A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants With Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN)
Phase: PHASE2
Conditions: Lupus Nephritis, Immunoglobulin A Nephropathy
Sponsor: Alexion Pharmaceuticals, Inc.

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TITLE PAGE 
Protocol Title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate 
the Efficacy and Safety of Ravulizumab in Adult Participants With Proliferative Lupus Nephritis 
(LN) or Immunoglobulin A Nephropathy (IgAN) 
Protocol Number: ALXN1210–NEPH–202 
Amendment Number: 4.0 
Compound: Ravulizumab (ALXN1210) 
Study Phase: 2 
Brief Title: Phase 2 Study of Ravulizumab in Proliferative Lupus Nephritis (LN) or 
Immunoglobulin A Nephropathy (IgAN)  
Sponsor Name: Alexion Pharmaceuticals, Inc. 
Legal Registered Address: 121 Seaport Boulevard, Boston MA 02210, USA 
Regulatory Agency Identifier Number(s) 
IND: 148192 
EudraCT: 2020-001537-13 (formerly) 
EU CT number: 2023-507977-16-00 
Release Date: 26 Mar 2024 
Sponsor Signatory: 
This document has been e-signed in ARISE (Veeva RIM). Please refer to last page for 
signature details. 
 
 
Alexion Pharmaceuticals, Inc. 
Date 
Medical Monitor Contact Information can be found in the Study Contact List distributed 
to study sites. 
The 24-hour Emergency Contact Phone Number can be found on the informed consent 
form. 
NCT #: NCT04564339

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INVESTIGATOR’S AGREEMENT 
I have read the study protocol and agree to conduct the study in accordance with this protocol, all 
applicable government regulations, the principles of the ICH E6 Guidelines for Good Clinical 
Practice, and the principles of the World Medical Association Declaration of Helsinki. I also 
agree to maintain the confidentiality of all information received or developed in connection with 
this protocol.  
 
 
 
 
____________________________________ 
Printed Name of Investigator 
 
_____________________________________ 
Signature of Investigator 
 
_______________ 
Date 

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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR’S AGREEMENT ...............................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF TABLES .........................................................................................................................10 
LIST OF FIGURES .......................................................................................................................10 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..........................................11 
1. 
PROTOCOL SUMMARY ..........................................................................................12 
1.1. 
Synopsis ......................................................................................................................12 
1.2. 
Study Design Schematics ...........................................................................................17 
1.3. 
Schedule of Activities .................................................................................................18 
2. 
INTRODUCTION ......................................................................................................35 
2.1. 
Study Rationale ...........................................................................................................35 
2.2. 
Background .................................................................................................................36 
2.2.1. 
Lupus Nephritis ..........................................................................................................36 
2.2.2. 
IgA Nephropathy ........................................................................................................37 
2.3. 
Benefit/Risk Assessment ............................................................................................38 
2.3.1. 
Risk Assessment .........................................................................................................38 
2.3.2. 
Benefit Assessment .....................................................................................................40 
2.3.3. 
Overall Benefit: Risk Conclusion ...............................................................................40 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................41 
3.1. 
Overview of Objectives and Endpoints ......................................................................41 
3.2. 
Definitions for Endpoints ...........................................................................................43 
3.2.1. 
Renal Flare (LN Cohort Only) ....................................................................................43 
3.2.2. 
Extrarenal Systemic Lupus Erythematosus Flare (LN Cohort Only) .........................44 
3.2.3. 
Suboptimal Response (LN Cohort Only) ...................................................................44 
3.2.4. 
Treatment Failure (LN Cohort Only) .........................................................................45 
3.2.5. 
Complete and Partial Renal Response (LN Cohort Only) ..........................................45 
3.2.6. 
Partial Remission (IgAN Cohort Only) ......................................................................46 
4. 
STUDY DESIGN .......................................................................................................47 
4.1. 
Overall Design ............................................................................................................47 
4.2. 
Scientific Rationale for Study Design ........................................................................48 

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4.2.1. 
Rationale for Primary Endpoint ..................................................................................49 
4.2.2. 
Rationale for Key Secondary Endpoints .....................................................................49 
4.3. 
Justification for Dose ..................................................................................................50 
4.4. 
Remote Visit Options in Times of Emergency ...........................................................51 
4.5. 
End of Study Definition ..............................................................................................52 
5. 
STUDY POPULATION .............................................................................................53 
5.1. 
Inclusion Criteria ........................................................................................................53 
5.1.1. 
Common Inclusion Criteria for Both Cohorts ............................................................53 
5.1.2. 
Inclusion Criteria Specific for LN Cohort ..................................................................54 
5.1.3. 
Inclusion Criteria Specific for IgAN Cohort ..............................................................54 
5.2. 
Exclusion Criteria .......................................................................................................54 
5.2.1. 
Common Exclusion Criteria for Both Cohorts ...........................................................54 
5.2.2. 
Exclusion Criteria Specific for LN Cohort .................................................................56 
5.2.3. 
Exclusion Criteria Specific for IgAN Cohort .............................................................56 
5.3. 
Lifestyle Considerations .............................................................................................56 
5.4. 
Screen Failures ............................................................................................................56 
6. 
STUDY INTERVENTION ........................................................................................58 
6.1. 
Study Intervention(s) Administered ...........................................................................58 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................62 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................63 
6.3.1. 
Randomization ............................................................................................................63 
6.3.2. 
Blinding ......................................................................................................................63 
6.4. 
Study Drug Compliance .............................................................................................64 
6.5. 
Allowed Concomitant Therapy ...................................................................................64 
6.5.1. 
Allowed Concomitant Therapy for LN Cohort ..........................................................64 
6.5.2. 
Allowed Concomitant Therapy for IgAN Cohort .......................................................67 
6.6. 
Additional Standard of Care Therapy for LN Cohort .................................................67 
6.7. 
Concomitant Therapy .................................................................................................68 
6.7.1. 
Allowed Medications and Therapies ..........................................................................68 
6.7.2. 
Disallowed Medications and Therapy ........................................................................68 
6.8. 
Dose Modification ......................................................................................................69 
6.9. 
Intervention After the End of the Study .....................................................................69 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL .......................................70 
7.1. 
Discontinuation of Study Drug ...................................................................................70 
7.2. 
Participant Withdrawal From the Study .....................................................................71 
7.3. 
Lost to Follow-up .......................................................................................................71 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................72 
8.1. 
General Assessments and Procedures .........................................................................72 
8.1.1. 
Informed Consent .......................................................................................................72 
8.1.2. 
Inclusion/Exclusion Criteria .......................................................................................72 
8.1.3. 
Demographics .............................................................................................................72 
8.1.4. 
Medical History ..........................................................................................................72 
8.1.5. 
Kidney Biopsy ............................................................................................................73 
8.1.5.1. 
Screening Kidney Biopsy ...........................................................................................73 
8.1.5.2. 
Kidney Biopsy During Study......................................................................................73 
8.1.5.3. 
Central Pathology Laboratory .....................................................................................73 
8.1.6. 
Vaccination and Antibiotic Prophylaxis .....................................................................74 
8.2. 
Efficacy Assessments .................................................................................................75 
8.2.1. 
24-hour Urine Collection ............................................................................................75 
8.2.2. 
Spot Urine Sample ......................................................................................................76 
8.2.3. 
Estimated Glomerular Filtration Rate .........................................................................76 
8.2.4. 
Hematuria ...................................................................................................................76 
8.3. 
Safety Assessments .....................................................................................................77 
8.3.1. 
Participant Safety Card ...............................................................................................77 
8.3.2. 
Physical Examinations ................................................................................................77 
8.3.3. 
Vital Signs and Pulse Oximetry ..................................................................................77 
8.3.4. 
Electrocardiograms .....................................................................................................78 
8.3.5. 
Clinical Safety Laboratory Assessments ....................................................................78 
8.3.5.1. 
Virus Serology ............................................................................................................79 
8.3.6. 
Pregnancy ...................................................................................................................79 
8.4. 
Adverse Events and Serious Adverse Events .............................................................79 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................80 
8.4.2. 
Method of Detecting AEs and SAEs ..........................................................................80 
8.4.3. 
Follow-up of AEs and SAEs .......................................................................................80 

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8.4.4. 
Regulatory Reporting Requirements for SAEs ...........................................................80 
8.4.5. 
Medication Error, Drug Abuse, and Drug Misuse ......................................................81 
8.4.5.1. 
Timelines ....................................................................................................................81 
8.4.5.2. 
Medication Error .........................................................................................................81 
8.4.5.3. 
Drug Abuse .................................................................................................................81 
8.4.5.4. 
Drug Misuse ................................................................................................................81 
8.4.6. 
Adverse Events of Special Interest .............................................................................81 
8.5. 
Review of Prior and Concomitant Medications and Procedures ................................81 
8.5.1. 
Prior Medications and Procedures ..............................................................................81 
8.5.2. 
Concomitant Medications and Procedures .................................................................82 
8.6. 
Treatment of Overdose ...............................................................................................83 
8.7. 
Pharmacokinetics and Pharmacodynamics .................................................................83 
8.8. 
Biomarkers ..................................................................................................................84 
8.8.1. 
Blood Exploratory Biomarkers ...................................................................................84 
8.8.2. 
Urine Exploratory Biomarkers ...................................................................................84 
8.8.3. 
Kidney Biopsy Tissue Exploratory Biomarkers .........................................................85 
8.8.4. 
Additional Biomarker Research .................................................................................85 
8.9. 
Other Exploratory Assessments ..................................................................................85 
8.9.1. 
Autoantibodies (LN Cohort Only) ..............................................................................85 
8.9.2. 
SLEDAI–2K (LN Cohort Only) .................................................................................85 
8.9.3. 
Real Time Complement Activity ................................................................................85 
8.9.4. 
Participant-Reported Outcome Measures ...................................................................86 
8.10. 
Immunogenicity Assessments ....................................................................................86 
8.11. 
Genetics ......................................................................................................................86 
8.12. 
Medical Resource Utilization .....................................................................................86 
8.13. 
Post-treatment Follow-up Period ................................................................................87 
9. 
STATISTICAL CONSIDERATIONS .......................................................................88 
9.1. 
Statistical Hypotheses .................................................................................................88 
9.1.1. 
Primary Hypothesis ....................................................................................................88 
9.2. 
Sample Size Determination ........................................................................................88 
9.3. 
Populations for Analyses ............................................................................................89 
9.4. 
Statistical Analyses .....................................................................................................89 
9.4.1. 
Efficacy Analyses .......................................................................................................89 

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9.4.1.1. 
Analyses of Primary Efficacy Endpoint .....................................................................89 
9.4.1.2. 
Analyses of Secondary Efficacy Endpoints ................................................................90 
9.4.1.3. 
Multiplicity Adjustment..............................................................................................92 
9.4.2. 
Safety Analyses ..........................................................................................................92 
9.4.2.1. 
Adverse Events ...........................................................................................................92 
9.4.2.2. 
Physical Examination and Vital Signs ........................................................................92 
9.4.2.3. 
Clinical Laboratory Tests ...........................................................................................93 
9.4.2.4. 
Electrocardiograms .....................................................................................................93 
9.4.3. 
Pharmacokinetic/Pharmacodynamic Analyses ...........................................................93 
9.4.4. 
Immunogenicity Analyses ..........................................................................................93 
9.4.5. 
Exploratory Analyses ..................................................................................................93 
9.4.5.1. 
Exploratory Efficacy Endpoints .................................................................................93 
9.4.5.2. 
Biomarkers ..................................................................................................................94 
9.4.5.3. 
Quality of Life ............................................................................................................94 
9.5. 
Planned Analyses ........................................................................................................94 
9.5.1. 
Dose Confirmation Analysis.......................................................................................94 
9.5.2. 
Interim Analysis for Primary Endpoint ......................................................................95 
9.5.3. 
Interim Analysis for Extension Period .......................................................................95 
9.5.4. 
Final Analysis .............................................................................................................95 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................96 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations .........................................96 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................96 
10.1.2. 
Financial Disclosure ...................................................................................................98 
10.1.3. 
Informed Consent Process ..........................................................................................98 
10.1.4. 
Recruitment Strategy ..................................................................................................99 
10.1.5. 
Data Protection ...........................................................................................................99 
10.1.6. 
Dissemination of Clinical Study Data ......................................................................101 
10.1.7. 
Data Quality Assurance ............................................................................................101 
10.1.8. 
Source Documents ....................................................................................................101 
10.1.9. 
Study and Site Start and Closure ..............................................................................102 
10.1.10. 
Publication Policy .....................................................................................................102 
10.1.11. 
COVID-19 Risk Assessment ....................................................................................103 

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10.1.12. 
COVID-19 Vaccine Risk Assessment ......................................................................104 
10.1.13. 
Remote Source Data Verification During COVID-19 Pandemic .............................105 
10.2. 
Clinical Laboratory Tests .........................................................................................107 
10.3. 
Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting .........................................................................................110 
10.3.1. 
Definition of AE .......................................................................................................110 
10.3.2. 
Definition of SAE .....................................................................................................111 
10.3.3. 
Recording and Follow-Up of AE and/or SAE ..........................................................112 
10.3.4. 
Reporting of SAEs ....................................................................................................114 
10.3.5. 
Unexpected Events ...................................................................................................114 
10.4. 
Management of Potential Infusion-related Adverse Events During 
Ravulizumab Administration ....................................................................................115 
10.5. 
Medication Error, Drug Abuse, and Drug Misuse ....................................................116 
10.6. 
Contraceptive Guidance and Collection of Pregnancy Information .........................119 
10.6.1. 
Definitions ................................................................................................................119 
10.6.2. 
Contraception Guidance ...........................................................................................119 
10.6.2.1. 
Guidance for Female Participants .............................................................................119 
10.6.2.2. 
Guidance for Male Participants ................................................................................121 
10.6.3. 
Collection of Pregnancy Information .......................................................................121 
10.6.3.1. 
Male Participants With Partners Who Become Pregnant .........................................122 
10.6.3.2. 
Female Participants Who Become Pregnant .............................................................122 
10.7. 
Handling of Human Biological Samples ..................................................................123 
10.7.1. 
Chain of Custody ......................................................................................................123 
10.7.2. 
Withdrawal of Informed Consent for Donated Biological Samples .........................123 
10.8. 
Biomarkers ................................................................................................................124 
10.9. 
Systemic Lupus Erythematosus Diagnosis Classification Criteria ...........................125 
10.10. 
Revised 2018 International Society of Nephrology/Renal Pathology Society 
(ISN/RPS) Classification ..........................................................................................126 
10.11. 
IgAN Diagnosis Classification Criteria ....................................................................127 
10.12. 
Systemic Lupus Erythematosus Disease Activity Index SELENA 
Modification (SLEDAI–2K) .....................................................................................128 
10.13. 
Short Form Health Survey (SF-36) ...........................................................................130 
10.14. 
EuroQol 5 Dimensions (EQ-5D-5L) ........................................................................136 
10.15. 
FACIT-Fatigue Subscale Version 4..........................................................................139 

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10.16. 
Abbreviations ............................................................................................................140 
10.17. 
Protocol Amendment History ...................................................................................144 
11. 
REFERENCES .........................................................................................................147 
 

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LIST OF TABLES 
Table 1: 
Schedule of Activities During the Initial Evaluation Period: Screening to 
Week 26 Visit (LN Cohort) ........................................................................................19 
Table 2: 
Schedule of Activities During the Initial Evaluation Period: Screening to 
Week 26 Visit (IgAN Cohort) ....................................................................................24 
Table 3: 
Schedule of Activities During the Extension Period: Week 26 Dose 
Administration, Week 34 to Week 50 Visits (LN Cohort) .........................................28 
Table 4: 
Schedule of Activities During the Extension Period: Week 26 Dose 
Administration, Week 28 to Week 50 Visits (IgAN Cohort) .....................................31 
Table 5: 
Schedule of Activities During Post-Treatment Follow-up Period (Both LN 
and IgAN Cohorts) .....................................................................................................34 
Table 6: 
Potential Risks and Mitigation Strategies ...................................................................38 
Table 7: 
Study Intervention(s) Administered ...........................................................................58 
Table 8: 
Weight-based Doses of Ravulizumab .........................................................................59 
Table 9: 
Reference Chart for Weight-Based Dosing in IgAN Cohort ......................................60 
Table 10: Corticosteroid Taper for Participants With Lupus Nephritis ......................................66 
Table 11: Potential Risks and Mitigation Measures due to COVID-19 ...................................103 
Table 12: Potential Risks and Mitigation Measures due to COVID-19 Vaccine .....................105 
Table 13: Protocol-Required Laboratory Assessments.............................................................107 
Table 14: Clinical Criteria for Diagnosing Anaphylaxis ..........................................................116 
LIST OF FIGURES 
Figure 1: 
Study Design Schematic – LN Cohort ........................................................................17 
Figure 2: 
Study Design Schematic – IgAN Cohort ....................................................................17 
 
 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE  
Amendment 4.0  
This modification is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC and in the European Union Clinical Trials Regulation (EU CTR) 536/2014 
Article 2, 2 (13) because it includes clarification of eligibility criteria and introduces the option 
to perform an interim analysis. 
Overall Rationale for the Amendment: 
The purpose of this amendment is to provide clarification for the exclusion criterion regarding 
history of hepatitis B and C. Consistent with the previous criteria, participants with active 
hepatitis B or C infection are excluded. Specified exclusion criteria has been implemented to 
align with ALXN1210-NEPH-202 local amendment 2.1 and other studies of ravulizumab. 
Potential inclusion of such participants does not have anticipated effects on efficacy or safety 
endpoints. Consistent with the IgAN cohort, the option to perform an early interim analysis for 
the LN cohort was added. This early interim analysis will not include hypothesis testing and will 
not impact the progression of the study. 
Section # and Title 
Description of Change 
Brief Rationale 
Section 2.3.1 Risk 
Assessment 
Revised the text of 
immunogenicity 
For clarification 
Section 5.2.1 Common 
Exclusion Criteria 
Revised the text of Exclusion 
Criterion #10  
To clarify the target patient 
population to allow for expanded 
participant recruitment and to align 
with ALXN1210-NEPH-202 local 
amendment 2.1 
Section 8.3.5.1 Virus 
Serology 
Revised the description of HBV 
and HCV testing at Screening 
To align with revision to Exclusion 
Criterion #10 
Section 8.10 
Immunogenicity 
Assessments 
Revised the text of 
immunogenicity 
For clarification 
Section 9.5.2 Interim 
Analysis for Primary 
Endpoint 
Revised the text for an early IA 
for either disease cohort 
To allow the option to perform an 
early interim analysis in the LN 
cohort. The early interim analysis 
will not include hypothesis testing 
and will not impact the progression 
of the study.   
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate 
the Efficacy and Safety of Ravulizumab in Adult Participants With Proliferative Lupus Nephritis 
(LN) or Immunoglobulin A Nephropathy (IgAN) 
Brief Title: Phase 2 Study of Ravulizumab in Proliferative Lupus Nephritis (LN) or 
Immunoglobulin A Nephropathy (IgAN)  
Regulatory Agency Identifier Number(s) 
IND: 148192 
EudraCT: 2020-001537-13 (formerly) 
EU CT number: 2023-507977-16-00 
Rationale: 
Chronic kidney disease (CKD) has become a worldwide public health issue due to its high 
incidence, poor prognosis, and substantial economic burden. When not properly diagnosed and 
managed, CKD can lead to many adverse outcomes such as end-stage renal disease (ESRD). 
Despite advances in immunosuppressive treatments, certain types of glomerulonephritis such as 
lupus nephritis (LN) and immunoglobulin A nephropathy (IgAN) continue to respond poorly to 
treatment, resulting over time in CKD. There has been some progress in terms of approved 
treatments for patients with LN with recent approval of belimumab in multiple regions, including 
the US, EU, and Japan, and voclosporin in the US. At two years, belimumab showed a complete 
renal response (CRR) of 30.0% vs 20.0% compared to placebo (Furie, 2020). At one year, 
voclosporin showed a CRR of 40.8% vs 22.5% compared to placebo (Arriens, 2020). However, 
there remains a significant unmet need for interventions that would allow more novel, definitive, 
and tolerable treatments for patients with LN as well as for patients with IgAN, particularly in 
those who are at risk of progressive kidney disease. 
The pathophysiology of glomerular diseases such as LN and IgAN involves a complex overlap 
of abnormal cellular immune response, loss of humoral immune tolerance, aberrant coagulation, 
and systemic inflammation. Complement dysregulation has emerged as an additional driving 
factor that interplays with these pathways in LN and IgAN. The narrow vessels and high 
perfusion in the kidney make this organ particularly susceptible to complement-mediated injury. 
Histologic evidence of complement deposition observed upon kidney biopsy of patients with 
either LN or IgAN suggests a pathological role. This theory is supported by the association of 
serum complement levels with disease activity and response to treatment, particularly in patients 
with LN. 
The objectives of this study are to evaluate the safety and efficacy of ravulizumab 
(ULTOMIRIS®) administered by intravenous (IV) infusion compared to placebo and 
demonstrate proof-of-concept of the efficacy of terminal complement inhibition in participants 
with LN or IgAN. 
 

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Objectives and Endpoints 
Objectives 
Endpoints 
Primary (Both Cohorts) 
To evaluate the efficacy of ravulizumab 
compared with placebo to reduce proteinuria in 
adult participants with LN or IgAN 
Percentage change in proteinuria from baseline to 
Week 26 (based on 24-hr urine collection[s] at each 
time point)  
Secondary (Both Cohorts) 
To evaluate the efficacy of ravulizumab 
compared with placebo to improve measures of 
kidney function in adult participants with LN 
or IgAN 
Percentage change in proteinuria from baseline to 
Week 50 (based on 24-hr urine collection[s] at each 
time point)  
Percentage of participants with > 30% and > 50% 
reduction in proteinuria at Week 26 and Week 50 
compared to baseline (based on 24-hr urine 
collection[s] at each time point) 
Change from baseline in eGFR at Week 26 and 
Week 50 
Absolute values and change from baseline in serum 
C3 and C4 concentrations at Week 26 and Week 50 
Secondary (LN Cohort Only) 
To evaluate the efficacy of ravulizumab 
compared with placebo to improve measures of 
kidney function in adult participants with LN 
Percentage of participants meeting the criteria for 
CRR at Week 26 and Week 50 
Percentage of participants meeting the criteria for 
PRR at Week 26 and Week 50  
 
Time to UPCR < 0.5 g/g as measured by spot urine 
sample 
 
Percentage of participants achieving corticosteroid 
taper to 7.5 mg/day at Weeks 14, 26, and 50  
 
Percentage of participants with Renal Flare through 
Week 50 
 
Percentage of participants with Extrarenal SLE Flare 
through Week 50 
 
Percentage of participants with Treatment Failure 
through Week 50 
Percentage of participants with Suboptimal Response 
through Week 50 
 
Absolute values and change from baseline in serum 
albumin at Week 26 and Week 50 
Secondary (IgAN Cohort Only) 
To evaluate the efficacy of ravulizumab 
compared with placebo on measures of kidney 
function in adult participants with IgAN 
Percentage of participants meeting the criteria for 
Partial Remission at Week 26 and Week 50  

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Objectives 
Endpoints 
PK/PD/Immunogenicity (Both Cohorts) 
To characterize the PK/PD of ravulizumab in 
adult participants with LN or IgAN 
Absolute values and change from baseline in total C5 
and free C5 concentrations over time 
Absolute values and change from baseline in 
ravulizumab concentrations over time 
To characterize the potential for 
immunogenicity of ravulizumab in adult 
participants with LN or IgAN 
Incidence of ADAs over time 
Safety (Both Cohorts) 
To characterize the safety and tolerability of 
ravulizumab in adult participants with LN or 
IgAN  
Incidence of AEs and SAEs over time 
Abbreviations: ADA = antidrug antibody; AE = adverse event; C3, C4, and C5 = complement components 3,4, and 
5; CRR = complete renal response; eGFR = estimated glomerular filtration rate; IgAN = immunoglobulin A 
nephropathy; LN = lupus nephritis; PD = pharmacodynamics; PK = pharmacokinetics; PRR = partial renal 
response; SAE = serious adverse event; SLE = systemic lupus erythematosus; UPCR = urine protein to creatinine 
ratio 
Overall Design 
Study ALXN1210-NEPH-202 is a Phase 2, randomized, double-blind, placebo-controlled, 
multicenter study of ravulizumab in addition to allowed concomitant therapy consistent with the 
standard of care in 120 adult participants (18 to 75 years of age) with either LN or IgAN. All 
participants must be naive to complement inhibitor treatment and have either a diagnosis of LN 
with an active flare or IgAN based on kidney biopsy, estimated glomerular filtration rate 
(eGFR) ≥ 30 mL/min/1.73m2, and proteinuria [defined as urine protein to creatinine ratio 
(UPCR) ≥ 1 g/g from one 24-hr urine collection (LN cohort) or as mean protein ≥ 1 g/24-hr from 
2 valid 24-hr collections (IgAN cohort)]. Participants in the IgAN cohort must have been treated 
with stable doses of the maximum tolerated renin-angiotensin system (RAS)-inhibiting 
medications and have controlled, stable blood pressure (< 140/90 mmHg) for ≥ 3 months prior to 
Screening.  
Approximately 60 participants in each disease cohort will be randomly assigned in a 2:1 ratio to 
receive ravulizumab or placebo (40 ravulizumab, 20 placebo). Randomization will be stratified 
by whether corticosteroid induction treatment was initiated prior to Screening versus during the 
Screening Period for participants in the LN cohort and by mean proteinuria (1 to 2 g/day versus 
> 2 g/day) from 2 valid 24-hr urine collections during Screening Period for participants in the 
IgAN cohort.  
The study consists of an up to 6-week Screening Period, a 26-week Initial Evaluation Period, a 
24-week Extension Period, and a 36-week post-treatment Follow-up Period.  
During the Initial Evaluation Period, all participants will receive a weight-based loading dose of 
ravulizumab or placebo on Day 1, followed by maintenance doses of ravulizumab or placebo on 
Day 15 and then once every 8 weeks (q8w) thereafter. Loading and maintenance doses will be 
determined based on body weight (see table below). All participants will receive allowed 

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concomitant therapy consistent with the standard of care for participants with LN and IgAN 
throughout the study.  
During the 24-week Extension Period, participants in the LN cohort will continue to receive their 
randomized allocation of study drug (ravulizumab or placebo) q8w. Participants in the LN cohort 
will receive additional standard of care therapy in the event of a protocol-defined Renal Flare or 
Severe Extrarenal systemic lupus erythematosus (SLE) Flare. Approved novel treatment(s) for 
LN is allowed. Additional standard of care therapy for participants with Suboptimal Response is 
allowed at the clinical discretion of the Investigator in conversation with the Medical Monitor. 
For the IgAN cohort, participants in the placebo group will receive a blinded loading dose of 
ravulizumab at Week 26 and participants in the ravulizumab group will receive a blinded 
ravulizumab dose of 900 mg at Week 26. Starting Week 28, all participants in the IgAN cohort 
will receive open-label weight-based doses of ravulizumab q8w until the end of the Extension 
Period. 
During the 36-week Post-treatment Follow-up Period, all participants will continue to receive 
standard of care and will be monitored for safety, clinical events of interest, and kidney function. 
Participants who discontinue study drug early and agree to remain in the study should continue 
to attend their scheduled protocol visits until Week 50. During these visits, all assessments 
except for study drug administration should be performed according to the Schedule of 
Assessments. Participants who withdraw from the study will be followed for safety until 8 weeks 
after the last dose of study drug. The end of study is defined as the last participant’s last visit in 
the Post-treatment Follow-up Period. 
To ensure the adequacy of the dose regimen, an interim pharmacokinetics (PK)/ 
pharmacodynamics (PD) analysis for dose confirmation will be conducted by an independent 
clinical pharmacologist. The interim PK analysis will be conducted using masked PK/PD data 
from the first 10 participants treated with ravulizumab (a minimum of 3 participants in each 
disease-specific cohort). In the event of dose adjustments, the participants treated with the 
previous dose will switch over to the new dose and continue treatment on study but will be 
excluded from the primary efficacy analysis. Replacement participants may be enrolled to 
preserve study power.  
Disclosure Statement: This is a parallel group treatment study with 2 disease cohorts of 
participants randomly assigned to 1 of 2 treatments that are participant, Investigator, and 
outcomes assessor blinded. 
Number of Participants: Approximately 120 adult participants will be randomized. This will 
include approximately 60 participants in the LN cohort and approximately 60 participants in the 
IgAN cohort. 
Intervention Groups and Duration: 
Eligible participants will be enrolled into the study and will be randomized in a 2:1 ratio to 
receive either ravulizumab IV infusion or placebo IV infusion in combination with allowed 
concomitant therapy.  
Ravulizumab will be supplied as a sterile, preservative-free 10 mg/mL solution in single-use 
vials, designed for administration via IV infusion by diluting into commercially available saline 

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(0.9% sodium chloride injection). Dosages will be based on the participant’s body weight, as 
shown in the table below: 
Body Weight Range (kg)a 
Ravulizumab Loading Dose 
(mg) 
Ravulizumab Maintenance Dose 
(mg) 
≥ 40 to < 60 
2400 
3000 
≥ 60 to < 100 
2700 
3900 
≥ 100 
3000 
5400 
a Dose regimen will be based on the last recorded study visit body weight. If the study drug is prepared the night 
before a visit, the weight from the most recent study visit should be used. 
Placebo will have an identical appearance to that of ravulizumab.  
For each participant, the total duration of study treatment (ravulizumab or placebo) will be up to 
50 weeks and the total duration of study participation will be up to 86 weeks.  
Data Monitoring Committee: No 
Ethical Considerations and Benefit-Risk Assessment 
This study will be conducted as specified in this protocol and in accordance with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
A thorough benefit-risk assessment has been performed for ravulizumab IV. Measures will be 
taken to minimize risk to study participants. The potential risks identified in association with 
ravulizumab IV are justified by the anticipated benefits that may be afforded to participants with 
LN or IgAN. 
 

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1.2. 
Study Design Schematics  
Figure 1: 
Study Design Schematic – LN Cohort  
 
Note: Randomization will be stratified by whether corticosteroid induction treatment was initiated prior to Screening 
versus during the Screening Period. Allowed concomitant therapy consists of corticosteroids and mycophenolate 
mofetil. Weight-based dosing regimen (see table above) will be based on the last recorded study visit body weight. 
a Participants will receive additional standard of care therapy in the event of a protocol-defined Renal Flare or Severe 
Extrarenal SLE Flare. Approved novel treatment(s) for LN is allowed. After Week 26, additional standard of care 
therapy for participants with Suboptimal Response is allowed at the clinical discretion of the Investigator in 
conversation with the Medical Monitor 
Abbreviations: LN = lupus nephritis; PK = pharmacokinetics; SLE = systemic lupus erythematosus 
Figure 2: 
Study Design Schematic – IgAN Cohort 
 
Note: Randomization will be stratified by mean proteinuria (1 to 2 g/day versus > 2 g/day) based on 2 valid 24-hr 
urine collections during the Screening Period. Allowed concomitant therapy consisting of stable maximally 
tolerated dose of ACE inhibitors or ARBs. Weight-based dosing regimen (see table above) will be based on the 
last recorded study visit body weight. 
Abbreviations: ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; 
IgAN = immunoglobulin A nephropathy; PK = pharmacokinetics 
 

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1.3. 
Schedule of Activities 
Schedules of activities are provided as follows: 
• Initial Evaluation Period: Screening to Week 26 (Day 183) Visit (LN cohort in 
Table 1 and IgAN cohort in Table 2) 
• Extension Period (LN cohort in Table 3 and IgAN cohort in Table 4) 
• Post-Treatment Follow-up (Both LN and IgAN cohorts in Table 5) 
 

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Table 1: 
Schedule of Activities During the Initial Evaluation Period: Screening to Week 26 Visit (LN Cohort) 
Period 
Screen-
ing 
Initial Evaluation Period  
Eval. for 
Renal 
Flare and 
Extrarenal 
SLE Flare 
Notes 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Additional visits can be performed 
as needed. An ED Visit is required 
if participants discontinue early. 
Week 
Up to  
6 W 
 
W1 
a 
W2 
W4 
W6
b 
W10 
W14 
W18 
W22 
W26/ 
EDc 
Days and Window 
D -42 
to -1 
D1 
 
D8 
± 2 
D15 
± 3 
D29 
± 3 
D43 
± 5 
D71 
± 5 
D99 
± 5 
D127 
± 5 
D155 
± 5 
D183 
± 5  
General Assessments/Procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
Confirm eligibility prior to first dose 
of ravulizumab; participants may be 
rescreened once 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
LN history/diagnosis 
X 
 
 
 
 
 
 
 
 
 
 
 
LN guidelines in Section 10.9 and 
Section 10.10  
Documentation of kidney 
biopsy  
X 
 
 
 
 
 
 
 
 
 
 
 
Biopsy obtained ≤ 6 months prior to 
Screening or during Screening. Send 
local pathology report and slides to 
Central Pathology Laboratory 
(Section 8.1.5.3) 
Meningococcal, Hib and 
S pneumoniae vaccination 
X 
 
 
 
Completion of vaccination series according to national 
and local schedule guidelines 
 
Section 8.1.6 
Prior LN therapy 
X 
 
 
 
 
 
 
 
 
 
 
 
Record corticosteroid and MMF 
usage (Section 6.5.1) 
Weightd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test  
(WOCBP only) 
X 
X 
X 
X 
X 
X 
 
Serum test required at Screening and 
ED; urine test all other visits 
HIV, HCV, and HBV  
X 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 1: 
Schedule of Activities During the Initial Evaluation Period: Screening to Week 26 Visit (LN Cohort) 
Period 
Screen-
ing 
Initial Evaluation Period  
Eval. for 
Renal 
Flare and 
Extrarenal 
SLE Flare 
Notes 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Additional visits can be performed 
as needed. An ED Visit is required 
if participants discontinue early. 
Week 
Up to  
6 W 
 
W1 
a 
W2 
W4 
W6
b 
W10 
W14 
W18 
W22 
W26/ 
EDc 
Days and Window 
D -42 
to -1 
D1 
 
D8 
± 2 
D15 
± 3 
D29 
± 3 
D43 
± 5 
D71 
± 5 
D99 
± 5 
D127 
± 5 
D155 
± 5 
D183 
± 5  
Dispense participant 
safety card 
X 
 
 
 
 
 
 
 
 
 
 
 
Instruct participants to carry safety 
card at all times and bring it to 
scheduled visits 
Efficacy Assessments 
24-hr urine collectione 
X 
 
 
 
 
 
 
 
 
 
X 
Xf 
One collection is needed as soon as 
possible during Screening.  
Two collections must be obtained 
within 2 weeks prior to Week 26 
(Section 8.2.1) 
Morning spot urine 
samplee 
X 
X 
X 
X 
X 
X 
X 
X 
Xg 
X 
X 
X 
Obtain sample prior to dosing, 
vaccination, and biopsy 
eGFR 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xf 
One additional blood draw for eGFR 
(serum creatinine) is required within 
2 weeks prior to the Week 26 visit. 
Monitor for Renal and 
Extrarenal SLE Flare f 
 
Continuous monitoring 
X 
Refer to Section 3.2.1 and 3.2.2 for 
definitions. Document use of 
additional standard of care therapy 
and/or repeat biopsyf, if applicable. 
Blood sample for C3, C4, 
and CH50 
X 
X 
 
X 
 
 
X 
 
X 
 
X 
X 
 
Safety Assessments 
Physical examination 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
Abbreviated PE 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 

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Table 1: 
Schedule of Activities During the Initial Evaluation Period: Screening to Week 26 Visit (LN Cohort) 
Period 
Screen-
ing 
Initial Evaluation Period  
Eval. for 
Renal 
Flare and 
Extrarenal 
SLE Flare 
Notes 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Additional visits can be performed 
as needed. An ED Visit is required 
if participants discontinue early. 
Week 
Up to  
6 W 
 
W1 
a 
W2 
W4 
W6
b 
W10 
W14 
W18 
W22 
W26/ 
EDc 
Days and Window 
D -42 
to -1 
D1 
 
D8 
± 2 
D15 
± 3 
D29 
± 3 
D43 
± 5 
D71 
± 5 
D99 
± 5 
D127 
± 5 
D155 
± 5 
D183 
± 5  
ECGi 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Prior medications and 
procedures 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications, 
nonpharmacologic 
therapies, and procedures  
 
Continuous monitoring 
X 
 
Adverse events 
Continuous monitoring 
X 
 
Clinical chemistry  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Hematology and 
coagulation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Urinalysis and sediment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Obtain sample from a morning void 
prior to dosing 
Participant safety card 
review 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Confirm participants carry safety card 
at all times 
Pharmacokinetic and Pharmacodynamic Assessments 
Blood samples for PK/PDj  
 
B/P 
X 
T/P 
X 
 
T/P 
 
T/P 
 
T 
X 
Samples can be obtained anytime at 
ED Visit 
Blood samples for ADA 
 
B 
 
 
X 
 
T 
 
 
 
T 
 
Samples can be obtained anytime at 
ED Visit 
Exploratory Assessments 
EQ-5D-5L 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
SF-36 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
FACIT-Fatigue  
 
X 
 
 
 
 
 
 
 
 
X 
 
 

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Table 1: 
Schedule of Activities During the Initial Evaluation Period: Screening to Week 26 Visit (LN Cohort) 
Period 
Screen-
ing 
Initial Evaluation Period  
Eval. for 
Renal 
Flare and 
Extrarenal 
SLE Flare 
Notes 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Additional visits can be performed 
as needed. An ED Visit is required 
if participants discontinue early. 
Week 
Up to  
6 W 
 
W1 
a 
W2 
W4 
W6
b 
W10 
W14 
W18 
W22 
W26/ 
EDc 
Days and Window 
D -42 
to -1 
D1 
 
D8 
± 2 
D15 
± 3 
D29 
± 3 
D43 
± 5 
D71 
± 5 
D99 
± 5 
D127 
± 5 
D155 
± 5 
D183 
± 5  
SLEDAI-2K 
 
X 
 
 
 
 
 
 
 
 
X 
X 
Perform as needed for evaluation of 
Extrarenal SLE Flare 
Blood and urine samples 
for biomarkers 
X 
X 
 
X 
 
 
X 
 
X 
 
X 
X 
 
Blood sample for 
anti-dsDNA and anti-C1q  
X 
B 
 
 
 
 
 
 
 
 
X 
X 
 
Blood and urine samples 
for RTCA 
X 
X 
 
X 
 
 
X 
 
X 
 
X 
 
To be performed at selected sites 
only. See Section 8.9.3  
Kidney biopsyk 
  
 
 
 
 
 
 
 
 
 
 
Xk 
Send local pathology report and 
microscopy slides to the Central 
Pathology Laboratory 
(Section 8.1.5.3) 
Administration of Study Intervention 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Allowed concomitant LN 
therapy 
X 
Continuous monitoring 
 
Section 6.5.1  
Ravulizumab or placebo 
 
X 
 
X 
 
 
X 
 
X 
 
--l 
 
Administer after all other required 
tests/procedures 
Note: All assessments should be performed prior to administration of study drug on dosing days, unless otherwise specified.  
a The Week 1 Visit is not required for participants enrolled after completion of the Dose Confirmation Analysis (Section 9.5.1). 
b Visit can be conducted at the discretion of the Investigator.  
 
c For participants who discontinue the study prior to the end of the Initial Evaluation Period, the ED Visit should be completed as soon as possible. In addition, a Follow-up Phone 
Call must be performed 8 weeks following the participant’s last dose of study drug to collect information on concomitant medications, nonpharmacologic therapies and 
procedures, and AEs.  

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Table 1: 
Schedule of Activities During the Initial Evaluation Period: Screening to Week 26 Visit (LN Cohort) 
d Weight should be obtained at every visit and measured predose on dosing visits. The dose regimen is based on the last recorded study visit body weight. If the study drug is 
prepared the night before a visit, the weight from the most recent study visit should be used. 
e  The 24-hr urine collection and spot urine samples must be obtained prior to or > 7 days after biopsy procedures. 
f Renal Flare (as defined in Section 3.2.1) and/or Extrarenal SLE Flare (as defined in Section 3.2.2) may occur at any time through Week 50. Evaluation of Renal Flare requires a 
UPCR from a spot urine sample that is confirmed on a 24-hr urine collection as well as 2 serum creatinine samples obtained within a 2-week period. Evaluation of Renal and 
Extrarenal SLE Flare must be performed as soon as possible upon notification to the Investigator of symptom onset. If Renal Flare or Extrarenal SLE Flare occurs between 
scheduled visits, only the assessments for the Renal Flare/Extrarenal SLE Flare visit are needed. If Renal Flare or Extrarenal SLE Flare occur on a scheduled visit, all scheduled 
assessments should be performed for that visit as well as any additional assessments required for the evaluation of the flare. 
g  Two spot urine samples should be obtained the same morning at Week 18. 
 
h Vital sign measurements include systolic and diastolic BP, pulse oximetry, heart rate, respiratory rate, and temperature. On dosing days, vital signs will be taken predose. 
i Single 12-lead ECG will be collected at Screening and predose on Day 183 and any time on the ED Visit day. Participants must be supine for approximately 5 to 10 minutes 
before ECG collection and remain supine but awake during ECG collection. 
j For indicated visits falling on dosing days, PK/PD samples will be collected predose (within 0.5 hours prior to the start of infusion) and at EOI (within 0.5 hours after the EOI 
from the participant’s opposite, noninfused arm). In order to minimize needle sticks to the participant, the predose sample may be drawn through the venous access created for 
the dose infusion, prior to administration of the dose. As noted, the postdose sample must be drawn from the opposite, noninfused arm. For indicated visits not falling on dosing 
days, samples may be collected at any time that visit day. 
k Participants may receive a kidney biopsy for clinical reasons or for evaluation of a Renal Flare (as defined in Section 3.2.1) at the discretion of the Investigator. The local 
pathology report and microsection slides from kidney biopsies performed at other times during the study prior to Week 86 should also be sent to the Central Pathology 
Laboratory for review as soon as possible. Since examination of the biopsy pathology results may potentially unblind the study treatment (ravulizumab or placebo), Investigators 
and study site personnel should not examine the biopsy pathology results for immunohistochemistry of complement prior to Week 50. 
l  The primary efficacy endpoint assessment will be obtained prior to dosing on Day 183. Dosing on Day 183 is the start of the Extension Period. Please refer to additional Day 183 
post-dose assessments in Table 3.  
Abbreviations: ADA = antidrug antibody; AE = adverse event; B = baseline; BP = blood pressure; C3, C4, C1q = complement component 3, 4, and C1q; CH50 = 50% hemolytic 
complement activity; D = day; dsDNA = double-stranded DNA; ECG = electrocardiogram; ED = early discontinuation; eGFR = estimated glomerular filtration rate; EOI = end 
of infusion; EQ-5D-5L = European Quality of Life Health 5-item questionnaire dimensions 5 level; Eval. = evaluation; FACIT = Functional Assessment of Chronic Illness 
Therapy; HBV = hepatitis B virus; HCV = hepatitis C virus; Hib = Haemophilus influenzae type b; HIV = human immunodeficiency virus; IgAN = immunoglobulin A 
nephropathy; LN = lupus nephritis; MMF = mycophenolate mofetil; P = postdose; PD = pharmacodynamics; PE = physical examination; PK = pharmacokinetics; RTCA = real 
time complement activity; SF-36 = Short Form (36) Health Survey; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 
Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA) Modification; T = trough (predose); UPCR = urine protein to creatinine ratio; W = week; 
WOCBP = woman of childbearing potential 
 

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Table 2: 
Schedule of Activities During the Initial Evaluation Period: Screening to Week 26 Visit (IgAN Cohort) 
Period 
Screen
-ing 
Initial Evaluation Period  
Notes 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Additional visits can be performed as 
needed. An ED Visit is required if 
participants discontinue early. 
Week 
Up to  
6 W 
 
W1a 
W2 
W4 
W10 
W14 
W18 
W22 
W26/ 
EDb 
Days and Window 
D -42 
to -1 
D1 
 
D8 
± 2 
D15 
± 3 
D29 
± 3 
D71 
± 5 
D99 
± 5 
D127 
± 5 
D155 
± 5 
D183 
± 5  
General Assessments/Procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
 
 
Confirm eligibility prior to first dose of 
ravulizumab; participants may be rescreened 
once 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
IgAN history/diagnosis 
X 
 
 
 
 
 
 
 
 
 
IgAN guidelines in Section 10.11  
Documentation of kidney 
biopsy  
X 
 
 
 
 
 
 
 
 
 
Kidney biopsy performed during or prior to 
Screening (any time prior to Day 1). Send local 
pathology report and microscopy slides to 
Central Pathology Laboratory (Section 8.1.5.3) 
Prior IgAN therapy  
X 
 
 
 
 
 
 
 
 
 
Record ACE/ARB usage (Section 6.5.2)  
Meningococcal, Hib and 
S pneumoniae vaccination 
X 
 
 
 
 
 
 
 
 
 
Section 8.1.6 
Weightd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
HIV, HCV, and HBV  
X 
 
 
 
 
 
 
 
 
 
 
Pregnancy test  
(WOCBP only) 
X 
X 
X 
X 
X 
X 
Serum test required at Screening and ED; urine 
test all other visits 
Dispense participant safety 
card 
X 
 
 
 
 
 
 
 
 
 
Instruct participants to carry safety card at all 
times and bring it to scheduled visits 
Efficacy Assessments 

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Table 2: 
Schedule of Activities During the Initial Evaluation Period: Screening to Week 26 Visit (IgAN Cohort) 
Period 
Screen
-ing 
Initial Evaluation Period  
Notes 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Additional visits can be performed as 
needed. An ED Visit is required if 
participants discontinue early. 
Week 
Up to  
6 W 
 
W1a 
W2 
W4 
W10 
W14 
W18 
W22 
W26/ 
EDb 
Days and Window 
D -42 
to -1 
D1 
 
D8 
± 2 
D15 
± 3 
D29 
± 3 
D71 
± 5 
D99 
± 5 
D127 
± 5 
D155 
± 5 
D183 
± 5  
24-hr urine collectionc 
X 
 
 
 
 
 
 
 
 
X 
2 valid 24-hour collections are required during 
Screening and within 2 weeks of the Week 26 
Visit (Section 8.2.1) 
Morning spot urine samplec 
X 
X 
X 
X 
X 
X 
X 
Xe 
X 
X 
Obtain sample prior to dosing 
eGFR 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood sample for C3, C4, 
and CH50 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Safety Assessments 
Physical examination 
X 
X 
 
 
 
 
 
 
 
X 
 
Abbreviated PE 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signsf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
ECGg 
X 
 
 
 
 
 
 
 
 
X 
 
Prior medications and 
procedures 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant medications, 
nonpharmacologic 
therapies, and procedures  
Continuous monitoring 
 
Adverse events 
Continuous monitoring 
 
Clinical chemistry  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Hematology and 
coagulation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis and sediment  
Xh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Obtain sample from a morning void prior to 
dosing 

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Table 2: 
Schedule of Activities During the Initial Evaluation Period: Screening to Week 26 Visit (IgAN Cohort) 
Period 
Screen
-ing 
Initial Evaluation Period  
Notes 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Additional visits can be performed as 
needed. An ED Visit is required if 
participants discontinue early. 
Week 
Up to  
6 W 
 
W1a 
W2 
W4 
W10 
W14 
W18 
W22 
W26/ 
EDb 
Days and Window 
D -42 
to -1 
D1 
 
D8 
± 2 
D15 
± 3 
D29 
± 3 
D71 
± 5 
D99 
± 5 
D127 
± 5 
D155 
± 5 
D183 
± 5  
Participant safety card 
review 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Confirm participants carry safety card at all 
times 
Pharmacokinetic and Pharmacodynamic Assessments 
Blood samples for PK/PDi  
 
B/P 
X 
T/P 
X 
T/P 
 
T/P 
 
T 
Samples can be obtained anytime at ED Visit 
Blood samples for ADA 
 
B 
 
 
X 
T 
 
 
 
T 
Samples can be obtained anytime at ED Visit 
Exploratory Assessments 
EQ-5D-5L 
 
X 
 
 
 
X 
 
 
 
X 
 
SF-36 
 
X 
 
 
 
X 
 
 
 
X 
 
Blood and urine samples 
for biomarkers 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Blood and urine samples 
for RTCA 
X 
X 
 
X 
 
X 
 
X 
 
X 
To be performed at selected sites only. See 
Section 8.9.3  
Kidney biopsy (if indicated 
per Investigator)j 
 
Continuous monitoring 
Send the site pathology report and microscopy 
slides to the Central Pathology Laboratory 
(Section 8.1.5.3) 
Administration of Study Intervention 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
Allowed concomitant IgAN 
therapy 
X 
Continuous monitoring 
Section 6.5.2  
Ravulizumab or placebo 
 
X 
 
X 
 
X 
 
X 
 
--k 
Administer after all other required 
tests/procedures. 

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Table 2: 
Schedule of Activities During the Initial Evaluation Period: Screening to Week 26 Visit (IgAN Cohort) 
a  The Week 1 Visit is not required for participants enrolled after completion of the Dose Confirmation Analysis (Section 9.5.1). 
b For participants who discontinue the study prior to the end of the Initial Evaluation Period, the ED Visit should be completed as soon as possible. In addition, a Follow-up Phone 
Call will be performed 8 weeks following the participant’s last dose of study drug to collect information on concomitant medications, nonpharmacological therapies and 
procedures, and AEs.  
c  The 24-hr urine collection and spot urine samples must be obtained prior to or > 7 days after biopsy procedures. 
d Weight should be obtained at every visit and measured predose on dosing visits. The dose regimen is based on the last recorded study visit body weight. If the study drug is 
prepared the night before a visit, the weight from the most recent study visit should be used. 
e Two spot urine samples should be obtained the same morning at Week 18.  
f Vital sign measurements include systolic and diastolic BP, pulse oximetry, heart rate, respiratory rate, and temperature. On dosing days, vital signs will be taken predose. 
g Single 12-lead ECG will be collected at Screening and predose on Day 183 and any time on the ED Visit day. Participants must be supine for approximately 5 to 10 minutes 
before ECG collection and remain supine but awake during ECG collection. 
h For participants in the IgAN cohort, eligibility for hematuria can be determined via the local laboratory. 
i The PK/PD samples will be collected predose (within 0.5 hours prior to the start of infusion) and at EOI (within 0.5 hours after the EOI from the participant’s opposite, 
noninfused arm). In order to minimize needle sticks to the participant, the predose sample may be drawn through the venous access created for the dose infusion, prior to 
administration of the dose. As noted, the postdose sample must be drawn from the opposite, noninfused arm. For indicated visits not falling on dosing days, samples may be 
collected at any time that visit day. 
j In the event that a participant has a kidney biopsy (performed at the discretion of the Investigator for clinical reasons as part of standard of care), the local pathology report and 
microscopy slides should be sent to the Central Pathology Laboratory as soon as possible. Because examination of the kidney biopsy pathology may potentially unblind the study 
treatment (ravulizumab or placebo), Investigators and study site personnel should not examine the biopsy pathology for immunohistochemistry of complement prior to Week 50. 
k The primary efficacy endpoint assessment will be obtained prior to dosing on Day 183. Dosing on Day 183 is the start of the Extension Period. Please refer to additional Day 183 
post-dose assessments in Table 4.  
Abbreviations: ADA = antidrug antibody; ACE = angiotensin-converting enzyme; AE = adverse event; ARB = angiotensin II receptor blocker; B = baseline; BP = blood pressure; 
C3, C4 = complement component 3 and 4; CH50 = 50% hemolytic complement activity; D = day; ECG = electrocardiogram; ED = early discontinuation; eGFR = estimated 
glomerular filtration rate; EOI = end of infusion; EQ-5D-5L = European Quality of Life Health 5-item questionnaire dimensions 5 level; HBV = hepatitis B virus; 
HCV = hepatitis C virus; Hib = Haemophilus influenzae type b; HIV = human immunodeficiency virus; IgAN = immunoglobulin A nephropathy; P = postdose; 
PD = pharmacodynamics; PE = physical examination; PK = pharmacokinetics; RTCA = real time complement activity; SF-36 = Short Form (36) Health Survey; T = trough 
(predose); W = week; WOCBP = woman of childbearing potential 
 
 

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Table 3: 
Schedule of Activities During the Extension Period: Week 26 Dose Administration, Week 34 to Week 50 Visits 
(LN Cohort) 
Period 
Extension Period 
Eval. for 
Renal Flare 
and 
Extrarenal 
SLE Flare 
and 
Suboptimal 
Response 
Notes 
Visit 
11 
12 
13 
14 
Additional visits can be performed as needed. An ED Visit 
should be performed if participants discontinue early. 
Week 
W26 
W34 
W42 
W50/EDa 
Days and Window 
D183 
D239 
± 7 
D295 
± 7 
D351 
± 7 
General Assessments/Procedures 
 
 
 
 
 
 
Weightb 
 
X 
X 
X 
 
 
Pregnancy test (WOCBP only) 
 
X 
X 
X 
 
Serum pregnancy test required at ED; urine pregnancy test all 
other visits. 
Efficacy Assessments 
 
 
 
 
 
 
24-hr urine collection 
 
 
 
X 
Xc 
Two 24-h urine collections required within 2 weeks prior to the 
Week 50 Visit (Section 8.2.1). Renal Flare and Suboptimal 
Response require a 24-hr urine for confirmation   
Morning spot urine sample 
 
X 
X 
X 
X 
Obtain sample prior to dosing 
eGFR 
 
X 
X 
X 
Xc 
One additional blood draw for eGFR (serum creatinine) is 
required within 2 weeks prior to the Week 50 Visit. 
Monitor for Renal Flare and/or Extrarenal 
SLE Flare and/or Suboptimal Responsec 
Continuous monitoring 
X 
Refer to Section 3.2.1, Section 3.2.2, and Section 3.2.3 for 
definitions. Document use of additional standard of care therapy 
and/or repeat biopsyf if applicable 
Blood sample for C3, C4, and CH50 
 
X 
X 
X 
X 
 
Safety Assessments 
 
 
 
 
 
 
Physical examination 
 
 
 
X 
 
 
Abbreviated physical examination 
 
X 
X 
 
 
 
Vital signsd 
 
X 
X 
X 
 
 
ECGe 
 
 
 
X 
 
 
Concomitant medications, nonpharmacologic 
therapies, and procedures  
Continuous monitoring 
X 
 

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Table 3: 
Schedule of Activities During the Extension Period: Week 26 Dose Administration, Week 34 to Week 50 Visits 
(LN Cohort) 
Period 
Extension Period 
Eval. for 
Renal Flare 
and 
Extrarenal 
SLE Flare 
and 
Suboptimal 
Response 
Notes 
Visit 
11 
12 
13 
14 
Additional visits can be performed as needed. An ED Visit 
should be performed if participants discontinue early. 
Week 
W26 
W34 
W42 
W50/EDa 
Days and Window 
D183 
D239 
± 7 
D295 
± 7 
D351 
± 7 
Adverse events 
Continuous monitoring 
X 
 
Clinical chemistry  
 
X 
X 
X 
X 
 
Hematology and coagulation 
 
X 
X 
X 
 
 
Urinalysis and sediment  
 
X 
X 
X 
 
Obtain sample from a morning void prior to dosing 
Participant safety card review 
 
X 
X 
X 
X 
Confirm participants carry safety card at all times  
Pharmacokinetic and Pharmacodynamic Assessments 
 
 
 
Blood samples for PK/PD  
 
T/P 
T/P 
X 
 
Collect samples at any time during the Week 50/ED Visit 
Blood samples for ADA 
 
T 
T 
X 
 
Collect samples at any time during the Week 50/ED Visit 
Exploratory Assessments 
 
 
 
 
 
 
SF-36  
 
 
 
X 
 
 
EQ-5D-5L 
 
 
 
X 
 
 
FACIT-Fatigue  
 
 
 
X 
 
 
SLEDAI-2K 
 
 
 
X 
X 
Perform as needed for evaluation of Extrarenal SLE Flare 
Blood samples for anti-dsDNA and anti-C1q  
 
 
 
X 
X 
 
Blood and urine samples for biomarkers 
 
X 
X 
X 
X 
 
Optional kidney biopsyf 
 
 
 
Xg 
Xf 
Send the local pathology report and microscopy slides to 
the Central Pathology Laboratory (Section 8.1.5.3) 
Administration of Study Intervention 
 
 
 
 
 
  
Allowed concomitant LN therapy 
Continuous monitoring 
X 
Section 6.5.1  
Ravulizumab or placebo 
X 
X 
X 
 
 
Administer after all other required tests/procedures 

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Table 3: 
Schedule of Activities During the Extension Period: Week 26 Dose Administration, Week 34 to Week 50 Visits 
(LN Cohort) 
Note: During the Extension Period, participants in the LN cohort will continue to receive their randomized allocation of study drug (ravulizumab or placebo). 
a  For participants who discontinue the study prior to the end of the Extension Period, the ED Visit should be completed as soon as possible. In addition, a Follow-up Phone Call 
will be performed 8 weeks following the participant’s last dose of study drug to collect concomitant medications, nonpharmacological therapies and procedures, and AEs.  
b  Weight should be obtained at every visit and measured predose on dosing visits. The dose regimen is based on the last recorded study visit body weight. If the study drug is 
prepared the night before a visit, the weight from the most recent study visit should be used. 
c Renal Flare (as defined in Section 3.2.1) and/or Extrarenal SLE Flare (as defined in Section 3.2.2) and/or Suboptimal Response (as defined in Section 3.2.3) may occur at any 
time through Week 50. Evaluation of Renal Flare requires a UPCR from a spot urine sample that is confirmed on a 24-hr urine collection as well as 2 serum creatinine samples 
obtained with a 2-week period. Evaluation of Renal and Extrarenal SLE Flare and Suboptimal Response must be performed as soon as possible upon notification to the 
Investigator of symptom onset or lack of response. If Renal Flare or Extrarenal SLE Flare or Suboptimal Response occurs between scheduled visits, only the assessments for the 
Renal Flare/Extrarenal SLE Flare/Suboptimal Response visit are needed. If Renal Flare or Extrarenal SLE Flare or Suboptimal Response occur on a scheduled visit, all 
scheduled assessments should be performed for that visit as well as any additional assessments required for the evaluation of the flare or lack of response. 
d Vital sign measurements include systolic and diastolic BP, pulse oximetry, heart rate, respiratory rate, and temperature. On dosing days, vital signs will be taken predose. 
e Single 12-lead ECG will be collected at any time on Day 351 and the ED Visit. Participants must be supine for approximately 5 to 10 minutes before ECG collection and remain 
supine but awake during ECG collection. 
f  Participants may have a kidney biopsy for clinical reasons or for evaluation of a Renal Flare (as defined in Section 3.2.1) at the discretion of the Investigator. The local pathology 
report and microscopy slides from kidney biopsies performed at other times during the study prior to Week 86 should be sent to the Central Pathology Laboratory as soon as 
possible. Because examination of the kidney biopsy pathology may potentially unblind the study treatment (ravulizumab or placebo), Investigators and study site personnel 
should not examine the biopsy pathology for immunohistochemistry of complement prior to Week 50. 
g Participants will be asked to undergo an optional repeat kidney biopsy after completion of the Extension Period. If a participant agrees to a repeat renal biopsy, it should be 
performed at the Week 50 Visit or within 4 weeks (by Week 54).  
Abbreviations: ADA = antidrug antibody; AE = adverse event; BP = blood pressure; C3, C4, C1q = complement components 3, 4, and C1q; CH50 = 50% hemolytic complement 
activity; D = day; dsDNA = double-stranded DNA; ECG = electrocardiogram; ED = early discontinuation; EQ-5D-5L = European Quality of Life Health 5-item questionnaire 
dimensions 5 level; eGFR = estimated glomerular filtration rate; Eval. = evaluation; FACIT = Functional Assessment of Chronic Illness Therapy; LN = lupus nephritis; 
P = postdose; PD =  pharmacodynamics; PK = pharmacokinetics; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 
Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA) Modification; SF-36 = Short Form (36) Health Survey; T = trough (predose); UPCR = urine protein 
to creatinine ratio; W = week; WOCBP = woman of childbearing potential 

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Table 4: 
Schedule of Activities During the Extension Period: Week 26 Dose Administration, Week 28 to Week 50 Visits 
(IgAN Cohort) 
Period 
Extension Period 
Notes 
Visit 
10 
11 
12 
13 
14 
Additional visits can be performed as needed. An ED Visit should 
be performed if participants discontinue early. 
Week 
W26 
W28 
W36 
W44 
W50/EDa 
Days and Window 
D183 
D197 
± 7 
D253 
± 7 
D309 
± 7 
D351 
± 7 
General Assessments/Procedures 
 
 
 
 
 
 
Weightb 
 
X 
X 
X 
X 
Pregnancy test (WOCBP only) 
 
X 
X 
X 
X 
Serum pregnancy test required at ED; urine pregnancy test all other 
visits 
Efficacy Assessments 
 
 
 
 
 
 
24-hr urine collection  
 
 
 
 
X 
Obtain 2 valid 24-hr urine collections within 2 weeks of the Week 50 
Visit (Section 8.2.1). 
Morning spot urine sample 
 
X 
X 
X 
X 
Obtain sample prior to dosing 
eGFR 
 
X 
X 
X 
X 
 
Blood sample for C3, C4, and CH50 
 
X 
X 
X 
X 
 
Safety Assessments 
Physical examination 
 
 
 
 
X 
 
Abbreviated physical examination 
 
X 
X 
X 
 
 
Vital signsc 
 
X 
X 
X 
X 
 
ECGd 
 
 
 
 
X 
 
Concomitant medications, nonpharmacologic 
therapies, and procedures  
Continuous monitoring 
 
Adverse events 
Continuous monitoring 
 
Clinical chemistry  
 
X 
X 
X 
X 
 
Hematology and coagulation 
 
X 
X 
X 
X 
 
Urinalysis and sediment  
 
X 
X 
X 
X 
Obtain sample from a morning void prior to dosing 

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Table 4: 
Schedule of Activities During the Extension Period: Week 26 Dose Administration, Week 28 to Week 50 Visits 
(IgAN Cohort) 
Period 
Extension Period 
Notes 
Visit 
10 
11 
12 
13 
14 
Additional visits can be performed as needed. An ED Visit should 
be performed if participants discontinue early. 
Week 
W26 
W28 
W36 
W44 
W50/EDa 
Days and Window 
D183 
D197 
± 7 
D253 
± 7 
D309 
± 7 
D351 
± 7 
Participant safety card review 
 
X 
X 
X 
X 
Confirm participants carry safety card at all times 
Pharmacokinetic and Pharmacodynamic Assessments 
 
 
 
 
Blood samples for PK/PD  
 
T/P 
T/P 
T/P 
X 
Collect samples at any time during the Week 50/ED Visit 
Blood samples for ADA 
 
T 
T 
T 
X 
Collect samples at any time during the Week 50/ED Visit 
Exploratory Assessments 
 
 
 
 
 
 
SF-36  
 
 
 
 
X 
 
EQ-5D-5L 
 
 
 
 
X 
 
Blood and urine samples for biomarkers 
 
X 
X 
X 
X 
 
Kidney biopsy (if indicated per Investigator)e 
Continuous monitoring 
Send the site pathology report and microscopy slides to the Central 
Pathology Laboratory (Section 8.1.5.3) 
Administration of Study Intervention 
Allowed concomitant IgAN therapy 
Continuous monitoring 
Section 6.5.2 
Ravulizumabf 
X 
X 
X 
X 
 
Administer after all other required tests/procedures 
Note: During the Extension Period, the IgAN placebo group will switch to ravulizumab such that all IgAN participants will be treated with ravulizumab when the study becomes 
open label for the IgAN group. Participants in the ravulizumab group will receive a blinded ravulizumab dose of 900 mg at Week 26 and continue to receive the weight-based 
dosing thereafter. 
a  For participants who discontinue the study prior to the end of the Extension Period, the ED Visit should be completed as soon as possible. In addition, a Follow-up Phone Call 
will be performed 8 weeks following the participant’s last dose of study drug to collect concomitant medications, nonpharmacological therapies and procedures, and AEs.  
b  Weight should be obtained at every visit and measured predose on dosing visits. The dose regimen is based on the last recorded study visit body weight. If the study drug is 
prepared the night before a visit, the weight from the most recent study visit should be used. 
c Vital sign measurements include systolic and diastolic BP, pulse oximetry, heart rate, respiratory rate, and temperature. On dosing days, vital signs will be taken predose. 
d Single 12-lead ECG will be collected at any time on Day 351 and the ED Visit. Participants must be supine for approximately 5 to 10 minutes before ECG collection and remain 
supine but awake during ECG collection. 

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Table 4: 
Schedule of Activities During the Extension Period: Week 26 Dose Administration, Week 28 to Week 50 Visits 
(IgAN Cohort) 
e Participants may receive kidney biopsy (performed at the discretion of the Investigator for clinical reasons as part of standard of care). The local pathology report and 
microscopy slides from kidney biopsies performed at other times during the study prior to Week 86 should be sent to the Central Pathology Laboratory as soon as possible. Since 
examination of the biopsy pathology results may potentially unblind the study treatment (ravulizumab or placebo), Investigators and study site personnel should not examine the 
biopsy pathology results for immunohistochemistry of complement prior to Week 50. 
f  Participants in the IgAN cohort will receive weight-based doses of ravulizumab (Table 9) q8w until the end of the Extension Period. 
Abbreviations: ADA = antidrug antibody; AE = adverse event; BP = blood pressure; C3, C4, = complement components 3, 4; CH50 = 50% hemolytic complement activity; 
D = day; ECG = electrocardiogram; ED = early discontinuation; eGFR = estimated glomerular filtration rate; EQ-5D-5L = European Quality of Life Health 5-item questionnaire 
dimensions 5 level; IgAN = immunoglobulin A nephropathy; P = postdose; PD = pharmacodynamics; PK = pharmacokinetics; q8w = once every 8 weeks; SF-36 = Short Form 
(36) Health Survey; T = trough (predose); W = week; WOCBP = woman of childbearing potential 
 
 

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Table 5: 
Schedule of Activities During Post-Treatment Follow-up Period (Both LN and IgAN Cohorts) 
Period 
Post-Treatment Follow-up Period 
Notes 
Visit 
15 
16 
17 
18 
 
Week 
W52a 
(IgAN only) 
W62 
W74 
W86/EoS 
Days and Window 
D365 
± 7 
D435 
D519 
D603 
Efficacy Assessments 
Record UPCR results (local laboratory) 
 
X 
X 
X 
Record local laboratory values from the participant’s most recent 
testing prior to or on the study visit. Spot urine samples are 
sufficient; morning voids are preferred. 
Record serum creatinine results (local laboratory) 
 
X 
X 
X 
Record local laboratory values from the participant’s most recent 
testing prior to or on the study visit 
Monitor for renal flare and extrarenal SLE flare  
(LN cohort) 
 
X 
X 
X 
Document in the participant’s CRF for the 12-week period since 
the previous study visit. 
Monitor for renal disease progression (IgAN cohort) 
 
X 
X 
X 
Allowed concomitant therapy for LN or IgAN 
Continuous monitoring 
Safety Assessments 
Concomitant medications, nonpharmacologic 
therapies, and procedures 
X 
 
 
X 
Phone visit 
Adverse events 
X 
 
 
X 
Phone visit 
a For participants in the IgAN cohort, a Follow-up Phone Call will be performed 8 weeks following the participant’s last dose of study drug to collect information on concomitant 
medications, nonpharmacological therapies, and procedures, and AEs. 
Abbreviations: AE = adverse event; CRF = case report form; D = day; EoS = End of Study; IgAN = immunoglobulin A nephropathy; LN = lupus nephritis; SLE = systemic lupus 
erythematosus; UPCR = urine protein to creatinine ratio; W = week 
 

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2. 
INTRODUCTION 
2.1. 
Study Rationale 
CKD has become a worldwide public health issue due to its high incidence, poor prognosis, and 
substantial economic burden (Lv, 2019). When not properly diagnosed and managed, CKD can 
lead to many adverse outcomes such as ESRD. Despite advances in immunosuppressive 
treatments, certain types of glomerulonephritis such as LN and IgAN continue to respond poorly 
to treatment, resulting over time in CKD. There has been some progress in terms of approved 
treatments for patients with LN with recent approval of belimumab in multiple regions, including 
the US, EU, and Japan, and voclosporin in the US. At two years, belimumab showed a CRR of 
30.0% vs 20.0% compared to placebo (Furie, 2020). At one year, voclosporin showed a CRR of 
40.8% vs 22.5% compared to placebo (Arriens, 2020). However, there remains a significant 
unmet need for interventions that would allow more novel, definitive, and tolerable treatments 
for patients with LN as well as for patients with IgAN, particularly in those who are at risk of 
progressive kidney disease. 
The pathophysiology of glomerular diseases such as LN and IgAN involves a complex overlap 
of abnormal cellular immune response, loss of humoral immune tolerance, aberrant coagulation, 
and systemic inflammation. Complement dysregulation has emerged as an additional driving 
factor that interplays with these pathways in LN and IgAN. The narrow vessels and high 
perfusion in the kidney make this organ particularly susceptible to complement-mediated injury. 
Histologic evidence of complement deposition observed upon kidney biopsy of patients with 
either LN or IgAN suggests a pathological role. This theory is supported by the association of 
serum complement levels with disease activity and response to treatment, in particular in patients 
with LN (Thurman, 2015). 
Ravulizumab (ULTOMIRIS®) is a humanized monoclonal antibody that, like eculizumab 
(SOLIRIS®), binds to complement component 5 (C5) and blocks its activation by complement 
pathway convertases, thereby preventing the release of the proinflammatory anaphylatoxin 
complement component 5a (C5a) and the formation of the terminal complement complex via 
C5b. Ravulizumab was designed through minimal targeted engineering to substitute 4 amino 
acids in the eculizumab heavy chain (Sheridan, 2018). These changes extend the half-life of 
ravulizumab relative to eculizumab, while preserving the high degree of specificity and 
selectivity of eculizumab for binding to C5 (Sahelijo, 2015). Both ravulizumab and eculizumab 
bind to the same site on C5. Ravulizumab is administered by IV infusion q8w in adults. The 
weight-based dosing regimen of ravulizumab, is approved in multiple global regions for 
treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) and adult and 
pediatric patients with atypical hemolytic uremic syndrome (aHUS). A detailed description of 
the chemistry, pharmacology, efficacy, and safety of ravulizumab is provided in the 
Investigator’s Brochure (IB). 
The objectives of this study are to evaluate the efficacy and safety of ravulizumab administered 
by IV infusion compared to placebo and demonstrate proof-of-concept of the efficacy of terminal 
complement inhibition in patients with LN or IgAN. 

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2.2. 
Background 
2.2.1. 
Lupus Nephritis 
Lupus nephritis occurs in approximately 50% of patients with SLE, an autoimmune disorder 
caused by loss of tolerance to self-antigens, the production of autoantibodies, and deposition of 
complement-fixing immune complexes (ICs) in injured tissues (Bao, 2015). The diagnosis of LN 
is determined by kidney biopsy according to the 2018 International Society of Nephrology/Renal 
Pathology Society (ISN/RPS) nomenclature and classification revised from the 2003 report 
(Bajema, 2018; Markowitz, 2007). In total, there are 6 classes of LN: Classes I to VI 
(Markowitz, 2007). The subset of patients with SLE that develop LN have the worst prognosis 
(Hoover, 2016). Lupus nephritis leading to CKD is an independent major risk factor for overall 
mortality and morbidity attributed to cardiovascular disease and septic shock. With current 
induction and maintenance therapies, the 5-year mortality is approximately 20% and the risk of 
developing ESRD at 5, 10, and 15 years is 11%, 17%, and 22%, respectively (Mageau, 2019). 
Recurrence of LN after treatment (renal flare) occurs within 1 year in up to 25% of patients and 
is associated with an increased risk of CKD progression (Almaani, 2017).  
The pathophysiology of LN involves multiple overlapping pathways where complement serves 
as a mediator of an abnormal immune response (Bao, 2015; Pickering, 2000; Schur, 1988). The 
terminal complement components (C5a and terminal complement complex [C5b-9]) trigger acute 
cellular inflammatory responses through activation of interleukin and cytokine signaling. 
Complement also serves to fix immunoglobulins and ICs in the kidney. In fact, complement and 
complement split products are a prominent histologic finding in kidney biopsies of patients with 
LN (Biesecker, 1981; Wilson, 2019). Serum levels of these autoimmune and complement 
biomarkers are linked with disease activity (Birmingham, 2015; Dall’Era, 2011). Decreases in 
complement components 3, 4, and 1q (C3, C4, and C1q) are associated with de novo LN and LN 
flares. Likewise, levels of complement biomarkers correlate with disease activity in SLE  
(Kim, 2019). Restoring complement regulation may improve renal responses through acute 
anti-inflammatory effects and lasting effects on IC deposition in the kidney. Thus, anti-C5 
therapy is promising for both induction treatment of active proliferative LN and maintenance 
treatment of chronic LN.  
The American College of Rheumatology (ACR), and joint recommendations from the European 
League Against Rheumatism (EULAR) and European Renal Association-European Dialysis and 
Transplant Association (ERA-EDTA), recommend immunosuppression treatment for Class III, 
IV, III/V, and IV/V LN also called “proliferative” LN (Bertsias, 2012). The guidelines agree on 
induction treatment with glucocorticoids plus mycophenolate mofetil (MMF) or 
cyclophosphamide. For maintenance therapy, the guidelines agree on MMF or azathioprine, with 
or without low dose glucocorticoids. In patients with LN, the main goal of therapy is prevention 
of CKD progression, ESRD, and death. Lack of achievement of remission, in particular complete 
remission, is one of the major risk factors for progression of renal disease. Hence, short-term 
complete and partial renal remissions are used to assess the efficacy of standard of care and 
novel therapies. However, after 6 to 12 months of treatment, only 10% to 40% of patients 
achieve a CRR with standard of care (Parikh, 2016).  

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2.2.2. 
IgA Nephropathy 
IgAN, also known as Berger’s disease, is the most common global primary 
glomerulonephropathy that can progress to renal failure (Lai, 2016). Immunoglobulin A (IgA) 
nephropathy is a lifelong disease leading to CKD and progresses to ESRD in 30% to 40% of 
patients over the course of 20 to 30 years (Lai, 2016). Patients initially present with hematuria 
and hypertension, and proteinuria develops as the disease progresses. Diagnosis of IgAN is made 
by renal biopsy demonstrating IgA immunofluorescence in the glomeruli usually co-dominant 
with C3 according to the Oxford Classification nomenclature (KDIGO, 2021; Rizk, 2019; 
Trimarchi, 2017). 
The pathophysiology of IgAN is related to the overproduction of under-glycosylated 
immunoglobulin A1 (IgA1) which accumulates in the kidney glomeruli. However, aberrant 
galactosylation alone is insufficient to induce renal injury; glycan-specific IgA and 
immunoglobulin G (IgG) autoantibodies that recognize the under-galactosylated IgA1 molecule 
likely also contribute. This process leads to the local inflammation and complement activation in 
the kidney (Oortwijn, 2008). Both the alternative and lectin complement pathways may be 
activated, leading to generation of anaphylatoxins, and the membrane attack C5b-9, with 
subsequent promotion of inflammatory mediators (Maillard, 2015). C4 and C3 complexes and 
activated C3 products are elevated in up to 30% of patients with IgAN. Activated C3 products 
are associated with elevated levels of proteinuria and hematuria compared to patients with IgAN 
who have normal levels, and correlate with deterioration of renal function (Zwirner, 1997). 
Complement activity on kidney biopsy and circulating complement proteins are associated with 
disease activity and progression of CKD. Together, these findings suggest a role of complement 
in the pathophysiology and the prognostic value of complement biomarkers in IgAN  
(Rizk, 2019). 
C5 inhibition is a potential target for treatment of patients with IgAN at high risk of progression 
to kidney disease (ie, significant proteinuria despite optimal RAS blockade) (Reich, 2007). 
Blocking the C5b-9 membrane attachment complex, and thereby preventing the downstream 
molecular and cellular consequences, has potential for therapeutic efficacy in patients with 
IgAN.  
Treatments for IgAN include RAS-blocking agents, such as angiotensin-converting enzyme 
(ACE) inhibitors or angiotensin II receptor blockers (ARBs). These therapies are aimed at 
controlling blood pressure, preserving kidney function through decreasing intraglomerular 
pressure which in turn reduces proteinuria, and suppressing the immune response. These 
treatments are insufficient in preserving renal function as the proportions of patients who 
progress to CKD and ESRD are high. Patients with baseline hypertension and proteinuria 
> 1 g/day are at increased risk for progression (Reich, 2007).  

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2.3. 
Benefit/Risk Assessment 
Detailed information about the known and expected benefits and risks of ravulizumab is 
provided in the IB. 
2.3.1. 
Risk Assessment  
Based on cumulative safety data from clinical studies of ravulizumab in patients with PNH and 
aHUS, and post-marketing experience, ravulizumab is well tolerated up to 5400 mg, and 
exposure to ravulizumab has not raised unexpected safety concerns. 
Ravulizumab functions by blocking terminal complement; therefore, participants have increased 
susceptibility to serious infections, in particular Neisseria meningitidis (refer to Ravulizumab 
IB). Specific risk mitigation measures available to support the safe use of ravulizumab in 
participants in this study are described in Table 6. 
As with any therapeutic protein, administration of ravulizumab may lead to the development of 
antidrug antibodies (ADAs). Monitoring of immunogenicity is planned during this study, as 
described in Section 8.10. IV administration of any investigational product may result in 
infusion-related reactions. Management of potential infusion-related reactions is described in 
Section 10.4. 
The coronavirus disease 2019 (COVID-19) pandemic is active in many countries at the time of 
this protocol amendment. Given this unique circumstance, specific consideration has been given 
to the risks and benefits of the study as they relate to COVID-19, and the global and local 
changes that exist as a result of the pandemic. This assessment is described in Section 10.1.11. 
Table 6: 
Potential Risks and Mitigation Strategies 
Risks of Clinical 
Significance 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Identified risk 
Meningococcal infection 
C5 inhibition is known to increase the 
susceptibility to infections caused by 
N meningitidis. 
Participants must be vaccinated against 
all available serotypes of N meningitidis 
(A, C, Y, W 135, and B) per the 
inclusion criteria and Schedule of 
Assessments. Prophylactic antibiotics 
will be required for participants (if 
initiated on C5 inhibition less than 
2 weeks after start of vaccination series). 
Each participant will be provided with a 
Participant Safety Card with signs and 
symptoms of meningococcal infection, 
instructions on when to contact a 
healthcare provider, and relevant contact 
information. The Participant Safety Card 
will be reviewed at each visit (Schedule 
of Assessments, Section 1.3).  

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Table 6: 
Potential Risks and Mitigation Strategies 
Risks of Clinical 
Significance 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Potential Risks 
Serious infection  
Apart from the predictable risk of 
infection with Neisseria species, 
which is well known and directly 
related to the mechanism of action of 
ravulizumab, the mechanism that may 
lead to other serious infections in 
participants treated with ravulizumab 
remains unclear. Since the relevance 
of serious infection with ravulizumab 
therapy has not been confirmed in 
clinical studies, this remains a 
potential risk. In this study, because 
participants with LN will be 
immunosuppressed due to 
concomitant steroid and MMF use, 
they will be at increased risk of 
serious infections due to the 
immunosuppressant use. 
All participants will be required to be 
vaccinated for Hib and S pneumonia, 
according to current national/local 
guidelines, in addition to N meningitidis. 
Healthcare professionals and 
participants should have increased 
awareness about the potential risk of 
serious infection. Monitoring for signs 
and symptoms of serious infections will 
be conducted as part of the safety 
assessments for this study.  
Immunogenicity  
Treatment with any therapeutic 
protein has the potential to induce an 
immune response. Potential clinical 
consequences may include 
hypersensitivity, anaphylaxis or 
related type of reactions or loss of 
efficacy. 
Fewer than 1% of participants in the 
ravulizumab Phase 2 and 3 studies had 
positive ADA samples.  
Monitoring for hypersensitivity and 
serious infusion-related reactions will be 
conducted as part of safety assessments 
for this study (Section 10.4). 
Infusion should be stopped in the event 
of any intervention-related severe 
adverse events like systemic 
hypersensitivity or anaphylaxis. 
In case of suspected SAEs of 
hypersensitivity or anaphylaxis, 
additional ADA samples may be 
collected during or in proximity of the 
event. 
Pregnancy 
exposure/lactation 
No studies of ravulizumab have been 
conducted in pregnant or 
breastfeeding women. There are no 
data available on excretion of 
ravulizumab in breast milk. 
Pregnant or nursing female participants 
will be excluded from the clinical study. 
Women and men enrolled in the study, 
and their spouses/partners, must use a 
highly effective or acceptable method of 
contraception for a period of 8 months 
following the final dose of study 
intervention. Breastfeeding should be 
discontinued during treatment and up to 
8 months after treatment with 
ravulizumab (Section 10.6). 
Abbreviations: ADA = antidrug antibodies; C5 = complement component 5; Hib = Haemophilus influenzae type b; 
LN = lupus nephritis; MMF = mycophenolate mofetil; SAE = serious adverse event 

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2.3.2. 
Benefit Assessment 
LN and IgAN are life-long diseases that lead to progressive loss of kidney function. As kidney 
function declines, patients may suffer the morbidity and mortality associated with advanced 
CKD, dialysis, and kidney transplant. While there has been some progress in terms of approved 
treatments for patients with LN with recent approval of belimumab in multiple regions and 
voclosporin in the US, there remains a large unmet need for novel interventions, particularly in 
patients who are at risk of progressive kidney disease. For patients with LN, current off-label 
immunosuppressive or cytotoxic therapies as well as recently approved drugs still provide 
inadequate clinical response (low rates of CRR and high risks of relapse) and are associated with 
significant side effects limiting their tolerability and long-term use. These side effects can lead to 
chronic diseases such as hypertension, osteoporosis, diabetes, obesity, and infertility. For patients 
with IgAN, patients with persistent proteinuria despite treatment with ACE inhibitors and ARBs 
are particularly at risk of progression of kidney disease. Available data from IgA studies on the 
role of immunosuppressive therapy are not conclusive as most are relatively small and have 
limited follow-up (Lai, 2016). Development of new therapies targeting the underlying pathologic 
processes is critical to improving the care of patients with LN or IgAN.  
Multiple sources of evidence suggest aberrant complement is a key mediator in the 
pathophysiology of LN and IgAN (Section 2.2). Participants in the study may benefit from 
clinical improvement and decreased risk of kidney disease progression. Additionally, though 
ravulizumab is being tested as add-on treatment to allowed concomitant therapy consistent with 
the standard of care, in patients with LN there is potential for a less intensive course of 
background immunosuppression and improved safety profile.  
2.3.3. 
Overall Benefit: Risk Conclusion 
There is a high unmet need for effective therapies for patients with LN or IgAN because clinical 
outcomes are poor with the currently available standard of care. Given the cumulative data on the 
role of complement in LN and IgAN disease progression, the potential risks of ravulizumab are 
justified by the anticipated clinical benefits. 
 

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3. 
OBJECTIVES AND ENDPOINTS 
3.1. 
Overview of Objectives and Endpoints 
Objectives 
Endpoints 
Primary (Both Cohorts) 
To evaluate the efficacy of ravulizumab 
compared with placebo to reduce proteinuria 
in adult participants with LN or IgAN 
Percentage change in proteinuria from baseline to 
Week 26 (based on 24-hr urine collection[s] at each 
time point)  
Secondary (Both Cohorts) 
To evaluate the efficacy of ravulizumab 
compared with placebo to improve measures 
of kidney function in adult participants with 
LN or IgAN 
Percentage change in proteinuria from baseline to 
Week 50 (based on 24-hr urine collection[s] at each 
time point)  
Percentage of participants with > 30% and > 50% 
reduction in proteinuria at Week 26 and Week 50 
compared to baseline (based on 24-hr urine 
collection[s] at each time point) 
Change from baseline in eGFR at Week 26 and 
Week 50 
Absolute values and change from baseline in serum 
C3 and C4 concentrations at Week 26 and Week 50 
Secondary (LN Cohort Only) 
To evaluate the efficacy of ravulizumab 
compared with placebo to improve measures 
of kidney function in adult participants with 
LN 
Percentage of participants meeting the criteria for 
CRR at Week 26 and Week 50 (as defined in 
Section 3.2.5) 
Percentage of participants meeting the criteria for PRR 
at Week 26 and Week 50 (as defined in Section 3.2.5) 
 
Time to UPCR < 0.5 g/g as measured by spot urine 
sample 
 
Percentage of participants achieving corticosteroid 
taper to 7.5 mg/day at Weeks 14, 26, and 50  
 
 
Percentage of participants with Renal Flare (as defined 
in Section 3.2.1) through Week 50 
 
Percentage of participants with Extrarenal SLE Flare 
(as defined in Section 3.2.2) through Week 50 
 
Percentage of participants with Treatment Failure (as 
defined in Section 3.2.4) through Week 50 
 
Percentage of participants with Suboptimal Response 
(as defined in Section 3.2.3) through Week 50 
 
Absolute values and change from baseline in serum 
albumin at Week 26 and Week 50 

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Objectives 
Endpoints 
Secondary (IgAN Cohort Only) 
To evaluate the efficacy of ravulizumab 
compared with placebo on measures of 
kidney function in adult participants with 
IgAN 
Percentage of participants meeting the criteria for 
Partial Remission at Week 26 and Week 50 (as 
defined in Section 3.2.6) 
PK/PD/Immunogenicity (Both Cohorts) 
To characterize the PK/PD of ravulizumab in 
adult participants with LN or IgAN 
Absolute values and change from baseline in total C5 
and free C5 concentrations over time 
Absolute values and change from baseline in 
ravulizumab concentrations over time 
To characterize the potential for 
immunogenicity of ravulizumab in adult 
participants with LN or IgAN 
Incidence of ADAs over time 
Safety (Both Cohorts) 
To characterize the safety and tolerability of 
ravulizumab in adult participants with LN or 
IgAN  
Incidence of AEs and SAEs over time 
Exploratory (Both Cohorts) 
To evaluate the efficacy of ravulizumab 
compared with placebo on hematuria in adult 
participants with LN or IgAN 
Effect on hematuria as measured by  
- Absolute value and change from baseline in RBC 
in urine from baseline to Week 26 and Week 50 
- Percentage of participants with < 10 RBC/hpf  
To assess quality of life based on 
participant-reported outcomes in adult 
participants with LN or IgAN based on 
treatment with ravulizumab compared with 
placebo 
Change from baseline in SF-36 at Week 26 and 
Week 50 
Change from baseline in EQ-5D-5L at Week 26 and 
Week 50 
To evaluate complement and autoimmune 
biomarkers in adult participants with LN or 
IgAN 
Absolute values and change from baseline in levels of 
biomarkers in blood, urine, and kidney tissue at 
Week 26 and Week 50 
Exploratory (LN Cohort Only) 
To assess the efficacy of ravulizumab in 
exploratory efficacy endpoints 
 
Time to CRR and PRR (using spot UPCR) 
Percentage of participants with Overall 
Renal Response at Week 26 and Week 50 (CRR and 
PRR) 
Time to UPCR > 50% decrease from baseline (using 
spot UPCR) 
To assess quality of life based on 
participant -reported outcomes 
Change from baseline in FACIT-Fatigue score at 
Week 26 and Week 50 

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Objectives 
Endpoints 
To assess the efficacy of ravulizumab in other 
exploratory endpoints 
Absolute values and change from baseline in 
anti-dsDNA and anti-C1q antibodies at Week 26 and 
Week 50 
 
Histology changes from baseline to Week 50 
Exploratory (IgAN Cohort Only) 
To assess the efficacy of ravulizumab in 
exploratory efficacy endpoints 
Slope of eGFR computed from baseline to Week 26 
and Week 50 
Abbreviations: ADA = antidrug antibody; AE = adverse event; C3, C4, C5, and C1q = complement components 3, 
4,  5, and C1q; CRR = complete renal response; dsDNA = double-stranded DNA; eGFR = estimated glomerular 
filtration rate; EQ-5D-5L = EuroQoL 5-Dimensions 5-Level; FACIT = Functional Assessment of Chronic Illness 
Therapy; IgAN = immunoglobulin A nephropathy; LN = lupus nephritis; PD = pharmacodynamics; 
PK = pharmacokinetics; PRR = partial renal response; RBC = red blood cell; SAE = serious adverse event; 
SF-36 = Short Form (36) Health Survey; SLE = systemic lupus erythematosus; UPCR = urine protein to creatinine 
ratio 
3.2. 
Definitions for Endpoints 
3.2.1. 
Renal Flare (LN Cohort Only) 
Renal Flare is determined in the opinion of the Investigator in addition to the criteria outlined 
below: 
• For participants who achieve CRR (Section 3.2.5), a Renal Flare is the reproducible 
recurrence of proteinuria ≥ 1 g/g 
• For all other participants, a Renal Flare is either of the following:  
− Reproducible increase of serum creatinine > 25% higher than baseline or above 
the upper limit of normal, plus any one of the following: 
• 
Reproducible proteinuria ≥ 75% higher than baseline 
• 
Worsening active urinary sediment compared to baseline as defined by an 
increase of ≥ 5 red blood cells (RBCs)/ high power field (hpf) or new RBC 
casts (based on local laboratory results from at least 2 samples)  
• 
Kidney biopsy newly conducted since the biopsy used for eligibility 
demonstrating LN Class III or IV activity 
− Reproducible doubling of the UPCR from a 24-hour urine collection compared 
with the lowest previous value obtained after the first dose of study drug.  
• Reproducibility of proteinuria requires that the proteinuria based on a UPCR from a 
morning spot urine collection is confirmed by UPCR calculated on a 24-hour urine 
collection obtained within a 2-week period.  
• Reproducibility of serum creatinine requires 2 blood tests within a 2-week period.  

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Participants who meet criteria for the protocol-defined Renal Flare will receive additional 
standard of care therapy (as defined in Section 6.6). The Medical Monitor should be notified of 
the Renal Flare by the Investigator or Sub-investigator.  
Any renal flare that does not meet the protocol-defined Renal Flare criteria may be treated with a 
limited duration of increased oral corticosteroids (< 14 days) after discussion with the Medical 
Monitor. Such treatment will not be considered additional standard of care therapy and will not 
be considered Treatment Failure.  
Renal Flare criteria will be recorded on the Renal Flare case report form (CRF).  
3.2.2. 
Extrarenal Systemic Lupus Erythematosus Flare (LN Cohort Only) 
Extrarenal SLE Flare is defined as an increase in Systemic Lupus Erythematosus Disease 
Activity Index Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA) 
Modification (SLEDAI–2K) ≥ 4 points (see Section 8.9.2 and Section 10.12) that is not 
accounted for by proteinuria, hematuria, urinary cellular casts, hypocomplementemia, or an 
increase in anti-double-stranded DNA (anti-dsDNA) antibody level.  
Participants in the LN cohort who meet the criteria for Extrarenal SLE Flare may receive 
additional standard of care therapy, if considered clinically appropriate by the Investigator (as 
defined in Section 6.6). If additional standard of care therapy is administered, the event is 
considered a Severe Extrarenal SLE Flare.  
Participants will be allowed to receive a limited number of corticosteroid treatments for 
non-severe extrarenal SLE flare, if clinically warranted as outlined below. Such treatment will 
not be considered additional standard of care therapy and will not be considered Treatment 
Failure. 
• Up to 2 corticosteroid treatments will be allowed for a non-severe extrarenal SLE 
flare. 
− One corticosteroid treatment will be allowed between Week 12 (end of steroid 
taper) and Week 22 (4 weeks prior to Week 26 primary endpoint). 
− One corticosteroid treatment will be allowed between Week 26 and Week 46 
(4 weeks prior to final analysis). 
• Each treatment course should be no longer than 14 days in duration with the steroid 
dose returning to 7.5 mg/day by Day 14. 
• Up to a total of 20 mg/day (prednisone or prednisone equivalent) is permitted. 
• There can be no concurrent worsening of renal disease (as defined by the criteria for a 
Renal Flare). 
3.2.3. 
Suboptimal Response (LN Cohort Only) 
A Suboptimal Response is determined in the opinion of the Investigator in addition to the 
following criteria after the Week 26 Visit:   
• Reproducible proteinuria ≤ 25% decreased compared to baseline based on UPCR on a 
24-hour urine collection performed by the central laboratory 

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Reproducibility of proteinuria requires that the proteinuria based on a UPCR from a spot urine 
collection is confirmed by a central laboratory UPCR calculated on a 24-hour urine collection 
obtained within a 2-week period.  
Participants with Suboptimal Response must be discussed with the Investigator and Medical 
Monitor. Participants with Suboptimal Response will stay in the study and continue to receive 
study drug. Intensification of current standard of care or introduction of new immunosuppressive 
therapies are allowed per the clinical discretion of the Investigator in conversation with the 
Medical Monitor and will be considered additional standard of care therapy.  
Participants with Suboptimal Response will be included as Treatment Failure.   
3.2.4. 
Treatment Failure (LN Cohort Only) 
Treatment Failure is defined as the occurrence of any of the following events: 
• Receipt of additional standard of care therapy (as defined in Section 6.6) at any time 
up to Week 50 for protocol-defined Renal Flare, Severe Extrarenal SLE Flare, or 
Suboptimal Response 
Increase in corticosteroids for extrarenal SLE flare not meeting the protocol definition of Severe 
Extrarenal SLE Flare, renal flare not meeting protocol definition for Renal Flare, lack of 
response not meeting the protocol definition for Suboptimal Response, other medical conditions 
or surgery limited to ≤ 14 days duration are not included in Treatment Failure.  
Participants who meet the criteria for Treatment Failure may continue to receive the study 
medication and stay in the study. 
3.2.5. 
Complete and Partial Renal Response (LN Cohort Only) 
CRR and partial renal response (PRR) will be assessed at Week 26 and Week 50.  
To achieve CRR (Rovin, 2019), participants in the LN cohort must meet all 3 of the following 
criteria:  
• A decrease in mean UPCR to ≤ 0.5 g/g based on two 24-hr urine collections obtained 
within 2 weeks prior to the study visit (Week 26 or Week 50) 
• eGFR > 60 mL/min/1.73 m2 or no eGFR reduction ≥ 20% from the baseline value 
based on the mean of 2 values. The first eGFR value must be obtained within 2 weeks 
prior to the study visit (Week 26 or Week 50) and the second eGFR value will be 
obtained on the study visit (Week 26 or Week 50). 
• No Treatment Failure (as defined in Section 3.2.4) 
To achieve PRR (Rovin, 2019), participants in the LN cohort must meet all 3 of the following 
criteria:  
• A decrease in UPCR > 50% compared to the baseline value based on the mean of two 
24-hr urine collections obtained within 2 weeks prior to the study visit (Week 26 or 
Week 50) 
• eGFR > 60 mL/min/1.73 m2 or no eGFR reduction ≥ 20% from the baseline value 
based on the mean of 2 values. The first eGFR value must be obtained within 2 weeks 

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prior to the study visit (Week 26 or Week 50) and the second eGFR value will be 
obtained on the study visit (Week 26 or Week 50) 
• No Treatment Failure (as defined in Section 3.2.4)  
3.2.6. 
Partial Remission (IgAN Cohort Only) 
Partial Remission will be defined as mean proteinuria < 1 g/24-hrs based on 2 valid 24-hr urine 
collections obtained within 2 weeks prior to the study visit (Week 26 or Week 50). 

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study of 
ravulizumab in addition to allowed concomitant therapy consistent with the standard of care in 
adult participants (18 to 75 years of age) with either LN or IgAN. All participants must be naive 
to complement inhibitor treatment and have either a diagnosis of LN with an active flare or IgAN 
based on kidney biopsy, eGFR ≥ 30 mL/min/1.73 m2, and proteinuria [defined as UPCR ≥ 1 g/g 
from one 24-hr urine collection (LN cohort) or as mean protein ≥ 1 g/24-hr from 2 valid 24-hr 
collections (IgAN cohort)]. Participants in the IgAN cohort must have been treated with stable 
doses of the maximum tolerated RAS-inhibiting medications and have controlled, stable blood 
pressure (< 140/90 mmHg) for ≥ 3 months prior to Screening.  
The study consists of an up to 6-week Screening Period, a 26-week Initial Evaluation Period, a 
24-week Extension Period, and a 36-week post-treatment Follow-up Period. Thus, the total 
treatment duration is 50 weeks and the total study duration is up to 86 weeks.  
Participants will be screened for eligibility for up to 6 weeks during the Screening Period. 
Approximately 120 adult participants with either LN or IgAN will be enrolled into the study. For 
each disease cohort, 60 participants will be randomly assigned in a 2:1 ratio to receive 
ravulizumab or placebo (40 ravulizumab, 20 placebo). Randomization will be stratified by 
whether corticosteroid induction treatment was initiated prior to Screening versus during the 
Screening Period for participants in the LN cohort and by mean proteinuria (1 to 2 g/day versus 
> 2 g/day) from 2 valid 24-hr urine collections during the Screening Period for participants in the 
IgAN cohort.  
For participants in the LN cohort, all screening laboratory assessments should be performed as 
soon as possible after signing of the informed consent form (ICF). All participants in the LN 
cohort should be randomized as soon as possible once eligibility is confirmed.  
All participants are required to have meningococcal vaccination; however, for participants in the 
IgAN cohort, every effort should be made to start the meningococcal vaccination series at least 
14 days prior to randomization in order to avoid antibiotic prophylaxis and minimize the 
potential triggering of innate immunity with possible effects on proteinuria and hematuria. 
During the Initial Evaluation Period, all participants will receive a weight-based loading dose of 
ravulizumab or placebo on Day 1, followed by weight-based maintenance doses of ravulizumab 
or placebo on Day 15 and then q8w thereafter (Table 8). All participants will receive allowed 
concomitant therapy consistent with the standard of care for participants with LN and IgAN 
throughout the study as defined in Section 6.5.  
During the 24-week Extension Period, participants will continue to receive study drug 
(ravulizumab or placebo): 
• Participants in the LN cohort will continue to receive their randomized allocation of 
study drug (ravulizumab or placebo) q8w until the end of the Extension Period. 
Participants will receive additional standard of care therapy in the event of a protocol-
defined Renal Flare or Severe Extrarenal SLE Flare. Additional standard of care 

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therapy for participants with Suboptimal Response is allowed at the clinical discretion 
of the Investigator in conversation with the Medical Monitor. 
• Participants in the IgAN cohort randomized to the placebo group will switch to 
receive a blinded loading dose of ravulizumab at Week 26 and then open-label 
weight-based dosing of ravulizumab q8w until the end of the Extension Period. 
• Participants in the IgAN cohort randomized to the ravulizumab group will receive a 
blinded dose of 900 mg ravulizumab at Week 26 and then open-label weight-based 
dosing of ravulizumab q8w until the end of the Extension Period.  
During the 36-week Post-treatment Follow-up Period, participants will continue to receive 
standard of care, at the discretion of the Investigator, and will be monitored for safety, clinical 
events of interest, and kidney function.  
Participants who discontinue study drug early and agree to remain in the study should continue 
to attend their scheduled protocol visits until Week 50. During these visits, all assessments 
except for study drug administration should be performed according to the Schedule of 
Assessments. 
Participants who withdraw from the study will be followed for safety until 8 weeks after the last 
dose of study drug.  
The end of study is defined as the last participant’s last visit in the Post-treatment Follow-up 
Period. 
To ensure the adequacy of the dose regimen, an interim PK/PD analysis for dose confirmation 
will be conducted by an independent clinical pharmacologist (Section 9.5.1). The interim PK 
analysis will be conducted using masked PK/PD data from the first 10 participants treated with 
ravulizumab (a minimum of 3 participants in each disease-specific cohort). In the event of dose 
adjustments, the participants treated with the previous dose will switch over to the new dose and 
continue treatment on study but will be excluded from the primary efficacy analysis. 
Replacement participants may be enrolled to preserve study power.  
4.2. 
Scientific Rationale for Study Design 
A randomized, double-blind, placebo-controlled study design is selected to provide the most 
robust evidence of the efficacy of ravulizumab on clinical response, disease progression, and 
safety. Randomization minimizes the effects of baseline differences and confounding factors on 
the study endpoints. The use of a placebo comparator allows for the analysis of the true treatment 
effect of ravulizumab by minimizing the risk of selection bias. An unequal randomization 
scheme was chosen to decrease the number of participants receiving placebo. A single 
randomization stratum was selected for each cohort to ensure equal distribution of baseline 
characteristics that may impact the endpoints. The 50-week treatment duration provides adequate 
time to assess the safety and efficacy endpoints to demonstrate proof of concept for both cohorts 
in a Phase 2 study.  
The standard of care allowed concomitant therapies employed in this protocol are consistent with 
recent clinical studies in patients with LN (Rovin, 2019) and IgAN (Rauen, 2015).  

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4.2.1. 
Rationale for Primary Endpoint 
The primary endpoint for the study is percent change from baseline to Week 26 in 24-hr 
proteinuria.  
Change in proteinuria is considered a valid surrogate endpoint for kidney survival in glomerular 
diseases. Change in proteinuria is also an acceptable endpoint for clinical studies as concluded 
during a scientific workshop facilitated by the National Kidney Foundation in collaboration with 
FDA and EMA in 2018 (Coresh, 2019). A decline in proteinuria in response to treatment is a 
strong predictor of kidney survival (Hebert, 2001; Wilmer, 2003) and a > 20% relative treatment 
effect over standard of care in change in proteinuria is considered clinically relevant  
(Holtkamp, 2020; Levey, 2020). Changes in proteinuria become evident before traditional 
markers of kidney survival (eg, ESRD, dialysis, or transplant); thus, it is especially useful to 
detect signs of efficacy for a proof-of-concept study. Accordingly, the effect of ravulizumab on 
the percentage reduction of proteinuria at Week 26 compared to baseline was selected as the 
primary endpoint for this study. It is expected that 26 weeks of treatment with ravulizumab will 
provide participants who respond to complement inhibition sufficient time to achieve reduction 
of proteinuria.  
The gold standard for measuring proteinuria is a complete 24-hr urine collection. 
Proteinuria is further justified in this Phase 2 study because of the role of active inflammation in 
both diseases leading to proteinuria as a clinical manifestation of active inflammation in the 
kidney. Ravulizumab has potent and rapid onset of anti-inflammatory effects that may be 
demonstrated through changes in proteinuria. Proteinuria may also result from irreversible 
scarring of renal tissue. Therefore, the presence of potentially reversible and active inflammatory 
kidney disease is ensured by requiring hematuria in participants with IgAN, and active class III 
or IV LN on kidney biopsy in participants with LN. Additionally, relatively preserved renal 
function with eGFR > 30 mL/min/1.73 m2 is required for both disease cohorts. 
4.2.2. 
Rationale for Key Secondary Endpoints 
Change in eGFR is a key secondary endpoint for both disease cohorts since it is considered a 
suitable surrogate marker for renal survival in clinical studies of glomerular diseases  
(Coresh, 2019).  
A key secondary endpoint for the LN cohort is CRR which predicts a beneficial prognosis and is 
often used in Phase 3 studies (KDIGO, 2021; Korbet, 2000; Pakchotanon, 2018; Chen, 2008). 
Some participants may not experience all components of CRR. Thus, additional secondary 
endpoints including the proportion of participants that achieve the individual components of 
CRR and PRR (Section 3.2.5) will be analyzed. Similarly, achievement of the CRR components 
may occur at different time points after study drug initiation. Thus, the time to achieve each 
CRR, PRR, the individual components, and UPCR < 0.5 g/g in participants will be evaluated to 
better characterize the potential benefit of ravulizumab treatment. Other secondary endpoints for 
the LN cohort aimed to provide additional characterization of ravulizumab treatment effect are 
described in Section 9.4.1.2.  
A key secondary endpoint for the IgAN cohort is the percentage of participants with Partial 
Remission as defined by mean proteinuria < 1 g/day on 2 valid 24-hr urine collections. 
Achievement of < 1 g/day proteinuria improves prognosis and is associated with kidney survival 

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through reduced risk of CKD progression to dialysis or transplant (Reich, 2007). Furthermore, 
proteinuria is an important risk factor in validated prediction tools used to stratify patients into 
risk categories and guide patient management (Barbour, 2019). 
4.3. 
Justification for Dose 
The ravulizumab dose regimen for the proposed study is based on the established PK-PD 
relationships that demonstrate the direct link between drug concentration and complement 
inhibition. Clinical studies of ravulizumab in PNH and aHUS have demonstrated the importance 
of maintaining concentration at the end of the dosage interval (Ctrough) above the established free 
C5-based PK threshold, and this target of complete terminal complement inhibition is expected 
to be necessary to achieve optimal efficacy in IgAN and LN. The proposed dosing regimen was 
identified using a modeling and simulation (M&S) framework previously used to support the 
approval of the PNH and aHUS indications for ULTOMIRIS (US Prescribing Information 
[USPI]). 
The proposed dosing regimen is modified from the approved dosing regimen in PNH and aHUS 
indications to account for the influence of the potential intrinsic factors, such as high levels of 
proteinuria and complement activation in renal pathology, on antibody PK. This is supported by 
the PK results from eculizumab clinical trials in idiopathic membranous glomerulopathy (IMG) 
patients with high proteinuria and rheumatoid arthritis (RA) patients with minimal proteinuria, 
confirming that patients with IMG had significantly lower drug levels at trough compared to RA 
patients at the same dosing regimen of 8 mg/kg eculizumab every 2 weeks (trough mean levels 
of approximately 18.5 µg/mL in participants with IMG versus 30 to 32 µg/mL in participants 
with RA) (Study C99-001 in RA and Study C99-004 in IMG). This observed impact of 
proteinuria on antibody PK is also in agreement with a clinical study of rituximab in 
membranous nephropathy with high proteinuria confirming that patients with membranous 
nephropathy exhibited a shorter half-life, decreased exposures, and increased antibody clearance 
compared to the reference patient populations (Fogueri, 2019). In a study of adalimumab in focal 
segmental glomerulosclerosis (FSGS) patients with proteinuria, a linear relationship was seen 
between increasing proteinuria and the increase in antibody clearance (Roberts, 2013). In light of 
this evidence demonstrating a relationship between proteinuria and antibody clearance, the 
results from M&S analysis show that the expected increase in ravulizumab clearance, based on 
mean proteinuria levels of approximately 3 to 4 g/day at baseline for participants in the study, 
may result in inadequate levels of C5 suppression in patients with ≥ 60 kg body weight using the 
labeled dosing regimen for PNH/aHUS. Therefore, an optimal dosing regimen should be 
identified to maintain immediate (after the loading dose), complete and sustained (throughout the 
entire active treatment course) terminal complement inhibition in all participants for the 
proposed study. 
The proposed dosing regimen presented in Table 8 was derived based on the established 
exposure-response relationships of ravulizumab Phase 3 studies, assuming an expected 30% 
higher clearance based on mean proteinuria levels of approximately 3 to 4 g/day at baseline for 
participants in the study. The PK simulations using the established population PK model of 
ravulizumab were conducted to identify maintenance doses to be the optimal population dose 
providing the majority of participants (defined as 97.5th percentile) with necessary PK coverage 
(ravulizumab trough concentrations > target threshold of 175 µg/mL) to achieve complete and 

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sustained terminal complement suppression, a level shown to be optimal for efficacy in PNH and 
aHUS Phase 3 studies. The impact of weight on exposure, namely higher exposures in lighter 
participants as compared to heavier participants, suggested the need for weight-based dosing, 
consistent with the labeled dosing regimen of ravulizumab for PNH/aHUS.  
As shown in Table 8, the loading regimen in this study for all 3 body weight categories is the 
same as the labeled regimen for aHUS/PNH. Further, the q8w maintenance regimen for 40 to 
< 60 kg participants is the same as the current labeled dose. Maintenance doses for participants 
in the 60 to < 100 kg and ≥ 100 kg body weight ranges are higher by 18% and 50%, respectively, 
than the currently labeled dosing regimen for PNH/aHUS. However, the exposures are predicted 
to be similar to those observed in Phase 3 studies due to the expected higher clearance. 
Ravulizumab IV has been tested at doses up to 5400 mg in Study ALXN1210-PNH-201 without 
demonstrating adverse findings, consistent with a large safety margin. In all cases, the predicted 
maximum (peak) serum concentration observed after study drug administration (Cmax) is 
estimated to be well below the highest observed Cmax for an individual patient in previous trials 
(ie, approximately 2680 μg/mL), even assuming no change in ravulizumab clearance due to 
proteinuria.  
Adequacy of the proposed dose regimen will be confirmed for adult participants with LN and 
IgAN through initial masked analysis of PK/PD data by an independent clinical pharmacologist 
in an initial cohort of participants with an option for dose adjustment for the subsequent 
participants (Section 9.5.1).   
4.4. 
Remote Visit Options in Times of Emergency 
To ensure participant safety and treatment continuity in times of emergency (eg, COVID-19 
pandemic), the following will apply where participants are not able to reach the study sites, and 
until participants are able to resume study visits at the site. 
Participants may have an opportunity to receive ravulizumab administration remotely at a 
medical facility that is located near the participant’s home with the permission of the Investigator 
in accordance with all national, state, and local laws or regulations of the pertinent regulatory 
authorities.  
Remote visit options may be at the Investigator’s discretion and oversight, in accordance with 
the local regulations, and conducted by a qualified medical professional. Remote visit options 
may include visits conducted at the participant’s home (excluding visits that require ravulizumab 
administration), an alternative qualified healthcare facility or virtually through phone or video 
conference. All assessments for the study visit day should be conducted according to the 
Schedule of Assessments (Section 1.3). Information about adverse events (AEs), concomitant 
medications, allowed concomitant therapies, and disease-related signs or symptomatology must 
be sent to the Investigator’s site for evaluation on the day of the remote visit. In case of any signs 
or symptoms indicating a serious adverse event (SAE) or Renal Flare, the participant will need to 
be evaluated at the study site. 

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4.5. 
End of Study Definition 
A participant is considered to have completed the study if they have completed all periods of the 
study including the last scheduled procedure shown in the Schedule of Activities (SoA) 
(Section 1.3). 
The end of the study is defined as the date of the last scheduled procedure shown in the SoA for 
the last participant in the study globally (Week 86, End of Study [EoS] Visit) (Section 1.3).  
 

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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.  
5.1. 
Inclusion Criteria 
To be eligible to participate in the study, participants in both cohorts must meet all of the below 
criteria. 
5.1.1. 
Common Inclusion Criteria for Both Cohorts 
Age  
1. Participant must be ≥ 18 and ≤ 75 years of age at the time of signing the informed 
consent. 
Weight 
2. Body weight ≥ 40 kg at Screening 
Sex 
3. Male or female 
Female participants of childbearing potential, male participants, and male participants 
with female partners of childbearing potential must follow protocol specified 
contraception guidance as described in Section 10.6   
Informed Consent 
4. Capable of giving informed consent as described in Section 10.1.3, which includes 
compliance with the requirements and restrictions listed in the ICF and in this protocol 
Vaccinations and Antibiotics  
5. To reduce the risk of meningococcal infection (N meningitidis), all participants must be 
vaccinated against meningococcal infection from serogroups A, C, W, Y, and B within 
3 years prior to, or at the time of, randomization according to national/local guidelines. 
Participants who do not meet this requirement will be vaccinated against meningococcal 
infection prior to randomization according to national/local guidelines and will receive 
prophylactic antibiotics for at least 2 weeks after meningococcal vaccination if 
randomization occurs < 2 weeks after initial vaccination.  
6. All participants must also receive vaccinations for Haemophilus influenzae type b (Hib) 
and Streptococcus pneumoniae prior to randomization, unless previously vaccinated, 
according to current national/local vaccination guidelines. 
Disease Characteristics 
7. Local pathology report from the biopsy used for diagnosis must be available 
(Section 8.1.5) 

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Prior/Concomitant Therapy 
8. Participants on sodium-glucose cotransporter-2 (SGLT-2) inhibitors (eg, empagliflozin) 
must be on a stable dose for ≥ 3 months with no planned change in dose during the study  
5.1.2. 
Inclusion Criteria Specific for LN Cohort 
Disease Characteristics 
9. Clinical diagnosis of SLE by 2019 ACR and EULAR criteria as outlined in Section 10.9  
10. Diagnosis of 2018 Revised ISN/RPS classification (Section 10.10) (active focal or diffuse 
proliferative LN Class III or IV confirmed by biopsy obtained ≤ 6 months prior to 
Screening or during Screening Period. Participants may co-exhibit Class V disease. 
Participants with de novo or relapsing disease may be eligible.  
11. Clinically active LN at Screening requiring/receiving immunosuppression induction 
treatment in the opinion of the Investigator 
12. Proteinuria with UPCR ≥ 1 g/g based on one 24-hour urine collection during the 
Screening Period (Section 8.2.1) 
5.1.3. 
Inclusion Criteria Specific for IgAN Cohort 
Disease Characteristics 
13. Established diagnosis of primary IgAN based on kidney biopsy obtained any time prior to 
or during the Screening Period  
14. Mean proteinuria ≥ 1 g/day on 2 complete and valid 24-hour urine collections during the 
Screening Period (Section 8.2.1) 
15. For participants with a kidney biopsy used for eligibility > 1 year prior to Screening: 
• Presence of hematuria as defined by a positive result on urine dipstick for blood or 
≥ 10 RBC/hpf microscopy on urine sediment as documented by the local laboratory. 
Presence of hematuria documented by the central laboratory may also be acceptable.    
16. Compliance with stable and optimal dose of RAS inhibitor treatment including maximum 
allowed or tolerated ACE inhibitor and/or angiotensin receptor blocker dose for 
≥ 3 months prior to Screening with no expected change in dose during the study 
(participants with established intolerance to RAS inhibitors may be included).  
17. Controlled and stable blood pressure over the past 3 months < 140/90 mmHg 
5.2. 
Exclusion Criteria  
5.2.1. 
Common Exclusion Criteria for Both Cohorts 
Participants from both cohorts are excluded from the study if any of the below criteria apply. 
Medical Conditions  
1. Estimated GFR < 30 mL/min/1.73 m2 during Screening calculated by Chronic Kidney 
Disease Epidemiology Collaboration (CKD-EPI)  

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2. For patients with eGFR < 45 mL/min/1.73 m2 at Screening, presence of any of the 
following in glomeruli on most recent kidney biopsy prior or during the Screening 
Period: 
a. ≥ 50% interstitial fibrosis and tubular atrophy  
b. ≥ 50% glomerular sclerosis 
c. ≥ 50% active crescent formation  
3. Concomitant significant renal disease other than LN or IgAN on the most recent biopsy 
prior to or during the Screening Period 
4. History of kidney transplant or planned kidney transplant during the Treatment Period  
5. History of other solid organ (heart, lung, small bowel, pancreas, or liver) or bone marrow 
transplant; or planned transplant during the Treatment Period  
6. Splenectomy or functional asplenia 
7. Institutionalization by administrative or court order or known medical or psychological 
condition(s) or risk factor that, in the opinion of the Investigator, might interfere with the 
participant’s full participation in the study, pose any additional risk for the participant, or 
confound the assessment of the participant or outcome of the study 
8. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to 
the start of the Screening Period 
9. History of malignancy within 5 years of Screening with the exception of nonmelanoma 
skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of 
recurrence 
10. Evidence of active hepatitis B infection (positive hepatitis surface antigen [HBsAg] or 
positive core antibody (anti-HBc) with negative surface antibody [anti-HBs]) or active 
hepatitis C viral infection (HCV antibody positive, except for patients with documented 
successful treatment and documented sustained virologic response [SVR]) at Screening  
11. Known history of human immunodeficiency virus (HIV) infection as documented by 
HIV-1/HIV-2 testing or positive HIV-1/HIV-2 antibody titer at Screening 
12. Bone marrow insufficiency with absolute neutrophil count < 1.3 x 103/μL; 
thrombocytopenia (platelet count < 50,000/mm3) 
13. Active systemic bacterial, viral, or fungal infection within 14 days prior to randomization 
14. History of N meningitidis infection 
15. Hypersensitivity to any ingredient contained in the study drug, including hypersensitivity 
to murine proteins or inability to take or tolerate the standard of care allowed concomitant 
therapies (Section 6.5), with the exception of RAS inhibitors for the IgAN cohort (IC 16). 
Prior/Concomitant Therapy 
16. Received biologic, including but not limited to belimumab or rituximab, ≤ 6 months prior 
to Screening 
17. Previously received a complement inhibitor (eg, eculizumab) at any time 

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Prior/Concurrent Clinical Study Experience  
18. Participation in another investigational drug or investigational device study within 
30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that 
investigational product, whichever is greater 
Other Exclusions  
19. Pregnant, breastfeeding, or intending to conceive during the course of the study 
5.2.2. 
Exclusion Criteria Specific for LN Cohort  
20. Participants who have initiated any of the following treatments for the current active LN 
flare: 
a. Cyclophosphamide ≤ 6 months prior to Screening  
b. Calcineurin inhibitors ≤ 3 months prior to Screening 
c. A cumulative dose of IV methylprednisolone > 3 g   
d. Mycophenolate mofetil > 2 g/day (or equivalent) for ≥ 4 consecutive weeks prior to 
Screening 
e. Oral corticosteroids ≥ 0.5 mg/kg/day for ≥ 4 consecutive weeks prior to Screening   
21. Uncontrolled hypertension (systolic blood pressure > 160 or diastolic blood pressure 
> 110 mmHg) on 2 or more measurements during the Screening Period 
22. Clinically active SLE-related cerebritis, seizures, pericarditis, stroke, or stroke syndrome 
requiring treatment 
5.2.3. 
Exclusion Criteria Specific for IgAN Cohort 
23. Diagnosis of rapid progressive glomerulonephritis as measured by eGFR loss ≥ 30% over 
a period of 3 months prior to or during the Screening Period 
24. Secondary etiologies of IgAN (eg, SLE, cirrhosis, celiac disease) 
25. Clinically active Henoch-Schonlein purpura (IgA vasculitis) requiring treatment 
26. Prednisone or prednisone equivalent > 20 mg/day for > 14 consecutive days or any other 
systemic immunosuppression for the treatment of IgAN ≤ 6 months prior to Screening  
27. Blood pressure of ≥ 140/90 mmHg during the Screening Period confirmed on 2 measures 
> 30 minutes apart 
28. Body mass index ≥ 38 kg/m2 
5.3. 
Lifestyle Considerations 
There is no lifestyle restriction for this study.  
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently treated with ravulizumab or are not randomized to either treatment group. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants to meet the Consolidated Standards of Reporting Trials (CONSORT) 

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publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details (eg, failed eligibility criteria), and any 
AEs, including any SAEs and any AEs related to concomitant medication, occurring during the 
Screening Period. 
Individuals who do not meet the criteria for participation in this study (screen failure) due to a 
reason that is expected to resolve or has resolved, may be rescreened up to a maximum of 1 time 
based on discussion and agreement between the Investigator and the Medical Monitor. If a 
potential participant is rescreened outside the 6-week Screening Period, then all Screening 
assessments and procedures must be repeated.  

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6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to the 
study protocol. 
For this study, the study intervention will include the administration of study drug (ravulizumab 
or placebo) in addition to allowed concomitant therapy consistent with the standard of care. 
6.1. 
Study Intervention(s) Administered  
Ravulizumab is formulated at pH 7.0 and is supplied in 30 mL single-use vials. Each vial of 
ravulizumab contains 300 mg of ravulizumab (10 mg/mL) in 10 mM sodium phosphate, 150 mM 
sodium chloride, 0.02% polysorbate 80, and water for injection. The comparator product 
(placebo) is formulated as a matching sterile, clear, colorless solution with the same buffer 
components, but without active ingredient. Additional details are presented in Table 7.  
Table 7: 
Study Intervention(s) Administered 
Study Drug Name 
Ravulizumab 
Placebo 
Dose formulation 
Vial 
Vial 
Physical 
description 
Liquid solution practically free from 
particles 
Liquid solution practically free from 
particles 
Unit dose 
Strength(s) 
300 mg (10 mg/mL concentrated 
solution) 
Placebo 
Route of 
administration 
IV infusion 
IV infusion 
IMP or 
NIMP/AxMP 
IMP 
IMP 
Use 
Experimental 
Placebo comparator 
Abbreviations: AxMP = auxiliary medicinal product; IMP = investigational medicinal product; IV = intravenous; 
NIMP = non-investigational medicinal product  
The dosing regimen (Table 8) consists of a loading dose followed by maintenance dosing 
administered q8w. The maintenance dosing will be initiated 2 weeks after the loading dose 
administration. 
Weight-based dosing will be based on the participant’s body weight recorded at the day of the 
infusion visit. If the weight at the day of the infusion cannot be obtained, the weight recorded 
during the most recent prior study visit may be used. 

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Table 8: 
Weight-based Doses of Ravulizumab 
Body Weight Range (kg)a 
Loading Dose (mg) 
Maintenance Dose (mg) 
≥ 40 to < 60 
2400 
3000 
≥ 60 to < 100 
2700 
3900 
≥ 100 
3000 
5400 
a  Dose regimen will be based on the last recorded study visit body weight. If the study drug is prepared the night 
before a visit, the weight from the most recent study visit should be used. 
At the scheduled dosing visits (Section 1.3), study drug should be administered after all other 
tests and procedures have been completed, excluding the postdose sample collections 
(PK/PD/biomarkers). 
During the Initial Evaluation Period (Day 1 through Week 26), participants in each cohort will be 
randomized 2:1 to receive blinded doses of ravulizumab or placebo. 
• Ravulizumab group: participants will receive a blinded loading dose of ravulizumab 
via IV infusion on Day 1, followed by a blinded maintenance dose at Week 2 then 
q8w thereafter through the end of the Initial Evaluation Period 
• Participants in the placebo group will receive a blinded matching placebo dose via IV 
infusion on Day 1, followed by a blinded matching placebo dose at Week 2, then q8w 
thereafter through the end of the Initial Evaluation Period. 
During the Extension Period (Week 26 through Week 50), participants in the LN cohort will 
continue on the same maintenance regimen. In the IgAN cohort, participants in the placebo 
group will switch to receive a blinded loading dose of ravulizumab at Week 26 and participants 
in the ravulizumab group will receive a blinded ravulizumab dose of 900 mg at Week 26. 
Starting at Week 28, all participants in the IgAN cohort will receive open-label weight-based 
doses of ravulizumab (Table 9) q8w until the end of the Extension Period. 
 

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Table 9: 
Reference Chart for Weight-Based Dosing in IgAN Cohort 
Study Period 
Ravulizumab or 
Placebo Dosing 
Body Weight 
(kg)a 
Ravulizumab 
Dose  
(mg) 
Ravulizumab 
Volume 
(mL) 
Placebo 
Volume 
(mL) 
Diluent (0.9% 
Sodium 
Chloride) 
Volume (mL) 
Total 
Volume  
(mL) 
Ravulizumab Group 
Initial Evaluation 
Period 
Loading dose 
(Day 1) 
 
≥ 40 to < 60 
2400 
240 
0 
240 
480 
≥ 60 to < 100 
2700 
270 
0 
270 
540 
≥ 100 
3000 
300 
0 
300 
600 
Maintenance dose 
(Days 15, 71, 127) 
≥ 40 to < 60 
3000 
300 
0 
300 
600 
≥ 60 to < 100 
3900 
390 
0 
390 
780 
≥ 100 
5400 
540 
0 
540 
1080 
Extension Period 
Blinded doseb 
(Day 183) 
≥ 40 to < 60 
900 
90 
150 
240 
480 
≥ 60 to < 100 
900 
90 
180 
270 
540 
≥ 100 
900 
90 
210 
300 
600 
Maintenance dose 
(Days 197 to 351 
q8w) 
≥ 40 to < 60 
3000 
300 
0 
300 
600 
≥ 60 to < 100 
3900 
390 
0 
390 
780 
≥ 100 
5400 
540 
0 
540 
1080 
Placebo Group 
≥ 40 to < 60 
0 
0 
240 
240 
480 

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Table 9: 
Reference Chart for Weight-Based Dosing in IgAN Cohort 
Study Period 
Ravulizumab or 
Placebo Dosing 
Body Weight 
(kg)a 
Ravulizumab 
Dose  
(mg) 
Ravulizumab 
Volume 
(mL) 
Placebo 
Volume 
(mL) 
Diluent (0.9% 
Sodium 
Chloride) 
Volume (mL) 
Total 
Volume  
(mL) 
Ravulizumab Group 
Initial Evaluation 
Period 
Loading dose 
(Day 1) 
≥ 60 to < 100 
0 
0 
270 
270 
540 
≥ 100 
0 
0 
300 
300 
600 
Maintenance dose 
(Days 15, 71, 127) 
≥ 40 to < 60 
0 
0 
300 
300 
600 
≥ 60 to < 100 
0 
0 
390 
390 
780 
≥ 100 
0 
0 
540 
540 
1080 
Extension Period 
Blinded loading 
dosec 
(Day 183) 
≥ 40 to < 60 
2400 
240 
0 
240 
480 
≥ 60 to < 100 
2700 
270 
0 
270 
540 
≥ 100 
3000 
300 
0 
300 
600 
Maintenance dose 
(Days 197 to 351, 
q8w) 
≥ 40 to < 60 
3000 
300 
0 
300 
600 
≥ 60 to < 100 
3900 
390 
0 
390 
780 
≥ 100 
5400 
540 
0 
540 
1080 
a  Dose regimen will be based on the participant’s most recently recorded body weight. Contact the Alexion Medical Monitor if a participant’s weight drops 
below 40 kg during the study treatment period (Initial Evaluation Period or the Extension Period). 
b  Blinded dose on Day 183 (Week 26) for participants who were randomized to the ravulizumab group and are entering into the Extension Period. 
c  Blinded loading dose on Day 183 (Week 26) for participants who were randomized to the placebo group and are entering into the Extension Period. 
 

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6.2. 
Preparation/Handling/Storage/Accountability 
Upon arrival of the study drug at the study site, the study drug kits should be removed from the 
shipping container and stored in their original cartons under refrigerated conditions at 2°C to 8°C 
(35°F to 46°F) and protected from light. Study drugs should not be frozen. 
Study drugs must be stored in a secure, limited-access storage area with temperature monitored 
daily. 
Infusions of study drug should be prepared using aseptic technique. Ravulizumab and placebo 
need to be further diluted in a 1:1 ratio with 0.9% sodium chloride. Ravulizumab and placebo 
will be filtered with a 0.2 micron filter during infusion. 
• The Investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study drug received and any discrepancies are 
reported and resolved before use of the study drug. 
• Only participants enrolled in the study may receive the study drug and only 
authorized site staff may supply or administer the study drug. All study drug must be 
stored in a secure, environmentally controlled, and monitored (manual or automated) 
area in accordance with the labeled storage conditions with access limited to the 
Investigator and authorized site staff. 
• The Investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study drug accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
− This responsibility includes the reporting of any product complaints to 
productcomplaints@alexion.com within 1 business day. A product complaint is 
defined as any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, usability, safety, 
effectiveness, or performance of a product or clinical study material and/or its 
packaging components after it is has been released for distribution to an end 
customer that affects the performance of such product. 
− The pharmacist or other designated individual will maintain records of study 
intervention delivered to the study site, the inventory at the study site, the 
distribution to and use by each participant, and the return of materials to the 
Sponsor for storage or disposal/destruction of materials at the study site. These 
records should include dates, quantities, batch/serial numbers, expiration dates, 
in-clinic temperature log, and unique code numbers assigned to the study 
intervention and study participants. 
− The Investigator will maintain records that adequately document that the 
participants were administered the correct study treatment kits and reconcile the 
products received from the drug dispensing center. Investigational product will 
not be returned to the Sponsor or disposed of until accountability has been fully 
monitored. 
• Further guidance regarding preparation, handling, storage, accountability and final 
disposition of unused study drug is provided in the Pharmacy Manual. 

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6.3. 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1. 
Randomization 
Participants will be randomized on Day 1 after the Investigator has verified that they are eligible. 
All eligible participants will be randomly assigned to ravulizumab or placebo in a 2:1 ratio using 
Interactive Response Technology (IRT).  
To balance the effects of potential confounding factors between the ravulizumab and placebo 
arms, randomization will be stratified by whether corticosteroid induction treatment was initiated 
prior to Screening versus during the Screening Period for participants in the LN cohort and by 
mean proteinuria (1 to 2 g/day versus > 2 g/day) from 2 valid 24-hour urine collections during 
the Screening Period for participants in the IgAN cohort.  
6.3.2. 
Blinding 
Participants, all investigative site personnel, and any Alexion employee, or designee, directly 
associated with the conduct of the study will be blinded to participant treatment assignments 
during the Initial Evaluation Period. The blinding will be maintained by using identical study 
drug kits and labels for ravulizumab and placebo. The placebo will have an identical appearance 
to that of ravulizumab. The randomization code will be maintained by the IRT provider. 
The primary endpoint evaluation will occur for each disease-specific cohort after all participants 
in the disease-specific cohort complete the Week 26 Visit or withdrawn from the study prior to 
Week 26. Alexion will be unblinded at this time to conduct the primary analysis.  
After completion of the Initial Evaluation Period, participants in the LN cohort will continue 
receiving their randomized study drug and both the participants and the investigative site 
personnel will remain blinded for the remaining 24-week Extension Period. For the IgAN cohort, 
participants in the placebo group will switch to receive a blinded loading dose of ravulizumab 
after completion of the protocol-required assessments at the Week 26 Visit and participants in 
the ravulizumab group will receive a blinded ravulizumab dose of 900 mg at Week 26. The 
900 mg dose at Week 26 was chosen to ensure maintenance of complete C5 inhibition until the 
next scheduled maintenance dose. Following completion of the Week 26 Visit, participants in the 
IgAN cohort will receive open-label ravulizumab treatment during the 24-week Extension 
Period. 
In case of an emergency, the Investigator has the sole responsibility for determining if 
unblinding of a patient’s intervention assignment is warranted. Patient safety must always be the 
first consideration in making such a determination. If the Investigator decides that unblinding is 
warranted, the Investigator will be able to unblind the patient’s treatment allocation directly 
using the IRT. If a patient’s intervention assignment is unblinded, the Sponsor 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, as applicable. 
When an AE is unexpected or related and serious, the blind will be broken for that specific 
participant only. The blind will be maintained for persons responsible for the ongoing conduct of 
the study (such as the management, monitors, Investigators, etc) and those responsible for data 
analysis and interpretation of results, such as biometrics personnel.  

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Unblinded information will only be accessible to those who need to be involved in the safety 
reporting to Health Authorities, Independent Ethics Committees (IECs), and/or Institutional 
Review Boards (IRBs). 
Any participant who is unblinded during the Initial Evaluation Period will be withdrawn from the 
study.  
Investigators will receive only blinded information unless unblinded information is judged 
necessary for safety reasons. 
6.4. 
Study Drug Compliance 
During this study, participants in both cohorts will receive all study drug infusions under the 
supervision of the Investigator, or designee.  
The date and time of each dose administered will be recorded in the source documents and in the 
CRFs.  
The dose of study drug and study participant identification will be confirmed at the time of 
dosing by a member of the study site staff other than the person administering the study drug. 
6.5. 
Allowed Concomitant Therapy 
Information regarding prior use of disease-specific treatment, including immunosuppression 
induction treatment for participants in the LN cohort, and ACE inhibitors and/or ARBs for 
participants in the IgAN cohort, will be documented in CRF. 
All information regarding allowed concomitant treatment during the study will be documented in 
CRF. 
6.5.1. 
Allowed Concomitant Therapy for LN Cohort 
During the course of the study, participants in the LN cohort will receive allowed concomitant 
therapy consistent with the standard of care for induction and maintenance treatment of LN.  
• For participants who have not started corticosteroid induction treatment prior to 
Screening: 
− Participants will receive a cumulative dose of 1 gram of methylprednisolone IV 
administered in 1 or multiple divided doses or oral equivalent during the 
Screening Period (prior to Day 1). 
− During the Screening Period and no later than Day 2, all participants will receive 
oral corticosteroids with prednisone or prednisone equivalent with starting doses 
as outlined in Table 10. The starting minimum and maximum dose allowed are 
30 mg/day and 60 mg/day, respectively. A corticosteroid taper will commence on 
Week 2 (Day 14). From Week 12 to Week 26, the target dose is 7.5mg/day. 
Following Week 26, participants may remain on 7.5 mg/day or continue to taper 
at the clinical discretion of the Investigator until Week 46. From Week 46 to 
Week 50, the dose of corticosteroids must not be changed.  
− During the Screening Period and no later than Day 1, participants will receive a 
cumulative dose of 1 to 1.5 g/day of MMF any time after completion of the IV 

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methylprednisolone during the Screening Period and no later than Day 1. The 
dose can be administered in multiple divided doses. Participants will continue to 
receive 1 to 1.5 g/day for 1 week.  
− After receiving 1 to 1.5 g/day for 1 week, the dose will be increased per the 
discretion of the Investigator to a cumulative dose of 2 to 3 g/day of MMF no 
later than by Week 4 (Day 28). The dose can be administered in multiple divided 
doses. Participants will continue to receive 2 to 3 g/day of MMF until Week 50 
after which it may be decreased or discontinued based on the Investigators’ 
judgment and the Kidney Disease Improving Global Outcomes (KDIGO) clinical 
practice guidelines (KDIGO, 2021). 
• For participants who have initiated corticosteroid induction treatment prior to 
Screening and do not meet Exclusion Criterion 20 (Section 5.2.2):  
− If the participant already received methylprednisolone IV ≥ 1 g or equivalent and 
is receiving MMF ≥ 2 g/day prior to Screening, then methylprednisolone IV will 
not be given. The participant may continue the current MMF dose during 
Screening and during the treatment period the dose of MMF should be adjusted to 
achieve 2 to 3 g/day no later than Day 28 (4 Weeks). MMF will be continued at 2 
to 3 g/day until Week 50, after which it may be decreased or discontinued based 
on the Investigator’s judgment and the KDIGO clinical practice guidelines  
(KDIGO, 2021).  
− If the participant already received methylprednisolone IV ≥ 1 g or equivalent and 
is receiving MMF < 2 g/day prior to Screening, then methylprednisolone IV will 
not be given and the MMF dose will be increased during the Screening Period (no 
later than Day 1) to a cumulative dose of 1 to 1.5 g/day. Participants will continue 
to receive 1 to 1.5 g/day for 1 week after which the MMF dose will be increased 
per the discretion of the Investigator to 2 to 3 g/day to be achieved no later than 
Week 4 (Day 28). These doses can be administered in multiple divided doses. 
Participants will continue to receive 2 to 3 g/day until Week 50, after which it 
may be decreased or discontinued based on the Investigator’s judgment and the 
KDIGO clinical practice guidelines (KDIGO, 2021).  
− If a participant is already receiving prednisone or prednisone equivalent, the dose 
will be continued until Day 2 at which time prednisone or prednisone equivalent 
should be administered (the minimum and maximum dose allowed are 30 mg/day 
and 60 mg/day, respectively) as outlined in Table 10. The prednisone dose will be 
tapered starting on Week 2 (Day 14) according to the schedule. From Week 12 to 
Week 26, the target dose is 7.5 mg/day. Following Week 26, participants may 
remain on 7.5 mg/day or continue to taper at the clinical discretion of the 
Investigator until Week 46. From Week 46 to Week 50, the dose of 
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Table 10: 
Corticosteroid Taper for Participants With Lupus Nephritis 
 
Prednisone or Equivalent Dose (mg/day) According to Baseline Body Weight 
Study week 
40 to 60 kg 
61 to 80 kg 
81 to 100 kg 
> 101 kg 
Screening to 
Week 2a 
30 
40 
50 
60 
2 
25 
35 
40 
50 
4 
25 
30 
30 
40 
6 
20 
25 
20 
30 
8 
15 
20 
15 
20 
10 
10 
15 
10 
10 
12 b 
7.5 
7.5 
7.5 
7.5 
a The minimum and maximum starting doses of prednisone are 30 mg and 60 mg, respectively.  
b From Week 12 to Week 26, the target dose is 7.5 mg/day. Following Week 26, participants may remain on 
7.5 mg/day or continue to taper at the clinical discretion of the Investigator until Week 46. From Week 46 to 
Week 50, the dose of corticosteroids must not be changed. 
Other considerations regarding MMF dosing: 
• An equivalent dose of enteric-coated mycophenolic acid sodium (MPS) may be used 
instead of MMF (ie, 360 mg dose MPS is equivalent to a 500 mg dose of MMF) 
• Investigators may adjust the dosage of MMF due to tolerance or AEs. After the 
symptoms resolve, the Investigator should attempt to increase MMF (or equivalent) to 
the goal level. If symptoms return, then the participant should be continued on the 
highest tolerable dose.  
• Any changes to the dose of MMF and the justification will to be documented in the 
CRF. 
Other considerations regarding the corticosteroid taper: 
• All participants will have a scheduled corticosteroid taper starting on Day 14. 
Participants will reduce their prednisone dose according to their baseline body weight 
over 10 weeks until the dose is 7.5 mg/day by Week 12 (Table 10). From Week 12 to 
Week 26, the target dose is 7.5 mg/day. Following Week 26, participants may remain 
on 7.5 mg/day or continue to taper at the clinical discretion of the Investigator until 
Week 46. From Week 46 to Week 50, the dose of corticosteroids must not be 
changed. 
• Deviations from the scheduled corticosteroid taper for any reason other than Renal 
Flare or Extrarenal SLE Flare will confound interpretation, so every attempt should 
be made to adhere to the tapering schedule.  
• If disease is too clinically active in the opinion of the Investigator to begin the 
corticosteroid taper after Week 2, then the participant may continue to receive his or 
her initial corticosteroid dose for up to an additional 28 days. Similarly, participants 
who have started the taper and whose disease is too clinically active to continue 

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tapering, may remain at the same taper dose achieved for up to an additional 28 days. 
Failure to achieve the corticosteroid taper by Week 12 will not be considered as 
Treatment Failure and will be captured as a secondary endpoint. 
• However, the prednisone dose may NOT be increased beyond the taper dose achieved 
unless participant meets the protocol-defined criteria for Renal Flare (Section 3.2.1) 
and/or Severe Extrarenal SLE Flare (Section 3.2.2) in which case these participants 
will receive additional standard of care therapy and will be included as Treatment 
Failures. 
6.5.2. 
Allowed Concomitant Therapy for IgAN Cohort 
The allowed concomitant therapies for participants in the IgAN cohort will be consistent with 
standard of care and include the maximally tolerated dose of RAS-blocking agents, such as ACE 
inhibitors or ARBs.  
The allowed concomitant treatment should be held stable throughout the Treatment Period of the 
study.  
6.6. 
Additional Standard of Care Therapy for LN Cohort 
Participants in the LN cohort will receive additional standard of care therapy in the event of a 
protocol-defined Renal Flare (Section 3.2) or Severe Extrarenal SLE Flare (Section 3.2.2). 
Additional standard of care therapy is defined as intensification of current standard of care or 
introduction of new immunosuppressive therapies. After Week 26, additional standard of care 
therapy for participants with Suboptimal Response (Section 3.2.3) is allowed at the clinical 
discretion of the Investigator in conversation with the Medical Monitor. 
The specific choice of additional standard of care therapy(ies) is generally at the discretion of the 
Investigator and may include approved medications for LN (eg, voclosporin, belimumab).  
The following guidelines for corticosteroid dosing for protocol-defined Renal Flare and Severe 
Extrarenal SLE Flares should be considered to maintain treatment consistency: 
• Participants with protocol-defined Renal Flare may be treated with prednisone up to 
0.5 mg/kg/day (not to exceed 60 mg/day) for up to 2 weeks. Prednisone will then be 
tapered weekly to 10 mg/day within 6 weeks after the initial prednisone increase. 
Prednisone may further be tapered to ≤ 7.5 mg/day at the discretion of the 
Investigator. 
• Participants with Severe Extrarenal SLE flare may be treated with prednisone up to 
1 mg/kg/day (not to exceed 60 mg/day) for up to 2 weeks. Prednisone will then be 
tapered every 2 weeks to achieve 7.5 mg/day within 12 weeks after the initial 
corticosteroid increase.  
• Intravenous corticosteroids in equivalent doses may be allowed if gastrointestinal 
involvement temporality precludes oral corticosteroid use. 
Prednisone ≥ 10 mg for ≤ 14 days will not be considered additional standard of care therapy in 
the following instances: 

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• Renal flares not meeting the protocol defined criteria for Renal Flare (see 
Section 3.2.1) 
• Mild and non-severe Extrarenal SLE flares (see Section 3.2.2)  
• Other medical conditions or surgery 
The use of additional standard of care therapy should be discussed directly between the 
Investigator and Medical Monitor. 
Additional standard of care therapy will be documented in the participant’s CRF according to the 
CRF completion guidelines with the indication entered as “Renal Flare”, “Severe Extrarenal SLE 
Flare”, or “Suboptimal Response.” 
6.7. 
Concomitant Therapy 
6.7.1. 
Allowed Medications and Therapies 
Any medication or therapy (including over-the-counter or prescription medicines, vaccines, 
vitamins, and/or herbal supplements) deemed necessary for the participant’s care during the 
study, or for the treatment of any AE, along with any other medications, other than those listed as 
disallowed medications in Section 6.7.2, may be given at the discretion of the Investigator. 
However, it is the responsibility of the Investigator to ensure that details regarding the 
medication are recorded on the CRF (Section 8.5.2).  
If adequate blood pressure control is not achieved during the study, participants may receive 
additional antihypertensive agents, but not agents that affect proteinuria during the study. It is 
recommended that nonsteroidal anti-inflammatory drugs (NSAIDs) not be initiated during the 
study due to the possibility of adverse effects on renal function. They may be used, however, if 
necessary for the control of symptoms. 
For participants in the LN cohort:  
• Pneumocystis pneumonia prophylaxis is allowed at the discretion of the Investigator. 
• Treatment with antimalarial agents such as hydroxychloroquine are strongly 
recommended unless contraindicated. 
• Measures to prevent and treat osteoporosis are strongly encouraged during the study; 
these measures may include any, or all, of the following: calcium carbonate or citrate, 
Vitamin D, and bisphosphonates. 
• Immunosuppressive drugs for additional standard of care therapy are allowed. 
6.7.2. 
Disallowed Medications and Therapy 
Participants in both cohorts are prohibited from receiving any of the following medications and 
therapies during the entire duration of study participation: 
• Experimental interventions or therapies 
• Eculizumab  

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• New use or modification of the dose of SGLT-2 inhibitors and direct renin 
antagonists  
• New use or modification of the dose of RAS inhibitor treatment 
In the event that a participant receives a prohibited medication and/or therapy, the participant 
should discontinue study drug (Section 7.1) with the exception of SGLT-2 inhibitors and direct 
renin antagonists (SGLT-2 inhibitors and direct renin antagonists are prohibited but may not 
require discontinuation of study drug based on the discussion and approval of the Investigator 
and Medical Monitor). 
Participants in the IgAN cohort are also prohibited from receiving any of the following 
medications and therapies during the entire duration of study participation: 
• Hydroxychloroquine  
• Immunosuppressive agents (eg, MMF) 
• Systemic corticosteroids for > 14 consecutive days (short-term steroid course for 
≤ 14 days for medical conditions not related to IgAN or surgery are permitted) 
6.8. 
Dose Modification 
Dose modification of the study drug for an individual participant is not permitted for this study.  
The adequacy of the dosing regimen will be confirmed through interim analysis of PK/PD data 
as described in Section 9.5.1. If the initial dosing regimen does not result in the anticipated 
PK/PD data, the dosing regimen may be modified for subsequent participants according to 
PK/PD data.  
6.9. 
Intervention After the End of the Study 
After a participant completes the Treatment Period (ie, end of Extension Period) or withdraws 
from the study, study drug will not be administered.  

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Drug 
A participant has the right to discontinue study drug at any time.  
Participants must permanently discontinue the study drug for any of the following reasons: 
• Serious hypersensitivity reaction 
• Severe uncontrolled infection 
• Serious infusion reaction (such as bronchospasm with wheezing or requiring 
ventilator support or symptomatic hypotension, refer to Section 10.4) or serum 
sickness-like reactions manifesting 1 to 14 days after drug administration 
• Use of disallowed medication as defined in Section 6.7.2 
• Pregnancy or planned pregnancy 
• Participant is unblinded during the Initial Evaluation Period 
In addition, the study drug may be permanently discontinued for any of the following reasons: 
• Adverse event that would, in the opinion of the Investigator, make continued 
participation in the study an unacceptable risk 
• Deviation(s) from the protocol 
• Significant non-compliance 
• Alexion or the Investigator deems it is necessary for the participant 
• Study termination 
The reason for discontinuation of study drug will be recorded in the source documents and CRF. 
If the study drug is definitively discontinued, every effort should be made to have the participant 
continue the study visits as per the SoA through Week 50/EoS. If a participant discontinues study 
drug due to an AE, including SAEs, the event should be followed as described in Section 10.3.3. 
Participants who discontinue study drug and remain on study may receive treatment consistent 
with local standard practice for their disease per Investigator judgment, as applicable.  
If the participant does not agree to continue with the study visits, the following activities should 
be completed: 
• Early Discontinuation Visit should be performed as outlined in the SoA (Section 1.3). 
• A Follow-up Phone Call will be performed 8 weeks following the participant’s last 
dose of study drug to collect information on concomitant medications, 
nonpharmacological therapies and procedures, and AEs. 

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7.2. 
Participant Withdrawal From the Study  
• All efforts should be made to ensure participants are willing to comply with study 
participation prior to conducting the screening procedures.  
• The study staff should notify Alexion and their site monitor of all study withdrawals 
as soon as possible. The reason for participant withdrawal must be recorded in the 
source documents and CRF. 
• A participant may withdraw from the study at any time at his/her own request, or may 
be withdrawn at any time at the discretion of the Investigator for safety, behavioral, 
compliance, or administrative reasons.  
• At the time of study withdrawal, an Early Discontinuation (ED) Visit should be 
conducted, whenever possible, per the Schedule of Assessments (Section 1.3). A 
Safety Follow-up Phone Visit should be conducted at least 8 weeks after the final 
dose of study drug to collect information on any AEs and concomitant medications. 
• The participant will be permanently discontinued from the study drug at the time of 
study withdrawal. 
• If the participant withdraws consent for disclosure of future information, Alexion may 
retain and continue to use any data collected before such a withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the Investigator must document this in the source 
records. 
7.3. 
Lost to Follow-up 
A participant 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 participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the Investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered lost to 
follow-up.  
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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol 
waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the Medical Monitor 
immediately upon occurrence or awareness to determine if the participant should 
continue or discontinue study drug. 
• Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), is essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log 
to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of the ICF may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the time frame defined in the SoA.  
8.1. 
General Assessments and Procedures 
8.1.1. 
Informed Consent 
The Investigator or qualified designee must obtain a signed and dated ICF for each participant 
prior to conducting any study-related procedures. The process for informed consent is outlined in 
Section 10.1.3. All efforts should be made to ensure participants are willing to comply with study 
participation prior to conducting the screening procedures. 
8.1.2. 
Inclusion/Exclusion Criteria 
All inclusion (Section 5.1) and exclusion (Section 5.2) criteria must be reviewed by the 
Investigator or qualified designee to ensure the participant qualifies for study participation. The 
Investigator will maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable. 
8.1.3. 
Demographics  
Demographic parameters, including age, sex, race, and ethnicity will be documented in the CRF. 
8.1.4. 
Medical History 
The participant’s relevant medical history, including prior and concomitant conditions/disorders, 
treatment history, disease status (naïve vs relapse) if available (LN cohort only), and family 
history of relevant diseases will be evaluated at Screening by the Investigator and documented in 
the source documents and CRF. Any changes to medical history occurring during the Screening 
Period and prior to first dose of study drug on Day 1 will be documented prior to study drug 
administration.  

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8.1.5. 
Kidney Biopsy  
8.1.5.1. 
Screening Kidney Biopsy  
The diagnosis of LN and IgAN is based on a kidney biopsy obtained prior to or during the 
Screening Period. Eligibility will be determined using the local pathology report according to 
standardized globally recognized guidelines, as follows: 
• For participants in the LN cohort, kidney biopsies must have been obtained 
≤ 6 months prior to Screening or during the Screening Period; eligibility will be based 
on the ISN/RPS classification guidelines (Section 10.10). 
• For participants in the IgAN cohort, kidney biopsies may have been obtained any 
time prior to Day 1 (Section 10.11; Haas, 1997; Trimarchi, 2017).  
The local pathology report must be entered in the CRF during Screening according to the CRF 
completion guidelines. In particular, the degree of IgG, IgA, immunoglobulin M (IgM), C3, and 
C1q (both cohorts); the activity score/class (LN cohort only); and the mesangial and 
endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and the 
presence of crescents (MEST-C) score (IgAN cohort only), will be obtained from the local 
pathology reports, if available, and documented in the CRF. 
8.1.5.2. 
Kidney Biopsy During Study 
Kidney biopsies may be performed any time during the study at the discretion of the Investigator 
for renal flare or other indications.  
For participants in the LN cohort, a repeat biopsy at the end of the Extension Period (Week 50) 
will be optional and may be performed up to Week 54.  
8.1.5.3. 
Central Pathology Laboratory  
A Central Pathology Laboratory will be used to confirm the diagnosis on the kidney biopsy used 
for eligibility to minimize interpersonal variation in histological scoring. The Central Pathology 
Laboratory will be blinded to treatment allocation. 
The Central Pathology Laboratory will review: 
• All kidney biopsies used for eligibility for participants in the LN cohort 
• Kidney biopsies performed within 1 year of Screening or during Screening for 
participants in the IgAN cohort 
• All kidney biopsies performed during the study any time prior to ED or completion of 
the Extension Period (Week 50)  
The following should be sent to the Central Pathology Laboratory as soon as feasible according 
to the instructions in the Central Pathology Laboratory Manual.  
• Copy of the local pathology report  
• All light microscopy slides (Hematoxylin and eosin stain [H/E], Periodic acid–Schiff, 
Jones & Trichrome stains)  

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• If available, unstained microscopy slides of the kidney biopsy should also be sent to 
the Central Pathology Laboratory for exploratory analyses of biomarkers 
(Section 8.8.3). The site should send all available unstained slides, up to a maximum 
of 8 slides. 
Every effort should be made to obtain the microscopy slides from the site pathology laboratory 
and ship them to the Central Pathology Laboratory. Upon confirmation with the Central 
Pathology Laboratory, the original biopsy slides from each participant will be returned to the 
study site as soon as possible. Unstained slides used for exploratory biomarker analyses will not 
be returned. If the shipment of microscopy slides to the Central Pathology Laboratory is 
prohibited due to local regulations, a slide scanner may be used to send digital images of the 
slides electronically, according to the instructions in the Central Pathology Laboratory Manual. 
8.1.6. 
Vaccination and Antibiotic Prophylaxis 
Due to its mechanism of action, the use of ravulizumab increases a participant’s susceptibility to 
meningococcal infection due to N meningitidis. To reduce the risk of infection, all participants 
must be vaccinated within 3 years prior to or at the time of the first infusion of study drug. 
Participants who have not been vaccinated prior to starting study drug for any reason, should 
receive appropriate prophylactic antibiotics prior to and for at least 2 weeks after vaccination. 
Vaccines against serotypes A, C, Y, W135, and B where available, are recommended in 
preventing the commonly pathogenic meningococcal serotypes. Participants must receive the 
complete primary vaccination series and be revaccinated if indicated according to current 
national vaccination guidelines. Vaccination may not be sufficient to prevent meningococcal 
infection. 
Participants should be administered prophylactic antibiotics for meningococcal infection until at 
least 2 weeks after vaccination if randomization occurs < 2 weeks after initial vaccination. 
Consideration should be given per official guidance and local practice on the appropriate use of 
prophylactic antibacterial agents. All participants should be monitored for early signs of 
meningococcal infection, evaluated immediately if infection is suspected, and treated with 
appropriate antibiotics, if necessary.   
To increase risk awareness and promote quick disclosure of any potential signs or symptoms of 
meningococcal infection experienced by the participants during the course of the study, 
participants will be provided a Participant Safety Card to carry with them at all times 
(Section 8.3.1). Additional discussion and explanation of the potential risks, signs, and 
symptoms will occur at specific time points as part of the review of the Participant Safety Card 
and throughout the study as described in the SoA. 
Meningococcal serogroups ACWY and B (where available) vaccinations are required during 
Screening for participants who do not meet criteria for previous vaccination. The vaccination 
series will be completed during the study according to national and local vaccination schedule 
guidelines. 
In participants with IgAN, every effort should be made to start the meningococcal vaccination 
series at least 14 days prior to randomization.  
All participants must also be vaccinated against Hib and S pneumoniae prior to randomization, 
unless previously vaccinated, according to current national/local vaccination guidelines.  

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Vaccination status and administration of any vaccines, including those for N meningitidis, Hib, 
and S pneumoniae will be recorded on the CRF. 
8.2. 
Efficacy Assessments 
8.2.1. 
24-hour Urine Collection 
For the determination of proteinuria, 24-hour urine collection will be obtained during Screening, 
Week 26, and Week 50, and will be analyzed by a central laboratory. In addition to protein, 
albumin, sodium, and creatinine will also be quantified in each of the 24-hour urine collections. 
Both UPCR as well as albumin to creatinine ratios (UACRs) will also be calculated in an aliquot 
of the 24-hour urine collection.  
Rigorous exercise and significant change in diet (in particular, salt intake) should be avoided 
within 48 hours before collection of 24-hour urine samples, whenever possible.  
The collection should be obtained prior to or > 7 days after biopsy procedures and prior to 
administration of ravulizumab or placebo on dosing days. 
The 24-hour urine collections could occur at the participant’s home by a mobile nurse if agreed 
upon with the Investigator and the participant, according to local regulations. The collection will 
be recorded in the CRF according to the CRF completion guidelines.  
LN Cohort 
For participants in the LN cohort, proteinuria will be measured by UPCR. A single 24-hour urine 
collection will be obtained at Screening to assess eligibility. Two separate 24-hour urine 
collections will be obtained within 2 weeks prior to the Week 26 Visit (to assess the primary 
endpoint) and Week 50 Visit (to assess a secondary endpoint). 
Confirmation of a protocol-defined Renal Flare or Suboptimal Response requires a single 
24-hour urine collection within 2 weeks of the spot urine sample (Section 3.2.1 and 
Section 3.2.3). 
IgAN Cohort 
Participants in the IgAN cohort will be required to provide 2 separate complete and valid 
24-hour urine collections during the Screening Period (to assess eligibility), at Week 26 (to 
assess the primary endpoint), and at Week 50 (to assess a secondary endpoint). The 2 valid 
24-hour urine collections should be obtained within 2 weeks before the Week 26 and Week 50 
Visits. 
Completeness of the 24-hour urine collection will be estimated from rate of creatinine excretion. 
Normal values of creatinine excretion vary with age and body weight. Hence, a 24-hour urine 
collection is considered valid if all the following criteria are met, otherwise the urine collection is 
required to be repeated:  
• The collection is between 22 to 26 hours in duration (ie, time from the initial 
discarded void to the last void/attempt to void). 
• No voids are missed between the start and end time of the collection as indicated by 
the participant’s urine collection diary. 

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• The 24-hour creatinine content is within 30% of expected range as estimated by the 
following formula: [(140-age) × weight]/5000, where weight is in kilograms. This 
result is multiplied by 0.85 in women (Ix, 2011).  
• The maximum variation in total 24-hour urine creatinine between the 2 urine 
collections must be ≤ 30%.  
Urine collections that deviate from the above criteria will be reviewed by the Medical 
Monitoring team and may be considered acceptable if determined to be not clinically significant. 
If any of the collections do not meet the validity criteria outlined above, the collection must be 
repeated as soon as possible within the time frames outlined in the SoA (Section 1.3) in order to 
ensure that 2 valid collections are obtained for each of the study time points. 
8.2.2. 
Spot Urine Sample 
Urinary protein, albumin, and creatinine levels from morning spot urine sample prior to dosing 
will also be measured during Screening and during the study per the SoA (Section 1.3) to assess 
the effect of ravulizumab on UPCR and UACR.  
Two consecutive spot urine samples will be obtained for participants in both disease cohorts at 
the Week 18 Visit.  
The spot urine sample should be obtained prior to or > 7 days after biopsy procedures and prior 
to administration of ravulizumab or placebo on dosing days. 
Spot urine samples conducted as routine standard of care will be used for UPCR during the 
Post-treatment Follow-up Period per the SoA (Section 1.3). The UPCR results will be recorded 
in the participant’s CRF. 
8.2.3. 
Estimated Glomerular Filtration Rate 
Changes in renal function will be monitored using measurements of eGFR (mL/min/1.73m2) and 
creatinine clearance on a 24-hour urine collection as outlined in the SoA (Section 1.3). The 
eGFR calculation will be based on the CKD-EPI formula for all participants using serum 
creatinine collected prior to study drug administration, if applicable. 
For the determination of CRR and PRR at Week 26 and Week 50, 2 serum creatinine samples 
will be obtained within 2 weeks prior to each of these study visits. The blood sample collection 
could occur at the participant’s home if agreed upon with the Investigator and the participant. 
The collection will be recorded in the CRF according to the CRF completion guidelines. 
The change from baseline in eGFR will be measured throughout the course of the study. In 
addition, the slope of eGFR will be computed through Week 26 and Week 50 for participants in 
the IgAN cohort.  
8.2.4. 
Hematuria 
For participants in both disease cohorts, hematuria from spot urine samples will be evaluated to 
assess the effect of ravulizumab on disease course. The degree of hematuria will be assessed by 
examination of the spun urine sediment by microscopy (RBC/hpf).  

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Single void collections for random spot urine sample for hematuria evaluation should be 
collected. If the Investigator determines that the hematuria is transient due to menses in women 
or exercise, the sample may need to be repeated. 
Random spot urine samples for hematuria measurement will be collected throughout the study as 
outlined in the SoA (Section 1.3) and will be analyzed by a central laboratory. On dosing days, 
samples should be collected prior to study drug administration, if applicable. 
The local hematuria evaluation by microscopy or urinary dipstick will be utilized to determine 
eligibility for the study at Screening for participants with IgAN. 
8.3. 
Safety Assessments 
8.3.1. 
Participant Safety Card  
Before the first dose of the study drug, a Participant Safety Card will be provided to participants 
to carry with them at all times until 8 months after the final dose of study drug. The card is 
provided to increase participant awareness of the risk of meningococcal infection and promote 
quick recognition and disclosure of any potential signs or symptoms of meningococcal infection 
experienced during the course of the study and to inform participants on what actions must be 
taken if they are experiencing signs or symptoms of infection. 
At each visit throughout the study, the study staff will ensure that the participant has the 
Participant Safety Card. 
8.3.2. 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessments of the 
following organs/body systems: skin, head, ears, eyes, nose, throat, neck, lymph 
nodes, chest, heart, abdomen, extremities, musculoskeletal, and neurological state 
(with emphasis on presence/degree of edema).  
• An abbreviated physical examination will include, at a minimum, a body-system 
relevant examination based upon Investigator judgment and participant symptoms. 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
• Additional physical examinations can be performed as medically indicated during the 
study at the Investigator’s discretion. 
• Height and weight will also be measured and recorded. 
8.3.3. 
Vital Signs and Pulse Oximetry 
• Temperature (°C or °F), heart rate, respiratory rate, systolic and diastolic blood 
pressure (mmHg), and pulse oximetry will be assessed. 
• Blood pressure and pulse measurements will be assessed with the participant in a 
seated position using a completely automated device. Manual techniques will be used 
only if an automated device is not available. 

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• Blood pressure and pulse measurements should be preceded by at least 5 minutes of 
rest for the participant in a quiet setting without distractions (eg, television, cell 
phones). Ideally, the same arm for each participant should be used for measurements. 
• Vital signs will be collected predose at study drug dosing visits.  
8.3.4. 
Electrocardiograms 
• Single 12-lead electrocardiogram (ECGs) will be conducted locally to obtain heart 
rate, PR, QRS, interval between the start of the Q wave and the end of the T wave in 
an ECG (QT), and corrected QT interval (QTc) intervals (QT interval will be 
corrected for heart rate using Fridericia’s formula [QTcF].)  
• Single 12-lead ECG will be performed at Screening, at the end of the Initial 
Evaluation Period (prior to dosing on Day 183), and at the end of the Extension 
Period (Day 351). For participants that discontinue study drug, an ECG should be 
performed at the ED Visit.  
• Participants must be supine for approximately 5 to 10 minutes before ECG collection 
and remain supine but awake during ECG collection. 
• The Investigator or Sub-investigator will be responsible for reviewing the ECG to 
assess whether the ECG is within normal limits and determine the clinical 
significance of the results.  
8.3.5. 
Clinical Safety Laboratory Assessments 
• All protocol-required laboratory assessments, as defined in Section 10.2, must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3). 
• The Investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the AE section of the 
CRF. The laboratory reports must be filed with the source documents. Clinically 
significant abnormal laboratory findings are those which are not associated with the 
underlying disease, unless judged by the Investigator to be more severe than expected 
for the participant’s condition. 
• All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 8 weeks after the last dose of study drug should be 
repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the Investigator or Medical Monitor. 
− If such values do not return to normal/baseline within a period of time judged 
reasonable by the Investigator, the etiology should be identified, and Alexion 
notified. 
− If laboratory values from non-protocol specified laboratory assessments 
performed at the institution’s local laboratory require a change in participant 
management or are considered clinically significant by the Investigator (eg, SAE 
or AE or dose modification), then the results must be recorded in the CRF.  

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8.3.5.1. 
Virus Serology 
Testing for HIV-1 and HIV-2 is required for all participants prior to enrollment. Participants who 
are HIV antibody positive will not be enrolled. 
Similarly, participants who are positive at the Screening Visit for HBsAg, anti-HBc with 
negative anti-HBs, or HCV antibody positive (except for participants with documented 
successful treatment and documented sustained viral response) will not be enrolled. 
8.3.6. 
Pregnancy 
Pregnancy testing must be performed on all women of childbearing potential (WOCBPs) at 
protocol-specified time points in the SoA (Section 1.3). Pregnancy tests (urine or serum) may 
also be performed at any time during the study at the Investigator’s discretion. 
A negative pregnancy test is required for WOCBPs before study drug administration. 
• Any female participant who becomes pregnant while participating in the study will be 
discontinued from the study drug.  
• If a pregnancy is reported, the Investigator must immediately inform Alexion within 
24 hours of awareness of the pregnancy and follow the procedures outlined in 
Section 10.6.3.  
• Details of all pregnancies in female participants and female spouses/partners of male 
participants will be recorded and the pregnancy followed to term and Alexion notified 
regarding the outcome, even if the participant discontinues the study drug or 
withdraws from the study. The corresponding infant must be followed-up with for 
3 months postpartum. 
• Pregnancy is not considered as an AE unless there is a suspicion that the study drug 
may have interfered with the effectiveness of a contraceptive medication. However, 
complications of pregnancy and abnormal outcomes of pregnancy are AEs and may 
meet the criteria for an SAE (eg, ectopic pregnancy, spontaneous abortion, 
intrauterine fetal demise, neonatal death, or congenital anomaly) (Section 10.3.2). 
Elective abortions without complications should not be reported as AEs.  
8.4. 
Adverse Events and Serious Adverse Events  
The definitions of AEs and SAEs can be found in Section 10.3. 
All AEs will be reported to the Investigator or qualified designee by the participant (or, when 
appropriate, by a caregiver, surrogate, or the participant’s legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study drug or study procedures, or that caused 
the participant to discontinue the study drug (see Section 7). 
Procedures for recording, evaluating, follow-up, and reporting AEs and SAEs are outlined in 
Section 10.3. 

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8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs (serious and nonserious) will be collected from the signing of the ICF until Week 86 or, 
if the participant discontinues study drug early, 8 weeks (56 days) after last dose of study drug is 
administered.  
All SAEs will be recorded and reported to Alexion or the designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.3. The Investigator will 
submit any updated SAE data to Alexion within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE data after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study drug or study participation, the Investigator must promptly notify Alexion. 
8.4.2. 
Method of Detecting AEs and SAEs  
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.3.  
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences.  
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow-up on each 
participant at subsequent visits/contacts. All SAEs will be followed up until resolution, 
stabilization, the event is otherwise explained, or the participant is lost to follow-up (as defined 
in Section 7.3). Further information on follow-up procedures is provided in Section 10.3. 
8.4.4. 
Regulatory Reporting Requirements for SAEs  
• Prompt notification of an SAE by the Investigator to Alexion is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the 
safety of a study intervention under clinical investigation are met. 
• Alexion has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. Alexion will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRBs/ IECs, and Investigators. 
• Alexion is required to submit individual suspected unexpected serious adverse 
reaction (SUSAR) reports (defined in Section 10.3.2) in the format of MedWatch 
3500 or CIOMS I Form and forwarded to Investigators as necessary. Consistent with 
Alexion policy and procedures for blinded clinical studies, these reports to 
Investigators will be blinded to treatment assignment. In limited circumstances, the 
blind may be broken in the case of urgent safety issues that could compromise 
participant safety. 
• An Investigator who receives an Investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from Alexion will 

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review and then file it along with the IB and will notify the IRB/IEC, if appropriate 
according to local requirements. 
• Under the EU CTR 536/2014, events other than SAEs (eg, unexpected events) that 
may impact the benefit-risk balance should be reported. See definitions in 
Section 10.3.5. 
8.4.5. 
Medication Error, Drug Abuse, and Drug Misuse 
Medication error, drug abuse, and drug misuse will be collected from signing of the applicable 
version of the ICF through the last scheduled procedure shown in the SoA (Section 1.3). 
8.4.5.1. 
Timelines 
If an event of medication error, drug abuse, or drug misuse occurs during the study, then the 
Investigator or other site personnel will report to Alexion or designee immediately but no later 
than 24 hours of when they become aware of it.  
The full definitions and examples of medication error, drug abuse, and drug misuse can be found 
in Section 10.5. 
8.4.5.2. 
Medication Error 
For the purposes of this clinical study a medication error is an unintended failure or mistake in 
the treatment process for a study intervention that either causes harm to the participant or has the 
potential to cause harm to the participant. 
8.4.5.3. 
Drug Abuse 
Drug abuse is the persistent or sporadic intentional, non-therapeutic excessive use of study 
intervention for a perceived reward or desired non-therapeutic effect. 
8.4.5.4. 
Drug Misuse 
Drug misuse is the intentional and inappropriate use of study intervention for medicinal purposes 
outside of the authorized product information, or for unauthorized study intervention, outside the 
intended use as specified in the protocol, including deliberate administration of the product by 
the wrong route. 
8.4.6. 
Adverse Events of Special Interest  
Meningococcal infections will be considered to be adverse events of special interest (AESIs). 
8.5. 
Review of Prior and Concomitant Medications and Procedures 
8.5.1. 
Prior Medications and Procedures 
Prior medications and/or vaccines (including vitamins, herbal preparations, and those discussed 
in the exclusion criteria [Section 5.2]) and procedures (any therapeutic drug, such as 
surgery/biopsy or physical therapy) that the participant takes or undergoes within 30 days before 
the start of Screening or during the Screening Period before the first dose of study drug, as well 

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as any meningococcal vaccine administered within the last 3 years, will be recorded in the 
participant’s CRF.  
For participants in the IgAN cohort: 
• ACE inhibitors and ARBs during 3 months prior to the first dose  
• Blood pressure medications received during the 3 months prior to the first dose  
Information regarding the prior use of disease-specific treatment will be recorded for both 
cohorts, including immunosuppression induction treatment for participants in the LN cohort.  
8.5.2. 
Concomitant Medications and Procedures 
Concomitant medications (including any medication, vitamin, herbal preparation or supplement) 
and procedures (defined in Section 6.7) are those received on or after the first study drug date 
(Day 1), including those started before Day 1 and continued after Day 1. At each study visit, 
participants should be questioned about any new medication or nondrug therapies or changes to 
concomitant medications and nondrug therapies since the last visit. Concomitant medications and 
nondrug therapies should be recorded in the source documents and the participant’s CRF 
including: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
Any concomitant medication deemed necessary for the participant’s care during the study, or for 
the treatment of any AE, along with any other medications, other than those listed as disallowed 
medications in Section 6.7.2, may be given at the discretion of the Investigator. However, it is 
the responsibility of the Investigator to ensure that details regarding all medications are recorded 
in full, in the participant’s source documents and CRF. 
Information regarding the use of disease-specific treatment received during the course of the 
study will be recorded in the source documents and the participant’s CRF, including: 
• For participants in the LN Cohort: 
− Additional standard of care therapy (Section 6.6) for protocol-defined Renal 
Flare, Severe Extrarenal SLE Flare, or Suboptimal Response   
− Treatment(s) for non-severe extrarenal SLE flare or other renal flare not defined 
in protocol  
Vaccination and antibiotics administered for prophylaxis of meningococcal infection (if 
applicable) will also be recorded. 
The Medical Monitor should be contacted if there are any questions regarding concomitant 
medications or procedures. 
Allowed concomitant therapy and corticosteroid tapering for participants with LN is discussed in 
Section 6.5.1 and allowed concomitant therapy for participants with IgAN is discuss in 
Section 6.5.2. 

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8.6. 
Treatment of Overdose 
For this study, any dose of ravulizumab greater than that specified in the protocol will be 
considered an overdose. If dose cannot be established during the Initial Evaluation Period due to 
blinding, suspected overdose should be defined by volume administered. 
Accidental overdose or suspected overdose without any association with laboratory 
abnormalities or clinical symptoms should not be considered as an AE. Overdose must be 
reported by the Investigator within 24 hours to Alexion regardless of its association with or 
without an AE. 
Alexion does not recommend specific treatment for an overdose. 
Overdoses are medication errors that are not considered AEs unless there is an untoward medical 
occurrence resulting from the overdose. 
In the event of an overdose or suspected overdose, the Investigator should: 
• Capture and forward the event, with or without associated AEs, to Alexion Global 
Patient Safety via email or facsimile (clinicalsae@alexion.com or + 1.203.439.9347) 
using the Alexion Clinical Study Overdose Report Form within 24 hours of 
awareness. 
• Contact the Medical Monitor immediately. 
• Evaluate the participant to determine, in consultation with the Medical Monitor, if 
possible, whether study intervention should be interrupted or whether the dose should 
be reduced. 
• Closely monitor the participant for any AE/SAE and laboratory abnormalities as 
medically appropriate and at least until the next scheduled follow-up.  
• Obtain a plasma sample for PK analysis from the date of the last dose of study 
intervention if requested by the Medical Monitor (determined on a case-by-case 
basis).  
• For unblinded participants, document the quantity of the excess dose as well as the 
duration of the overdose in the CRF. 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
8.7. 
Pharmacokinetics and Pharmacodynamics 
• Blood samples for determination of serum drug concentrations and PD assessments 
(free and total C5) will be collected before and after administration of study drug at 
the time points specified in the SoA (Section 1.3). 
• Instructions for the collection and handling of biological samples will be provided by 
Alexion. The actual date and time (24-hour clock time) of each sample will be 
recorded. 
• Additional information on sample collection, including blood volume requirements, is 
provided in the Laboratory Manual. 

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• The Day 1 baseline PK and PD blood samples will be collected at predose, within 
90 minutes before administering study drug at visits specified in the SoA 
(Section 1.3). The predose blood sample may be drawn through the venous access 
created for the dose infusion, prior to administration of the dose. 
• For all subsequent visits falling on dosing days, samples will be collected predose 
(within 0.5 hours prior to the start of infusion). In order to minimize needle sticks to 
the participant, the predose sample may be drawn through the venous access created 
for the dose infusion, prior to administration of the dose.  
• Postdose PK and PD blood samples will be collected within 0.5 hours after 
completing study drug infusion. The postdose blood samples will be drawn from the 
participant’s opposite, noninfused arm. 
• For indicated visits not falling on dosing days, samples may be collected at any time 
that visit day. 
• In the event of an unscheduled visit, PK and PD blood sample will be collected as 
soon as possible. 
• Ravulizumab PK in urine may be conducted as an exploratory analysis based on 
findings from impact of proteinuria on serum PK. 
Study intervention concentration information that may unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded. 
8.8. 
Biomarkers 
Please refer to the Laboratory Study Manual for details on sample collection, including blood 
volume requirements. Biomarker samples may be analyzed after study completion by the 
absolute value and change from baseline.  
8.8.1. 
Blood Exploratory Biomarkers 
Blood (whole blood, serum & plasma) samples for biomarker research will be collected from all 
participants at the time points specified in the SoA (Section 1.3).  
Biomarkers to be measured may include, but are not limited to, assessments of the following: 
• Complement pathway dysregulation (eg, soluble C5b-9 [sC5b-9] etc)   
8.8.2. 
Urine Exploratory Biomarkers 
Urine samples for biomarker research will be collected from all participants at the time points 
specified in the SoA (Section 1.3).  
Biomarkers to be measured may include, but are not limited to, assessments of the following: 
• Complement pathway dysregulation (sC5b-9 etc)  
• Renal injury biomarkers (eg, neutrophil gelatinase-associated lipocalin [N-GAL], etc) 
• Creatinine 

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8.8.3. 
Kidney Biopsy Tissue Exploratory Biomarkers 
Kidney tissue biopsies will be stained for the presence of biomarkers which provide clinical 
evidence of the disease pathophysiology and response to treatment (eg, C5b-9, etc).  
For participants in the LN cohort who undergo repeated kidney biopsy(s) during the study, the 
LN classification will be assessed.  
8.8.4. 
Additional Biomarker Research 
Residual blood, urine, and biopsy samples from exploratory biomarkers, PK, PD, and 
immunogenicity, as well as residual samples from 24-hour urine collections will be stored for 
additional method developments of assays (eg, prognostics and/or companion diagnostics related 
to the study drug target, disease process, pathways associated with disease state, other 
complement-related diseases, and/or mechanism of action of ravulizumab). 
Samples will be retained to enable further analysis on ravulizumab continues but no longer than 
5 years after termination of the study or other period as per local requirements. 
8.9. 
Other Exploratory Assessments 
8.9.1. 
Autoantibodies (LN Cohort Only) 
Blood samples will be collected for anti-dsDNA and anti-C1q) autoantibodies during Screening 
and according to the SoA (Section 1.3) through the end of the Extension Period (Day 351).  
8.9.2. 
SLEDAI–2K (LN Cohort Only) 
The SLEDAI–2K tool (Section 10.12) assesses disease activity across 24 disease descriptors. 
The total score ranges from 0 to 105, with higher scores representing more significant degrees of 
disease activity.  
The 18 disease descriptors of the SLEDAI–2K assessment will be used for the determination of 
Extrarenal SLE Flare (Section 3.2.2). Extrarenal SLE Flare is defined as an increase in 
SLEDAI-2K ≥ 4 points that is not accounted for by the disease descriptors of proteinuria, 
hematuria, urinary casts, hypocomplementemia, pyuria, or an increase in anti-dsDNA antibody 
level. Each disease descriptor is evaluated if present at the time of the visit or within the 
preceding 30 days.  
8.9.3. 
Real Time Complement Activity 
Blood and urine samples will be collected (at selected study sites only) for exploratory Real 
Time Complement Activity (RTCA) during Screening and according to the SoA (Section 1.3) 
through the end of the Initial Evaluation Period (Day 183). The RTCA analysis will be 
performed at clinical sites using freshly collected whole blood dipotassium 
ethylenediaminetetraacetic acid (K2EDTA) and urine samples. Blood and urine samples for 
RTCA will be collected prior to administration of study drug on dosing days, if applicable. The 
results will be de-identified using the participant study identification number and all site 
personnel will be blinded from the RTCA results.  

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8.9.4. 
Participant-Reported Outcome Measures 
Quality of life scales will be administered by the Investigator or a qualified site staff prior to 
other study procedures at visits specified in the SoA (Section 1.3).  
Participants in both cohorts will have the following validated quality of life scales administered:  
• The Short Form (36) (SF-36v2) Health Survey (Section 10.13) will be used to assess 
the participant’s quality of life. In the SF-36v2 Questionnaire, participants will be 
instructed to rate their health and capacity to perform activities of daily living in 
8 domains including physical functioning, physical role limitations, bodily pain, 
general health, vitality, social functioning, emotional role limitations, and mental 
health during the last 4 weeks. Raw domain scores will be determined and 
transformed to a 0 to 100 scale as described in the SF-36v2 manual. Domains get 
scored from 0 to 100 with lower scores indicating increased disability.  
• The EuroQoL 5-Dimensions 5-Level (EQ-5D-5L) (Section 10.14) is a self-assessed, 
standardized instrument to measure health-related quality of life and has been used in 
a wide range of health conditions. The EQ-5D-5L is a 5-scale participant-reported 
outcome tool measuring pain/discomfort, mobility, self-care, usual activities and 
anxiety/depression.  
Participants in the LN cohort will also have the following validated quality of life scales 
administered:  
• The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale 
(Section 10.15), Version 4.0, is a 13-item questionnaire that assesses self-reported 
fatigue and its impact upon daily activities and function over the preceding 7 days. 
8.10. 
Immunogenicity Assessments 
Antidrug antibodies to ravulizumab (ie, ADAs) will be evaluated in serum samples collected 
from all participants according to the SoA (Section 1.3). Additionally, serum samples should also 
be collected at the final visit from participants who discontinued the study drug or were 
withdrawn from the study. These samples will be tested by Alexion or Alexion’s designee. 
ADA positive samples will be further characterized for antibody titer and presence of 
neutralizing antibodies. Additional analyses may be performed on collected ADA samples for 
further analysis or characterization. 
The detection and characterization of antibodies to ravulizumab will be performed using a 
validated assay method.  
8.11. 
Genetics 
Genetics data are not collected in this study. There are no prespecified genetic analyses in this 
study. 
8.12. 
Medical Resource Utilization 
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study. 

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8.13. 
Post-treatment Follow-up Period 
During the 36-week Post-treatment Follow-up Period, participants will continue to receive 
standard of care and will be monitored for clinical events of interest and kidney function.  
All participants will be followed for safety until 8 weeks after the participant’s last dose of study 
drug to collect information on concomitant medications, nonpharmacological therapies and 
procedures, and AEs. The final safety evaluation for participants in the LN will occur at the 
Week 50 Visit and participants in the IgAN cohort will have a Follow-up Phone Call performed 
at Week 52. 
Participants are not required to come into the clinic for the Post-treatment Follow-up Period 
visits. At each Post-treatment Follow-up Visit through Week 86, the information described 
below will be documented in the participant’s CRF for the 12-week period since the previous 
study visit. 
For participants in both cohorts, the following laboratory results will be documented: 
• Record the UPCR results from the participant’s most recent standard of care testing 
conducted by local laboratory. Spot urine studies may be used; a morning void is 
preferred. 
• Record serum creatinine results from the participant’s most recent standard of care 
testing conducted by local laboratory. 
For participants in the LN cohort, information will include, but is not limited to: 
• In the Investigator’s opinion, did the patient experience a renal flare or extrarenal 
flare 
• Documentation of any changes in immunosuppression therapy (intensified, new 
agent, or change in dose) 
• Progression of kidney disease including dialysis and kidney transplant 
For participants in the IgAN cohort, information will include, but is not limited to: 
• Progression of kidney disease including dialysis and kidney transplant 
• Documentation of any changes in immunosuppressive therapy (new agent or change 
in dose) 
• Documentation of any changes in alternative therapy (new agent or change in dose) 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
9.1.1. 
Primary Hypothesis 
The primary hypothesis for this study is that ravulizumab is superior to placebo in decreasing 
proteinuria. Hypothesis testing will be one-sided and performed at the 0.05 level of significance.  
9.2. 
Sample Size Determination 
This study plans to enroll 60 participants in both the IgAN and LN cohorts in a 2:1 ratio to 
ravulizumab and placebo, for a total of 120 participants.  
In March 2018, a National Kidney Foundation (NKF)-sponsored workshop on surrogate 
endpoints for clinical studies in early stages of CKD proposed that a 20% to 30% reduction in 
the geometric mean of proteinuria was likely to be necessary to ensure a significant treatment 
effect on the clinical outcome (Levey, 2020; Holtkamp, 2020). 
Individual patient data from relevant studies in IgAN was previously used to estimate variability 
and expected changes in proteinuria for patients treated with placebo in addition to allowed 
concomitant standard of care treatment (Fellstrom, 2017). Based on this data, the geometric 
mean ratio (GMR) of 26-week to baseline proteinuria values is assumed to be 0.85 (ie, a 15% 
reduction in proteinuria) for the placebo group. In order to target at least a 30% relative treatment 
effect, the GMR is assumed to be 0.55 (ie, a 45% reduction in proteinuria) for the ravulizumab 
group.  
Expected changes in proteinuria and associated variability were not available on the log-scale for 
patients with LN; however, 2 studies of patients with LN who were treated with MMF showed 
mean proteinuria values of approximately 4.0 g/day at baseline and approximately 2.0 g/day at 
Week 24 (Appel, 2009; Ginzler, 2005). The GMR of 26-week to baseline proteinuria values is 
assumed to be 0.60 (ie, a 40% reduction in proteinuria) for the placebo group. In order to target 
at least a 30% relative treatment effect, the GMR is assumed to be 0.40 (ie, a 60% reduction in 
proteinuria) for the ravulizumab group. 
Sample size calculations are based on a one-sided two-sample t-test of log-transformed 
proteinuria values. The log change from baseline in proteinuria is calculated as log(0.85) and 
log(0.55) for the placebo and ravulizumab treatment groups, respectively, for the IgAN cohort, 
and as log(0.60) and log(0.40) for the placebo and ravulizumab treatment groups, respectively, 
for the LN cohort. A common standard deviation (SD) of log change is assumed to be 0.60  
(Fellstrom, 2017). Under these assumptions and an anticipated 10% drop out rate, a sample size 
of 60 participants (40 participants randomized to ravulizumab, 20 participants randomized to 
placebo) will provide approximately 80% power to detect a treatment difference with a one-sided 
significance level of 0.05 in each cohort.  

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9.3. 
Populations for Analyses 
The following populations are defined for this study: 
Population 
Description 
Randomized Set 
All randomized participants. Participants will be analyzed as 
randomized for reporting disposition, demographics, and baseline 
characteristics. 
Full Analysis Set (FAS) 
All randomized participants who receive at least 1 dose of study drug. 
Participants will be analyzed as randomized for reporting efficacy data. 
Modified Full Analysis Set 
(mFAS) 
The mFAS is a subset of the FAS, excluding participants who were 
impacted by COVID-19.  
Safety Set 
All participants who receive at least 1 dose of study drug. Participants 
will be analyzed according to the study drug they actually received for 
reporting exposure and safety data. 
Per Protocol Set 
All randomized participants who receive at least 1 dose of study drug 
and without important protocol deviations. 
Pharmacokinetic (PK) 
Analysis Set 
All participants who receive at least 1 dose of study drug and who have 
evaluable PK data. 
Pharmacodynamic (PD) 
Analysis Set 
All participants who receive at least 1 dose of study drug and who have 
evaluable PD data. 
Abbreviations: PD = pharmacodynamic; PK = pharmacokinetics 
9.4. 
Statistical Analyses 
Statistical methods described in this section will be further elaborated in a separate Statistical 
Analysis Plan (SAP). All efficacy and safety analyses will be summarized separately for the 
Initial Evaluation Period, Extension Period, and Post-treatment Follow-up Period. Limited data 
will be collected during the Post-treatment Follow-up Period and will be summarized 
descriptively as applicable. 
Summary statistics will be computed and displayed by treatment group and by visit, where 
applicable. Descriptive statistics for continuous variables will minimally include the number of 
participants, mean, SD, minimum, median, and maximum. For categorical variables, frequencies, 
and percentages will be presented. Graphical displays will be provided as appropriate. 
Analyses will be performed using the SAS® software Version 9.4 or higher. 
The analyses for participants in the LN cohort and participants with IgAN cohort will be 
conducted and reported separately. Participants in each disease-specific cohort will be analyzed 
as randomized, regardless of actual treatment received. 
9.4.1. 
Efficacy Analyses 
9.4.1.1. 
Analyses of Primary Efficacy Endpoint 
The primary analysis of the primary efficacy endpoint will be based on the Full Analysis Set 
(FAS).  

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For the LN cohort, proteinuria will be measured by UPCR in g/g derived from a single 24-hour 
urine collection at Screening and the mean of 2 separate 24-hour urine collections at Week 26. 
For the IgAN cohort, proteinuria will be measured by absolute protein in g/day derived from the 
mean of 2 valid 24-hour urine collections.  
To reduce skewness, the natural logarithm will be used to transform proteinuria values before 
analysis. An analysis of covariance (ANCOVA) will be used for the primary efficacy endpoint to 
compare reductions in proteinuria between the ravulizumab and placebo treatment groups. The 
ANCOVA model will include change from baseline in log-transformed proteinuria as the 
response variable and will adjust for baseline log proteinuria and the randomization stratification 
factor. The treatment effect will be evaluated using the least squares mean difference between 
treatment groups. The point estimate and two-sided 90% confidence interval (CI) for the mean 
difference of log-transformed proteinuria will be back-transformed (via exponentiation) to obtain 
the GMR and corresponding two-sided 90% CI. The values will then be expressed as percentage 
change in adjusted geometric mean of proteinuria at Week 26 relative to baseline. 
For the LN cohort, data collected on or after receipt of additional standard of care therapy will be 
imputed using the proteinuria value from the 24-hour urine collection performed at the time of 
Renal Flare for the primary efficacy analysis. Additional sensitivity analyses will be performed 
to assess the impact of the missing data and assumptions.  
For the IgAN cohort, participants initially randomized to the placebo group will receive 
ravulizumab in the Extension Period. Therefore, analysis of the secondary endpoints during the 
Extension Period will be summarized separately for each treatment group and baseline for the 
placebo group will be re-defined as the last measurement taken before the first dose of 
ravulizumab during the Extension Period (ie, the Week 26 measurement). 
The primary efficacy endpoint analysis will also be performed on the Per Protocol Set. 
Full details of these analyses will be provided in the SAP. 
9.4.1.2. 
Analyses of Secondary Efficacy Endpoints 
The secondary efficacy analyses will be descriptive in nature and will be based on the FAS.  
9.4.1.2.1. Secondary Efficacy Analyses for Both LN Cohort and IgAN Cohort 
• The percentage change from baseline in proteinuria at Week 50 will be analyzed 
using a mixed effect model for repeated measures (MMRM). The model will include 
change from baseline in log-transformed proteinuria as the response variable and 
fixed, categorical effects of treatment group, randomization stratification factor, visit, 
and treatment group by visit interaction as well as a fixed, continuous effect of 
baseline log proteinuria as a covariate. An unstructured covariance matrix will be 
used to model the correlations among repeated measurements within each participant. 
If this analysis fails to converge, a first-order autoregressive covariance matrix will be 
used. The Kenward-Roger approximation will be used to estimate denominator 
degrees of freedom.  
• For the IgAN cohort, participants initially randomized to the placebo treatment group 
will switch to receive ravulizumab at Week 26. Therefore, the percentage change 

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from baseline in proteinuria at Week 50 will be summarized descriptively for each 
treatment group from the MMRM analysis and no formal treatment comparison will 
be made. For the LN cohort, the treatment effect will be evaluated using a contrast for 
treatment group-by-visit term at Week 50. The point estimate and two-sided 90% CI 
for the mean difference of log-transformed proteinuria will be back-transformed (via 
exponentiation) to obtain the GMR and corresponding two-sided 90% CI. The values 
will then be expressed as percentage change in adjusted geometric mean of 
proteinuria at Week 50 relative to baseline. 
• The percentage of participants with > 30% and > 50% reduction in proteinuria at 
Week 26 and Week 50 will be summarized by treatment group by calculating the 
point estimate and two-sided 95% CI, based on exact confidence limits using the 
Clopper-Pearson method. 
• The following endpoints will be summarized at baseline and each postbaseline time 
point by treatment group using descriptive statistics for the observed value as well as 
the change from baseline: 
− eGFR 
− Serum C3 and C4 concentrations 
9.4.1.2.2. Secondary Efficacy Analyses for LN Cohort Only 
The following secondary endpoints will be summarized by treatment group by calculating the 
point estimate and two-sided 95% CI, based on exact confidence limits using the 
Clopper-Pearson method: 
− Percentage of participants meeting the criteria for CRR as well as individual 
components of CRR (defined in Section 3.2.5) at Week 26 and Week 50  
− Percentage of participants meeting the criteria for PRR (defined in Section 3.2.5) 
at Week 26 and Week 50  
− Percentage of participants with achieving corticosteroid taper (defined in 
Section 6.5.1) at Week 14, Week 26, and Week 50 
− Percentage of participants with protocol-defined Renal Flare (defined in 
Section 3.2.1) through Week 50  
− Percentage of participants with protocol-defined Severe Extrarenal SLE Flare 
(defined in Section 3.2.2) through Week 50  
− Percentage of participants with Treatment Failure (defined in Section 3.2.4) 
through Week 50  
− Percentage of participants with Suboptimal Response (defined in Section 3.2.3) 
through Week 50 
Time to UPCR ≤ 0.5 g/g will be summarized based on spot urine samples. A Kaplan-Meier 
cumulative distribution curve will be generated for treatment group, and a log-rank test 
comparing the curves will be performed. The corresponding summary table will present by 
treatment group the cumulative distribution function (CDF) estimate, the number of participants 

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at risk, the number of participants responding, and the number of participants censored at each 
postbaseline time point. The table will also present the first quartile, median, and third quartile, 
along with two-sided 95% CI, of time to UPCR ≤ 0.5 g/g. 
Serum albumin will be summarized at baseline and each postbaseline time point by treatment 
group using descriptive statistics for the observed value as well as the change from baseline. 
9.4.1.2.3. Secondary Efficacy Analyses for IgAN Cohort Only 
The percentage of participants meeting the criteria for Partial Remission (defined in 
Section 3.2.6) at Week 26 and Week 50 will be summarized by treatment group by calculating 
the point estimate and two-sided 95% CI, based on exact confidence limits using the 
Clopper-Pearson method.  
9.4.1.3. 
Multiplicity Adjustment 
The secondary efficacy analyses will be descriptive in nature and no adjustment for multiplicity 
will be performed.  
9.4.2. 
Safety Analyses 
All safety analyses will be performed on the Safety Set and will be based on the actual treatment 
received.  
9.4.2.1. 
Adverse Events 
The following definitions will be used for AEs: 
• Treatment-emergent adverse event (TEAE): Any AE that starts during or after the 
first dose of study drug. Adverse events that start 56 days or later after the last dose of 
study drug will not be considered as treatment emergent. 
• Treatment-emergent SAE (TESAE): A TEAE that is serious 
The incidence of TEAEs, TEAEs leading to withdrawal from the study, TEAEs leading to study 
drug discontinuation, drug-related TEAEs, and TESAEs will be summarized by treatment group 
for each disease cohort separately. All AEs will be coded using Medical Dictionary for 
Regulatory Activities (MedDRA) version 23.0 or higher and will be summarized by System 
Organ Class (SOC) and Preferred Term overall, by severity, and by relationship to study drug.  
Detailed by-participant listings of TEAEs, SAEs, related TEAEs, TEAEs leading to withdrawal 
from the study, and TEAEs leading to study drug discontinuation will be provided. 
9.4.2.2. 
Physical Examination and Vital Signs 
Adverse changes from baseline in physical examination findings will be classified as AEs and 
analyzed accordingly. 
Vital signs will be summarized descriptively by treatment group at baseline and postbaseline 
time points and for changes from baseline separately for each disease cohort. 

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9.4.2.3. 
Clinical Laboratory Tests 
Observed values and changes from baseline in clinical chemistry, hematology, and urinalysis 
will be summarized descriptively by treatment group at baseline and at each postbaseline time 
point separately for each disease cohort. For laboratory results that can be classified as normal, 
low, or high based on normal range values, shifts from baseline in classification will be 
summarized for all study visits. 
9.4.2.4. 
Electrocardiograms 
By-participant data listings of ECG parameters will be provided separately for each disease 
cohort. Electrocardiograms will be evaluated and summarized as normal, abnormal not clinically 
significant, or abnormal clinically significant. A shift from baseline to worst on-study ECG table 
will be presented for ECG results. Observed values and change from baseline in ECG intervals 
(PR, RR, QT, and QTc) will be summarized descriptively at baseline and each postbaseline time 
point. The QT interval will be corrected for heart rate using Fridericia’s formula (QTcF). 
9.4.3. 
Pharmacokinetic/Pharmacodynamic Analyses  
Graphs of mean serum ravulizumab concentration-time profiles will be constructed. Graphs of 
serum concentration-time profiles for individual participants may also be provided. Actual dose 
administration and sampling times will be used for all calculations. Descriptive statistics will be 
calculated for serum concentration data at each sampling time, as appropriate. 
The PD effects of ravulizumab will be evaluated by assessing the absolute values and changes 
and percentage changes from baseline in serum free C5 concentrations over time, as appropriate. 
Descriptive statistics will be calculated for the PD data at each sampling time, as appropriate. 
9.4.4. 
Immunogenicity Analyses   
The incidence and titers for ADAs to ravulizumab will be presented at each postbaseline time 
point in tabular format separately for each disease cohort. Additionally, any confirmed ADA 
positive samples will be tested for the presence of neutralizing antibodies to ravulizumab. 
9.4.5. 
Exploratory Analyses 
9.4.5.1. 
Exploratory Efficacy Endpoints 
The exploratory efficacy analyses will be descriptive in nature and will be based on the FAS. 
Full details regarding the exploratory efficacy analyses will be described in the SAP.  
For continuous endpoints, data will be summarized at baseline and each postbaseline time point 
by treatment group using descriptive statistics for the observed value as well as the change from 
baseline. 
For categorical endpoints, data will be summarized by treatment group by calculating the point 
estimate and two-sided 95% CI, based on exact confidence limits using the Clopper-Pearson 
method. 
For the LN cohort, time to CRR, time to PRR, and time to UPCR > 50% decrease from baseline 
will be summarized using spot urine samples. Participants will be assigned as responders at the 
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earliest of their discontinuation time, receipt of additional standard of care therapy, or at 
Week 50 if they have not responded or received additional standard of care therapy by then. 
Kaplan-Meier cumulative distribution curves will be generated for each treatment group, and a 
log-rank test comparing the curves will be performed. A corresponding summary table will 
present the CDF estimate, the number of participants at risk, the number of participants 
responding, and the number of participants censored at each postbaseline time point by treatment 
group. The table will also present first quartile, median, and third quartile, along with 
corresponding 2-sided 95% CI, of time to response. 
Slope of eGFR for the IgAN cohort will be computed using a mixed effect model including data 
through Week 26 or Week 50, respectively. The model will include eGFR as the response 
variable, random patient effects for intercepts and slopes, fixed categorical effects of treatment 
group, visit, randomization stratification factor, and treatment group by visit interaction as well 
as a fixed, continuous effect of baseline eGFR.   
9.4.5.2. 
Biomarkers 
Analyses of exploratory biomarkers will be described in a separate SAP.  
9.4.5.3. 
Quality of Life 
The following quality of life assessments will be summarized by treatment group at baseline and 
each postbaseline time point using descriptive statistics for continuous variables for the observed 
value as well as the change from baseline: 
• EQ-5D-5L 
• SF-36 score   
• FACIT-Fatigue (LN cohort only)   
Additional details will be described in the SAP. 
9.5. 
Planned Analyses  
9.5.1. 
Dose Confirmation Analysis 
To ensure the adequacy of the dose regimen, an interim PK/PD analysis for dose confirmation 
will be conducted by an independent clinical pharmacologist. The interim PK confirmation 
analysis will be conducted using masked PK/PD data from the first 10 participants treated with 
ravulizumab (a minimum of 3 participants in each disease-specific cohort), using data cut when 
the tenth participant reaches 2 weeks post first dose (ie, at Day 15). The PK dataset for review 
will include: 
• Day 1 Cmax, Day 15 Ctrough, and Cmax for all 10 participants. 
• Pharmacokinetics data beyond Day 15 Cmax timepoint (eg, Day 29 PK) may be included 
in the dataset (availability depending upon the enrollment rate). 
• Free and total C5 data associated with above timepoints and ADA data will be included 
in the dataset as supportive evidence. 

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If observed Day 1 Cmax, Day 15 Cmax and Ctrough values, and other available PK/PD data are 
within the expected range, the study will proceed unchanged. If the totality of the available 
PK/PD data are not within the expected range, a dose regimen adjustment may be necessary for 
all participants or for a subset of participants. If all participants require a dose regimen 
adjustment, enrollment will be paused until a new regimen is determined. If dose regimen 
adjustment is only required for a subset of participants, enrollment may continue in the subset 
not requiring dose adjustment. In the event of dose adjustments, the participants treated with the 
previous dose will switch over to the new dose and continue treatment on study but will be 
excluded from the primary efficacy analysis. Replacement participants may be enrolled to 
preserve study power. 
9.5.2. 
Interim Analysis for Primary Endpoint 
The primary efficacy analysis will be performed for each disease-specific cohort at the end of the 
26-week Initial Evaluation Period after all participants in the disease-specific cohort have 
completed or withdrawn from the 26-week Initial Evaluation Period. This analysis will allow for 
evaluation of the primary endpoint and Phase 3 planning and will have no impact on the 
progression of this study. 
In addition, an early interim analysis may be conducted for either disease cohort at the discretion 
of Alexion (based on feasibility) when at least 50% of participants have been randomly assigned 
to study treatment and have had the opportunity to complete the 26-week Initial Evaluation 
Period. These interim analyses, if performed, will be conducted by a separate unblinded team to 
preserve the integrity of the study design and minimize risk of bias. The interim analysis for the 
IgAN cohort will be for Phase 3 planning purposes only with no impact on the progression of the 
study. The interim analysis for the LN cohort will not include hypothesis testing and will not 
impact the progression of the study. 
9.5.3. 
Interim Analysis for Extension Period  
An interim efficacy analysis will be performed for each disease-specific cohort at the end of the 
50-week Extension Period after all participants in the disease-specific cohort have completed or 
withdrawn from the 50-week Extension Period. 
9.5.4. 
Final Analysis 
The final study analysis will be conducted at the end of the study (Section 4.5). The SAP will 
describe the planned analysis in greater detail. 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
− Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines 
− Applicable ICH GCP Guidelines 
− Applicable laws and regulations 
• The protocol, substantial protocol amendments, ICF, IB, and other relevant 
documents (eg, advertisements) must be submitted to an IRB/IEC by the Investigator 
and reviewed and approved by the IRB/IEC and regulatory authority before the study 
is initiated.  
• Any substantial amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants.  
• The Investigator will be responsible for the following, as applicable: 
− 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 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
− Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the 
IRB/IEC, European clinical trial regulation (CTR) 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations 
− Promptly notifying Alexion of any (potential) serious breach of the protocol or 
regulations (including if a data breach compromises the integrity, confidentiality, 
or availability of the personal data of participants) so that legal and ethical 
obligations are met. A “serious breach” means a breach likely to affect to a 
significant degree the safety and rights of a participant or the reliability and 
robustness of the data generated in the clinical study. 
• In certain regions/countries, Alexion has a legal responsibility to notify both the local 
regulatory authority and other regulatory agencies about such breaches.  
− Alexion will comply with country-specific regulatory requirements relating to 
serious breach reporting to the regulatory authority (including data protection 
authorities and, if applicable, affected participants in case of a personal data 

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breach), IRB/IEC, and Investigators. Under EU CTR 536/2014, Alexion is 
required to enter details of serious breaches into the European Medicines Agency 
(EMA) Clinical Trials Information System (CTIS). It is important to note that 
redacted versions of serious breach reports will be available to the public via 
CTIS. 
• The Investigator should have a process in place to ensure that: 
− The site staff or service providers delegated by the Investigator/institution are able 
to identify the occurrence of a (potential) serious breach, including personal data 
breaches. 
− A (potential) serious breach is promptly reported to Alexion or delegated party, 
through the contacts (email address or telephone number) provided by Alexion. 
− Alexion and the site have taken all necessary steps to avoid personal data 
breaches and have undertaken measures to prevent such breaches from occurring 
in the first place and to mitigate the impact of occurred data breaches (eg, 
applying encryption, maintaining and keeping systems and information 
technology (IT) security measures up-to-date, regular reviews and testing, regular 
training of employees, and developed security policies and standards).  
− Both Alexion and the study site have developed an internal data breach reporting 
and investigation process and internal protocols with guidance on how to respond 
swiftly and diligently to the occurrence of a personal data breach. 
− In compliance with applicable laws, the data controller for the processing activity 
where the personal data breach occurred (Alexion or respectively the study site) 
will notify the data protection authorities without undue delay within the legal 
terms provided for such notification and within the prescribed form and content. 
− If the personal data breach needs to be notified to participants, the notification to 
participants is done by the site for the data breaches that occurred within the 
processing activities for which the site is the data controller and for data breaches 
occurred within the processing activities of Alexion as the data controller, the 
notification is done in collaboration with the site and is performed by the site 
and/or Investigator, acting on behalf of Alexion, so that Alexion has no access to 
the identifying personal information of the participants. The site and/or 
Investigator shall conduct the notification by contacting the participants using the 
information that they gave for communication purposes in clinical research. 
− If a personal data breach occurs in a processor's systems, engaged by Alexion, the 
processor under contractual obligations with Alexion promptly and in due course 
after discovering the breach notifies Alexion and provides full cooperation with 
the investigation. In these cases, to the extent Alexion is the data controller for the 
processing activity where the breach occurred, it will be responsible for the 
notification to data protection authorities and, if applicable, to participants. If the 
personal data breach needs to be notified to the participants, the notification to 
participants is done in collaboration with the site and is performed by the site 

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and/or Investigator, acting on behalf of Alexion, so that Alexion has no access to 
the identifying personal information of the participants. 
− Where a personal data breach is suffered by the Study Monitor, the latter will 
provide Alexion with all of the information needed for notification of the breach, 
without disclosing data that allows Alexion directly or indirectly to identify the 
participants. The notification will be done by Alexion solely with the information 
provided by the Study Monitor and in no event with access to information that 
could entail a risk of reidentification of the participants. If the data breach must be 
notified to the data participants, the notification will be done directly by the Study 
Monitor in collaboration with the site and/or Investigator, acting on behalf of 
Alexion, so that Alexion has no access to the identifying personal information of 
the participants. The contract between Alexion and the Study Monitor shall 
expressly specify these conditions. 
− The contract between the study site and Alexion for performing the clinical 
research includes the provisions and rules regarding who is responsible for 
coordinating and directing the actions in relation to the breaches and performing 
the mandatory notifications to authorities and participants, where applicable. 
• The Coordinating Investigator will be identified among the enrolling Investigators 
during the course of the study and will be responsible for reviewing the clinical study 
report (CSR) and confirming that it accurately describes the conduct and results of the 
study. 
10.1.2. 
Financial Disclosure 
Investigators and Sub-Investigators will provide Alexion with sufficient, accurate financial 
information as requested to allow Alexion to submit complete and accurate financial certification 
or disclosure statements to the appropriate regulatory authorities. Investigators are responsible 
for providing information on financial interests during the course of the study and for 1 year after 
completion of the study. 
10.1.3. 
Informed Consent Process 
• It is the responsibility of the Investigator to obtain signed (written or electronic 
signature) informed consent from all study participants prior to performing any 
study-related procedures including screening assessments.  
• The Investigator or designee will explain the nature of the study (including but not 
limited to the objectives, potential benefits and risks, inconveniences, and the 
participant’s rights and responsibilities) to the participant, defined according to local 
and country regulations where the study is taking place, and answer all questions 
regarding the study.  
• Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent or a certified translation if 
applicable, that meets the requirements of 21 CFR 50, local regulations, EU General 
Data Protection Regulation (GDPR), ICH GCP guidelines, Health Insurance 

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Portability and Accountability Act (HIPAA) requirements, where applicable, and the 
IRB/IEC or study center.  
• The participant’s medical record must include a statement that signed (written or 
electronic) informed consent was obtained before any screening procedures were 
performed and the date the written consent was obtained. The authorized person 
obtaining the informed consent must also sign the ICF(s).  
• Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study, as applicable.  
• A copy of the signed (written or electronic) informed consent documentation (ie, a 
complete set of participant information sheets and fully executed signature pages) 
must be provided to the participant. This document may require translation into the 
local language. Signed (written or electronic) consent forms must remain in each 
participant’s study file and must be available for verification at any time. 
Participants who are rescreened outside of the screening window are required to sign a new ICF 
(see Section 5.4). 
10.1.4. 
Recruitment Strategy 
Participants will be identified by qualified research staff. This may be done through a review of 
medical records, external referrals or using databases. Recruitment strategies may include study 
posters, referral letters, recruitment brochures, advertisements, social media posts, and websites, 
where permitted by local regulations. All recruitment materials will be submitted to local 
IRB/EC as required, for review and approval for use. 
10.1.5. 
Data Protection 
• Participants will be assigned a unique identifier by Alexion. Any participant records 
or datasets that are transferred to Alexion will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred.  
• Participants must be informed about the uses of their personal study-related and 
coded (pseudonymized) data, who will have access to their personal data, how and 
how long it will be used, and that it will be used by Alexion in accordance with local 
data protection law. In addition, multiple local laws require that participants must also 
be informed of any individuals rights they may have with regard to their personal 
data. Participants will be informed about how their personal study-related data will be 
disclosed and are provided with the appropriate legal basis for which a controller 
processes their personal data. The level of disclosure, the security controls used to 
protect their data, and information regarding any transfer of their personal data 
outside of their country or region must also be explained to the participant. 
• Participants must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by Alexion, by 
appropriate IRB/IEC members, any third parties acting on behalf of Alexion ,and by 
inspectors from regulatory authorities. 

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• Alexion and the site as a data controller has implemented privacy and security 
controls designed to help protect participant personal data, including information 
security controls, firewalls, incident detection, and secure transfer measures. 
• The contract between Alexion and study sites specifies responsibilities of the parties 
related to data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 
• Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect 
such data against accidental or unlawful loss, alteration, or unauthorized disclosure or 
access. 
• The EU GDPR defines pseudonymization as the processing of personal data in such a 
way that the personal data can no longer be attributed to a specific individual without 
the use of additional information, provided that such additional information is kept 
separately and protected by technical and organizational measures to ensure that the 
personal data are not attributed to an identified or identifiable natural person. 
• Appropriate safeguards will be implemented to protect coded data during and after 
the study that include: 
− Access to the coded data will be limited to specific individuals subject to 
confidentiality obligations (including the obligation to not attempt to re-identify 
individuals/decode the clinical data). 
− The coded data will be protected with security measures to avoid data alteration, 
loss, and unauthorized accesses and further de-identification techniques may be 
applied. 
− A data protection impact assessment (DPIA), where required, will apply to 
identify and mitigate privacy risks, if any, associated with each scientific research. 
− The coded data will not be shared for direct marketing purposes or other purposes 
that are not legal duties or are not considered scientific research according to the 
applicable data protection legislation. In particular, it will not be used to make 
decisions about future services available to the participant, such as insurance. 
• In addition to having the participants’ data and biosamples coded, the data are also 
protected by high-standard technical security means, such as strong access control 
and encryption. 
• Participants are also protected legally by the following means if the level of 
disclosure of the coded data includes sharing of the latter with other third parties, as 
the participants will be explained in the ICF: 
− The participants’ coded data are protected by contractual arrangements, Codes of 
Conduct, or certifications that set the rules for personal information protection to 
those available in European countries or other alternatives set forth in the law, as 
well as any supplementary technical and organizational measures that may results 
out of conducted transfer impact assessments. 

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10.1.6. 
Dissemination of Clinical Study Data 
Study-related information and study results may be posted on publicly accessible clinical study 
databases (eg, the US website www.clinicaltrials.gov or the EU website 
www.clinicaltrialsregister.eu), as appropriate, and in accordance with national, regional, and 
local regulations. 
10.1.7. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic CRF 
unless transmitted to Alexion or designee electronically (eg, laboratory data). The 
Investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF.  
• 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.  
• Alexion or designee is responsible for the data management of this study including 
quality checking of the data.  
• Study 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 participants 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.  
− Remote source data verification may be employed where permitted by local 
regulations.  
− The scope of the source data verification will be described in detail in the 
Monitoring Plan. 
• Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the Investigator for at least 25 years after study completion 
unless local regulations or institutional policies require a longer retention period. No 
records may be destroyed during the retention period without the written approval of 
Alexion. No records may be transferred to another location or party without written 
notification to Alexion. Clinical study documents and records required as part of the 
trial master file (TMF) are archived and stored by Alexion for at least 30 years. 
10.1.8. 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. The Investigator or designee will prepare and maintain adequate 
and accurate source documents (eg, medical records, ECGs, AE and concomitant medication 
reporting, raw data collection forms) designed to record all observations and other pertinent data 
for each participant. 

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Data reported on the 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. Source documents are filed at the Investigator’s site. 
10.1.9. 
Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site activation and will be the study start date.  
Alexion reserves the right to close the study site or terminate the study at any time for any reason 
at the sole discretion of Alexion. Study sites will be closed after the study is completed or 
following the decision to close or terminate the study. A study site is considered closed when all 
participants have completed the EoS or ED Visit, all data have been collected and entered into 
electronic data capture (EDC) system, all required documents and study supplies have been 
collected and reconciled, and a study-site closure visit has been performed. 
The Investigator must initiate study-site closure if there is reasonable cause; sufficient notice 
must be given in advance of the intended termination. 
Reasons for the early closure of a study site by Alexion or Investigator include but are not 
limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, Alexion’s procedures, or ICH GCP guidelines 
• Inadequate recruitment of participants by the Investigator 
• Discontinuation of further study intervention development 
• Withdrawal of the local ethics committee/health authority favorable opinion or 
approval 
Alexion or health authority have the ability to terminate the study for reasonable cause. 
Conditions that may warrant termination of the study include, but are not limited to: 
• Discovery of an unexpected, serious, or unacceptable risk of the study drug to 
patients enrolled or continuing in the study  
• Sponsor decision to suspend or discontinue testing, evaluation, or development of the 
study drug in IgAN and LN indications   
If the study is prematurely terminated or suspended, Alexion shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by the 
applicable regulatory requirements. The Investigator shall promptly inform the participant and 
should assure appropriate participant therapy and/or follow-up. 
10.1.10. 
Publication Policy 
The full terms regarding publication of the results of this study are outlined in the applicable 
Clinical Study Agreement. 

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10.1.11. 
COVID-19 Risk Assessment 
Proliferative LN and IgAN can cause irreversible morbidity and even mortality, if untreated. As 
such, and due to the limited number of available treatment options, the benefit a participant may 
receive from joining an investigational study with a therapeutic treatment is potentially 
significant. Given that treatment for these conditions does involve immunosuppression, there is a 
theoretical concern that the risk for infection may be higher than in participants not receiving 
immunosuppressants. However, there is no specific data to further inform this risk. Apart from 
the predictable risk of infection with Neisseria species, which is well known and directly related 
to the mechanism of action of ravulizumab, the mechanism that might lead to other serious 
infections including viral infections in patients treated with ravulizumab remains unclear. The 
site Investigator will therefore balance the benefit/risk considerations for the study participant 
taking these factors into account.  
The potential risks identified and mitigation measures put in place in light of the COVID-19 
pandemic are provided in Table 11. 
Table 11: 
Potential Risks and Mitigation Measures due to COVID-19 
Risks category 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Potential risks 
Potentially higher 
risk population for 
SARS-CoV-2 
infection 
Participants in this study will receive 
allowed concomitant therapy that may 
include immunosuppressants.  
Participants in this study may receive 
meningococcal vaccination and 
prophylactic antibiotics prior to 
treatment with a C5 inhibitor.  
It is unknown how this may impact their 
risk for SARS-CoV-2 infection. 
During the time that the COVID-19 
pandemic is active, Alexion will 
recommend that sites in a position 
to start the study and enroll 
participants follow the national and 
institutional guidances regarding 
prevention of SARS-CoV-2 
infection. 
Additionally, during that time 
period, it is encouraged that 
Investigators and their staff follow 
all possible precautions and 
monitoring recommended by 
national/local health authority 
guidelines in order to minimize a 
participant’s potential exposure to 
COVID-19 and identify 
SARS-CoV-2 infection. Depending 
on the site, this will consist of 
measures such as social distancing, 
temperature screening, enhanced 
cleaning, use of personal protective 
equipment for participants, staff, 
and caregivers, and COVID-19 
testing as necessary. Physical 
exams and vital signs monitoring 

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Table 11: 
Potential Risks and Mitigation Measures due to COVID-19 
Risks category 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
are also required at each study visit 
for all sites. 
Healthcare 
institution 
availability for 
non-COVID-19 
related activities  
COVID-19 pandemic may impact the 
workload of healthcare institutions 
globally and may reduce staff 
availability to perform non-urgent 
activities and non-COVID-19 related 
activities. 
 
During the time that the COVID-19 
pandemic is active, Alexion will not 
open study sites or enroll new 
participants at sites unless the sites 
have the resourcing and capabilities 
to implement the study per protocol. 
Data quality and 
integrity 
Lack of availability of site personnel to 
perform study assessments and capture 
study specific data in a timely manner 
and to maintain adequate quality 
standards. 
Lack of availability of site personnel to 
ensure adequate and continuous chain of 
custody, storage conditions, and 
monitoring for investigational product 
and biological samples. 
Inability of study monitors and quality 
personnel to conduct in-person visits to 
exercise adequate oversight of study 
execution at investigational sites. 
Missing data (COVID-19 pandemic may 
impact study visit schedules, and 
increase missed visits and/or participant 
study discontinuations inadvertently 
resulting in missing data [eg, for 
protocol-specified procedures]). 
During the time that the COVID-19 
pandemic is active, Alexion will 
only open study sites that report 
enough personnel capacity to 
sufficiently conduct clinical 
study-related activities.  
During this timeframe, participants 
eligibility as well as site capacity 
will be reviewed by the site 
Investigator and the study Medical 
Monitor prior to Screening. Each 
site is also evaluated for the 
capacity to perform remote 
monitoring visits and remote source 
data verification. 
During the time that the COVID-19 
pandemic is active, it will be 
important to capture specific 
information in the eCRF that 
explains the reason the data is 
missing (eg, missed study visits or 
participant study discontinuations 
due to COVID-19). 
Abbreviations: C5 = complement component 5; COVID-19 = coronavirus disease 2019; eCRF = electronic case 
report form; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2 
10.1.12. 
COVID-19 Vaccine Risk Assessment 
Following a review of the available COVID-19 vaccine data (eg, Pfizer/BioNTech, Moderna, 
AstraZeneca, Johnson & Johnson), it is unlikely that the immune response to a COVID-19 
vaccine (and therefore the efficacy of the vaccination) would be diminished with concomitant 
ravulizumab administration, based on ravulizumab’s mechanism of action. There is currently no 
information available evaluating the safety and efficacy of COVID-19 vaccines in participants 
treated with ravulizumab.  

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Vaccination may further activate complement. As a result, patients with complement-mediated 
diseases may experience increased signs and symptoms of their underlying disease. Therefore, 
patients should be closely monitored for disease symptoms after recommended vaccination. 
Because vaccines may activate complement, if possible, consider vaccination when the 
underlying complement mediated disease is clinically controlled and when systemic C5 inhibitor 
concentration (and subsequent complement blockade) is relatively high, shortly after 
administration. 
Local and national guidelines should be consulted for recommendations related to COVID-19 
vaccination. The potential risks identified and mitigation measures put in place in light of the 
COVID-19 vaccination rollout are provided in Table 12. 
Table 12: 
Potential Risks and Mitigation Measures due to COVID-19 Vaccine 
Risks Category 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Potential risks 
Data quality and 
integrity 
Missing data due to appointments for 
COVID-19 vaccination or side effects of 
COVID-19 vaccine may impact study visit 
schedules, and increase missed visits and/or 
participant study discontinuations, 
inadvertently resulting in missing data (eg, 
for protocol-specified procedures). 
Capture specific information in 
the eCRF that explains the 
reason for missing data (eg, 
missed study visits due to 
appointments for COVID-19 
vaccination or side effects of 
COVID-19 vaccine). 
Abbreviations: COVID-19 = coronavirus disease 2019; eCRF = electronic case report form 
10.1.13. 
Remote Source Data Verification During COVID-19 Pandemic 
To ensure the rights, safety, and well-being of trial participants, as well as the integrity of the 
trial and its data during the COVID-19 pandemic, when onsite study monitoring activities are 
restricted, remote source data verification (rSDV) may be employed wherever permitted by local 
regulations. 
ALXN1210-NEPH-202 is a Phase 2 trial in patients with LN and IgAN. Alexion has assessed 
that the inability to complete ongoing source data verification (SDV) could pose a risk to the 
robustness of the study data. Delaying ongoing verification of key efficacy (primary and 
secondary) endpoints and important safety endpoints could result in late identification of 
incorrect or missing data, which could impact the integrity of the study data.  
Remote SDV will be carried out in written agreement with the Investigator and, if applicable, the 
institution, under conditions ensuring adequate data protection and participants’ rights. 
Depending on local regulation and agreement with the site Investigator and institution 
preference, rSDV may be conducted through direct and controlled read-only monitor access to 
institution electronic medical records systems, passive access to source documents via live image 
transmission, and/or sharing of redacted copies of source documents via a secure, validated, and 
access-restricted system. Regarding the electronic sharing of redacted copies of source 
documents, the following requirements must be followed:  

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• Scanned or electronic documents to be uploaded (as PDF, jpeg, or other image 
format) that are of sufficient resolution to ensure readability, in black and white or 
color. 
• To ensure completeness of the shared content, the monitor will prepare a written 
request to the investigative site listing the source data needed to conduct rSDV and 
will perform a quality check on the list of documents shared by the site against the list 
of requested source data. 
• Site staff must perform a quality check ensuring source documents are redacted 
before making them available to monitors. A data breach management policy and a 
security team will be in place to identify violations and to ensure correct and timely 
action. 
• To prevent loss of or unauthorized access to source data, investigative site personnel 
will need to actively grant access to their specific monitor. The monitor will only 
have viewing rights, thereby preventing loss, alteration, or download of source data. 
• Traceability of pseudonymized documents reviewed remotely will be kept by the 
monitor for verification onsite. 
The detailed scope of rSDV will be outlined in supporting study plans (eg, Clinical Monitoring 
Plan). Conduct of rSDV will only be performed during the COVID-19 pandemic. 
 

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10.2. 
Clinical Laboratory Tests 
• The tests detailed in Table 13 will be performed by the study central laboratory, 
unless otherwise noted.  
• Local laboratory results are required in the event that the central laboratory results are 
not available in time for either study intervention administration and/or response 
evaluation. If a local sample is required, it is important that the sample for central 
analysis is obtained at the same time. Additionally, if the local laboratory results are 
used to make either a study intervention decision or response evaluation, the results 
must be entered into the CRF. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5 of the protocol. 
• Additional tests may be performed at any time during the study as determined 
necessary by the Investigator or required by local regulations. 
• Pregnancy testing: WOCBPs should only be enrolled after a negative serum 
pregnancy test result at Screening. Additional urine pregnancy testing will be 
standard for the protocol unless serum testing is required by site policies, local 
regulation, or IRB/IEC and should be performed per the time points specified in the 
Schedule of Activities (Section 1.3). 
• Investigators must document their review of each laboratory safety report. 
Table 13: 
Protocol-Required Laboratory Assessments 
Laboratory Assessments 
Parameters 
Hematology 
• Red blood cell count 
• Hemoglobin 
• Hematocrit 
• RBC indices 
o Mean corpuscular volume 
o Mean corpuscular hemoglobin 
o Percentage of reticulocytes 
o Corpuscular hemoglobin content 
• White blood cell count with differential (including early progenitors): 
o Neutrophils, segmented 
o Lymphocytes 
o Monocytes 
o Eosinophils 
o Basophils  
o Platelet count  
o Mean platelet volume  

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Table 13: 
Protocol-Required Laboratory Assessments 
Laboratory Assessments 
Parameters 
Coagulation panel 
• INR 
• PT 
• APTT 
• D-Dimer 
• Fibrinogen 
Clinical chemistry 
• Liver function tests:  
o ALT  
o AST  
o ALP 
o Albumin  
o Total protein 
o Bilirubin (total, direct and indirect)  
o GGT 
o Glucose  
• Renal function:  
o Blood urea nitrogen 
o Calcium  
o Chloride 
o Creatinine and eGFR calculated using CKD-EPI formula  
o Magnesium 
o Phosphate 
o Potassium 
o Sodium  
o Total carbon dioxide 
o Urea 
24-h urine  
• Total protein, total creatinine, total albumin, total sodium, creatinine 
clearance, and protein to creatinine ratio, albumin to creatinine ratio. 
Spot urine studies  
• Protein, albumin, creatinine, and protein to creatinine and 
albumin/creatinine ratio 
Routine urinalysis 
and urine sediment 
• Albumin 
• Bilirubin 
• Blood 
• Erythrocytes  
• Glucose 
• Ketones 
• Leukocyte esterase 

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Table 13: 
Protocol-Required Laboratory Assessments 
Laboratory Assessments 
Parameters 
• Nitrite 
• pH 
• Protein 
• Specific gravity 
• Urobilinogen 
• Urine sediment: number of RBCs/high-power field and number of 
RBC casts b 
PK/PD and 
immunogenicity 
• Serum PK  
• Serum PD (free and total C5) 
• Immunogenicity (ADA)  
Other study-specific tests 
• HCV PCR viral load, HBV antigen and serology panel 
• HIV-1 and HIV-2 antibody  
• Serum follicle-stimulating hormone (as needed in women of 
nonchildbearing potential only) 
• Serum or urine human chorionic gonadotropin pregnancy test (as 
needed for WOCBPs)a  
• Complement: C3, C4, and CH50  
• Autoantibody profile: ANA, anti-dsDNA, anti-Sm, anti-RNP, 
anti-Ro, anti-La, anti-C1q, anti-phospholipid antibodies (LN cohort 
only) 
 
• Anti-ds-DNA antibody: to be measured by ELISA at all visits as part 
of SLEDAI Assessment (LN cohort only) 
a Serum pregnancy test at Screening and End of Study Visit/Early Discontinuation Visit, and local urine pregnancy 
test at all other times as specified in Schedule of Assessments. 
b For participants in the IgAN cohort, eligibility for hematuria can be determined via the local laboratory. 
Abbreviations: ADA = antidrug antibody; ALP =alkaline phosphatase; ALT = alanine aminotransferase; 
ANA = antinuclear antibody; anti-C1q = anti-complement component C1q; anti-La = anti-small RNA binding 
exonuclease protection factor La; anti-Ro = anti-Sjögren’s-syndrome-related antigen A; anti-Sm= anti-Smith 
antibody; APTT =activated partial thromboplastin time; AST = aspartate aminotransferase; C3, C4, and 
C5 = complement components 3, 4, and 5; CH50 = 50% hemolytic complement activity; CKD-EPI = Chronic 
Kidney Disease Epidemiology Collaboration; dsDNA = double-stranded DNA; eGFR = estimated glomerular 
filtration rate; ELISA = enzyme-linked immunosorbent assay; GGT = gamma-glutamyltransferase; 
HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; 
IgAN = immunoglobulin A nephropathy; INR = international normalized ratio; LN = lupus nephritis; 
RNP = ribonucleoprotein; PCR = polymerase chain reaction; PD = pharmacodynamic; PK = pharmacokinetic; 
PT = prothrombin time; RBC = red blood cell; SLEDAI = Systemic Lupus Erythematosus Disease Activity Index; 
WOCBP = women of childbearing potential 

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10.3. 
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a participant, temporally associated with the use of 
study intervention, whether or not considered related to the study intervention. 
• 
Note: An AE 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 study intervention. 
 
Events Meeting the AE Definition  
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen 
from baseline, 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 study intervention 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 study intervention or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
• 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be reported as an 
AE or SAE. 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 AE or SAE if 
they fulfil the definition of an AE or SAE.  
 
Events Not Meeting the AE Definition  
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): The condition that leads to the 
procedure is the AE. Situations in which an untoward medical occurrence did not occur (eg, 
hospitalization for elective surgery if planned before the signing the ICF, admissions for social 
reasons or for convenience).  
• 
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.  
• 
A medication error (including intentional misuse, abuse, and overdose of the product) or use other 
than what is defined in the protocol is not considered an AE unless there is an untoward medical 
occurrence as a result of a medication error.  

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Events Not Meeting the AE Definition  
• 
Cases of pregnancy that occur during maternal or paternal exposure to study drug are to be reported 
within 24 hours of Investigator/site awareness. Data on fetal outcome and breastfeeding will be 
collected for regulatory reporting and safety evaluation.  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which 
are associated with the underlying disease, unless judged by the Investigator to be more severe than 
expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s condition. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
10.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose: 
1. Results in death 
2. Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the participant 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 was more severe. 
3. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant 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 AEs. 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 AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is 
not considered an AE. 
4. Results in persistent 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. 
5. Is a congenital anomaly/birth defect 
6. Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE 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 participant or may require 

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An SAE is defined as any untoward medical occurrence that, at any dose: 
medical or surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually 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. 
 
An SUSAR is defined as: 
A serious event that is not listed in the IB and that the Investigator identifies as related to 
investigational product or procedure. United States Title 21 CFR 312.32 and European Union Clinical 
Trial Directive 2001/20/EC and the associated detailed guidances or national regulatory requirements 
in participating countries require the reporting of SUSARs. Alexion has procedures that will be 
followed for the recording and expedited reporting of SUSARs that are consistent with global 
regulations and the associated detailed guidances. Suspected unexpected serious adverse reactions will 
be reported to the national competent authority and IRBs/IECs where applicable.  
10.3.3. 
Recording and Follow-Up of AE and/or SAE 
Recording of AE and/or SAE 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records to 
Alexion in lieu of completion of the AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by 
Alexion. In this case, all participant identifiers, with the exception of the participant number, will 
be redacted on the copies of the medical records before submission to Alexion. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to one of the following categories from National Cancer Institute Common Terminology 
Criteria for Adverse Events (CTCAE) v5.0, published 27 Nov 2017:  
• 
Grade 1: Mild (awareness of sign or symptom, but easily tolerated) 
• 
Grade 2: Moderate (discomfort sufficient to cause interference with normal activities) 
• 
Grade 3: Severe (incapacitating, with inability to perform normal activities) 
• 
Grade 4: Life-threatening 
• 
Grade 5: Fatal 
An event is defined as “serious” when it meets at least one of the predefined outcomes as described in 
the definition of an SAE, not when it is rated as severe. 
 

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Assessment of Causality 
• 
The Investigator is obligated to assess the relationship between the study intervention and each 
occurrence of each AE or SAE. An Investigator causality assessment must be provided for all AEs 
(both nonserious and serious). This assessment must be recorded in the CRF and on any additional 
forms, as appropriate. The definitions for the causality assessments are as follows: 
− 
Not related: There is no reasonable possibility the study intervention caused the AE.  
 
The AE has a more likely alternative etiology; it may be due to underlying or 
concurrent illness, complications, concurrent treatments, or effects of another 
concurrent drug.  
 
The event does not follow a reasonable temporal relationship to administration 
of the study intervention. 
− 
Related: There is a reasonable possibility the study intervention caused the AE. 
 
The AE has a temporal relationship to the administration of the study 
intervention. 
 
The event does not have a likely alternative etiology.  
 
The event corresponds with the known pharmaceutical profile of the study 
intervention. 
 
There is improvement on discontinuation and/or reappearance on rechallenge. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study intervention administration will be 
considered and investigated. 
• 
The Investigator will also consult the IB and/or Product Information, for marketed products, in 
his/her assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to Alexion. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial transmission 
of the SAE data to Alexion. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Alexion to elucidate 
the nature and/or causality of the AE or SAE as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals. 
• 
If a participant dies during participation in the study or during a recognized Follow-up Period, the 
Investigator will provide Alexion with a copy of any postmortem findings including 
histopathology. 

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Follow-up of AEs and SAEs 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The Investigator will submit any updated SAE data to Alexion within 24 hours of receipt of the 
information. 
10.3.4. 
Reporting of SAEs  
SAE Reporting to Alexion via an Electronic Data Collection Tool 
• 
All SAEs will be recorded and reported to Alexion or designee immediately and within 24 hours 
of awareness. 
• 
The primary mechanism for reporting an SAE to Alexion will be the electronic data collection 
tool. 
• 
If the electronic system is unavailable at the time that the Investigator or site becomes aware of 
an SAE, the site will use the paper Contingency Form for SAE reporting via fax or email. 
Facsimile transmission or email may be used in the event of electronic submission failure. 
− 
Email: clinicalsae@alexion.com or Fax: + 1.203.439.9347 
• 
The site will enter the SAE data into the EDC system as soon as it becomes available. 
• 
When further information becomes available, the EDC should be updated within 24 hours with 
the new information and an updated SAE report should be submitted to Alexion global drug 
safety (GDS).  
• 
After the study is completed at a given site, the electronic data collection tool 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 SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then the 
site can report this information on a paper SAE form. 
10.3.5. 
Unexpected Events 
Apart from the reporting of SUSARs, there may be other events which are relevant in terms of 
benefit-risk balance and which should be reported in a timely manner according to regional and 
national requirements [eg, EU CTR 536/2014 (48)]. It is important for participant safety that, in 
addition to SAEs and reactions, all unexpected events that might materially influence the 
benefit-risk assessment of the study intervention or that would lead to changes in the 
administration of the study intervention or in overall conduct of a clinical trial should be 
reported. Examples of such unexpected events include an increase in the rate of occurrence of 
expected serious adverse reactions which may be clinically important, a significant hazard to the 
patient population, such as lack of efficacy of a medicinal product, or a major safety finding from 
a newly completed animal study (such as, carcinogenicity). 
Under the EU CTR 536/2014 (49), where unexpected events require an urgent modification of a 
clinical trial, it should be possible for Alexion and the Investigator to take urgent safety measures 
without awaiting prior authorization. If such measures constitute a temporary halt of the clinical 
trial, Alexion should apply for a substantial modification before restarting the clinical trial. 
 

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10.4. 
Management of Potential Infusion-related Adverse Events During 
Ravulizumab Administration 
Intravenous and infusion-related reactions are a potential risk with the use of monoclonal 
antibodies; these reactions can be nonimmune or immune mediated (eg, hypersensitivity 
reactions). Signs and symptoms may include headache, fever, facial flushing, pruritus, myalgia, 
nausea, chest tightness, dyspnea, vomiting, erythema, abdominal discomfort, diaphoresis, 
shivers, hypertension, lightheadedness, hypotension, palpitations, and somnolence. Signs and 
symptoms of hypersensitivity or allergic reactions may include hives, swollen face, eyelids, lips, 
or tongue, or trouble with breathing. 
All administration-, IV-, and infusion-related reactions will be reported to the Investigator and 
qualified designee. The Investigator and qualified designee are responsible for detecting, 
documenting, and recording events that meet the definition of AE or SAE and remain 
responsible for following up events that are serious, considered related to the study drug, or 
study procedures; or that caused the participant to discontinue ravulizumab (Section 7). 
Definitions and procedures for recording, evaluating, follow-up, and reporting AEs and SAEs are 
outlined in Section 10.3. 
Participants who experience a reaction during the administration of ravulizumab should be 
treated according to institutional guidelines. 
Participants who experience a severe reaction during administration of ravulizumab resulting in 
discontinuation of ravulizumab should undergo all scheduled safety, PK, and PD evaluations 
required by the protocol. Alexion must be notified within 24 hours of any infusion-related 
reaction requiring interruption or discontinuation of ravulizumab. All AEs that may indicate an 
infusion-related response will be graded according to CTCAE v5.0 or higher.  
If anaphylaxis occurs according to the criteria listed in Table 14, then administration of 
subcutaneous epinephrine (1/1000, 0.3 mL to 0.5 mL, or equivalent) should be considered. In the 
case of bronchospasm, treatment with an inhaled beta agonist also should be considered. 
Participants administered an antihistamine for the treatment or prevention of an infusion-related 
reaction should be given appropriate warnings about drowsiness and impairment of driving 
ability before being discharged from the center. 

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Table 14: 
Clinical Criteria for Diagnosing Anaphylaxis 
Anaphylaxis is highly likely when any 1 of the following 3 criteria is fulfilled: 
• 
Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, 
or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula), and at least 1 of 
the following: 
o Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia) 
o Reduced blood pressure or associated symptoms of end-organ dysfunction (eg, hypotonia 
[collapse], syncope, incontinence)  
• 
Two or more of the following that occur rapidly after exposure to a likely allergen for that 
participant (minutes to several hours): 
o Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen 
lips/tongue/uvula) 
o Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia) 
o Reduced blood pressure or associated symptoms (eg, hypotonia [collapse], syncope, 
incontinence) 
o Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)  
• 
Reduced blood pressure after exposure to known allergen for that participant (minutes to several 
hours): 
o 
Systolic blood pressure of less than 90 mmHg or greater than 30% decrease from that 
participant’s baseline 
Source: Sampson, 2006 
10.5. 
Medication Error, Drug Abuse, and Drug Misuse 
Medication Error 
For the purposes of this clinical study a medication error is an unintended failure or mistake in 
the treatment process for a study intervention that either causes harm to the participant or has the 
potential to cause harm to the participant.  
Any events of medication error, with or without associated AEs, are to be captured and 
forwarded to Alexion Global Patient Safety via email or facsimile (clinicalsae@alexion.com or 
+ 1.203.439.9347) using the Alexion Clinical Study Medication Error Report Form. 
A medication error is not lack of efficacy of the study intervention, but rather a human or process 
related failure while the intervention is under the control of the study site staff or participant. 
Medication error includes situations where an error:  
• Occurred 
• Was identified and intercepted before the participant received the drug 
• Did not occur, but circumstances were recognized that could have led to an error 
Examples of events to be reported in clinical studies as medication errors:  

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• Drug name confusion 
• Dispensing error, eg, medication prepared incorrectly, even if it was not actually 
given to the participant 
• Drug not administered as indicated, eg, wrong route or wrong site of administration 
• Drug not taken as indicated, eg, tablet dissolved in water when it should be taken as a 
solid tablet  
• Drug not stored as instructed, eg, kept in the refrigerator when it should be at room 
temperature  
• Wrong participant received the medication (excluding IRT/Randomization and Trial 
Supply Management [RTSM] errors) 
• Wrong drug administered to participant (excluding IRT/RTSM errors) 
Examples of events that do not require reporting as medication errors in clinical studies: 
• Errors related to or resulting from IRT/RTSM - including those which led to one of 
the above listed events that would otherwise have been a medication error  
• Participant accidentally missed drug dose(s), eg, forgot to take medication 
• Accidental overdose (will be captured as an overdose [refer to Section 8.6 for 
information on overdose]) 
• Participant failed to return unused medication or empty packaging  
Medication errors are not regarded as AEs but AEs may occur as a consequence of the 
medication error. 
Drug Abuse 
For the purpose of this study, drug abuse is defined as the persistent or sporadic intentional, 
nontherapeutic excessive use of study intervention for a perceived reward or desired 
nontherapeutic effect. 
Any events of drug abuse, with or without associated AEs, are to be captured and forwarded to 
Alexion Global Patient Safety via email or facsimile (clinicalsae@alexion.com or 
+ 1.203.439.9347) using the Alexion Clinical Study Drug Misuse or Drug Abuse Report Form. 
This form should be used both if the drug abuse happened in a study participant or if the drug 
abuse involves a person not enrolled in the study (such as a relative of the study participant). 
Examples of drug abuse include but are not limited to: 
• The drug is used with the intent of getting a perceived reward (by the study 
participant or a person not enrolled in the study) 
• The drug in the form of a tablet is crushed and injected or snorted with the intent of 
getting high  
Drug Misuse 
Drug misuse is the intentional and inappropriate use of study intervention for medicinal purposes 
outside of the authorized product information, or for unauthorized study intervention, outside the 

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intended use as specified in the protocol, including deliberate administration of the product by 
the wrong route. 
Events of drug misuse, with or without associated AEs, are to be captured and forwarded to 
Alexion Global Patient Safety via email or facsimile (clinicalsae@alexion.com or 
+ 1.203.439.9347) using the Alexion Clinical Study Drug Misuse or Drug Abuse Report Form. 
This form should be used both if the drug misuse happened in a study participant or if the drug 
misuse involves a person not enrolled in the study (such as a relative of the study participant). 
Examples of drug misuse include but are not limited to: 
• The drug is used with the intention to cause an effect in another person 
• The drug is sold to other people for recreational purposes  
• The drug is used to facilitate assault in another person 
• The drug is deliberately administered by the wrong route 
• The drug is split in half because it is easier to swallow, when it is stated in the 
protocol that it must be swallowed whole 
• Only half the dose is taken because the study participant feels that he/she is feeling 
better when not taking the whole dose 
• Someone who is not enrolled in the study intentionally takes the drug 

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10.6. 
Contraceptive Guidance and Collection of Pregnancy Information 
10.6.1. 
Definitions 
Woman of Childbearing Potential 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study drug, additional evaluation should be considered. 
Women in the following categories are not considered WOCBPs. 
1. Premenarchal 
2. Premenopausal female with one of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
• For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, Mullerian agenesis, androgen insensitivity), Investigator discretion should 
be applied to determining study entry. 
• Note: Documentation can come from the site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.  
− A high follicle stimulating hormone (FSH) level in the postmenopausal range may 
be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence 
of 12 months of amenorrhea, confirmation with more than 1 FSH measurement 
may be required.  
• Females on HRT and whose menopausal status is in doubt will be required to use one 
of the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
10.6.2. 
Contraception Guidance 
10.6.2.1. Guidance for Female Participants 
Female participants of non-childbearing potential are exempt from contraception requirements. 
Non-childbearing potential for female participants is defined as any of the following:  
1. Prior to first menses  

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2. Postmenopausal, as documented by amenorrhea for at least 1 year prior to the Day 1 Visit. 
Confirmatory FSH serum levels consistent with postmenopausal status may be obtained by 
the Investigator at Screening. In the absence of 12 months of amenorrhea, multiple elevated 
FSH levels will be required. The reason for not obtaining an FSH should be documented by 
the Investigator at the time of Screening 
3. Permanent sterilization at least 6 weeks prior to the Day 1 Visit  
4. Hysteroscopic sterilization  
5. Bilateral tubal ligation or bilateral salpingectomy  
6. Hysterectomy  
7. Bilateral oophorectomy  
Female participants of child-bearing potential must use a highly effective method of 
contraception, including at least 1 of the following until at least 8 months after the final dose of 
study drug:  
1. Intrauterine device in place for at least 6 weeks prior to first dose.  
2. Progestogen-only hormonal contraception (either oral, injectable, or implantable) for at least 
6 weeks prior to first dose.  
3. Intrauterine progestogen releasing system for at least 6 weeks prior to first dose.  
4. Bilateral tubal occlusion for at least 6 weeks prior to first dose.  
5. Combined (estrogen- and progestogen-containing) hormonal contraception (either oral, 
intravaginal, or transdermal) for at least 6 weeks prior to first dose.  
6. Surgical sterilization of the male partner (medical assessment of azoospermia is required if 
vasectomy was performed within 6 months prior to first dose).  
7. Sexual abstinence for female participants:  
• Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse. In this study, abstinence is only acceptable 
if consistent with the participant’s preferred and usual lifestyle. Abstinent female 
participants who wish to initiate a highly effective method of contraception during the 
study must refrain from heterosexual intercourse for at least 8 months after the final 
dose of study drug.  
• Periodic abstinence (eg, calendar, symptothermal, or post-ovulation methods) is not 
considered a highly effective method of contraception for female participants.  
Other methods of contraception that are not considered highly effective for female participants:  
1. Barrier methods, such as male or female condoms, diaphragm, or cervical cap, used alone or 
in combination, are not acceptable.  
2. Spermicides or spermicidal sponges, used alone or in combination with barrier methods, are 
not acceptable.  
Withdrawal (coitus interruptus) is not acceptable.  

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Lactational amenorrhea is not acceptable. 
Female participants must not donate ova from the Day 1 visit until 8 months after the final dose 
of study drug.  
10.6.2.2. Guidance for Male Participants  
Contraception is the responsibility of the heterosexually active male participants, regardless of 
his female partner’s method of contraception.  
Male participants who have had a vasectomy > 6 months prior to first dose must use a condom 
during heterosexual intercourse. Male participants who have had a vasectomy < 6 months prior 
to first dose must use a condom and spermicide during heterosexual intercourse.  
Male participants who have not had a vasectomy must use a condom and spermicide during 
heterosexual intercourse 8 months after their final dose of study drug.  
10.6.2.2.1. Sexual Abstinence for Male Participants  
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse. In this study, abstinence is only acceptable if consistent with the 
participants’ s preferred and usual lifestyle. Abstinent male participants who become 
heterosexually active must use a condom and spermicide during intercourse.  
Periodic abstinence (eg, calendar, symptothermal, or post-ovulation methods for a female 
partner) is not considered a highly effective method of contraception for male participants.  
Male participants must not donate sperm from the Day 1 visit until 8 months after their final dose 
of study drug.  
10.6.3. 
Collection of Pregnancy Information 
Pregnancy data will be collected during this study for all female participants and female 
spouses/partners of male participants from the signing of the ICF until 8 weeks after last dose of 
the study drug is administered. Any female participant who becomes pregnant while 
participating in the study will be discontinued from the study drug. Exposure during pregnancy 
(also referred to as exposure in utero) can be the result of either maternal exposure or 
transmission of study drug via semen following paternal exposure. If a female participant or a 
male participant’s female partner becomes pregnant during the conduct of this study, the 
Investigator must submit the “Pregnancy Reporting and Outcome/Breastfeeding” form to 
Alexion GDS via facsimile or email. When the outcome of the pregnancy becomes known, the 
form should be updated and submitted to Alexion GDS. If additional follow-up is required, the 
Investigator will be requested to provide the information.  
Exposure of an infant to study drug during breastfeeding must also be reported (via the 
“Pregnancy Reporting and Outcome Form/Breastfeeding”) and any AEs experienced by the 
infant must be reported to Alexion GDS or designee via email or facsimile.  
Pregnancy is not regarded as an AE unless there is a suspicion that the study drug may have 
interfered with the effectiveness of a contraceptive medication. However, complications of 
pregnancy and abnormal outcomes of pregnancy are AEs and may meet the criteria for an SAE 

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(eg, ectopic pregnancy, spontaneous abortion, intrauterine fetal demise, neonatal death, or 
congenital anomaly). Elective abortions without complications should not be reported as AEs.  
Any female participant who becomes pregnant while participating in the study will be 
discontinued from study drug.  
10.6.3.1. Male Participants With Partners Who Become Pregnant 
• The Investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while the male participant is in 
this study. This applies only to male participants who receive study drug. 
• After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the Investigator will record pregnancy information on the appropriate 
Pregnancy Outcome/Breastfeeding form and submit it to Alexion within 24 hours of 
learning of the partner’s pregnancy. The female partner will also be followed to 
determine the outcome of the pregnancy. Information on the status of the mother and 
child will be forwarded to Alexion. Generally, the follow-up will be no longer than 
3 months following the estimated delivery date. Any termination of the pregnancy 
will be reported regardless of fetal status (presence or absence of anomalies) or 
indication for the procedure.  
10.6.3.2. Female Participants Who Become Pregnant 
• The Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. The initial Information will be 
recorded on the appropriate form and submitted to Alexion within 24 hours of 
learning of a participant’s pregnancy.  
• The participant will be followed up to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on the participant and the neonate and 
the information will be forwarded to Alexion. Generally, follow-up will not be 
required for longer than 3 months beyond the estimated delivery date. Any 
termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. A spontaneous abortion (occurring at < 22 weeks 
gestational age) or still birth (occurring at > 22 weeks gestational age) is always 
considered to be an SAE and will be reported as such. Any post-study pregnancy 
related SAE considered reasonably related to the study drug by the Investigator will 
be reported to Alexion as described in Section 8.4.4. While the Investigator is not 
obligated to actively seek this information in former study participants, he or she may 
learn of an SAE through spontaneous reporting. 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study drug. 
 

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10.7. 
Handling of Human Biological Samples 
All research and biological samples, including those for possible future research, are subject to 
national regulations and will only be conducted in a specified country if approved in that 
country. 
Handling, storage, and shipment of biological samples are detailed in the laboratory manual. 
10.7.1. 
Chain of Custody 
A full chain of custody is maintained for all samples throughout their lifecycle. 
The Investigator at each site keeps full traceability of collected biological samples from the 
participants while in storage at the site until shipment or disposal (where appropriate) and 
records relevant processing information related to the samples while at the site. 
The sample receiver keeps full traceability of the samples while in storage and during use until 
used or disposed of or until further shipment and keeps record of receipt of arrival and onward 
shipment or disposal. 
Alexion or delegated representatives will keep oversight of the entire life cycle through internal 
procedures, monitoring of study sites, auditing or process checks, and contractual requirements 
of external laboratory providers. 
Samples retained for further use will be stored in the Alexion-assigned biobanks or other sample 
archive facilities and will be tracked by the appropriate Alexion team for the remainder of the 
sample life cycle. 
All appropriately consented samples will be retained for a maximum of 25 years from study 
completion or other period as per local requirements. 
10.7.2. 
Withdrawal of Informed Consent for Donated Biological Samples  
If a participant withdraws consent to the use of donated biological samples, the samples will be 
disposed of/destroyed/repatriated, and the action documented. If samples are already analyzed, 
Alexion is not obliged to destroy the results of this research. 
Following withdrawal of consent for biological samples, further study participation should be 
considered in relation to the withdrawal processes outlined in the informed consent. 
The Investigator: 
• Ensures the participant’s withdrawal of informed consent to the use of donated 
samples is communicated immediately to Alexion or delegate. 
• Ensures that relevant human biological samples from that participant, if stored at the 
study site, are immediately identified, disposed of as appropriate, and the action 
documented. 
• Ensures that the participant and Alexion are informed about the sample disposal. 
Alexion ensures the organization(s) holding the samples is/are informed about the withdrawn 
consent immediately and that samples are disposed of or repatriated as appropriate, the action is 
documented, and study site is notified. 

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10.8. 
Biomarkers  
• Blood, urine, and kidney tissue samples will be collected for biomarker analyses and 
the data will be used for research (eg, exploratory) related to ravulizumab, or LN, 
IgAN, and related diseases. The samples may also be used to develop methods, 
assays, prognostics and/or companion diagnostics related to the study drug target, 
disease process, pathways associated with disease state, and/or mechanism of action 
of ravulizumab.  
• The samples may be analyzed as part of a multistudy assessment of biomarkers in the 
response to ravulizumab to understand study disease or related conditions. 
• The results of biomarker analyses may be reported in the CSR or in a separate study 
summary. 
• Alexion or designee will store the samples obtained for biomarker analyses in a 
secure storage space with adequate measures to protect confidentiality. 
• The samples will be retained while research on ravulizumab continues but no longer 
than 5 years after termination of the study or other period as per local requirements. 
 

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10.9. 
Systemic Lupus Erythematosus Diagnosis Classification Criteria 
The 2019 European League Against Rheumatism / American College of Rheumatology 
Classification Criteria for SLE (Aringer, 2019) will be used for eligibility of the LN Cohort.  
 
 

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10.10. 
Revised 2018 International Society of Nephrology/Renal Pathology 
Society (ISN/RPS) Classification 
Category  
Recommendation 
Class II 
Definition for mesangial hypercellularity adjusted: Four or more nuclei fully 
surrounded by matrix in the mesangial area not including the hilar region  
Class III and IV 
The term endocapillary proliferation is replaced by endocapillary 
hypercellularity  
 
The term crescent is used for a lesion consisting of extracapillary 
hypercellularity, composed of a variable mixture of cells. Fibrin and fibrous 
matrix may be present; 10% or more of the circumference of Bowman’s 
capsule should be involved. 
 
Cellular crescent: more than 75% cells and fibrin and less than 25% fibrous 
matrix  
 
Fibrous crescent: more than 75% fibrous matrix and less than 25% cells and 
fibrin  
 
Fibrocellular crescent: 25% to 75% cells and fibrin and the remainder 
fibrous matrix  
 
Adhesion: an area of isolated continuity of extracellular matrix material 
between the tuft and capsule even when the underlying segment does not 
have overt sclerosis 
 
Fibrinoid necrosis: fibrin associated with glomerular basement membrane 
disruption and/or lysis of the mesangial matrix; this lesion does not require 
the presence of karyorrhexis 
 
Elimination of segmental and global subdivisions of Class IV  
 
Modification of the NIH lupus nephritis activity and chronicity scoring 
system to be used instead of the currently used A, C, and A/C parameters  
Tubulointerstitial 
lesions 
Indicate whether interstitial inflammation occurs in presence or absence of 
interstitial fibrosis 
Source: Bajema, 2018 
 

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10.11. 
IgAN Diagnosis Classification Criteria 
2016 Oxford Classification from the IgA Nephropathy Classification Working Group  
Detailed description of the features present on: 
• Light microscopy 
• Immunohistochemistry or immunofluorescence 
• Electron microscopy 
Summary of 5 key pathologic features 
• Mesangial score < 0.5 (M0) or > 0.5 (M1) 
• Endocapillary hypercellularity absent (E0) or present (E1) 
• Segmental glomerulosclerosis absent (S0) or present (S1); presence or absence of 
podocyte hypertrophy/tip lesions in biopsy specimens with S1 
• Tubular atrophy/interstitial fibrosis #25% (T0), 26% to 50% (T1), or > 50% (T2) 
• Cellular/fibrocellular crescents absent (C0), present in at least 1 glomerulus (C1), in 
> 25% of glomeruli (C2) 
Quantitative data 
• Total number of glomeruli 
• Number of glomeruli with endocapillary hypercellularity, necrosis, extracapillary 
hypercellularity (cellular/fibrocellular crescents), global glomerulosclerosis, and 
segmental glomerulosclerosis 
Source: Trimarchi, 2017 
 

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10.12. 
Systemic Lupus Erythematosus Disease Activity Index SELENA 
Modification (SLEDAI–2K) 
The SLEDAI–2K is used to define Extrarenal SLE Flare defined by ≥ 4 points that is not 
accounted for by proteinuria, hematuria, urinary casts, hypocomplementemia, pyuria, or an 
increase in anti-dsDNA antibody level (ie, the shaded sections below). 
Physicians Global Assessment: 
 
 
 
 
 
0  
None 
1 
Mild 
2 
Med 
3 
Severe 
SLEDAI SCORE 
Check box: If descriptor is present at the time of visit or in the proceeding 30 days 
Wt 
Present 
Descriptor  
Definition 
8 
□ 
Seizure 
Recent onset. Exclude metabolic, infectious or drug cause 
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. Excluded uremia and drug 
causes. 
8 
□ 
Organic Brain 
Syndrome 
Altered mental function with impaired orientation, memory or other 
intelligent function, with rapid onset fluctuating clinical features. Include 
clouding of consciousness with reduced capacity to focus, and 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, infectious or drug causes. 
 
8 
□ 
Visual 
Disturbance 
Retinal changes of SLE. Include cytoid bodies, retinal hemorrhages, 
serious exodate or hemorrhages in the choroids, or optic neuritis. Exclude 
hypertension, infection, or drug causes. 
8 
□ 
Cranial Nerve 
Disorder 
New onset of sensory or motor neuropathy involving cranial nerves. 
8 
□ 
Lupus Headache 
Severe persistent headache: may be migrainous, but must be nonresponsive 
to narcotic analgesia. 
8 
□ 
CVA 
New onset of cerebrovascular accident(s). Exclude arteriosclerosis 
8 
□ 
Vasculitis 
Ulceration, gangrene, tender finger nodules, periungual, infarction, 
splinter hemorrhages, or biopsy or angiogram proof of vasculitis 
4 
□ 
Arthritis 
More than 2 joints with pain and signs of inflammation (ie, tenderness, 
swelling, or effusion). 
4 
□ 
Myositis 
Proximal muscle aching/weakness, associated with elevated creatine 
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. 

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Wt 
Present 
Descriptor  
Definition 
4 
□ 
Proteinuria 
> 0.5 gm/24 hours. New onset or recent increase of more than 0.5 gm/24 
hours. 
4 
□ 
Pyuria 
> 5 white blood cells/high power field. Exclude infection. 
2 
□ 
New Rash 
New onset or recurrence of inflammatory type rash 
2 
□ 
Alopecia 
New onset or recurrence of abnormal, patchy or diffuse loss of hair. 
2 
□ 
Mucosal Ulcers 
New onset or recurrence of oral or nasal ulcerations 
2 
□ 
Pleurisy 
Pleuritic chest pain with pleural rub or effusion, or pleural thickening 
2 
□ 
Pericarditis 
Pericardial pain with at least 1 of the following: rub, effusion, or 
electrocardiogram confirmation. 
2 
□ 
Low Complement 
Decrease in CH50, C3, or C4 below the lower limit of normal for testing 
laboratory. 
2 
□ 
Increased DNA 
binding 
> 25% binding by Farr assay or above normal range for testing laboratory. 
1 
□ 
Fever 
> 38°C. Exclude infectious cause 
1 
□ 
Thrombocytopenia 
< 100,000 platelets/mm3 
1 
□ 
Leukopenia 
< 3000 White blood cell/mm3. Exclude drug causes. 
_____   TOTAL SCORE (Sum of weights next to descriptors marked present) 

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10.13. 
Short Form Health Survey (SF-36) 
 
 
 
 

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Short Form Health Survey (SF-36) (Continued) 
 
 

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Short Form Health Survey (SF-36) (Continued) 
 
 
 

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Short Form Health Survey (SF-36) (Continued) 
 
 

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Short Form Health Survey (SF-36) (Continued) 
 
 
 

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Short Form Health Survey (SF-36) (Continued) 
 
 

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10.14. 
EuroQol 5 Dimensions (EQ-5D-5L) 
 
 
 
 

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EuroQol 5 Dimensions (EQ-5D-5L) (Continued) 
 

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EuroQol 5 Dimensions (EQ-5D-5L) (Continued) 
 

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10.15. 
FACIT-Fatigue Subscale Version 4 
 
 

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10.16. 
Abbreviations 
 
Abbreviation 
Definition 
ACE 
angiotensin-converting enzyme  
ACR 
American College of Rheumatology 
ADA 
antidrug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
aHUS 
atypical hemolytic uremic syndrome 
ANCOVA 
analysis of covariance 
anti-ds DNA 
anti-double-stranded DNA 
ANA 
antinuclear antibody 
ARB 
angiotensin II receptor blocker 
C1q 
complement component C1q 
C3 
complement component 3 
C4 
complement component 4 
C5 
complement component 5 
C5a 
complement component 5a 
C5b-9 
terminal complement complex 
CDF 
cumulative distribution function 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CKD 
chronic kidney disease  
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration  
Cmax 
maximum (peak) serum concentration observed after drug administration 
CONSORT 
Consolidated Standards of Reporting Trials  
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CRR 
complete renal response 
CSR 
clinical study report 
CTIS 
Clinical Trials Information System 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTR 
clinical trial regulation 

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Abbreviation 
Definition 
Ctrough 
concentration at the end of the dosage interval 
DPIA 
data protection impact assessment 
dsDNA 
double-stranded DNA 
ECG 
electrocardiogram 
ED 
early discontinuation 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate 
EMA 
European Medicines Agency 
EoS 
End of Study 
EQ-5D-5L 
European Quality of Life Health 5-item questionnaire dimensions 5 level 
ERA-EDTA 
European Renal Association-European Dialysis and Transplant Association 
ESRD 
end-stage renal disease 
EU CTR 
European Union Clinical Trials Regulation 
EULAR 
European League Against Rheumatism 
FACIT 
Functional Assessment of Chronic Illness Therapy 
FAS 
Full Analysis Set 
FSGS 
focal segmental glomerulosclerosis 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
GDS 
global drug safety 
GDPR 
General Data Protection Regulation 
GMR 
geometric mean ratio 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
H/E 
hematoxylin and eosin stain 
Hib 
Haemophilus influenzae type b 
HIPAA 
Health Insurance Portability and Accountability Act  
HIV 
human immunodeficiency virus 
hpf 
high power field 
HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure 
IC 
immune complex 

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Abbreviation 
Definition 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IgA 
immunoglobulin A 
IgA1 
immunoglobulin A1 
IgAN  
immunoglobulin A nephropathy 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IMG 
idiopathic membranous glomerulopathy 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ISN/RPS 
International Society of Nephrology/renal Pathology Society 
IT 
information technology 
IV 
intravenous(ly) 
K2EDTA 
dipotassium ethylenediaminetetraacetic acid 
KDIGO 
Kidney Disease Improving Global Outcomes 
LN 
lupus nephritis 
MedDRA 
Medical Dictionary for Regulatory Activities 
MEST-C 
mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial 
fibrosis/tubular atrophy, and the presence of crescents 
MMF 
mycophenolate mofetil 
MMRM 
mixed effect model for repeated measures 
MPS 
mycophenolic acid sodium  
M&S 
modeling and simulation 
N-GAL 
neutrophil gelatinase-associated lipocalin 
NKF 
National Kidney Foundation 
NSAID 
nonsteroidal anti-inflammatory drug 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic(s) 
PK 
pharmacokinetic(s) 
PNH 
paroxysmal nocturnal hemoglobinuria 

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Abbreviation 
Definition 
PRR 
partial renal response 
q8w 
every 8 weeks 
QT 
interval between the start of the Q wave and the end of the T wave in an ECG 
QTc 
corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
RA 
rheumatoid arthritis 
RAS 
renin-angiotensin system 
rSDV 
remote source data verification 
RBC 
red blood cell 
RTCA 
Real Time Complement Activity 
RTSM 
Randomization and Trial Supply Management 
sC5b-9 
soluble C5b-9 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SD 
standard deviation 
SDV 
source data verification 
SELENA  
Safety of Estrogen in Lupus Erythematosus National Assessment 
SF-36  
Short Form (36) Health Survey 
SGLT-2 
sodium-glucose cotransporter-2 
SLE 
systemic lupus erythematosus 
SLEDAI–2K 
Systemic Lupus Erythematosus Disease Activity Index SELENA Modification 
SoA 
Schedule of Activities 
SOC 
System Organ Class 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
TMF 
trial master file 
UACR 
albumin to creatinine ratio 
UPCR 
urine protein to creatinine ratio 
USPI 
US Prescribing Information 
WOCBP 
woman of childbearing potential 

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10.17. 
Protocol Amendment History 
The protocol amendment summary of changes table for the current amendment is located 
directly after the Table of Contents. 
 
DOCUMENT HISTORY 
Document 
Type of 
Amendment 
(Global or 
Country-specific) 
Date 
Summary of Key Changes in the Amendment 
Amendment 3.0 
Global 
21 Nov 
2023 
• Modifications have been added to address the 
requirements for transitioning a clinical study 
under the EU CTR. Further modifications 
include non-substantial changes, minor 
corrections, and harmonized terminology. 
Amendment 2.1 
SGP, KOR, TWN 
28 Apr 
2022 
• The primary purpose of this amendment is to 
provide clarification for the exclusion criterion 
regarding history of hepatitis B. Patients with 
active hepatitis B or C infection are excluded. 
Patients with previous exposure to hepatitis B 
characterized by positive core antibody 
(anti-HBc) with a positive surface antibody 
(anti-HBs) and patients with past hepatitis C 
effectively treated with documented sustained 
virologic response at the time of Screening may 
be included. Enrollment in the study is not a 
safety risk to the patients based on the specified 
exclusion criteria. Potential inclusion of such 
patients does not have anticipated effects on 
efficacy or safety endpoints. 

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DOCUMENT HISTORY 
Document 
Type of 
Amendment 
(Global or 
Country-specific) 
Date 
Summary of Key Changes in the Amendment 
Amendment 2.0 
Global 
02 Nov 
2021 
• Addressed feedback from local regulatory 
authorities, Institutional Review Boards, and 
Ethics Committees 
• Modified and clarified the inclusion and 
exclusion criteria and minor requirements 
throughout the protocol to allow for expanded 
participant recruitment 
• Added a secondary efficacy endpoint to assess 
suboptimal response in the LN cohort  
• Increased the visit windows for specified visits 
for the IgAN cohort 
• Increased the maximum dose of MMF a LN 
participant can receive, allow for additional 
corticosteroid taper following Week 26 
• Updated the criteria to determine valid 24-hour 
urine collections 
• Removed the option of home infusion visits 
• Clarified the process for unblinding a 
participant’s treatment assignment for safety 
reasons 
• Added clarification for the statistical analyses 
• Provided additional COVID-19 related 
mitigation and monitoring guidance. 
Amendment 1.5 
UK 
29 Jun 
2021 
• To provide COVID-19 vaccine risk assessment 
Amendment 1.4 
DEU 
17 Jun 
2021 
• To reimplement recommendations from the EC 
that were removed from Amendment 1.3 
Amendment 1.3 
DEU 
13 May 
2021 
• To clarify entry criteria, as done in Amendment 
1.2, but remove the changes in Amendment 1.2 
that included recommendations from the EC. 
Amendment 1.2 
DEU 
07 May 
2021 
• To clarify entry criteria, remove legally 
authorized representative/legal guardian from 
the informed consent process, and provide 
additional COVID-19 related mitigation and 
monitoring guidance 

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DOCUMENT HISTORY 
Document 
Type of 
Amendment 
(Global or 
Country-specific) 
Date 
Summary of Key Changes in the Amendment 
Amendment 1.1 
FRA 
11 Feb 
2021 
• To exclude participants from enrollment who 
have hypersensitivity to any ravulizumab 
excipient, and to clarify the process for 
unblinding a participant’s treatment assignment 
for safety reasons 
Amendment 1 
Global 
24 Sep 
2020 
• To clarify allowed and disallowed medications, 
to provide information on COVID-19 related 
risk mitigations, and to clarify other procedural 
items 
Original 
protocol 
Not applicable 
28 Jul 
2020 
Not applicable 
 

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11. 
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