCRFs, the original ICFs and all study-related 
documentation at the study center for a period of fifteen (15) years after 
termination of the study unless CRO authorizes, in writing, earlier destruction. 
Notify CRO before destroying any study records after the required retention 
period. 
It 
is 
the 
responsibility 
of 
the 
Sponsor 
to 
inform 
the 
Investigator/institution as to when these documents no longer need to be 
retained. 
• Make available all study patients’ records to study personnel and representatives 
from CRO, Sponsor, the IEC/IRB and FDA, or other Regulatory Agency 
personnel. 
• Return to Sponsor or their agent, study materials (which may include unused 
study supplies) following completion, discontinuation or suspension of the 
study. 
• Be thoroughly familiar with the properties of the investigational product as 
described in the Clinical Investigator’s Brochure. 
• Ensure that sufficient time is allotted to conduct and complete the study; ensure 
adequate study personnel and facilities are available for the duration of the 
study; and ensure that other studies do not divert essential patients or facilities 
from the study at hand. 
• Provide information to all study personnel involved with the study or with other 
elements of the patient’s management. 
• Notify CRO and Sponsor immediately in the event the blind is broken. 
• Ensure that the confidentiality of all information about patients and the 
information supplied by CRO and Sponsor is respected by all persons. 
• There is no obligation to complete financial disclosure forms and also no 
obligation to notify CRO or Sponsor of Regulatory inspections. 

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Appendix 3 American College of Rheumatology 1987 Revised Criteria for the 
Classification of Acute Arthritis of Rheumatoid Arthritis 
Criterion 
Definition 
Morning stiffness 
Morning stiffness in and around the joints, lasting at least 1 hour before 
maximal improvement. 
Arthritis of 3 or more 
joint areas 
At least 3 joint areas simultaneously have had soft tissue swelling of fluid 
(not bony overgrowth alone) observed by a physician. The 14 possible areas 
are right or left Proximal Interphalangeal (PIP), metacarpophalangeal 
(MCP), wrist, elbow, knee, ankle, and metatarsophalangeal (MTP) joints. 
Arthritis of hand joints 
At least 1 area swollen (as defined above) in a wrist, MCP, or PIP joint. 
Symmetric arthritis 
Simultaneous involvement of the same joint areas (as defined in 2) on both 
sides of the body (bilateral involvement of PIPs, MCPs, or MTPs is 
acceptable without absolute symmetry). 
Rheumatoid nodules 
Subcutaneous nodules, over bony prominences, or extensor surfaces, or in 
juxta-articular regions, observed by a physician. 
Serum rheumatoid 
factor 
Demonstration of abnormal amounts of serum rheumatoid factor by any 
method for which the result had been positive in <5% of normal control 
patients. 
Radiographic changes 
Radiographic changes typical of rheumatoid  arthritis on posteroanterior 
hand and wrist radiographs, which must include erosions or unequivocal 
bony decalcification localized in or most marked adjacent to the involved 
joints (osteoarthritis changes alone do not qualify). 
*For classification purposes, a patient shall be said to have rheumatoid arthritis if he/she has satisfied at 
least 4 of these 7 criteria. Criteria 1 through 4 must have been present for at least 6 weeks. Patients with 
2 clinical diagnoses are not excluded. Designation as classic, definite, or probable rheumatoid arthritis is 
not to be made. 
 
Reference: 
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al.   
The American Rheumatism Association 1987 revised criteria for the classification of 
rheumatoid arthritis.  Arthritis Rheum 1988; 31: 315-24. 

Protocol Number: AGB 001 
 
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Appendix 4 
Functional Class 
Classification of Global Functional Status in Rheumatoid Arthritis (as per ACR 
1991 Revised Criteria) 
Class I 
Able to perform usual activities of daily living (self-care, vocational, and 
avocational) 
Class II 
Able to perform 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 
* 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. 
 

Protocol Number: AGB 001 
 
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Appendix 5 
DAS28 and EULAR Response Criteria  
DAS28 is a formula combining: 
• 
Tender Joint Count (28 joints) 
• 
Swollen Joint Count (28 joints) 
• 
ESR (mm/hour) or CRP (mg/L)  
• 
General Health - Patient’s Global Assessment of Disease Activity (VAS) 
DAS28-CRP = [0.56 x √(TJC28) + 0.28*√(SJC28) + 0.36* lognat(CRP+1)] x 1.10 + 1.15 
A calculator is available online at the following website: 
http://www.das-score.nl/das28/DAScalculators/dasculators.html 
A representation and example is given below:

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Based on the DAS28 score, disease activity is classified as: 
≤ 2.6 
Remission 
>2.6 ≤ 3.2 
Low disease activity 
>3.2 ≤ 5.1 
Moderate disease activity 
>5.1 
High disease activity 
 
EULAR response Criteria: 
Based on the DAS, response criteria have been developed, the EULAR response criteria. 
The EULAR response criteria include not only change in disease activity but also current 
disease activity.  To be classified as responders, patients should have a significant change 
in DAS (at least >0.6 from Baseline) and also low current disease activity. Three categories 
are defined: good, moderate, and non-responders. 
The EULAR response criteria using the DAS28 
Improvement in DAS28 from Baseline  
 DAS28 at endpoint 
 > 1.2  
 >0.6 and ≤1.2  
 ≤0.6  
  ≤3.2  
 Good  
 Moderate  
 None  
 > 3.2 and ≤5.1  
 Moderate  
 None  
 None  
 > 5.1  
 Moderate  
 None  
 None