Conditions: Systemic Lupus Erythematosus (SLE)
Keywords: Standard of Care therapies Oral Corticosteroids Inmunosuppressants Immunomodulators Systemic Lupus Erythematosus B cell Activating Factor (BAFF) Inducible T cell costimulator ligand (ICOSL)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 244
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine if Rozibafusp Alfa could be a useful therapeutic agent in the current treatment landscape where subjects with SLE have ongoing disease activity despite treatment with standard of care therapies.

Detailed description:
This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized, placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and inadequate response to SOC therapies including oral corticosteroids (OCS), immunosuppressants and immunomodulators. Previous biologic use is allowed with an adequate washout period.

Arms:
arm 1: Investigational product solution in vial arm 2: Investigational product solution in vial arm 3: Investigational product solution in vial arm 4: Placebo Investigational product solution in vial

Interventions: intervention 1: Rozibafusp Alfa intervention 2: Placebo for Rozibafusp Alfa
Intervention descriptions: intervention 1: Rozibafusp Alfa will be presented in 5 mL glass vial intervention 2: Placebo for Rozibafusp Alfa will be presented in 5 mL glass vial

Protocol document:
Prot_000.pdf: 
Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 1 of 121 
 
CONFIDENTIAL 
FORM-001520, v.22, 05 February 2018 
 
Title Page 
Protocol Title: 
A Phase 2b Dose Ranging Study to Evaluate the 
Efficacy and Safety of Rozibafusp Alfa (AMG 570) 
in Subjects With Active Systemic Lupus 
Erythematosus (SLE) With Inadequate Response 
to Standard of Care (SOC) Therapy 
Short Protocol Title: 
Safety and Efficacy of AMG 570 in Subjects With 
Active Systemic Lupus Erythematosus (SLE) 
Protocol Number: 
20170588 
Investigational Product: 
Rozibafusp Alfa (AMG 570) 
Sponsor 
Name of Sponsor: Amgen Inc. 
Address: 
One Amgen Center Drive, 
Thousand Oaks, CA, 91320, USA 
Telephone 
Number: 
+1 (805) 447-1000 
Protocol 
Approver 
Name: 
MD 
Function: 
Vice President Global Development 
Key 
Sponsor 
Contact 
 
Name: 
MD, PhD 
Address: 
One Amgen Center Drive,  
Thousand Oaks, CA, 91320, USA 
Telephone 
Number: 
Email Address: 
EudraCT Number: 
2019-000328-16 
NCT Number: 
04058028 
Protocol Date: 
Document Version 
Date 
Original 
26 February 2019 
Amendment 1 
28 February 2020 
Amendment 2 
13 October 2020 
Superseding 
Amendment 2 
11 November 2020 
Amendment 3 
24 May 2022 
Version/Date: 
 
Data Element Standards Version 
6.1 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 2 of 121 
 
CONFIDENTIAL 
FORM-001520, v.22, 05 February 2018 
 
Confidentiality Notice 
This document contains confidential information of Amgen Inc. 
This document must not be disclosed to anyone other than the site study staff and 
members of the institutional review board/independent ethics committee/institutional 
scientific review board or equivalent. 
The information in this document cannot be used for any purpose other than the 
evaluation or conduct of the clinical investigation without the prior written consent of 
Amgen Inc. 
If you have questions regarding how this document may be used or shared, call the 
Amgen Medical Information number: US sites, 1- 800-77-AMGEN; Canadian sites, 
1-866-50-AMGEN; for all other countries, call 1-800-772-6436; Amgen’s general 
number in the US, 1-805-447-1000. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
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CONFIDENTIAL 
FORM-001520, v.22, 05 February 2018 
 
Investigator’s Agreement: 
I have read the attached protocol entitled A Phase 2b Dose Ranging Study to Evaluate 
the Efficacy and Safety of Rozibafusp Alfa (AMG 570) in Subjects With Active Systemic 
Lupus Erythematosus (SLE) With Inadequate Response to Standard of Care (SOC) 
Therapy, dated 24 May 2022, and agree to abide by all provisions set forth therein. 
I agree to comply with the International Council for Harmonisation (ICH) Tripartite 
Guideline on Good Clinical Practice (GCP), Declaration of Helsinki, and applicable 
national or regional regulations/guidelines. 
I agree to ensure that Financial Disclosure Statements will be completed by: me 
(including, if applicable, my spouse or legal partner and dependent children) and my 
sub investigators (including, if applicable, their spouses or legal partners and dependent 
children) at the start of the study and for up to 1 year after the study is completed, if 
there are changes that affect my financial disclosure status. 
I agree to ensure that the confidential information contained in this document will not be 
used for any purpose other than the evaluation or conduct of the clinical investigation 
without the prior written consent of Amgen Inc. 
 
_______________________________ 
Signature 
_______________________________ 
 
____________________________ 
Name of Investigator  
 
 
 
Date (DD Month YYYY) 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
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Table of Contents 
Table of Contents ................................................................................................... 4 
1. 
Protocol Synopsis ................................................................................................. 10 
2. 
Study Schema and Schedule of Activities ............................................................. 18 
2.1 
Study Schema ........................................................................................... 18 
2.2 
Schedule of Activities ................................................................................ 19 
3. 
Introduction ........................................................................................................... 28 
3.1 
Study Rationale ......................................................................................... 28 
3.2 
Background ............................................................................................... 28 
3.2.1 
Disease ..................................................................................... 28 
3.2.2 
Amgen Investigational Product Background:  
AMG 570 ................................................................................... 29 
3.3 
Clinical Studies With AMG 570 .................................................................. 29 
3.3.1 
First in Human (FIH) Study 20140322 ....................................... 29 
3.3.1.1 
FIH Study 20140322 – Clinical 
Pharmacokinetics .................................................... 30 
3.3.1.2 
FIH Study 20140322 – Clinical 
Pharmacodynamics ................................................. 30 
3.3.2 
Amgen Study 20160344 ............................................................ 30 
3.3.3 
Amgen Study 20150196 ............................................................ 31 
3.4 
Toxicology ................................................................................................. 31 
3.5 
Benefit/Risk Assessment ........................................................................... 31 
3.5.1 
Therapeutic Context .................................................................. 32 
3.5.2 
Key Benefits .............................................................................. 32 
3.5.3 
Key Risks .................................................................................. 32 
4. 
Objectives, Endpoints and Hypothesis .................................................................. 34 
4.1 
Objectives and Endpoints .......................................................................... 34 
4.2 
Hypothesis ................................................................................................ 38 
5. 
Study Design ........................................................................................................ 38 
5.1 
Overall Design .......................................................................................... 38 
5.2 
Number of Subjects ................................................................................... 40 
5.2.1 
Replacement of Subjects ........................................................... 40 
5.2.2 
Number of Sites ......................................................................... 40 
5.3 
End of Study ............................................................................................. 40 
5.3.1 
End of Study Definition .............................................................. 40 
5.3.2 
Study Duration for Subjects ....................................................... 41 
5.4 
Justification for Investigational Product Dose ............................................ 41 
5.5 
Patient Input on Study Design ................................................................... 43 
6. 
Study Population .................................................................................................. 43 
6.1 
Inclusion Criteria Screening Visit  .............................................................. 44 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
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6.2 
Exclusion Criteria Screening Visit  ............................................................. 45 
6.3 
Inclusion Criteria Baseline/Day 1 Visit ....................................................... 49 
6.4 
Subject Enrollment .................................................................................... 49 
6.5 
Screen Failures ......................................................................................... 50 
7. 
Treatments ........................................................................................................... 50 
7.1 
Treatment Procedures............................................................................... 51 
7.1.1 
Investigational Products ............................................................ 51 
7.1.2 
Non-investigational Products ..................................................... 53 
7.1.3 
Medical Devices ........................................................................ 53 
7.1.4 
Other Therapies ........................................................................ 53 
7.1.4.1 
Immunosuppressants/Immunomodulators ............... 53 
7.1.4.2 
Oral, Intramuscular, and Intravenous 
Corticosteroids ........................................................ 53 
7.1.4.3 
Topical Corticosteroids and Topical 
Calcineurin Inhibitors ............................................... 54 
7.1.4.4 
Non-steroidal Anti-inflammatory Drugs 
(NSAIDs) and Other Analgesic Therapies ............... 54 
7.1.4.5 
Anti-proteinuria Agents ............................................ 54 
7.1.5 
Other Treatment Procedures ..................................................... 54 
7.1.5.1 
Home Health Care Visits ......................................... 54 
7.1.6 
Product Complaints ................................................................... 55 
7.1.7 
Excluded Treatments, Medical Devices, and/or 
Procedures During Study Period ............................................... 56 
7.2 
Method of Treatment Assignment ............................................................. 56 
7.3 
Blinding ..................................................................................................... 56 
7.3.1 
Site Personnel Access to Individual Treatment 
Assignments ............................................................................. 57 
7.3.2 
Access to Individual Subject Treatment Assignments 
by Amgen or Designees ............................................................ 57 
7.3.3 
Unblinding Procedure For Investigators ..................................... 58 
7.4 
Dose Modification ...................................................................................... 58 
7.4.1 
Dose-cohort Study Escalation/De-escalation and 
Stopping Rules .......................................................................... 58 
7.4.2 
Dosage Adjustments, Delays, Rules for Withholding or 
Restarting, Permanent Discontinuation ..................................... 58 
7.4.2.1 
Amgen Investigational Product:  AMG 570 
or Placebo ............................................................... 58 
7.4.2.2 
Non-Amgen Non-Investigational Product:  
SLE Standard of Care Therapy and Oral 
Corticosteroids ........................................................ 58 
7.4.3 
Hepatotoxicity Stopping and Rechallenge Rules ....................... 59 
7.5 
Preparation/Handling/Storage/Accountability ............................................ 59 
7.6 
Treatment Compliance .............................................................................. 59 
7.7 
Treatment of Overdose ............................................................................. 59 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
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7.8 
Prior and Concomitant Treatment ............................................................. 59 
7.8.1 
Prior Treatment ......................................................................... 59 
7.8.2 
Concomitant Treatment ............................................................. 59 
8. 
Discontinuation Criteria ......................................................................................... 60 
8.1 
Discontinuation of Investigational Product ................................................. 60 
8.2 
Discontinuation From the Study ................................................................ 61 
8.2.1 
Reasons for Removal From Study ............................................. 61 
8.3 
Lost to Follow-up ....................................................................................... 62 
9. 
Study Assessments and Procedures .................................................................... 62 
9.1 
General Study Periods .............................................................................. 62 
9.1.1 
Screening, Enrollment and/or Randomization ............................ 62 
9.1.2 
Treatment Period ....................................................................... 64 
9.1.3 
Safety Follow-up ........................................................................ 64 
9.1.4 
Long-term Follow-up .................................................................. 64 
9.1.5 
End of Study .............................................................................. 64 
9.1.5.1 
End of Study for Individual Subject .......................... 64 
9.1.5.2 
End of Study ........................................................... 65 
9.2 
Description of General Study Assessments and Procedures ..................... 65 
9.2.1 
General Assessments ............................................................... 65 
9.2.1.1 
Informed Consent .................................................... 65 
9.2.1.2 
Demographics ......................................................... 65 
9.2.1.3 
Medical History ........................................................ 65 
9.2.1.4 
Physical Examination .............................................. 65 
9.2.1.5 
Concomitant Medications ........................................ 65 
9.2.1.6 
Physical Measurements .......................................... 65 
9.2.1.7 
Substance Abuse History ........................................ 66 
9.2.2 
Efficacy Assessments ................................................................ 66 
9.2.2.1 
Hybrid Systemic Lupus Erythematosus 
Disease Activity Index ............................................. 66 
9.2.2.2 
British Isles Lupus Assessment Group 
Index ....................................................................... 67 
9.2.2.3 
Cutaneous Lupus Erythematosus Disease 
Area and Severity Index .......................................... 67 
9.2.2.4 
Photography ............................................................ 67 
9.2.2.5 
Swollen and Tender Joint Count ............................. 67 
9.2.2.6 
Physician Global Assessment – Visual 
Analogue Scale ....................................................... 68 
9.2.2.7 
SELENA-SLEDAI Flare Index ................................. 69 
9.2.2.8 
BILAG Flare Index ................................................... 69 
9.2.2.9 
Lupus Low Disease Activity State (LLDAS) ............. 69 
9.2.2.10 
Systemic Lupus International 
Collaborating Clinics/American College of 
Rheumatology Damage Index ................................. 69 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
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9.2.2.11 
Systemic Lupus Erythematosus 
Responder Index ..................................................... 69 
9.2.2.12 
BICLA Index Response ........................................... 70 
9.2.3 
Safety Assessments .................................................................. 70 
9.2.3.1 
Adverse Events and Serious Adverse 
Events ..................................................................... 71 
9.2.3.2 
Vital Signs ............................................................... 73 
9.2.4 
Clinical Laboratory Assessments ............................................... 74 
9.2.4.2 
Pregnancy Testing .................................................. 74 
9.2.4.3 
Tuberculosis Testing ............................................... 75 
9.2.4.4 
HIV Antibodies, Hepatitis B, and 
Hepatitis C Testing .................................................. 75 
9.2.5 
Pharmacokinetic Assessments .................................................. 75 
9.2.6 
Pharmacodynamic Assessments ............................................... 76 
9.2.6.1 
Biomarker Assessment During the Study ................ 76 
9.2.7 
Pharmacogenetic Assessments................................................. 76 
9.2.9 
Biomarker Development ............................................................ 77 
9.2.10 
Clinical Outcome Assessments:  Patient Reported 
Outcomes .................................................................................. 77 
9.2.10.1 
Medical Outcomes Short Form-36 
Questionnaire Version 2 .......................................... 77 
9.2.10.2 
Patient-Reported Outcome Measurement 
Information System Fatigue Short Form 7a 
Instrument (PROMIS Fatigue SF 7A) ...................... 77 
9.2.10.3 
LupusQoL ............................................................... 78 
9.2.10.4 
Patient Global Assessment ..................................... 78 
10. 
Statistical Considerations ...................................................................................... 80 
10.1 
Sample Size Determination ....................................................................... 80 
10.2 
Analysis Sets, Subgroups, and Covariates ................................................ 80 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
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10.2.1 
Analysis Sets ............................................................................. 80 
10.2.1.1 
Full Analysis Set ...................................................... 80 
10.2.1.2 
Safety Analysis Set ................................................. 80 
10.2.1.3 
PK Concentration Analysis Set ................................ 80 
10.2.1.4 
PK Parameter Analysis Set ..................................... 81 
10.2.1.5 
PD Analysis Set ...................................................... 81 
10.2.2 
Covariates ................................................................................. 81 
10.2.3 
Subgroups ................................................................................. 81 
10.3 
Statistical Analyses ................................................................................... 81 
10.3.1 
Planned Analyses ...................................................................... 82 
10.3.1.1 
Interim Analysis and Early Stopping 
Guidelines ............................................................... 82 
10.3.1.2 
Primary Analysis ..................................................... 83 
10.3.1.3 
Final Analysis .......................................................... 83 
10.3.2 
Methods of Analyses ................................................................. 83 
10.3.2.1 
General Considerations ........................................... 83 
10.3.2.2 
Efficacy Analyses .................................................... 84 
10.3.2.3 
Safety Analyses ...................................................... 84 
10.3.2.4 
Other Analyses ........................................................ 85 
11. 
References ........................................................................................................... 86 
12. 
Appendices ........................................................................................................... 88 
12.1 
Appendix 1.  List of Abbreviations and Definitions of Terms ...................... 89 
12.2 
Appendix 2.  Clinical Laboratory Tests ...................................................... 92 
12.3 
Appendix 3.  Study Governance Considerations ....................................... 95 
12.4 
Appendix 4.  Safety Events:  Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting ..................................... 103 
12.5 
Appendix 5.  Contraceptive Guidance and Collection of 
Pregnancy and Lactation Information ...................................................... 111 
12.6 
Appendix 6.  Sample Storage and Destruction ........................................ 116 
12.7 
Appendix 7.  Hepatotoxicity Stopping Rules:  Suggested Actions 
and Follow-up Assessments and Investigational Product 
Rechallenge Guidelines .......................................................................... 118 
 


Product:  Rozibafusp Alfa (AMG 570) 
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Date:  24 May 2022 
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List of Tables 
Table 1-1.  Analyses Schedule:  Decisions at each Interim Analysis,  Primary 
Analysis, and Final Analysis ................................................................... 16 
Table 2-1.  Schedule of Activities – Treatment Period ................................................... 19 
Table 2-2.  Schedule of Activities – Safety Follow-up Perioda ........................................ 25 
Table 7-1.  Investigational Products ............................................................................... 52 
Table 12-1.  Analyte Listinga .......................................................................................... 93 
Table 12-2.  Conditions for Withholding and/or Permanent Discontinuation of 
Amgen Investigational Product and Other Protocol-required 
Therapies Due to Potential Hepatotoxicity ............................................ 119 
List of Figures 
Figure 2-1.  Study Schema ............................................................................................ 18 
Figure 6-1.  Screening and Enrollment .......................................................................... 44 
Figure 12-1.  Sample Electronic Serious Adverse Event Contingency Report 
Form ..................................................................................................... 108 
Figure 12-2.  Pregnancy Notification Form .................................................................. 114 
Figure 12-3.  Lactation Notification Form ..................................................................... 115 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
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1. 
Protocol Synopsis 
Protocol Title:  A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of 
Rozibafusp Alfa (AMG 570) in Subjects With Active Systemic Lupus Erythematosus 
(SLE) With Inadequate Response to Standard of Care (SOC) Therapy 
Short Protocol Title:  Safety and Efficacy of AMG 570 in Subjects With Active Systemic 
Lupus Erythematosus (SLE) 
Study Phase:  2b 
Indication:  systemic lupus erythematosus (SLE) 
Rationale: 
This is a phase 2b dose-ranging study to assess efficacy and safety of rozibafusp alfa 
(AMG 570) in subjects with active SLE.  AMG 570 could be a viable treatment option for 
SLE patients who are not responding to current standard of care. 
Objectives/Endpoints 
Objectives 
Endpoints 
Primary 
 
Evaluate the efficacy of AMG 570 
at week 52 as measured by the 
Systemic Lupus Erythematosus 
(SLE) Responder Index (SRI-4) 
 
SRI-4 response at week 52 
The primary estimand is the difference in SRI-4 response between each AMG 570 
dose group and placebo at week 52 for all subjects with SLE with inadequate 
response to SOC therapy who are randomized, regardless of investigational product 
discontinuation; subjects using more than protocol-allowed therapies will be 
considered as non-responders.   
Secondary 
 
Evaluate the efficacy of AMG 570 
at week 24 
 
SRI-4 response at week 24 
 
British Isles Lupus Assessment 
Group (BILAG) based Combined Lupus 
Assessment (BICLA) response at 
week 24 
 
Evaluate the efficacy of AMG 570 
at week 52 
 
Lupus Low Disease Activity State 
(LLDAS) response at week 52 
 
BICLA response at week 52 
 
Evaluate the efficacy of AMG 570 
as measured by SRI-4 response 
with oral corticosteroid 
(OCS)-tapering 
 
SRI-4 response at week 52 with 
reduction of OCS to  7.5 mg/day by 
week 44 and sustained through week 52 
in subjects with a baseline OCS dose 
 10 mg/day 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
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Objectives 
Endpoints 
 
Evaluate the efficacy of AMG 570 
on disease flares 
 
Annualized moderate and severe flare 
rate (as measured by SELENA-SLEDAI 
Flare Index) over 52 weeks 
 
Annualized severe flare rate (as 
measured by SELENA-SLEDAI Flare 
Index) over 52 weeks 
 
Annualized flare rate (as measured by 
BILAG score designation of “worse” or 
“new” resulting in a B score in  2 organs 
or an A score in  1 organ) over 
52 weeks 
 
Evaluate the efficacy of AMG 570 
on joints and skin 
 
Total tender and swollen joint count 
(limited to hands and wrists):   50 
improvement from baseline at week 12, 
24, 36, and 52 in subjects with  6 tender 
and swollen joints in hands and wrists at 
baseline 
 
Cutaneous Lupus Erythematosus Area 
and Severity Index (CLASI) activity 
score:   50 improvement from 
baseline at week 12, 24, 36, and 52 in 
subjects with a CLASI activity score  8 
at baseline 
 
Describe the efficacy of AMG 570 
using patient reported outcomes 
 
Patient-Reported Outcome 
Measurement Information System 
Fatigue Short Form 7a Instrument 
(PROMIS-Fatigue SF7A) score and 
change from baseline at week 12, 24, 
36, 44, and 52 
 
Medical Outcomes Short Form 36 
version 2 Questionnaire (SF-36v2) 
change from baseline in the physical 
component score, mental component 
score individual domains of the 
Medical Outcomes Short Form 36 
version 2 questionnaire (SF-36v2) at 
week 12, 24, 36, 44, and 52 
 
Lupus Quality of Life questionnaire 
(LupusQoL) score and change from 
baseline at week 12, 24, 36, 44, and 52 
 
Patient Global Assessment (PtGA) score 
and change from baseline at week 12, 
24, 36, 44, and 52 


Product:  Rozibafusp Alfa (AMG 570) 
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Objectives 
Endpoints 
 
Characterize the safety of 
AMG 570 
 
Treatment-emergent adverse events 
 
Serious adverse events 
 
Clinically significant changes in 
laboratory values and vital signs 
 
To characterize the 
pharmacokinetics (PK) of AMG 570 
 
Trough serum concentrations and 
terminal elimination half-life of AMG 570 
Exploratory 


Product:  Rozibafusp Alfa (AMG 570) 
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Objectives 
Endpoints 
Hypothesis 
AMG 570 administered for 52 weeks will be well tolerated and have greater efficacy than 
placebo as measured by Systemic Lupus Erythematosus Responder Index (SRI-4) 


Product:  Rozibafusp Alfa (AMG 570) 
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response at week 52 in subjects with active SLE and an inadequate response to 
standard of care therapy. 
Overall Design 
This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized, 
placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and 
inadequate response to SOC therapies including oral corticosteroids (OCS), 
immunosuppressants, and immunomodulators.  Subjects will be randomized to receive 
either placebo or 1 of 3 doses of AMG 570 with the last dose at week 50.  Treatment 
will be administered every 2 weeks (Q2W).  Study duration for a single subject will be 
52 weeks plus the screening period and safety follow-up period.  Tapering of OCS from 
the baseline dose is allowed up to week 44 at the discretion of the investigator.  The 
first interim analysis (IA) will be executed after the first 40 enrolled subjects have had the 
opportunity to complete the week 24 assessment.  Additional IAs may be executed after 
approximately every 32 newly enrolled subjects have had the opportunity to complete 
the week 24 assessment.  The last IA will occur when all 320 subjects are randomized 
and have had the opportunity to complete the week 24 assessment.  This IA will be 
referred to as the ‘all-subjects-week-24 IA’.  The purpose and analyses planned at each 
IA are listed in Table 1-1. 
Number of Subjects 
Approximately 320 subjects will be enrolled.  Because enrollment can be stopped if early 
stopping rules for futility are met, the actual sample size could be smaller. 
Summary of Subject Eligibility Criteria 
Eligible subjects must be between the ages of 18 and 75 years of age, inclusive, and be 
able to provide informed consent.  Subjects must fulfill the classification criteria for SLE 
according to the 2019 European League Against Rheumatism (EULAR)/American 
College of Rheumatology (ACR) classification criteria for SLE, with antinuclear antibody 
 1:80 by immunofluorescence on Hep-2 cells being present at screening.  In addition, at 
screening, subjects must have a Hybrid Systemic Lupus Erythematosus Disease 
Activity Index (hSLEDAI) ≥ 6 and a clinical hSLEDAI  4.  Subjects must be on a stable 
dose of OCS ( 20mg/day of prednisone or equivalent) for  2 weeks prior to screening 
and stable dose of other standard treatment for SLE such as 
immunosuppressants/immunomodulators for  8 weeks prior to screening.  Subjects with 
active or unstable neuropsychiatric SLE or unstable lupus nephritis, or any disease other 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
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than SLE requiring treatment with oral or parenteral corticosteroids for more than 
2 weeks within 6 weeks of the screening visit or any clinically significant concurrent 
medical conditions and/or significant laboratory abnormalities will not be eligible 
(Section 6.2).  Female subjects must not be pregnant or breastfeeding or plan to 
become pregnant or breastfeed during treatment or for at least 10 additional weeks after 
the last dose of investigational product in the study. 
For a full list of eligibility criteria, please refer to Sections 6.1 to 6.3. 
Treatments 
AMG 570 and placebo will be manufactured and packaged by Amgen Inc. and 
distributed using Amgen clinical investigational product distribution procedures.  Both are 
liquid formulations presented in identical glass vials and stored in the same manner.  
AMG 570 or placebo will be administered by subcutaneous (SC) injection Q2W by the 
Principal Investigator (PI) or appropriately trained designee. 
Procedures 
Written informed consent must be obtained from all subjects (or his/her legally 
authorized representative) before any study-specific screening procedures are 
performed.  The following procedures will occur per the Schedule of Activities: medical 
history; physical examination; physical measures; vital signs; prior and concomitant 
medication assessment; tuberculosis testing; urinalysis; and blood draw for serum 
chemistry, hematology, Human Immunodeficiency Virus (HIV) antibodies, hepatitis B 
and C testing,
, biomarker development, and pharmacogenetics 
sampling.  Women of childbearing potential will have pregnancy tests performed at 
screening and at regular intervals during the study.  Disease assessments (hSLEDAI, 
BILAG, Physician Global Assessment [PGA], swollen and tender joints count, 
Cutaneous Lupus Erythematosus Area and Severity Index [CLASI], photography of 
skin lesions in selected cases, and patient reported outcomes) will also be obtained.  
Safety assessments including adverse events, serious adverse events, and clinically 
significant changes in laboratory values and vital signs will be performed throughout the 
entire study including the safety follow-up. 
For a full list of study procedures, including the timing of each procedure, please refer to 
Section 9.2 and the Schedule of Activities in Table 2-2. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 16 of 121 
 
CONFIDENTIAL 
FORM-001520, v.22, 05 February 2018 
 
Statistical Considerations 
A total of approximately 320 subjects will be randomized to receive AMG 570 at 70 mg 
Q2W, 280 mg Q2W, 420 mg Q2W, or placebo.  The approximate sample size of 320 is 
chosen to provide 80% power to detect ≥ 25% absolute improvement for at least 1 
AMG 570 dose group relative to placebo in the primary endpoint of SRI-4 response rate 
at week 52 at a significance level of 0.025 (1-sided) using a Bayesian Hierarchical 
Model, assuming a 40% response rate in the placebo group. 
Randomization will be stratified by geographic region and screening hSLEDAI score 
( 10 or < 10) and start with a fixed and equal allocation (1:1:1:1).  At the time of the IAs 
(if before full enrollment), the randomization probability for each of the 3 active doses 
may be updated based on clinical efficacy, while the randomization allocation probability 
to placebo will be kept constant, ie, 25%.  IAs will be conducted as described in 
Table 1-1.  IAs will be implemented by an Independent Biostatistics Group (IBG) as 
described in Appendix 3 with decision rules specified in Section 10.3.1.1. 
The primary analysis of the primary endpoint, SRI-4 at week 52, will be based on a 
Bayesian Hierarchical Model which borrows dynamically in order to share information 
across the 3 active AMG 570 treatment groups while controlling the overall type I error at 
the 1-sided 2.5% level across multiple comparisons. 
Categorical variables will be summarized using the number and percent of subjects 
falling into each category.  All continuous variables will be summarized using mean, 
standard error or standard deviation, median, minimum, maximum, and number of 
subjects with observations.  Safety endpoints will be summarized descriptively. 
Table 1-1.  Analyses Schedule:  Decisions at each Interim Analysis,  
Primary Analysis, and Final Analysis 
Time point 
Adaptive Decision 
Number of subjects with 
opportunity to complete week 24 
1st IA  
RAR 
40 
2nd IA 
Futility, RAR 
72 
3rd IA 
Futility, RAR 
104 
4th IA 
Futility, RAR 
136 
5th IA 
Futility, RAR 
168 
6th IA 
Futility, RAR 
200 
7th IAa 
Futility, RAR 
232 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 17 of 121 
 
CONFIDENTIAL 
FORM-001520, v.22, 05 February 2018 
 
Last IAb 
Administrative Success 
320 
Primary Analysis 
Not applicable 
All subjects have had the opportunity 
to complete week 52 
Final Analysis 
Not applicable 
All subjects reach EOS 
IA  interim analysis; RAR  response adaptive randomization; EOS end of study 
a Interim analyses are planned after every 32 subjects are randomized and have had the opportunity 
to complete the week 24 assessment until full enrollment.  Number of IAs will depend on the actual 
enrollment rate. 
b Last IA is the all-subjects-week-24 IA.  The administrative success analysis at the last IA will not result in 
any adaptive decision for the ongoing study. 
Refer to Section 10 for a full description of the statistical analysis methods. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
 
Page 18 of 121 
 
CONFIDENTIAL  
FORM-001520, v.22, 05 February 2018 
 
2. 
Study Schema and Schedule of Activities 
2.1 
Study Schema 
Figure 2-1.  Study Schema 
 
 
EOS  end of study; IA  interim analysis; Q2W  every 2 weeks; RAR  Response Adaptive Randomization. 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
 
Page 19 of 121 
 
CONFIDENTIAL  
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2.2 
Schedule of Activities 
Table 2-1.  Schedule of Activities – Treatment Period 
 Study Week 
Screening 
 
Treatment Period 
Baseline 
visit/Day 1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
50 
52/ET 
Study Day ± 
Visit 
Window 
Scr visit 
1 (pre-rand) 
1 (pre-dose) 
1 (dose) 
15 ±3 
29 ±3 
43 ±3 
57 ±3 
71 ±3 
85 ±3 
99 ±3 
113 ±3 
127 ±3 
141 ±3 
155 ±3 
169 ±3 
183 ±3 
197 ±3 
211 ±3 
225 ±3 
239 ±3 
253 ±3 
267 ±3 
281 ±3 
295 ±3 
309 ±3 
323 ±3 
337 ±3 
351 ±3 
365 ±3 
GENERAL AND SAFETY ASSESSMENTS 
Informed 
consent 
X 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Eligibility 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Demographics 
X 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical exam  
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
2019 EULAR / 
ACR criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Weight 
X 
 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
Medical 
historya 
X 
 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vital signs 
X 
 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chest X-rayb 
X 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Adverse events 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serious 
adverse 
eventsc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Page 1 of 5 
Footnotes defined on last page of the table. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
 
Page 20 of 121 
 
CONFIDENTIAL  
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Table 2-1.  Schedule of Activities – Treatment Period  
 Study Week 
Screening 
 
Treatment Period 
Baseline 
visit/Day 1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
50 
52/ET 
Study Day ± Visit 
Window 
Scr visit  
1 (pre-rand) 
1 (pre-dose) 
1 (dose) 
15 ±3 
29 ±3 
43 ±3 
57 ±3 
71 ±3 
85 ±3 
99 ±3 
113 ±3 
127 ±3 
141 ±3 
155 ±3 
169 ±3 
183 ±3 
197 ±3 
211 ±3 
225 ±3 
239 ±3 
253 ±3 
267 ±3 
281 ±3 
295 ±3 
309 ±3 
323 ±3 
337 ±3 
351 ±3 
365 ±3 
Concomitant 
medication 
review 
X 
X 
 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
GENERAL AND SAFETY ASSESSMENTS (Continued) 
Randomizationd 
 
 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Home Health 
Visite 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
LABORATORY ASSESSMENTS  
Serum pregnancy 
test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy 
test 
 
 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
Tuberculosis testf 
X 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hepatitis B & Cg 
X 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
HIV serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood SLE SOC 
drug levelsh 
X 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Antinuclear 
antibody  
X 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Page 2 of 5 
Footnotes defined on last page of the table. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
 
Page 21 of 121 
 
CONFIDENTIAL  
FORM-001520, v.22, 05 February 2018 
 
Table 2-1.  Schedule of Activities – Treatment Period  
 Study Week 
Screening 
 
Treatment Period 
Baseline 
visit/Day 1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
50 
52/ET 
Study Day ± Visit 
Window 
Scr visit  
1 (pre-rand) 
1 (pre-dose) 
1 (dose) 
15 ±3 
29 ±3 
43 ±3 
57 ±3 
71 ±3 
85 ±3 
99 ±3 
113 ±3 
127 ±3 
141 ±3 
155 ±3 
169 ±3 
183 ±3 
197 ±3 
211 ±3 
225 ±3 
239 ±3 
253 ±3 
267 ±3 
281 ±3 
295 ±3 
309 ±3 
323 ±3 
337 ±3 
351 ±3 
365 ±3 
Coagulation 
testingk 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Hematologyi 
X 
 
X 
  
  
X 
  
X 
  
X 
  
X  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
ESRl 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Chemistryi 
X 
 
X 
  
  
X 
  
X 
  
X 
  
X 
 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
 
X 
  
X 
LABORATORY ASSESSMENTS (Continued) 
Urinalysism 
X 
 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
Urine protein/ 
creatininem 
X 
 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
SLE CLINICAL ASSESSMENTS 
Tender/swollen 
joint countn 
X 
 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
PGA VASo 
X 
 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
hSLEDAI 
X 
 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
Clinical hSLEDAI 
X 
X 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
SELENA-SLEDAI 
Flare Index 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
BILAG 
X 
 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
Page 3 of 5 
Footnotes defined on last page of the table. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
 
Page 22 of 121 
 
CONFIDENTIAL  
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Table 2-1.  Schedule of Activities – Treatment Period  
 Study Week 
Screening 
Treatment Period 
Baseline 
visit/Day
1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
50 
52/ET 
Study Day ± 
Visit Window 
Scr visit  
1 (pre-rand) 
1 (pre-dose) 
1 (dose) 
15 ±3 
29 ±3 
43 ±3 
57 ±3 
71 ±3 
85 ±3 
99 ±3 
113 ±3 
127 ±3 
141 ±3 
155 ±3 
169 ±3 
183 ±3 
197 ±3 
211 ±3 
225 ±3 
239 ±3 
253 ±3 
267 ±3 
281 ±3 
295 ±3 
309 ±3 
323 ±3 
337 ±3 
351 ±3 
365 ±3 
CLASI activity 
and damage 
X 
 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
SDI 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Photographyp 
 
 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
IMMUNOGENICITY 
BIOMARKER AND PHARMACOGENETICS 
Biomarker 
development 
samplei 
   
 
X 
  
  
X 
  
  
  
X 
  
  
  
  
  
X 
  
  
  
  
  
X 
  
  
  
X 
  
 
  
X 
Pharmaco- 
genetics i, s  
   
 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
CLINICAL OUTCOME ASSESSMENTS:  PATIENT REPORTED OUTCOMES 
SF-36v2t 
   
 
X 
  
  
X 
  
  
  
X 
  
  
  
  
  
X 
  
  
  
  
  
X 
  
  
  
X 
  
  
  
X 
PROMIS-Fatiguet 
   
 
X 
  
  
X 
  
  
  
X 
  
  
  
  
  
X 
  
  
  
  
  
X 
  
  
  
X 
  
  
  
X 
LupusQoLt 
   
 
X 
  
  
X 
  
  
  
X 
  
  
  
  
  
X 
  
  
  
  
  
X 
  
  
  
X 
  
  
  
X 
Patient Global 
Assessment 
(PtGA)t 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Page 4 of 5 
Footnotes are defined on last page of the table. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
 
Page 23 of 121 
 
CONFIDENTIAL  
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Table 2-1.  Schedule of Activities – Treatment Period  
 Study Week 
Screening 
Treatment Period 
Baseline  
visit/Day 1 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
50 
52/ET 
Study Day ± 
Visit Window 
Scr visit  
1 (pre-rand) 
1 (pre-dose) 
1 (dose) 
15 ±3 
29 ±3 
43 ±3 
57 ±3 
71 ±3 
85 ±3 
99 ±3 
113 ±3 
127 ±3 
141 ±3 
155 ±3 
169 ±3 
183 ±3 
197 ±3 
211 ±3 
225 ±3 
239 ±3 
253 ±3 
267 ±3 
281 ±3 
295 ±3 
309 ±3 
323 ±3 
337 ±3 
351 ±3 
365 ±3 
INVESTIGATIONAL PRODUCT ADMINISTRATION 
Investigational 
Product 
(AMG  570/ 
placebo)u 
   
 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
PHARMACOKINETIC ASSESSMENTS  
PK samplesi, q 
   
 
X 
  
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
 
 
 
  
X 
  
 
 
X 
  
  
  
X 
Page 5 of 5 
ACR = American College of Rheumatology;
aPTT  activated partial thromboplastin time; BILAG = British Isles Lupus 
Assessment Group; CLASI = Cutaneous Lupus Erythematosus Disease and Severity Index; Clinical hSLEDAI = hybrid SLEDAI assessment score without the 
inclusion of points attributable to any laboratory parameter, including urine and immunologic parameters; eCRF = electronic Case Report Form; ESR  erythrocyte 
sedimentation rate; ET = early termination visit; EULAR = European League Against Rheumatism; HBcAb = hepatitis B core antibody; HBsAg = hepatitis B surface 
antigen; HIV = Human Immunodeficiency Virus;
INR = international normalized ratio; 
 PCR = polymerase chain reaction; 
PD = pharmacodynamics; PGA = Physician Global Assessment; PK = pharmacokinetic; PPD = purified protein derivative; PROMIS = Patient-reported Outcomes 
Measures Information System; PT = prothrombin time; PTT = partial thromboplastin time; LupusQoL  Lupus Quality of Life questionnaire; 
; 
SDI = Systemic Lupus International Collaborating Clinic/American College of Rheumatology Damage Index; Scr = screening; SF-36v2 = Medical Outcomes Short 
Form 36 version 2 questionnaire; SLE = systemic lupus erythematosus; hSLEDAI = Hybrid Systemic Lupus Erythematosus Disease Activity Index; VAS = visual 
analogue scale. 
a Including substance abuse history.  
b Only for subjects with a positive tuberculosis test (ie, positive PPD [purified protein derivative] or positive or indeterminate QuantiFERON®-TB or T-spot test). 
c After end of study, serious adverse events suspected to be related to investigational product will be reported to Amgen.  Please refer to Section 9.2.3.1.1.3 
or additional details.   
d Randomization may occur at any time after confirmation of all eligibility criteria, but the maximum time between initiation of screening and randomization is 33 days. 
e In addition to administration of investigational product, safety assessments including vital signs, adverse events, serious adverse events, and concomitant 
medications review will be collected.  Home health care visits will be optional after week 20 for subjects who do not experience any adverse effects from 
investigational product administration. 
f Either a centrally or locally performed QuantiFERON®-TB or locally performed PPD or T-spot test will be done during screening per Section 6.2 criterion 206. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
 
Page 24 of 121 
 
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g For subjects with HBsAg negative, HBcAb positive and undetectable viral DNA by PCR; and for subjects with HCVAb positive and undetectable viral RNA by PCR, 
serum viral DNA (Hepatitis B virus) or RNA (Hepatitis C virus) will be monitored by PCR in peripheral blood at approximately every 3 months during treatment 
period, and up to a minimum of 16 weeks after last administration of the investigational product.  
h Blood levels will be measured for the following: azathioprine, mycophenolate mofetil and hydroxychloroquine.  
i Blood samples must be collected prior to administration of investigational product. 
j Lupus reflex will be done if aPTT is prolonged. 
k PT/INR and aPTT (in case of drug-induced liver injury [DILI] events, fibrinogen and D-dimers will also be included). 
l ESR will be performed at a local laboratory. 
m Clean catch urine specimen required.  
n Tender and swollen joint counts will be performed as described in Section 9.2.2.5. 
o Should be completed by a health care provider before assessing the hSLEDAI and BILAG scores. See Section 9.2.2.6. 
p Whenever possible and only in subjects with a CLASI activity score ≥ 8 at screening per Section 9.2.2.4. 
q If a subject discontinues investigational product prior to completing week 52 visit, they should be encouraged to maintain the planned scheduled assessment for 
monthly efficacy and safety visits through week 52 (Table 2-1). 
and PK samples should be collected at the first 4 visits after 
investigational product discontinuation. 
s DNA will be extracted only if subject provides additional consent for pharmacogenetics testing. 
t Patient reported outcomes should be completed as described in Section 9.2.10. 
u Investigational product (AMG 570 or placebo) will be administered as described in Section 7.1.1.  Subjects will be observed for at least 30 minutes at the site or by the 
home health care provider following investigational product administration. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
 
Page 25 of 121 
 
CONFIDENTIAL  
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Table 2-2.  Schedule of Activities – Safety Follow-up Perioda 
Safety Follow-up Week  Visit Window 
4 Weeks  5 days 
after last IP dose 
4 Weeks  5 days 
after prior safety 
follow-up visit 
4 Weeks  5 days 
after prior safety 
follow-up visit 
4 Weeks  5 days 
after prior safety 
follow-up visit 
EOS 
GENERAL AND SAFETY ASSESSMENTS 
Vital signs 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
Serious adverse eventsb 
X 
X 
X 
X 
Concomitant medications review 
X 
X 
X 
X 
LABORATORY ASSESSMENTS  
Urine pregnancy test 
X 
X 
Hematology  
X 
X 
Hepatitis B and Cc 
 
 
X  
 
IMMUNOGENICITY 
PHARMACOKINETIC ASSESSMENTS  
Pharmacokinetic Samples  
X 
X 
X 
X 
EOS  end of study; IP  investigational product; PCR  polymerase chain reaction 
a This table applies for subjects who have completed the planned 52-week treatment period.  Subjects are required to attend as many follow-up visits as 
necessary to ensure a minimum of 16 weeks of safety follow-up after the last administration of the investigational product. 
b After end of study, serious adverse events suspected to be related to investigational product will be reported to Amgen.  Please refer to Section 9.2.3.1.1.3 
for additional details.   
c For subjects who require monitoring, PCR test to assess viral load should be performed at approximately every 3 months from baseline and up to a minimum 
of 16 weeks after the last administration of the investigational product.  See Section 6.2 criterion 208. 
  
 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
 
Page 26 of 121 
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Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
 
Page 27 of 121 
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Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 28 of 121 
 
CONFIDENTIAL  
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3. 
Introduction 
3.1 
Study Rationale 
This is a phase 2b dose-ranging study to assess efficacy and safety of rozibafusp alfa 
(AMG 570) in subjects with active systemic lupus erythematosus (SLE). 
This study will help determine if AMG 570 could be a useful therapeutic agent in the 
current treatment landscape where subjects have ongoing disease activity despite 
treatment with standard of care therapies. 
Three dose levels of AMG 570 (70 mg subcutaneous [SC] every 2 weeks [Q2W], 
280 mg SC Q2W, and 420 mg SC Q2W) were selected based on pharmacokinetic 
(PK)/pharmacodynamic (PD) modeling and analysis of emerging PK, B cell activating 
factor (BAFF) inhibition (ie, % change in % naïve B-cells), and inducible co-stimulator 
ligand (ICOSL) % receptor occupancy (RO) data from previous studies (AMG 570 
Investigator’s Brochure [IB]).  These dose regimens are proposed to promote 
characterization of exposure-response relationships in this phase 2b SLE study and 
inform dose selection for future studies. 
3.2 
Background 
3.2.1 
Disease 
Systemic lupus erythematosus is a multisystem autoimmune disease of unknown cause 
with diverse clinical manifestations that disproportionately affects minorities (eg, in the 
United States [US], blacks and Hispanics) and women of childbearing potential 
(Rhaman and Isenberg, 2008; Kotzin, 1996).  In the US, moderate to severe SLE is 
estimated to affect one-third of the more than 250,000 patients diagnosed with lupus.  
SLE disease activity may vary from mild episodes to severe, even fatal outcomes with 
symptoms varying widely in individuals over time and characterized by periods of 
remission and flare.  SLE can affect the skin (rash), musculoskeletal system (arthritis) 
nervous system (seizures, psychosis), lungs (pleuritis, pneumonitis), and the blood 
(venous or arterial thrombosis, anemia, thrombocytopenia, and leukopenia).  In addition, 
approximately 65% of patients will develop lupus nephritis that can range from mild 
glomerulonephritis to severe diffuse proliferative glomerulonephritis (Adams et al, 2006). 
Current treatment options include antimalarials, corticosteroids (CS), and other 
immunomodulators/immunosuppressants, and few biologics (including Benlysta), which 
have limited efficacy and may have toxicities that impede a patient’s ability to remain on 
therapy.  Therefore, significant need exists for effective therapies with limited toxicities.  
SLE is both clinically and immunologically heterogenous; however, the presence of 


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class-switched, hypermutated immunoglobulin G (IgG) autoantibodies implicate immune 
dysregulation as a driving force for disease pathogenesis, with T cells playing a role in 
the development of autoantibody production by B cells. 
3.2.2 
Amgen Investigational Product Background:  AMG 570 
AMG 570 is a bispecific IgG2 antibody-peptide conjugate inhibiting both ICOSL and 
BAFF.  AMG 570 contains 2 tandem copies of BAFF-binding peptides fused to the 
C-terminus of a fully human IgG2 against ICOSL.  In terms of anti-BAFF effect, 
AMG 570 has similar binding affinity and cellular potency to relevant BAFF inhibitors.  
AMG 570 binds and inhibits cynomolgus monkey ICOSL and BAFF, but not rodent 
ICOSL.  A mouse surrogate ICOSL/BAFF bispecific molecule showed dual-target 
inhibition in vivo and was more efficacious than single ICOSL or BAFF inhibitors in the 
mouse NZB/NZW lupus model (AMG 570 Investigator’s Brochure).  Thus, we 
hypothesize that targeting both ICOSL and BAFF by AMG 570 will achieve a large effect 
size in the treatment of autoantibody associated diseases, such as SLE. 
3.3 
Clinical Studies With AMG 570 
3.3.1 
First in Human (FIH) Study 20140322 
In the first in human (FIH) study in healthy volunteers, a total of 56 subjects were 
enrolled and randomized to receive AMG 570 or placebo; 42 subjects received AMG 570 
(6 per dosing cohort; dose range:  7 to 700 mg), and 14 subjects received placebo.  Four 
subjects (7.1%, AMG 570 group) discontinued from the study; of these, 3 subjects 
(5.4%) were lost to follow-up and 1 subject (1.8%) withdrew consent.  AMG 570 was 
generally well tolerated with most adverse events being mild in severity.  One subject 
from the 7 mg cohort had a serious adverse event of injury, which was considered not 
related to investigational product.  No subject had any clinically significant, 
life-threatening, or fatal adverse event.  No dose limiting toxicities or withdrawals due to 
adverse events were reported. 
The FIH study included 2 humoral immune status stopping rules that accounted for the 
potential of AMG 570 to decrease total circulating B cells and/or serum IgG levels.  If a 
single subject in the FIH study satisfied the humoral immune status stopping rules, 
further studies with AMG 570 would shift from healthy volunteers to patients.  No subject 
satisfied these rules during the course of the study. 


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3.3.1.1 
FIH Study 20140322 – Clinical Pharmacokinetics 
The PK of AMG 570 were assessed in the FIH study. 
After a single SC dose, AMG 570 exposure was greater than dose proportional in the 
dose range of 7 to 700 mg.  However, exposures across the dose range from 210 to 
700 mg SC suggested that approximately dose-proportional exposure as assessed by 
maximum concentration (Cmax) may be observed in the dose range of 210 to 700 mg. 
3.3.1.2 
FIH Study 20140322 – Clinical Pharmacodynamics 
A validated, semi-quantitative flow cytometry assay was developed to monitor the PD 
properties of the constituent arms of the bispecific in whole blood specimens. 
The effect of AMG 570 on ICOSL receptor occupancy was substantial with more than 
90% receptor occupancy on total B cells at 8 days after dosing in 420 mg and 700 mg 
AMG 570 dose groups.  A prominent effect of AMG 570 was observed on B cell 
populations, with a decreased percentage of naïve and increased percentage of memory 
B cells.  No treatment effect was observed on serum IgG, IgM, natural killer cells, and 
T cells. 
3.3.2 
Amgen Study 20160344 
The safety, tolerability, and PK of single doses of AMG 570 was evaluated in healthy 
Japanese subjects in Study 20160344.  A total of 12 subjects were enrolled and 
randomized to receive a single dose of AMG 570 210 or 420 mg SC (6 subjects per 
cohort).  One subject (8.3%, AMG 570 420 mg group) withdrew consent and 
discontinued from the study.  AMG 570 was generally well tolerated with 2 adverse 
events being mild (grade 1) in severity and considered not related to investigational 
product.  No subject had serious, life-threatening, or fatal adverse events. 
Following a single SC dose of AMG 570 210 or 420 mg in healthy Japanese subjects, 
mean Cmax, and AUCinf increased 2.4- and 3.9-fold, respectively, for a 2-fold increase in 
dose. 
Inducible co-stimulator ligand receptor occupancy was > 85% on total peripheral B cells 
at 8 days after dosing in both AMG 570 210 and 420 mg treatment groups.  A prominent 
effect of AMG 570 was observed on B cell populations, with a reduction of naïve B cells 
and an increase in memory B cells. 
One subject (8.3%) had pre-existing anti-AMG 570 antibodies at baseline and 
11 subjects (91.7%) developed anti-AMG 570 antibodies after dosing; the effect of 
anti-AMG 570 antibodies on the PK after a single SC dose of AMG 570 could not be 


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determined.  There was no association between AMG 570 binding antibodies and any 
adverse events. 
3.3.3 
Amgen Study 20150196 
The safety, tolerability, and PK of multiple ascending doses of AMG 570 was evaluated 
in subjects with rheumatoid arthritis (RA) in Study 20150196.  The study had 4 cohorts, 
each receiving 6 doses of AMG 570 ranging from 70 to 420 mg SC given Q2W based on 
cohort.  A total of 32 subjects were planned (8 per cohort); 34 subjects were treated as 
9 subjects were enrolled in both cohorts 1 and 4 (7 subjects received AMG 570 and 
2 received placebo).  There were no deaths or drug-related serious adverse events, 
dose-limiting toxicities, or withdrawals due to adverse events.  In general, AMG 570 had 
an acceptable safety profile at the doses tested. 
3.4 
Toxicology 
The AMG 570 safety profile was evaluated in 3- and 6-month Good Laboratory Practice 
(GLP) repeat-dose toxicology studies in the cynomolgus monkey as well as in several in 
vitro test systems.  In both the 3-month toxicology study with an 8-month recovery 
(30, 100, and 200 mg/kg, 13 weekly SC injections) and 6-month study (100 and 
200 mg/kg, 26 weekly SC injections), the no-observed-adverse effect-level (NOAEL) 
was 200 mg/kg.  AMG 570 pharmacology-related effects (ie, decreased B cells, IgG, and 
lymphoid depletion of the lymphoid tissues) were observed at all dose levels.  In the 
3-month study, all changes were shown to be reversible within 8 months after the end of 
the dosing phase.  Increased reticulocyte counts and subsequently increased red blood 
cell (RBC) mass were observed in a limited number of animals (4 animals in total; 
1 animal at 100 mg/kg in the 3-month study and 1 and 2 animals at 100 and 200 mg/kg, 
respectively, in the 6-month study) but no adverse consequences were observed. 
All the clinical dose levels in the ongoing and planned clinical studies are supported by 
adequate exposure margins based on the NOAEL (200 mg/kg) from the 3-and 6-month 
GLP repeat-dose toxicology studies in the cynomolgus monkey (NOAEL exposure in the 
monkey corresponded to ≥ 16-fold above exposures expected/observed at clinical 
doses).  A detailed description of nonclinical safety studies is provided in the 
AMG 570 Investigator’s Brochure. 
3.5 
Benefit/Risk Assessment 
The following benefit-risk assessment supports the conduct of this clinical trial.  
Reference should be made to the AMG 570 Investigator’s Brochure (IB) for further data 
on AMG 570. 


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3.5.1 
Therapeutic Context 
Systemic Lupus Erythematosus is a chronic autoimmune disease with no known cure 
and unpredictable disease flares that can lead to progressive disability, marked by 
moderate or severe exacerbations and sometimes fatal outcomes.  Inflammation can 
arise in almost any major organ system of the body leading to manifestations such as 
rash, arthritis, bone tissue death, leukopenia, seizures, psychosis, pleuritis, pneumonitis, 
thromboses, anemia, nephritis and renal failure.  Current treatment options include 
antimalarials, CS, immunomodulators, immunosuppressants, and few biologics 
(including Benlysta), these therapies have limited efficacy and may have toxicities that 
impede a patient’s ability to remain on therapy.  A substantial unmet medical need exists 
for these patients who have active disease despite SOC therapy. 
3.5.2 
Key Benefits 
Phase 1 studies for AMG 570 have completed, and predicate evidence indicates 
potential biological and/or clinical benefits in lupus patients upon targeting either ICOSL 
or BAFF in isolation (Cheng et al, 2018; Zhang et al, 2018; Doria et al, 2018; 
Sullivan et al, 2016; Furie et al, 2011; Navarra et al, 2011; Chandran et al, 2007). 
3.5.3 
Key Risks 
The safety, tolerability, and PK/PD of single ascending doses of AMG 570 were 
evaluated in the FIH Study 20140322 in healthy subjects.  A total of 56 subjects received 
blinded investigational product at SC doses up to 700 mg.  All subjects receiving dose 
levels up to 700 mg SC in the single ascending dose study demonstrated acceptable 
safety and tolerability with no drug-related severe, life-threatening, or fatal events 
reported.  All adverse events were of mild to moderate severity.  Safety, tolerability, and 
PK of multiple ascending doses of AMG 570 were evaluated in subjects with RA in 
Amgen Study 20150196.  There were no deaths or drug-related serious adverse events, 
dose-limiting toxicities, or withdrawals due to adverse events.  Adverse events occurring 
2 or more times include: headache, arthralgia, pain in extremity, upper respiratory tract 
infection, dizziness, RA flare, and sciatica.  All these events were mild or moderate.  In 
general, AMG 570 was well tolerated at the doses tested. 
An additional assessment of potential side effects of multiple doses of AMG 570 is 
based on the preclinical studies conducted to date and by observations of safety and 
tolerability of molecules that inhibit only ICOSL or BAFF.  Summaries of findings from 
the nonclinical studies with AMG 570 can be found in the AMG 570 IB.  No target organs 
beyond pharmacologic effects of AMG 570 were identified up to the high dose in the 


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GLP cynomolgus monkey toxicology study (200 mg/kg:  11 to 64.5 times higher than 
planned clinical doses [70 to 420 mg]). 
Potential side effects of AMG 570 could also be related to the biological nature of the 
molecule and mode of administration. 
Please refer to the AMG 570 IB, Section 7 for a description of these potential side 
effects. 
 


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4. 
Objectives, Endpoints and Hypothesis 
4.1 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
Evaluate the efficacy of AMG 570 at 
week 52 as measured by the Systemic 
Lupus Erythematosus (SLE) 
Responder Index (SRI-4) 
 
SRI-4 response at week 52 
The primary estimand is the difference in SRI-4 response between each AMG 570 
dose group and placebo at week 52 for all subjects with SLE with inadequate 
response to SOC therapy who are randomized regardless of investigational product 
discontinuation; subjects using more than protocol-allowed therapies will be 
considered as non-responders.   
Secondary 
 
Evaluate the efficacy of AMG 570 at 
week 24 
 
SRI-4 response at week 24 
 
British Isles Lupus Assessment 
Group (BILAG) based Combined 
Lupus Assessment (BICLA) 
response at week 24 
 
Evaluate the efficacy of AMG 570 at 
week 52 
 
Lupus Low Disease Activity State 
(LLDAS) response at week 52 
 
BICLA response at week 52 
 
Evaluate the efficacy of AMG 570 as 
measured by SRI-4 response with oral 
corticosteroid (OCS)-tapering 
 
SRI-4 response at week 52 with 
reduction of OCS to  7.5 mg/day by 
week 44 and sustained through 
week 52 in subjects with a baseline 
OCS dose  10 mg/day 
 
Evaluate the efficacy of AMG 570 on 
disease flares 
 
Annualized moderate and severe 
flare rate (as measured by 
SELENA-SLEDAI Flare Index) over 
52 weeks 
 
Annualized severe flare rate (as 
measured by SELENA-SLEDAI Flare 
Index) over 52 weeks 
 
Annualized flare rate (as measured 
by BILAG score designation of 
“worse” or “new” resulting in a B 
score in  2 organs or an A score in 
 1 organ) over 52 weeks 
 
Evaluate the efficacy of AMG 570 on 
joints and skin 
 
Total tender and swollen joint count 
(limited to hands and wrists):   50 
improvement from baseline at week 


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Objectives 
Endpoints 
12, 24, 36, and 52 in subjects with 
 6 tender and swollen joints in 
hands and wrists at baseline 
 
Cutaneous Lupus Erythematosus 
Area and Severity Index (CLASI) 
activity score:   50 improvement 
from baseline at week 12, 24, 36, 
and 52 in subjects with a CLASI 
activity score  8 at baseline 
 
Describe the efficacy of AMG 570 
using patient reported outcomes 
 
Patient-Reported Outcome 
Measurement Information System 
Fatigue Short Form 7a Instrument 
(PROMIS-Fatigue SF7A) score and 
change from baseline at week 12, 24, 
36, 44, and 52 
 
Medical Outcomes Short Form 36 
version 2 Questionnaire (SF-36v2) 
change from baseline in the 
physical component score, mental 
component score individual 
domains of the Medical Outcomes 
Short Form 36 version 2 
questionnaire (SF-36v2) at week 
12, 24, 36, 44, and 52 
 
Lupus Quality of Life questionnaire 
(LupusQoL) score and change from 
baseline at week 12, 24, 36, 44, and 
52 
 
Patient Global Assessment (PtGA) 
score and change from baseline at 
week 12, 24, 36, 44, and 52 
 
Characterize the safety of AMG 570 
 
Treatment-emergent adverse events 
 
Serious adverse events 
 
Clinically significant changes in 
laboratory values and vital signs 
 
To characterize the pharmacokinetics 
(PK) of AMG 570 
 
Trough serum concentrations and 
terminal elimination half-life of 
AMG 570 


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Objectives 
Endpoints 
Exploratory 


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Objectives 
Endpoints 
 


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4.2 
Hypothesis 
AMG 570 administered for 52 weeks will be well tolerated and have greater efficacy than 
placebo as measured by Systemic Lupus Erythematosus Responder Index (SRI-4) 
response at week 52 in subjects with active SLE and an inadequate response to SOC 
therapy. 
5. 
Study Design 
5.1 
Overall Design 
This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized, 
 placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and 
inadequate response to SOC therapies including oral corticosteroids (OCS), 
immunosuppressants, and immunomodulators.  Previous biologic use is allowed with an 
adequate washout period (see Exclusion Criterion 215). 
Approximately 320 subjects will be enrolled and randomized to receive AMG 570 SC at 
70 mg Q2W, 280 mg Q2W, 420 mg Q2W, or placebo.  The randomization starts as 
1:1:1:1 and then could be adapted at each interim analysis (IA) (if before full enrollment) 
based on the clinical efficacy (Response Adaptive Randomization [RAR]) for allocating 
more subjects to more efficacious doses and fewer subjects to less efficacious doses.  
The randomization allocation probability for placebo group will be kept constant at 25%.  
Randomization will be stratified by geographic region (North America + Western Europe 
vs rest of the world [ROW]) and screening Hybrid Systemic Lupus Erythematosus 
Disease Activity Index (hSLEDAI) score ( 10 or < 10). 
Study duration for a single subject will be 52 weeks (treatment period) plus the screening 
period and safety follow-up period.  Investigational product will be administered Q2W 
with the final dose at week 50.  If a subject discontinues investigational product prior to 
completing week 52 visit, the subject will be encouraged to continue in the study and 
maintain the planned scheduled assessment for monthly efficacy and safety visits 
through week 52 (Table 2-1).  Subjects are required to attend as many follow-up 
visits as necessary to ensure a minimum of 16 weeks of safety follow-up after the 
last administration of the investigational product.  For subjects who discontinue 
investigational product prior to week 36, the safety follow-up visits will be 
included within the 52-week period and no additional safety follow-up visits will be 
required.  Immunogenicity 
 and PK samples should be 
collected at the first 4 visits after investigational product discontinuation. 


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Subjects will undergo a screening visit to confirm eligibility requirements.  Baseline/day 1 
visit should not occur prior to confirmation of subject’s SLE-related eligibility by the 
adjudication team and must occur up to 33 days from the screening visit.  At 
baseline/day 1 visit, prior to randomization, the subject must present with disease activity 
(defined by clinical hSLEDAI score  4) and stability and compliance with OCS and other 
immunosuppressant/immunomodulator doses (by reviewing medication history).  
Subjects may be randomized at any time after confirmation of all eligibility criteria, but 
the maximum time between initiation of screening and randomization is 33 days.  
Subjects who do not meet all the eligibility requirements at the baseline/day 1 visit will be 
considered screen failures.  Subjects may be allowed to rescreen as detailed in 
Section 9.1.1. 
After randomization, adjudication reviews will be completed throughout the study 
period on blinded endpoint data from enrollment to week 52 for all randomized 
subjects and for all visits.  This includes review of all efficacy-related endpoint 
data. 
Immunosuppressant/immunomodulator dose should remain stable through week 52.  
For OCS, initiation of, or temporary increases in OCS are allowed from weeks 0 to 8, 
provided that return to baseline dose occur within the subsequent 2 weeks, as outlined 
in Section 7.1.4.2.  OCS can be tapered at the investigator’s discretion but shall not be 
changed during the last 8 weeks (week 44 to 52) of the 52-week treatment period. 
Subjects listed below will be allowed to continue the study but will be considered 
treatment failures for primary efficacy endpoint analyses for the subsequent time points. 
These subjects will also be allowed to continue investigational product at the 
investigator's discretion, except subjects who initiate any 
immunosuppressant/immunomodulator listed in Section 7.1.7 (treatments 
a through i). 
 
Subjects requiring initiation or increase in OCS dose  5 mg/day (prednisone or 
equivalent), or intramuscular (IM) CS or intravenous (IV) CS at any time point 
during the study, subjects requiring initiation or increase in OCS dose  5 mg/day 
(prednisone or equivalent) after week 10, or subjects requiring initiation or increase 
in OCS dose  5 mg/day (prednisone or equivalent) from week 0 to week 8 who 
cannot return to their baseline dose within the following 2 weeks (Section 7.1.4.2). 
 
Subjects requiring either dose increases of the current 
immunosuppressants/immunomodulators or initiation of new 
immunosuppressant/immunomodulator(s) at any time point during the study 
(Section 7.1.7). 


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This study will utilize adaptive design elements based on the results of planned IAs: 
 
IAs will be conducted by an Independent Biostatistics Group (IBG) and will be 
reviewed by a Data Monitoring Committee (DMC), both external to Amgen.  The 
study team, investigators and subjects will remain blinded to the results of the IAs. 
 
Adaptive randomization begins after a fixed allocation period.  After each IA (if before 
full enrollment), the randomization probability for each of the 3 active doses may be 
changed based on clinical efficacy, while the randomization probability for placebo is 
kept constant, ie, 25%. 
 
Efficacy is assessed against predefined early stopping rules for futility from the 
second IA until before the last IA.  If futility is triggered, the study could be 
terminated, eg, continued enrollment and follow-up activities for previously enrolled 
subjects would be stopped, etc. 
 
Efficacy is assessed against predefined rules for administrative success only at the 
last IA.  If administrative success is determined, downstream activities may be 
planned/initiated (eg, a phase 3 study), but the execution of this study would not be 
stopped or altered. 
5.2 
Number of Subjects 
Approximately 320 subjects will be enrolled in the study; however, the actual sample 
size could be smaller as the study can be stopped earlier if futility is reached at IAs. 
Participants in this clinical investigation shall be referred to as “subjects.”  For the 
sample size justification, see Section 10.1. 
5.2.1 
Replacement of Subjects 
Subjects who are withdrawn or removed from treatment or the study will not be replaced. 
5.2.2 
Number of Sites 
Approximately 150 investigative sites globally will be included in the study.  Sites that do 
not enroll subjects within 6 months of site initiation may be considered for closure. 
5.3 
End of Study 
5.3.1 
End of Study Definition 
Primary Completion:  The primary completion date is defined as the date when the last 
subject is assessed or receives an intervention for the final collection of data for the 
primary endpoint(s), for the purposes of conducting the primary analysis, whether the 
study concluded as planned in the protocol or was terminated early. 
If the study concludes prior to the primary completion date originally planned in the 
protocol (ie, early termination of the study), then the primary completion will be the date 
when the last subject is assessed or receives an intervention for evaluation in the study 
(ie, last subject last visit). 


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End of Study:  The end of study date is defined as the date when the last subject 
across all sites is assessed or receives an intervention for evaluation in the study (ie, last 
subject last visit), following any additional parts in the study (eg, safety follow-up), as 
applicable. 
5.3.2 
Study Duration for Subjects 
Study duration for a single subject will be 52 weeks plus the screening period (up to 
33 calendar days) and safety follow-up period (a minimum of 16 weeks after the last 
administration of the investigational product). 
If a subject discontinues investigational product prior to completing week 52 visit, 
the subject will be encouraged to continue in the study and maintain the planned 
scheduled assessment for monthly efficacy and safety visits through week 52 
(Table 2-1).   
For subjects who discontinue investigational product prior to or at week 36, the 
safety follow-up visits will be included within the 52-week period and no additional 
safety follow-up visits will be required.  Subjects who discontinue investigational 
product after week 36 are required to attend as many follow-up visits as necessary 
to ensure a minimum of 16 weeks of safety follow-up period after the last 
administration of the investigational product (Table 2-2).   
Subjects have completed the study when:  1) have completed 52-week treatment 
period regardless of investigational product compliance, and 2) have completed a 
minimum of 16 weeks of safety follow-up after the last administration of the 
investigational product.  
5.4 
Justification for Investigational Product Dose 
Three dose levels of AMG 570 (ie, 70, 280, and 420 mg) were chosen for the study.  
Preclinical and clinical data supporting the safety of a 420 mg SC Q2W dose are as 
follows: the NOAEL from nonclinical 6-month toxicology studies of 200 mg/kg SC 
weekly, corresponding to a maximum concentration (Cmax) of 2490 g/mL, and area 
under the curve from time 0 to 7 days (AUC0-7d) of 13800 g•day/mL.  These exposures 
are 16-fold and 23-fold higher than the predicted steady-state mean Cmax and AUC0-14d, 
in humans at the 420 mg SC Q2W dose.  Predicted steady-state AUC0-14d from the 
420 mg SC Q2W dosing regimen is also anticipated to be within the range of the 
exposures observed in previous AMG 570 clinical studies.  Multiple doses up to 420 mg 
are expected to be well tolerated in subjects with moderate to severe SLE as it was 


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shown in healthy subjects following single dose administration up to 700 mg SC.  
Multiple dose administration up to 420 mg Q2W X 6 (Study 20150196) in subjects with 
RA was also well tolerated.  Exposure (AUC0-inf) after a single dose of 700 mg was 35% 
higher than the projected steady-state exposure (AUC0-14d) of 420 mg Q2W at 
steady-state.  Thus, the highest selected dose is predicted to result in exposures that are 
16- to 23-fold lower than those achieved at the NOAEL dose in preclinical toxicology 
studies and are lower than what was achieved with the 700 mg SC dose in humans, 
which was generally well tolerated. 
The 3 dose levels were also chosen with the intent to characterize the dose-response 
and exposure-response relationships and to inform dose selection for the phase 3 
program.  The dose selection strategy integrates the 2 targets of AMG 570.  Impact of 
BAFF inhibition on naïve B cell reduction and efficacy in the SLE patient population was 
previously demonstrated for BAFF inhibitors (eg, Benlysta) (Arthritis & Rheumatism, 
2009).  Impact of inhibition of ICOSL was previously demonstrated for AMG 557 
(Sullivan et al, 2016), where maximal inhibition of the anti-KLH IgG response occurred at 
doses associated with ICOSL saturation. 
The dosing regimens for this phase 2b study were selected using PK/PD modeling and 
simulation based on available data from the single ascending dose study in healthy 
subjects (Study 20140322) and multiple ascending dose study in RA subjects 
(Study 20150196). 
The PK/PD analysis was based on biologic changes consistent with BAFF inhibition 
(ie, % change in % naïve B cells) and modeling of the AMG 570 Exposure-ICOSL 
% receptor occupancy relationship. 
The highest planned dose of 420 mg Q2W was chosen to evaluate attainment of 
maximal coverage of both targets.  This dose is predicted to achieve maximal reduction 
in % change naïve B cells and achieve maximal saturation of ICOSL (mean percent 
receptor occupancy of > 90%) in ~98% of simulated subjects at steady-state trough. 
The lowest planned dose of 70 mg Q2W will provide additional dose-ranging information 
for characterization of the dose-response and exposure-response relationships.  This 
dose is predicted to achieve maximal reduction in % change naïve B cells and achieve 
minimal saturation of ICOSL (mean percent receptor occupancy of 50% to 90% in ~80% 
of simulated subjects) at steady-state trough.  Efficacy at this dose may also allow 
comparison of AMG 570 to the efficacy associated with BAFF inhibitors (ie, Benlysta).  


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The dose of 280 mg SC Q2W is predicted to achieve maximal reduction in naïve B cells 
and near maximal ICOSL coverage (mean percent receptor occupancy of > 90% in 
~90% of simulated subjects at steady-state trough). 
Overall, the safety of the selected doses is supported by the clinical and preclinical data, 
and the 3 doses have been selected to evaluate dose-response and exposure-response 
relationships. 
5.5 
Patient Input on Study Design 
Patient input was obtained for this study in various international regions.  Patients were 
able to understand and comment on the requirements for study participation. 
6. 
Study Population 
Screening:  Investigators will be expected to maintain a screening log of all potential 
study candidates that includes limited information about the potential candidate (eg, date 
of screening).  This log may be completed and updated via an Interactive Response 
Technology (IRT) system.  Eligibility criteria will be evaluated at screening visit and at 
baseline/day 1 visit, prior to randomization. 
The screening visit will confirm all eligibility requirements described in Section 6.1 and 
6.2 and Table 2-1.  All SLE-related screening criteria will be reviewed by the adjudication 
team.  The site will be notified by electronic communication of the results of this review 
and baseline/visit 1 should not occur prior to this notification.  Subjects who do not meet 
the eligibility criteria will be considered screen fails but may be eligible for rescreening as 
described in Section 9.1.1. 
The baseline/day 1 visit will occur up to 33 calendar days following the screening visit (it 
can be earlier if all eligibility requirements for screening visit are met).  Baseline/day 1 
visit will confirm eligibility requirements prior to randomization, as described in 
Section 6.3.  Subject who meet all eligibility criteria may proceed to randomization and 
dosing.  Subjects who do not meet criteria may be eligible for rescreening as described 
in Section 9.1.1. 
Before any study-specific activities/procedures, the appropriate written informed consent 
must be obtained (see Section 12.3). 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions will not be provided. 


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Figure 6-1.  Screening and Enrollment 
 
PD = pharmacodynamic; PK = pharmacokinetic; SLE = systemic lupus erythematosus  
6.1 
Inclusion Criteria Screening Visit  
Subjects are eligible to be included in the study only if all the following criteria apply: 
101 
Subject has provided informed consent prior to initiation of any study-specific 
activities/procedures. 
102 
Age  18 years to  75 years at screening visit. 
103 
Fulfills classification criteria for SLE according to the 2019 European League 
Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 
classification criteria for SLE (Aringer et al, 2019), with antinuclear antibody 
 1:80 by immunofluorescence on Hep-2 cells being present at screening. 
104 
Hybrid SLEDAI score  6 points with a "Clinical" hSLEDAI score  4 points. 
The "Clinical" hSLEDAI is the hSLEDAI assessment score without the inclusion 
of points attributable to laboratory results, including urine or immunologic 
parameters.  
Additional protocol-specific rules are applied at screening and throughout the 
study, as follows: 
 
Arthritis:  Arthritis (at least 3 tender and swollen joints) must involve joints in 
the hands or wrists for the hSLEDAI scoring. 
 
Alopecia:  Subjects should have hair loss without scarring; should neither 
have alopecia areata nor androgenic alopecia; and should have a CLASI 
activity score for alopecia  2. 
 
Oral ulcers:  Ulcers location and appearance must be documented by the 
investigator. 
 
Scleritis and Episcleritis:  the presence of stable SLE-related scleritis and 
episcleritis (ie, that will likely not require initiation/increase in 
immunosuppressants/immunomodulators as outlined in the 


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inclusion/exclusion criteria) must be documented by an ophthalmologist and 
other causes excluded. 
 
Renal:  subjects with urine protein/creatinine ratio  3000 mg/g (or equivalent 
method) in a clear catch spot urine sample can enroll and be scored in the 
hSLEDAI, provided the subject has a clinical hSLEDAI  4 and did not 
receive induction treatment for nephritis within the last year. 
 
Pleurisy and Pericarditis: symptoms of pleurisy and pericarditis must be 
accompanied by objective findings to be scored in the hSLEDAI. 
105 
Unless there is a documented intolerance, subjects must be taking:   
 
Only 1 of the following SLE treatments:  anti-malarial (hydroxychloroquine, 
chloroquine, or quinacrine), azathioprine, methotrexate, leflunomide, 
mycophenolate mofetil/acid mycophenolic, or dapsone.   
OR 
 
2 of the above-mentioned SLE treatments in which 1 must be anti-malarial 
(hydroxychloroquine, chloroquine, or quinacrine). 
Treatment should be taken for  12 weeks prior to screening and must be a 
stable dose for  8 weeks prior to screening.   
106 
For subjects taking OCS, dose must be  20 mg/day of prednisone or OCS 
equivalent, and the dose must be stable at baseline visit for  2 weeks prior to 
screening visit. 
6.2 
Exclusion Criteria Screening Visit  
Subjects are excluded from the study if any of the following criteria apply: 
Disease Related 
201 
Urine protein creatinine ratio  3000 mg/g (or equivalent) at screening or 
induction therapy for lupus nephritis within 1 year prior to screening visit. 
202 
Active CNS lupus within 1 year prior to screening including, but not limited to, 
aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating 
syndrome, optic neuritis, psychosis, seizures, or transverse myelitis. 
Other Medical Conditions 
203 
Diagnosis of any inflammatory joint or skin disease other than SLE (confirmed 
accurate by the PI) currently present or within 1 year prior to screening which 
would interfere with SLE disease assessment based on investigator judgment.  
204 
Any disease other than SLE that has required treatment with oral or parenteral 
CS for > 2 weeks within 6 weeks prior to screening. 
205 
Active infection (including chronic or localized infections), OR infection for which 
anti-infectives were initiated within 4 weeks prior to screening OR presence of 
serious infection, defined as requiring hospitalization or IV anti-infectives within 
8 weeks prior to screening. 


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206 
Active tuberculosis or latent tuberculosis with no documented past history of 
adequate treatment per local standard of care. 
207 
Positive test for tuberculosis during screening defined as:  either positive or 
indeterminate QuantiFERON®-TB OR T-spot test OR positive purified protein 
derivative (PPD) ( 5 mm of induration at 48 to 72 hours after test is placed). 
 
Subjects with a positive PPD and a history of Bacillus Calmette-Guérin 
vaccination are allowed to enroll with a negative QuantiFERON®-TB or 
T-Spot test. 
 
Indeterminate QuantiFERON®-TB or T-spot test can be repeated once, based 
on investigator judgment.  Subjects can enroll if second result is negative.  
Subjects with persistent indeterminate or positive test results should proceed 
as below. 
 
Subjects with a positive PPD test (without a history of Bacillus 
Calmette-Guérin vaccination) or a positive or indeterminate 
QuantiFERON®-TB or T-Spot test (including repeated results when 
performed) are allowed to enroll if they meet ALL the following criteria at 
screening: 
 
no symptoms per tuberculosis worksheet provided by Amgen 
 
documented history of adequate TB treatment or prophylactic treatment 
for latent TB (completed per local standard of care prior to the start of 
investigational product) 
 
no known exposure to a case of active tuberculosis after most recent 
treatment/prophylaxis 
 
chest X-ray with no new radiographic findings suggestive of active TB (to 
be read by local facility) 
Note:  1) these tests do not need to be repeated at the time of rescreening, 
unless rescreening occurs  12 months from screening visit or subject’s 
medical/epidemiologic history suggests newly acquired infection or 
recent contact with TB cases and 2) repeat testing of an indeterminate 
QuantiFERON test using the T-spot test may be performed. 
208 
Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core 
antibody (HBcAb) in the presence of detectable viral DNA in peripheral blood, 
assessed by polymerase chain reaction (PCR).  Subjects positive for HBcAb 
without detectable viral DNA by PCR are allowed to enroll, provided the subject 
undergoes monitoring of viral DNA by PCR at approximately every 3 months 
during the treatment period, up to a minimum of 16 weeks after last 
administration of the investigational product.  If viral DNA becomes 
detectable during the study period, the subject should be evaluated by an 
hepatologist before stopping the treatment to evaluate the need to start specific 
hepatitis B treatment before investigational product discontinuation.  A history of 
hepatitis B vaccination without history of hepatitis B infection (ie, positive 
hepatitis B surface antibody (HBsAb), negative HBsAg and negative HBcAb) is 
allowed. 


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Positive for hepatitis C antibody in the presence of detectable viral ribonucleic 
acid (RNA) in peripheral blood, assessed by PCR.  Subjects positive for hepatitis 
C antibody without detectable viral RNA by PCR are allowed to enroll, provided 
the subjects undergo monitoring of viral RNA by PCR at approximately every 
3 months during treatment period up to a minimum of 16 weeks after last 
administration of the investigational product.  If viral RNA become detectable 
during the study period, the subject should be evaluated by an hepatologist 
before stopping the treatment to evaluate the need to start specific hepatitis C 
treatment before investigational product discontinuation. 
Note:  these tests do not need to be repeated at the time of rescreening, unless 
rescreening occurs  12 months from screening or there is evidence or suspicion 
of recent infection. 
209 
Known history of HIV or positive serology for HIV antibodies at screening. 
Note: these tests do not need to be repeated at the time of rescreening, unless 
rescreening occurs  12 months from screening or there is evidence or suspicion 
of recent infection. 
210 
Presence of 1 or more significant concurrent medical conditions per investigator 
judgment, including but not limited to the following: 
 
poorly controlled diabetes or hypertension 
 
symptomatic heart failure (New York Heart Association class III or IV) 
 
myocardial infarction or unstable angina pectoris within the past 12 months 
prior to screening 
 
severe chronic pulmonary disease requiring oxygen therapy 
 
multiple sclerosis or any other demyelinating disease 
 
major chronic inflammatory disease or connective tissue disease other than 
SLE (eg, RA, Primary Sjogren Syndrome, Mixed Connective Tissue Disease) 
Note:  Subjects with positive antiphospholipid antibodies or diagnosis of 
antiphospholipid antibody syndrome according to the revised Sapporo 
classification criteria (Miyakis et al, 2006) can enroll in the study provided they 
have no current or past history of thrombotic events and meet all the other 
eligibility criteria.  
211 
Any history of malignancy with the following exceptions: 
 
resolved non-melanoma skin cancers > 5 years prior to screening 
 
resolved cervical carcinoma > 5 years prior to screening 
 
resolved malignant colon polyps > 5 years prior to screening 
Prior/Concomitant Therapy 
212 
Currently receiving or had treatment with:  cyclophosphamide, chlorambucil, 
nitrogen mustard, or any other alkylating agent within 6 months prior to 


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screening; sirolimus or oral calcineurin inhibitors (eg, cyclosporine, tacrolimus, 
voclosporin) or thalidomide within 4 weeks prior screening. 
213 
Currently receiving or had treatment with a Janus kinase (JAK) inhibitor within 
1 month prior to screening. 
214 
Currently receiving or had treatment with an immune checkpoint inhibitor (eg, 
PD-1 inhibitor, PD-L1 inhibitor, CTLA-4 inhibitor). 
Note:  Abatacept is not considered a CTLA-4 inhibitor and is referred to below. 
215 
Current or previous treatment with a biologic agent with 
immunosuppressive/immunomodulatory activity for SLE or other conditions 
as follows: rituximab within 6 months prior to screening; abatacept, belimumab, 
and anifrolumab within the past 3 months prior to screening; other biologics 
within less than 5 drug half-lives or within the period of pharmacodynamic 
activity, when relevant, prior to screening. 
216 
Subjects who have received intra-articular, intra-lesional, or systemic 
corticosteroid injections within 6 weeks prior to screening. 
217 
Subjects who have received live vaccines within 5 weeks prior to screening, or 
plan to receive live vaccines during the treatment period and up to 16 weeks after 
last administration of the investigational product. 
Prior/Concurrent Clinical Study Experience 
218 
Currently receiving treatment in another investigational device or drug study. 
219 
Ending a treatment with an investigational drug or investigational device less 
than 5 drug half-lives from the last dose of the investigational product or within 
the period of its pharmacodynamic activity when relevant, at screening. 
220 
Subject previously randomized in this study. 
Diagnostic Assessments 
221 
Presence of laboratory abnormalities at screening including the following: 
 
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)  
> 2 x upper limit of normal (ULN) 
 
Serum total bilirubin (TBL) ≥ 1.2 mg/dL (≥ 26 mol/L) except for 
Gilbert’s Syndrome 
 
Hemoglobin < 8 g/dL (< 80 g/L) 
 
Platelet count < 75,000/mm3 (75 x 109/L) 
 
White blood cell count < 2000 cells/mm3 (2 x 109/L) 
 
Absolute neutrophil count (ANC) < 1,000/mm3 (1 x 109/L) 
 
Calculated glomerular filtration rate of  30 mL/min/1.73 m2 using the 
Modification of Diet in Renal Disease (MDRD) formula 


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222 
Any other laboratory abnormality, which in the opinion of the investigator or 
Central Review Team, poses a safety risk, will prevent the subject from 
completing the study or will interfere with the interpretation of the study results, or 
might cause the study to be detrimental to the subject. 
Other Exclusions 
223 
Female subject is pregnant or breastfeeding or planning to become pregnant or 
breastfeed during treatment and for at least 10 additional weeks after the last 
dose of investigational product. 
224 
Female subjects of childbearing potential unwilling to use 1 highly effective 
method of contraception during treatment and for at least 10 additional weeks 
after the last dose of investigational product administration.  Refer to 
Section 12.5 for additional contraceptive information. 
225 
Female subjects of childbearing potential with a positive pregnancy test (serum 
pregnancy test required at screening, and urine pregnancy test required at 
day 1 visit). 
226 
Subject has known sensitivity to any of the products to be administered during 
dosing. 
227 
Subject likely to not be available to complete all protocol-required study visits or 
procedures, and/or to comply with all required study procedures (eg, Clinical 
Outcome Assessments) to the best of the subject and investigator’s knowledge. 
228 
History or evidence of any other clinically significant disorder, condition or 
disease (with the exception of those outlined above) that, in the opinion of the 
investigator or Central Review Team would pose a risk to subject safety or 
interfere with the study evaluation, procedures, or completion. 
6.3 
Inclusion Criteria Baseline/Day 1 Visit 
Baseline/day 1 visit should occur after confirmation of SLE-related eligibility by the 
adjudication team and up to 33 days after screening visit.  At baseline/day 1 visit, the 
following 2 criteria should be assessed prior to randomization:   
107 
Stability of SLE treatments:  OCS and other immunosuppressants/ 
immunomodulators doses must be stable since screening visit, by reviewing 
subject’s medication history. 
108 
Disease activity:  active disease as indicated by clinical hSLEDAI score  4 must 
be observed (clinical hSLEDAI score is the hSLEDAI assessment score without 
the inclusion of points attributable to laboratory results). 
6.4 
Subject Enrollment 
Before subjects begin participation in any study-specific activities/procedures, Amgen 
requires a copy of the site’s written institutional review board/independent ethics 


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committee (IRB/IEC) approval of the protocol, informed consent form, and all other 
subject information as applicable (see Section 12.3). 
The subject must personally sign and date the IRB/IEC and Amgen approved informed 
consent before commencement of study-specific procedures. 
A subject is considered enrolled when the investigator decides and all eligibility criteria 
(from screening visit and baseline/day 1 visit) are met.  The investigator is to document 
this decision and date, in the subject’s medical record and in the enrollment case report 
form (CRF).  At baseline/day 1 visit, if the subject meets all eligibility criteria, he/she is 
subsequently enrolled and randomized to a treatment regimen.  Subjects who meet 
screening visit eligibility but do not meet baseline/day 1 visit eligibility criteria are 
considered screen fails.  Subjects may rescreen up to 2 times, as described in 
Section 9.1.1. 
Each subject who enters into the screening period for the study (defined as the point at 
which the subject signs the informed consent form) receives a unique subject 
identification number before any study-related activities/procedures are performed.  The 
subject identification number will be assigned by IRT.  This number will be used to 
identify the subject throughout the clinical study and must be used on all study 
documentation related to that subject. 
The subject identification number must remain constant throughout the entire clinical 
study; it must not be changed after initial assignment, including if a subject is 
rescreened.  This number will not necessarily be the same as the randomization number 
assigned for the study. 
6.5 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study 
but are not subsequently enrolled in the study.  A minimal set of screen failure 
information will be collected that includes demography, screen failure details, eligibility 
criteria, and any serious adverse events. 
Individuals who do not meet the criteria for participation in this study (screen failure) may 
be rescreened up to 2 additional times.  Refer to Section 9.1.1. 
7. 
Treatments 
Investigational product is defined as any investigational product(s), non-investigational 
product(s), placebo, or medical device(s) intended to be administered to a study subject 
according to the study protocol. 


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Note that in several countries, investigational product and non-investigational product 
are referred to as investigational medicinal product and non-investigational medicinal 
product, respectively. 
The Investigational Product Instruction Manual (IPIM), a document external to this 
protocol, contains detailed information regarding the storage, preparation, destruction, 
and administration of each treatment shown in Section 7.1.1 below. 
7.1 
Treatment Procedures 
7.1.1 
Investigational Products 
AMG 570 will be manufactured and packaged by Amgen Inc. and distributed using 
Amgen clinical investigational product distribution procedures.  AMG 570 is a clear 
colorless sterile solution which will be packaged in open-label 5 mL glass vials 
containing 70 mg/ml of AMG 570 formulated with 
 Placebo will be presented in identical 
containers and stored/packaged the same as AMG 570, but will not contain AMG 570 
protein.  All AMG 570 and placebo will be shipped to the study site and should be stored 
the same as AMG 570 at 2C to 8C with limited exposure to light. 
For more information regarding investigational product handling and preparation please 
see the study-specific IPIM which is provided as a separate document. 


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Table 7-1.  Investigational Products 
Investigational Product Name 
Amgen Investigational Product:  AMG 570a 
Placebo 
Dosage Formulation 
Clear colorless sterile solution in 5 mL glass vials 
containing 70 mg/mL of AMG 570 
Placebo will be presented in identical containers, 
and stored/packaged the same as AMG 570 
Unit Dose Strength(s)/ 
Dosage Level(s) and Dosage Frequency 
70 mg/Q2W 
280 mg/Q2W 
420 mg/Q2W 
 
Route of Administration 
SC injection 
 
Accountability 
 Total volume of preparation, quantity 
administered start date, start time, and box 
number of AMG 570 is to be recorded on each 
subject's CRF. 
 
Dosing Instructions 
PI or designee will administer product in subject’s 
abdomen.  Dosing must be administered on day 
of scheduled visit after all clinical assessments 
have been completed.  No dose adjustments for 
weight or restrictions with food intake are 
required. 
 
CRF  Case Report Form; PI  Principal Investigator; SC  subcutaneous; Q2W  every 2 weeks  
aAMG 570 will be manufactured and packaged by Amgen and distributed using Amgen clinical investigational product distribution procedures. 
 


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7.1.2 
Non-investigational Products 
No non-investigational products will be used. 
7.1.3 
Medical Devices 
There are no investigational medical devices used in this study. 
Non-investigational medical devices may be used in the conduct of this study as part of 
standard care. 
Non-investigational, non-Amgen medical devices (eg, syringes, sterile needles), that are 
commercially available are not usually provided or reimbursed by Amgen (except, for 
example, if required by local regulation).  The investigator will be responsible for 
obtaining supplies of these devices. 
7.1.4 
Other Therapies 
7.1.4.1 
Immunosuppressants/Immunomodulators 
Subjects should receive stable doses of immunomodulators and/or immunosuppressants 
agents from  8 weeks prior to screening through week 52.  If a subject requires a higher 
dose of an immunosuppressant/immunomodulator or requires a new 
immunosuppressant/immunomodulator at any time during the study period (other than 
CS, see below), the subject may continue the study but will be considered treatment 
failures for primary efficacy endpoint analyses for the subsequent time points.  
These subjects will also be allowed to continue investigational product at the 
investigator's discretion, except subjects who initiate any 
immunosuppressant/immunomodulator listed in Section 7.1.7 (treatments 
a through i). 
Subjects may reduce dosage in immunomodulators and/or immunosuppressants if the 
subject develops unacceptable side effects or abnormal laboratory values attributable to 
these medications. 
7.1.4.2 
Oral, Intramuscular, and Intravenous Corticosteroids 
Initiation or temporary increases in the OCS dosage are not encouraged but are allowed 
if initiated at any time between weeks 0 to 8 with a return to baseline dose within the 
subsequent 2 weeks.  In such cases, initiation or temporary increase of OCS is limited to 
a dose  5 mg/day of prednisone (or equivalent).  Subjects who require higher dose 
increase of OCS (> 5 mg/day of prednisone or equivalent), or IM CS or IV CS, or those 
who cannot return to baseline dose within the following 2 weeks or subjects who require 
initiation or CS dose increase at any time point after week 10 can continue the study or 


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investigational product at the investigator's discretion but will be considered 
treatment failures for the primary efficacy endpoint. 
Subjects may begin tapering OCS up to the week 44 assessment with initiation of 
tapering based upon clinical judgment of the treating physician.  The tapering schedule 
should be directed at the discretion of the investigator but should generally not be 
tapered more than 10% to 20% of the prior dose per week.  Between weeks 44 and 52, 
the OCS dosing should again remain stable. 
7.1.4.3 
Topical Corticosteroids and Topical Calcineurin Inhibitors 
Subjects who are using topical CS or topical calcineurin inhibitors must remain on a 
stable regimen but may discontinue topical corticosteroids at any time if clinically 
indicated. 
7.1.4.4 
Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Other 
Analgesic Therapies 
Subjects taking non-steroidal anti-inflammatory drugs (NSAIDs) or other analgesic 
therapies should remain on stable dose from day 1 through week 52.  NSAIDs or other 
analgesic therapies used for SLE disease activity should be held for 24 hours prior to the 
scheduled monthly efficacy assessments.  Subjects can return to their regular doses 
immediately after the clinical visit is complete.  Discontinuation or reduction of NSAIDs or 
other analgesic therapy dose during the study is allowed based on the investigator’s 
judgment.  Initiation or increases in the NSAIDs or other analgesic therapy dose during 
the study are allowed if:  1) not initiated within 24 hours of the scheduled monthly 
efficacy assessments, 2) the subject returns to baseline dose within the subsequent 
2 weeks, and 3) it is not within 2 weeks prior to the week 52 visit. 
7.1.4.5 
Anti-proteinuria Agents 
Subjects with SLE-related proteinuria taking anti-proteinuria agents (eg, angiotensin II 
receptor blockers, angiotensin-converting enzyme inhibitors), should remain on stable 
dose through week 52.  Discontinuation or dose reduction of anti-proteinuria agents 
during the study is allowed in case of intolerance or toxicity.  Initiation or dose increase 
of anti-proteinuria agents (eg, angiotensin II receptor blockers, angiotensin-converting 
enzyme inhibitors) for the purpose of SLE-related proteinuria during the study should be 
avoided. 
7.1.5 
Other Treatment Procedures 
7.1.5.1 
Home Health Care Visits 
Section 7.1.5.1 is not applicable for participating sites in Bulgaria. 


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If permitted by national and/or local regulations, the investigator may utilize a qualified 
home health care service provider, selected and approved by the sponsor, for 
investigational product administration.  This service can be offered to subjects that have 
not experienced adverse events considered to be related to investigational product that 
in the opinion of the investigator may pose a risk for home health care administration of 
investigational product.  The study may include up to 8 home visits, including weeks 22, 
26, 30, 34, 38, 42, 46, and 50.  
 
 
.  In addition to 
administration of investigational product, safety assessments including vital signs, 
adverse events, serious adverse events, and concomitant medications review will be 
collected. 
Home health care staff must be included on the study delegation log (authorized by the 
investigator) before any study-related tasks to be conducted by each home health care 
provider are started.  In addition, study-specific training including requirements for 
recording source documentation for the home health care provider, must be completed 
before they conduct any study-related tasks. 
Following home health care visit, all the information collected will be documented on the 
home health care services visit worksheet and forwarded to the investigator.   
A comprehensive list of all home health care services, as well as mandatory procedural 
and data collection requirements, will be separately provided in a home health care 
manual. 
7.1.6 
Product Complaints 
A product complaint is any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a drug, combination product, or device after it is released for 
distribution to market or clinic by either (1) Amgen or (2) distributors or partners for 
whom Amgen manufactures the material.  This includes all components distributed 
with the drug, such as packaging drug containers, delivery systems, labeling, and 
inserts.  This includes AMG 570/placebo provisioned and/or repackaged/modified by 
Amgen. 
Any product complaint(s) associated with an investigational product supplied by Amgen 
are to be reported according to the instructions provided in the IPIM. 


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7.1.7 
Excluded Treatments, Medical Devices, and/or Procedures During 
Study Period 
Subjects who are receiving treatments listed below are allowed to remain in the 
study at the investigator’s discretion.  Subjects are also allowed to continue 
investigational product at the investigator’s discretion except those who initiate 
any treatment listed below from a through i:   
a. 
investigational therapies or commercially available biologic agents with 
immunosuppressive/immunomodulatory activity for SLE or other conditions (eg, 
rituximab or belimumab) 
b. cytotoxic agents including: chlorambucil, cyclophosphamide, nitrogen mustard, or 
other alkylating agents 
c. 
thalidomide 
d. sirolimus 
e. 
oral calcineurin inhibitors (eg, tacrolimus, cyclosporine, etc.) 
f. 
T cell depleting agents (eg, antithymocyte globulin, Campath) 
g. recombinant IL-2 (eg, Proleukin) 
h.  JAK inhibitors  
i. 
live vaccines  
j. 
intra-articular, IM, or IV CS, including adrenocorticotropic hormone 
k. 
intra-articular hyaluronic acid injections 
 
7.2 
Method of Treatment Assignment 
Subjects who meet all eligibility criteria will be randomized to receive AMG 570 at 70 mg 
Q2W, 280 mg Q2W, 420 mg Q2W, or placebo in a double-blind manner.  The 
randomization starts as 1:1:1:1 and then could be adapted at each IA (if before full 
enrollment) based on the clinical efficacy (RAR) for allocating more subjects to more 
efficacious doses and fewer subjects to less efficacious doses.  The randomization 
allocation probability for placebo group will be kept constant at 25%.  The randomization 
will be stratified by geographic region (North America + Western Europe vs ROW) and 
screening hSLEDAI score (≥ 10 or < 10). 
Each randomized subject will receive a single, unique randomization number via IRT at 
randomization.  The randomization date is to be documented in the subject’s medical 
record as registered in the IRT and on the enrollment CRF. 
7.3 
Blinding 
This is a double-blind study.  Treatment assignment will be blinded to all subjects, site 
personnel, and Amgen as described below. 


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7.3.1 
Site Personnel Access to Individual Treatment Assignments 
A subject’s treatment assignment is to only be unblinded by the investigator when 
knowledge of the treatment is essential for the further management of the subject on this 
study or may potentially impact the safety of the subject.  Unblinding at the study site for 
any other reason will be considered a protocol deviation.  It is encouraged that the 
Amgen Trial Manager be notified before the blind is broken unless the investigator 
believes that identification of the investigational product is required for a medical 
emergency.  If this is not possible, the Amgen Trial Manager must be notified within 
24 hours after breaking the blind.  The date and reason that the blind was broken must 
be recorded in the source documentation and CRF, as applicable.  Continuation of such 
subjects in the study should be discussed with the medical monitor. 
7.3.2 
Access to Individual Subject Treatment Assignments by Amgen or 
Designees 
Blinded individuals will not have access to unblinded information until the study is 
formally unblinded.  Unblinding and potentially unblinding information is not to be 
distributed to the study team, investigators or subjects prior to the study being formally 
unblinded which will occur at the final analysis except as specified (eg, Section 7.3.2).  
Otherwise, if unblinding occurs, only the subject and investigators will have access to 
what investigational product treatment was received and Amgen will not have access to 
this information. 
Individual subject treatment assignments will be maintained by the IRT System.  Any 
unplanned unblinding occurring during the study period will be documented and reported 
in the final clinical study report.  Staff from Clinical Supply Chain, Biological Sample 
Management, PK and Drug Metabolism, Clinical Pharmacology Modelling and 
Simulation, Clinical Immunology, Department of Molecular Sciences and Computational 
Biology, Safety, internal team, and Global Biostatistical Science departments who are 
responsible for tracking, assaying, or analyzing biological samples during the conduct of 
this study are considered to be unblinded to the treatment assignments in this study.  
These individuals will not have access to subject level clinical data apart from the 
samples they are assaying and analyzing during the course of the study.  If 
exposure-response analysis is performed, the exposure-response analysis team, 
including Clinical Pharmacology Modeling and Simulation (CPMS) and Global 
Biostatistics Sciences, who are independent of the study team, may be unblinded.  If 
needed by the Development/Therapeutic Area (TA) Head to make decisions after 
receiving DMC recommendations at IAs, pre-specified independent biostatistician(s), 


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programmer(s), and/or CPMS scientist(s) outside the study team may be unblinded to 
carry out ad-hoc analyses as requested by the Development/TA Head at IAs (details will 
be specified in data access plan for IA). 
7.3.3 
Unblinding Procedure For Investigators 
A subject's treatment assignment must only be unblinded when this knowledge is 
essential for management of the subject.  Before unblinding, the investigator (or site) 
should contact Amgen.  In the interest of subject safety, where this is not possible, the 
investigator must contact Amgen within 1 working day of the unblinding event.  The 
actual treatment assignment must only be shared to those who require it for treatment of 
the subject and should not be recorded in the CRF.  The IRT system will assign each 
subject, at each dispensing visit, with individually numbered Investigational Product 
containers.  This unique number will form the basis of the unblinding information.  For 
unblinding, only authorized staff assigned with access to the unblinding module in the 
IRT can obtain unblinding information.  For further details on access and unblinding, 
refer to the IRT Manual. 
Contact details for emergency unblinding: 
Amgen, Inc. 
Address: One Amgen Center Drive 
Thousand Oaks, CA 91320, USA 
Telephone: +1 (805) 447-1000 
7.4 
Dose Modification 
7.4.1 
Dose-cohort Study Escalation/De-escalation and Stopping Rules 
All subjects will receive a fixed dose of the investigational product (AMG 570/placebo).  
No dose adjustments will be allowed. 
7.4.2 
Dosage Adjustments, Delays, Rules for Withholding or Restarting, 
Permanent Discontinuation 
7.4.2.1 
Amgen Investigational Product:  AMG 570 or Placebo 
No dose adjustments will be allowed. 
7.4.2.2 
Non-Amgen Non-Investigational Product:  SLE Standard of Care 
Therapy and Oral Corticosteroids  
The reason for dose change of OCS (Section 7.1.4.2) and/or other medications including 
for SLE SOC therapies (Section 7.1.4; anti-malarials, azathioprine, methotrexate, 
leflunomide, mycophenolate mofetil, or dapsone) is to be recorded on each subject’s 
CRF(s). 


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7.4.3 
Hepatotoxicity Stopping and Rechallenge Rules 
Refer to Section 12.7 for details regarding drug-induced liver injury guidelines, as 
specified in the Guidance for Industry Drug-Induced Liver Injury:  Premarketing Clinical 
Evaluation, July 2009.  This will be used for stopping and rechallenge with the agent. 
7.5 
Preparation/Handling/Storage/Accountability 
Guidance and information on preparation, handling, storage, accountability, destruction, 
or return of the investigational product during the study are provided in the IPIM. 
7.6 
Treatment Compliance 
Subjects will receive the 26 doses of investigational product (AMG 570 or placebo) at the 
research facility or via home health care visits, administered by qualified study personnel 
for the duration of the study.  The investigational product will be administered Q2W and 
dosing should occur within a visit window of ± 3 business days from the scheduled 
dosing date.  There should also be a minimum of 11 days between administrations of 
investigational product.  If any scheduled dose after study day 1 is delayed 7 or more 
calendar days from the scheduled visit date, this will be considered a missed dose and 
recorded as such on the CRF.  The next dose is to be given on the next scheduled visit 
date (based on study day 1).  Subjects will be observed for at least 30 minutes following 
dose administration.  Vital signs, adverse events, serious adverse events, concomitant 
medications and efficacy assessments will be obtained prior to administration of the 
investigational product. 
7.7 
Treatment of Overdose 
The effects of overdose of this product are not known. 
7.8 
Prior and Concomitant Treatment 
7.8.1 
Prior Treatment 
Prior therapies that were being taken/used from time of initial diagnosis with SLE 
through the date of randomization will be collected.  For prior therapies, collect therapy 
name, indication, dose, unit, frequency, start date, and stop date. 
7.8.2 
Concomitant Treatment 
Throughout the study, investigators may prescribe any concomitant medications or 
treatments deemed necessary to provide adequate supportive care except for those 
listed in Section 7.1.7. 
Concomitant therapies are to be collected from randomization through the end of the 
safety follow-up period.  For concomitant therapies, collect therapy name, indication, 


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dose, unit, frequency, start date, and stop date.  Guidelines for immunomodulators, 
immunosuppressants, and OCS are provided in Section 7.1.4.1 through Section 7.1.4.5. 
8. 
Discontinuation Criteria 
Subjects have the right to withdraw from investigational product and/or other 
protocol-required therapies, protocol procedures, or the study as a whole at any time 
and for any reason without prejudice to their future medical care by the physician or at 
the institution.  The investigator and/or sponsor can decide to withdraw a subject(s) from 
investigational product, device, and/or other protocol-required therapies, protocol 
procedures, or the study as a whole at any time prior to study completion for the reasons 
listed in Sections 8.1, 8.2, and 8.2.1. 
8.1 
Discontinuation of Investigational Product 
Subjects (or a legally acceptable representative) can decline to continue receiving 
investigational product and/or other therapies or procedures at any time during the study 
but continue participation in the study.  If this occurs, the investigator is to discuss with 
the subject the appropriate processes for discontinuation from investigational product or 
other therapies and must discuss with the subject the possibilities for continuation of the 
Schedule of Activities (see Table 2-1 and Table 2-2) including different options of 
follow-up (eg, in person, by phone/mail, through family/friends, in 
correspondence/communication with other treating physicians, from the review of 
medical records) and collection of data, including endpoints and adverse events, as 
applicable and must document this decision in the subject’s medical records.  Subjects 
who have discontinued investigational product and/or therapies or procedures should not 
be automatically removed from the study and will be encouraged to maintain the planned 
scheduled assessments for monthly efficacy and safety visits (Table 2-1 and Table 2-2) 
to allow safety surveillance and collection of outcome data up to week 52 or for a 
minimum of 16 weeks after the last dose of investigational product (see Section 9.1.2 for 
additional details). 
Subjects may be eligible for continued treatment with Amgen investigational product(s) 
and/or other therapies by a separate protocol or as provided for by the local country’s 
regulatory mechanism, based on parameters consistent with Section 12.3. 
Reasons for removal from protocol-required investigational product(s) or procedural 
assessments may include any of the following:   
 
Decision by Sponsor 


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 
Lost to follow-up 
 
Death 
 
Ineligibility determined 
 
Protocol deviation 
 
Non-compliance  
 
Adverse event 
 
Subject request 
 
Pregnancy 
 
Disease flare  
8.2 
Discontinuation From the Study 
Withdrawal of consent for a study means that the subject does not wish to receive 
further protocol-required therapies or procedures, and the subject does not wish to or is 
unable to continue further study participation.  Subject data up to withdrawal of consent 
will be included in the analysis of the study, and where permitted, publicly available data 
can be included after withdrawal of consent.  The investigator is to discuss with the 
subject appropriate procedures for withdrawal from the study and must document the 
subject’s decision to withdraw in the subject’s medical records. 
If a subject withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must notify Amgen accordingly 
(see Section 12.6 for further details).  Refer to the Schedule of Activities (Section 2) for 
data to be collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed. 
8.2.1 
Reasons for Removal From Study 
Reasons for removal of a subject from the study are:   
 
Decision by sponsor 
 
Withdrawal of consent from study 
 
Death 
 
Lost to follow-up 


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8.3 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a subject fails to return to the clinic for a required 
study visit: 
 
The site must attempt to contact the subject and reschedule the missed visit as soon 
as possible and counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or is able to 
continue in the study. 
 
In cases in which the subject is deemed lost to follow-up, the investigator or 
designee must make every effort to regain contact with the subject (where possible, 
3 telephone calls and, if necessary, a certified letter to the subject’s last known 
mailing address or local equivalent methods).  These contact attempts are to be 
documented in the subject’s medical record. 
 
If the subject continues to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.  
 
For subjects who are lost to follow-up, the investigator can search publicly available 
records where permitted to ascertain survival status.  This ensures that the data 
set(s) produced as an outcome of the study is/are as comprehensive as possible. 
9. 
Study Assessments and Procedures 
Study procedures and their time points are summarized in the Schedule of Activities 
(Section 2). 
As protocol waivers or exemptions are not allowed if an enrolled subject is subsequently 
determined to be ineligible for the study, this must be discussed with the sponsor 
immediately upon occurrence or awareness to determine if the subject is to continue or 
discontinue investigational product. 
Adherence to the study design requirements, including those specified in the Schedule 
of Activities (Section 2), is essential and required for study conduct. 
9.1 
General Study Periods 
9.1.1 
Screening, Enrollment and/or Randomization 
Informed consent must be obtained before completing any screening procedure or 
discontinuation of standard therapy for any disallowed therapy.  After the subject has 
signed the informed consent form, the site will register the subject in the IRT and screen 
the subject in order to assess eligibility for participation.  The screening window is up to 
33 calendar days. 


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All eligibility evaluations (at screening visit and baseline/day 1 visits, prior to 
randomization) must be completed to confirm that potential subjects meet all eligibility 
criteria (Section 6).  The investigator will maintain a screening log to record details of all 
subjects screened, to confirm eligibility or record reasons for screening failure (see 
Section 6.5), as applicable.  If a lab retest is required, the sponsor should approve prior 
to being retested. 
A subject is considered enrolled when the investigator decides and all eligibility criteria 
(from screening visit and baseline/day 1 visit) are met.  The investigator is to document 
this decision and date, in the subject’s medical record and in/on the enrollment CRF.  At 
baseline/day 1 visit, if the subject meets all eligibility criteria, he/she is subsequently 
enrolled and randomized to a treatment regimen. 
If a subject has not met all eligibility criteria either during or at the end of the screening 
period (maximum 33 days), the subject will be registered in IRT as a screen fail.  
Subjects should always complete the 33-day screening period before being considered 
for re-screening.  At that point, subjects may be rescreened, as follows: 
 
Subjects who do not meet the hSLEDAI criteria (total hSLEDAI score  6 at 
screening visit or clinical hSLEDAI score  4 at baseline/day 1 visit) must wait at 
least 2 weeks before rescreening. 
 
Subjects who have not maintained stable OCS dosing at day 1 will be required to 
wait at least 2 weeks prior to rescreening (Section 6.1). 
 
Subjects who have not maintained stable immunosuppressant/immunomodulatory 
dosing at day 1 will be required to wait at least 8 weeks prior to rescreening 
(Section 6.1).  
 
Subjects who met eligibility criteria but were not able to enroll within the screening 
period (within the 33 days), can rescreen immediately. 
Once the subject is registered as rescreened, a new 33-day screening window will 
begin.  All procedures noted in Section 6, including the informed consent and all 
laboratory parameters (Section 9.2.4) must be repeated with the following exception: 
 
tuberculosis screening tests (QuantiFERON®-T, T-spot test OR PPD), serologies for 
hepatitis B virus, hepatitis C virus and HIV may not be repeated provided that 
rescreening occurs  12 months of screening visit (where those test results were 
negative) and there is no patient’s medical/epidemiological history suggestive of 
infection or recent exposure to cases of infection. 
Screen fail subjects may be eligible for re-screening up to 2 times. 


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9.1.2 
Treatment Period 
The 52-week treatment period is the study period following randomization to the planned 
week 52 visit (regardless of investigational product compliance).   
Visits will occur per the Schedule of Activities (Section 2.2).  On-study visits may be 
completed within ± 3 business days of the scheduled visits.  The date of the first dose of 
investigational product is defined as day 1.  All subsequent doses and study visits will be 
scheduled based on the day 1 date.  The investigational product is to be administered 
following the completion of all other study required procedures for that visit. 
9.1.3 
Safety Follow-up 
Following last administration of the investigational product, a minimum of 16-weeks 
of safety follow-up assessments is required to ensure safety surveillance of 
subjects in the study.   
For subjects who discontinue investigational product prior to or at week 36, the 
safety follow-up visits will be included within the 52-week period and no additional 
safety follow-up visits will be required (Table 2-1).  Subjects who discontinue 
investigational product after week 36 are required to attend as many follow-up 
visits as necessary to ensure a minimum of 16 weeks of safety follow-up period 
after the last administration of the investigational product (Table 2-2).   
 and PK samples should be collected during the first 
4 safety follow-up visits after last administration of the investigational product. 
Subjects who are unwilling or unable to complete the follow-up visits as scheduled will 
be contacted by phone and may be requested to provide documentation from their 
primary provider. 
9.1.4 
Long-term Follow-up 
Not applicable to this study. 
9.1.5 
End of Study 
9.1.5.1 
End of Study for Individual Subject 
The end of study for an individual subject is defined as the last day the protocol-specific 
procedures are conducted for an individual subject.  An individual subject has 
completed the study when: 1) has completed 52-week treatment period regardless 
of investigational product compliance, and 2) has completed a minimum of 
16 weeks of safety follow-up after the last administration of the investigational 
product.  


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9.1.5.2 
End of Study  
The end of study is defined as the date when the last subject across all sites is assessed 
or receives an intervention for evaluation in the study (ie, last subject last visit), following 
any additional parts in the study (eg, safety follow-up), as applicable. 
9.2 
Description of General Study Assessments and Procedures 
The sections below provide a description of the individual study procedures for required 
time points. 
9.2.1 
General Assessments  
9.2.1.1 
Informed Consent 
All subjects must sign and personally date the IRB/IEC approved informed consent 
before any study-specific procedures are performed. 
9.2.1.2 
Demographics 
Demographic data collection including sex, age, race, and ethnicity will be collected in 
order to study their possible association with subject safety and treatment effectiveness.  
Additionally, the correlation between specific demographic data and PK, PD, and 
biomarkers may be explored. 
9.2.1.3 
Medical History 
The Investigator or designee will collect a relevant medical, psychiatric, and surgical 
history that started within 5 years of enrollment or as necessary to describe chronic or 
co-morbid conditions prior to enrollment through the start of the adverse event reporting 
period.  Medical history will include information on the subject's concurrent medical 
conditions.  Findings are to be recorded on the medical history CRF.  In addition to the 
medical history above, SLE history must date back to the original diagnosis.  The current 
toxicity grade and severity will be collected for each condition that has not resolved. 
9.2.1.4 
Physical Examination  
Physical examination will be performed as per SOA.  Physical examination findings 
should be recorded on the appropriate CRF (eg, medical history, event). 
9.2.1.5 
Concomitant Medications 
All concomitant medications including over-the-counter products and vitamins 
administered while the subject is on study will be recorded on the eCRF. 
9.2.1.6 
Physical Measurements 
Height in centimeters should be measured without shoes.  Weight in kilograms should 
be measured without shoes. 


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9.2.1.7 
Substance Abuse History  
Obtain a detailed history of prior and/or concurrent use of alcohol and tobacco. 
Note:  Subjects who are taking methotrexate should be advised to limit alcohol 
consumption to no more than 4 ounces per week. 
9.2.2 
Efficacy Assessments 
Efficacy assessments are recommended to be performed prior to obtaining any blood 
samples.  Data will be captured on paper source.  Data will be entered into the study 
database.  It is highly recommended that the same investigator performs efficacy 
assessments at every timepoint for a given subject. 
9.2.2.1 
Hybrid Systemic Lupus Erythematosus Disease Activity Index  
The hSLEDAI is a global index that evaluates disease activity and includes 24 items 
collecting specific manifestations in 9 organ systems: neurological, musculoskeletal, 
renal, mucocutaneous, general, heart, respiratory, vascular, and hematological.  The 
maximum score is 105.  Hybrid SLEDAI is the index score used during the validation of 
the SRI (Navarra et al, 2011; Furie et al, 2011).  The hSLEDAI is identical to the 
SELENA-SLEDAI score except for the scoring of proteinuria, which uses the SLEDAI-2K 
definition (proteinuria is scored 4 points if proteinuria is > 0.5 grams/24 hours [or 
equivalent urine protein/creatinine ratio]).  The hSLEDAI differs from SLEDAI-2K in 2 
main aspects:  the hSLEDAI includes scleritis and episcleritis for visual disturbances 
assessments and scores arthritis only if > 2 joints manifest signs of inflammation.  In the 
hSLEDAI score, inflammation is strictly defined as the presence of tenderness plus one 
of the following: swelling, effusion, warmth or erythema.  Unlike SLEDAI-2K, the 
presence of tenderness alone is not sufficient and at least 3 joints, and not only 2, must 
be affected.  In this study, for hSLEDAI scoring purposes, arthritis is required to involve 
the small joints of hands and/or wrists.  Additionally, in this study, scleritis and episcleritis 
will be considered for scoring purposes in the hSLEDAI only if SLE-relatedness is 
confirmed by an ophthalmologist. 
A total hSLEDAI  6 is used for eligibility purposes, together with the presence of a 
clinical hSLEDAI  4.  A clinical hSLEDAI score is a hSLEDAI score without the inclusion 
of points attributable to laboratory results. 
Hybrid SLEDAI descriptors will be scored based on a review of medical history, physical 
examination, and clinical laboratory findings.  Findings should reflect activity during the 
30 calendar days prior to the current visit. 


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9.2.2.2 
British Isles Lupus Assessment Group Index 
The British Isles Lupus Assessment Group (BILAG) index (BILAG 2004) evaluates 
disease activity in 9 separate organ systems and comprises a total of 97 items.  Each 
item is measured qualitatively by review of medical history and physical examination 
(yes/no, improving/same/worse/new) or quantitatively by measuring laboratory values.  
Based on these items, each of the 9 organ systems allocated an alphabetical score of A 
(most active), B (moderate activity), C (minor activity), D (no activity) or E (never 
present).  BILAG descriptors will be scored based on a review of medical history, 
physical examination, and clinical laboratory findings.  Findings should reflect activity 
during the 4-week period prior to the current visit and should be related to the subject’s 
SLE. 
9.2.2.3 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
The CLASI consists of 2 scores, the first summarizes the activity of the disease while the 
second is a measure of the damage done by the disease.  Activity is scored based on 
erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and 
non-scarring alopecia.  Damage is scored in terms of dyspigmentation and scarring, 
including scarring alopecia.  Subjects are asked whether dyspigmentation due to 
cutaneous lupus lesion usually remains visible for more than 12 months, which is 
considered permanent.  If so, the dyspigmentation score is doubled.  The scores are 
calculated by simple addition based on the extent of the symptoms.  The CLASI is 
designed as a table where the rows denote anatomical areas, while the columns score 
major clinical symptoms.  The extent of involvement for each of the skin symptoms is 
documented according to specific anatomic areas that are scored according to the worst 
affected lesion within that area for each symptom. 
9.2.2.4 
Photography 
In subjects who have a CLASI activity score  8 at screening, half body (from the neck 
down, anterior and posterior views) and cutaneous lupus lesion target area (global and 
close up excluding the face) photography will be taken and collected, if possible, per the 
photography manual.  Photographs will be taken by the study staff at the time points 
specified in the Schedule of Activities (Section 2) and reviewed by vendor’s team for 
quality and to ensure subject’s de-identification before being reviewed by Amgen 
external adjudicator to ensure the visual characteristics of the rash are consistent with 
the CLASI score assigned. 
9.2.2.5 
Swollen and Tender Joint Count 


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Swollen and tender joint counts will be performed as noted in the Schedule of Activities 
(Section 2). 
It is highly recommended that the same investigator/assessor should perform the 
assessments throughout the study for a given subject.  The initials of the joint assessor 
should be recorded in the CRF.  The score for each joint will be recorded on a paper 
source.  Data will be entered into the study database. 
Joints that have been replaced during the study, or have suffered trauma or received 
intra-articular injections, are considered non-evaluable.  Joints from subjects with 
osteoarthritis or other condition that in the investigator’s opinion can cofound the 
assessment of lupus arthritis, are considered non-evaluable. 
Swollen Joint Count Assessments:  A total 28 joints will be scored for presence or 
absence of swelling.  A separated score for joints in the hands and wrists will be 
calculated. 
Tender Joint Count Assessments:  A total 28 joints will be scored for presence or 
absence of tenderness.  A separated score for joints in the hands and wrists will be 
calculated. 
Swollen and Tender Joint Count Assessments:  joints in hands and wrists will be scored 
for the simultaneous presence or absence of swelling and tenderness. 
9.2.2.6 
Physician Global Assessment – Visual Analogue Scale 
The Physician Global Assessment (PGA) is a visual analogue scale (VAS) using 3 
benchmarks for assessing disease activity over the last 4 weeks.  When scoring the 
PGA, the previous visit score should be noted, and the current score should be relative 
to that previous visit.  The score ranges from 0 to 3 with 3 indicating severe disease.  
This refers to the most severe possible disease and does not reflect the most severe 
ever seen in a particular subject, but the most severe disease ever seen in all SLE 
patients.  Therefore, a score of 3 should rarely be seen.  Any disease rated greater than 
2.5 is very severe.  The range of moderate disease covers approximately 1.5 to 2.4.  
Mild disease falls below 1.5. 
This is a global assessment, factoring in all aspects of the subject’s lupus disease 
activity.  It should not reflect non-lupus medical conditions.  An increase of  0.3 points 
( 10% on the 3 point-VAS) from baseline is considered clinically significant worsening 
of disease.  This assessment will be completed by a health care provider (HCP) and 
should be done before assessing the hSLEDAI and BILAG.  The assessment will be 


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recorded on a paper source with both sources using the same dimensions and 
benchmarks for the VAS.  Data will be transmitted or entered into the study database. 
9.2.2.7 
SELENA-SLEDAI Flare Index  
The SELENA-SLEDAI Flare Index will be used to evaluate the presence of 
mild-moderate and severe flares as detailed in Buyon et al, 2005.  An additional question 
will be added to the classic instrument if, based on the investigators’ clinical judgment, 
the flare is mild or moderate. 
9.2.2.8 
BILAG Flare Index  
The BILAG flare index will be derived from BILAG 2004, as measured by BILAG score 
designation of “worse” or “new” resulting in a B score in  2 organs or an A score in  1 
organ (Gordon et al, 2003). 
9.2.2.9 
Lupus Low Disease Activity State (LLDAS) 
The LLDAS will be calculated as detailed in Franklyn et al, 2016. 
9.2.2.10 
Systemic Lupus International Collaborating Clinics/American 
College of Rheumatology Damage Index 
The Systemic Lupus International Collaborating Clinic/American College of 
Rheumatology Damage Index global score will be calculated as detailed in Gladman 
et al, 1996. 
9.2.2.11 
Systemic Lupus Erythematosus Responder Index  
The SRI-4 will be calculated as detailed in Luijten et al, 2012.  A subject achieves 
SRI-4 response if all of the following criteria are met:   4-point reduction from 
baseline in hSLEDAI score, AND no new BILAG 2004 A score and no  1 new 
BILAG B domain scores compared with baseline (eg, no B, C, D, or E scores at 
baseline becomes A or no more than 1 C, D, or E score at baseline becomes B), 
AND no 0.3-point deterioration from baseline in PGA VAS score (scale 0 to 3), AND 
no use of more than protocol-allowed therapies (ie, initiation or increase in OCS 
dose  5 mg/day prednisone [or equivalent] or IM CS or IV CS at any time point 
during the study; initiation or increase in OCS dose  5 mg/day prednisone [or 
equivalent] after week 10; initiation or increase in OCS dose  5 mg/day 
prednisone [or equivalent] between week 0 and week 8 that was not returned to 
baseline dose within the following 2 weeks; increase in current or initiation of new 
immunosuppressant/immunomodulator(s) at any time during the study).  The 
latest visit date among hSLEDAI, BILAG, and PGA will be considered the SRI-4 


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visit date.  In the case when all 3 visit dates are missing, the upper limit of the 
analytic window of this visit will be the SRI-4 visit date.  When all 4 criteria are met, 
the subject is a responder at that time point according to the SRI-4 definition. 
9.2.2.12 
BICLA Index Response 
The BICLA response is defined as at least 1 gradation of improvement in baseline 
BILAG domain scores in all body systems with moderate or severe disease activity at 
entry (eg, all A [severe disease] domain scores falling to B [moderate], C [mild], or D [no 
activity], and all B domain scores falling to C or D); no new BILAG 2004 A domain score 
and no  1 new BILAG 2004 B domain scores compared with baseline; no worsening 
of the hSLEDAI score from baseline; no  0.3-point deterioration from baseline in 
PGA (scale 0 to 3); and no use of more than protocol-allowed therapies (ie, 
initiation or increase in OCS dose  5 mg/day prednisone [or equivalent] or IM CS 
or IV CS at any time point during the study; initiation or increase in OCS dose 
 5 mg/day prednisone [or equivalent] after week 10; initiation or increase in OCS 
dose  5 mg/day prednisone [or equivalent] between week 0 and week 8 that was 
not returned to baseline dose within the following 2 weeks; increase in current or 
initiation of new immunosuppressant/immunomodulator(s) at any time during the 
study); and no initiation of non-protocol treatment for SLE (Wallace et al, 2011; Wallace 
et al, 2014). 
9.2.3 
Safety Assessments 
Planned time points for all safety assessments are listed in the Schedule of Activities 
see Section 2.  The investigator may utilize a qualified home health care service provider 
selected by Amgen at up to 8 home visits (including weeks 22, 26, 30, 34, 38, 42, 46, 
and 50), for subjects that have not experienced adverse events considered to be related 
to investigational product that in the opinion of the investigator may pose a risk for home 
health care administration of investigational product (home health care visits are not 
applicable for participating sites in Bulgaria).  During those visits, in addition to 
administration of investigational product, safety assessments including vital signs, 
adverse events, serious adverse events, and concomitant medications review will be 
collected, as described in Section 7.8.2. 


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9.2.3.1 
Adverse Events and Serious Adverse Events 
9.2.3.1.1 
Time Period and Frequency for Collecting and Reporting Safety 
Event Information 
9.2.3.1.1.1 
Adverse Events 
The adverse event grading scale to be used for this study will be the Common 
Terminology Criteria for Adverse Events (CTCAE) version 5 and is described in 
Section 12.4. 
The investigator is responsible for ensuring that all adverse events observed by the 
investigator or reported by the subject that occur after the first dose of investigational 
product (AMG 570/placebo) through the EOS are reported using the Event CRF. 
9.2.3.1.1.2 
Serious Adverse Events 
The investigator is responsible for ensuring that all serious adverse events observed by 
the investigator or reported by the subject that occur after signing of the informed 
consent through the EOS are reported using the Events CRF. 
All serious adverse events will be collected, recorded and reported to the sponsor or 
designee within 24 hours, as indicated in Section 12.4.  The investigator will submit any 
updated serious adverse event data to the sponsor within 24 hours of it being available. 
Since the criteria the CTCAE grading scale differs from the regulatory criteria for serious 
adverse events, if adverse events correspond to grade 4 CTCAE toxicity grading 
scale criteria (eg, laboratory abnormality reported as grade 4 without 
manifestation of life threatening status), it will be left to the investigator’s judgment to 
also report these abnormalities as serious adverse events.  For any adverse event that 
applies to this situation, comprehensive documentation of the event’s severity 
must be recorded in the subject medical records. 
9.2.3.1.1.3 
Serious Adverse Events After the Protocol-required Reporting 
Period 
After end of study, there is no requirement to actively monitor study subjects after the 
study has ended with regards to study subjects treated by the investigator.  
However, if the investigator becomes aware of serious adverse events suspected to 
be related to the investigational product, then these serious adverse events will be 
reported to Amgen within 24 hours following the investigator’s awareness of the event. 
Serious adverse events reported outside of the protocol-required reporting period will be 
captured within the safety database as clinical trial cases and handled accordingly based 
on relationship to investigational product.   


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If further safety related data is needed to fulfill any regulatory reporting 
requirements for a reportable event, then additional information may need to be 
collected from the subject’s records after the subject ends the study. 
9.2.3.1.2 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting adverse events and/or serious 
adverse events.  Open-ended and non-leading verbal questioning of the subject is the 
preferred method to inquire about adverse event occurrence. 
9.2.3.1.3 
Follow-up of Adverse Events and Serious Adverse Events 
After the initial adverse event/serious adverse event report, the investigator is required to 
proactively follow each subject at subsequent visits/contacts.  All adverse events and 
serious adverse events will be followed until resolution, stabilization, until the event is 
otherwise explained, or the subject is lost to follow-up (as defined in Section 8.3).  
Further information on follow-up procedures is given in Section 12.4. 
All new information for previously reported serious adverse events must be sent to 
Amgen within 24 hours following knowledge of the new information.  If specifically 
requested, the investigator may need to provide additional follow-up information, such as 
discharge summaries, medical records, or extracts from the medical records.  
Information provided about the serious adverse event must be consistent with that 
recorded on the Events CRF. 
9.2.3.1.4 
Regulatory Reporting Requirements for Serious Adverse Events 
If a subject is permanently withdrawn from protocol-required therapies because of a 
serious adverse event, this information must be submitted to Amgen. 
Prompt notification by the investigator to the sponsor of serious adverse events is 
essential so that legal obligations and ethical responsibilities towards the safety of 
subjects and the safety of an investigational product under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of an investigational product under clinical 
investigation.  The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRBs/IECs, and investigators. 
Individual safety reports must be prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and sponsor policy and forwarded 
to investigators as necessary. 


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An investigator who receives an individual safety report describing a serious adverse 
event or other specific safety information (eg, summary or listing of serious adverse 
events) from the sponsor will file it along with the IB and will notify the IRB/IEC, if 
appropriate according to local requirements. 
To comply with worldwide reporting regulations for serious adverse events, the treatment 
assignment of subjects who develop serious, unexpected, and related adverse events 
may be unblinded by Amgen before submission to regulatory authorities.  Aggregate 
analyses may also be unblinded by the Safety Assessment Team as appropriate.  
Investigators will receive notification of related serious adverse events reports sent to 
regulatory authorities in accordance with local requirements. 
9.2.3.1.5 
Safety Monitoring Plan 
Subject safety will be routinely monitored as defined in Amgen’s safety surveillance and 
signal management processes. 
9.2.3.1.6 
Pregnancy and Lactation 
Details of all pregnancies and/or lactation in female subjects will be collected after the 
start of investigational product through the EOS. 
If a pregnancy is reported, the investigator is to inform Amgen within 24 hours of learning 
of the pregnancy and/or lactation and is to follow the procedures outlined in 
Section 12.5.  Amgen Global Patient Safety will follow-up with the investigator regarding 
additional information that may be requested. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered serious adverse events. 
Further details regarding pregnancy and lactation are provided in Section 12.5. 
9.2.3.2 
Vital Signs 
The following measurements must be performed: systolic/diastolic blood pressure, heart 
rate, respiratory rate, and temperature.  Subject must be in a supine or seated position in 
a rested and calm state for at least 5 minutes before blood pressure assessments are 
conducted.  The position selected for a subject should be the same that is used 
throughout the study and documented on the vital sign CRF.  The temperature location 
should be oral or tympanic (with oral preferred).  Once a location for temperature 
assessment is selected for a subject, the location should be the same throughout the 
study and documented on the vital signs CRF.  Record all measurements on the vital 
signs CRF. 


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9.2.4 
Clinical Laboratory Assessments 
Refer to Section 12.2 for the list of clinical laboratory tests to be performed and to the 
Schedule of Activities (Section 2) for the timing and frequency. 
The investigator is responsible for reviewing laboratory test results and recording any 
clinically relevant changes occurring during the study in the Event CRF.  The investigator 
must determine whether an abnormal value in an individual study subject represents a 
clinically significant change from the subject’s baseline values.  In general, abnormal 
laboratory findings without clinical significance (based on the investigator's judgment) 
are not to be recorded as adverse events.  However, laboratory value changes that 
require treatment or adjustment in current therapy are considered adverse events.  
Where applicable, clinical sequelae (not the laboratory abnormality) are to be recorded 
as the adverse event. 
All protocol-required laboratory assessments, as defined in Section 12.2, must be 
conducted in accordance with the laboratory manual and the Schedule of Activities. 
After baseline, PK/PD parameters that could unblind the study will not be reported to 
investigative sites or other blinded personnel until the study has been unblinded. 
9.2.4.2 
Pregnancy Testing 
A highly sensitive serum pregnancy test should be completed at screening and a highly 
sensitive urine pregnancy test should be completed at the Day 1 visit for females of 
childbearing potential. 
Note:  Females who have undergone a bilateral tubal ligation/occlusion should have 
pregnancy testing per protocol requirements.  (If a female subject, or the partner of a 
male subject, becomes pregnant it must be reported on the Pregnancy Notification 
Worksheet, see Section 12.5).  Refer to Section 12.5 for contraceptive requirements. 
Additional pregnancy testing using a high sensitivity urine pregnancy test should be 
performed at monthly intervals during the treatment period and at the first 2 safety 
follow-up visits. 


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Additional on-treatment pregnancy testing may be performed at the investigator’s 
discretion or as required per local laws and regulations. 
9.2.4.3 
Tuberculosis Testing 
All subjects must receive either a PPD, QuantiFERON-TB, or T-spot test at screening. 
9.2.4.3.1 
Purified Protein Derivative 
The PPD test must be read by a trained health care professional 48 to 72 hours after the 
test is placed.  The PPD reader must be identified on the delegation of authority for this 
responsibility.  PPD test kits will not be provided by the sponsor and must be procured 
locally. 
9.2.4.3.2 
QuantiFERON-TB or T-spot Testing 
If a QuantiFERON-TB test is performed for eligibility, the test can be performed 
centrally with test kits provided, or locally using a local kit procured by the site.  If a 
T-spot test is performed for eligibility, the test will be performed locally with test kits 
procured locally. 
9.2.4.4 
HIV Antibodies, Hepatitis B, and Hepatitis C Testing 
Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C 
(HCAb), and HIV antibodies will be assessed at screening.  If the results show a 
negative HBsAg and positive for HBcAb, quantification of hepatitis B virus DNA by PCR 
is necessary.  Similarly, if the results show a positive HCAb, a quantification of hepatitis 
C virus RNA by PCR is necessary.  The above mentioned PCR test results must be 
negative at screening for the subject to be eligible for this study. 
9.2.5 
Pharmacokinetic Assessments 
All subjects randomized to treatment with AMG 570 will have PK samples assessed.  
Blood samples of approximately 4 mL will be collected for measurement of serum 
concentrations of AMG 570 as specified in the Schedule of Activities (Table 2-1 and 
Table 2-2).  A maximum of 2 samples may be collected at additional time points during 
the study if warranted and agreed upon between the investigator and the sponsor.  
Instructions for the collection and handling of biological samples will be provided by the 
sponsor.  The actual date and time (24-hour clock time) of each sample will be recorded.  
Drug concentration information that may unblind the study will not be reported to 
investigative study centers or blinded personnel until the study has been unblinded. 


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9.2.6 
Pharmacodynamic Assessments 
Blood samples for PD assessments will be collected as specified in the Schedule of 
Activities (Table 2-1 and Table 2-2). 
9.2.6.1 
Biomarker Assessment During the Study 
Blood samples will be collected for measurement of 
 
 
 at time points indicated in the Schedule of Activities 
(Table 2-1 and Table 2-2). 
9.2.7 
Pharmacogenetic Assessments 
If the subject consents to the optional pharmacogenetic portion of this study, DNA 
analyses may be performed.  These optional pharmacogenetic analyses focus on 
inherited genetic variations to evaluate their possible correlation to the disease and/or 
responsiveness to the therapies used in this study.  The goals of the optional studies 
include the use of genetic markers to help in the investigation of inflammatory conditions 
and/or to identify subjects who may have positive or negative response to AMG 570.  No 
additional samples are collected for this part of the study.  For subjects who consent to 
this/these analysis/analyses, DNA may be extracted. 
The final disposition of samples will be described in Section 12.6. 


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9.2.9 
Biomarker Development 
Biomarkers are objectively measured and evaluated indicators of normal biologic 
processes, pathogenic processes, or pharmacologic responses to a therapeutic 
intervention. 
The development of biomarkers can be useful to identify disease subtypes, guide 
therapy, and/or predict disease severity. 
Amgen may attempt to develop test(s) designed to identify subjects most likely to 
respond positively or negatively to AMG 570. 
Blood samples are to be collected for biomarker development at the time points 
specified in the Schedule of Activities (Table 2-1 and Table 2-2). 
9.2.10 
Clinical Outcome Assessments:  Patient Reported Outcomes 
Patient reported outcomes should be completed by the patient alone before being 
clinically evaluated by the study nurse or physician. 
The assessments will be recorded directly into the electronic tablet which will serve as 
the source documentation and will not be transposed to a CRF. 
9.2.10.1 
Medical Outcomes Short Form-36 Questionnaire Version 2 
The SF-36v2 (acute version) Health Survey (Ware et al, 2000) contains 36 items and is 
a revised version of the SF-36 Health Survey.  The SF-36v2 acute version is a 
patient-reported generic measure of health status.  This survey yields assessments of 
8 domains of health-related quality of life: 1) limitations in physical activities because of 
health problems; 2) limitations in social activities because of physical or emotional 
problems; 3) limitations in usual role activities because of physical health problems; 
4) bodily pain; 5) general mental health (psychological distress and well-being); 
6) limitations in usual role activities because of emotional problems; 7) vitality (energy 
and fatigue); and 8) general health perceptions.  The scores from the 8 domains will be 
evaluated independently and aggregated into 2 norm-based summary component 
measures of physical and mental health.  The recall period is the past 7 days. 
This survey takes approximately 10 to 15 minutes to complete. 
9.2.10.2 
Patient-Reported Outcome Measurement Information System 
Fatigue Short Form 7a Instrument (PROMIS Fatigue SF 7A) 
The PROMIS Fatigue Short Form 7a is a 7-item instrument originally constructed by the 
PROMIS Fatigue team to represent the range of the fatigue trait (PROMIS Fatigue 
Scoring Manual).  It assesses the experience of fatigue as well as its impact on physical, 


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mental, and social activities.  Both psychometric properties and clinical input were used 
in the development of the short form from the PROMIS item bank.  Estimates of 
responsiveness and minimally important differences have been reported for the 4 item 
PROMIS Fatigue instrument in SLE patients (Katz et al, 2019).  The PROMIS Fatigue 
has also been able to differentiate disease activity in other rheumatologic diseases 
(Wohlfahrt et al, 2019). 
The PROMIS Fatigue Short Form 7a takes 1 to 2 minutes to complete. 
9.2.10.3 
LupusQoL 
The Lupus Quality of Life questionnaire (LupusQoL) is a SLE-specific health-related 
quality of life instrument (Jolly et al, 2010; McElhone et al, 2007).  The LupusQoL 
consists of 8 domains: physical health (8 items), pain (3 items), planning (3 items), 
intimate relationships (2 items), burden to others (3 items), emotional health (6 items), 
body image (5 items), and fatigue (4 items).  The final instrument has demonstrated 
good internal reliability (Cronbach's 0.88 to 0.95), good test-retest reliability (r 0.72 to 
0.93), good concurrent validity with the comparable domains of the SF-36 (r 0.71 to 
0.79) and good discriminant validity for different levels of disease activity, measured by 
BILAG index, and damage (Systemic Lupus International Collaborating Clinics/ACR 
damage index) but not for all domains.  The instrument also has acceptable ceiling 
effects and minimal floor effects. 
Subjects typically complete the LupusQoL in less than 10 minutes.  The scoring and the 
transformation of the scores takes approximately 5 minutes per subject. 
9.2.10.4 
Patient Global Assessment 
The patient global assessment (PtGA) of disease activity typically assesses disease 
activity on a 10 cm numerical rating scale (NRS; 0 to 10 cm).  The scale for the 
assessment ranges from “very well” (0) to “very poor” (10) (Furie et al, 2009).  The 
validity of the PtGA in SLE has been established (Khraishi et al, 2014; Liang et al, 1989).  
The PtGA scale has a 7-day recall. 


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10. 
Statistical Considerations 
10.1 
Sample Size Determination 
The approximate sample size of 320 subjects is chosen to provide 80% power to detect 
≥ 25% absolute improvement for at least 1 AMG 570 dose group relative to placebo in 
the primary endpoint of SRI-4 response rate at week 52 at a significance level of 
0.025 (1-sided) using a Bayesian Hierarchical Model, assuming a 40% response rate in 
placebo group. 
Because enrollment can be stopped if early stopping rules for futility are met at an IA, 
the actual sample size could be smaller and cannot be pre-specified.  The approximate 
sample size of 320 ensures if there is no interim signal for early termination based on 
futility of all AMG 570 doses, the trial will have adequate power to achieve the primary 
objective once all subjects have had the opportunity to complete week 52. 
10.2 
Analysis Sets, Subgroups, and Covariates 
10.2.1 
Analysis Sets 
10.2.1.1 
Full Analysis Set 
The Full Analysis Set (FAS) includes all subjects randomized in the study, with treatment 
assignment based on subjects’ randomized treatment assignment.  
10.2.1.2 
Safety Analysis Set 
The Safety Analysis Set includes all randomized subjects who received at least 1 dose 
of investigational product and will be used to perform safety analyses according to the 
actual treatment received. 
10.2.1.3 
PK Concentration Analysis Set 
The PK Analysis Concentration Set is defined as the subset of subjects in the Safety 
Analysis Set who had at least 1 evaluable serum concentration (including results below 
the level of detection) of investigational product.  PK concentration data will be analyzed 
according to the actual treatment received. 


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10.2.1.4 
PK Parameter Analysis Set 
The PK parameter analysis set is defined as the subset of subjects in the Safety 
Analysis Set who had at least one PK parameter adequately derived.  PK parameter will 
be analyzed according to the actual treatment received. 
10.2.1.5 
PD Analysis Set 
The PD analysis set is defined as the subset of subjects in the Safety Analysis Set who 
had at least one evaluable PD parameter measurement collected.  PD parameter will be 
analyzed according to the actual treatment received. 
10.2.2 
Covariates 
The baseline covariates may include but are not limited to:  
 
Age, region, race, sex 
 
Baseline SLE disease activity 
 
Baseline background medications (detectable vs undetectable baseline SLE SOC 
drug levels) 
Other covariates may be evaluated as necessary.  Stratification factors will be included 
as covariates in the model or be used to examine treatment effect in subgroups.  If 
included as covariates in the model for treatment comparisons, the IRT value will be 
used to be consistent with the randomization scheme.  The impact of the baseline 
covariates on the treatment effect may be explored and adjusted in the model for the 
primary and secondary endpoints as deemed necessary. 
10.2.3 
Subgroups 
In addition to stratification factors, some covariates mentioned above may be used for 
further exploration in subgroups.  For subgroup analysis, the value collected from 
source-verified eCRF will be used to reflect the true clinical relevance of the covariate. 
10.3 
Statistical Analyses 
The statistical analysis plan (SAP) will be developed and finalized before any database 
lock.  To preserve study integrity, the primary analysis will be conducted after all 


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subjects have had the opportunity to complete week 52 and the final analysis will be 
conducted and reported following the EOS, as defined in Section 5.3.1. 
10.3.1 
Planned Analyses 
10.3.1.1 
Interim Analysis and Early Stopping Guidelines 
Interim analyses will be conducted to allow adaptation of the randomization ratio to the 3 
AMG 570 treatment groups, holding the allocation to placebo constant at 25%, and 
assessing efficacy for early futility or administrative success decisions: 
 
The study team, investigators, and subjects will remain blinded to the investigational 
product, changes in randomization allocation probabilities, and results of the interim 
analyses. 
 
The first IA will be executed after the first enrolled 40 subjects are randomized and 
have had the opportunity to complete the week 24 assessment.  Subsequent IAs are 
scheduled after every additional 32 subjects are randomized and have had the 
opportunity to complete the week 24 assessment until full enrollment.  The last IA will 
occur when all 320 subjects are randomized and have had the opportunity to 
complete the week 24 assessment.  This IA will be referred to as the ‘all-subjects-
week-24’ IA. 
 
Efficacy analyses will be performed at IAs to assess the likelihood of AMG 570 being 
superior to placebo by a clinically meaningful difference. 
 
If this likelihood is unacceptably low for all dose levels, the trial is recommended 
to stop for futility. 
 
Additionally, at the ‘all-subjects-week-24 IA’, if this likelihood is sufficiently high at, at 
least 1 dose level, IA triggers an administrative success signal.  This would not alter 
ongoing or planned activities of this phase 2b study, but downstream activities may 
be planned/initiated (eg, a phase 3 study).  Analysis planned at each IA are listed in 
Table 1-1. 
At IAs, 
 
Beginning with the second IA and before the last IA, enrollment to the study may be 
stopped for futility if the posterior probability of achieving a clinically meaningful 
difference in SRI-4 response rates of at least 15% between each active treatment 
group and placebo is below 2.5%. 
 
Once all subjects have had the opportunity to complete the week 24 visit, the primary 
efficacy analysis model, a Bayesian Hierarchical Model will be fitted to the week 52 
SRI-4 response data with longitudinal modeling of earlier visits week 16, 20, and 24 
to compute the predictive probability of success in a hypothetical, future phase 3 
study If the predictive probability of success in this hypothetical future phase 3 study 
is larger than 80% for any of the AMG 570 dose groups, downstream activities may 
be planned/initiated.  Regardless of the result of this IA, the conduct of the current 
study will not be impacted; the current study will continue until all subjects have had 
the opportunity to complete the week 52 visit and safety follow-up. 


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10.3.1.2 
Primary Analysis 
The primary analysis will take place when all subjects have had the opportunity to 
complete week 52. 
At primary analysis: 
 
The efficacy goal of the study is to demonstrate the superiority of AMG 570 relative 
to placebo. 
 
The primary analysis of the primary endpoint SRI-4 at week 52 is a Bayesian 
Hierarchical Model which borrows information dynamically across the 3 active 
AMG 570 treatment groups while controlling the overall type I error at the 1-sided 
2.5% level. 
 
The null hypothesis will be rejected (ie, study will be claimed successful) if the 
posterior probability of superiority of any active AMG 570 treatment group is above 
0.981.  This threshold was chosen to preserve a simulated overall 1-sided type I 
error rate to be less than 2.5%. 
10.3.1.3 
Final Analysis 
The final analysis will be completed after study completion is reached, after the last 
subject reaches the last visit during the safety follow-up period, and all data are collected 
for the study. 
10.3.2 
Methods of Analyses 
10.3.2.1 
General Considerations 
All categorical variables will be summarized using the number and percent of subjects 
falling into each category and all continuous variable will be summarized using mean, 
standard error or standard deviation, median, Q1, Q3, minimum, maximum, and number 
of subjects with observations.  Subgroup analyses (by certain demographic variables 
and stratification factors as appropriate) will be presented if deemed necessary.  Safety 
endpoints will be summarized descriptively. 


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10.3.2.2 
Efficacy Analyses 
Endpoint 
Statistical Analysis Methods to Support Estimands 
Primary 
Bayesian Hierarchical Model will be used to evaluate primary efficacy 
estimand. 
Secondary 
Bayesian Hierarchical Model/Generalized linear model will be used to 
evaluate secondary efficacy endpoints.  Details will be described in the 
SAP. 
Exploratory 
Details of the analysis of exploratory endpoints will be specified in the 
SAP. 
10.3.2.3 
Safety Analyses 
10.3.2.3.1 
Analyses of Primary Safety Endpoint(s) 
 
Endpoint 
Statistical Analysis Methods 
Primary* 
All safety analyses will be performed using the Safety Analysis Set 
based on subject’s actual treatment received.  Safety analysis will 
include analyses of AEs, clinical laboratory tests, vital signs, and 
 
*Safety endpoints are not primary endpoints for this study 
10.3.2.3.2 
Adverse Events  
Subject incidence of all treatment-emergent adverse events will be tabulated by system 
organ class and preferred term.  Tables of fatal adverse events, serious adverse events, 
and adverse events leading to withdrawal from investigational product or other 
protocol-required therapies will also be provided. 
10.3.2.3.3 
Laboratory Test Results 
Clinical laboratory test results and change from baseline will be summarized over time 
by each treatment group.  In addition, shift tables, from baseline to the worst on-study 
laboratory toxicity based on the latest version of CTCAE grading, will be presented. 
10.3.2.3.4 
Vital Signs 
Vital sign data (observed and change from baseline) will be summarized using 
descriptive statistics by each treatment group. 
10.3.2.3.5 
Physical Measurements 
Clinically significant findings from physical examinations will be listed by subject and 
assessed for clinical significance which will be included in the adverse event listings and 
summaries. 


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10.3.2.3.7 
Exposure to Investigational Product 
Summary statistics will be provided for the total number of doses administered, total 
dose received, and total duration of investigational product exposure by treatment. 
10.3.2.3.8 
Exposure to Other Protocol-required Therapy 
Descriptive statistics of total dose (mg), dosage categories, duration of usage, number 
and percentage of subjects with dose modifications, and reasons for modification will be 
produced to describe the exposure by treatment group from baseline to end of study. 
10.3.2.3.9 
Exposure to Concomitant Medication 
Number and proportion of subjects receiving therapies of interest will be summarized by 
preferred term or category for each treatment group as coded by latest version of the 
World Health Organization Drug dictionary. 
10.3.2.4 
Other Analyses 
Serum concentrations will be summarized descriptively by treatment for each PK 
sampling time point using PK Concentration Analysis Set.  PK parameter (if deemed 
necessary) will be summarized with PK parameter analysis set.  PD parameter (if 
deemed necessary) will be summarized with PD analysis set.  Medical history will be 
summarized by SOC and PT and tabulated by treatment group and total using the 
Safety Analysis Set according to the actual treatment received. 


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11. 
References 
AMG 570 Investigator’s Brochure.  Thousand Oaks, CA.  Amgen Inc.  
Adams A, MacDermott EJ, Lehman TJ. Pharmacotherapy of lupus nephritis in children: 
a recommended treatment approach. Drugs. 2006;66:1191-1207. 
Aringer M, Costenbader K, Daikh D, et al.  2019 European League Against 
Rheumatism/American College of Rheumatology Classification Criteria for Systemic 
Lupus Erythematosus.  Arthritis & Rheum 2019; 71(9):1400-1412 
Arthritis & Rheumatism (Arthritis Care & Research), Vol. 61, No. 9, September 15, 2009, 
pp 1168-1178. 
Buyon JP, Petri MA, Kim MY, et. al. The effect of combined estrogen and progesterone 
hormone replacement therapy on disease activity in systemic lupus erythematosus: A 
randomized trial.  Ann Intern Med. 2005;142:953. 
Chandran V, Bhella S, Schentag C, Gladman DD. Functional assessment of chronic 
illness therapy-fatigue scale is valid in patients with psoriatic arthritis. Ann Rheum Dis. 
2007;66: 936-939. 
Cheng LE, Amoura Z,Cheah B, et al. Brief Report: A Randomized, Double-Blind, 
Parallel-Group, Placebo-Controlled, Multiple-Dose Study to Evaluate AMG 557 in 
Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis. Arthritis 
Rheumatol. 2018 Jul;70(7):1071-1076. 
Doria A, Stohl W, Schwarting A, et al. Efficacy and Safety of Subcutaneous Belimumab 
in Anti-Double-Stranded DNA-Positive, Hypocomplementemic Patients With Systemic 
Lupus Erythematosus. Arthritis Rheumatol. 2018 Aug;70(8):1256-1264. 
Franklyn K, Lau CS, Navarra SV, et al. Definition and initial validation of a Lupus Low 
Disease Activity State (LLDAS). Ann Rheum Dis. 2016 Sep;75(9):1615-1621. 
Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of 
belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with 
systemic lupus erythematosus. Arthritis Rheum. 2011 Dec;63(12):3918-30. 
Furie RA, Petri MA, Wallace DJ, et al. Novel evidence-based systemic lupus 
erythematosus responder index. Arthritis & Rheum. 2009;61(9):1143-1151. 
Gladman D, Ginzler E, Goldsmith C, et al.  The development and initial validation of the 
systemic lupus international collaborating clinics/American College of Rheumatology 
Damage Index for Systemic Lupus Erythematosus. Arthritis Rheum.  
1996;39(3):363-369. 
Gordon C, Sutcliffe N, Skan J, et al. Definition and treatment of lupus flares measured by 
the BILAG index. Rheumatology. 2003;42(11):1372-1379. 
Jolly M, Pickard AS, Wilke C et al. Lupus-specific health outcome measure for US 
patients: the LupusQoL-US version. Ann Rheum Dis. 2010;69:29-33. 
Katz P, Pedro S, Alemao E, et al.  Estimates of responsiveness, minimally import 
differences and patient acceptable symptom state in five patient-reported outcomes 
measurement information system short forms in systemic lupus erythematosus.  ACR 
Open. 2019: 1-8.  Doi 10.1002/acr2.11100. 
Khraishi M, Aslanov R, Dixit S, et al 2014. The validity of patient and physician global 
disease activity assessments of systemic lupus erythematosus: results from the lupus 
activity coring tool (LAST) as compared to the Selena Sledai (SS) modification 
multicentre study. ACR 2014. 


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Kotzin BL. Systemic lupus erythematosus. Cell. 1996;85:303-306. 
Liang MH, Socher SA, Larson MG, Schur PH. Reliability and validity of six systems for 
the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis 
Rheum. 1989;32(9):1107-18. 
Luijten KMAC, Tekstra J, Bijlsma JWJ, Bijl M.  The Systemic Lupus Erythematosus 
Responder Index (SRI):  A new SLE disease activity assessment.  Autoimmun Rev.  
2012;11(5):326-329. 
McElhone K, Abbott J, Shelmerdine J et al. Development and validation of a 
disease-specific health-related quality of life measure, the LupusQol, for adults with 
systemic lupus erythematosus. Arthritis Rheum. 2007;57:972-979. 
Miyakis S, et al. International consensus statement on an update of the classification 
criteria for definite antiphospholipid syndrome (APS). Journal of Thrombosis and 
Haemostasis, 2006; 4: 295–306. 
Navarra SV, Guzmán RM, Gallacher AE, et al.  Efficacy and safety of belimumab in 
patients with active systemic lupus erythematosus: a randomised, placebo-controlled, 
phase 3 trial. Lancet. 2011 Feb 26;377(9767):721-731. 
Pisetsky DS, Clowse MEB, Criscione-Schreiber LG, et al.  A Novel System to Categorize 
the Symptoms of Systemic Lupus Erythematosus. Arth Care Res. 2019; 71 (6): 735-741. 
PROMIS Fatigue Scoring Manual. Accessed at 
http://www.healthmeasures.net/images/PROMIS/manuals/PROMIS_Fatigue_Scoring_M
anual.pdf on 29 Jan 2020 
Rhaman A and Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358: 
929-939. 
Sullivan BA, Tsuji W, Kivitz A, et al. Inducible T-cell co-stimulator ligand (ICOSL) 
blockade leads to selective inhibition of anti-KLH IgG responses in subjects with 
systemic lupus erythematosus. Lupus Science & Medicine 2016;3: e000146. 
Wallace, D, Kalunian K, Petri, M, et al.  Efficacy and safety of epratuzumab in patients 
with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a 
phase IIb, randomised, double-blind, placebo-controlled, multicentre study.  Ann Rheum 
Dis.  2014;73:183-190. 
Wallace D, Strand V, Furie R, et al.  Evaluation of Treatment Success in Systemic Lupus 
Erythematosus Clinical Trials; Development of the British Isles Lupus Assessment 
Group-Based Composite Lupus Assessment Endpoint.  Arth Rheum.  2011;63-s894 
ACR. 
Ware JE. SF-36 Health Survey Update. SPINE. 2000; 25:3130-3139. 
Wohlfahrt A, Bingham CO, Marder W, et al. Responsiveness of patient-reported 
outcomes measurement information system measures in rheumatoid arthritis patients 
starting or switching a disease-modifying antirheumatic drug. Arth Car Res 2019: (4): 
521-529. 
Zhang F, Bae SC, Bass D, et al. A pivotal phase III, randomised, placebo-controlled 
study of belimumab in patients with systemic lupus erythematosus located in China, 
Japan and South Korea. Ann Rheum Dis. 2018 Mar;77(3):355-363. 


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12. 
Appendices 


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12.1 
Appendix 1.  List of Abbreviations and Definitions of Terms 
 
Abbreviation or Term 
Definition/Explanation 
ACR 
American College of Rheumatology 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BAFF 
B cell activating factor 
BICLA 
BILAG based Combined Lupus Assessment 
BILAG 
British Isles Lupus Assessment Group 
CFR 
Code of Federal Regulations 
CLASI 
Cutaneous Lupus Erythematosus Area and Severity Index 
Clinical hSLEDAI 
hybrid SLEDAI assessment score without the inclusion of points 
attributable to any laboratory parameter, including urine and 
immunologic parameters.   
Cmax 
maximum observed concentration 
CNS 
central nervous system 
CPK 
creatine phosphokinase 
CS 
corticosteroids 
CTCAE 
common terminology criteria for adverse events 
DILI 
drug-induced liver injury 
DMC 
data monitoring committee 
eCRF 
electronic case report form 
EDC 
electronic data capture 
End of Study for 
individual Subject 
defined as the last day that protocol-specified procedures are 
conducted for an individual subject 
End of Study (end of 
trial) 
defined as the date when the last subject is assessed or receives an 
intervention for evaluation in the study (ie, last subject last visit), 
following any additional parts in the study (eg, safety follow up), as 
applicable 
EOS 
end of study 
Exposure-response 
analysis 
mechanism-based modeling & simulation and statistical analyses 
based on individual pharmacokinetic [PK] exposure (eg, population 
pharmacokinetic modeling) and response, which may include 
biomarkers, pharmacodynamic (PD) effects, efficacy and safety 
endpoints. 
FAS 
Full Analysis Set  
FIH 
first in human 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
HBcAb 
hepatitis B core antibody 
HCP 
health care provider 
HBsAg 
hepatitis B surface antigen 


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Abbreviation or Term 
Definition/Explanation 
HepCAb 
hepatitis C antibody 
HIV 
Human Immunodeficiency Virus 
HRT 
hormonal replacement therapy 
hSLEDAI 
Hybrid Systemic Lupus Erythematosus Disease Activity Index  
IA 
interim analysis  
IB 
Investigator’s Brochure 
IBG 
Independent Biostatistics Group 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
ICOS 
inducible co-stimulator 
ICOSL 
inducible co-stimulator ligand 
IEC 
Independent Ethics Committee 
Ig 
Immunoglobulin 
 
IL-2 
Interleukin 2 
IM 
intramuscular 
INR 
international normalized ratio 
IPIM 
Investigational Product Instruction Manual 
IRB 
Institutional Review Boards 
IRT 
interactive response technology 
IV 
intravenous 
JAK 
janus kinase  
KLH 
Keyhole limpet hemocyanin 
LDH 
lactate dehydrogenase 
LLDAS 
Lupus Low Disease Activity State 
LupusQoL 
Lupus Quality of Life questionnaire  
MCTD 
mixed connective tissue disease 
MDRD 
Modification of Diet in Renal Disease 
NOAEL 
NSAID 
no-observed-adverse-effect-level 
Non-steroidal Anti-inflammatory Drugs  
OCS 
oral corticosteroids 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic 
PtGA 
Patient Global Assessment 
PGA 
Physician Global Assessment 
PI 
Principal Investigator 
PK 
pharmacokinetic 
PPD 
purified protein derivative 
PROMIS 
Patient-Reported Outcome Measurement Information System 
PT 
preferred term 
Q2W 
every 2 weeks 
Q4W 
every 4 weeks 


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Abbreviation or Term 
Definition/Explanation 
QW 
once-weekly  
RA 
rheumatoid arthritis 
RAR 
Response Adaptive Randomization  
RBC 
red blood cell 
RO 
receptor occupancy 
ROW 
rest of the world 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous 
SDI 
Systemic Lupus International Collaborating Clinic / American College 
of Rheumatology Damage Index 
SF-36v2 
Medical Outcomes Short Form 36 version 2 questionnaire 
SLE 
systemic lupus erythematosus 
SLEDAI-2K 
Systemic Lupus Erythematosus Disease Activity Index 2000 
SLICC 
Systemic Lupus International Collaborating Clinics 
SOA 
schedule of assessments 
SOC 
standard of care 
Source Data 
information from an original record or certified copy of the original 
record containing patient information for use in clinical research.  The 
information may include, but is not limited to, clinical findings, 
observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial.  Source data are contained 
in source documents (original records or certified copies).  (ICH 
Guideline [E6]).  Examples of source data include Subject 
identification, Randomization identification, and Stratification Value. 
SRI 
Systemic Lupus Erythematosus Responder Index 
study day 1 
defined as the first day that protocol-specified investigational product 
is administered to the subject 
TBL 
total bilirubin 
ULN 
upper limit of normal 
VAS 
visual analogue scale 
 


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12.2 
Appendix 2.  Clinical Laboratory Tests 
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations.


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Table 12-1.  Analyte Listinga 
Central Laboratory: Chemistry 
Central Laboratory: 
Coagulation 
Central Laboratory: 
Urinalysis 
Central Laboratory: 
Hematology 
Central Laboratory:  
Other Labs 
Sodium 
Potassium 
Chloride 
Bicarbonate 
Total protein 
Albumin 
Calcium 
Adjusted calcium 
Magnesium 
Phosphorus 
Glucose 
BUN or Urea 
Creatinine 
Uric acid 
Total bilirubin 
Direct bilirubin 
ALP 
LDH 
AST (SGOT) 
ALT (SGPT) 
Creatinine clearance by MDRD 
GGT 
C-reactive protein 
Total Cholesterol 
HDL 
LDL 
Triglycerides 
Creatinine Phosphokinase 
PT/INR 
aPTT 
Fibrinogenb 
D-dimerb 
Protein/creatinine ratio 
Specific gravity 
pH 
Blood 
Protein 
Glucose 
Bilirubin 
WBC 
RBC 
Epithelial cells 
Bacteria 
Casts 
Crystals 
Central Laboratory: 
RBC 
Nucleated RBC 
Hemoglobin 
Hematocrit 
MCV  
MCH 
MCHC 
RDW 
Reticulocytes 
Platelets 
WBC 
Differential 
 Bands/stabs 
 Eosinophils 
 Basophils 
 Lymphocytes 
 Monocytes  
 Total neutrophils 
 Segmented neutrophils 
Local Laboratory: 
Erythrocyte sedimentation 
rate 
 
Central Laboratory: 
Hep B surface antigen 
Hep B core antibody 
Hep B virus DNAc 
Hep C antibody 
Hep C virus RNAd 
Antinuclear antibody  
HIV antibody  
Serum pregnancy test 
QuantiFERON-TBf 
Local Laboratory: 
Urine Pregnancy 
T-spotf 
FSHg 
Coombs testh 
 
Footnotes defined on next page 


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ALP  alkaline phosphatase; ALT  alanine aminotransferase;
aPTT  activated partial thromboplastin time; 
AST  aspartate aminotransferase; BUN  blood urea nitrogen; FSH  follicle stimulating hormone; GGT  gamma glutamyl transpeptidase; HDL  high density 
lipoprotein; Hep  hepatitis; HIV  Human Immunodeficiency Virus;
 INR  international normalized ratio; LDH  lactate dehydrogenase; 
LDL  low density liproprotein; MCH  mean corpuscular hemoglobin; MCHC  mean corpuscular hemoglobin concentration; MCV  mean corpuscular volume; 
MDRD  Modification of Diet in Renal Disease; PD  pharmacodynamic; PK  pharmacokinetic; PT  prothrombin time; PTT  partial thromboplastin time; RBC  red 
blood cell count; RDW  Red cell distribution width; SGOT  serum glutamic-oxaloacetic transaminase; SGPT  serum glutamic-pyruvic transaminase; WBC  white 
blood cell count 
After baseline, PK/PD parameters that could unblind the study will not be reported to investigative sites or other blinded personnel until the study has been unblinded. 
a. Approval for applicable local lab testing may be granted by sponsor as needed in the event that central lab testing is unavailable.   
b In case of drug-induced liver injury (DILI) events.   
c In case of Hep B surface antigen negative and Hep B core antibody positive. 
d In case of Hep C antibody positive. 
e Lupus reflex will be done if aPTT is prolonged. 
f For tuberculosis testing at screening, QuantiFERON-TB OR T-spot test OR purified protein derivative (PPD) test can be used.  QuantiFERON-TB can also be 
done locally. 
g In case the investigator needs to confirm postmenopausal status (and patient is not taking hormone replacement therapy). 
h For suspicion of hemolytic anemia (per the investigator’s judgment). 
 


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12.3 
Appendix 3.  Study Governance Considerations 
Independent Data Monitoring Committee 
An Independent Biostatistics Group (IBG) will perform the interim analysis and provide 
the interim report to an independent unblinded Data Monitoring Committee (DMC).  The 
DMC will review all available safety and efficacy data periodically (Table 1-1).  The IBG 
and DMC will have access to subjects’ individual treatment assignments.  To minimize 
the potential introduction of bias to the conduct of the study, members of the DMC and 
Data Monitoring Group will not have any direct contact with study site personnel or 
subjects.  The DMC will communicate major safety concerns and recommendations 
regarding study modification or termination based on the safety and efficacy parameters 
to Amgen in accordance with the DMC charter. 
Records of all meetings will be maintained by the DMC for the duration of the study.  
Records of all meetings will be transferred and stored in the trial master folder (TMF) at 
the conclusion of the study.  Further details are provided in the DMC charter. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with: 
 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines 
 
Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines 
 
Applicable ICH laws and regulations 
The protocol, protocol amendments, informed consent form, IB, and other relevant 
documents (eg, subject recruitment advertisements) must be submitted to an 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) by the investigator 
and reviewed and approved by the IRB/IEC.  A copy of the written approval of the 
protocol and informed consent form must be received by Amgen before recruitment of 
subjects into the study and shipment of Amgen investigational product. 
Amgen may amend the protocol at any time.  The investigator must submit and, where 
necessary, obtain approval from the IRB/IEC for all subsequent protocol amendments 
and changes to the informed consent document.  The investigator must send a copy of 
the approval letter from the IRB/IEC and amended protocol Investigator’s Signature 
page to Amgen prior to implementation of the protocol amendment at their site. 
The investigator will be responsible for the following: 


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 
Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
 
Obtaining annual IRB/IEC approval/renewal throughout the duration of the study.  
Copies of the investigator’s reports and the IRB/IEC continuance of approval 
must be sent to Amgen 
 
Notifying the IRB/IEC] of serious adverse events occurring at the site, deviations 
from the protocol or other adverse event reports received from Amgen, in 
accordance with local procedures 
 
Overall conduct of the study at the site and adherence to requirements of Title 21 
of the U.S. Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, and 
all other applicable local regulations 
Recruitment Procedures 
Site staff will identify potential subjects from their existing patient population or may seek 
referral patients through existing professional networks or other community sources such 
as patient advocacy groups.  All patient facing materials must be reviewed/approved by 
the sponsor (Amgen Inc.) and the local IRB/IEC. 
Informed Consent Process 
An initial sample informed consent form is provided for the investigator to prepare the 
informed consent document to be used at his or her site.  Updates to the sample 
informed consent form are to be communicated formally in writing from the Amgen Trial 
Manager to the investigator.  The written informed consent form is to be prepared in the 
language(s) of the potential patient population. 
The investigator or his/her delegated representative will explain to the subject or his/her 
legally authorized representative the aims, methods, anticipated benefits, and potential 
hazards of the study before any protocol-specific screening procedures or any 
investigational product(s) is/are administered and answer all questions regarding the 
study.   
Subjects must be informed that their participation is voluntary.  Subjects or his/her legally 
authorized representative will then be required to sign a statement of informed consent 
that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health 
Insurance Portability and Accountability Act requirements, where applicable, and the 
IRB/IEC or study site.  
The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was 


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obtained.  The authorized person obtaining the informed consent must also sign the 
informed consent form. 
The investigator is also responsible for asking the subject if the subject has a primary 
care physician and if the subject agrees to have his/her primary care physician informed 
of the subject’s participation in the clinical study unless it is a local requirement.  The 
investigator shall then inform the primary care physician.  If the subject agrees to such 
notification, the investigator is to inform the subject’s primary care physician of the 
subject’s participation in the clinical study.  If the subject does not have a primary care 
physician and the investigator will be acting in that capacity, the investigator is to 
document such in the subject’s medical record. 
The acquisition of informed consent and the subject’s agreement or refusal of his/her 
notification of the primary care physician is to be documented in the subject’s medical 
records, and the informed consent form is to be signed and personally dated by the 
subject or his/her legally authorized representative and by the person who conducted the 
informed consent discussion.  Subject withdrawal of consent or discontinuation from 
investigational product and/or procedures must also be documented in the subject’s 
medical records; refer to Section 8. 
Subjects must be re-consented to the most current version of the informed consent 
form(s) during their participation in the study.  
The original signed informed consent form is to be retained in accordance with 
institutional policy, and a copy of the informed consent form(s) must be provided to the 
subject or the subject’s legally authorized representative.  
A subject who is rescreened is not required to sign another informed consent form if the 
rescreening occurs within 33 days from the previous informed consent form signature 
date. 
The informed consent form (ICF) will contain a separate section that addresses the use 
of remaining mandatory samples for optional future research.  The investigator or 
authorized designee will explain to each subject the objectives of the future research.  
Subjects will be told that they are free to refuse to participate and may withdraw their 
specimens at any time and for any reason during the storage period.  A separate 
signature will be required to document a subject’s agreement to allow any remaining 
specimens to be used for future research.  Subjects who decline to participate will not 
provide this separate signature. 


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Data Protection/Subject Confidentiality 
The investigator must ensure that the subject’s confidentiality is maintained for 
documents submitted to Amgen. 
Subject will be assigned a unique identifier by the sponsor.  Any subject records or 
datasets that are transferred to the sponsor will contain the identifier only; subject names 
or any information which would make the subject identifiable will not be transferred.  
On the case report form (CRF) demographics page, in addition to the unique subject 
identification number, include the age at time of enrollment. 
For serious adverse events reported to Amgen, subjects are to be identified by their 
unique subject identification number, initials (for faxed reports, in accordance with local 
laws and regulations), and age (in accordance with local laws and regulations). 
Documents that are not submitted to Amgen (eg, signed informed consent forms) are to 
be kept in confidence by the investigator, except as described below. 
In compliance with governmental regulations/ICH GCP Guidelines, it is required that the 
investigator and institution permit authorized representatives of the company, of the 
regulatory agency(s), and the IRB/IEC direct access to review the subject’s original 
medical records for verification of study-related procedures and data.  Direct access 
includes examining, analyzing, verifying, and reproducing any records and reports that 
are important to the evaluation of the study.   
The investigator is obligated to inform and obtain the consent of the subject to permit 
such individuals to have access to his/her study-related records, including personal 
information. 
Publication Policy 
To coordinate dissemination of data from this study, Amgen may facilitate the formation 
of a publication committee consisting of several investigators and appropriate Amgen 
staff, the governance and responsibilities of which are set forth in a Publication Charter.  
The committee is expected to solicit input and assistance from other investigators and to 
collaborate with authors and Amgen staff, as appropriate, as defined in the Publication 
Charter.  Membership on the committee (both for investigators and Amgen staff) does 
not guarantee authorship.  The criteria described below are to be met for every 
publication. 


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Authorship of any publications resulting from this study will be determined on the basis 
of the Uniform Requirement for Manuscripts Submitted to Biomedical Journals 
International Committee of Medical Journal Editors Recommendations for the Conduct of 
Reporting, Editing, and Publications of Scholarly Work in Medical Journals, which states:  
Authorship credit is to be based on:  (1) substantial contributions to conception and 
design, acquisition of data, or analysis and interpretation of data; (2) drafting the article 
or revising it critically for important intellectual content; (3) final approval of the version to 
be published; and (4) agreement to be accountable for all aspects of the work in 
ensuring that questions related to the accuracy or integrity of any part of the work are 
appropriately investigated and resolved.  Authors need to meet conditions 1, 2, 3, and 4. 
When a large, multi-center group has conducted the work, the group is to identify the 
individuals who accept direct responsibility for the manuscript.  These individuals must 
fully meet the criteria for authorship defined above. Acquisition of funding, collection of 
data, or general supervision of the research group, alone, does not justify authorship.  All 
persons designated as authors must qualify for authorship, and all those who qualify are 
to be listed.   Each author must have participated sufficiently in the work to take public 
responsibility for appropriate portions of the content. All publications (eg, manuscripts, 
abstracts, oral/slide presentations, book chapters) based on this study must be 
submitted to Amgen for review.  The Clinical Trial Agreement among the institution, 
investigator, and Amgen will detail the procedures for, and timing of, Amgen’s review of 
publications. 
Investigator Signatory Obligations 
Each clinical study report is to be signed by the investigator or, in the case of 
multi-center studies, the coordinating investigator. 
The coordinating investigator, identified by Amgen, will be any or all of the following: 
 
A recognized expert in the therapeutic area 
 
An Investigator who provided significant contributions to either the design or 
interpretation of the study 
 
An Investigator contributing a high number of eligible subjects 
Data Quality Assurance 
All subject data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data, centrally or 
adjudicated data).  The investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the CRF.  


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The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.  
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.   
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.  
Clinical monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and verifiable 
from source documents; that the safety and rights of subjects are being protected; and 
that the study is being conducted in accordance with the currently approved protocol and 
any other study agreements, ICH GCP, and all applicable regulatory requirements per 
the sponsor’s monitoring plan.  
The investigator agrees to cooperate with the clinical monitor to ensure that any 
problems detected in the course of these monitoring visits, including delays in 
completing CRFs, are resolved. 
The Amgen representative(s) and regulatory authority inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting the facilities and, 
upon request, inspecting the various records of the clinical study (eg, CRFs and other 
pertinent data) provided that subject confidentiality is respected. 
In accordance with ICH GCP and the sponsor’s audit plans, this study may be selected 
for audit by representatives from Amgen’s Global Research and Development 
Compliance and Audit function (or designees).  Inspection of site facilities (eg, 
pharmacy, protocol-required therapy storage areas, laboratories) and review of 
study-related records will occur to evaluate the study conduct and compliance with the 
protocol, ICH GCP, and applicable regulatory requirements. 
Retention of study documents will be governed by the Clinical Trial Agreement. 
All written information and other material to be used by subjects and investigative staff 
must use vocabulary and language that are clearly understood. 
Source Documents 
The investigator is to maintain a list of appropriately qualified persons to whom he/she 
has delegated study duties.  All persons authorized to make entries and/or corrections 
on CRFs will be included on the Amgen Delegation of Authority Form. 


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Source documents provide evidence for the existence of the subject and substantiate 
the integrity of the data collected.  Source documents are filed at the investigator’s site. 
Source documents are original documents, data, and records from which the subject’s 
CRF data are obtained.  These include but are not limited to hospital records, clinical 
and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, 
and correspondence.  Source documents may also include data captured in the 
Interactive Response Technology (IRT) system (if used, such as subject ID and 
randomization number) and CRF entries if the CRF is the site of the original recording 
(ie, there is no other written or electronic record of data, such as paper questionnaires 
for a clinical outcome assessment). 
Data reported on the CRF or entered in the electronic CRF that are transcribed from 
source documents must be consistent with the source documents or the discrepancies 
must be explained.  The investigator may need to request previous medical records or 
transfer records, depending on the study.  Also, current medical records must be 
available. 
The Investigator and study staff are responsible for maintaining a comprehensive and 
centralized filing system of all study-related (essential) documentation, suitable for 
inspection at any time by representatives from Amgen and/or applicable regulatory 
authorities. 
To include the following: 
 
Subject files containing completed CRFs, informed consent forms, and subject 
identification list 
 
Study files containing the protocol with all amendments, IB, copies of prestudy 
documentation, and all correspondence to and from the IRB/IEC and Amgen 
 
Investigational product-related correspondence including Proof of Receipts, 
Investigational Product Accountability Record(s), Return of Investigational 
Product for Destruction Form(s), Final Investigational Product Reconciliation 
Statement, as applicable 
Retention of study documents will be governed by the Clinical Trial Agreement. 
Study and Site Closure 
Amgen or its designee may stop the study or study site participation in the study for 
medical, safety, regulatory, administrative, or other reasons consistent with applicable 
laws, regulations, and GCP.  


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Both Amgen and the Investigator reserve the right to terminate the Investigator’s 
participation in the study according to the Clinical Trial Agreement.  The investigator is to 
notify the IRB/IEC in writing of the study’s completion or early termination and send a 
copy of the notification to Amgen. 
Subjects may be eligible for continued treatment with Amgen investigational product(s) 
by an extension protocol or as provided for by the local country’s regulatory mechanism.  
However, Amgen reserves the unilateral right, at its sole discretion, to determine 
whether to supply Amgen investigational product(s) and by what mechanism, after 
termination of the study and before the product(s) is/are available commercially. 
Compensation 
Any arrangements for compensation to subjects for injury or illness that arises in the 
study are described in the Compensation for Injury section of the Informed Consent that 
is available as a separate document. 


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12.4 
Appendix 4.  Safety Events:  Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting 
Definition of Adverse Event 
Adverse Event Definition 
 
An adverse event is any untoward medical occurrence in a clinical study subject 
irrespective of a causal relationship with the investigational product.   
 
Note: An adverse event can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or 
exacerbated) temporally associated with the use of a treatment, combination 
product, medical device or procedure. 
 
Note:  Treatment-emergent adverse events will be defined in the SAP. 
 
Events Meeting the Adverse Event Definition 
 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, electrocardiogram, radiological scans, vital signs 
measurements), including those that worsen from baseline, that are considered 
clinically significant in the medical and scientific judgment of the investigator 
(ie, not related to progression of underlying disease). 
 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
 
New conditions detected or diagnosed after investigational product administration 
even though it may have been present before the start of the study. 
 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
investigational product or a concomitant medication.  Overdose per se will not be 
reported as an adverse event/serious adverse event unless it is an intentional 
overdose taken with possible suicidal/self-harming intent.  Such overdoses are to 
be reported regardless of sequelae. 
 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an adverse event or serious adverse event.  Such instances will be 
captured in the efficacy assessments.  However, the signs, symptoms, and/or 
clinical sequelae resulting from lack of efficacy will be reported as adverse event 
or serious adverse event if they fulfill the definition of an adverse event or serious 
adverse event.  
 
Events NOT Meeting the Adverse Event Definition 
 
Medical or surgical procedure (eg, endoscopy, appendectomy):  the condition that 
leads to the procedure is the adverse event. 
 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 


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Definition of Serious Adverse Event 
A Serious Adverse Event is defined as any untoward medical occurrence 
that, meets at least 1 of the following serious criteria: 
Results in death (fatal) 
Immediately life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which 
the subject was at risk of death at the time of the event.  It does not refer to an 
event, which hypothetically might have caused death, if it were more severe. 
Requires in-patient hospitalization or prolongation of existing 
hospitalization 
In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting.  Complications that occur during 
hospitalization are an adverse event.  If a complication prolongs hospitalization or 
fulfills any other serious criteria, the event is serious.  When in doubt as to 
whether “hospitalization” occurred or was necessary, the adverse event is to be 
considered serious.  Hospitalization for elective treatment of a pre-existing 
condition that did not worsen from baseline is not considered an adverse event. 
Results in persistent or significant disability/incapacity 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.  This definition is not intended to include experiences of 
relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma (eg, sprained ankle) which 
may interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
Is a congenital anomaly/birth defect 
Other medically important serious event 
Medical or scientific judgment is to be exercised in deciding whether serious 
adverse event reporting is appropriate in other situations such as important 
medical events that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the subject or may require medical or surgical 
intervention to prevent 1 of the other outcomes listed in the above definition.  
These events are typically to be considered serious. 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 


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Recording Adverse Events and Serious Adverse Events 
Adverse Event and Serious Adverse Event Recording 
 
When an adverse event or serious adverse event occurs, it is the responsibility of 
the investigator to review all documentation (eg, hospital progress notes, 
laboratory, and diagnostics reports) related to the event. 
 
The investigator will then record all relevant adverse event/serious adverse event 
information in the Event case report form (CRF). 
 
The investigator must assign the following adverse event attributes: 
o Adverse event diagnosis or syndrome(s), if known (if not known, signs or 
symptoms); 
o Dates of onset and resolution (if resolved); 
o Did the event start prior to first dose of investigational product 
o Assessment of seriousness; 
o Severity (or toxicity defined below); 
o Assessment of relatedness to investigational product (AMG 570/placebo), 
protocol-required therapies and/or study-mandated activity/study procedure;  
o Action taken 
 
If the severity of an adverse event changes from the date of onset to the date of 
resolution, record as a single event with the worst severity on the Events CRF. 
 
It is not acceptable for the investigator to send photocopies of the subject’s 
medical records to the sponsor in lieu of completion of the Events CRF page. 
 
If specifically requested, the investigator may need to provide additional follow-up 
information, such as discharge summaries, medical records, or extracts from the 
medical records.  In this case, all subject identifiers, with the exception of the 
subject number, will be blinded on the copies of the medical records before 
submission to Amgen. 
 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  In such cases, the diagnosis (not the 
individual signs/symptoms) will be documented as the adverse event/serious 
adverse event. 
Evaluating Adverse Events and Serious Adverse Events 
Assessment of Severity 
The investigator will make an assessment of severity for each adverse event and 
serious adverse event reported during the study.  The assessment of severity will be 
based on: 
The Common Terminology Criteria for Adverse Events, version 5 which is available at 
the following location:  
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 


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Assessment of Causality 
 
The investigator is obligated to assess the relationship between investigational 
product (AMG 570/placebo), study-mandated activity/study procedure and/or 
other protocol-required therapies and each occurrence of each adverse 
event/serious adverse event. 
 
Relatedness means that there are facts or reasons to support a relationship 
between investigational product and the event. 
 
The investigator will use clinical judgment to determine the relationship. 
 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to investigational 
product administration will be considered and investigated. 
 
The investigator will also consult the Investigator’s Brochure and/or Product 
Information, for marketed products, in his/her assessment. 
 
For each adverse event/serious adverse event, the investigator must document in 
the medical notes that he/she has reviewed the adverse event/serious adverse 
event and has provided an assessment of causality. 
 
There may be situations in which a serious adverse event has occurred, and the 
investigator has minimal information to include in the initial report.  However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the serious adverse event data. 
 
The investigator may change his/her opinion of causality in light of follow-up 
information and send a serious adverse event follow-up report with the updated 
causality assessment. 
 
The causality assessment is 1 of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of Adverse Event and Serious Adverse Event 
 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by 
Amgen to elucidate the nature and/or causality of the adverse event or serious 
adverse event as fully as possible.  This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other health 
care professionals. 
 
If a subject is permanently withdrawn from protocol-required therapies because of 
a serious adverse event, this information must be submitted to Amgen. 
 
If a subject dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Amgen with a copy of any post-mortem 
findings including histopathology. 
 
New or updated information will be recorded in the originally completed Events 
CRF. 
 
The investigator will submit any updated serious adverse event data to Amgen 
within 24 hours of receipt of the information. 


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Reporting of Serious Adverse Event 
Serious Adverse Event Reporting via Electronic Data Collection Tool 
 
The primary mechanism for reporting serious adverse event will be the electronic 
data capture (EDC) system. 
 
If the EDC system is unavailable for more than 24 hours, then the site will report 
the information to Amgen using the electronic Serious Adverse Contingency 
Report Form (this is a paper-based form) (see Figure 12-1) within 24 hours of the 
investigator’s knowledge of the event. 
 
The site will enter the serious adverse event data into the electronic system as 
soon as it becomes available. 
 
After the study is completed at a given site, the EDC system will be taken off-line 
to prevent the entry of new data or changes to existing data. 
 
If a site receives a report of a new serious adverse event from a study subject or 
receives updated data on a previously reported serious adverse event after the 
EDC has been taken off-line, then the site can report this information on the 
paper-based Serious Adverse Event Contingency Report Form (see Figure 12-1). 
 
Once the study has ended, serious adverse event(s) suspected to be related 
to investigational product will be reported to Amgen if the investigator 
becomes aware of a serious adverse event.  The investigator should use the 
paper-based Serious Adverse Event Contingency Report Form to report the 
event. 
 


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Figure 12-1.  Sample Electronic Serious Adverse Event Contingency Report Form 
 


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12.5 
Appendix 5.  Contraceptive Guidance and Collection of Pregnancy 
and Lactation Information 
Study-specific contraception requirements for females of childbearing potential are 
outlined in Section 6.2. 
Contraceptive use and methods should be consistent with local regulations for subjects 
participating in clinical studies. 
Female subjects of childbearing potential should be advised of the pregnancy prevention 
requirements and the potential risk to the fetus if they become pregnant during treatment 
and for a period of at least 10 weeks after the last dose of protocol-required therapies. 
Definition of Females of Childbearing Potential 
A female is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile.  Permanent sterilization methods include documented 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.  Females with 
documented permanent infertility due to an alternative medical cause (eg. Mullerian 
agenesis, androgen insensitivity, and gonadal dysgenesis), can be considered not of 
childbearing potential.  
Note:  bilateral tubal ligation/occlusion is not considered a permanent sterilization 
method. 
Note:  Documentation from the following sources is acceptable to provide confirmation of 
each sterilization method:  1) review of subject’s medical records; 2) subject’s medical 
examination; or 3) subject’s medical history interview. 
A postmenopausal female is defined as: 
 
A woman of ≥ 55 years with no menses for 12 months without an alternative medical 
cause OR 
 
A woman age < 55 years with no menses for at least 12 months and with a follicle 
stimulating hormone (FSH) level within the definition of “postmenopausal range” for 
the laboratory involved.  In the absence of 12 months of amenorrhea, confirmation 
with more than one FSH measurement is required. 
 
Contraception Methods for Female Subjects 
Highly Effective Contraceptive Methods 
 
Combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation (oral, intravaginal, or transdermal) 
 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable, implantable) 
 
Intrauterine device 


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 
Intrauterine hormonal-releasing system 
 
Bilateral tubal ligation/occlusion 
 
Vasectomized partner (provided that partner is the sole sexual partner of the female 
subject of childbearing potential and that the vasectomized partner has received 
medical assessment of the surgical success) 
 
Sexual abstinence (defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the investigational products; the reliability of 
sexual abstinence must be evaluated in relation to the duration of the trial and the 
preferred and usual lifestyle of the subject) 
Collection of Pregnancy Information 
Female Subjects Who Become Pregnant 
 
Investigator will collect pregnancy information on any female subject who becomes 
pregnant while taking protocol-required therapies through the final safety 
assessment. 
 
Information will be recorded on the Pregnancy Notification Form (see Figure 12-2).  
The worksheet must be submitted to Amgen Global Patient Safety within 24 hours of 
learning of a subject’s pregnancy.  (Note: Sites are not required to provide any 
information on the Pregnancy Notification Form that violates the country or regions 
local privacy laws). 
 
After obtaining the female subject’s signed authorization for release of pregnancy 
and infant health information, the investigator will collect pregnancy and infant health 
information and complete the pregnancy questionnaire for any female subject who 
becomes pregnant while taking protocol-required therapies through at least 
10 additional weeks after the last dose of the study drug.  This information will be 
forwarded to Amgen Global Patient Safety.  Generally, infant follow-up will be 
conducted up to 12 months after the birth of the child (if applicable). 
 
Any termination of pregnancy will be reported to Amgen Global Patient Safety, 
regardless of fetal status (presence or absence of anomalies) or indication for 
procedure. 
 
While pregnancy itself is not considered to be an adverse event or serious adverse 
event, any pregnancy complication or report of a congenital anomaly or 
developmental delay, fetal death, or suspected adverse reactions in the neonate will 
be reported as an adverse event or serious adverse event.  Note that an elective 
termination with no information on a fetal congenital malformation or maternal 
complication is generally not considered an adverse event, but still must be reported 
to Amgen as a pregnancy exposure case. 
 
Any serious adverse event occurring as a result of a post-study pregnancy which is 
considered reasonably related to the investigational product by the investigator, will 
be reported to Amgen Global Patient Safety as described in Section 12.4.  While the 
investigator is not obligated to actively seek this information in former study subjects, 
he or she may learn of a serious adverse event through spontaneous reporting. 
 
Any female subject who becomes pregnant while participating will discontinue 
investigational product (see Section 8.1 for details). 
Male Subjects With Partners Who Become Pregnant or Were Pregnant at the Time of 
Enrollment 


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 
In the event a male subject fathers a child during treatment, and for at least 
10 additional weeks after discontinuing protocol-required therapies, the information 
will be recorded on the Pregnancy Notification Form.  The form (see Figure 12-2) 
must be submitted to Amgen Global Patient Safety within 24 hours of the site’s 
awareness of the pregnancy.  (Note: Sites are not required to provide any 
information on the Pregnancy Notification Form that violates the country or regions 
local privacy laws). 
 
The investigator will attempt to obtain a signed authorization for release of pregnancy 
and infant health information directly from the pregnant female partner to obtain 
additional pregnancy information. 
 
After obtaining the female partner’s signed authorization for release of pregnancy 
and infant health information, the investigator will collect pregnancy outcome and 
infant health information on the pregnant partner and her baby and complete the 
pregnancy questionnaires.  This information will be forwarded to Amgen Global 
Patient Safety. 
 
Generally, infant follow-up will be conducted up to 12 months after the birth of the 
child (if applicable). 
 
Any termination of the pregnancy will be reported to Amgen Global Patient Safety 
regardless of fetal status (presence or absence of anomalies) or indication for 
procedure. 
Collection of Lactation Information 
 
Investigator will collect lactation information on any female subject who breastfeeds 
while taking protocol-required therapies through at least 10 additional weeks after the 
last dose of investigational product (Section 9.1.5). 
 
Information will be recorded on the Lactation Notification Form (Figure 12-3) and 
submitted to Amgen Global Patient Safety within 24 hours of the investigator’s 
knowledge of event. 
 
Investigational product will be discontinued if female subject breastfeeds during the 
study as described in exclusion criterion 223. 
 
With the female subjects signed authorization for release of mother and infant health 
information, the investigator will collect mother and infant health information and 
complete the lactation questionnaire on any female subject who breastfeeds while 
taking protocol-required therapies through the final safety assessment after 
discontinuing protocol-required therapies. 


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Figure 12-2.  Pregnancy Notification Form 
 
 


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Figure 12-3.  Lactation Notification Form 
 


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12.6 
Appendix 6.  Sample Storage and Destruction 
Any blood sample collected according to the Schedule of Activities (Section 2) can be 
analyzed for any of the tests outlined in the protocol and for any tests necessary to 
minimize risks to study subjects.  This includes testing to ensure analytical methods 
produce reliable and valid data throughout the course of the study.  This can also 
include, but is not limited to, investigation of unexpected results, incurred sample 
reanalysis, and analyses for method transfer and comparability. 
All samples and associated results will be coded prior to being shipped from the site for 
analysis or storage.  Samples will be tracked using a unique identifier that is assigned to 
the samples for the study.  Results are stored in a secure database to ensure 
confidentiality. 
If informed consent is provided by the subject, Amgen can do additional testing on 
remaining samples (ie, residual and back-up) to investigate and better understand the 
Inflammatory conditions, the dose-response and/or prediction of response to AMG 570 
and characterize aspects of the molecule (eg, mechanism of action/target, metabolites).  
Results from this analysis are to be documented and maintained but are not necessarily 
reported as part of this study.  Samples can be retained for up to 20 years. 
Since the evaluations are not expected to benefit the subject directly or to alter the 
treatment course, the results of pharmacogenetic, [biomarker development,] or other 
exploratory studies are not placed in the subject’s medical record and are not to be 
made available to the subject, members of the family, the personal physician, or other 
third parties, except as specified in the informed consent. 
The subject retains the right to request that the sample material be destroyed by 
contacting the investigator.  Following the request from the subject, the investigator is to 
provide the sponsor with the required study and subject number so that any remaining 
blood samples and any other components from the cells can be located and destroyed.  
Samples will be destroyed once all protocol-defined procedures are completed.  
However, information collected from samples prior to the request for destruction, will be 
retained by Amgen. 
The sponsor is the exclusive owner of any data, discoveries, or derivative materials from 
the sample materials and is responsible for the destruction of the sample(s) at the 
request of the subject through the investigator, at the end of the storage period, or as 
appropriate (eg, the scientific rationale for experimentation with a certain sample type no 


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Protocol Number:  20170588 
Date:  24 May 2022 
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CONFIDENTIAL  
FORM-001520, v.22, 05 February 2018 
 
longer justifies keeping the sample).  If a commercial product is developed from this 
research project, the sponsor owns the commercial product.  The subject has no 
commercial rights to such product and has no commercial rights to the data, information, 
discoveries, or derivative materials gained or produced from the sample.  See 
Section 12.3 for subject confidentiality. 


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12.7 
Appendix 7.  Hepatotoxicity Stopping Rules:  Suggested Actions and 
Follow-up Assessments and Investigational Product Rechallenge 
Guidelines 
Subjects with abnormal hepatic laboratory values (ie, alkaline phosphatase [ALP], 
aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBL]) 
and/or international normalized ratio (INR) and/or signs/symptoms of hepatitis (as 
described below) may meet the criteria for withholding or permanent discontinuation of 
Amgen investigational product or other protocol-required therapies, as specified in the 
Guidance for Industry Drug-Induced Liver Injury:  Premarketing Clinical Evaluation, 
July 2009. 
Criteria for Withholding and/or Permanent Discontinuation of Amgen 
Investigational Product and Other Protocol-required Therapies Due to Potential 
Hepatotoxicity 
The following stopping and/or withholding rules apply to subjects for whom another 
cause of their changes in liver biomarkers (TBL, INR and transaminases) has not been 
identified.  
Important alternative causes for elevated AST/ALT and/or TBL values include, but are 
not limited to: 
 
Hepatobiliary tract disease 
 
Viral hepatitis (eg, hepatitis A/B/C/D/E, Epstein-Barr Virus, cytomegalovirus, herpes 
simplex virus, varicella, toxoplasmosis, and parvovirus) 
 
Right sided heart failure, hypotension or any cause of hypoxia to the liver causing 
ischemia 
 
Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and dietary 
supplements, plants and mushrooms 
 
Heritable disorders causing impaired glucuronidation (eg, Gilbert’s syndrome, 
Crigler-Najjar syndrome) and drugs that inhibit bilirubin glucuronidation (eg, indinavir, 
atazanavir) 
 
Alpha-one antitrypsin deficiency 
 
Alcoholic hepatitis 
 
Autoimmune hepatitis 
 
Wilson’s disease and hemochromatosis 
 
Nonalcoholic fatty liver disease including steatohepatitis 
 
Non-hepatic causes (eg, rhabdomyolysis, hemolysis) 
If investigational product(s) is/are withheld, the subject is to be followed for possible 
drug-induced liver injury (DILI) according to recommendations in the last section of this 
appendix. 


Product:  Rozibafusp Alfa (AMG 570)  
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Rechallenge may be considered if an alternative cause for impaired liver tests (ALT, 
AST, ALP) and/or elevated TBL, is discovered and the laboratory abnormalities resolve 
to normal or baseline (see next section in this appendix). 
Table 12-2.  Conditions for Withholding and/or Permanent Discontinuation of 
Amgen Investigational Product and Other Protocol-required Therapies Due to 
Potential Hepatotoxicity 
Analyte 
Temporary Withholding 
Permanent Discontinuation 
TBL 
 3x ULN  
at any time 
 2x ULN 
 
 
OR 
INR 
-- 
 1.5x (for subjects not on 
anticoagulation therapy) 
 
OR 
AND 
AST/ALT 
 8x ULN at any time 
 5x ULN but  8x ULN for  2 weeks 
 5x ULN but  8x ULN and unable to 
adhere to enhanced monitoring schedule 
 3x ULN with clinical signs or symptoms 
that are consistent with hepatitis (such as 
right upper quadrant pain/tenderness, 
fever, nausea, vomiting, and jaundice) 
In the presence of no important 
alternative causes for elevated 
AST/ALT and/or TBL values 
 3x ULN (when baseline was  ULN) 
 
OR 
ALP 
 8x ULN at any time 
-- 
ALP  alkaline phosphatase; ALT  alanine aminotransferase; AST  aspartate aminotransferase; 
INR  international normalized ratio; TBL  total bilirubin; ULN  upper limit of normal 
Criteria for Rechallenge of Amgen Investigational Product and Other 
Protocol-required Therapies After Potential Hepatotoxicity 
The decision to rechallenge the subject is to be discussed and agreed upon 
unanimously by the subject, investigator, and Amgen. 
If signs or symptoms recur with rechallenge, then Amgen 570 is to be permanently 
discontinued.  Subjects who clearly meet the criteria for permanent discontinuation (as 
described in Table 12-2) are never to be rechallenged. 
Drug-induced Liver Injury Reporting and Additional Assessments 
Reporting 
To facilitate appropriate monitoring for signals of DILI, cases of concurrent AST or ALT 
and TBL and/or INR elevation, according to the criteria specified in the above, require 
the following: 


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 
The event is to be reported to Amgen as a serious adverse event within 24 hours of 
discovery or notification of the event (ie, before additional etiologic investigations 
have been concluded) 
 
The appropriate case report form (CRF) (eg, Event CRF) that captures information 
necessary to facilitate the evaluation of treatment-emergent liver abnormalities is to 
be completed and sent to Amgen 
Other events of hepatotoxicity and potential DILI are to be reported as serious adverse 
events if they meet the criteria for a serious adverse event defined in Section 12.4. 
Additional Clinical Assessments and Observation 
All subjects in whom investigational product(s) or protocol-required therapies is/are 
withheld (either permanently or conditionally) due to potential DILI as specified in 
Table 12-2 OR who experience AST or ALT elevations  3 x upper limit of normal (ULN) 
or 2-fold increases above baseline values for subjects with elevated values before drug 
are to undergo a period of “close observation” until abnormalities return to normal or to 
the subject’s baseline levels. Tests may be performed locally as required per 
investigator discretion. 
Assessments that are to be performed during this period include: 
 
Repeat AST, ALT, ALP, bilirubin (BIL) (total and direct), and INR within 24 hours 
 
In cases of TBL  2x ULN or INR  1.5, retesting of liver tests, BIL (total and direct), 
and INR is to be performed every 24 hours until laboratory abnormalities improve 
Testing frequency of the above laboratory tests may decrease if the abnormalities 
stabilize or the investigational product(s) or protocol-required therapies has/have been 
discontinued AND the subject is asymptomatic. 
Initiate investigation of alternative causes for elevated AST or ALT and/or elevated TBL.  
The following are to be considered depending on the clinical situation: 
 
Complete blood count with differential to assess for eosinophilia 
 
Serum total immunoglobulin (Ig)G, antinuclear antibody anti-smooth muscle 
antibody, and liver kidney microsomal antibody-1 to assess for autoimmune hepatitis 
 
Serum acetaminophen (paracetamol) levels 
 
A more detailed history of: 
 
Prior and/or concurrent diseases or illness 
 
Exposure to environmental and/or industrial chemical agents 
 
Symptoms (if applicable) including right upper quadrant pain, 
hypersensitivity-type reactions, fatigue, nausea, vomiting and fever 
 
Prior and/or concurrent use of alcohol, recreational drugs and special diets 


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Protocol Number:  20170588 
Date:  24 May 2022 
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 
Concomitant use of medications (including non-prescription medicines and 
herbal and dietary supplements), plants, and mushrooms 
 
Viral serologies 
 
Creatine phosphokinase, haptoglobin, lactate dehydrogenase and peripheral blood 
smear 
 
Appropriate liver imaging if clinically indicated 
 
Appropriate blood sampling for pharmacokinetic analysis if this has not already been 
collected 
 
Hepatology consult (liver biopsy may be considered in consultation with a 
hepatologist) 
Follow the subject and the laboratory tests (ALT, AST, TBL, INR) until all laboratory 
abnormalities return to baseline or normal or considered stable by the investigator.  The 
“close observation period” is to continue for a minimum of 4 weeks after discontinuation 
of all investigational product(s) and protocol-required therapies. 
The potential DILI event and additional information such as medical history, concomitant 
medications and laboratory results must be captured in the corresponding CRFs. 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 1 of 7 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Amendment 3 
Protocol Title:  A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of 
Rozibafusp Alfa (AMG 570) in Subjects With Active Systemic Lupus Erythematosus (SLE) 
With Inadequate Response to Standard of Care (SOC) Therapy 
 
Amgen Protocol Number AMG 570 20170588 
EudraCT Number 2019-000328-16  
NCT Number 04058028 
 
Amendment Date: 
24 May 2022 
 
Rationale: 
This protocol amendment removes the requirement for an independent blind joint assessor to 
conduct joint count assessments (number of tender and swollen joints).  There is no need to 
have a separate blinded assessor to perform joint count, since for the primary endpoint and 
other main efficacy endpoints this assessment is performed by the investigator from each site, 
who have the required training and are performing all efficacy assessments.  Additional minor 
updates were incorporated into this amendment which in general represent clarifications and 
grammatical corrections.  The following changes were included:   
1. 
Efficacy Assessments: 
o Remove requirement for a separate blinded joint assessor (section 9.2.2.5). 
o Clarify that the same investigator must perform all efficacy assessments at every 
time point for a given subject.  In order to ensure consistency, it is clarified that 
the same investigator/assessor should perform the assessments throughout the 
study for a given subject (sections 9.2.2 and 9.2.2.5). 
o Clarify data collection process (sections 9.2.2, 9.2.2.5, and 9.2.2.6). 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 2 of 7 
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o Improve clarity of the definition of Systemic Lupus Erythematosus Responder 
Index (SRI-4) response in section 9.2.2.11 and British Isles Lupus Assessment 
Group (BILAG)-based Combined Lupus Assessment (BICLA) response in 
section 9.2.2.12. 
o Clarify events that classify joints as non-evaluable (section 9.2.2.5). 
2. 
Updates to Primary Estimand include (sections 1.1 and 4.1):  
o Clarify that SRI-4 response cannot be achieved regardless of protocol deviations, 
since the Important Protocol Deviation list is now used to define 'more than 
protocol-allowed therapies'. 
o Remove language defining SRI-4 response from the Objectives/Endpoints table, 
as it is described in detail in other sections of the protocol. 
3. 
Clarifications to Objectives and Endpoints include (sections 1 and 4.1):  
o Endpoint for secondary objective aiming to evaluate efficacy of AMG 570 on joint 
count was updated to clarify that the combined tenderness and swelling of joint 
count will be conducted for joints in hands and wrists, as it is described in 
section 9.2.2.5.   
o Clarify that the endpoint for secondary objective aiming to describe efficacy of 
AMG 570 using patient-reported outcomes includes the 2 component measures 
of physical and mental health to be assessed by the Medical Outcomes Short 
Form 36 version 2 Questionnaire, as it is described in section 9.2.10.1. 
4. 
Clarifications were provided on study duration and safety follow-up for subjects that 
complete the 52-week treatment period and for subjects who discontinue the 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 3 of 7 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
investigational product earlier.  These clarifications were incorporated to multiple 
sections of the protocol (sections 5.1, 5.3.2, 9.1.3, 9.1.5.1, and Table 2-2).   
o Timing of sample collection for pharmacokinetic (PK) and 
 
assessments during safety follow-up was described for clarity purposes 
(section 9.1.3). 
o Additionally, for simplification and improved clarity, information pertaining to 
safety follow-up was removed from protocol synopsis, overall design description, 
and treatment period (sections 1.1, 5.1, and 9.1.2)  
5. 
Clarification of when an individual subject is considered to have completed the study 
(sections 5.3.2 and 9.1.5.1). 
6. 
Clarify within the table for Analyses Schedule that after the 7th interim analysis, 
additional interim analyses are planned after every 32 subjects are randomized and 
have had the opportunity to complete the week 24 assessment until full enrollment 
(Table 1-1).   
7. 
Interim analysis language was updated to remove details related to the hypothetical 
Phase 3 study as they do not impact the conduct of this study and will be pre-specified in 
the study data monitoring committee charter, statistical analysis plan, and simulation 
report, as appropriate (section 10.3.1). 
8. 
Clarify that the adjudication reviews occur at study entry to determine eligibility and 
throughout the study period on blinded endpoint data from enrollment to week 52 for all 
randomized subjects and for all visits (section 5.1). 
9. 
Clarify that subjects taking more that protocol-allowed therapies are considered 
treatment failures for the primary efficacy endpoint analyses but will be allowed to 
continue investigational product and/or the study at the investigator’s discretion except 
those initiating specific treatments with immunosuppressant/immunomodulators 
(sections 5.1, 7.1.4.1, and 7.1.7). 
o Section 7.1.7 is listing all the treatments preventing a subject from continuing 
treatment with investigational product.   


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 4 of 7 
Amgen Proprietary - Confidential 
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10. 
Title of section 9.2.6.1 was changed to Biomarker Assessment During the Study given 
that not all biomarkers listed in that section have established pharmacodynamic activity.  
11. 
Specify that all subjects who at the end of study visit have clinical sequelae considered 
potentially related to an 
 response will be asked to return for 
additional testing.  Additionally, it was clarified that follow-up results will be 
communicated to sites after database is locked to prevent potential risk of unblinding the 
sites for treatment assignment (section 9.2.8). 
12. 
Clarify what is included in baseline covariates (section 10.2.2). 
13. 
Inclusion criteria:  
o Clarify inclusion criterion 105 by re-organizing Systemic Lupus Erythematosus 
(SLE) treatments that subjects must be taking to meet protocol-specific rules 
applied during screening.  One treatment was included to this criterion, 
leflunomide (update also incorporated in section 7.4.2.2). 
14. 
Exclusion criteria:   
Other Medical Conditions  
o For consistency, criterion 208 was updated to align with the updates made to 
Schedule of Activities regarding monitoring of viral load frequency to evaluate 
hepatitis B and C.  
Prior/Concomitant Therapy was updated to: 
o Add thalidomide treatment within 4 weeks prior to screening to the treatment 
listed in exclusion criterion 212.  For consistency, thalidomide was also added as 
an excluded treatment during study period (section 7.1.7). 
o Decreased washout period for Janus kinase (JAK) inhibitor from 3 to 1 month 
prior to screening based on information available for the 
pharmacokinetic/pharmacodynamic profile of these drugs (criterion 213). 
o Clarify criterion 215 by adding immunosuppressive or immunomodulatory activity 
to treatment with a biologic agent, reduce washout period for abatacept to 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 5 of 7 
Amgen Proprietary - Confidential
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3 months prior to screening based on its pharmacokinetic/pharmacodynamic 
profile, and clarify that pharmacodynamic activity of other biologics at screening 
should be considered when evaluating washout periods. 
o
Clarify the timeframe within which a subject must not plan to receive a live
vaccine (criterion 217).
Prior/Concurrent Clinical Study Experience: 
o
Revise washout period for treatment with an investigational product or device to
consider the pharmacokinetic and pharmacodynamic profile of those products at
screening (criterion 219).
Diagnostic Assessments: 
o
Include Gilbert’s Syndrome as an exception for presence of laboratory
abnormalities during screening in serum total bilirubin since these patients
present non clinically relevant elevated bilirubin levels (criterion 221).
Other Exclusions was updated to: 
o
Clarify that serum pregnancy test is required at screening and urine pregnancy
test is required at day 1 visit (criterion 225).
15.
Schedule of Activities-Safety Follow-up Period was updated to (Table 2-2):
o
Clarify that this table applies for the subset of subjects that completed the
planned 52-week treatment period and emphasize that subjects are required to
attend as many visits as necessary to ensure a minimum of 16 weeks of safety
follow-up after last dose of the investigational product.
o
Clarify that safety follow-up visits should be scheduled in relation to last
administration of the investigational product and not visit week 52.
o
Add frequency for monitoring viral load to evaluate hepatitis B and C.
o
Remove urine pregnancy tests from the last two safety follow-up visits.


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 6 of 7 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
16. 
Minor updates were included in the footnotes of the Schedule of Activities Treatment 
Period to clarify information regarding starting time of home health care visits, the option 
of conducting a QuantiFERON-TB test locally, assessment frequency of serum viral 
DNA and RNA for hepatitis B and C, and 
.  Additionally, for 
clarity purposes details no longer relevant to the assessments were removed (Table 2-1 
footnotes e, f, g, i, q, and r). 
17. 
Accountability instructions for AMG 570 was updated to remove requirement to record 
the amount used in AMG 570 preparation on the electronic case report form for each 
subject (Table 7-1). 
18. 
Simplify language around disease flares as a possible reason to discontinue 
protocol-required investigational product or procedural assessments (section 8.1). 
19. 
The description of AMG 570 was updated (section 3.2.2). 
20. 
For rescreening, it was clarified that tuberculosis tests and serologies for hepatitis B 
virus, hepatitis C virus, and human immunodeficiency virus (HIV) are not required to be 
repeated when rescreening occurs within 12 months of screening visit, provided that 
those test results were negative and there is no patient’s medical/epidemiological history 
suggestive of infection or recent exposure to cases of infection (section 9.1.1). 
21. 
Clarify the types of corticosteroid treatments that are allowed in the study and specify 
that subjects requiring such treatments can continue the investigational product at the 
investigator’s discretion (section 7.1.4.2).   
22. 
Simplify Treatment Period section by removing information outside the scope of this 
section (section 9.1.2). 
23. 
Include the option for local laboratory to conduct the QuantiFERON-TB test for eligibility 
using a local kit procured by the site (section 9.2.4.3.2). 
24. 
Clarify the rating scale used for patient global assessment of disease activity 
(section 9.2.10.4). 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  24 May 2022 
Page 7 of 7 
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25. 
Information collected for screen failure was updated to remove medical history and prior 
therapies as these are not considered required forms for screen failure per electronic 
case report form standard instructions (section 6.5).   
26. 
Remove the efficacy analysis set (section 10.2.1.2). 
27. 
Include a footnote in Analyte Listing table to instruct that local lab testing may be 
conducted if central lab testing is unavailable and add that QuantiFERON-TB test can 
also be conducted locally.  For clarity purposes, details no longer relevant to the analyte 
listing were removed (Table 12-1 footnotes a, b, and f). 
28. 
Add a clarification note that clinical assessments to evaluate hepatoxicity in subjects for 
whom investigational product is withheld due to potential drug-induced liver injury can be 
performed locally as required per investigator discretion (section 12.7). 
29. 
Updates have been implemented to align collection and reporting of safety events with 
current procedures (Table 2-1, Table 2-2, sections 7.1.6, 9.2.3.1.1.2, 9.2.3.1.1.3, and 
12.4). 
30. 
Clarify that tapering of oral corticosteroids is allowed before week 24 at the investigator’s 
discretion (sections 1.1 and 7.1.4.2).  
32. 
The definition of the alphabetical score used to evaluate disease activity in 9 separate 
organ system was updated only for D by replacing stable with no activity 
(section 9.2.2.2).   
33. 
Administrative, typographical, abbreviations, and formatting changes were made 
throughout the protocol. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  11 November 2020 
Page 1 of 2 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Superseding Amendment 2 
Protocol Title:  A Phase 2b Dose Ranging Study to Evaluate the Efficacy and 
Safety of Rozibafusp Alfa (AMG 570) in Subjects with Active Systemic Lupus 
Erythematosus (SLE) with Inadequate Response to Standard of Care (SOC) 
Therapy 
 
Amgen Protocol Number AMG 570 20170588 
 
Amendment Date: 
13 October 2020 
Superseding Amendment Date: 
11 November 2020 
 
Superseding Amendment 2 Summary of Changes: 
 
Incorporate changes to align with the Data Monitoring Committee (DMC) Charter: 
 
Change ‘Futility’ to ‘Administrative Success’ in Table 1-1. 
 
Revise administrative success cutoff value from 85 to 80. 
 
Remove ‘moderate to severe’ from BILAG flare endpoint. 
 
Relocate the SLEDAI-2K proteinuria definition for clarity. 
 
Clarify efficacy assessment data will be captured either on an electronic or paper 
source and transmitted or entered into the study database. 
 
Clarify SLE-related eligibility will be reviewed and confirmed by the adjudication 
team. 
 
Delete Appendix 8. Data Collection to align with the updated Amgen protocol 
template. 
Amendment 2 Summary of Changes: 
 
Incorporate changes to the study design to enable the study to support registration, if 
the results are positive; these changes include: 
 
Update study from phase 2 to phase 2b. 
 
Revise primary endpoint to SRI-4 response rate at week 52 and make SRI-4 
response rate at week 24 a secondary endpoint. 
 
Change all key secondary endpoints to secondary endpoints and add secondary 
disease flare endpoints. 
 
 
Revise statistical methods, including sample size estimate, planned analyses, 
and efficacy analyses methods for primary and secondary endpoints. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  11 November 2020 
Page 2 of 2 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
 
Clarify options for a subject to proceed in the study if the subject discontinues 
investigational product prior to week 52. 
 
Clarify contraceptive guidance and pregnancy and lactation information: 
 
Adjust the duration for contraceptive requirements and collection of pregnancy 
and lactation information to at least 10 additional weeks after the last dose of 
investigational product for female subjects of childbearing potential. 
 
Specify that pregnancy testing should be performed monthly during both the 
treatment period and at the first 2 safety follow-up visits. 
 
Clarify the definition of females of childbearing potential. 
 
Specify home health care visits will be centrally provided by the sponsor starting at 
week 22 and will be optional for subjects who have not experienced adverse effects 
from investigational product administration. 
 
Clarify initiation or increase in oral corticosteroid dosing. 
 
Add Independent Data Monitoring Committee description. 
 
Administrative, typographical, and formatting changes were made throughout the 
protocol. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  13 October 2020 
Page 1 of 2 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Amendment 2 
Protocol Title:  A Phase 2b Dose Ranging Study to Evaluate the Efficacy and 
Safety of Rozibafusp Alfa (AMG 570) in Subjects with Active Systemic Lupus 
Erythematosus (SLE) with Inadequate Response to Standard of Care (SOC) 
Therapy 
 
Amgen Protocol Number AMG 570 20170588 
 
Amendment Date: 
13 October 2020 
 
Summary of Changes: 
 
Incorporate changes to the study design to enable the study to support registration, if 
the results are positive; these changes include: 
 
Update study from phase 2 to phase 2b. 
 
Revise primary endpoint to SRI-4 response rate at week 52 and make SRI-4 
response rate at week 24 a secondary endpoint. 
 
Change all key secondary endpoints to secondary endpoints and add secondary 
disease flare endpoints. 
 
Revise statistical methods, including sample size estimate, planned analyses, 
and efficacy analyses methods for primary and secondary endpoints. 
 
Clarify options for a subject to proceed in the study if the subject discontinues 
investigational product prior to week 52. 
 
Clarify contraceptive guidance and pregnancy and lactation information: 
 
Adjust the duration for contraceptive requirements and collection of pregnancy 
and lactation information to at least 10 additional weeks after the last dose of 
investigational product for female subjects of childbearing potential. 
 
Specify that pregnancy testing should be performed monthly during both the 
treatment period and at the first 2 safety follow-up visits. 
 
Clarify the definition of females of childbearing potential. 
 
Specify home health care visits will be centrally provided by the sponsor starting at 
week 22 and will be optional for subjects who have not experienced adverse effects 
from investigational product administration. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  13 October 2020 
Page 2 of 2 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
 
Clarify initiation or increase in oral corticosteroid dosing. 
 
Add Independent Data Monitoring Committee description. 
 
Administrative, typographical, and formatting changes were made throughout the 
protocol. 


Product:  AMG 570 
Protocol Number:  20170588 
Date:  28 February 2020 
Page 1 of 70 
CONFIDENTIAL 
 
 
Amendment 1 
Protocol Title:  A Phase 2 Dose Ranging Study to Evaluate the Efficacy and Safety 
of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE) With 
Inadequate Response to Standard of Care (SOC) Therapy 
 
Amgen Protocol Number 20170588 
 
Amendment Date: 
28 February 2020 
 
Rationale for Major Changes: 
 
Remove detectable systemic lupus erythematosus (SLE) standard of care 
(SOC) drug levels from the inclusion criteria list - recent evidence of 
important technical limitations in the methods used to assess levels of those 
therapies that may lead to a high rate of false negative results (which are 
particularly significant for some SLE SOC therapies).  Therefore, assessments of 
drug levels of methotrexate, chloroquine and dapsone will be removed from 
protocol, while assessment of drug levels of hydroxychloroquine, mycophenolate 
mofetil and azathioprine will remain.  Results of those assessments will be used 
only for exploratory analyses and not for eligibility purposes, as current available 
evidence is still insufficient to establish a clear correlation between drug levels 
assessed by the methods used in this protocol and adherence to those therapies. 
 
Substitute Systemic Lupus Erythematosus Disease Activity Index 2000 
(SLEDAI 2K) by hybrid SLEDAI as part of the efficacy assessment - hybrid 
SLEDAI was the SLEDAI version used to validate Systemic Lupus 
Erythematosus Responder Index (SRI) 4 index (Navarra et al, 2011; 
Furie et al, 2011).  The arthritis definition in the hybrid SLEDAI improves the 
specificity of the instrument for inflammatory arthritis, reducing the probability of 
false positive scores at baseline and throughout the study. 
 
Simplify and reduce screening period - removal of SLE drug levels from 
eligibility criteria allows shortening screening period, which simplifies screening 
process and reduce timelines.  
 
Introduce home health care visits - frequent number of visits to the site 
(every 2 weeks) has been pointed out by many patients and investigators as a 
barrier for enrollment.  The offer of home care visits is expected to increase study 
participation. 
Rationale for Minor Changes: 
 
Add Lupus Low Disease Activity State (LLDAS) to key secondary endpoints. 
 
Reduce period required for oral corticosteroids (OCS) stable dose prior to 
screening visit - from 4 to 2 weeks. 


Product:  AMG 570 
Protocol Number:  20170588 
Date:  28 February 2020 
Page 2 of 70 
CONFIDENTIAL 
 
 
 
Changes to OCS dose permitted between 0 to 4 weeks - from up to 20 mg/day 
increase in prednisone dose (or equivalent) over baseline to up to 5 mg/day 
increase (10 mg/day of prednisone or equivalent allowed if OCS being 
temporarily initiated between 0 to 4 weeks).  In both cases, return to baseline 
dose within 2 weeks is required. 
 
Remove body surface requirements for rash sore in SLEDAI at screening 
visit-rash is being evaluated through Cutaneous Lupus Erythematosus Area and 
Severity Index (CLASI) instrument and there is no need to impose restrictions 
relatively to the extension of rash (which are difficult to achieve in SLE patients). 
 
Add language relative to management of Non-steroidal Anti-inflammatory Drugs 
(NSAIDs) and analgesic therapies throughout the study - Initiation or increases in 
the NSAIDs or other analgesic therapy dose during the study are allowed if: 
1) not initiated within 24 hours of the scheduled monthly efficacy assessments 
and 2) the subject returns to baseline dose within the subsequent 2 weeks.  For 
patients taking these therapies at baseline, stable dose is recommended 
throughout the study.  
 
Substitute FACIT-Fatigue by Patient-Reported Outcome Measurement 
Information System (PROMIS)-Fatigue scale as part of Patient Reported 
outcomes (PROs) – PROMIS able to assess impact of fatigue. 
 
Revise washout period for prior biologic drugs –abatacept 6 months, belimumab 
and anifrolumab 3 months prior to screening.  
 
Add additional lab parameters – added CRP, ESR, GGT as part of regular 
chemistry assessments, add lipid profile (baseline and week 52 only), add 
(baseline, week 24 and 52), add aPTT as part of 
regular coagulation assessments.  

SAP_001.pdf: 
Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 1 of 60 
CONFIDENTIAL  
 
 
Statistical Analysis Plan 
 
Protocol Title: 
A Phase 2b Dose Ranging Study to Evaluate the 
Efficacy and Safety of Rozibafusp Alfa (AMG 570) in 
Subjects With Active Systemic Lupus 
Erythematosus (SLE) With Inadequate Response to 
Standard of Care (SOC) Therapy 
Short Protocol Title: 
Safety and Efficacy of Rozibafusp Alfa in Subjects 
With Active Systemic Lupus Erythematosus (SLE) 
Protocol Number: 
20170588 
NCT Number: 
04058028 
Authors: 
 
Sponsor: 
Amgen Inc. 
One Amgen Center Drive, 
Thousand Oaks, CA, 91320, USA 
SAP Date: 
Document Version 
Date 
Original  
27 MAY 2020 
Amendment 1  
18 JAN 2022 
Amendment 2 
03 NOV 2022 
Amendment 3 
03 OCT 2023 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 2 of 60 
CONFIDENTIAL  
 
 
Version Number 
Date 
(DDMMMYYYY) 
Summary of Changes,  
including rationale for changes 
Original (v1.0) 
27MAY2020 
 
Amendment 1 
18JAN2022 
Incorporate changes in protocol 
superseding Amendment 2: 
 
Updated the analyses schedule 
of interim analyses and primary 
analysis, and updated features at 
last interim 
 
Added independent Data 
Monitoring Committee to monitor 
safety and interim data 
 
Added language on using 
adjudicated data for primary, 
secondary and exploratory 
endpoints.  
 
Revise primary endpoint to SRI-4 
response rate at week 52, and 
the primary analysis method of 
primary endpoint using Bayesian 
Hierarchical Model 
 
Change key secondary endpoints 
to secondary endpoints and add 
secondary disease flare 
endpoints  
 
Revise the exploratory endpoints  
 
Added derivation rules for LLDAS 
 
Administrative, typographical, 
and formatting changes 
throughout  
 
Amendment 2 
03NOV2022 
Incorporate changes in protocol 
amendment 3: 
 
Updated estimand definition. 
 
Updated the imputation rules for 
missing data. 
 
Updated the analyses of adverse 
events to include events of 
interests. 
 
Administrative, typographical, 
and formatting changes 
throughout 
Amendment 3 
03OCT2023 
Incorporate changes in the scope of 
planned analyses due to early 
termination of the study: 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 3 of 60 
CONFIDENTIAL  
 
 
 
Removed subsequent IAs 
following study early 
termination 
 
Removed some exploratory 
endpoints 
 
Removed statistical 
comparisons of treatment 
groups; descriptive statistics 
by treatment groups will be 
generated instead 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 4 of 60 
CONFIDENTIAL  
 
 
Table of Contents 
Table of Contents ................................................................................................... 4 
1. 
Introduction ............................................................................................................ 9 
2. 
Objectives, Endpoints and Hypotheses .................................................................. 9 
2.1 
Objectives and Endpoints/Estimands .......................................................... 9 
2.2 
Hypotheses and/or Estimations ................................................................ 11 
3. 
Study Overview .................................................................................................... 12 
3.1 
Study Design ............................................................................................ 12 
3.2 
Sample Size ............................................................................................. 13 
3.3 
Adaptive Design ....................................................................................... 13 
4. 
Covariates and Subgroups ................................................................................... 14 
4.1 
Planned Covariates .................................................................................. 14 
4.2 
Subgroups ................................................................................................ 14 
5. 
Definitions ............................................................................................................ 14 
5.1 
Basic Definition ......................................................................................... 14 
5.2 
Study Points of Reference ........................................................................ 16 
5.3 
Study Dates .............................................................................................. 16 
5.4 
Study Time Intervals ................................................................................. 17 
5.5 
Arithmetic Calculations ............................................................................. 17 
5.6 
Efficacy Assessments ............................................................................... 17 
5.7 
Patient-reported Outcome (PRO) Assessments ........................................ 23 
6. 
Analysis Sets........................................................................................................ 25 
6.1 
Full Analysis Set ....................................................................................... 25 
6.2 
Safety Analysis Set ................................................................................... 25 
6.3 
Pharmacokinetic/Pharmacodynamic Analyses Set(s) ............................... 25 
6.4 
Interim Analysis Set(s) .............................................................................. 25 
7. 
Planned Analyses ................................................................................................ 25 
7.1 
Interim Analysis and Early Stopping Guidelines ........................................ 25 
7.2 
Final Analysis ........................................................................................... 27 
8. 
Data Screening and Acceptance .......................................................................... 28 
8.1 
General Principles .................................................................................... 28 
8.2 
Data Handling and Electronic Transfer of Data ......................................... 28 
8.3 
Handling of Missing and Incomplete Data ................................................. 28 
8.4 
Detection of Bias ...................................................................................... 31 
8.5 
Outliers ..................................................................................................... 31 
8.6 
Distributional Characteristics .................................................................... 31 
8.7 
Validation of Statistical Analyses .............................................................. 31 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 5 of 60 
CONFIDENTIAL  
 
 
9. 
Statistical Methods of Analysis ............................................................................. 31 
9.1 
General Considerations ............................................................................ 31 
9.2 
Subject Accountability ............................................................................... 32 
9.3 
Important Protocol Deviations ................................................................... 32 
9.4 
Demographic and Baseline Characteristics .............................................. 32 
9.5 
Efficacy Analyses...................................................................................... 35 
9.6 
Safety Analyses ........................................................................................ 38 
9.6.1 
Adverse Events ......................................................................... 38 
9.6.2 
Laboratory Test Results ............................................................ 38 
9.6.3 
Vital Signs ................................................................................. 39 
9.6.4 
Physical Measurements ............................................................ 39 
9.6.5 
Exposure to Investigational Product (IP) ................................... 39 
9.6.6 
Exposure to Other Protocol-required Therapy ........................... 39 
9.7 
Other Analyses ......................................................................................... 39 
9.7.1 
Analyses of Pharmacokinetic or 
Pharmacokinetic/Pharmacodynamic Endpoints ........................ 39 
10. 
Changes From Protocol-specified Analyses. ........................................................ 40 
11. 
Literature Citations / References .......................................................................... 40 
12. 
Appendices .......................................................................................................... 42 
Appendix A.  Reference Values/Toxicity Grades .................................................. 42 
Appendix B.  SLE Assessment Forms/Instruments .............................................. 42 
Appendix C.  Patient-reported Outcome Forms/Instruments ................................. 52 
Appendix D.  Analytical Windows ......................................................................... 54 
Appendix E.  Handling of Dates, Incomplete Dates and Missing Dates ................ 60 
 
List of Table 
Table 3-1. Planned Analyses Schedule:  Decisions at each Interim Analysis,  
Primary Analysis, and Final Analysis ...................................................... 13 
Table 9-1.  Primary Efficacy Endpoint Summary Table ................................................. 36 
Table 9-2.  Secondary Efficacy Endpoints Summary Table ........................................... 37 
Table 9-3.  Exploratory Efficacy Endpoints Summary Table .......................................... 38 
Table 9-4 Selected Safety Laboratory Tests ................................................................. 40 
 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 6 of 60 
CONFIDENTIAL  
 
 
List of Abbreviations and Definition of Terms 
 
Abbreviation or Term 
Definition/Explanation 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
APPT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
BHM 
Bayesian Hierarchical Model 
BICLA 
BILAG-based Composite Lupus Assessment 
BILAG 
British Isles Lupus Assessment Group 
BMI 
Body mass index 
BUN 
Blood urea nitrogen 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity 
Index 
CNS 
Central nervous system 
CPMS 
Amgen Clinical Pharmacology Modeling and Simulation 
CRF 
Case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
CVA 
Cerebrovascular accident 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EOS 
End of study 
FAS 
Full Analysis Set 
GGT 
Gamma glutamyl transpeptidase 
GLM 
Generalized linear model 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
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CONFIDENTIAL  
 
 
GSO-DM 
Global Study Operations – Data Management 
HDL 
High density lipoprotein 
IA 
Interim analysis 
IARSC 
Interim Analysis Review Steering Committee 
IBG 
Independent Biostatistics Group 
Ig 
Immunoglobin 
INR 
International normalized ratio 
IP 
Investigational product 
IPD 
Important protocol deviation 
IRT 
Interactive response technology 
LDL 
Low density lipoprotein 
LLDAS 
Lupus Low Disease Activity State 
LOCF 
Last observation carried forward 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple imputation 
NSAID 
Non-steroidal anti-inflammatory drug 
OCS 
Oral corticosteroid 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PGA 
Physician Global Assessment 
PtGA 
Patient Global Assessment 
PTT 
Partial thromboplastin time 
PRO 
Patient-Reported Outcome 
PROMIS-Fatigue SF7A 
Patient-Reported Outcome Measurement Information System 
Fatigue Short Form 7a Instrument 
QoL 
Quality of Life 
Q1 
First quartile 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
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CONFIDENTIAL  
 
 
Q3 
Third quartile 
Q2W 
Every two weeks  
Q4W 
Every four weeks 
RAR 
Response adaptive randomization 
RBC 
Red blood cells 
ROW 
Rest of the world 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SE 
Standard error 
SFI 
SLE Flare Index 
SF36v2 
Medical Outcomes Short Form-36 Questionnaire Version 2 
SLE 
Systemic Lupus Erythematosus 
hSLEDAI 
Hybrid Systemic Lupus Erythematosus Disease Activity Index 
SGOT 
Serum glutamic-oxaloacetic transaminase 
SGPT 
Serum glutamic-pyruvic transaminase 
SOC 
Standard of care 
SRI 
Systemic Lupus Erythematosus Responder Index 
SSAP 
Supplemental statistical analysis plan 
WBC 
White blood cells 
WHO 
World Health Organization 
VAS 
Visual analog scale 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 9 of 60 
CONFIDENTIAL  
 
 
1. 
Introduction 
The purpose of this Statistical Analysis Plan (SAP) is to provide details of the statistical 
analyses that have been outlined within the protocol amendment 3 for study 20170588, 
AMG 570 dated 24 May 2022.  The scope of this plan is reduced from those outlined 
in the protocol due to determination of futility at a preplanned interim analysis and 
subsequent study early termination.  It includes the final analysis that is planned and 
will be executed by the Amgen Global Biostatistical Science department unless 
otherwise specified.  
2. 
Objectives, Endpoints and Hypotheses 
2.1 
Objectives and Endpoints/Estimands 
 
Objectives 
Endpoints 
Primary 
 
Evaluate the efficacy of rozibafusp 
alfa at week 52 as measured by the 
Systemic Lupus Erythematosus 
Responder Index (SRI-4)  
 
SRI-4 response at week 52  
Primary Estimand 
The primary estimand is the difference in SRI-4 response rates between each 
rozibafusp alfa dose group and placebo at week 52 for all subjects with SLE with 
inadequate response to SOC therapy who are randomized, regardless of 
investigational product (IP) discontinuation; subjects will be considered non-
responders for using more than protocol-allowed therapies as follows:  
 
initiation or increase from baseline in oral corticosteroid (OCS) dose > 5 mg/day 
(prednisone or equivalent) or intravenous (IV) or intramuscular (IM) at any time 
point during the study  
 
initiation or increase from baseline in OCS dose ≤ 5 mg/day (prednisone or 
equivalent) after week 10 
 
initiation or increase from baseline in OCS dose ≤ 5 mg/day (prednisone or 
equivalent) between week 0 and week 8 that was not returned to baseline dose 
within the following 2 weeks 
 
initiation or increase from baseline of immunosuppressant/immunomodulator(s) at 
any time during the study 
Secondary 
 
Evaluate the efficacy of rozibafusp 
alfa at week 24 
 
SRI-4 response at week 24 
 
British Isles Lupus Assessment Group 
(BILAG)-based Combined Lupus 
Assessment (BICLA) response at 
week 24 
 
Evaluate the efficacy of rozibafusp 
alfa at week 52 
 
Lupus Low Disease Activity State 
(LLDAS) at week 52 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 10 of 60 
CONFIDENTIAL  
 
 
Objectives 
Endpoints 
 
BICLA response at week 52 
 
Evaluate the efficacy of rozibafusp 
alfa as measured by SRI-4 response 
with oral corticosteroid (OCS)-tapering  
 
SRI-4 response at week 52 with 
reduction of OCS to  7.5 mg/day by 
week 44 and sustained through week 
52 in subjects with a baseline OCS 
dose  10 mg/day 
 
Evaluate the efficacy of rozibafusp 
alfa on disease flares 
 
Annualized moderate and severe flare 
rate (as measured by 
SELENA-SLEDAI Flare Index) over 
52 weeks 
 
Annualized severe flare rate (as 
measured by SELENA-SLEDAI Flare 
Index) over 52 weeks 
 
Annualized flare rate (as measured by 
BILAG score designation of “worse” or 
“new” resulting in a B score in 
 2 organs or an A score in  1 organ) 
over 52 weeks 
 
Evaluate the efficacy of rozibafusp 
alfa on joints and skin 
 
 
Total tender and swollen joints count 
(limited to hands and wrists): ≥ 50% 
improvement from baseline at week 
12, 24, 36, and 52 in subjects with 
≥ 6 tender and swollen joints involving 
hands and wrists at baseline 
 
Cutaneous Lupus Erythematosus 
Area and Severity Index (CLASI) 
activity score  50% improvement 
from baseline at week 12, 24, 36, and 
52 in subjects with a CLASI activity 
score  8 at baseline 
 
Describe the efficacy of rozibafusp 
alfa using patient reported outcomes 
(PRO) 
 
 
Patient-Reported Outcome 
Measurement Information System 
Fatigue Short Form 7a Instrument 
(PROMIS-Fatigue SF7A) score and 
change from baseline at week 12, 24, 
36, 44, and 52 
 
Medical Outcomes Short Form 36 
version 2 Questionnaire (SF36v2) 
change from baseline in the physical 
component score, mental component 
score and individual domains of 
SF36v2 at week 12, 24, 36, 44, and 
52 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
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CONFIDENTIAL  
 
 
Objectives 
Endpoints 
 
Lupus Quality of Life questionnaire 
(LupusQoL) score and change from 
baseline at week 12, 24, 36, 44, and 
52 
 
Patient Global Assessment (PtGA) 
score and change from baseline at 
week 12, 24, 36, 44, and 52 
 
Characterize the safety of rozibafusp 
alfa 
 
Treatment-emergent adverse events 
 
Serious adverse events 
 
Clinically significant changes in 
laboratory values and vital signs 
 
Characterize the pharmacokinetics 
(PK) of rozibafusp alfa 
 
Trough serum concentrations and 
terminal elimination half-life of 
rozibafusp alfa 
 
 
Objectives 
Endpoints 
Exploratory 
 
2.2 
Hypotheses and/or Estimations 
Rozibafusp alfa administered for 52 weeks will be well tolerated and will have greater 
efficacy than placebo as measured by the SRI-4 response at week 52 in subjects with 
active SLE with inadequate response to SOC therapy. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 12 of 60 
CONFIDENTIAL  
 
 
3. 
Study Overview 
3.1 
Study Design 
This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized, placebo 
controlled, 52-week, dose-ranging study in subjects with active SLE and inadequate 
response to SOC therapies including OCS, immunosuppressants, and 
immunomodulators. Subjects will be randomized to receive either placebo or 1 of 3 
doses of rozibafusp alfa with the last dose at week 50. Study duration for a single 
subject will be 52 weeks plus the screening period and safety follow-up period. 
Treatment will be administered every 2 weeks (Q2W). Subjects are required to attend as 
many follow-up visits as necessary to ensure a minimum of 16 weeks of safety follow-up 
after the last administration of the investigational product. Tapering of OCS from the 
baseline dose will be allowed from week 24 through week 44. The first interim analysis 
(IA) will be executed after the first 40 enrolled subjects have had the opportunity to 
complete the week 24 assessment. Additional IAs may be executed after approximately 
every 32 newly enrolled subjects have had the opportunity to complete the week 24 
assessment. The last IA will occur when all 320 subjects are randomized and have had 
the opportunity to complete the week 24 assessment.  This IA will be referred to as the 
‘all-subjects-week-24 IA’.  The purpose and analyses planned at each IA are listed in 
Table 3-1. 
Based on the Data Monitoring Committee’s recommendation following review of 
the results from the 6th IA and subsequent decision by the Data Access Plan 
Team, the study was terminated due to futility and further enrollment in the study 
was stopped. Previously enrolled subjects were discontinued from IP and 
terminated the study after being followed for an additional 16 weeks following last 
dose of IP. The remaining planned IAs, including the last IA (‘all-subjects-week-24-
IA’) and the primary analysis, were not conducted.  
 
Table 3-1. Planned Analyses Schedule:  Decisions at each Interim Analysis,  
Primary Analysis, and Final Analysis 
Time point 
Adaptive Decision 
Number of subjects with 
opportunity to complete week 24 
1st IA  
RAR 
40 
2nd IA 
Futility, RAR 
72 
3rd IA 
Futility, RAR 
104 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
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CONFIDENTIAL  
 
 
4th IA 
Futility, RAR 
136 
5th IA 
Futility, RAR 
168 
6th IA 
Futility, RAR 
200 
7th IAac 
Futility, RAR 
232 
Last IAbc 
 Administrative Success  
320 
Primary Analysisc 
Not applicable 
All subjects have had the opportunity 
to complete week 52 
Final Analysis 
Not applicable 
All subjects reach EOS 
IA  interim analysis; RAR  response adaptive randomization; EOS  end of study 
a Interim analyses are planned after every 32 subjects are randomized and have had the opportunity to 
complete the week 24 assessment until full enrollment. Number of IAs will depend on the actual enrollment 
rate. 
b Last IA is the all-subjects-week-24 IA.  The administrative success analysis at the last IA will not result in 
any adaptive decision for the ongoing study. 
c  Canceled due to study early termination. 
3.2 
Sample Size 
The approximate sample size of 320 subjects is chosen to provide 80% power to detect 
≥ 25% absolute improvement for at least 1 rozibafusp alfa dose group relative to placebo 
in the primary endpoint of SRI-4 response rate at week 52 at a significance level of 
0.025 (1-sided) using a Bayesian Hierarchical Model (BHM), assuming a 40% response 
rate in placebo group.  
Because enrollment was stopped early, the actual sample size is smaller. 
3.3 
Adaptive Design 
The prospectively defined adaptive features include RAR, early decision for futility and 
an early trigger for administrative success. The following adaptations are based on the 
planned IA results:  
 
Adaptive randomization begins after a fixed allocation period. After each IA (if before 
full enrolment), the randomization probability for each of the 3 active doses may be 
changed based on clinical efficacy after an IA, while the randomization allocation for 
placebo is kept constant at 25%.   
 
Efficacy is assessed against predefined early stopping rules for futility from the 
second IA until before the last IA. If futility is triggered, the study could be terminated, 
e.g., continued enrollment and IP dosing for previously enrolled subjects would be 
stopped, etc.  
 
Efficacy is assessed against predefined rules for early administrative success only at 
the last planned IA. If administrative success is determined, downstream activities 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
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CONFIDENTIAL  
 
 
may be planned/initiated, but the execution of the trial would not be stopped or 
altered. 
 
All adaptive decisions will be based on the SRI-4 response at week 52 with 
longitudinal modeling of SRI-4 response data.  For a subject who has not yet 
completed through week 52, their 52-week value will be imputed using a longitudinal 
model based on their week 16, 20, or 24 SRI-4 response data, whichever is the 
latest. 
Modeling and simulations were used to design this Bayesian adaptive trial and refine 
study design features to achieve optimal operating characteristics, including but not 
limited to type I error, power and estimation bias. 
The IAs will be conducted by an Independent Biostatistics Group (IBG) and will be 
reviewed by a Data Monitoring Committee (DMC), both external to Amgen. The study 
team, investigators and subjects will remain blinded to the results of the IAs.  
4. 
Covariates and Subgroups 
4.1 
Planned Covariates 
Not applicable.  
4.2 
Subgroups 
The primary endpoint will be summarized within each of the subgroups listed below. If a 
subgroup sample size is less than 10% of the population, this subgroup may not be 
evaluated. The subgroups of interest include the following:  
 
baseline hSLEDAI (< 10, ≥ 10) 
 
region (North America + Western Europe, ROW) 
5. 
Definitions 
5.1 
Basic Definition 
Investigational Product (IP) 
Rozibafusp alfa and placebo. 
Enrollment/Randomization Date 
The enrollment/randomization date is the date on which a subject is assigned to a 
treatment group.  
First Dose Date 


Product:  Rozibafusp Alfa (AMG 570) 
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CONFIDENTIAL  
 
 
The first dose date is the date of administration of the first dose of IP; this may or may 
not be the same as randomization date.  
Actual Treatment Received 
The actual treatment received is the IP the subject actually received, regardless of what 
the subject was randomized to. In cases where a subject received both rozibafusp alfa 
and placebo, the actual treatment received will be the rozibafusp alfa dose.  In cases 
where a subject received multiple rozibafusp alfa doses, the actual treatment received 
will be based on the highest rozibafusp alfa dose received.  
Duration of IP exposure 
The duration of IP exposure will be derived as the date of the last IP administration plus 
13 days (14-day window - 1), end of study or cutoff date, whichever occurs first, minus 
the date of first IP administration plus 1 day. 
Flare Exposure Time 
The flare exposure time is the time from study day 1 up to the last flare assessment 
date. 
Treatment-emergent adverse event 
Treatment emergent adverse events are defined as events categorized as Adverse 
Events (AEs) starting on or after first dose of IP as determined by "Did event start before 
first dose of investigational product?" equal to "No" or missing on the Events eCRF and 
up to the end of study date. 
Baseline medication 
Baseline medication is defined as any medication with start date on or before study day 
1 and ongoing while on study. 
Concomitant medication 
Concomitant medication is defined as any medication with start date prior to the study 
day 1 and ongoing while on study or any medication with start date on or after study day 
1 and up to the end of study.  
Prednisone-equivalent dose 
Prednisone-equivalent dose will be computed based on the table below. Additionally, a 
multiplier will be applied depending on the dosing frequency: 2 for ‘twice daily’ or ‘every 


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CONFIDENTIAL  
 
 
12 hours’ and 0.5 for every other day. For example, cortisone 25 mg is equivalent to 
prednisone 5 mg and a cortisone 25 mg twice daily is equivalent to prednisone 10 
mg/day. 
Corticosteroid 
Equivalent daily dose 
Prednisone 
5 mg 
Betamethasone 
0.75 mg 
Cortisone 
25 mg 
Deflazacort 
6 mg 
Dexamethasone 
0.75 mg 
Hydrocortisone 
20 mg 
Methylprednisolone/Meprednisone/Methylprednisolone 
Acetate 
4 mg 
Prednisolone 
5 mg 
Triamcinolone 
4 mg 
5.2 
Study Points of Reference 
Baseline 
Baseline is defined as the closest recorded measurements prior to or on the first dose of 
study treatment for subjects receiving study treatment regardless of time collected. For 
subjects not receiving treatment, baseline is defined as the closest recorded 
measurements prior to or on the enrollment date. 
Study Day 1 
Study day 1 for each subject is the first day of IP administration or the day of 
randomization for subjects who did not receive IP. 
Study Day 
Study day for each subject is defined as (day of interest – study day 1) + 1 for dates on 
or after study day 1, or (day of interest – study day 1) for dates prior to study day 1. 
5.3 
Study Dates 
End of 52-Week Treatment Period Date 
End of 52-week treatment period date for each subject is defined as the date of the last 
assessment for the week 52 visit, the end of study date in case of subject early 
termination, study day 394, or February 28, 2023 (end of study date due to early 
termination decision), whichever occurs first.  


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Start of Safety Follow-up Period Date 
Start of safety follow-up period date for each subject is defined as the end of 52-week 
treatment period date plus one day. 
End of Study Date 
End of study for each subject is the date recorded on the End of Study CRF page. 
5.4 
Study Time Intervals  
Treatment Period 
The time period from study day 1 to the end of 52-week treatment period date inclusive.  
Safety Follow-up Period 
The time period from the end of treatment period date plus one day to the end of study 
date, inclusive.  
5.5 
Arithmetic Calculations 
Change from baseline 
The arithmetic difference between a post-baseline value and baseline for a given 
timepoint: 
(post-baseline value – baseline value). 
Percent change from baseline  
The change from baseline divided by baseline value and multiplied by 100:  
(change from baseline / baseline) * 100. 
If the change from baseline is not equal to zero and the baseline value is zero then 
percent change from baseline is not defined. If the change from baseline is equal 
to zero and the baseline value is also zero then percent change from baseline is 
100. 
Fold change from baseline or ratio from baseline 
Fold change from baseline equals the post-baseline value divided by the baseline 
value. If the change from baseline is not equal to 0 and the baseline value is 0 then 
fold change is not defined. If the change from baseline is equal to 0 and the 
baseline value is also 0 then fold change is 1. 
5.6 
Efficacy Assessments 
Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) 


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The hSLEDAI is a global index that evaluates disease activity and includes 24 items 
collecting specific manifestations in 9 organ systems: neurological, musculoskeletal, 
renal, mucocutaneous, general, heart, respiratory, vascular, and hematological. The 
maximum score is 105.  
The hSLEDAI is identical to the SELENA-SLEDAI score except for the scoring of 
proteinuria, which uses the SLEDAI-2K definition (proteinuria is scored 4 points if 
proteinuria > 0.5 grams/24 hours [or equivalent urine protein/creatinine ratio]). The 
hSLEDAI includes scleritis and episcleritis for visual disturbances assessments and 
scores arthritis only if > 2 joints manifest signs of inflammation.  In the hSLEDAI score, 
inflammation is strictly defined as the presence of tenderness plus one of the following: 
swelling, effusion, warmth or erythema.  In this study, for hSLEDAI scoring purposes, 
arthritis is required to involve the small joints of hands and/or wrists.   
Additional specifications were added in the protocol to reduce potential false positive 
scores and improve the instrument’s ability to score inflammatory manifestations 
attributable to the disease activity, as described below. 
1. Scleritis and episcleritis will be scored only if stability and SLE-relatedness are 
confirmed by an ophthalmologist. 
2. For alopecia to be scored, subjects should have hair loss without scarring; should 
neither have alopecia areata nor androgenic alopecia; and should have a CLASI 
activity score for alopecia ≥ 2.  
3. For oral ulcers to be scored, location and appearance must be documented by 
the clinician. 
4. Pericarditis and pleurisy will be scored if symptoms of pericarditis and pleurisy 
are accompanied by objective findings (e.g. EKG, echocardiogram, and/or chest 
X-ray, among others). 
hSLEDAI descriptors will be scored based on a review of medical history, physical 
examination, and clinical laboratory findings. Findings should reflect activity during the 
30 calendar days prior to the current visit. Details of hSLEDAI descriptors and the 
scoring algorithm are described in Appendix B.  
British-Isles Lupus Assessment Group (BILAG) 
The BILAG index (BILAG 2004) evaluates disease activity in 9 separate organ systems 
and comprises a total of 97 items. Each item is measured qualitatively by review of 
medical history and physical examination (yes/no, improving/same/worse/new) or 


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quantitatively by measuring laboratory values. Based on these items, each of the 9 
organ systems allocated an alphabetical score of A (most active), B (moderate activity), 
C (minor activity), D (no current activity) or E (never active).  
BILAG descriptors will be scored based on a review of medical history, physical 
examination, and clinical laboratory findings. Findings should reflect activity during the 4- 
week period prior to the current visit and should be related to the subject’s SLE. Details 
of BILAG descriptors and the scoring algorithm are described in Appendix B. 
Physician Global Assessment (PGA) 
The PGA is a visual analog scale (VAS) using 3 benchmarks for assessing disease 
activity over the last 4 weeks. When scoring the PGA, the previous visit score should be 
noted, and the current score should be relative to that previous visit. The score ranges 
from 0 to 3 with 3 indicating severe disease. This refers to the most severe possible 
disease and does not reflect the most severe ever seen in a particular subject, but the 
most severe disease ever seen in all SLE patients.  
This is a global assessment, factoring in all aspects of the subject’s lupus disease 
activity. It should not reflect non-lupus medical conditions. An increase of ≥ 0.3 points 
(scale 0 to 3) from baseline is considered clinically significant worsening of disease.  
Systemic Lupus Erythematosus Responder Index (SRI-4)  
A subject achieves SRI-4 response if all of the following criteria are met: 
1. ≥ 4-point reduction from baseline in hSLEDAI score 
2. no new BILAG 2004 A and no > 1 new BILAG 2004 B domain scores compared 
with baseline (e.g. no B, C, D or E scores at baseline becomes A or no more 
than 1 C, D or E score at baseline becomes B) 
3. and < 0.3-point deterioration from baseline in PGA (scale 0 to 3). 
4. no use of more than protocol-allowed therapies (i.e. initiation or increase from 
baseline in oral corticosteroid (OCS) dose > 5 mg/day (prednisone or equivalent) 
or intravenous (IV) or intramuscular (IM) at any time point during the study; 
initiation or increase in OCS dose ≤ 5 mg/day (prednisone or equivalent) after 
week 10; initiation or increase in OCS dose ≤ 5 mg/day (prednisone or 
equivalent) between week 0 and week 8 that was not returned to baseline dose 
within the following 2 weeks; initiation or increase from baseline of 
immunosuppressant/immunomodulator(s) at any time during the study.) 


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The latest visit date among hSLEDAI, BILAG and PGA will be considered the SRI-4 visit 
date. In the case when all three visit dates are missing, the upper limit of the analytic 
window of this visit will be the SRI-4 visit date. 
BILAG-based Composite Lupus Assessment (BICLA) 
A subject achieves BICLA response if all of the following criteria are met: 
1. at least one gradation of improvement in baseline BILAG domain scores in all 
body systems with moderate or severe disease activity at entry (e.g., all A 
(severe disease) domain scores at baseline falling to B (moderate), C (mild), or D 
(no activity), and all B domain scores at baseline falling to C or D)  
2. no new BILAG 2004 A domain score and no > 1 new BILAG 2004 B domain 
scores compared with baseline 
3. no worsening of the hSLEDAI score from baseline 
4. < 0.3-point deterioration from baseline in PGA (scale 0 to 3) 
5. and no use of more than protocol-allowed therapies (i.e. initiation or increase 
from baseline in oral corticosteroid (OCS) dose > 5 mg/day (prednisone or 
equivalent) or intravenous (IV) or intramuscular (IM)  at any time point during the 
study; initiation or increase in OCS dose ≤ 5 mg/day (prednisone or equivalent) 
after week 10; initiation or increase in OCS dose ≤ 5 mg/day (prednisone or 
equivalent) between week 0 and week 8 that was not returned to baseline dose 
within the following 2 weeks; initiation or increase from baseline of 
immunosuppressant/immunomodulator(s) at any time during the study.  
Swollen and Tender Joint Count 
Joints that have been replaced during the study, or have suffered trauma or received 
intra-articular injections, are considered non-evaluable.  
Swollen Joint Count Assessments – A total 28 joints will be scored for presence or 
absence of swelling. A separated score for joints in the hands and wrists will be 
calculated.  
Tender Joint Count Assessments – A total 28 joints will be scored for presence or 
absence of tenderness. A separated score for joints in the hands and wrists will be 
calculated.  


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Swollen and Tender Joint Count Assessments: joints in hands and wrists will be scored 
for the simultaneous presence of absence of swelling and tenderness.  
Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) 
The CLASI consists of 2 scores, the first summarizes the activity of the disease while the 
second is a measure of the damage done by the disease. Activity is scored based on 
erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and 
non-scarring alopecia. Damage is scored in terms of dyspigmentation and scarring, 
including scarring alopecia. Subjects are asked whether dyspigmentation due to 
cutaneous lupus lesion usually remains visible for more than 12 months, which is taken 
to be permanent. If so, the dyspigmentation score is doubled. The scores are calculated 
by simple addition based on the extent of the symptoms. The CLASI is designed as a 
table where the rows denote anatomical areas, while the columns score major clinical 
symptoms. The extent of involvement for each of the skin symptoms is documented 
according to specific anatomic areas that are scored according to the worst affected 
lesion within that area for each symptom. 
A CLASI response is defined as ≥ 50% improvement of CLASI activity score from 
baseline. 
Lupus Low Disease Activity State (LLDAS)  
A subject achieves LLDAS response if all of the following criteria are met:  
1. hSLEDAI ≤ 4 with no activity in major organ systems (renal [proteinuria, 
haematuria, pyuria, urinary casts], central nervous system (CNS) [seizure, 
psychosis, organic brain syndrome, cranial nerve disorder, CVA], 
cardiopulmonary [pericarditis, pleurisy], vasculitis, fever) and no haemolytic 
anaemia or gastrointestinal activity in BILAG 
2. no new lupus disease activity (i.e. no new descriptor scores in hSLEDAI, and no 
new activity in haemolytic anaemia or gastrointestinal domain in BILAG) 
compared with the previous assessment  
3.   PGA (scale 0-3) ≤1 
4.  Current prednisolone (or equivalent) dose ≤ 7.5 mg/day 
5.  Well tolerated standard maintenance doses of immunosuppressive drugs and 
approved biological agents (i.e. no increase or initiation of immunosuppressive 
drugs).  


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BILAG Flare Index 
The BILAG flare index will be derived from BILAG 2004, as measured by BILAG score 
designation of “worse” or “new” resulting in a B score in ≥ 2 organs or an A score in ≥ 1 
organ (Gordon et al, 2003) compared to previous available assessment. 
SELENA-SLEDAI Flare Index 
A mild or moderate flare is defined as satisfying 1 or more of the following compared 
with previous assessment: 
a. change in SELENA-SLEDAI instrument score of 3 points or more points (but not 
more than 12)  
b. new or worse discoid, photosensitive, lupus profundus, cutaneous vasculitis, or 
bullous lupus, nasopharyngeal ulcers, pleuritis, pericarditis, arthritis, or fever 
(SLE) 
c. increase in prednisone, but not to ≥ 0.5 mg/kg/day  
d. added nonsteroidal anti-inflammatory drugs (NSAIDs) or hydrochloroquine for 
SLE activity 
e. ≥ 1 increase in PGA score but not to more than 2.5  
A severe flare is defined as satisfying 1 or more of the following compared with previous 
visit:  
a. change in SELENA-SLEDAI instrument score to greater than 12 
b. New or worsening CNS-SLE, vasculitis, nephritis, myositis, platelet count < 60 X 
109 cells/L, or hemolytic anemia (hemoglobin level < 70 g/L or decrease in 
hemoglobin level > 30 g/L requiring double prednisone or prednisone increase to 
> 0.5 mg/kg/day or hospitalization 
c. increase in prednisone to >0.5 mg/kg/day  
d. new cyclophosphamide, azathioprine, mycophenolate mofetil, or methotrexate 
e. Hospitalization for SLE activity  
f. increase of PGA to ≥ 2.5 
To distinguish between mild and moderate flare an additional question, “Status”, 
was added to the classic instrument.  Based on the investigator’s clinical 
judgement, the flare is to be classified as one of the following 4 options: No Flare, 


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Mild Flare, Moderate Flare, Severe Flare. SELENA-SLEDAI flare data collected in 
ClinicalInk were transcribed to Rave and hence will be excluded from analyses to 
avoid duplicate records.  
Annualized Flare Rate 
The annualized flare rate will be calculated as the number of flares divided by the flare 
exposure time in days multiplied by 365.25.  
Systemic Lupus International Collaborating Clinics/American College of 
Rheumatology Damage Index (SDI) 
The SDI global score will be calculated as the sum of the damage scores (0-47)  from 12 
organ systems with the following possible scores: ocular (0-2), neuropsychiatric (0-6), 
renal (0-3), pulmonary (0-5), cardiovascular (0-6), peripheral vascular (0-5), 
gastrointestinal (0-6), musculoskeletal (0-7), skin (0-3), premature gonadal failure (0-1), 
diabetes (0-1) and malignancy (0-2). 
5.7 
Patient-reported Outcome (PRO) Assessments 
Medical Outcome Short Form-36 Questionnaire Version 2 (SF36v2) 
The SF-36v2 (acute version) Health Survey (Ware et al, 2000) contains 36 items and is 
a revised version of the SF-36 Health Survey. The SF-36v2 acute version is a patient-
reported generic measure of health status. This survey yields assessments of 8 domains 
of health-related quality of life: 1) limitations in physical activities because of health 
problems; 2) limitations in social activities because of physical or emotional problems; 3) 
limitations in usual role activities because of physical health problems; 4) bodily pain; 5) 
general mental health (psychological distress and well-being); 6) limitations in usual role 
activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general 
health perceptions. The scores from the 8 domains will be evaluated independently and 
aggregated into 2 norm-based summary component measures of physical and mental 


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health. The recall period is the past 7 days. The scoring of SF-36v2 will be processed by 
QualityMetric’s PRO CoRE Software. 
Patient-Reported Outcome Measurement Information System Fatigue Short Form 
7a Instrument (PROMIS Fatigue SF 7A v1.0) 
The PROMIS Fatigue Short Form 7a is a 7-item instrument originally constructed by the 
PROMIS Fatigue team to represent the range of the fatigue trait (PROMIS Fatigue 
Scoring Manual).  It assesses the experience of fatigue as well as its impact on physical, 
mental and social activities.  Both psychometric properties and clinical input were used 
in the development of the short form from the PROMIS item bank.  Estimates of 
responsiveness and minimally important differences have been reported for the 4 item 
PROMIS Fatigue instrument in SLE patients (Katz et al, 2019).  The PROMIS Fatigue 
has also been able to differentiate disease activity in other rheumatologic diseases.  
(Wohlfahrt et al, 2019). Details of the scoring algorithm are described in Appendix C. 
LupusQoL 
The LupusQoL is a SLE-specific health-related quality of life instrument (Jolly et al, 
2010; McElhone et al, 2007) for use in adults. The LupusQoL consists of 8 domains: 
physical health (8 items), pain (3 items), planning (3 items), intimate relationships (2 
items), burden to others (3 items), emotional health (6 items), body image (5 items), and 
fatigue (4 items). The final instrument has demonstrated good internal reliability 
(Cronbach's 0.88 to 0.95), good test-retest reliability (r 0.72 to 0.93), good concurrent 
validity with the comparable domains of the SF-36 (r 0.71 to 0.79) and good discriminant 
validity for different levels of disease activity, measured by BILAG index, and damage 
(Systemic Lupus International Collaborating Clinics/ACR damage index) but not for all 
domains. The instrument also has acceptable ceiling effects and minimal floor effects. 
Details of the scoring algorithm are described in Appendix C.  
Patient Global Assessment (PtGA) 
The patient global assessment of disease activity (PtGA) typically assesses disease 
activity on a 10 cm numeric rating scale (NRS; 0 to 10 cm) or 0-100 response. The scale 
for the assessment ranges from “very well” (0) to “very poor” (10) (Furie et al, 2009). The 
validity of the PtGA in SLE has been established (Khraishi et al, 2014; Liang et al, 1989). 
The PtGA scale has a 7-day recall. 


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6. 
Analysis Sets 
6.1 
Full Analysis Set 
The Full Analysis Set (FAS) includes all randomized subjects. Data will be analyzed 
based on subjects’ randomized treatment assignment.  
6.2 
Safety Analysis Set 
The Safety Analysis Set includes all randomized subjects who received at least 1 dose 
of IP. Subjects in this set will be analyzed according to the actual treatment received. 
6.3 
Pharmacokinetic/Pharmacodynamic Analyses Set(s) 
The PK concentration analysis set will contain all subjects who received at least one 
dose of IP and have at least one quantifiable PK sample collected. PK concentration 
data will be analyzed according to the actual treatment received.  
The PK parameter analysis set will contain all subjects who received at least one dose of 
IP and for whom at least one PK parameter can be adequately estimated. PK parameter 
will be analyzed according to the actual treatment received. 
6.4 
Interim Analysis Set(s) 
Each Interim Analysis Set include all subjects randomized on or before the interim 
analysis cutoff date and had the opportunity to complete week 16 (actual week 16 visit 
date ≤ the cutoff date, or randomization date + 126 - 1 < cutoff date). The interim data 
cutoff dates are defined as the date the last enrolled subject among those that 
trigger an interim analysis (Table 3-1) has the opportunity to complete the week 24 
visit. 
7. 
Planned Analyses 
7.1 
Interim Analysis and Early Stopping Guidelines 
Interim analyses (IAs) will be conducted to allow adaptation of the randomization ratio to 
the 3 rozibafusp alfa treatment groups, holding the allocation to placebo constant at 
25%, and to assess efficacy for early futility or administrative success decisions: 
 
Data will be subject to ongoing checks for integrity, completeness and accuracy 
in accordance with the Data Management Plan with the expectation that 
outstanding data issues are resolved ahead of the snapshot to the extent 


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possible. All available data up to and including the data cut-off date will be 
included in the analysis based on an “as-is” snapshot of the database without 
data locking. 
 
The study team, investigators, and patients will remain blinded to the study 
treatment, changes in randomization allocation probabilities, and results of the 
interim analyses unless futility is determined.  
 
The first IA will be executed after the first enrolled 40 subjects are randomized 
and have had the opportunity to complete the week 24 assessment. Subsequent 
IAs will be scheduled after every additional 32 subjects are randomized and have 
had the opportunity to complete the week 24 assessment until full enrollment. 
The last IA will occur when all 320 subjects are randomized and have had the 
opportunity to complete the week 24 assessment. This IA will be referred to as 
the ‘all-subjects-week-24’ IA. 
 
Efficacy analyses will be performed at the IAs to assess the likelihood of 
rozibafusp alfa being superior to placebo by a clinically meaningful difference. 
From the second IA until before the last IA, if this likelihood is unacceptably low 
for all dose levels, the trial is recommended to stop for futility. 
 
Additionally, at the ‘all-subjects-week24 IA’, if this likelihood is sufficiently high in 
at least 1 rozibafusp alfa dose level, IA triggers an administrative success signal. 
This would not alter ongoing or planned activities of this study, but downstream 
planning for subsequent trials (e.g. a phase 3 study) may commence. Analysis 
planned at each IA are listed in Table 3-1.  This interim analysis was cancelled 
due to the study being terminated for futility prior to this analysis. 
At IAs,  
 
For all IAs before full enrollment, the randomization ratio to each active treatment 
group is proportional to the posterior probability that each group has the highest 
response rate among the three active treatment groups with power scale of 2.  
𝐴𝑙𝑙𝑜𝑐𝑎𝑡𝑖𝑜𝑛𝑑∝Pr ( 𝑝𝑑,52 = max
𝑐
𝑝𝑐,52 ∣∣∣Interim Data ), 𝑐, 𝑑∈{𝑙𝑜𝑤, 𝑚𝑒𝑑𝑖𝑢𝑚, ℎ𝑖𝑔ℎ} 
where 𝑝𝑑,52 is the posterior probability of achieving SRI-4 response for group d, 
calculated using a Bayesian independent logistic model with non-informative 
priors. 


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 
From the second IA until before the last IA, the interim futility analysis will be 
performed based on the BHM as described in the primary efficacy analysis. 
Enrollment to the study may be stopped for futility if the posterior probability of 
achieving a clinically meaningful difference in SRI-4 response rates of at least 
15% between each active treatment group and placebo is below 2.5% for all 3 
rozibafusp alfa doses.  
max Pr( 𝑝𝑑,52 −𝑝𝑝𝑙𝑎𝑐𝑒𝑏𝑜,52 > 𝛿∣∣Interim Data ) < 0.025, 𝑑∈{𝑙𝑜𝑤, 𝑚𝑒𝑑𝑖𝑢𝑚, ℎ𝑖𝑔ℎ} 
where 𝛿= 0.15 and 𝑝𝑑,52is the posterior probability of achieving SRI-4 response 
for group d, calculated using a BHM. 
 
The futility rule trigger is made using estimates of the response rate 𝑝𝑑,52 for 
each dose. However, due to the covariate adjustment, the Bayesian models 
provide estimates of 𝑝𝑑∣𝑍, the response rate in each dose conditional on the 
stratification factor 𝑍. The population level estimate for each dose is obtained 
using a weighted average of the response rate in each stratification group. 
𝑝𝑑= ∑𝑤𝑧⋅
𝑍∈𝒵
𝑝𝑑∣𝑍    for  𝑑∈{𝑝𝑙𝑎𝑐𝑒𝑏𝑜, 𝑙𝑜𝑤, 𝑚𝑒𝑑𝑖𝑢𝑚, ℎ𝑖𝑔ℎ} 
The set 𝑍 indicates the four possible stratification combinations (hSLEDAI 
stratification [≥10, <10] and region [North America + Western Europe vs ROW]). 
The weights 𝑤𝑧 will be set equal to the observed proportion of patients in each 
stratification group at the time of the analysis.  
 
To address the challenge of the lag time between randomization and the week 
52 outcome in the adaptive design, a longitudinal model is used to impute week 
52 outcome for subjects not yet complete week 52 using their week 16, week 20, 
or week 24 response data. 
7.2 
Final Analysis 
The final analysis will take place after study completion is reached or study is early 
terminated, i.e. after the last subject completes last visit or early terminates from the 
study, and all data are collected for the study. 
Data will be subject to ongoing checks for integrity, completeness and accuracy in 
accordance with the Data Management Plan with the expectation that all outstanding 
data issues are resolved ahead of the final lock. The data supporting the final analysis 
will be locked to prevent further changes. 


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8. 
Data Screening and Acceptance 
8.1 
General Principles 
The objective of the data screening is to assess the quantity, quality, and statistical 
characteristics of the data relative to the requirements of the planned analyses. 
8.2 
Data Handling and Electronic Transfer of Data 
The Amgen Global Study Operations-Data Management (GSO-DM) department will 
provide all data to be used in the planned analyses.  This study will use the RAVE 
database. All laboratory, PK, 
 and biomarker data from the 
central laboratory or vendor will be transferred to GSO-DM. All efficacy and PRO data 
from the central vendor will be transferred to GSO-DM. All other data will be captured on 
the eCRF. 
8.3 
Handling of Missing and Incomplete Data 
Subjects may have missing specific data points for a variety of reasons. In general, data 
may be missing due to a subject’s early withdrawal from study, a missed visit, or non-
evaluability of a specific clinical or laboratory measurement at its planned clinical visit. 
Additionally, as the study was terminated before the planned completion, subjects 
may have missed clinical visits including not completing the week 52 visit. For 
efficacy and PRO outcomes, subjects who terminated early due to sponsor 
decision will be excluded from analyses of data from visits for which they did not 
have the opportunity to participate in by the date of study termination decision 
being communicated to sites, i.e. February 28, 2023.  Efficacy data collected after 
this date will be censored and excluded from analyses for that particular visit.  
Unless specified, no imputation will be used. The general procedures outlined below 
describe what will be done when a data point is missing. 
Hybrid SLEDAI 
In case of completely missing hSLEDAI assessment (e.g. missed visit) or partially 
missing (e.g. laboratory measurements not available), the missing post-baseline 
hSLEDAI items will be imputed using last observation carried forward (LOCF) if the 
previous analysis visit is not missing. Baseline hSLEDAI will not be carried forward to 
post-baseline.  


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The hSLEDAI total score will then be computed based on the non-missing and imputed 
data. If the hSLEDAI total score cannot be evaluated after imputation, the hSLEDAI 
score ≥ 4 points reduction from baseline will be considered not met. 
CLASI 
In case of completely missing CLASI assessment (e.g. missed visit) or partially 
missing, the missing post-baseline CLASI items will be imputed using LOCF if the 
previous analysis visit is not missing. Baseline CLASI will not be carried forward 
to post-baseline.  
The CLASI activity score will then be computed based on the non-missing and 
imputed data. If the CLASI activity score cannot be evaluated after imputation, the 
CLASI activity score ≥ 50% improvement endpoint will be considered not met. 
BILAG 
In case of completely missing BILAG assessment (e.g. missed visit), the missing post 
baseline BILAG item scores will be imputed using LOCF if the previous analysis visit is 
not missing.  
In case of partially missing, missing laboratory items (e.g. UPCR, creatinine, etc.), 
nephrotic syndrome or urinary sediment will be imputed using LOCF if the previous 
visit is not missing; other missing items (e.g. active nephritis, Coombs' test positive, etc.) 
will be imputed as ‘No’ or ‘Not Present’.  
Baseline BILAG will not be carried forward to missing post-baseline BILAG. 
The BILAG organ domain scores will be based on the non-missing and imputed 
components. If the non-missing and imputed components are not sufficient to identify the 
organ domain score, worst scenario approach will be used to determine the BILAG 
organ domain scores. 
PGA 
Missing post-baseline PGA score will be imputed using LOCF if the previous analysis 
visit is not missing. Baseline PGA will not be carried forward to missing post-baseline 
PGA.  
SRI-4, BICLA and LLDAS 
The criteria for SRI-4, BICLA and LLDAS responses will be evaluated based on the non-
missing and imputed PGA, hSLEDAI and BILAG data. If any criteria based on the non-


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missing and imputed PGA, hSLEDAI and BILAG data cannot be evaluated, then the 
subject will be considered non-responder. 
BILAG Flare index 
BILAG flare index will be evaluated based on BILAG scores. In case of partially 
missing BILAG assessment, imputed BILAG scores will be used. In case of 
completely missing BILAG assessment, BILAG flare index will remain missing. 
Tender and Swollen Joint Counts 
If a joint is excluded (non-evaluable, missing or not done), the joint counts will be 
prorated based on the algorithm described below.  
Prorated Joint Counts: If at least half but not all joints are evaluable (at least 14 joints for 
the total 28 joint count, at least 11 joints for the 22 hands and wrists joint count) then the 
observed prorated tender or swollen joint count will be calculated. The prorated scores 
will be adjusted based upon the number of evaluable joints: the counted score will be 
multiplied by 28 (for total) or 22 (for hands and wrists) as applicable and divided by the 
number of joints evaluated. If less than half of the joints are evaluable, the number of 
tender or swollen joints is missing. For example, if only 25 of the 28 joints are assessed 
at a visit and 10 of those 25 are tender and 8 of those 25 are swollen, the prorated total 
joint counts are:  
Tender: (10/25)*28 = 11.20,  
Swollen: (8/25)*28 = 8.96.  
That is, the values of 11.20 and 8.96 will be used in calculating the % reductions in total 
joint counts, not the values of 10 and 8. Similar proration will be conducted for hands 
and wrists joint count.  
If the tender and swollen joint counts cannot be evaluated after proration, the 
tender and swollen joint count ≥ 50% improvement from baseline endpoint will be 
considered not met. 
Dates 


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Missing and incomplete dates will be imputed as outlined in Appendix E. 
Laboratory Toxicity Grading 
In cases when supplemental information for laboratory toxicity grading is missing 
or the result is ambiguous, the worse toxicity grade possible will be assigned. 
Laboratory Measurements 
Laboratory measurements that are below the lower quantification limits will be 
considered equal to the lower limit of quantification for all analyses unless 
explicitly noted otherwise. 
8.4 
Detection of Bias 
Important protocol deviations and early withdrawal from treatment and from study may 
bias the results of the study. The incidence of these factors will be assessed and reason 
for early withdrawals will be tabulated.  
8.5 
Outliers 
Scatter plots will be examined to identify potential outliers in any of the continuous 
variables and frequencies of the categorical data will be examined to identify 
questionable values. The validity of any questionable values will be verified, and 
observations found to be due to data entry errors will be queried. Potential outliers that 
are not due to data entry error will be included in the analysis.  
8.6 
Distributional Characteristics 
Not applicable. 
8.7 
Validation of Statistical Analyses 
Programs will be developed and maintained, and outputs will be verified in accordance 
with current risk-based quality control procedures.   
Tables, figures, and listings will be produced with validated standard macro programs 
where standard macros can produce the specified outputs.   
The production environment for statistical analyses consists of Amgen-supported 
versions of statistical analysis software; for example, the SAS System version 9.4 or 
later. 
9. 
Statistical Methods of Analysis 
9.1 
General Considerations 
All categorical variables will be summarized using the number and percent of subjects 
falling into each category and all continuous variables will be summarized using mean, 


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standard error (SE) or standard deviation (SD), median, first quartile (Q1), third quartile 
(Q3), minimum, maximum, and number of subjects with observations. Safety endpoints 
will be summarized descriptively, including the treatment-emergent adverse events and 
serious adverse events, clinically significant changes in laboratory values and vital signs, 
and incidence of 
. All safety analyses will be performed using the 
Safety Analysis Set based on subject’s actual treatment received. 
9.2 
Subject Accountability 
The study dates for the first subject enrolled, last subject enrolled, last subject’s end of 
IP and last subject last visit will be presented by randomized treatment group. 
The number and percent of subjects who were enrolled, randomized, received 
investigational product, completed investigational product, discontinued investigational 
product and reasons for discontinuing, completed study, discontinued study and reasons 
for discontinuing study will be summarized by randomized treatment group. Summary of 
subjects who discontinue investigational product/study due to COVID-19 control 
measures will be included. 
9.3 
Important Protocol Deviations 
Important Protocol Deviations (IPDs) categories are defined by the study team before 
the first subject’s initial visit and updated during the IPD reviews throughout the study 
prior to database lock. These definitions of IPD categories, subcategory codes, and 
descriptions will be used during the course of the study.  Eligibility deviations are defined 
in the protocol. The final IPD list will be used to produce the summary of IPDs table and 
the list of subjects with IPDs. IPDs related to COVID-19 control measures will be 
summarized separately. 
9.4 
Demographic and Baseline Characteristics 
The following demographic, baseline characteristics, baseline disease characteristics 
and baseline therapies of interest will be summarized descriptively by randomized 
treatment group.   
Demographics: 
 
sex (female, male) 
 
age (years) 
 
age groups (≥ 18 to < 50, ≥ 50 and 18 – 64, 65 – 74, 75 - 84) 


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 
race (American Indian or Alaska Native, Asian, Black or African-American, Native 
Hawaiian or Other Pacific Islander, White, Other) 
 
ethnicity (Hispanic or Latino, Not Hispanic or Latino) 
 
geographic region (North America [Canada and United States] + Western Europe 
[France, Germany, Sweden, Austria, Switzerland, and United Kingdom], ROW 
[Bulgaria, Czech Republic, Hungary, Italy, Poland, Russia, Turkey, Brazil, 
Australia, Japan, New Zealand, South Korea, Mexico, Hong Kong, Argentina, 
Spain, Portugal and Greece]) 
Baseline characteristics: 
 
height (cm) 
 
weight (kg) 
 
body mass index (BMI) (kg/m2) 
Baseline disease characteristics: 
 
years since SLE diagnosis 
 
hSLEDAI score (continuous, ≥ 10 or < 10) 
 
baseline hSLEDAI organ involvement (CNS [seizure, psychosis, organic brain 
syndrome, visual disturbance, cranial nerve disorder, lupus headache, 
cerebrovascular accident], vascular [vasculitis], renal [urinary casts, hematuria, 
proteinuria, pyuria], musculoskeletal [arthritis, myositis], serosal [pleurisy, 
pericarditis], dermal [rash, alopecia, mucosal ulcers], immunologic [low 
complement, increased DNA binding], constitutional [fever], hematologic 
[thrombocytopenia, leukopenia]) 
 
BILAG domain score (A, B, C, D, E) 
o constitutional  
o mucocutaneous  
o neuropsychiatric 
o musculoskeletal 
o cardiorespiratory 
o gastrointestinal 


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o ophthalmic 
o renal 
o haematological 
 
CLASI score (continuous, 0, > 0 to < 8, ≥ 8)  
 
total swollen and tender joint counts 
 
hand and wrist swollen and tender joint counts 
 
PGA score 
 
baseline biomarkers 
Baseline medications  
 
background medications (detectable vs undetectable baseline SLE SOC 
drug levels) 
 
immunosuppressant/immunomodulator (yes, no) 
o mycophenolate mofetil  
o azathioprine 
o methotrexate 
o hydroxychloroquine 


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o chloroquine 
o dapsone 
o other 
 
daily OCS dose (prednisone-equivalent mg/day; continuous, 0 mg/day, > 0 to < 
10 mg/day, ≥ 10 mg/day) 
9.5 
Efficacy Analyses 
Unless stated otherwise, the Full Analysis Set (FAS) will be used for analysis of efficacy 
endpoints. The efficacy analyses are summarized in Table 9-1, Table 9-2 and Table 9-3. 
The SLE efficacy assessment data (BILAG, hSLEDAI, PGA, CLASI, swollen and tender 
joint counts, and SELENA-SLEDAI flare index) will be submitted to an external 
independent clinician adjudicator with expertise in managing and assessing SLE 
disease and clinical trials for adjudication. The committee will adjudicate the data and 
determine whether the efficacy assessments are scored correctly and consistently based 
on the instruments’ specifications. 
Unless stated otherwise, the analysis of the SLE efficacy assessment data and their 
derived endpoints (SRI-4, BICLA, LLDAS and BILAG flare index) will be based on the 
data resulting from the adjudication. Additionally, to assess the concordance between 
the investigators and adjudicators, the SRI-4 responses at week 16, 20, 24 and 52 
based on the two sources will be cross-tabulated and the concordance rate will be 
computed as the frequency of cases where the data based on the investigator's 
assessment and the data resulting from adjudication agree on classification of a subject 
as an SRI-4 responder/non-responder. If the overall concordance rate at week 52 is < 
0.95, the primary endpoint may be summarized using SRI-4 responses derived based 
on the investigator-reported data as a sensitivity analysis. 


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Table 9-1.  Primary Efficacy Endpoint Summary Table 
Endpoint 
Primary Summary and 
Analysis Method 
Sensitivity and 
Supplementary Analysis 
SRI-4 response at week 52 
Number and percentage of 
subjects achieving SRI-4 
response will be 
summarized by randomized 
treatment arm.  
 
 
To assess different data 
source, the analysis may be 
repeated using SRI-4 
responses based on the 
investigator data, if the 
concordance rate is < 0.95. 
 
  
Table 9-2.  Secondary Efficacy Endpoints Summary Table 
Endpoint 
Primary Summary and Analysis Method  
 
SRI-4 response at week 24 
 
LLDAS response at week 52 
 
BICLA response at week 24  
 
BICLA response at week 52 
 
SRI-4 response at week 52 with 
reduction of OCS to ≤7.5 mg/day by 
week 44 and sustained through 
week 52 in subjects with a baseline 
OCS dose ≥10 mg/day 
Number and percentage of subjects 
achieving response of interest will be 
summarized by randomized treatment arm. 
 
Annualized moderate and severe 
flare rate (as measured by SELENA-
SLEDAI Flare Index) over 52 weeks 
 
Annualized severe flare rate (as 
measured by SELENA-SLEDAI 
Flare Index) over 52 weeks 
 
Annualized flare rate (as measured 
by BILAG score designation of 
“worse” or “new” resulting in a B 
score in ≥ 2 organs or an A score in 
≥ 1 organ) over 52 weeks 
Descriptive statistics will be summarized by 
randomized treatment arm. 
 
Total tender and swollen joint count 
(limited to hands and wrists) ≥ 50% 
improvement from baseline at week 
12, 24, 36, and 52 in subjects with 
≥ 6 tender and swollen joints 
involving the hands and wrists at 
baseline 
 
CLASI activity score  50% 
improvement from baseline at week 
12, 24, 36, and 52 in subjects with a 
CLASI activity score  8 at baseline 
Number and percentage of subjects 
achieving response of interest will be 
summarized by randomized treatment arm. 
 


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Table 9-3.  Exploratory Efficacy Endpoints Summary Table 
Endpoint 
Primary Summary and Analysis Method 
 
PROMIS-Fatigue score and change 
from baseline at week 12, 24, 36, 
44, and 52 
 
SF36v2 score and change from 
baseline at week 12, 24, 36, 44, and 
52 
 
LupusQoL score and change from 
baseline at week 12, 24, 36, 44, and 
52 
 
PtGA score and change from 
baseline at week 12, 24, 36, 44, and 
52 
 
Descriptive statistics will be summarized by 
randomized treatment arm.  


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9.6 
Safety Analyses 
In the safety analyses, data up to the end of study will be summarized in the final 
analysis. The safety analyses will be based on the safety analysis set. 
9.6.1 
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) version 26.0 or later will be 
used to code all adverse events to a system organ class and a preferred term. The 
severity of each event will be graded using Common Terminology Criteria for Adverse 
Events (CTCAE) version 5. 
The subject incidence of adverse events will be summarized for all treatment-emergent 
adverse events, serious adverse events, adverse events leading to withdrawal of IP, 
fatal adverse events, treatment-related adverse events, treatment-related serious 
adverse events, treatment-related adverse events leading to withdrawal of IP, treatment-
related fatal adverse events and adverse events of interest. Subject incidence of 
treatment-emergent adverse events identified by COVID-19 standardized MedDRA 
queries and serious adverse events occurring on or after the COVID-19 infection will 
also be summarized. 
Subject incidence of all treatment-emergent adverse events, serious adverse events, 
adverse events leading to withdrawal of IP, and fatal adverse events will be tabulated by 
system organ class in alphabetical order and preferred term in descending order of 
frequency. 
Subject incidence of events of interest (standardized MedDRA queries [SMQ] and/or 
Amgen Medical Queries [AMQ]) will also be summarized according to their categories, 
preferred term and severity grade. The events of interests will include but not limited to 
hypersensitivity (SMQ), injection site reactions (AMQ), infections (infections and 
infestations system organ class) and malignancy (SMQ). 
Summaries of treatment-emergent and serious adverse events will be tabulated by 
system organ class, preferred term and grade. An overall summary of adverse events by 
severity grade will be provided. 
9.6.2 
Laboratory Test Results 
Selected clinical laboratory test results, change and percent change from baseline will 
be summarized over time by treatment arm. In addition, shift tables from baseline to the 
worst on-study laboratory toxicity based on the CTCAE version 5, will be presented.  


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Table 9-4 Selected Safety Laboratory Tests 
Chemistry 
Hematology 
Urinalysis 
Creatinine 
Total bilirubin 
AST (SGOT) 
ALT (SGPT) 
C-reactive Protein 
 
RBC 
Hemoglobin 
Hematocrit 
MCV 
Reticulocytes Platelets 
WBC 
Differential 
 
Eosinophils 
 
Basophils 
 
Lymphocytes 
Protein/creatinine ratio 
WBC 
RBC 
 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; MCV = mean corpuscular volume; 
RBC = red blood cell count; SGOT = serum glutamic-oxaloacetic transaminase; SGPT = serum glutamic-
pyruvic transaminase; WBC = white blood cell count 
9.6.3 
Vital Signs 
The actual value, change and percent change from baseline in vital signs will be 
summarized over time by treatment arm for systolic/diastolic blood pressure, heart rate, 
respiratory rate, and temperature.  
9.6.4 
Physical Measurements 
The actual value, change and percent change from baseline in weight will be 
summarized by treatment arm by scheduled visit.  
9.6.5 
Exposure to Investigational Product (IP) 
Descriptive statistics will be produced to describe the exposure to IP by treatment arm. 
Summary statistics will be provided for the total dose received, and total duration of IP 
exposure by treatment arm. 
9.6.6 
Exposure to Other Protocol-required Therapy 
Other protocol-required therapies for this study are immunomodulators and 
immunosuppressants, OCS, NSAIDs, topical corticosteroids and topical calcineurin 
inhibitors and anti-proteinuria agents. 
The baseline exposure to OCS and immunomodulators/immunosuppressants will 
be summarized using descriptive statistics (number and percentages). 
9.7 
Other Analyses 
9.7.1 
Analyses of Pharmacokinetic or Pharmacokinetic/Pharmacodynamic 
Endpoints 
Amgen Clinical Pharmacology Modeling and Simulation (CPMS) group will conduct PK 
analysis. Serum concentration data will be summarized by treatment for each PK 
sampling time point. PK parameters may be summarized if adequately estimated.  


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10. 
Changes From Protocol-specified Analyses. 
Based on the Data Monitoring Committee’s recommendation after interim analysis 
6 and subsequent decision by the Data Access Plan Team, enrollment in the study 
was stopped and the study terminated as the study met the pre-specified futility 
criteria.  As such, some analyses that were initially planned in the protocol will not 
be performed. Key changes from protocol-specified analyses are as follows:  
 
Removal of subsequent IAs following study early termination. 
 
Removal of some exploratory endpoints. 
 
Removal of statistical comparisons of treatment groups; descriptive 
statistics by treatment groups will be generated instead. 
11. 
Literature Citations / References 
Agresti A. Categorical Data Analysis, New York: John Wiley & Sons, Inc, 1990. 
Buyon JP, Petri MA, Kim MY, et. al. The effect of combined estrogen and progesterone 
hormone replacement therapy on disease activity in systemic lupus erythematosus: A 
randomized trial. Ann Intern Med. 2005;142:953. 
Franklyn K, Lau CS, Navarra SV, et al. Definition and initial validation of a Lupus Low 
Disease Activity State (LLDAS). Ann Rheum Dis. 2016 Sep;75(9):1615-1621. 
Furie RA, Petri MA, Wallace DJ, et al. Novel evidence-based systemic lupus 
erythematosus responder index. Arthritis & Rheum. 2009;61(9):1143-1151. 
Ge M, Durham LK, Meyer RD, Xie W, Thomas N.  Covariate-adjusted difference in 
proportions from clinical trials using logistic regression and weighted risk 
differences.  Drug Inf J.  2011;45:481-493. 
Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the 
systemic lupus international collaborating clinics/American College of Rheumatology 
Damage Index for Systemic Lupus Erythematosus. Arthritis Rheum. 1996; 39(3):363-
369. 
Gordon C, Sutcliffe N, Skan J, et al. Definition and treatment of lupus flares measured by 
the BILAG index. Rheumatology. 2003;42(11):1372-9. 
Jolly M, Pickard AS, Wilke C et al. Lupus-specific health outcome measure for US 
patients: the LupusQoL-US version. Ann Rheum Dis. 2010;69:29-33. 
Katz P, Pedro S, Alemao E, et al.  Estimates of responsiveness, minimally import 
differences and patient acceptable symptom state in five patient-reported outcomes 
measurement information system short forms in systemic lupus erythematosus.  ACR 
Open. 2019: 1-8.  Doi 10.1002/acr2.11100 
Kenward MG and Roger JH. Small sample inference for fixed effects from restricted 
maximum likelihood. Biometrics. 1997; 53: 983-997 


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Khraishi M, Aslanov R, Dixit S, et al 2014. The validity of patient and physician global 
disease activity assessments of systemic lupus erythematosus: results from the lupus 
activity coring tool (LAST) as compared to the Selena Sledai (SS) modification 
multicentre study. ACR 2014.  
Liang MH, Socher SA, Larson MG, Schur PH. Reliability and validity of six systems for 
the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis 
Rheum. 1989;32(9):1107-18. 
Longford NT. Random Coefficient Models, New York: Oxford University Press, Inc, 1993 
McElhone K, Abbott J, Shelmerdine J et al. Development and validation of a disease 
specific health-related quality of life measure, the LupusQol, for adults with systemic 
lupus erythematosus. Arthritis Rheum. 2007;57:972-979.  
Navarra SV, Guzmán RM, Gallacher AE, et al.  Efficacy and safety of belimumab in 
patients with active systemic lupus erythematosus: a randomised, placebo-controlled, 
phase 3 trial. Lancet. 2011 Feb 26;377(9767):721-731. 
PROMIS Fatigue Scoring Manual. Accessed at 
http://www.healthmeasures.net/images/PROMIS/manuals/PROMIS_Fatigue_Scoring_M
anual.pdf on 29 Jan 2020  
Ware JE. SF-36 Health Survey Update. SPINE. 2000; 25:3130-3139. 
Wohlfahrt A, Bingham CO, Marder W, et al. Responsiveness of patient-reported 
outcomes measurement information system measures in rheumatoid arthritis patients 
starting or switching a disease-modifying antirheumatic drug. Arth Car Res 2019: (4): 
521-529. 
Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. Measuring fatigue and other 
anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) 
measurement system. J Pain Symptom Manage 1997; 13: 63-74.  
 


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12. 
Appendices 
Appendix A.  Reference Values/Toxicity Grades 
Assessment of severity for each adverse event and serious adverse event reported 
during the study will be based on:  
The Common Terminology Criteria for Adverse Events (CTCAE), version 5 which is 
available at the following location: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
Appendix B.  SLE Assessment Forms/Instruments 
HSLEDAI  
The hSLEDAI score is computed as sum of the score across the descriptors. 
Weight 
Score 
Descriptor 
Definition  
8 
 
Seizure 
Recent onset, exclude metabolic, infectious or 
drug causes 
8 
 
Psychosis 
Altered ability to function in normal activity due 
to severe disturbance in the perception of 
reality. Include hallucinations, incoherence, 
marked loose associations, impoverished 
thought content, marked illogical thinking, 
bizarre, disorganized or catatonic behavior. 
Exclude uremia and drug causes 
8 
 
Organic brain 
syndrome 
Altered mental function with impaired 
orientation, memory, or other intellectual 
function, with rapid onset and fluctuating clinical 
features, inability to sustain attention to 
environment, plus at least two of the following: 
perceptual disturbance, incoherent speech, 
insomnia or daytime drowsiness, or increased or 
decreased psychomotor activity. Exclude 
metabolic, infection, or drug causes. 
8 
 
Visual 
disturbance 
Retinal changes of SLE. Include cystoid bodies, 
retinal hemorrhages, serous exudate or 
hemorrhages in the choroid, optic neuritis, 
scleritis or episcleritis. Exclude hypertension, 
infection, or drug causes. 
8 
 
Cranial nerve 
disorder 
New onset of sensory or motor neuropathy 
involving cranial nerves.  


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8 
 
Lupus headache Severe, persistent headache; may be 
migrainous, but must be non-responsive to 
narcotic analgesia.  
8 
 
CVA 
New onset of cerebrovascular accident(s). 
Exclude arteriosclerosis. 
8 
 
Vasculitis 
Ulceration, gangrene, tender finder nodules, 
periungual infarction, splinter hemorrhages, or 
biopsy or angiogram proof of vasculitis. 
4 
 
Arthritis 
>2 joints of hands and wrists with signs of 
inflammation (i.e., tenderness and swelling or 
effusion) 
4 
 
Myositis 
Proximal muscle aching/weakness, associated 
with elevated creatinine phosphokinase/aldolase 
or electromyogram changes or a biopsy showing 
myositis. 
4 
 
Urinary casts 
Heme-granular or red blood cell casts 
4 
 
Hematuria 
> 5 red blood cells/high power field. Exclude 
stone, infection, or other cause. 
4 
 
Proteinuria 
More than 0.5 gram/24 hours.  
4 
 
Pyuria 
> 5 WBC/high power field. Exclude infection. 
2 
 
Rash 
Inflammatory type rash. 
2 
 
Alopecia 
Abnormal, patchy or diffuse loss of hair 
2 
 
Mucosal ulcers 
Oral or nasal ulcerations 
2 
 
Pleurisy 
Pleuritic chest pain or pleural rub with effusion 
or pleural thickening. 
2 
 
Pericarditis 
Classic pericardial pain and/or rub effusion with 
ECG confirmation 
2 
 
Low 
complement 
Decrease in CH50, C3, or C4 below the lower 
limit of normal for testing laboratory 
2 
 
Increased DNA 
binding 
Increased DNA binding above normal range for 
testing laboratory 
1 
 
Fever 
> 38 °C. Exclude infectious cause. 
1 
 
Thrombocytope
nia 
< 100 x 109 platelets / L, exclude drug causes.  


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1 
 
Leukopenia 
< 3 x 109 WBC/ L, exclude drug causes. 
 
BILAG-2004 Index Form 
 
 
 
 
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DI 
DI 
DI 
DI 
DI 
DI 
Oaie of B!!E.e!l!!lllent : _________ _ 
AMBEN® 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 45 of 60 
CONFIDENTIAL  
 
 
 
Scoring based on the principle of physician’s intention to treat 
 
 
Category 
 
 
Definition 
 
 
A 
Severe disease activity requiring any of the following treatment: 
1. systemic high dose oral glucocorticoids (equivalent to 
prednisolone > 20 mg/day) 
2. intravenous pulse glucocorticoids (equivalent to pulse 
methylprednisolone ≥ 500 mg) 
3. systemic immunomodulators (include biologicals, 
immunoglobulins and plasmapheresis) 
4. therapeutic high dose anticoagulation in the presence of high 
dose steroids or immunomodulators  
e.g.: warfarin with target INR 3 - 4 
 
B 
 
Moderate disease activity requiring any of the following treatment: 
1. systemic low dose oral glucocorticoids (equivalent to 
prednisolone ≤ 20 mg/day) 
2. intramuscular or intra-articular or soft tissue glucocorticoids 
injection (equivalent to methylprednisolone < 500mg) 
3. topical glucocorticoids 
4. topical immunomodulators 
5. antimalarials or thalidomide or prasterone or acitretin 
6. symptomatic therapy 
      e.g.: NSAIDs for inflammatory arthritis 
 
C 
 
Mild disease 
 
D 
 
 
Inactive disease but previously affected 
 
 
E 
 
System never involved 
BILAG Constitutional Scoring Algorithm 
Grade 
Criteria 
A 
1. Pyrexia recorded as 2 (same), 3 (worse) or 4 (new) AND  
2. Any 2 or more of the following recorded as 2 (same), 3 (worse) or 4 
(new): 
a) Weight loss 
b) Lymphadenopathy/splenomegaly 
c) Anorexia 
 
B 
1. Pyrexia recorded as 2 (same), 3 (worse) or 4 (new) OR  
2. Any 2 or more of the following recorded as 2 (same), 3 (worse) or 4 
(new): 
a) Weight loss 
b) Lymphadenopathy/splenomegaly 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 46 of 60 
CONFIDENTIAL  
 
 
c) Anorexia 
3. BUT do not fulfil criteria for Category A 
 
C 
1. Pyrexia recorded as 1 (improving) OR 
2. One or more of the following recorded as > 0:  
a) Weight loss 
b) Lymphadenopathy/Splenomegaly 
c) Anorexia 
3. BUT does not fulfil criteria for category A or B 
D 
Previous involvement (i.e. A, B, C or D domain grade at any previous visits 
or domain previous involvement is yes) 
E 
No previous involvement 
Missing 
 
BILAG Mucocutaneous Scoring Algorithm 
Grade 
Criteria 
A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
a) Skin eruption - severe  
b) Angio-oedema - severe 
c) Mucosal ulceration - severe 
d) Panniculitis/Bullous lupus - severe 
e) Major cutaneous vasculitis/thrombosis 
B 
1. Any Category A features recorded as 1 (improving) OR  
2. Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
1. Skin eruption - mild 
2. Panniculitis/Bullous lupus - mild 
3. Digital infarcts or nodular vasculitis 
4. Alopecia - severe 
C 
1. Any Category B features recorded as 1 (improving) OR 
2. Any of the following recorded as > 0: 
a) Angio-oedema - mild 
b) Mucosal ulceration - mild 
c) Alopecia - mild 
d) Periungual erythema/chilblains 
e) Splinter haemorrhages 
D 
Previous involvement (i.e. A, B, C or D domain grade at any previous visits 
or domain previous involvement is yes) 
E 
No previous involvement 
Missing 
 
BILAG Neuropsychiatric Scoring Algorithm 
Grade 
Criteria 
A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
1. Aseptic meningitis 
2. Cerebral vasculitis 
3. Demyelinating syndrome 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 47 of 60 
CONFIDENTIAL  
 
 
4. Myelopathy 
5. Acute confusional state 
6. Psychosis 
7. Acute inflammatory demyelinating polyradiculoneuropathy 
8. Mononeuropathy (single/multiplex) 
9. Cranial neuropathy 
10. Plexopathy 
11. Polyneuropathy 
12. Status epilepticus 
13. Cerebellar ataxia 
B 
1. Any Category A features recorded as 1 (improving) OR 
2. Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
a) Seizure disorder  
b) Cerebrovascular disease (not due to vasculitis) 
c) Cognitive dysfunction 
d) Movement disorder 
e) Autonomic disorder  
f) Lupus headache - severe unremitting 
g) Headache due to raised intracranial hypertension 
C 
Any Category B features recorded as 1 (improving) 
D 
Previous involvement (i.e. A, B, C or D domain grade at any previous visits 
or domain previous involvement is yes) 
E 
No previous involvement 
Missing 
 
 
BILAG Musculoskeletal Scoring Algorithm 
Grade 
Criteria 
A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
a) Severe Myositis 
b) Severe Arthritis 
B 
1. Any Category A features recorded as 1 (improving) OR 
2. Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
a) Mild Myositis 
b) Moderate Arthritis/Tendonitis/Tenosynovitis 
C 
1. Any Category B features recorded as 1 (improving) OR  
2. Any of the following recorded as > 0: 
a) Mild Arthritis/Arthralgia/Myalgia 
 
D 
Previous involvement (i.e. A, B, C or D domain grade at any previous visits 
or domain previous involvement is yes) 
E 
No previous involvement 
Missing 
 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 48 of 60 
CONFIDENTIAL  
 
 
BILAG Cardiorespiratory Scoring Algorithm 
Grade 
Criteria 
A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
a) Myocarditis/Endocarditis + Cardiac failure 
b) Arrhythmia 
c) New valvular dysfunction 
d) Cardiac tamponade 
e) Pleural effusion with dyspnoea 
f) Pulmonary haemorrhage/vasculitis  
g) Interstitial alveolitis/pneumonitis  
h) Shrinking lung syndrome 
i) Aortitis 
j) Coronary vasculitis 
B 
1. Any Category A features recorded as 1 (improving) OR  
2. Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
a) Pleurisy/Pericarditis 
b) Myocarditis - mild 
C 
Any Category B features recorded as 1 (improving) 
D 
Previous involvement (i.e. A, B, C or D domain grade at any previous visits 
or domain previous involvement is yes) 
E 
No previous involvement 
Missing 
 
 
BILAG Gastrointestinal Scoring Algorithm 
Grade 
Criteria 
A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
a) Peritonitis 
b) Lupus enteritis/colitis 
c) Intestinal pseudo-obstruction  
d) Acute lupus cholecystitis 
e) Acute lupus pancreatitis 
 
B 
1. Any Category A feature recorded as 1 (improving) OR 
2. Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
a) Abdominal serositis and/or ascites  
b) Malabsorption 
c) Protein losing enteropathy 
d) Lupus hepatitis 
 
C 
Any Category B features recorded as 1 (improving)  
D 
Previous involvement (i.e. A, B, C or D domain grade at any previous visits 
or domain previous involvement is yes) 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 49 of 60 
CONFIDENTIAL  
 
 
E 
No previous involvement 
Missing 
 
 
BILAG Ophthalmic Scoring Algorithm 
Grade 
Criteria 
A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
a) Orbital inflammation/myositis/proptosis 
b) Keratitis - severe 
c) Posterior uveitis/retinal vasculitis - severe 
d) Scleritis - severe 
e) Retinal/choroidal vaso-occlusive disease 
f) Optic neuritis 
g) Anterior ischaemic optic neuropathy  
B 
1. Any Category A features recorded as 1 (improving) OR  
2. Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
a) Keratitis - mild 
b) Anterior uveitis 
c) Posterior uveitis/retinal vasculitis - mild 
d) Scleritis - mild 
C 
1. Any Category B features recorded as 1 (improving) OR  
2. Any of the following recorded as > 0: 
a) Episcleritis 
b) Isolated cotton-wool spots (cystoid bodies) 
 
D 
Previous involvement (i.e. A, B, C or D domain grade at any previous visits 
or domain previous involvement is yes) 
E 
No previous involvement 
Missing 
 
 
BILAG Renal Scoring Algorithm 
Grade 
Criteria 
A 
Two or more of the following providing 1, 4 or 5 is included: 
1. Deteriorating proteinuria (severe) defined as   
a) urine dipstick increased by ≥ 2 levels (used only if other methods of 
urine protein estimation not available); or  
b) 24-hour urine protein > 1 g that has not decreased (improved) by  
25% from previous visit; or 
c) urine protein-creatinine ratio > 100 mg/mmol that has not decreased 
(improved) by  25%; or 
d) urine albumin-creatinine ratio > 100 mg/mmol that has not 
decreased (improved) by  25% 
2. Accelerated hypertension  
3. Deteriorating renal function (severe) defined as  


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 50 of 60 
CONFIDENTIAL  
 
 
a) plasma creatinine > 130 mol/l and having risen to > 130% of 
previous value; or  
b) GFR < 80 ml/min per 1.73 m2 and having fallen to < 67% of previous 
value; or  
c) GFR < 50 ml/min per 1.73 m2, and last time was > 50 ml/min per 
1.73 m2 or was not measured. 
4. Active urinary sediment 
5. Histological evidence of active nephritis within last 3 months  
6. Nephrotic syndrome 
B 
One of the following: 
1. One of the Category A feature 
2. Proteinuria (that has not fulfilled Category A criteria) 
a) urine dipstick which has risen by 1 level to at least 2+ (used only if 
other methods of urine protein estimation not available); or 
b) 24-hour urine protein ≥ 0.5 g that has not decreased (improved) by  
25%; or 
c) urine protein-creatinine ratio ≥ 50 mg/mmol that has not decreased 
(improved) by  25%; or 
d) urine albumin-creatinine ratio ≥ 50 mg/mmol that has not decreased 
(improved) by  25% 
3. Plasma creatinine > 130 mol/l and having risen to ≥ 115% but ≤ 130% 
of previous value 
C 
One of the following: 
1. Mild/Stable proteinuria defined as 
a) urine dipstick ≥ 1+ but has not fulfilled criteria for Category A & B 
(used only if other methods of urine protein estimation not available); 
or 
b) 24 hour urine protein > 0.25 g but has not fulfilled criteria for 
Category A & B; or 
c) urine protein-creatinine ratio > 25 mg/mmol but has not fulfilled 
criteria for Category A & B; or  
d) urine albumin-creatinine ratio > 25 mg/mmol but has not fulfilled 
criteria for Category A & B 
2. Rising blood pressure (providing the recorded values are > 140/90 mm 
Hg) which has not fulfilled criteria for Category A & B, defined as 
a) systolic rise of ≥ 30 mm Hg; and  
b) diastolic rise of ≥ 15mm Hg 
D 
Previous involvement (i.e. A, B, C or D domain grade at any previous visits 
or domain previous involvement is yes) 
E 
No previous involvement 
Missing  
Since the urine albumin-creatinine ratio and 24-hour urine protein are not collected in 
this study, the criteria for BILAG proteinuria will be based on urine dipstick and urine 
protein-creatinine ration only. 
BILAG Hematological Scoring Algorithm 
Grade 
Criteria 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 51 of 60 
CONFIDENTIAL  
 
 
A 
1. TTP recorded as 2 (same), 3 (worse) or 4 (new) or 
2. Any of the following: 
a) Evidence of haemolysis and Haemoglobin < 8 g/dl 
b) Platelet count < 25 x 109/l 
B 
1. TTP recorded as 1 (improving) or 
2. Any of the following:  
a) Evidence of haemolysis and Haemoglobin 8 - 9.9 g/dl 
b) Haemoglobin  < 8 g/dl (without haemolysis) 
c) White cell count < 1.0 x 109/l 
d) Neutrophil count < 0.5 x 109/l 
e) Platelet count  25 - 49 x 109/l 
C 
Any of the following: 
a) Evidence of haemolysis and Haemoglobin ≥ 10g/dl 
b) Haemoglobin   8 - 10.9 g/dl (without haemolysis) 
c) White cell count  
1 - 3.9 x 109/l 
d) Neutrophil count  
0.5 - 1.9 x 109/l 
e) Lymphocyte count  
< 1.0 x 109/L 
f) Platelet count  
50 - 149 x 109/l 
g) Isolated Coombs’ test positive 
D 
Previous involvement (i.e. A, B, C or D domain grade at any previous visits 
or domain previous involvement is yes) 
E 
No previous Involvement. 
Missing 
 
 
LLDAS 
Criteria 
Derivation 
HSLEDAI ≤ 4 with no activity in major 
organ systems (renal, CNS, 
cardiopulmonary, vasculitis, fever) and no 
activity in haemolytic anaemia or 
gastrointestinal in BILAG 
HSLEDAI score ≤ 4. 
proteinuria, haematuria, pyuria, urinary 
casts, seizure, psychosis, organic brain 
syndrome, cranial nerve disorder, CVA, 
pericarditis, pleurisy, vasculitis and fever 
in hSLEDAI are marked ‘not present.’ 
BILAG items 56-64 are marked as ‘not 
present’ and 96 are marked as ‘No.’ 
No new lupus activity compared with the 
previous assessment 
All hSLEDAI items that are ‘not present’ 
in the previous assessment are also ‘not 
present’ in the current visit. 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 52 of 60 
CONFIDENTIAL  
 
 
PGA ≤ 1 
PGA ≤ 1 
Current prednisolone (or equivalent) dose 
≤ 7.5 mg/day 
Prednisone equivalent is ≤ 7.5 mg/day at 
the visit 
Well tolerated standard maintenance 
doses of immunosuppressive drugs and 
approved biological agents (i.e. no 
increase or initiation of 
immunosuppressive drugs.) 
No new or increase in 
immunosuppressant at the visit 
 
Appendix C.  Patient-reported Outcome Forms/Instruments 
C1. SF-36 Version 2 
The scoring of SF-36v2 will be processed by QualityMetric’s PRO CoRE Software.C2. 
Scoring algorithm for PROMIS Fatigue SF 7A. 
PROMIS SF v1.0 – Fatigue 7A will be scored according to the PROMIS Fatigue Brief 
Guide including the scoring in the Instrument Section downloaded from  
http://www.healthmeasures.net/images/PROMIS/manuals/PROMIS_Fatigue_Scoring_M
anual.pdf on 28 Feb 2019.  
To calculate the score for PROMIS Fatigue SF 7A, sum the values of the 
responses to each of the 7 questions. The lowest and highest possible sum is 7 
and 35, respectively. Then, use the table below to rescale the score into a 
standardize score with a mean of 50 and a standard deviation of 10. 
Conversion Table 
Raw score 
T-score 
7 
29.4 
8 
33.4 
9 
36.9 
10 
39.6 
11 
41.9 
12 
43.9 
13 
45.8 
14 
47.6 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 53 of 60 
CONFIDENTIAL  
 
 
15 
49.2 
16 
50.8 
17 
52.2 
18 
53.7 
19 
55.1 
20 
56.4 
21 
57.8 
22 
59.2 
23 
60.6 
24 
62.0 
25 
63.4 
26 
64.8 
27 
66.3 
28 
67.8 
29 
69.4 
30 
71.1 
31 
72.9 
32 
74.8 
33 
77.1 
34 
79.8 
35 
83.2 
 
C3. Scoring algorithm for Modified LupusQoL 
The Lupus QoL will be scored using the scoring algorithm from the RWS Life Science 
website accessed 10 April 2020. http://www.corptransinc.com/sites/lupusqol/instrument-
information/instrument-scoring 
To compute the LupusQOL raw domain score, sum the values of the responses to 
each question by domain based on the tables below and divide by the number of 
items. Then, transform the raw domain score by dividing by 4 and multiplying by 
100. 
Item 
Response 
All the 
time 
Most of the 
time 
A good bit 
of the time 
Occasionally 
Never 
Not 
applicable 
Score 
0 
1 
2 
3 
4 
Do not 
score 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 54 of 60 
CONFIDENTIAL  
 
 
 
Domain 
Number of Items 
Item Numbers 
Physical Health 
8 
1-8 
Pain 
3 
9-11 
Planning 
3 
12-14 
Intimate Relationship 
2 
15, 16 
Burden to Others 
3 
17-19 
Emotional Health 
6 
20-25 
Body Image 
5 
36-30 
Fatigue 
4 
31-34 
C4. Scoring algorithm for Patient Global Assessment 
The Patient Global Assessment (PtGA) is a 10 cm numeric rating scale with 0 being  
very well and 10 very poor.  
 
Appendix D.  Analytical Windows 
The last measurement for the endpoint of interest taken prior to or on the first dose of IP 
in this study, unless stated otherwise, will be defined as a baseline visit and the analysis 
visit name will be 'Baseline'. For any visit up to Day 1 pre-dose which is not a baseline 
visit, the analysis visit will be 'Pre-analysis'. 
Since the actual visit for a subject may not exactly coincide with their scheduled visit 
date, to allow for variations in scheduling, the following visit windows will be used to 
assign evaluations to a most appropriate nominal visit for analysis and summarization. 
Furthermore, there will be no gaps between visit windows in order to include as many 
data points as possible for summarization.  
If more than one actual visit (including the unscheduled visits) falls within the same 
defined window, the visit closest to the target day with non-missing data will be 
considered for analysis. If two actual visit dates are at the same distance from the target 
day, the latest visit with non-missing data will be considered for analysis.  
The rules above for selecting a visit from multiple ones within the same visit window are 
not applicable to retest values of lab data. If the lab measurement is a retest, the retest 
value will be used.  


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 55 of 60 
CONFIDENTIAL  
 
 
Efficacy assessment (tender/swollen joint count, hSLEDAI, BILAG, SELENA-
SLEDAI Flare Index, PGA, CLASI), weight, and laboratory assessment 
, chemistry, urinalysis) 
Study Visit 
Target Day 
Study Day 
Baseline 
1 
Last evaluation prior to or on Study Day 1 
Week 4 
29 
2 - 42 
Week 8 
57 
43 - 70 
Week 12 
85 
71 - 98 
Week 16 
113 
99 - 126 
Week 20 
141 
127 - 154 
Week 24 
169 
155 - 182 
Week 28 
197 
183 - 210 
Week 32 
225 
211 - 238 
Week 36 
253 
239 - 266 
Week 40 
281 
267 - 294 
Week 44 
309 
295 - 322 
Week 48 
337 
323 - 350 
Week 52 
365 
351 - 394 
Hematology 
Study Visit 
Target Day 
Study Day 
Baseline 
1 
Last evaluation prior to or on Study Day 1 
Week 4 
29 
2 - 42 
Week 8 
57 
43 - 70 
Week 12 
85 
71 - 98 
Week 16 
113 
99 - 126 
Week 20 
141 
127 - 154 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 56 of 60 
CONFIDENTIAL  
 
 
Week 24 
169 
155 - 182 
Week 28 
197 
183 - 210 
Week 32 
225 
211 - 238 
Week 36 
253 
239 - 266 
Week 40 
281 
267 - 294 
Week 44 
309 
295 - 322 
Week 48 
337 
323 - 350 
Week 52 
365 
351 - 392 
Week 60 
421 
393 - 448 
Week 68 
477 
≥ 449 
 
Vital sign 
Study Visit 
Target Day 
Study Day 
Baseline 
1 
Last evaluation prior to or on Study Day 1 
Week 2 
15 
2 - 21 
Week 4 
29 
22 - 35 
Week 6 
43 
36 - 49 
Week 8 
57 
50 - 63 
Week 10 
71 
64 - 77 
Week 12 
85 
78 - 91 
Week 14 
99 
92 - 105 
Week 16 
113 
106 - 119 
Week 18 
127 
120 - 133 
Week 20 
141 
134 - 147 
Week 22 
155 
148 - 161 
Week 24 
169 
162 - 175 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 57 of 60 
CONFIDENTIAL  
 
 
Week 26 
183 
176 - 189 
Week 28 
197 
190 - 203 
Week 30 
211 
204 - 217 
Week 32 
225 
218 - 231 
Week 34 
239 
232 - 245 
Week 36 
253 
246 - 259 
Week 38 
267 
260 - 273 
Week 40 
281 
274 - 287 
Week 42 
295 
288 - 301 
Week 44 
309 
302 - 315 
Week 46 
323 
316 - 329 
Week 48 
337 
330 - 343 
Week 50 
351 
344 - 357 
Week 52 
365 
358 - 378 
Week 56 
393 
379 - 406 
Week 60 
421 
407 - 434 
Week 64 
449 
435 - 462 
Week 68 
477 
≥ 463 
, SDI 
Study Visit 
Target Day 
Study Day 
Baseline 
1 
Last evaluation prior to or on Study Day 1 
Week 24 
169 
2 - 266 
Week 52 
365 
267 - 394 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 58 of 60 
CONFIDENTIAL  
 
 
Pharmacokinetic assessment 
Study Visit 
Target Day 
Study Day 
Baseline 
1 
Last evaluation prior to or on Study Day 1 
Week 4 
29 
2 - 42 
Week 8 
57 
43 - 70 
Week 12 
85 
71 - 98 
Week 16 
113 
99 - 126 
Week 20 
141 
127 - 154 
Week 24 
169 
155 - 210 
Week 36 
253 
211 - 280 
Week 44 
309 
281 - 336 
Week 52 
365 
337 - 378 
Week 56 
393 
379 - 406 
Week 60 
421 
407 - 434 
Week 64 
449 
435 - 462 
Week 68 
477 
≥ 463 
PROs (SF-36v2, PROMIS Fatigue SF 7A, LupusQOL, PtGA) 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 59 of 60 
CONFIDENTIAL  
 
 
Study Visit 
Target Day 
Study Day 
Baseline 
1 
Last evaluation prior to or on Study Day 1 
Week 4 
29 
2 - 56 
Week 12 
85 
57 - 98 
Week 24 
169 
99 - 210 
Week 36 
253 
211 - 280 
Week 44 
309 
281 - 336 
Week 52 
365 
337 - 394 
 


Product:  Rozibafusp Alfa (AMG 570) 
Protocol Number:  20170588 
Date:  03 OCT 2023 
Page 60 of 60 
CONFIDENTIAL  
 
 
Appendix E.  Handling of Dates, Incomplete Dates and Missing Dates 
The reference date for the following rules is the date of first dose rozibafusp alfa. 
 
 
 
 
Start Date 
Stop Date 
Complete: 
yyyymmdd 
Partial: 
yyyymm 
Partial: 
yyyy 
Missing 
< 1st 
dose 
≥ 1st 
dose 
< 1st 
dose 
yyyymm 
≥ 1st 
dose 
yyyymm 
< 1st 
dose 
yyyy 
≥ 1st 
dose 
yyyy 
 
Partial: 
yyyymm 
= 1st dose 
yyyymm 
 
2 
1 
n/a 
1 
n/a 
1 
1 
≠ 1st dose 
yyyymm 
2 
2 
2 
2 
2 
2 
Partial: 
yyyy 
= 1st dose 
yyyy 
 
3 
1 
 
3 
1 
n/a 
1 
1 
≠ 1st dose 
yyyy 
3 
3 
3 
3 
3 
Missing 
4 
1 
4 
1 
4 
1 
1 
1=Impute the date of first dose or the randomization date if not treated; 2=Impute the first of the month; 
3=Impute January 1 of the year; 4=Impute January 1 of the stop year 
Note: For subjects who were never treated (first dose date is missing), partial start dates will be set to the 
first day of the partial month or first day of year if month is also missing. 
Imputation Rules for Partial or Missing Stop Dates 
Initial imputation 
 
If the month and year are present, impute the last day of that month. 
 
If only the year is present, impute December 31 of that year. 
 
If the stop date is entirely missing, assume the event or medication is ongoing. 
If the imputed stop date is before the start date, set stop date to missing. 
If the imputed stop date is after the death date, impute as death date.