Conditions: C3 Glomerulopathy (C3G)
Keywords: C3 Glomerulonephritis C3 glomerulopathy C3G DDD dense deposit disease membranoproliferative glomerulonephritis MPGN C3GN idiopathic MPGN
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 57
Healthy volunteers: no

Brief summary:
The aim of this trial is to evaluate the effect of avacopan treatment on renal disease activity in patients with complement component 3 glomerulopathy (C3G). Funding Source - FDA OOPD

Detailed description:
C3 glomerulopathy (C3G) is characterized by evidence of alternative complement activation based on C3 deposition in the glomeruli. There are two forms of the disease: dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). There is no approved treatment for patients with C3G.

This is a randomized, double blind, placebo controlled Phase 2 study to evaluate the safety and efficacy of avacopan (CCX168) in patients with C3G. Patients receive avacopan 30mg or matching placebo orally twice-daily. The placebo-controlled treatment period is 26 weeks (182 days). This will be followed by 26 weeks during which time all patients will receive avacopan (results for this second period will be reported in due course in a follow-up publication). Thereafter, all patients will be followed for eight weeks (56 days) without study drug treatment. The primary objective is to evaluate the efficacy of avacopan compared to placebo based on histologic changes in kidney biopsies taken at baseline and after 26 weeks of treatment. The primary endpoint will be based on the percent change from baseline in the C3G Histologic Index for disease activity.

Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.

Arms:
arm 1: Avacopan (formerly CCX168) 10 mg capsules x 3 administered twice daily during the blinded 26 week blinded treatment period arm 2: Matching placebo capsules x 3 administered twice daily during the 26 week blinded treatment period period

Interventions: intervention 1: Avacopan intervention 2: Avacopan Matching Placebo
Intervention descriptions: intervention 1: Orally administered intervention 2: avacopan matching placebo

Protocol document:
Prot_000.pdf: 
CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
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PROTOCOL 
Protocol Amendment 4.0 
 
TITLE PAGE 
Study Title: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study 
to Evaluate the Safety and Efficacy of Avacopan (CCX168) in 
Patients with C3 Glomerulopathy 
Protocol Number: CL011_168 
Investigational Product: Avacopan (formerly CCX168) 
Indication: Treatment of patients with C3 glomerulopathy 
Sponsor: ChemoCentryx, Inc. 
Development Phase: 2 
IND number 132321 
EudraCT number 2017-001821-42 
Sponsor's Responsible 
Medical Officer: ChemoCentryx, Inc. 
Mountain View, California 94043, USA 
Sponsor Signatory: 
Approval Date: 29 June 2017 
13 September 2017 – Protocol Amendment 1.0 
16 April 2018 – Protocol Amendment 2.0 
10 September 2018 – Protocol Amendment 3.0 
20 March 2019 – Protocol Amendment 4.0 
 
Confidential 
The information contained herein is the property of the Sponsor and may not be reproduced, 
published, or disclosed to others without written authorization of the Sponsor. 
This study will be conducted according to the principles of Good Clinical Practice as described 
in International Conference on Harmonisation guidelines, including the archiving of essential 
documents. 


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INVESTIGATOR SIGNATORY PAGE 
Protocol Number: CL011_168 
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the 
Safety and Efficacy of Avacopan (CCX168) in Patients with C3 Glomerulopathy 
I agree: 
• To assume responsibility for the proper conduct of the study at this site. 
• To conduct the study in compliance with this protocol, any future amendments, and with any 
other study conduct procedures provided by ChemoCentryx, Inc. 
• Not to implement any deviations from or changes to the protocol without agreement from the 
Sponsor and prior review and written approval from the Institutional Review Board 
(IRB)/Ethics Committee (EC), except where necessary to eliminate an immediate hazard to 
the patients, or for administrative aspects of the study (where permitted by all applicable 
regulatory requirements). 
• That I am thoroughly familiar with the appropriate use of the investigational drug(s), as 
described in this protocol, and any other information provided by the Sponsor including, but 
not limited to the following: the current version of the Investigator’s Brochure prepared by 
ChemoCentryx, Inc. and approved product label, if applicable. 
• That I am aware of and will comply with current International Conference on Harmonisation 
ICH/ Food and Drug Administration (FDA) good clinical practices guidelines (GCP) and all 
regulatory requirements. 
• To ensure that all persons assisting me with the study are adequately informed about the 
investigational drug(s) and their study-related duties and function as described in the 
protocol. 
__________________________________  
 
 
 
___________________ 
Principal Investigator  
 
 
 
 
 
 
 
 
 
Date 
 
__________________________________ 
Printed Name 
Address*_____________________________________________________________ 
____________________________________________________________________ 
Phone Number* ___________________________________________ 
* If the address or phone number needs to be changed during the course of the study, this will be 
done by the Investigator, with written notification to the Sponsor, and will not require (a) 
protocol amendment(s). 


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SPONSOR CONTACT INFORMATION 
Protocol Number: CL011_168 
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the 
Safety and Efficacy of Avacopan (CCX168) in Patients with C3 Glomerulopathy 
 
Medical Officer 
Vice President, Clinical Development and Translational Medicine 
ChemoCentryx, Inc. 
850 Maude Avenue 
Mountain View, CA 94043 USA 
Tel:
Fax: +
Email:
 
Clinical Operations Manager 
Director of Clinical Operations, 
ChemoCentryx, Inc. 
850 Maude Avenue 
Mountain View, CA 94043 USA 
Mobile telephone number:
Fax number: 
Email:
 
 
 




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SUMMARY OF CHANGES: PROTOCOL AMENDMENT 3.0 TO 4.0 
1. The protocol Title Page was updated with the new amendment number and date. 
2. Changed subject(s) to patient(s) throughout the document for consistency. 
3. Protocol updated to specify that the study drug or study medication is blinded throughout 
the document, where applicable. 
4. Details on the study drug or medication updated to be avacopan or placebo throughout 
the document. 
5. SYNOPSIS: study period increased from 26 months to 32 months to reflect previous 
increase of sample size and slower than expected enrollment. 
6. SYNOPSIS – Methodology, Section 3.2 Randomization and Section 8.9 Interim Analysis 
have been updated to specify the earliest timepoint for the primary efficacy analysis and 
to clarify that the primary analysis of the primary population (elevated C5b-9 stratum) 
can occur at a timepoint independent of the secondary population. 
7. SYNOPSIS – Methodology has been updated: 
a. To increase the frequency of hematology testing based on the recommendation of the 
DMC. 
b. To clarify the time allowed to differentiate between common fluctuations of renal 
function and true deterioration of renal function and to prevent unnecessary 
discontinuation. 
8. SYNOPSIS – Test Product has been updated to clarify that the medication will be 
administered orally and that placebo contains no active ingredient. 
9. Hematology testing was added to study weeks 23, 35, 41 and 48 to increase the testing 
frequency based on the recommendation of the DMC. The following sections have been 
updated: Time & Events Table, Section 6.10. Study Week 23, Section 6.14. Study Week 
35, 6.16. Study Week 41 and Section 6.18. Study Week 48. 
10. Study Schema simplified for better overview and to present duration of individual 
treatments and to eliminate redundancies (Visit days, Study procedures) and to align with 
the Time and Events Table. 
11. LIST OF ABBREVIATIONS AND ACRONYMS has been updated to include missing 
acronyms. 
12. Section 1.2 Previous Clinical Studies has been updated to include current status of 
clinical studies and additional details on the review of safety data. 
13. Section 3.3.2. Adolescent Patients – Study Treatments, added a statement to clarify the 
procedure to keep study team blinded. 
14. Section 3.4 Study Flow has been updated: 
a. To increase the frequency of hematology testing based on the recommendation of the 
DMC. 


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b. To make statement more concise and reduce redundancies within the protocol; the 
reader is directed to “Section 4.4 Removal of Patients from Therapy” where 
important lab observations are presented that would cause pausing or discontinuation 
of study drug (avacopan or placebo). 
15. Section 4.4 Removal of Patients From Therapy have been updated: 
a. To ensure that liver function tests are repeated in a timely manner, that study drug 
(avacopan or placebo) dosing is paused during investigation into the causality of 
abnormal liver tests and to permanently discontinue study drug when applicable. 
b. To ensure that study drug (avacopan or placebo) dosing is paused during investigation 
into the causality of abnormal hematology and serum chemistry tests. 
c. To relocate paragraph from Section 3.4 to Section 4.4 to ensure that study drug 
(avacopan or placebo) dosing is permanently discontinued if a patient experiences 
deteriorating renal function; for clarification of time allowed to differentiate between 
common fluctuations of renal function and true deterioration of renal function, and to 
prevent unnecessary discontinuation. 
d. To relocate text for laboratory abnormalities from 7.2.4.6. Laboratory Abnormalities  
and consolidate in “Section 4.4 Removal of Patients from Therapy” 
16. Section 5.6 Blinding has been updated to clarify that the actual value, if within normal 
range, will be blinded and reported as “normal” but that values outside the normal range 
will be made available for safety monitoring. 
17. Section 5.9 Concomitant Medications and Restrictions has been updated relocate text to 
“Section 4.4 Removal of Patients from Therapy” where its presentation is more 
appropriate. 
18. Section 7.2.1. Physical Examinations, Vital Signs and 12-lead ECGs has been updated to 
clarify that only clinically significant changes will be recorded as Adverse Events. 
19. Section 7.2.2 Clinical Safety Laboratory Assessments has been updated: 
a. To clarify that safety laboratory assessments are performed through a central 
laboratory for safety monitoring of lab thresholds. 
b. To specify the components of the bilirubin test 
c. To add coagulation test in the case of elevated ALT and ASN 
20. Section 7.2.4.6. Laboratory Abnormalities has been update to make statement more 
concise and reduce redundancies within the protocol. The reader is directed to Section 4.4 
Removal of Patients from Therapy where important lab observations are presented that 
would cause pausing or discontinuation of study drug. 
21. Section 12.3.2 Clinical Evaluation has been updated to include current clinical status, 
clarify patient safety information and to include the clinical safety information based on 
DMC review of safety data from all completed and ongoing studies of avacopan. 
 


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TABLE OF CONTENTS 
INVESTIGATOR SIGNATORY PAGE .........................................................................................2 
SPONSOR CONTACT INFORMATION .......................................................................................3 
SPONSOR SIGNATURE FOR APPROVAL .................................................................................4 
SUMMARY OF CHANGES: PROTOCOL AMENDMENT 3.0 TO 4.0 ......................................5 
TABLE OF CONTENTS .................................................................................................................7 
LIST OF TABLES .........................................................................................................................11 
PROTOCOL SYNOPSIS ..............................................................................................................12 
STUDY SCHEMA.........................................................................................................................26 
TIME AND EVENTS TABLE ......................................................................................................27 
LIST OF ABBREVIATIONS AND ACRONYMS ......................................................................30 
1. 
INTRODUCTION ......................................................................................................33 
1.1. 
Complement and Avacopan ........................................................................................33 
1.2. 
Previous Clinical Studies ............................................................................................34 
1.3. 
Rationale for the Study ...............................................................................................36 
2. 
OBJECTIVES .............................................................................................................37 
2.1. 
Primary Objective .......................................................................................................37 
2.2. 
Secondary Objectives .................................................................................................37 
2.3. 
Exploratory Objectives ...............................................................................................38 
3. 
STUDY DESIGN .......................................................................................................38 
3.1. 
Stratification ...............................................................................................................38 
3.2. 
Randomization ............................................................................................................39 
3.3. 
Study Treatments ........................................................................................................39 
3.3.1. 
Adult Patients - Study Treatments ..............................................................................39 
3.3.2. 
Adolescent Patients - Study Treatments .....................................................................40 
3.4. 
Study Flow ..................................................................................................................41 
4. 
STUDY POPULATION .............................................................................................43 
4.1. 
Size of the Population .................................................................................................43 
4.2. 
Inclusion Criteria ........................................................................................................43 
4.3. 
Exclusion Criteria .......................................................................................................44 
4.4. 
Removal of Patients from Therapy .............................................................................45 


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5. 
STUDY MEDICATION/TREATMENT ...................................................................47 
5.1. 
Product Characteristics ...............................................................................................47 
5.2. 
Randomization and Method of Treatment Assignment ..............................................47 
5.3. 
Doses and Regimens ...................................................................................................47 
5.4. 
Rationale for Dose Selection ......................................................................................48 
5.5. 
Drug Supply ................................................................................................................49 
5.5.1. 
Packaging and Labeling ..............................................................................................49 
5.5.2. 
Storage ........................................................................................................................49 
5.6. 
Blinding ......................................................................................................................49 
5.7. 
Drug Accountability ...................................................................................................50 
5.8. 
Treatment Compliance ................................................................................................50 
5.9. 
Concomitant Medications and Restrictions ................................................................50 
6. 
STUDY PROCEDURES ............................................................................................51 
6.1. 
Screening and Enrollment ...........................................................................................51 
6.2. 
Study Day 1 ................................................................................................................52 
6.3. 
Study Week 1 (Day 8) ................................................................................................53 
6.4. 
Study Week 2 (Day 15) ..............................................................................................54 
6.5. 
Study Week 4 (Day 29) ..............................................................................................55 
6.6. 
Study Week 8 (Day 57) ..............................................................................................56 
6.7. 
Study Week 12 (Day 85) ............................................................................................57 
6.8. 
Study Week 16 (Day 113) ..........................................................................................57 
6.9. 
Study Week 20 (Day 141) ..........................................................................................58 
6.10. 
Study Week 23 (Day 162) ..........................................................................................59 
6.11. 
Study Week 26 (Day 183) ..........................................................................................60 
6.12. 
Study Week 28 (Day 197) ..........................................................................................61 
6.13. 
Study Week 32 (Day 225) ..........................................................................................62 
6.14. 
Study Week 35 (Day 246) ..........................................................................................62 
6.15. 
Study Week 38 (Day 267) ..........................................................................................63 
6.16. 
Study Week 41 (Day 288) ..........................................................................................64 
6.17. 
Study Week 44 (Day 309) ..........................................................................................64 
6.18. 
Study Week 48 (Day 337) ..........................................................................................65 
6.19. 
Study Week 52 (Day 365) ..........................................................................................65 


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6.20. 
Study Week 54 (Day 379) ..........................................................................................66 
6.21. 
Study Week 57 (Day 400) ..........................................................................................67 
6.22. 
Study Week 60 (Day 421) ..........................................................................................67 
6.23. 
Early Termination Visit ..............................................................................................68 
7. 
STUDY ASSESSMENTS ..........................................................................................69 
7.1. 
Efficacy Assessments .................................................................................................69 
7.1.1. 
Renal Histology ..........................................................................................................69 
7.1.2. 
Urinary Measurements ................................................................................................70 
7.1.3. 
Estimated Glomerular Filtration Rate .........................................................................71 
7.1.4. 
Health-Related Quality of Life Assessments ..............................................................72 
7.2. 
Safety Assessments .....................................................................................................72 
7.2.1. 
Physical Examinations, Vital Signs and 12-lead ECGs..............................................72 
7.2.2. 
Clinical Safety Laboratory Assessments ....................................................................72 
7.2.3. 
Complement Panel ......................................................................................................73 
7.2.4. 
Adverse Events ...........................................................................................................73 
7.2.4.1. 
Adverse Event Severity Assessment ..........................................................................74 
7.2.4.2. 
Causality Assessment .................................................................................................74 
7.2.4.3. 
Serious Adverse Events ..............................................................................................74 
7.2.4.4. 
Infections ....................................................................................................................75 
7.2.4.5. 
SARs and SUSARs .....................................................................................................75 
7.2.4.6. 
Laboratory Abnormalities ...........................................................................................76 
7.2.4.7. 
Pregnancies .................................................................................................................76 
7.2.5. 
Special Situation Reporting ........................................................................................76 
7.2.6. 
Serious Adverse Event Reporting ...............................................................................77 
7.3. 
Pharmacokinetic Assessments ....................................................................................78 
7.4. 
Pharmacodynamic Assessments .................................................................................78 
7.5. 
Study Completion and Withdrawal ............................................................................79 
7.6. 
Data Monitoring Committee .......................................................................................79 
8. 
STATISTICAL METHODS .......................................................................................79 
8.1. 
Patient Populations .....................................................................................................80 
8.1.1. 
Intent-to-Treat Population ..........................................................................................80 
8.1.2. 
Per Protocol Population ..............................................................................................80 


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8.1.3. 
Safety Population ........................................................................................................80 
8.2. 
Target Patient Population ...........................................................................................80 
8.2.1. 
C5b-9 Elevated Stratum ..............................................................................................80 
8.2.2. 
C5b-9 Non-Elevated Stratum .....................................................................................80 
8.2.3. 
Exploratory Population ...............................................................................................80 
8.3. 
Efficacy Endpoints ......................................................................................................80 
8.3.1. 
Primary Endpoint ........................................................................................................80 
8.3.2. 
Secondary and Other Endpoints .................................................................................80 
8.4. 
Safety Endpoints .........................................................................................................81 
8.5. 
Pharmacokinetic Endpoints ........................................................................................81 
8.6. 
Exploratory Pharmacodynamic Endpoints .................................................................81 
8.7. 
Statistical Analysis Methodology ...............................................................................82 
8.7.1. 
Patient Disposition ......................................................................................................82 
8.7.2. 
Demographics and Baseline Characteristics ...............................................................82 
8.7.3. 
Prior and Concomitant Medications ...........................................................................83 
8.7.4. 
Study Drug Exposure and Compliance .......................................................................83 
8.7.5. 
Efficacy Analyses .......................................................................................................83 
8.7.6. 
Handling of Missing Data ...........................................................................................84 
8.7.7. 
Covariates and Subgroups ..........................................................................................85 
8.7.8. 
Safety Analyses ..........................................................................................................85 
8.7.9. 
Pharmacokinetic and Exploratory Pharmacodynamic Marker Analysis ....................86 
8.8. 
Sample Size Justification ............................................................................................86 
8.9. 
Interim Analysis ..........................................................................................................87 
8.10. 
Protocol Deviations ....................................................................................................87 
9. 
STUDY COMPLETION AND TERMINATION ......................................................87 
9.1. 
Study Completion .......................................................................................................87 
9.2. 
Study Termination ......................................................................................................87 
10. 
REGULATORY AND ADMINISTRATIVE REQUIREMENTS ............................87 
10.1. 
Investigator Responsibilities .......................................................................................87 
10.2. 
Institutional Review Board or Ethics Committee .......................................................88 
10.3. 
Informed Consent/Assent ...........................................................................................88 
10.4. 
Protocol Modifications ...............................................................................................88 


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10.5. 
Regulatory Aspects .....................................................................................................89 
10.6. 
Patient Identification Register ....................................................................................89 
10.7. 
Record Retention ........................................................................................................89 
10.8. 
Case Report Form Completion ...................................................................................90 
10.9. 
Monitoring ..................................................................................................................90 
10.10. 
On-site Visits and Audits ............................................................................................90 
10.11. 
Study Registration, Use of Information and Publication ............................................90 
11. 
REFERENCES ...........................................................................................................92 
12. 
APPENDICES ............................................................................................................93 
12.1. 
Statement of Obligations of Sponsor, Monitor, and Clinical Investigator .................93 
12.2. 
Informed Consent/Assent Form ..................................................................................95 
12.2.1. 
ADDITIONAL ELEMENTS OF INFORMED CONSENT ......................................96 
12.3. 
Benefit-Risk Assessment ............................................................................................96 
12.3.1. 
Nonclinical Evaluation ...............................................................................................96 
12.3.2. 
Clinical Evaluation .....................................................................................................97 
12.3.3. 
Pediatric Testing .........................................................................................................99 
12.3.4. 
Summary Benefit-Risk Statement ............................................................................100 
 
LIST OF TABLES 
Table 1: 
Dosing Groups in the First and Last 26 Weeks of Treatment in Adults .....................40 
Table 2: 
Avacopan/Placebo Starting Dose and Dose Adjustments Based on Avacopan 
Plasma Exposure in Adolescent Patients ....................................................................41 
Table 3: 
CKD-EPI Equation Based on Race and Gender .........................................................71 
 
 


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PROTOCOL SYNOPSIS 
Name of Sponsor 
ChemoCentryx, Inc. 
Name of Active Ingredient 
Avacopan (CCX168) 
Study number:  
CL011_168 
Title 
A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety and 
Efficacy of Avacopan (CCX168) in Patients with C3 Glomerulopathy 
Investigators 
Several 
Study centers 
Multi-center 
Study period 
32 months (first patient enrolled 
to last patient last study visit) 
Phase of development 
Phase 2 
Aim 
The aim of this study is to evaluate the effect of avacopan treatment on renal disease activity in 
patients with complement component 3 glomerulopathy (C3G). 
Objectives 
The primary objective is to evaluate the efficacy of avacopan compared to placebo based on 
histologic changes in kidney biopsies taken before and during treatment. 
The secondary objectives of this study include evaluation of: 
1. The safety of avacopan compared to placebo based on the incidence of adverse events, 
changes in clinical laboratory measurements and changes in vital signs; 
2. Changes in laboratory parameters of renal disease including estimated glomerular 
filtration rate (eGFR), proteinuria, and urinary excretion of monocyte chemoattractant 
protein-1 (MCP-1) with avacopan compared to placebo; 
3. Health-related quality-of-life changes based on Short Form-36 version 2 (SF-36 v2) and 
EuroQOL-5D-5L (EQ-5D-5L) with avacopan compared to placebo; 
4. The pharmacokinetic profile of avacopan in patients with C3G. 
Additionally, changes from baseline in markers of alternative complement pathway 
involvement and other markers of inflammation may be assessed in plasma/serum or urine over 
the course of the treatment period. 
Rationale 
C3G is characterized by evidence of alternative complement activation based on C3 deposition 
in the glomeruli. There are two forms of the disease: dense deposit disease (DDD, formerly 


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called membranoproliferative glomerulonephritis [MPGN] Type II) and C3 glomerulonephritis 
(C3GN, formerly called idiopathic MPGN). Genetic mutations leading to defective complement 
regulation, including reduced-function mutations of complement factor H (CFH), have been 
described in some of these patients. Patients with C3G often have progressive deterioration in 
renal function, ultimately leading to end-stage renal disease. 
There is no approved treatment for patients with C3G. Immunosuppressive drugs such as 
cyclophosphamide, mycophenolate mofetil, and glucocorticoids, as well as biologics such as 
rituximab have been used with limited success. The anti-C5 antibody eculizumab previously 
showed evidence of improvement in some patients with C3G. Eculizumab blocks the formation 
of C5a and C5b-9 (membrane attack complex) from C5. Evidence from animal models suggests 
that inhibition of C5a may be more important than inhibition of C5b-9 in C3G, because deletion 
of C6 (which is part of the C5b-9 complex) in CFH knockout mice failed to protect the mice 
from developing symptoms of C3G (Pickering et al., 2006). This provides support for testing 
drugs that target C5aR, such as avacopan. 
Avacopan is an orally administered, selective inhibitor of the complement 5a receptor (C5aR) 
which is in Phase 3 clinical development for treatment of patients with anti-neutrophil 
cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Phase 2 study data with avacopan 
in patients with AAV indicate efficacy with 30 mg avacopan given twice daily based on 
improvement in disease activity (Birmingham Vasculitis Activity Score), a significant anti-
proteinuric effect, and improvement in quality of life among other improved disease parameters 
(Jayne et al., 2017). This treatment effect was observed in patients receiving avacopan plus 
cyclophosphamide or rituximab, but without oral glucocorticoids. 
One patient with treatment refractory C3GN, one of the subtypes of C3G, has been treated 
successfully with 30 mg avacopan twice daily from September 2015 until Lost to Follow up in 
December 2016 under a “Special Needs” program in the UK. This patient had progressive 
decline in renal function despite previous treatment with immunosuppressants, rituximab, and 
glucocorticoids, as well as a kidney transplant. 
Kidney histology prior to treatment with avacopan showed endocapillary hypercellularity and 
abundance of CD68-positive cells (macrophages) in the glomeruli. After 2 months of treatment 
with avacopan, histology showed no evidence of endocapillary hypercellularity and only a 
small number of CD68-positive cells in the glomeruli. A renal biopsy conducted approximately 
6 months after starting avacopan treatment showed no hypercellularity and no crescents, and 
very few CD68-positive cells in the glomeruli. There was attenuation of eGFR decline. The 
patient’s quality of life showed a significant improvement since starting avacopan treatment 
until the patient was lost for follow up. 
Based on the results in the patient with C3GN and the Phase 2 study in AAV, testing avacopan 
more broadly in patients with C3G is indicated. 


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Methodology 
This is a clinical trial to test the efficacy, safety, and tolerability of avacopan in patients with 
C3G, including both C3GN and DDD. 
Patients with biopsy-proven C3G (biopsy has occurred within 12 weeks prior to signing 
informed consent or is to occur after consenting during the screening period), with or without a 
renal transplant, will be stratified by elevated or normal levels of C5b-9 and then will be 
randomized 1:1 using a minimization algorithm to receive 30 mg avacopan BID or placebo BID 
for 26 weeks in a double-blind manner: 
 
Both strata, i.e., C5b-9 level >244 ng/ml and ≤244 ng/mL, will include approximately 
44 patients each; each level will have approximately 22 patients randomized to the avacopan or 
the placebo arm, respectively. Enrollment for the stratum with C5b-9 levels ≤244 ng/ml could 
terminate early if patient enrollment in the other stratum (“C5b-9 level >244 ng/mL”) reaches 
target enrollment first. 
Eligible patients within each of the C5b-9 level strata will be further stratified based on two 
factors: 
1. C3GN or DDD, and 
2. Whether the patient has received a kidney transplant or not. 
The earliest timepoint at which the primary efficacy analysis can occur is when the last enrolled 
patient in the elevated stratum has completed the Week 26 visit. After the 26-week double-blind 
period, the avacopan group will continue receiving avacopan for another 26 weeks and the 
placebo group patients will be switched over in a blinded manner to receive 30 mg avacopan 
twice daily treatment, instead of placebo, for another 26 weeks. 
Patients will be screened for enrollment based on biopsy-proven C3G (i.e., ≥2 levels of 
magnitude greater staining of C3 than any combination of IgG, IgM, IgA, kappa and lambda 
light chains, and C1q) and evidence of proliferative glomerulonephritis (mesangial 
hypercellularity and/or endocapillary hypercellularity based on the Mayo Clinic/Renal 
Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of 
GN; Sethi et al., 2016). 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 15 of 100 
The screening period will be up to 42 days (6 weeks). Screening procedures will include written 
Informed Consent/Assent, demographics, medical history, medication history (medication given 
prior to Day 1 of dosing is considered medication history), physical examination and vital signs, 
12-lead ECGs, serum pregnancy test for women of childbearing potential, serum chemistry 
(including serum creatinine), hematology, urinalysis, urinary albumin creatinine ratio (UACR) 
and protein: creatinine ratio (UPCR), viral and TB screening. If a patient did not have a renal 
biopsy in the past 12 weeks, a renal biopsy needs to be done prior to dosing. Prior to starting 
blinded study drug treatment (avacopan or placebo), blood samples will be collected for the 
following measurements to create a baseline profile for all patients: 
3. Plasma C3a, C5a, C5b-9, and C5; 
4. Serum C3 and C4; 
5. Serum C3 nephritic factor; 
6. Plasma complement factor H and factor B; 
7. Serum factor H autoantibody; 
8. Serum paraprotein detection; 
9. Complement factor H related protein 5 (CFHR5) mutation. 
Results obtained within 4 weeks prior to screening, or any time in the past for CFHR5 mutation, 
will be acceptable for the study. Patients who do not provide consent for genetic evaluation are 
allowed to participate in the study without the collection of genetic information. 
Patients meeting eligibility criteria will start blinded study drug treatment on Day 1. Patients 
will take avacopan 30 mg or matching placebo orally twice daily. The placebo-controlled 
treatment period is 26 weeks (182 days). This placebo-controlled treatment period will be 
followed by an open-label 26-week treatment period during which all patients will receive 
avacopan. Thereafter, all patients will be followed for 8 weeks (56 days) without study drug 
treatment. 
At post-Day 1 study visits, blood and urine samples will be collected for safety, efficacy, and 
pharmacokinetic and biomarker measurements. A serum pregnancy test for women of 
childbearing potential will be done regularly during the 52-week treatment period and at the end 
of the 8-week follow-up period. Physical examinations and vital signs assessments and 12-lead 
ECGs will be performed throughout the study. Liver function and hematology including 
differential blood work will be monitored at least every 4 weeks throughout the study. Health-
related quality of life using the EQ-5D-5L and SF-36 v2 surveys will be assessed periodically 
over the course of the study. Blinded study drug will be dispensed and drug accountability will 
be done. Concomitant medication and adverse event assessments will be made at every study 
visit. A follow-up renal biopsy will be performed at the following time points: 
1. Within 2 weeks of the Week 26 visit, and completed before dosing with open-label 
treatment; 
2. If a patient is withdrawn early from the study, and 
3. After the 52-week treatment period. 


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Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 16 of 100 
The Week 52 biopsy is optional in adolescent patients. 
If a patient is on other immunosuppressive treatment at the start of dosing, the dose(s) of 
concomitant immunosuppressive treatment may not be increased during the study. Treatment 
with these other drugs may be reduced or stopped during the study at the discretion of the 
Investigator, if the patient’s condition justifies it. Adjustments of tacrolimus and cyclosporine 
doses to ensure these medications are at goal trough levels for maintenance of 
immunosuppression in transplant patients will be allowed during the study. No new treatments 
for C3G, except for renin-angiotensin-aldosterone system (RAAS) blockers, may be added 
during the study period (52-week treatment period or 8-week follow up), unless the patient’s 
condition deteriorates to the extent that the investigator deems it in the best interest of the 
patient to do so. Addition of new treatments for C3G during the treatment period will be 
considered a treatment failure. 
Patients who experience deteriorating renal function based on an increase in serum creatinine of 
at least 50% (confirmed by a repeat measurement after at least 2 weeks) which is otherwise not 
explained (e.g., dehydration, new medication), or an increase in proteinuria of >3 g/g creatinine 
(confirmed by a repeat measurement after at least 2 weeks) from Screening or baseline during 
the 52-week treatment period, will exit the treatment phase of the study and be treated at the 
discretion of their physician. The increase of serum creatinine or proteinuria will be calculated 
from the higher value that is measured either at Screening or baseline. They will remain in the 
study and complete the remaining study visits and procedures. If a patient refuses further study 
participation, the Early Termination visit procedures will be performed, if possible. These 
patients will be considered treatment failures. 
Dose strengths given to study patients will differ for adult and adolescents. Adolescent patients 
(12 to 17 years old) are allowed to be enrolled only in countries and at study centers for which 
approval by Regulatory Authorities and IRBs/ECs was granted. 
All adults will receive an avacopan dose of 30 mg twice daily or matching placebo twice daily 
in the initial 26-week, placebo-controlled treatment period. When they enter the open-label 
26-week treatment period, all study patients regardless of their prior treatment will receive 
avacopan 30 mg twice daily. 
For study centers where enrollment of adolescent patients (12 to 17 years old) is approved, the 
dose of avacopan or placebo dose will be given based on their body weight and avacopan 
plasma exposure (AUC0-6hr) or avacopan trough concentrations. This is further specified in the 
main protocol. 
Patients will visit the study center for Screening and on Day 1 (baseline) and on Weeks 1, 2, 4, 
8, 12, 16, 20, 23 26, 28, 32, 35,  38, 41, 44,  48, 52, 54, 57 and 60. 
Patients will be discharged from the study when all the Week 60 visit procedures have been 
completed. The patient’s condition will be evaluated by the Investigator at the end of the 
clinical trial (Week 60) and appropriate standard of care medical treatment will be provided to 
all patients as needed. 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 17 of 100 
Number of Patients 
Approximately 88 male or female patients with C3G will be enrolled in this study with 
approximately 44 patients in each of the two C5b-9 level strata. Patients who drop out early will 
not be replaced. 
Main Criteria for Inclusion 
1. Biopsy-proven C3G, either DDD or C3GN, with or without a renal transplant, and with 
the following observations upon renal biopsy taken within 12 weeks prior to screening 
or during screening: 
a. ≥2 levels of magnitude greater staining of C3 than any combination of IgG, IgM, 
IgA, kappa and lambda light chains, and C1q by immunohistochemistry, and 
b. Evidence of proliferative glomerulonephritis (mesangial hypercellularity of greater 
than 3 mesangial cells per mesangial area and/or endocapillary hypercellularity 
defined as an increased number of cells within glomerular capillary lumina, 
causing luminal narrowing) based on light microscopy, and 
c. Confirmation of the presence of electron dense deposits in the glomeruli on 
electron microscopy corresponding with the C3 immunofluorescence positivity. 
The site will use their site-specific standard technique for taking the biopsy, which can 
include ultrasound guidance. 
2. Male or female patients, aged at least 18 years; where approved, adolescents (12 to 
17 years old) may be enrolled; female patients of childbearing potential (i.e., those who 
have experienced menarche and who are not permanently sterile or postmenopausal, 
defined as at least 12 consecutive months with no menses without an alternative medical 
cause) may participate if adequate contraception is used during and for at least the three 
months after study completion; male patients with partners of childbearing potential 
may participate in the study if they had a vasectomy at least 6 months prior to 
randomization or if adequate contraception is used during and for at least the 3 months 
after study completion; male patients with partners of childbearing potential must be 
excluded if they plan to father a child during the study. Adequate contraception is 
defined as resulting in a failure rate of less than 1% per year (combined estrogen and 
progestogen [oral, intravaginal, or transdermal], or progestogen-only hormonal 
contraception (oral, injectable, or implantable), intra-uterine device, intra-uterine 
hormone releasing system, bilateral tubal occlusion, vasectomized partner, or true sexual 
abstinence, i.e., in line with the preferred and usual lifestyle of the patient); In addition, 
a barrier method (i.e., cervical cap, diaphragm or condom) must be used during 
intercourse between a male patient and a female of child-bearing potential. 
3. Willing and able to give written Informed Consent and to comply with the requirements 
of the study protocol; written Assent and Informed Consent must be obtained from the 
legal guardian in accordance with regional laws or regulations for patients 12 to 17 years 
of age; and 
4. Judged to be otherwise fit for the study by the Investigator, based on medical history, 
physical examination, and clinical laboratory assessments. Patients with clinical 
laboratory values that are outside of normal limits (other than those specified in the 
Exclusion Criteria) and/or with other abnormal clinical findings that are judged by the 
Investigator not to be of clinical significance, may be entered into the study. 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 18 of 100 
Main Criteria for Exclusion 
1. Pregnant or nursing; 
2. Tubulointerstitial fibrosis appears to be more than 50% based on standard assessment 
using trichrome staining of the renal biopsy; 
3. Use of eculizumab or another anti-C5 antibody within 26 weeks prior to dosing; 
4. Secondary C3 disease, e.g., infection-associated disease, or associated with another 
systemic or autoimmune disease; presence of a monoclonal spike on serum or urine 
protein electrophoresis or immunofixation assay; 
5. Currently on dialysis or likely will require dialysis within 7 days after screening; 
6. History or presence of any form of cancer within the 5 years prior to screening, with the 
exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in 
situ such as cervical or breast carcinoma in situ that has been excised or resected 
completely and is without evidence of local recurrence or metastasis; 
7. Positive HBV, HCV, or HIV viral screening test indicative of acute or chronic infection; 
8. Evidence of tuberculosis based on interferon γ release assay (IGRA), tuberculin purified 
protein derivative (PPD) skin test, or chest radiography done at screening or within 
6 weeks prior to screening; a CT scan or chest X-ray are not mandatory if evidence of 
tuberculosis was excluded by any of the other methods specified above; 
9. Active uncontrolled infection; 
10. WBC count less than 3500/µL, or neutrophil count less than 1500/µL, or lymphocyte 
count less than 500/µL before start of dosing; 
11. Evidence of hepatic disease; AST, ALT, alkaline phosphatase, or bilirubin >3x the 
upper limit of normal before start of dosing; 
12. Currently using a strong inducer of the cytochrome P450 3A4 (CYP3A4) enzyme, such 
as carbamazepine, phenobarbital, phenytoin, rifampin, or St. John’s wort; 
13. Known hypersensitivity to ava opan o  inactive ingredients of the avacopan capsules 
(including 
) or inability to swallow the 
capsules; 
14. Participated in any clinical study of an investigational product within 30 days prior to 
screening or within 5 half-lives after taking the last dose; and 
15. History or presence of any medical condition (for example, contraindication to local 
anesthesia required for renal biopsy, or recurring serious infections) or disease which, in 
the opinion of the Investigator, may place the patient at unacceptable risk for study 
participation. 
Test Product 
Avacopan will be administered orally as hard gelatin capsules containing 10 mg avacopan. The 
avacopan capsules will be supplied to the study centers in plastic bottles containing 180 
capsules. 
Matching placebo will be administered orally as matching hard gelatin capsules containing no 
avacopan but inactive ingredients. The placebo capsules will be supplied to the study centers in 
plastic bottles containing 180 capsules. 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 19 of 100 
Patients will receive one bottle of avacopan or placebo capsules on Day 1 and Weeks 4, 8, 12, 
and 16, and two bottles at Weeks 20, 26, 32, 38, and 44. 
Patients will be asked to take 3 capsules every morning and 3 capsules every evening orally 
with water, approximately 12 hours after the morning dose, as instructed. Study medication 
(avacopan or placebo) should be taken preferably with food. If a patient misses a dose, the next 
dose should be taken as soon as possible. If it is close to the time for their next dose (within 3 
hours), the missed dose should not be taken and the next dose should be taken at the regular 
time. 
Duration of Treatment and Observation 
Patients will be screened within a period not to exceed 42 days prior to Day 1. The total 
treatment period is 52 weeks (364 days) and all patients will be followed for 8 weeks (56 days) 
after the dosing period. 
To the extent possible, any adverse events that are deemed study drug-related and are ongoing 
at discharge will be followed-up to resolution or until a determination is made that the 
unresolved event is stable. The patient’s condition will be evaluated by the Investigator at the 
end of the clinical trial and appropriate standard of care medical treatment will be provided to 
all patients as needed. 
Safety Assessments 
Safety assessments include adverse events, physical examination abnormalities, vital signs, 12-
lead ECG, and clinical laboratory tests (including blood chemistry, hematology, and urinalysis). 
Efficacy Assessments 
Efficacy assessments include: 
1. Renal biopsy to perform light microscopy, immunohistochemistry, and electron 
microscopy; light microscopy and immunohistochemistry will be used to determine the 
C3G Histologic Index for disease activity and chronicity; 
2. eGFR calculated from serum creatinine using the Chronic Kidney Disease-Epidemiology 
Collaboration study (CKD-EPI) equation (Levey et al., 2009) in adult patients and the 
modified Schwartz equation in adolescents (Schwartz et al., 2009); 
3. Urinary protein:creatinine ratio (UPCR); 
4. Urinary MCP-1:creatinine ratio; 
5. Health-related quality of life based on the EQ-5D-5L and SF-36 v2. 
Pharmacokinetic Assessments 
Concentrations of avacopan and its metabolite CCX168-M1 will be determined in plasma 
according to the Time and Events Table, using a validated analytical method. 
Exploratory Pharmacodynamic Markers 
Plasma/serum samples will be collected according to the Time and Events Table for 
pharmacodynamic marker measurements, which may include, for example, complement 
fragments, and inflammatory cytokine and chemokine levels. Urine samples will also be 
collected according to the Time and Events Table for biomarker assessments including, for 
example, complement fragments, sCD163, and inflammatory cytokine and chemokine levels. 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 20 of 100 
Renal Histology 
For eligibility assessment, renal biopsy samples taken within 12 weeks prior to screening or 
during screening will be assessed by immunofluorescence staining for C3 and 
immunoglobulins, as well as electron microscopy to confirm the presence of electron dense 
deposits. Eligibility assessment will be made by the Investigator based on their local 
pathologist’s evaluation. Patients must have biopsy-proven C3G, either DDD or C3GN, with 
≥2 levels of magnitude greater staining of C3 than any combination of IgG, IgM, IgA, kappa 
and lambda light chains, and C1q, and with evidence of proliferative glomerulonephritis 
(mesangial hypercellularity and/or endocapillary hypercellularity). 
All renal biopsies will be analyzed with the routine panel of stains which includes hematoxylin-
eosin (H&E), periodic acid–Schiff (PAS), trichrome, and Jones methenamine silver. A 
minimum of 4 (preferably 6) unstained slides from paraffin-embedded renal tissue will be 
provided by study centers to the central histopathology laboratory for additional 
immunostaining (e.g., CD45, CD68, MPO, C5a, C5aR, etc.). 
Renal biopsies will be evaluated by a central reader, an expert in C3G renal pathology, who will 
be blinded to treatment assignment from either slides or digitized high-resolution images. 
The central reader will determine the degree of disease activity and chronicity based on the 
C3G Histologic Index. A semi-quantitative scale of 0 to 3 will be used, indicating either the 
proportion (%) of glomeruli involved or the proportion of cortex involved (for tubular atrophy 
and interstitial fibrosis). 
The C3G Histologic Index for disease activity will consider 7 lesions: 
1. Mesangial hypercellularity, defined as >3 mesangial cells per mesangial area; 
2. Endocapillary hypercellularity/proliferation, defined as an increased number of cells 
within glomerular capillary lumina, causing luminal narrowing; 
3. Membranoproliferative morphology; 
4. Leukocyte infiltration; 
5. Crescent formation, defined as extracapillary cell proliferation of more than two cell 
layers with >50% of the lesion occupied by cells; 
6. Fibrinoid necrosis; 
7. Interstitial inflammation. 
Definitions are based on the Mayo Clinic/Renal Pathology Society Consensus Report on 
Pathologic Classification, Diagnosis, and Reporting of GN (Sethi et al., 2016) and the activity 
index score uses the glomerulopathy histologic score as described by Bomback et al. (Bomback 
et al., 2018). 
For endocapillary hypercellularity/proliferation, mesangial hypercellularity, 
membranoproliferative morphology, and leukocyte infiltration the following scale will be used: 
0 = none, 1 = 1-25%, 2 = 26-50%, 3 = >50% involvement. For crescent formation and fibrinoid 
necrosis, the following scale will be used: 0 = none, 1 = 1-10%, 2 = 11-25%, and 3 = >25% 
involvement. For interstitial inflammation, a score according to percentage of cortical 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 21 of 100 
tubulointerstitial area involved will be used: 0 = <10%, 1 = 10-25%, 2 = 26-50%, 3 = >50% 
involvement.  
The C3G Histologic Index for disease activity can assume a score from 0-21. 
The C3G Histologic Index for disease chronicity will consider 4 lesions (Bomback et al., 2018): 
1. Glomerulosclerosis (% glomeruli with global and segmental sclerosis), 
2. Tubular atrophy, and 
3. Interstitial fibrosis 
4. Arterio- and arteriolosclerosis 
Glomerulosclerosis (global plus segmental), tubular atrophy, and interstitial fibrosis will be 
assigned a score of 0 to 3 based on the percentage of glomeruli or cortical tubulointerstitial area 
involved. The following scale will be used for the chronicity index: 0 = <10%, 1 = 10-25%, 
2 = 26-50%, 3 = >50% involvement. For vascular disease, a score of 0 will be assigned if 
intimal thickening is < thickness of media and 1 if intimal thickening is ≥ thickness of media. 
The C3G Histologic Index for disease chronicity can assume a score from 0-10. 
Electron microscopy will be performed to evaluate the treatment effect of avacopan on electron 
microscopic features of the disease such as dense deposits. 
Immunohistochemistry evaluation will be performed by the central pathologist to evaluate the 
treatment effect of avacopan on specific immune cell populations, such as total leukocytes, 
macrophages, and neutrophils. 
Statistical Methods 
This study will enroll and treat two patient populations: patients in the elevated stratum of 
C5b-9 levels (i.e., >244 ng/mL) and patients in the non-elevated stratum of C5b-9 levels (i.e., 
≤244 ng/mL). Data summaries and statistical analyses will be presented for each of the two 
strata as well as combined. The elevated stratum will be considered as the primary population, 
the non-elevated stratum will be considered as the secondary population, and the two strata 
combined will be considered the exploratory population. Enrollment for the stratum with C5b-9 
levels ≤244 ng/mL could terminate early, if patient enrollment in the other stratum (C5b-9 level 
>244 ng/mL) reaches target enrollment first. Further, both strata can be analyzed separately and 
independently. The stratum with elevated levels (primary population) will be analyzed first 
should the stratum with C5b-9 ≤244 ng/mL (secondary population) continue a blinded follow 
up – further details will be provided in the statistical analysis plan (SAP). 
For efficacy analysis, to control for the Type I error rate, a gate-keeping procedure will be 
applied for the analysis of the primary efficacy endpoint (percent change in C3G Histologic 
Index for disease activity). The primary endpoint will be tested in the elevated stratum first with 
a two-sided α = 0.05. If this test reaches statistical significance, then the primary endpoint will 
be tested in the non-elevated stratum with a two-sided α = 0.05. If the test in the elevated 
stratum fails to reach statistical significance, then the test in the non-elevated stratum will only 
be performed as an exploratory analysis. 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 22 of 100 
The statistical analysis for the secondary endpoint (C3G Histologic Index for disease 
chronicity) will be tested at a 0.05 α-level only if the primary endpoint in the same stratum 
reaches statistical significance. 
Demographics and Baseline Characteristics 
All patient baseline characteristics and demographic data (age, sex, race, ethnicity, weight, 
height, body mass index, viral test results, C3G disease type and duration [from time of first 
diagnosis based on renal biopsy], eGFR, proteinuria [UPCR], complement marker levels, 
urinary MCP-1:creatinine ratio, physical examination abnormalities, medical history, previous 
[within 6 months of screening] and concomitant medications [including other treatments for 
C3G] at study entry) will be listed by study center and patient number, and will also be 
summarized. 
Efficacy Analysis 
The primary efficacy endpoint is the percent change from baseline to Week 26 in the C3G 
Histologic Index for disease activity. 
The avacopan and placebo groups will be compared by ANCOVA with treatment group as 
factor and baseline C3G Histologic Index for disease activity as covariate. A point estimate and 
corresponding 95% confidence interval will be estimated for the treatment main effect. The 
heterogeneity of the treatment effect across disease diagnoses and renal transplant strata will be 
investigated through subgroup analyses. The treatment effect based on the baseline complement 
profile of patients will also be investigated. If data are not normally distributed, in addition to 
the ANCOVA for the percent change in C3G Histologic Index for disease activity and 
chronicity, the Cochran-Mantel-Haenszel (CMH) test will be applied to the percent change 
results and ANCOVA will be applied to the change in C3G Histologic Index disease activity 
and chronicity scores. 
Data from patients who are treatment failures, i.e., requiring treatment rescue measures such as 
high dose glucocorticoids during the treatment period, will be excluded from efficacy analysis 
after the point of rescue treatment. Missing data will be imputed with the last observation 
carried forward (LOCF). Multiple-imputation using Markov Chain Monte Carlo (MCMC) or 
other statistical method may also be performed. 
Since the placebo group will receive avacopan during the second 26 weeks of the study, the 
change from Week 26 to Week 52 in the C3G Histologic Index in the placebo control group 
will be compared to the change from baseline to Week 26 in this group. This analysis will be 
done by the paired t-test. Point estimates and corresponding 95% confidence intervals will be 
estimated for the difference between the second 26 weeks (avacopan treatment) and the first 26 
weeks (placebo treatment). 
The change from baseline to Week 52 in the C3G Histologic Index in the avacopan group will 
also be compared to the change from baseline to Week 26 in placebo control group using 
similar methodology as described for the primary efficacy endpoint. 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 23 of 100 
Other efficacy endpoints include: 
1. The proportion of patients who have a histologic response, defined as a decrease 
(improvement) in the C3G Histologic Index for disease activity of at least 35% from 
baseline to Week 26; 
2. The percent change from baseline in the C3G Histologic Index for disease chronicity 
over the placebo-controlled 26-week treatment period; 
3. The change and percent change from baseline in eGFR over the placebo-controlled 
26-week treatment period; 
4. The percent change from baseline in UPCR over the placebo-controlled 26-week 
treatment period; 
5. The percent change from baseline in urinary MCP-1:creatinine ratio over the 
placebo-controlled 26-week treatment period; 
6. Change from baseline in EQ-5D-5L (visual analogue scale and index) and SF-36 v2 
(domains and component scores) over the placebo-controlled 26-week treatment period. 
Continuous variables, including eGFR, UPCR, urinary MCP-1: creatinine ratio, EQ-5D-5L, and 
SF-36 v2 will be analyzed using a mixed effects model for repeated measures (MMRM) with 
treatment group, visit, and treatment-by-visit interaction as factors, and baseline as covariate. 
Patients will be considered as repeated measure units over visits. The interaction term may be 
dropped if it is not significant at α = 0.25 level. Point estimates and corresponding 95% 
confidence intervals will be estimated for the difference between the avacopan group and the 
control group at Week 26 using simple contrast from the model. 
Similar to the primary endpoint, the second 26 weeks will be compared to the first 26 weeks for 
the placebo group. Changes in the efficacy parameters across 52 weeks will also be assessed. 
Change and percent change in the efficacy parameters during the 8-week follow-up period will 
also be assessed to determine the off-treatment effect. 
Change from baseline in individual components of the C3G Histologic Index for disease 
activity and chronicity as well as glomerular leukocytes and leukocyte subsets based on 
immunohistochemistry will be summarized and, where appropriate, analyzed using similar 
methodologies as describe above. 
The endpoint of the proportion of patients who have a histologic response will be analyzed by 
the CMH chi-square test. Data from patients who are treatment failures, i.e., require rescue 
medication during the treatment period, will be summarized. 
Summary statistics will be calculated for each of the efficacy endpoints. For continuous 
variables, numbers of patients, means, medians, minimum, maximum, standard deviations, 
standard errors, and 95% confidence intervals will be calculated. Geometric means will be 
calculated for UPCR and MCP-1: creatinine, and other measurements that are not normally 
distributed. For the categorical variable of histologic response, the number and percentage of 
patients, as well as the 95% confidence intervals will be calculated. 
The primary efficacy analysis will be based on the intent-to-treat (ITT) population, defined as 
all patients who are randomized. If data are still missing after all efforts made to collect post-
baseline C3G Histologic Index data, missing data will be imputed using the last observation 


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Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 24 of 100 
carried forward method. This method may impute Week 26 missing data with the baseline value 
if there are no unscheduled data from visits prior to the missing time point. 
Safety Analysis 
Safety endpoints include: 
1. Patient incidence of treatment-emergent serious adverse events, adverse events, and 
study withdrawals due to adverse events; 
2. Change from baseline and shifts from baseline in all safety laboratory parameters; 
3. Change from baseline in vital signs. 
All patients who are randomized and received at least one dose of study medication will be 
included in the safety population. 
All clinical safety and tolerability data will be listed by treatment group and by patient, and will 
be summarized by treatment group. 
All reported adverse events will be coded using MedDRA and listed by System Organ Class, 
preferred term, and verbatim term. 
Treatment-emergent adverse events will be listed and summarized by treatment group by 
System Organ Class and Preferred Term, by relatedness and by maximum severity. 
Treatment-emergent serious adverse events and adverse events leading to study withdrawal will 
be summarized by treatment group. 
Individual vital signs and change from baseline in vital signs will be listed by treatment group, 
patient, and study visit, and summarized by treatment group. 
Laboratory data (actual values and change from baseline) will be listed by treatment group, 
patient, and study visit. Abnormal laboratory values will be flagged. Laboratory data will also 
be summarized by treatment group and study visit. Shift tables will be generated for shifts in 
laboratory parameters by study visit. 
Sample Size Assumptions 
A sample size of 22 patients per treatment group (avacopan and placebo, respectively) in each 
of the C5b-9 level strata is based on the between-treatment difference of -35% in the C3G 
Histologic Index for disease activity at Week 26, standard deviation (SD) 34%, power 90%, and 
2-sided α = 0.05. The sample size also provides approximately 90% power to detect a delta 
of -35% in the C3G Histologic Index for disease activity between the percent change from 
baseline in the first 26 weeks and in the second 26 weeks, assuming an SD of 34% for each 
change. 
Pharmacokinetic and Exploratory Pharmacodynamic Marker Analysis 
Individual plasma concentrations of avacopan (and metabolite CCX168-M1) will be listed, 
plotted, and summarized descriptively and graphically. When possible, the mean steady state 
trough concentrations and the terminal elimination half-life will be calculated. 
The following parameters will be determined, where possible, in 12-17 year-old patients: 
Cmax 
Maximum plasma concentration 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
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tmax 
Time of maximum plasma concentration  
AUC0-6hr 
Area under the plasma concentration-time curve from Time 0 to Hour 6 on 
Day 1 and Day 183 
Cmin 
Trough level plasma concentrations at post-Day 1 visits 
Plasma and urinary PD markers will be summarized and may be analyzed using methods 
analogous to the efficacy parameters. 
The relationship between PK parameters and renal function based on eGFR will be evaluated. 
The data may also be used to evaluate the PK/PD relationship of avacopan treatment for both 
C5b-9 level strata separately as well as combined. To this end, the change and/or percent 
change from baseline in the C3G Histologic Index, UPCR, eGFR, urinary MCP-1: creatinine 
ratio, and other biomarkers may be used as PD markers. 


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Protocol CL011_168 
 
 
Amendment 4.0 
 ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 26 of 100 
STUDY SCHEMA 
 


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Protocol CL011_168 
 
 
Amendment 4.0 
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Page 27 of 100  
TIME AND EVENTS TABLE 
 
Screening 
Double-Blind Treatment 
 
Active Treatment 
Follow-up 
Study Daya 
≤42 days 
1 
8 
15 
29 
57 
85 
113 
141 
162 
183 
197 
225 
246 
267 
288 
309 
337 
365 
 
 
 
Study Week1 
≤6 
 
1 
2 
4 
8 
12 
16 
20 
23 
26  
28 
32 
35 
38 
41 
44 
48 
52 
54 
57 
60 
Informed 
Consent/Assent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics, 
medical history, 
prior medications 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examinationb 
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Vital signs 
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
12-lead ECG 
X 
Xc 
X 
 
 
 
 
 
 
 
X 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
Serum pregnancy 
test for women of 
childbearing 
potential 
X 
Xc 
 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
HIV, HBV, HCV 
testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening for 
tuberculosisd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistry 
X 
Xc 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Urine albumin, 
protein and 
creatinine  
X 
Xc 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Renal biopsy for 
light and electron 
microscopy, 
immunostaining, 
morphometry, and 
C3G Histologic 
Index 
calculatione,f 
Xe 
 
 
 
 
 
 
 
 
 
Xe 
 
 
 
 
 
 
 
X 
 
 
 


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Protocol CL011_168 
 
 
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Screening 
Double-Blind Treatment 
 
Active Treatment 
Follow-up 
Study Daya 
≤42 days 
1 
8 
15 
29 
57 
85 
113 
141 
162 
183 
197 
225 
246 
267 
288 
309 
337 
365 
 
 
 
Study Week1 
≤6 
 
1 
2 
4 
8 
12 
16 
20 
23 
26  
28 
32 
35 
38 
41 
44 
48 
52 
54 
57 
60 
Complement 
profilingg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stratification and 
randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine MCP-1 and 
creatinine 
 
Xc 
X 
X  
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
 
 
 
X 
 
 
X 
EQ-5D-5L and 
SF-36 v2 
 
Xc 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
X 
Avacopan/Placebo 
dispensing  
 
Xc 
 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Avacopan 
dispensing 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
Avacopan/Placebo 
double-blind 
dosing  
 
X→ 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
 
→X 
 
 
 
 
 
 
 
 
 
 
 
Avacopan dosing 
 
 
 
 
 
 
 
 
 
 
Xh 
→ 
→ 
→ 
→ 
→ 
→ 
→ 
Xi 
 
 
 
Avacopan/Placebo 
accountability 
 
 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
PD plasma/serum 
sample collectionj 
 
Xc 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
 
 
 
X 
X 
X 
X 
Blood sample for 
lymphocyte subset 
analysisk 
 
Xc 
X 
X 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
PD urine sample 
collection 
 
Xc 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
 
 
 
X 
 
 
X 
PK plasma sample 
collection 
 
Xc 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
 
 
 
X 
X 
X 
X 
Concomitant 
medications 
X 
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event 
assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
a Week 1 through 20 visits may occur within a ± 2 day window. Week 26 through 60 visits may occur within a ± 7 day window. 
b Physical examination will include body weight measurements. Height will be measured only at Screening in adults, but at all visits for adolescents. 
c These procedures must be performed before taking the first dose of avacopan. 


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d Any one of the following may be done for TB screening: Interferon γ release assay (IGRA), tuberculin purified protein derivative (PPD) skin test, or chest 
radiography (done within 6 weeks prior to Screening or done during Screening). 
e Renal biopsy required for eligibility if not performed within 12 weeks prior to screening; renal biopsy -2 weeks prior to the Week 26 visit, and should be 
completed before open-label medication is started. 
f In adolescents, only the baseline and one follow-up renal biopsy (at Week 26) are required; the 52-week biopsy is optional. 
g Plasma C3a, C5, C5a, and C5b-9; serum C3, C4, and C3 nephritic factor; plasma complement Factor H and factor B; serum factor H auto-antibody; serum 
paraprotein detection; CFHR5 mutation. Results obtained within 4 weeks prior to screening or any time in the past for CFHR5 mutation will be acceptable for 
the study. 
h Only in adolescent patients, plasma samples for avacopan measurements will be taken at pre-dose, 0.5, 1, 2, 3, 4, and 6 hours after dosing on Day 1 and on Day 
183 (Week 26). For all other visits, single time point samples approximately 12 hours post the most recent dose and immediately prior to the dose on the visit 
day will be taken. The date and time of the last dose of study drug prior to the PK sample collection will be recorded. Note: For adolescents only - it is 
important that on Day 183 (Week 26) the adolescent patients take the dose when instructed at the study center, NOT at home, and they should be reminded 
through a telephone call two days before the Day 183 (Week 26) visit. 
i For both adults and adolescents, the final dose of avacopan should NOT be taken on the morning of the scheduled Week 52 visit. Note: Patients should be 
reminded through a telephone call two days before the scheduled Week 52 visit. 
j Blood samples will be put in wet ice immediately after collection, centrifuged in a refrigerated centrifuge and plasma or serum stored at ≤ -70 °C. 
k For T cell, B cell, and natural killer T cell counts. 
 


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LIST OF ABBREVIATIONS AND ACRONYMS 
AAV 
ANCA-Associated Vasculitis 
AE 
adverse event 
aHUS 
atypical Hemolytic Uremic Syndrome 
ALT 
Alanine aminotransferase 
ANC 
Absolute Neutrophil Count 
ANCA 
Anti-Neutrophil Cytoplasmic Autoantibody 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
ATC 
Anatomic Therapeutic Chemistry 
AUC 
Area under the plasma concentration-time curve 
AUC0-6hr 
Area under the plasma concentration-time curve for 0 to 6 hours after dosing 
b.i.d. or BID 
Twice daily 
BVAS 
Birmingham Vasculitis Activity Score 
C1q 
Complement component C1q 
C3 
Complement component 3 
C3G 
C3 glomerulopathy 
C3GN 
C3 glomerulonephritis 
C3NeF 
C3 nephritic factor 
C4 
Complement component 4 
C5a 
Complement component 5a fragment 
C5aR 
Receptor for C5a 
C5b-9 
Membrane attack complex or terminal complement complex 
C6 
Complement 6 
CA 
Competent Authority 
CBC 
Complete Blood Count 
CD11b 
Cluster of differentiation 11b 
CD45 
Cluster of differentiation 45 
CD60 
Cluster of differentiation 60 
CD68 
Cluster of differentiation 68 
CD163 
A protein that in humans is encoded by the CD163 gene 
CFH 
Complement factor H 
CFR 
Code of Federal Regulations 
CFHR5 
Complement factor H related protein 5 
Cmax 
Maximum (maximal) plasma concentration 
Cmin 
Minimum plasma concentration 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CMH 
Cochran-Mantel-Haenszel 
CPK 
Creatine phosphokinase 
CRA 
Clinical Research Associate 
CRF/eCRF 
Case Report File 
CRO 
Clinical Research Organization 
CSR 
Clinical Study Report 
 


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Protocol CL011_168 
 
 
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CT 
Computerized Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events  
CYP3A4 
Cytochrome P450 3A4 enzyme 
DDD 
Dense Deposit Disease 
DMC 
Data Monitoring Committee 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
eGFR 
estimated Glomerular Filtration Rate  
EQ-5D-5L 
EuroQuality of Life-5 Domains-5 Levels 
EU 
European Union 
FDA 
Food and Drug Administration 
g 
gram 
GCP 
Good Clinical Practices 
GMP 
Good Manufacturing Practices 
GFR 
Glomerular Filtration Rate 
H or hr 
Hour 
H&E 
Hematoxylin-eosin 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HDPE 
High Density Polyethylene 
hERG 
Potassium channel encoded by the human ether-à-gogo related gene 
HIV 
Human Immunodeficiency Virus 
ICH 
International Conference on Harmonisation  
IHC 
Immunohistochemistry 
IC50 
Concentration associated with 50% inhibition 
Ig 
Immunoglobulin 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IgAN 
Immunoglobulin A Nephropathy 
IGRA 
Interferon γ Release Assay 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITT 
Intent-To-Treat 
IV 
Intravenous(ly) 
kD 
kilodalton 
kg 
kilogram 
lbs. 
Pound (weight) 
LOCF 
Last observation carried forward 
LVFS 
Swedish Medical Products Agency’s Code of Statues 


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Protocol CL011_168 
 
 
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MAC 
Membrane Attack Complex 
MCMC 
Markov Chain Monte Carlo (statistical method) 
MCP-1 
Monocyte Chemoattractant Protein-1, also known as CCL2 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
mL 
milliliter 
MMRM 
Mixed effects Model for Repeated Measures 
MPGN 
Membranoproliferative Glomerulonephritis 
MPO 
myeloperoxidase 
N 
Number 
PAS 
periodic acid Schiff 
PD 
Pharmacodynamics(s) 
PK 
Pharmacokinetic(s) 
PP 
Per Protocol 
PPD 
Purified Protein Derivative 
QT/QTc 
Q-T interval on ECG; corrected Q-T interval 
RAAS 
Renin-Angiotensin-Aldosterone System 
RBC 
Red Blood Cell(s) 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAR 
Serious Adverse Reaction 
SD 
Standard Deviation 
SEM 
Standard Error of the Mean 
SF-36 v2 
Short Form-36 version 2.0 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TB 
Tuberculosis 
TCC 
Terminal Complement Complex, also known as membrane attack complex 
Tmax 
Time of Maximal Concentration 
UACR 
Urinary Albumin:Creatinine Ratio 
UPCR 
Urinary Protein:Creatinine Ratio 
UK 
United Kingdom 
WBC 
White Blood Cell 
WHODD 
World Health Organization Drug Dictionary 
 


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Protocol CL011_168 
 
 
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1. 
INTRODUCTION 
1.1. 
Complement and Avacopan 
The activation of the complement pathway generates biologically active fragments of 
complement proteins, e.g., C3a, C4a and C5a anaphylatoxins, and the C5b-9 membrane attack 
complex (MAC) or terminal complement complex (TCC), all of which mediate inflammatory 
responses by inducing leukocyte chemotaxis, activating macrophages, neutrophils, platelets, 
mast cells and endothelial cells, and by increasing vascular permeability, cytolysis, and tissue 
injury. 
C5a is one of the most potent pro-inflammatory mediators of the complement system, being at 
least 100 times more potent than C3a. This 12 to 14.5 kD polypeptide, along with a C5b 
fragment, is produced by enzymatic cleavage of a C5 precursor during activation of any of the 3 
complement pathways. C5a induces expression of adhesion molecules and chemotactic 
migration of neutrophils, eosinophils, basophils, and monocytes. It also mediates inflammatory 
reactions by causing smooth muscle contraction, increasing vascular permeability, inducing 
basophil and mast cell degranulation, and inducing release of lysosomal proteases and oxidative 
free radicals. The anaphylactic and chemotactic effects of C5a are mediated through its 
interaction with the C5aR, a G protein-coupled receptor expressed on human neutrophils, 
monocytes, basophils, eosinophils, renal glomerular tissues, and lung smooth muscle and 
endothelial cells. 
Avacopan (formerly CCX168) is an orally administered, small molecule, selective inhibitor of 
the complement 5a receptor (C5aR). 
As measured in vitro, avacopan functionally inhibits C5a-mediated chemotaxis, displaces 
[125I]-C5a from human C5aR, and inhibits C5a-mediated increase in cytoplasmic calcium levels 
with a potency (IC50) of 0.2 to 0.9 nM in buffer (Bekker et al., 2016). 
Avacopan was also evaluated for its ability to inhibit the C5a-mediated chemotaxis of 
neutrophils in freshly collected human whole blood. Avacopan produced 50% inhibition (IC50) 
of C5a-mediated neutrophil migration at a concentration of 1.7 nM; 90% inhibition (A10 value) 
occurred at an avacopan concentration of 15.4 nM. Avacopan also inhibits C5aR in cynomolgus 
monkeys and hamsters at potencies similar to that observed with human whole blood. However, 
avacopan possesses moderate potency for rabbit C5aR (IC50 ~ 1.4 µM) and lacks affinity for 
mouse, rat, or dog C5aR (IC50 >10 µM). 
The efficacy of avacopan was assessed using genetically modified mice where the mouse C5aR 
coding region was substituted for the human C5aR coding region. In these studies, intravenous 
injection of mouse anti-myeloperoxidase (anti-MPO) IgG into the human C5aR knock-in mice 
caused glomerulonephritis in a manner mimicking ANCA disease in humans. At daily oral doses 
of 30 mg/kg avacopan, a marked inhibition of anti-MPO induced glomerulonephritis was 
documented histologically, as assessed by the number of necrotic and crescent-containing 
glomeruli. These results were consistent with reduced protein, leukocytes, and red blood cells in 
the urine, and reduced serum blood urea nitrogen and creatinine in mice receiving avacopan 
(Xiao et al, 2014). 


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Studies assessing the effects of avacopan upon the central nervous, respiratory, and renal systems 
did not reveal any adverse findings following the oral administration of avacopan. Additionally, 
in vitro data suggest that avacopan and its only major metabolite CCX168-M1 are unlikely to 
pose a pro-arrhythmic risk in humans. Nonclinical toxicity studies of up to 26 weeks and 44 
weeks in duration (in rats and cynomolgus monkeys, respectively) involving exposures higher 
than those expected in the clinic did not identify any safety concerns with avacopan. No adverse 
effects upon fertility or embryo-fetal development were seen in reproductive toxicity studies 
conducted in hamsters and rabbits. No evidence of any immunotoxicity was noted as 
immunological, clinical, and anatomical pathological parameters were, with limited exceptions 
(e.g., minor clinical pathology changes in rats in the 26-week study), unaffected by treatment. An 
in vitro study indicated that avacopan was not phototoxic. Thus, results from these nonclinical 
studies support chronic oral dosing of 30 mg avacopan twice daily to humans. Refer to the 
Investigator’s Brochure for details of these studies. 
1.2. 
Previous Clinical Studies 
Five Phase 1 studies and four Phase 2 studies with avacopan have previously been completed. A 
Phase 3 study in patients with AAV previously completed enrollment but follow up is ongoing 
and the study remains blinded. A total of 182 healthy volunteers participated in the five Phase 1 
studies; 153 of these patients received avacopan at doses ranging from 1 mg up to 100 mg 
(CL001_168, CL004_168, CL007_168, and CL008_168, and Japanese Phase 1 study 
CCX1101). Avacopan was generally well tolerated in these studies. 
Following oral administration, avacopan was absorbed rapidly and reached peak plasma levels 
after a median time of approximately 2.5 hours. After reaching the peak plasma level, avacopan 
appears to have a biphasic elimination profile (as observed from the log-linear concentration-
time profiles), with a rapid early phase followed by a long terminal phase, a moderate to high 
apparent clearance in humans, and a large apparent volume of distribution. Despite the long 
observed terminal half-life, repeat administration for 7 days resulted in only modest 
accumulation (~2-fold) at the higher dose levels. Co-administration with a high fat, high calorie 
meal did not affect Cmax but increased the plasma exposure (AUC) approximately 72% and 
delayed tmax by approximately 3 hours (study CL007_168). 
Avacopan dose-dependently inhibited the C5a-induced upregulation of CD11b in patients’ 
neutrophils in study CL001_168. At a mean avacopan plasma concentration of 150.9 ng/mL, 
C5a-induced upregulation of CD11b was inhibited by ~95% (Bekker et al., 2016). In Phase 2 
studies in patients with AAV, an average steady state plasma trough concentration of 
~200 ng/mL was observed with the therapeutic dose of 30 mg avacopan given twice daily. 
Results from a mass balance study (CL004_168) showed that avacopan was mostly metabolized 
in the liver by cytochrome P450 3A4 (CYP3A4). 
Avacopan did not show evidence of a detrimental effect on QT/QTc based on results from an 
intensive ECG study (CL007_168). 
Co-administration of the strong CYP3A4 enzyme inducer, rifampicin, in study CL008_168 
resulted in an approximately 93% reduction of systemic exposure of avacopan; this reduction 
may result in a loss of efficacy of avacopan. Therefore, the use of strong CYP3A4 enzyme 
inducers with avacopan is an exclusion criterion for the study. Co-administration of the strong 


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Protocol CL011_168 
 
 
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CYP3A4 enzyme inhibitor itraconazole resulted in a 119% increase of systemic exposure of 
avacopan. This approximate doubling of the avacopan plasma concentrations indicates a modest 
interaction and should not pose a safety concern, given that the safety margins for 30 mg 
avacopan twice daily in humans compared to animals are at least 6 to 19-fold, respectively, 
based on the long-term cynomolgus monkey and rat toxicology studies. Nevertheless, strong 
CYP3A4 enzyme inhibitors with avacopan should be used with caution. 
Two Phase 2 clinical trials in 109 patients with anti-neutrophil cytoplasmic antibody (ANCA)-
associated vasculitis (AAV) were conducted. The first study in 67 patients (CL002_168) 
included three dose groups: 30 mg avacopan twice daily plus low dose prednisone (20 mg/day), 
30 mg avacopan twice daily plus no prednisone, and placebo plus full dose prednisone 
(60 mg/day). All patients received either IV cyclophosphamide or rituximab as standard of care 
treatment. Avacopan, alone or with low dose prednisone, was associated with a rapid onset of 
action based on a global disease activity index, the Birmingham Vasculitis Activity Score 
(BVAS), renal parameters such as albuminuria, and health-related quality of life measurements 
over a 12-week treatment period (Jayne et al., 2017). The steady state mean avacopan plasma 
concentration was approximately 204 ng/mL in these patients, corresponding to >95% projected 
inhibition of the C5aR in the circulation. Avacopan also showed a favorable safety profile. 
The second study in 42 patients (CL003_168) included three dose groups: 10 mg avacopan twice 
daily plus full dose prednisone (60 mg), 30 mg avacopan twice daily plus full dose prednisone, 
and placebo plus full dose prednisone. All patients received either IV cyclophosphamide or 
rituximab as standard of care treatment. Avacopan appeared to be safe when added on top of full 
dose prednisone plus cyclophosphamide or rituximab and the efficacy data support 30 mg 
avacopan twice daily as the therapeutic dose in AAV. There was no rebound effect when 
avacopan treatment was stopped. Refer to the Investigator’s Brochure for more details. 
A Phase 3 clinical trial with patients with AAV previously completed enrollment of >300 
patients and follow up is ongoing (ADVOCATE, CL010_168). In this study in patients with 
AAV, avacopan (or placebo) is being compared with standard of care glucocorticoids as added 
medications to background therapy of either cyclophosphamide followed by azathioprine, or of 
rituximab. The study remains blinded. 
The Data Monitoring Committee (DMC) for that study has commented on a 
. The DMC further 
commented on a potential risk of
ter an unblinded review of safety data from 
enrolled patients because 
 
Specifically, 
 patients receiving blinded study drug had Grade 2 (>3-5 times upper limit 
of normal [ULN]), and 
 patients receiving blinded study drug had Grade 3 transaminase 
elevations (>5 to 20 times ULN). In one patient, the transaminase elevation recurred when study 
drug was restarted. The interpretation was confounded by use of other immunosuppressive 
agents and other drugs known to be liver irritants including Sulfamethoxazole-Trimethoprim. 
The Reference Safety Information section of the Investigator’s Brochure has been updated to 
include the potential risk of 
, 
, and 
, and to state that general 
gastrointestinal adverse events (e.g., nausea, diarrhea) as previously observed in Phase 2 AAV 


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Protocol CL011_168 
 
 
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studies have been observed in the ongoing Phase 3 CL010_168 study at approximately the same 
frequency and severity. 
An open-label Phase 2 clinical trial in 7 patients with IgA nephropathy (IgAN) has been 
conducted (CL005_168). Results showed that avacopan was effective in improving proteinuria 
over a 12-week treatment period; 3 of 7 patients showed approximately 50% decrease in either 
urinary protein:creatinine ratio (UPCR) or albumin:creatinine ratio (UACR). An open-label 
Phase 2 clinical trial in 6 patients with atypical hemolytic uremic syndrome (aHUS) was 
conducted (CL006_168). Results showed that serum collected from patients dosed with 
avacopan caused a mean percent reduction of 82% in thrombus size compared to baseline in an 
ex vivo assay. 
A benefit and risk assessment of avacopan is presented in Section 12.3; detailed information 
about non-clinical and clinical trials with avacopan is presented in the Investigator’s Brochure. 
Results from nonclinical and clinical studies conducted to date showed a positive risk-benefit 
profile of avacopan in treatment of patients with AAV (Section 12.3.1 and Section 12.3.2 ). 
1.3. 
Rationale for the Study 
C3 glomerulopathy (C3G) is characterized by evidence of alternative complement activation 
based on C3 deposition in the glomeruli. There are two forms of the disease: dense deposit 
disease (DDD, formerly called membranoproliferative glomerulonephritis [MPGN] Type II) and 
C3 glomerulonephritis (C3GN, formerly called idiopathic MPGN). 
The major defect underlying C3G is excessive activation of the alternative complement pathway, 
resulting in the deposition of multiple complement components in the glomerulus, including 
components of C3 and C5 (Pickering et al., 2013), in the absence of antibody or immune 
complex deposition. The mechanism by which complement deposition leads to renal damage is 
not well understood, but likely involves chemotaxis of leukocytes resulting from cleavage of C5 
to generate C5a, as well as the cytolytic effects of C5b-9 (Hou et al., 2014). 
There is no approved treatment for patients with C3G. Immunosuppressive drugs such as 
cyclophosphamide, mycophenolate mofetil, and glucocorticoids, as well as biologics such as 
rituximab have been used with limited success. The anti-C5 antibody eculizumab has shown 
evidence of improvement in some patients with C3G (Bomback et al., 2012; Herlitz et al., 2012). 
Eculizumab blocks the formation of C5a and C5b-9 (membrane attack complex) from C5. 
Evidence from animal models suggests that inhibition of C5a may be more important than 
inhibition of C5b-9 in C3G because deletion of C6 (which is part of the C5b-9 complex) in 
complement factor H (CFH) knockout mice failed to protect the mice from developing 
symptoms of C3G (Pickering et al., 2006). This provides support for testing drugs such as 
avacopan that target C5aR. 
We used mice deficient in complement factor H (CFH) which develop spontaneous 
glomerulonephritis resembling C3G in humans (Pickering et al., 2002; Pickering et al., 2006) to 
evaluate the effect of avacopan. These CFH-deficient mice, carrying human C5aR, were treated 
with avacopan from 3 months of age. Plasma and urine were collected periodically and plasma 
creatinine, blood urea nitrogen, and urine albumin to creatinine ratio were measured. At 
7 months of age, CFH deficient mice that have been treated with vehicle showed elevated plasma 
creatinine comparing to CFH wild-type mice treated with vehicle (CFH deficient mice 1038 ± 


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15.48 µg/mL vs. CFH wild-type mice 863.5 ± 13.50 µg/mL; mean ± SEM; p = 0.002 for 
comparison of the two groups). The avacopan-treated CFH deficient mice had lower plasma 
creatinine compared to vehicle-treated CFH deficient mice (avacopan 843.0 ± 23.43 µg/mL vs. 
vehicle 1038 ± 15.48 µg/mL mean ± SEM, p = 0.0003 for comparison of the two groups). These 
data indicate that administration of avacopan to CFH-deficient mice protects renal function and 
provides a strong rationale for blocking the C5a receptor with a drug such as avacopan as a novel 
therapeutic approach for patients with C3G. 
One patient with treatment refractory C3GN, one of the subtypes of C3G, has been treated with 
30 mg avacopan twice daily from September 2015 until Lost to Follow up in December 2016 
under  a “Special Needs” program in the UK (CL009_168). This patient had progressive decline 
in renal function despite previous treatment with immunosuppressants, rituximab, and 
glucocorticoids, as well as a kidney transplant. Kidney histology prior to treatment with 
avacopan showed endocapillary hypercellularity and abundance of CD68-positive cells 
(macrophages) in the glomeruli. After 2 months of treatment with avacopan, histology showed 
no evidence of endocapillary hypercellularity and only a small number of CD68-positive cells in 
the glomeruli. A renal biopsy conducted approximately 6 months after starting avacopan 
treatment showed no hypercellularity and no crescents, and very few CD68-positive cells in the 
glomeruli. There was attenuation of eGFR decline with avacopan treatment. Refer to the 
Investigator’s Brochure for more detail. 
Based on the results in mice, the patient with C3GN, and the Phase 2 studies in AAV, IgAN, and 
aHUS, testing avacopan more broadly in patients with C3G is indicated. 
For more detail regarding the pharmacology and toxicology, and in-depth descriptions of clinical 
studies conducted with avacopan, please refer to the Investigator’s Brochure. 
This clinical trial will be conducted in compliance with the protocol, good clinical practice 
(GCP), and applicable regulatory requirements. 
2. 
OBJECTIVES 
2.1. 
Primary Objective 
The primary objective is to evaluate the efficacy of avacopan compared to placebo based on 
histologic changes in kidney biopsies taken before and during treatment. 
2.2. 
Secondary Objectives 
The secondary objectives of this study include evaluation of: 
1. The safety of avacopan compared to placebo based on the incidence of adverse events, 
changes in clinical laboratory measurements, and vital signs; 
2. Changes in laboratory parameters of renal disease including estimated glomerular 
filtration rate (eGFR), proteinuria, and urinary excretion of monocyte chemoattractant 
protein-1 (MCP-1) with avacopan compared to placebo; 
3. Health-related quality-of-life changes based on Short Form-36 version 2 (SF-36 v2) and 
EuroQOL-5D-5L (EQ-5D-5L) with avacopan compared to placebo; 


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4. The pharmacokinetic profile of avacopan in patients with C3G. 
2.3. 
Exploratory Objectives 
Additionally, changes from baseline in markers of the alternative complement pathway 
involvement and other markers of inflammation may be assessed in plasma/serum or urine over 
the course of the treatment period. 
3. 
STUDY DESIGN 
There is no approved treatment for patients with C3G. Immunosuppressive drugs such as 
cyclophosphamide, mycophenolate mofetil, and glucocorticoids, as well as biologics such as 
rituximab have been used but with limited success. The anti-C5 antibody eculizumab has shown 
evidence of improvement in some patients with C3G. 
Based on results both from preclinical studies and clinical results from treatment of a patient 
with C3GN in a “Special Needs” protocol, avacopan has the potential to be an effective therapy 
for patients with C3G. The safety and efficacy of avacopan will be evaluated in this randomized, 
double-blind, placebo-controlled clinical trial in approximately 88 patients with C3G. 
3.1. 
Stratification 
This is a clinical trial to test the efficacy, safety, and tolerability of avacopan in patients with 
C3G, including both C3GN and DDD. 
Patients with biopsy-proven C3G (within 12 weeks prior to signing informed consent or after 
consenting during screening or during screening), with or without a renal transplant, will be 
stratified by elevated or normal levels of C5b-9, and then will be randomized using a 
minimization algorithm to receive 30 mg avacopan twice daily or avacopan-matching placebo 
twice daily for 26 weeks in a double-blind manner: 
 
Both strata, (i.e., C5b-9 levels >244 ng/ml and ≤244 ng/mL) will include approximately 
44 patients; each level will have approximately 22 patients randomized (1:1) to the avacopan or 


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avacopan-matching placebo arm, respectively. However, enrollment for the stratum with C5b-9 
levels ≤244 ng/ml could terminate early if patient enrollment in the other stratum (C5b-9 level 
>244 ng/mL) reaches target enrollment first. 
To obtain balance across treatment groups, eligible patients within each of the C5b-9 level strata 
will be further stratified based on two factors: 
1. C3GN or DDD, and 
2. Whether the patient has received a kidney transplant or not. 
3.2. 
Randomization 
Patients will be randomized using an interactive response technology (IRT) system and a 
minimization algorithm, using the stratification factors, in a 1:1 ratio to one of two treatment 
groups: 
Group A: avacopan-matching placebo twice daily 
Group B: avacopan 30 mg twice daily 
The earliest timepoint at which the primary efficacy analysis can occur is when the last enrolled 
patient in the primary population (patients in the elevated C5b-9 stratum, see Section 8.2.1) has 
completed the Week 26 visit. After the 26-week double-blind period, the avacopan group will 
continue receiving avacopan for another 26 weeks, and the avacopan-matching placebo group 
will be switched over in a blinded manner to receive 30 mg avacopan twice daily treatment, 
instead of avacopan-matching placebo, for another 26 weeks. 
3.3. 
Study Treatments 
Treatments for each group are shown in Table 1 and Table 2. 
The treatment period is 52 weeks (364 days).  
Study drug (avacopan or placebo) will be taken as described in Section 5.3. 
Dose strengths given to study patients will differ for adults and adolescents. Adolescent patients 
(12 to 17 years old) are allowed to be enrolled only in countries and at study centers for which 
approval by Regulatory Authorities and IRBs/ECs was granted. 
3.3.1. 
Adult Patients - Study Treatments 
All adults will receive an avacopan dose of 30 mg twice daily or avacopan-matching placebo 
twice daily in the initial 26-week, placebo-controlled treatment period (Table 1).When they enter 
the open-label 26-week treatment period, all study patients regardless of their prior treatment will 
receive avacopan 30 mg twice daily. 


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Table 1: 
Dosing Groups in the First and Last 26 Weeks of Treatment in Adults 
 
First 26 Weeks 
(Placebo-controlled treatment period) 
Last 26 Weeks 
(Open-label treatment period) 
Group 
Avacopan 
Active 
Avacopan-Matching 
Placebo 
Avacopan         
Active 
Avacopan-Matching 
Placebo 
A 
None 
3 placebo capsules 
orally twice daily 
3 x 10 mg 
avacopan 
capsules orally 
twice daily 
None 
B 
3 x 10 mg 
avacopan 
capsules orally 
twice daily 
None 
3 x 10 mg 
avacopan 
capsules orally 
twice daily 
None 
3.3.2. 
Adolescent Patients - Study Treatments 
For study centers where enrollment of adolescent patients (12 to 17 years old) is approved, the 
dose of avacopan or placebo on Day 1 of the placebo-controlled period will be given based on 
the body weight determined at screening. Depending on the avacopan plasma exposure 
(AUC0-6hr) from Day 1, the dose will be adjusted as shown in Table 2. These dose adjustments 
will be made as soon as the plasma exposure results are available. 
When they enter the open-label 26-week treatment period, all adolescent patients will receive 
avacopan twice daily. Starting on Day 183, their dose will be reset based on the body weight 
determined on that day according to Table 2. Depending on the avacopan plasma exposure 
(AUC0- 6hr) from Day 183 the dose will be adjusted as shown in Table 2. These dose adjustments 
will be made as soon as the plasma exposure results are available. If adolescent patients were 
treated with avacopan in the first 26 weeks, their dose adjustment in the open-label treatment 
period may be determined based on Day 183 trough concentration rather than exposure 
(AUC0-6hr). 
In all adolescents, blood samples will be taken at pre-dose and at 0.5, 1, 2, 3, 4, and 6 hours after 
the first avacopan dose on Day 1 and Day 183, respectively, to determine the avacopan plasma 
exposure (AUC0-6hr). Plasma samples will be sent to the central laboratory for expeditious 
measurement of avacopan and CCX168-M1 in these patients. 
These AUC0-6hr thresholds are based on the mean avacopan plasma exposure (525 ng•hr/mL) and 
one standard deviation (174 ng•hr/mL) above or below the mean in adult patients from Phase 2 
study CL002_168 in AAV. 
In order to maintain the blind in the first 26 weeks of the study, some patients on placebo will 
also be instructed to modify the number of placebo capsules taken. The laboratory personnel 
conducting the PK assays will communicate the dosage changes, without sharing the PK results 
with the study site personnel or study team (see Section 5.6). 


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Table 2: 
Avacopan/Placebo Starting Dose and Dose Adjustments Based on Avacopan 
Plasma Exposure in Adolescent Patients 
Body 
weight 
Avacopan/Placebo Dose on 
Day 1 and Day 183, 
respectively 
Avacopan Plasma AUC0-6hr 
(ng•hr/mL) on Day 1 (or Day 183 
if the patient was on placebo in 
the first 26 weeks) 
Avacopan Dose 
Adjustment 
<40 kg          
(88 lbs.) 
10 mg (1 capsule) twice daily 
≥351  
None 
 
 
<351  
Increase dose to 20 mg     
(2 capsules) twice daily 
40-55 kg   
(88-121 
lbs.) 
20 mg (2 capsules) twice daily 
351 to 699 
None 
 
 
<351 
Increase dose to 30 mg     
(3 capsules) twice daily 
 
 
>699 
Decrease dose to 10 mg    
(1 capsule) twice daily 
>55 kg        
(121 lbs.) 
30 mg (3 capsules) twice daily 
≤699 
None 
 
 
>699 
Decrease dose to 20 mg    
(2 capsules) twice daily 
3.4. 
Study Flow 
Patients will be screened for enrollment based on biopsy-proven C3G (i.e., ≥2 levels of 
magnitude greater staining of C3 than any combination of IgG, IgM, IgA, kappa and lambda 
light chains, and C1q) and evidence of proliferative glomerulonephritis (mesangial 
hypercellularity and/or endocapillary hypercellularity based on the Mayo Clinic/Renal Pathology 
Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN; 
Sethi et al., 2016). 
The screening period will be up to 42 days (6 weeks). Screening procedures will include written 
Informed Consent/Assent, demographics, medical history, medication history (medication given 
prior to Day 1 of dosing is considered medication history), physical examination, 12-lead ECG, 
and vital signs, serum pregnancy test for females of childbearing potential, serum chemistry 
(including serum creatinine), hematology, urinalysis, urinary protein:creatinine ratio (UPCR) and 
albumin:creatinine ratio (UACR), viral and tuberculosis (TB) screening. If a patient did not have 
a renal biopsy in the past 12 weeks, a renal biopsy is required prior to Day 1. Prior to starting 
blinded study drug treatment, blood samples will be collected for the following measurements to 
create a baseline profile for all patients: 
1. Plasma C3a, C5a, C5b-9 and C5; 
2. Serum C3 and C4; 
3. Serum C3 nephritic factor; 
4. Plasma complement factor H and factor B; 


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5. Serum factor H autoantibody; 
6. Serum paraprotein detection; 
7. Complement factor H related protein 5 (CFHR5) mutation. 
Results obtained within 4 weeks prior to screening, or any time in the past for CFHR5 mutation, 
will be acceptable for the study. Patients who do not provide consent for genetic evaluation will 
not be excluded from the study. 
Patients meeting eligibility criteria will start blinded study drug treatment on Day 1. Patients will 
take avacopan 30 mg or matching placebo orally twice daily. The placebo-controlled treatment 
period is 26 weeks (182 days). This will be followed by 26 weeks during which all patients will 
receive avacopan. 
Thereafter, all patients will be followed for 8 weeks (56 days) without study drug treatment. 
As specified in the Time and Events Table, blood and urine samples will be collected for safety, 
efficacy, and pharmacokinetic and biomarker measurements. A serum pregnancy test for women 
of childbearing potential will be done regularly during the 52-week treatment period and at the 
end of the 8-week follow-up period. Liver function and hematology including differential blood 
work will be monitored at least every 4 weeks throughout the study. Physical examinations and 
vital signs assessments will be performed throughout the study. Health-related quality of life 
using the EQ-5D-5L and SF-36 v2 surveys will be assessed periodically over the course of the 
study. Study drug (avacopan or placebo) will be dispensed and drug accountability will be done. 
Concomitant medication and adverse event assessments will be made at every study visit. A 
follow-up renal biopsy will be performed at the following time points: 
1. Within 2 weeks prior to the Week 26 visit, and should be completed before open-label 
medication is started; 
2. If a patient is withdrawn early from the study, and 
3. After the 52-week treatment period. 
The Week 52 biopsy is optional in adolescent patients. 
If a patient is on other immunosuppressive or glucocorticoid treatment at the start of dosing, the 
dose(s) of concomitant immunosuppressive or glucocorticoid treatment may not be increased 
during the study (see Section 5.9). Treatment with these other drugs may be reduced or stopped 
during the study at the discretion of the Investigator, if the patient’s condition justifies it. 
Adjustments of tacrolimus and cyclosporine doses to ensure these medications are at goal trough 
levels for maintenance of immunosuppression in transplant patients will be allowed during the 
study. No new treatments for C3G, except for renin-angiotensin-aldosterone system (RAAS) 
inhibitors, may be added during the study period (52-week treatment period or 8-week follow 
up), unless the patient’s condition deteriorates to the extent that the investigator deems it in the 
best interest of the patient to do so. Addition of new treatments for C3G during the treatment 
period will be considered a treatment failure. 
Patients who experience deteriorating renal function based on an increase in serum creatinine of 
at least 50%, or an increase in proteinuria of >3 g/g creatinine from Screening or baseline during 


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the 52-week treatment period, will be considered treatment failures (see Section 4.4. Removal of 
Patients from Therapy). 
Patients will visit the study center for Screening and on Day 1 (baseline) and Weeks 1, 2, 4, 8, 
12, 16, 20, 23, 26, 28, 32, 35, 38, 41, 44, 48, 52, 54, 57, and 60 (follow-up visit). 
Patients will be discharged from the study when all the Week 60 visit procedures have been 
completed. The patient’s condition will be evaluated by the Investigator at the end of the clinical 
trial (Week 60) and appropriate standard of care medical treatment will be provided to all 
patients as needed. 
To the extent possible, any adverse events that are deemed study drug-related and are ongoing at 
discharge will be followed to resolution or until a determination is made that the unresolved 
event is stable. 
4. 
STUDY POPULATION 
4.1. 
Size of the Population 
The aim is to enroll approximately 88 patients in this clinical trial with approximately 44 patients 
in each of the two C5b-9 level strata. Patients who drop out early will not be replaced. 
4.2. 
Inclusion Criteria 
Patients must meet all of the following inclusion criteria in order to enter the study: 
1. Biopsy-proven C3G, either DDD or C3GN, with or without a renal transplant, and with the 
following observations upon renal biopsy taken within 12 weeks prior to screening or during 
screening: 
a. ≥2-levels of magnitude greater staining of C3 than any combination of IgG, IgM, 
IgA, kappa and lambda light chains, and C1q by immunohistochemistry, and 
b. Evidence of proliferative glomerulonephritis (mesangial hypercellularity of greater 
than 3 mesangial cells per mesangial area and/or endocapillary hypercellularity 
defined as an increased number of cells within glomerular capillary lumina, causing 
luminal narrowing) based on light microscopy, and 
c. Confirmation of the presence of electron dense deposits in the glomeruli on electron 
microscopy corresponding with the C3 immunofluorescence positivity. 
The site will use their site-specific standard technique for taking the biopsy, which can 
include ultrasound guidance. 
2. Male or female patients, aged at least 18 years; where approved, adolescents (12-17 years 
old) may be enrolled; female patients of childbearing potential (i.e., those who have 
experienced menarche and who are not permanently sterile or postmenopausal, defined as at 
least 12 consecutive months with no menses without an alternative medical cause) may 
participate if adequate contraception is used during, and for at least the three months after 
study completion; Male patients with partners of childbearing potential may participate in the 
study if they had a vasectomy at least 6 months prior to randomization or if adequate 
contraception is used during, and for at least the 3 months after study completion; male 


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patients with partners of childbearing potential must be excluded if they plan to father a child 
during the study. Adequate contraception is defined as resulting in a failure rate of less than 
1% per year (combined estrogen and progestogen [oral, intravaginal, or transdermal], or 
progestogen-only hormonal contraception (oral, injectable, or implantable), intra-uterine 
device, intra-uterine hormone releasing system, bilateral tubal occlusion, vasectomized 
partner, or true sexual abstinence, i.e., in line with the preferred and usual lifestyle of the 
patient). In addition, a barrier method (i.e., cervical cap, diaphragm or condom) must be used 
during intercourse between a male patient and a female of child-bearing potential. 
3. Willing and able to give written Informed Consent and to comply with the requirements of 
the study protocol; written Assent and Informed Consent must be obtained from the legal 
guardian in accordance with regional laws or regulations for patients 12 to 17 years of age; 
and 
4. Judged to be otherwise fit for the study by the Investigator, based on medical history, 
physical examination, and clinical laboratory assessments. Patients with clinical laboratory 
values that are outside of normal limits (other than those specified in the Exclusion Criteria) 
and/or with other abnormal clinical findings that are judged by the Investigator not to be of 
clinical significance, may be entered into the study. At sites in which adolescents are allowed 
to be enrolled, the Investigator assures that the adolescent patient is willing and able to ingest 
the size “0” study drug. 
4.3. 
Exclusion Criteria 
1. Pregnant or nursing; 
2. Tubulointerstitial fibrosis appears to be more than 50% based on standard assessment 
using trichrome staining of the renal biopsy; 
3. Use of eculizumab or another anti-C5 antibody within 26 weeks prior to dosing; 
4. Secondary C3 disease, e.g., infection-associated disease, or associated with another 
systemic or autoimmune disease; presence of a monoclonal spike on serum or urine 
protein electrophoresis or immunofixation assay; 
5. Currently on dialysis or likely will require dialysis within 7 days after screening; 
6. History or presence of any form of cancer within the 5 years prior to screening, with the 
exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in 
situ such as cervical or breast carcinoma in situ that has been excised or resected 
completely and is without evidence of local recurrence or metastasis; 
7. Positive hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency 
virus (HIV) viral screening test indicative of acute or chronic infection; 
8. Evidence of tuberculosis based on interferon γ release assay (IGRA), tuberculin purified 
protein derivative (PPD) skin test, or chest radiography done at screening or within 6 
weeks prior to screening; a CT scan or chest X-ray are not mandatory if evidence of 
tuberculosis was excluded by any of the other methods specified above; 
9. Active uncontrolled infection; 


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10. WBC count less than 3500/μL, or neutrophil count less than 1500/μL, or lymphocyte 
count less than 500/μL before start of dosing; 
11. Evidence of hepatic disease; AST, ALT, alkaline phosphatase, or bilirubin >3x the upper 
limit of normal before start of dosing; 
12. Currently using a strong inducer of the CYP3A4 enzyme, such as carbamazepine, 
phenobarbital, phenytoin, rifampin, or St. John's wort; 
13. Known hypersensitivity to avacopan or inactive ingredients of the avacopan capsules 
(including 
) or inability to swallow the 
capsules; 
14. Participated in any clinical study of an investigational product within 30 days prior to 
screening or within 5 half-lives after taking the last dose; and 
15. History or presence of any medical condition (for example: contraindication to local 
anesthesia required for renal biopsy, or recurring serious infections) or disease which, in 
the opinion of the Investigator, may place the patient at unacceptable risk for study 
participation. 
4.4. 
Removal of Patients from Therapy 
Investigators must clearly distinguish between discontinuation of study drug treatment (avacopan 
or placebo) and withdrawal from the study. Patients who discontinue study drug treatment or 
who initiate medication changes (including those prohibited by the protocol that comprise 
treatment failure) will not be automatically withdrawn from the study, but all efforts must be 
made to continue to follow the patients for all regularly scheduled visits. 
Investigators must take appropriate measures to make sure that patients are motivated to comply 
with all requirements of the protocol in order to minimize the amount of missing data. Patients 
who discontinue study treatment early or initiate medication changes (including those prohibited 
by the protocol) should continue to be followed for all regularly scheduled visits for safety and 
efficacy assessments. Investigators and their staff must take measures to actively maintain 
contact with their patients in the study, such as telephone calls, texts, or emails between visits, 
and offers for transportation support to visit the study site. 
Patients may be withdrawn from the study for only one of the following two reasons: 
1. Patient withdrawal of consent to contribute additional outcome information; 
2. Loss to follow-up.  
Patients may discontinue study drug treatment for any of the following reasons: 
1. Patient withdrawal of consent; 
2. The Investigator may discontinue study drug treatment if, in his/her clinical judgment, it 
is in the best interest of the patient; 
3. The Sponsor may request discontinuation of study drug treatment for safety reasons. If a 
patient develops any of the following lab abnormalities: 


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If a patient develops ALT or AST >3x ULN, additional testing should be performed immediately 
and repeated in one week to assay for total and fractionated serum bilirubin concentration, serum 
albumin concentration, and prothrombin time or INR, in addition to repeat transaminase (ALT, 
AST) testing. In addition, if a patient develops Grade 3 or greater increased hepatic 
transaminases (>5 times the upper limit of normal), or if a patient develops Grade 2 or greater 
increased transaminases (>3 times the upper limit of normal) with elevation of bilirubin to >2 
times the upper limit of normal, dosing with study drug must be paused in this patient. 
Study medication must be permanently discontinued (FDA Guidance 2009) if any of the 
following markers of hepatic injury and/or impaired liver synthetic function are observed, and 
cannot be attributed to a reversible etiology unrelated to study medication (e.g., cholelithiasis): 
• 
ALT or AST >8x ULN 
• 
ALT or AST >5x ULN for more than 2 weeks 
• 
ALT or AST >3x ULN and (Total Bilirubin >2x ULN or INR >1.5) 
• 
ALT or AST >3x ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%) 
If a patient develops Grade 3 or greater leukopenia (WBC count <2 x 109/L) or neutropenia 
(<1 x 109/L), or Grade 4 lymphopenia (<0.2 x 109/L), then study drug (avacopan or placebo) 
must be paused in this patient. In addition, if a patient develops Grade 2 leukopenia (WBC count 
<3 x 109/L, but ≥2 x 109/L), the patient must be followed closely for infection and for further 
significant reduction (reduction by an additional 0.5 x 109/L or more, or to <2 x 109/L) in WBC 
count; if either occurs, then study drug must be paused in this patient. Study drug may be 
resumed only if the abnormal value returns to normal and the Investigator deems resumption to 
be appropriate. 
If a patient develops Grade 3 or worse CPK increase (>5 times the upper limit of normal), dosing 
with study drug must be paused in this patient. Study drug may be resumed only if the CPK 
returns to normal levels. 
Patients who experience deteriorating renal function based on an increase in serum creatinine of 
at least 50% (confirmed by a repeat measurement after at least 2 weeks) which is otherwise not 
explained (e.g., dehydration, new medication), or an increase in proteinuria of >3 g/g creatinine 
(confirmed by a repeat measurement after at least 2 weeks) from Screening or baseline during 
the 52-week treatment period, will exit the treatment phase of the study and be treated at the 
discretion of their physician. The increase of serum creatinine or proteinuria will be calculated 
from the higher value that is measured either at Screening or baseline. They will remain in the 
study for follow up and complete the remaining study visits and procedures. If a patient refuses 
further study participation, the Early Termination visit procedures will be performed, if possible. 
These patients will be considered treatment failures. 
In the event of early withdrawal from the study, the tests and evaluations listed for the Early 
Termination visit in Section 6.23 will be performed, whenever possible. Data collected at this 
visit will be designated as an “Early Termination” visit in the EDC. The Sponsor should be 
notified of all study drug treatment and study withdrawals in a timely manner. 


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5. 
STUDY MEDICATION/TREATMENT 
5.1. 
Product Characteristics 
Avacopan will be administered orally as hard gelatin capsules containing 10 mg avacopan. The 
capsules are manufactured under current good manufacturing practices. All doses of study 
medication will be administered orally. The avacopan capsules will be supplied to the study 
centers in plastic bottles containing 180 capsules. This is sufficient for 30 days of dosing at 
30 mg avacopan twice daily. 
Avacopan-matching placebo will be administered orally as matching hard gelatin capsules 
containing no avacopan but inactive ingredients. The capsules are manufactured under current 
good manufacturing practices. All doses of study medication will be administered orally. The 
placebo capsules will be supplied to the study centers in plastic bottles containing 180 capsules. 
This is sufficient for 30 days of twice daily dosing. 
5.2. 
Randomization and Method of Treatment Assignment 
Eligible patients with biopsy-proven C3G (within 12 weeks prior to signing Informed Consent or 
after consenting during screening or during screening), with or without a renal transplant, will be 
stratified by elevated or normal plasma levels of C5b-9 and then further stratified based on two 
stratification factors (C3GN or DDD and renal transplant or no renal transplant), and eventually 
randomized to one of the two treatment groups in a ratio of 1 placebo: avacopan. 
Randomization will be performed centrally via an interactive response technology (IRT) system 
and minimization algorithm, using the stratification factors. In order to protect the blinding, the 
randomization schedule will not be accessible to study personnel who have contact with study 
centers or who are involved in data management and analysis. 
5.3. 
Doses and Regimens 
Treatments for each group are shown in Table 1. Adult patients will receive 30 mg avacopan or 
avacopan-matching placebo twice daily. For patients who are 12 to 17 years old, initial avacopan 
or avacopan-matching placebo doses will be selected based on body weight and further refined 
based on avacopan plasma exposure according to Table 2. 
The treatment period is 52 weeks (364 days), followed by an 8-week (56 days) follow-up period. 
Study drug (avacopan or placebo) within each of the C5b-9 level strata will be taken as follows 
by study patients: 
Group A (placebo): 
• Three avacopan-matching placebo capsules in the morning, preferably with food, and three in 
the evening, preferably with food, approximately 12 hours after the morning dose, daily for 
26 weeks (182 days). 
• This will be followed by three avacopan capsules in the morning, preferably with food, and 
three in the evening, preferably with food, approximately 12 hours after the morning dose, 
daily for the next 26 weeks (182 days). 


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Group B (avacopan): 
• Three 10 mg avacopan capsules in the morning, preferably with food, and three 10 mg 
avacopan capsules in the evening, preferably with food, approximately 12 hours after the 
morning dose, daily for 52 weeks (364 days). 
The placebo capsules will be identical in appearance to the avacopan capsules. 
Patients in Group A will receive one bottle of avacopan-matching placebo capsules on Day 1 and 
Weeks 4, 8, 12, and 16, and two bottles at the Week 20 visit. These patients will then receive 2 
bottles of avacopan capsules at the Week 26, 32, 38, and 44 visits. Patients will be asked to take 
3 capsules every morning, preferably with food, and 3 capsules every evening, preferably with 
food, as instructed. Patients will be asked to bring all bottles, whether empty or not, to the study 
center at each study visit. Capsules will be taken with water. 
Patients in Group B will receive one bottle of avacopan capsules on Day 1 and Weeks 4, 8, 12, 
and 16, and two bottles of avacopan capsules at the Week 20, 26, 32, 38, and 44 visits. Patients 
will be asked to take 3 capsules every morning, preferably with food, and 3 capsules every 
evening, preferably with food, as instructed. Patients will be asked to bring all bottles, whether 
empty or not, to the study center at each study visit. Capsules will be taken with water. 
If a patient misses a dose, the next dose should be taken as soon as possible. If it is close to the 
time for their next dose (within 3 hours), the missed dose should not be taken and the next dose 
should be taken at the regular time. 
5.4. 
Rationale for Dose Selection 
Single doses of 1 mg up to 100 mg avacopan were studied in a Phase 1 study (CL001_168) in 48 
healthy volunteers; once daily doses of 1, 3, and 10 mg avacopan and twice daily doses of 30 mg 
and 50 mg for up to 7 days were studied in the multiple dose period of this study. Doses from 
3 mg up to 100 mg twice daily for 7 days were tested in 16 healthy volunteers in Phase 1 study 
CL007_168; 30 mg single doses and 30 mg twice daily doses were tested for 17 days in 32 
healthy volunteers in Phase 1 study CL008_168. The various avacopan doses given in these 
studies were found to be safe. 
A dose of 30 mg avacopan twice daily given for 12 weeks was studied in clinical trial 
CL002_168 in patients with AAV. This dose regimen was shown to be effective and well 
tolerated in study CL002_168. Doses of 10 mg and 30 mg avacopan twice daily given for 12 
weeks were studied in clinical trial CL003_168 in patients with AAV and found to be well 
tolerated. Refer to the Investigator’s Brochure for details. 
An avacopan dose regimen of 30 mg twice daily was well tolerated in a patient with C3GN in a 
“Special Needs” study (CL009_168); this patient had been dosed continuously from September 
2015 until Lost to Follow-up in December 2016. 
A dose of 30 mg avacopan twice daily has been selected for adults in this study, which is lower 
than the maximum dose of 100 mg twice daily tested in study CL007_168. Adolescent patients 
may receive a lower starting dose, depending on their body weight (see Table 2). A dose regimen 
of 30 mg avacopan twice daily provides steady state trough (Cmin) a plasma avacopan 
concentration of approximately 200 ng/mL. This concentration was shown to provide at least 
95% C5aR blockade of blood neutrophils continuously throughout the day; the blockade level is 


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based on ex vivo C5a-induced CD11b upregulation assays conducted in whole blood samples 
obtained from patients in Phase 1 clinical trial CL001_168. This level of C5aR coverage is 
deemed appropriate to achieve optimal pharmacology. 
Based on the favorable safety profile observed in the long-term toxicology studies (26 weeks in 
rats and 44 weeks in cynomolgus monkeys; see Investigator’s Brochure), and on the safety and 
tolerability results from the clinical trials conducted to date, 30 mg avacopan twice daily is 
considered an appropriate dose to test in adults in this study. 
5.5. 
Drug Supply 
5.5.1. 
Packaging and Labeling 
Avacopan capsules containing 10 mg avacopan and identical appearing placebo capsules will be 
packaged in high density polyethylene (HDPE) bottles with child-resistant screw caps and 
provided to the study sites for dispensing. Each bottle will contain 180 capsules. 
5.5.2. 
Storage 
Avacopan and avacopan-matching placebo capsules will be stored according to label 
instructions. Access should be restricted to pharmacy staff or to the designated responsible 
member of the Investigator’s staff, and to the study monitor. The Investigator agrees that neither 
s/he nor any of the study staff will supply study medication to any persons other than those 
enrolled in the study. 
5.6. 
Blinding 
This study is double-blinded. Blinding of the study will be achieved by the following measures: 
1. The blinded study drug bottles and capsule appearance for avacopan and its matching 
placebo will be identical; 
2. Limited access to the randomization code; Sponsor personnel, study site personnel, study 
patients, personnel responsible for study monitoring, and biostatisticians and data 
managers involved in data analysis of the study will remain blinded to treatment 
assignment for the duration of the study; 
3. While laboratory personnel conducting the PK assays will not be blinded to treatment 
assignment, unblinded avacopan plasma concentration results will not be shared with the 
study site personnel or study staff who have direct contact with study sites during the 
study; 
4. Data that could potentially be unblinding, i.e., UPCR, UACR, and WBC and neutrophil 
count data within the normal range (i.e., values outside the normal range will be made 
available for safety monitoring), histology results from the central pathologist analysis, 
and urinary MCP-1:creatinine ratio will not be made available to study site personnel, 
study patients, personnel responsible for study monitoring, biostatisticians and data 
managers during the study unless required for safety monitoring. Investigators, however, 
will be provided with safety laboratory data reports, flagging abnormally high and low 
values in order to make informed decisions regarding patient care. 


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Treatment assignments for individual patients will remain blinded to the study team, 
investigators, and patients until after the study database has been cleaned and locked. Designated 
study staff will be provided with instructions regarding how to unblind an individual patient 
treatment assignment. An individual patient treatment assignment may be unblinded only in the 
case of an adverse event that requires knowledge of the study medication received by the patient 
in order to provide appropriate treatment or management of the adverse event. The study monitor 
and Sponsor should be notified as soon as possible in the event that unblinding of an individual 
patient’s treatment assignment occurs prior to study completion. 
An external data monitoring committee (DMC) will be constituted prior to start of the study (see 
Section 7.6). The DMC members will review data periodically over the course of the study in an 
unblinded manner. The DMC will provide recommendations to the Sponsor regarding further 
conduct of the study. The DMC will operate according to a charter developed prior to study 
initiation. 
5.7. 
Drug Accountability 
The study pharmacist and Investigator must maintain accurate records of dates and quantities of 
product(s) received, to whom dispensed (patient-by-patient accounting), and accounts of any 
product accidentally or deliberately destroyed. The Investigator must retain all unused and/or 
expired study supplies until the study monitor has confirmed the accountability data. All 
remaining study medication will be returned to the central depots for destruction. 
5.8. 
Treatment Compliance 
The avacopan and avacopan-matching placebo capsules will be self-administered by 
participating study patients. The morning dose of blinded study drug on Day 1 will be taken in 
the presence of study site personnel. Patients will be provided with dosing instructions at the start 
of the study and will be encouraged by study site personnel to take the study medication 
according to the instructions for the duration of the study. Patients will be instructed to bring the 
assigned bottles of study medication to the site staff at each study visit, whether empty or not. 
The study drug dispensed will be checked and a capsule count will be done from Week 4 through 
Week 52 of any remaining avacopan or placebo capsules. This information will be recorded and 
entered into the EDC system. 
Avacopan plasma concentration measurements over the course of the study may also be used to 
assess patient compliance. Any events of non-compliance to the protocol will be documented in 
the study records. 
5.9. 
Concomitant Medications and Restrictions 
In order not to disrupt patient care, the protocol will allow initial continuation of treatment with 
glucocorticoids, immunosuppressants, calcineurin inhibitors, or RAAS inhibitors at the start of 
the study, at the same or lower dose than what was given prior to the study. Treatment with these 
other drugs may be reduced or stopped during the study if, in the opinion of the treating 
physician, the patient’s condition justifies it. Adjustments of tacrolimus and cyclosporine doses 
to ensure these medications are at goal trough levels for maintenance of immunosuppression in 
transplant patients will be allowed during the study. 


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With the exception of RAAS inhibitors, dose increases of these concomitant treatments, or 
introduction of new treatments for C3G, will not be allowed during the study period (active 
treatment period) unless the patient’s condition deteriorates to the extent that the Investigator 
deems it in the best interest of the patient to do so. This will be considered a treatment failure. 
Eculizumab (and other anti-C5 antibodies) and investigational drugs will not be allowed during 
the study. The rationale for excluding anti-C5 antibodies is that these drugs act on the same 
branch of the complement pathway (C5), even though avacopan is selective for the C5aR. 
Therefore, eculizumab may interfere with the safety and efficacy assessment of avacopan. 
Investigational drugs have unknown effects and will therefore be excluded from the study. 
Plasma exchange or infusion during the study will also not be allowed, since these may interfere 
with the efficacy and safety evaluation of avacopan. 
Drugs that are strong inducers of the CYP3A4 enzyme, such as carbamazepine, phenobarbital, 
and phenytoin, rifampin, or St. John’s wort are prohibited during the study because these drugs 
may substantially reduce the plasma concentrations of avacopan and reduce its effectiveness. If a 
patient requires one of these drugs, the Medical Monitor needs to be contacted to discuss the 
situation. 
Substances that are strong inhibitors of CYP3A4, such as boceprevir, clarithromycin, conivaptan, 
indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, 
posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and voriconazole, and grapefruit 
juice should be avoided during the study because these may modestly increase (~2-fold) the 
plasma concentrations of avacopan. However, these substances are not absolutely 
contraindicated. In case it is unavoidable that these substances are used concomitantly with 
avacopan, patients should be monitored carefully for any untoward side effects. 
All concomitant medications taken during the course of the study must be recorded meticulously 
on the concomitant medication pages of the CRF. 
6. 
STUDY PROCEDURES 
6.1. 
Screening and Enrollment 
Informed Consent (and Assent, if relevant) must be obtained prior to performance of any study-
specific tests or evaluations. Within a period not to exceed 42 days prior to randomization, 
patients will undergo the following evaluations to determine their eligibility for study 
participation: 
• Recording of demographic data and relevant medical history in the EDC; 
• Recording of all prior medications for C3G for the 12-month period prior to screening in the 
EDC; 
• Recording of all other prior medications for the 6-month period prior to screening in the 
EDC; 


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• Recording of all other concomitant medications on the screening day(s) in the EDC, 
including alcohol intake, recreational drug use, non-prescription medications, herbal 
preparations or special diets; 
• A physical examination will be performed; body weight and height will be measured; 
• Vital signs (temperature, sitting blood pressure, heart rate) will be measured after at least 
3 minutes of rest; 
• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Serum pregnancy test (in women of childbearing potential); 
• Virology assessments as detailed in Section 7.2.2, unless done within 6 weeks prior to 
screening; 
• At least one of the following tests to exclude tuberculosis: interferon γ release assay (IGRA), 
tuberculin purified protein derivative (PPD) skin test, or chest radiography (X rays or CT 
scan); tests performed within 6 weeks prior to screening are allowed to assess eligibility; 
• Serum chemistry and hematology tests (results from tests done within 72 hours prior to 
screening may be used for eligibility assessment); 
• A clean catch, midstream urine sample will be collected for urinalysis, and urine protein, 
urine albumin and urine creatinine measurement for UPCR and UACR; 
• A renal biopsy will be taken if renal histology has not been performed within 12 weeks prior 
to screening; 
• Complement profiling as detailed in Section 7.2.3. Results obtained within 4 weeks prior to 
screening, or any time in the past for CFHR5 mutation, will be acceptable for the study. Also, 
the results from these tests do not need to be available before start of dosing on Day 1, except 
for the C5b-9 levels that are needed for eligibility assessment. 
Results from tests that have been performed prior to screening may be used to determine study 
eligibility if these tests were performed as part of the practice of medicine and were done 
whether or not study entry was contemplated, such as for diagnosis or treatment of the patient’s 
condition. Results from the prior tests must be recorded in the EDC. 
After all screening procedures have been completed, and the patient satisfies all eligibility 
criteria, the study schedule will be discussed with the patient and the schedule will be provided 
to the patient to ensure compliance with the study visits. 
6.2. 
Study Day 1 
If eligible for the study, the patient will visit the study center on Day 1. The following 
procedures will be performed before taking the first dose of avacopan or placebo: 
• Stratification and randomization in the IRT system; 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 


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• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Blood samples will be collected for shipment to the central laboratory for serum chemistry, 
hematology, serum pregnancy test (in women of childbearing potential), lymphocyte subset 
analysis, and PK and PD baseline measurements; 
• A clean catch, midstream urine sample will be collected, aliquoted, and sent to the central 
laboratory for urinalysis (including blood, protein, and nitrites; if positive for blood, protein, 
or nitrites, a microscopic assessment for RBC count will be performed), albumin, protein, 
MCP-1, and creatinine measurement (for UACR, UPCR and MCP-1:creatinine ratio), and 
urinary PD markers related to inflammation and the complement system; 
• Patients will be asked to complete the SF-36 v2 and EQ-5D-5L; 
• Any pre-treatment adverse events (from time of the screening visit) will be recorded; 
The patient will be stratified and randomized, and the following procedures will be performed: 
• Blinded study medication (1 bottle of avacopan or avacopan-matching placebo) will be 
provided to the patient with dosing instructions (see Section 5.3); 
• The patient will be asked to take the first dose of blinded study medication while at the study 
center; 
• The time of the dosing of avacopan or avacopan-matching placebo will be recorded; 
• If the patient is 12 to 17 years old, blood samples will be taken before dosing and at Hour 
0.5, 1, 2, 3, 4, and 6 after the first dose of avacopan or avacopan-matching placebo; plasma 
samples will be frozen and sent to the central laboratory for expeditious measurement of 
avacopan and metabolite plasma concentrations. Precise dosing and sampling times need to 
be recorded; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any post-dosing adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 1 study visit; 
− Store the blinded study medications in a cool and dry place according to label instructions 
for the duration of the study;  
− Take the avacopan or avacopan-matching placebo, as instructed, and 
− Continue taking all their other concomitant medications as usual. 
6.3. 
Study Week 1 (Day 8) 
The Study Week 1 visit must occur within ± 2 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 


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• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Blood samples will be collected for shipment to the central laboratory for hematology, 
lymphocyte subset analysis, and for PK and PD measurements. Record the date and time of 
blood draw; 
• The date and time of the last dose of avacopan/ avacopan-matching placebo prior to 
collection of the PK sample will be recorded;  
• If the patient has not yet taken the morning dose of avacopan/placebo for this day, the patient 
will be asked to take the dose; 
• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• The bottle of blinded study medication will be checked to make sure the patient is taking the 
blinded study medication as instructed; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 2 study visit; 
− Store the blinded study medications in a cool and dry place according to label instructions 
for the duration of the study; 
− Take the avacopan or avacopan-matching placebo as instructed, and 
− Continue taking all their other concomitant medications as usual. 
6.4. 
Study Week 2 (Day 15) 
The Study Week 2 visit must occur within ± 2 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• Blood samples will be collected for shipment to the central laboratory for serum chemistry, 
hematology, lymphocyte subset analysis, and for PK and PD measurements. Record the date 
and time of blood draw; 
• The date and time of the last dose of avacopan/ avacopan-matching placebo prior to 
collection of the PK sample will be recorded; 


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• If the patient has not yet taken the morning dose of avacopan/ avacopan-matching placebo 
for this day, the patient will be asked to take the dose; 
• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• The bottle of blinded study medication will be checked to make sure the patient is taking the 
blinded study medication as instructed; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 4 study visit; 
− Store the blinded study medications in a cool and dry place according to label instructions 
for the duration of the study; 
− Take the avacopan or avacopan-matching placebo as instructed, and 
− Continue taking all their other concomitant medications as usual. 
6.5. 
Study Week 4 (Day 29) 
The Study Week 4 visit must occur within ± 2 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• Blood samples will be collected for shipment to the central laboratory for serum chemistry, 
hematology, serum pregnancy test (in women of childbearing potential), lymphocyte subset 
analysis, and PK and PD measurements. Record the date and time of blood draw; 
• The date and time of the last dose of avacopan/ avacopan-matching placebo prior to 
collection of the PK sample will be recorded; 
• If the patient has not yet taken the morning dose of avacopan/avacopan-matching placebo for 
this day, the patient will be asked to take the dose; 
• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• Patients will be asked to complete the SF-36 v2 and EQ-5D-5L; 
• Drug accountability will be performed on the returned avacopan/placebo bottle; 


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• A new bottle of avacopan/avacopan-matching placebo will be dispensed; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 8 study visit; 
− Store the blinded study medications in a cool and dry place according to label instructions 
for the duration of the study; 
− Take the avacopan or avacopan-matching placebo as instructed, and 
− Continue taking all their other concomitant medications as usual. 
6.6. 
Study Week 8 (Day 57) 
The Study Week 8 visit must occur within ± 2 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• Blood samples will be collected for shipment to the central laboratory for serum chemistry, 
hematology, and serum pregnancy test (in women of childbearing potential). Record the date 
and time of blood draw; 
• If the patient has not yet taken the morning dose of avacopan/avacopan-matching placebo for 
this day, the patient will be asked to take the dose; 
• A clean catch, midstream urine sample will be collected for urinalysis and for urine protein, 
urine albumin, and urine creatinine measurement for calculation of UPCR and UACR; the 
sample will be sent to the central laboratory; 
• Drug accountability will be performed on the returned avacopan/avacopan-matching placebo 
bottle; 
• A new bottle of avacopan/placebo will be dispensed; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded;  
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 12 study visit; 
− Store the blinded study medications in a cool and dry place according to label instructions 
for the duration of the study;  
− Take the avacopan or avacopan-matching placebo as instructed, and 


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− Continue taking all their other concomitant medications as usual. 
6.7. 
Study Week 12 (Day 85) 
The Study Week 12 visit must occur within ± 2 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• Blood samples will be collected for shipment to the central laboratory for a serum pregnancy 
test (in women of childbearing potential), serum chemistry, hematology, lymphocyte subset 
analysis, and PK and PD measurements. Record the date and time of blood draw; 
• The date and time of the last dose of avacopan/ avacopan-matching placebo prior to 
collection of the PK sample will be recorded; 
• If the patient has not yet taken the morning dose of avacopan/ avacopan-matching placebo 
for this day, the patient will be asked to take the dose; 
• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• Patients will be asked to complete the SF-36 v2 and EQ-5D-5L; 
• Drug accountability will be performed on the returned avacopan/ avacopan-matching placebo 
bottle; 
• A new bottle of avacopan/ avacopan-matching placebo will be dispensed; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 16 study visit; 
− Store the blinded study medications in a cool and dry place according to label instructions 
for the duration of the study; 
− Take the avacopan/ avacopan-matching placebo as instructed, and 
− Continue taking all their other concomitant medications as usual. 
6.8. 
Study Week 16 (Day 113) 
The Study Week 16 visit must occur within ± 2 days of the scheduled date. During this visit, the 
following study procedures will be performed: 


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• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• Blood samples will be collected for shipment to the central laboratory for serum chemistry, 
hematology, and serum pregnancy test (in women of childbearing potential). Record the date 
and time of blood draw; 
• If the patient has not yet taken the morning dose of avacopan/ avacopan-matching placebo 
for this day, the patient will be asked to take the dose; 
• A clean catch, midstream urine sample will be collected for urinalysis and for urine protein, 
urine albumin, and urine creatinine measurement for calculation of UPCR and UACR; the 
sample will be sent to the central laboratory; 
• Drug accountability will be performed on the returned avacopan/ avacopan-matching placebo 
bottle; 
• One new bottle of avacopan/ avacopan-matching placebo will be dispensed; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 20 study visit; 
− Store the blinded study medications in a cool and dry place according to label instructions 
for the duration of the study; 
− Take the avacopan/ avacopan-matching placebo as instructed, and 
− Continue taking all their other concomitant medications as usual. 
6.9. 
Study Week 20 (Day 141) 
The Study Week 20 visit must occur within ± 2 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• Blood samples will be collected for shipment to the central laboratory for a serum pregnancy 
test (in women of childbearing potential), serum chemistry, hematology, and PK and PD 
measurements. Record the date and time of blood draw; 
• The date and time of the last dose of avacopan/ avacopan-matching placebo prior to 
collection of the PK sample will be recorded; 


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• If the patient has not yet taken the morning dose of avacopan/ avacopan-matching placebo 
for this day, the patient will be asked to take the dose; 
• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• Patients will be asked to complete the SF-36 v2 and EQ-5D-5L; 
• Drug accountability will be performed on the returned avacopan/ avacopan-matching placebo 
bottle; 
• Two new bottles of avacopan/ avacopan-matching placebo will be dispensed; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
• Come to the study center for the Week 23 study visit; 
− Store the blinded study medication in a cool and dry place according to label instructions 
for the duration of the study; 
− Take the avacopan/avacopan-matching placebo as instructed, and 
− Remember not to take the morning dose of avacopan or /avacopan-matching placebo at 
home on the morning of the next visit at the study center, and 
− Continue taking all their other concomitant medications as usual. 
6.10. 
Study Week 23 (Day 162) 
The Study Week 23 visit must occur within ± 7 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A blood sample will be collected for measurement of serum chemistry and hematology. 
Record the date and time of blood draw. 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or changes to a 
special diet; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 26 study visit 
− Take the avacopan/ avacopan-matching placebo as instructed, and 
− Remember not to take the morning dose of avacopan or avacopan-matching placebo at 
home on the morning of the next visit at the study center, and 


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− Continue taking all their other concomitant medications as usual. 
6.11. 
Study Week 26 (Day 183) 
The Study Week 26 visit must occur within ± 7 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Blood samples will be collected before the morning dose for shipment to the central 
laboratory for a serum pregnancy test (in women of childbearing potential), serum chemistry, 
hematology, lymphocyte subset analysis, and PK and PD measurements. Record the date and 
time of blood draw; 
• The date and time of the last dose of avacopan/ avacopan-matching placebo prior to 
collection of the PK sample will be recorded; 
• The patient will be asked to take the morning dose of avacopan while at the study center; 
• The time of the dosing of avacopan will be recorded; 
• If the patient is 12 to 17 years old, blood samples will be taken before dosing and at Hour 
0.5, 1, 2, 3, 4, and 6 after the morning dose of avacopan; plasma samples will be frozen and 
sent to the central laboratory for expeditious measurement of avacopan and metabolite 
plasma concentrations. Note: it is important that on Day 183 the adolescent patients take the 
dose when instructed at the study center, NOT at home, and they should be reminded through 
a telephone call two days before the Day 183 visit. 
• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• Renal biopsy, performed within -2 weeks prior to the Week 26 visit and BEFORE patient is 
started on open-label treatment; 
• Patients will be asked to complete the SF-36 v2 and EQ-5D-5L; 
• Drug accountability will be performed on the returned avacopan/ avacopan-matching placebo 
bottles; 
• Two new bottles of avacopan will be dispensed; 
• For adolescents, two new bottles of avacopan will be provided to the patient with dosing 
instructions according to body weight (see Section 5.3); 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 


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• Any adverse events will be recorded;  
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 28 study visit; 
− Store the study medication in a cool and dry place according to label instructions for the 
duration of the study;  
− Take the avacopan as instructed, and 
− Continue taking all their other concomitant medications as usual. 
6.12. 
Study Week 28 (Day 197) 
The Study Week 28 visit must occur within ± 2 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Blood samples will be collected for shipment to the central laboratory for a serum pregnancy 
test (in women of childbearing potential), serum chemistry, hematology, and PK and PD 
measurements. Record the date and time of blood draw; 
• If the patient has not yet taken the morning dose of avacopan for this day, the patient will be 
asked to take the dose; 
• The date and time of the last dosing of avacopan prior to the collection of the PK sample will 
be recorded; 
• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded; 
• The dose for this visit and doses forward for adolescent patients may be adjusted based on 
the PK result of Day 183, per directions from the Sponsor; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 32 study visit; 
− Store the study medication in a cool and dry place according to label instructions for the 
duration of the study;  
− Take the avacopan as instructed, and 


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− Continue taking all their other concomitant medications as usual. 
6.13. 
Study Week 32 (Day 225) 
The Study Week 32 visit must occur within ± 7 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 year 
old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Blood samples will be collected for shipment to the central laboratory for a serum pregnancy 
test (in women of childbearing potential), serum chemistry, hematology, and PK and PD 
measurements. Record the date and time of blood draw; 
• If the patient has not yet taken the morning dose of avacopan for this day, the patient will be 
asked to take the dose; 
• The date and time of the last dose of avacopan prior to collection of the PK sample will be 
recorded; 
• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• Patients will be asked to complete the SF-36 v2 and EQ-5D-5L; 
• Drug accountability will be performed on the returned avacopan bottles; 
• Two new bottles of avacopan will be dispensed; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 35 study visit; 
− Store the study medication in a cool and dry place according to label instructions for the 
duration of the study; 
− Take the avacopan as instructed, and 
− Continue taking all their other concomitant medications as usual. 
6.14. 
Study Week 35 (Day 246) 
The Study Week 35 visit must occur within ± 7 days of the scheduled date. During this visit, the 
following study procedures will be performed: 


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• A blood sample will be collected for measurement of serum chemistry and hematology. 
Record the date and time of blood draw. 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or changes to a 
special diet; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 38 study visit 
− Take the avacopan/ avacopan-matching placebo as instructed, and 
− Remember not to take the morning dose of avacopan or avacopan-matching placebo at 
home on the morning of the next visit at the study center, and 
− Continue taking all their other concomitant medications as usual. 
6.15. 
Study Week 38 (Day 267) 
The Study Week 38 visit must occur within ± 7 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 year 
old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• Blood samples will be collected for shipment to the central laboratory for a serum pregnancy 
test (in women of childbearing potential), serum chemistry, hematology, lymphocyte subset 
analysis, and PK and PD measurements. Record the date and time of blood draw; 
• If the patient has not yet taken the morning dose of avacopan for this day, the patient will be 
asked to take the dose; 
• The date and time of the last dose of avacopan prior to collection of the PK sample will be 
recorded; 
• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• Patients will be asked to complete the SF-36 v2 and EQ-5D-5L; 
• Drug accountability will be performed on the returned avacopan bottles; 
• Two new bottles of avacopan will be dispensed; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded;  


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• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 41 study visit; 
− Store the study medication in a cool and dry place according to label instructions for the 
duration of the study;  
− Take the avacopan as instructed, and  
− Continue taking all their other concomitant medications as usual. 
6.16. 
Study Week 41 (Day 288) 
The Study Week 41 visit must occur within ± 7 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A blood sample will be collected for measurement of serum chemistry and hematology. 
Record the date and time of blood draw. 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or changes to a 
special diet; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 44 study visit 
− Take the avacopan as instructed, and 
− Remember not to take the morning dose of avacopan at home on the morning of the next 
visit at the study center, and 
− Continue taking all their other concomitant medications as usual. 
6.17. 
Study Week 44 (Day 309) 
The Study Week 44 visit must occur within ± 7 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 
17 year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• Blood samples will be collected for shipment to the central laboratory for a serum pregnancy 
test (in women of childbearing potential), serum chemistry, and hematology. Record the date 
and time of blood draw; 
• If the patient has not yet taken the morning dose of avacopan for this day, the patient will be 
asked to take the dose; 
• The date and time of the last dose of avacopan prior to collection of the PK sample will be 
recorded; 


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• A clean catch, midstream urine sample will be collected for urinalysis and for urine protein, 
urine albumin, and urine creatinine measurement for calculation of UPCR and UACR; the 
sample will be sent to the central laboratory; 
• Drug accountability will be performed on the returned avacopan bottles; 
• Two new bottles of avacopan will be dispensed; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded;  
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 48 study visit; 
− Store the study medication in a cool and dry place according to label instructions for the 
duration of the study;  
− Take the avacopan as instructed 
− Continue taking all their other concomitant medications as usual. 
6.18. 
Study Week 48 (Day 337) 
The Study Week 48 visit must occur within ± 7 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A blood sample will be collected for measurement of serum chemistry and hematology. 
Record the date and time of blood draw. 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or changes to a 
special diet; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 52 study visit 
− NOT take any study medication the morning of the Week 52 visit 
6.19. 
Study Week 52 (Day 365) 
The Study Week 52 visit must occur within ± 7 days of the scheduled date. Two days prior to the 
expected visit, the Investigator must telephone the patient (this applies to both adults and 
adolescents) to remind him or her to NOT take any avacopan in the morning of this visit. The 
dose will also NOT be taken at the study center on this day. During this visit, the following study 
procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 
17 year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 


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• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Blood samples will be collected for shipment to the central laboratory for a serum pregnancy 
test (in women of childbearing potential), serum chemistry, hematology, lymphocyte subset 
analysis, and PK and PD measurements. Record the date and time of blood draw; 
• The date and time of the last dose of avacopan prior to collection of the PK sample will be 
recorded; 
• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• Renal biopsy, performed within ± 2 weeks of the Week 52 visit; this procedure is optional for 
adolescent patients; 
• Patients will be asked to complete the SF-36 v2 and EQ-5D-5L; 
• Drug accountability will be performed on the returned avacopan bottles; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded;  
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 54 study visit, and 
− Continue taking all their other concomitant medications as usual. 
6.20. 
Study Week 54 (Day 379) 
The Study Week 54 visit must occur within ± 7 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Blood samples will be collected for shipment to the central laboratory for a serum pregnancy 
test (in women of childbearing potential), serum chemistry, hematology, and PK and PD 
measurements. Record the date and time of blood draw; 
• A clean catch, midstream urine sample will be collected for urinalysis and for urine protein, 
urine albumin, and urine creatinine measurement for calculation of UPCR and UACR; the 
sample will be sent to the central laboratory; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 


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• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 57 study visit, and 
− Continue taking all their other concomitant medications as usual. 
6.21. 
Study Week 57 (Day 400) 
The Study Week 57 visit must occur within ± 7 days of the scheduled date. During this visit, the 
following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Blood samples will be collected for shipment to the central laboratory for a serum pregnancy 
test (in women of childbearing potential), serum chemistry, hematology, and PK and PD 
measurements. Record the date and time of blood draw; 
• A clean catch, midstream urine sample will be collected for urinalysis and for urine protein, 
urine albumin, and urine creatinine measurement for calculation of UPCR and UACR; the 
sample will be sent to the central laboratory; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be reminded to: 
− Come to the study center for the Week 60 study visit, and 
− Continue taking all their other concomitant medications as usual. 
6.22. 
Study Week 60 (Day 421) 
The Study Week 60 visit (follow-up visit) must occur within ± 7 days of the scheduled date. 
During this visit, the following study procedures will be performed: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Blood samples will be collected for shipment to the central laboratory for a serum pregnancy 
test (in women of childbearing potential), serum chemistry, hematology, lymphocyte subset 
analysis, and PK and PD measurements. Record the date and time of blood draw; 


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• A clean catch, midstream urine sample will be collected for urinalysis, for PD assessment, 
and for urine protein, urine albumin, urinary MCP-1 and urine creatinine measurement for 
calculation of UPCR, UACR and urinary MCP-1:creatinine ratio; the sample will be sent to 
the central laboratory; 
• Patients will be asked to complete the SF-36 v2 and EQ-5D-5L; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded; 
• After all study procedures have been completed, the patient will be discharged from the 
study. The patient’s condition will be evaluated by the Investigator at the end of the clinical 
trial (Week 60) and appropriate standard of care medical treatment will be provided to all 
patients as needed. 
6.23. 
Early Termination Visit 
If a patient is withdrawn early from the study, the following termination procedures must be 
completed whenever possible: 
• A physical examination including body weight; height will also be measured in 12 to 17 
year-old patients; 
• Vital signs (temperature, sitting blood pressure, heart rate) after at least 3 minutes of rest; 
• A 12-lead ECG will be performed after at least 3 minutes of rest in a supine position; 
• Blood samples will be collected for shipment to the central laboratory for serum chemistry, 
hematology, lymphocyte subset analysis and serum pregnancy test (in women of childbearing 
potential) measurement. Record the date and time of blood draw; 
• A clean catch, midstream urine sample will be collected for urinalysis at the central 
laboratory; 
• Drug accountability will be performed on the returned avacopan/avacopan-matching placebo 
bottles; 
• Any changes in concomitant medication use will be recorded, including alcohol intake, 
recreational drug use, non-prescription medications, herbal preparations or special diets; 
• Any adverse events will be recorded. If an adverse event remains unresolved at the 
conclusion of the study, a clinical assessment will be made by the Investigator and the 
Sponsor’s Medical Monitor to determine whether continued follow-up of the adverse event is 
warranted. 
• A follow-up renal biopsy will be performed if a patient is withdrawn early from the study. 


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7. 
STUDY ASSESSMENTS 
7.1. 
Efficacy Assessments 
7.1.1. 
Renal Histology 
For eligibility assessment, renal biopsy samples taken within 12 weeks prior to screening or 
during screening will be assessed by immunofluorescence staining for C3 and immunoglobulins, 
as well as electron microscopy to confirm the presence of electron dense deposits. Eligibility 
assessment will be made by the Investigator based on their local pathologist’s evaluation. 
Patients must have biopsy-proven C3G, either DDD or C3GN, with ≥2-levels of magnitude 
greater staining of C3 than any combination of IgG, IgM, IgA, kappa and lambda light chains, 
and C1q, and with evidence of proliferative glomerulonephritis (mesangial hypercellularity 
and/or endocapillary hypercellularity). 
All renal biopsies will be analyzed with the routine panel of stains which includes hematoxylin-
eosin (H&E), periodic acid–Schiff (PAS), trichrome, and Jones methenamine silver. A minimum 
of 4 (preferably 6) unstained slides from paraffin-embedded renal tissue will be provided by 
study centers to the central histopathology laboratory for additional immunostaining (e.g., CD45, 
CD68, MPO, C5a, C5aR, etc.). 
Renal biopsies will be evaluated by a central reader, an expert in C3G renal pathology, who will 
be blinded to treatment assignment from either slides or digitized high-resolution images. 
The central reader will determine the degree of disease activity and chronicity based on the C3G 
Histologic Index. A semi-quantitative scale of 0 to 3 will be used, indicating either the 
proportion (%) of glomeruli involved or the proportion of cortex involved (for tubular atrophy 
and interstitial fibrosis). 
The C3G Histologic Index for disease activity will consider 7 lesions: 
1. Mesangial hypercellularity, defined as >3 mesangial cells per mesangial area; 
2. Endocapillary hypercellularity/proliferation, defined as an increased number of cells 
within glomerular capillary lumina, causing luminal narrowing; 
3. Membranoproliferative morphology; 
4. Leukocyte infiltration; 
5. Crescent formation, defined as extracapillary cell proliferation of more than two cell 
layers with >50% of the lesion occupied by cells; 
6. Fibrinoid necrosis; 
7. Interstitial inflammation. 
Definitions are based on the Mayo Clinic/Renal Pathology Society Consensus Report on 
Pathologic Classification, Diagnosis, and Reporting of GN (Sethi et al., 2016) and the activity 
index score uses the glomerulopathy histologic score as described by Bomback and colleagues 
(Bomback et al., 2018). 
For endocapillary hypercellularity/proliferation, mesangial hypercellularity, 
membranoproliferative morphology, and leukocyte infiltration the following scale will be used: 


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0 = none, 1 = 1-25%, 2 = 26-50%, 3 = >50% involvement. For crescent formation and fibrinoid 
necrosis, the following scale will be used: 0 = none, 1 = 1-10%, 2 = 11-25%, and 3 = >25% 
involvement. For interstitial inflammation, a score according to percentage of cortical 
tubulointerstitial area involved will be used: 0 = <10%, 1 = 10-25%, 2 = 26-50%, 3 = >50% 
involvement. 
The C3G Histologic Index for disease activity can assume a score from 0-21. 
The C3G Histologic Index for disease chronicity will consider 4 lesions (Bomback et al., 2018): 
1. Glomerulosclerosis (% glomeruli with global and segmental sclerosis), 
2. Tubular atrophy, 
3. Interstitial fibrosis, and 
4. Arterio- and arteriolosclerosis 
Glomerulosclerosis (global plus segmental), tubular atrophy, and interstitial fibrosis will be 
assigned a score of 0 to 3 based on the percentage of glomeruli or cortical tubulointerstitial area 
involved. The following scale will be used for the chronicity index: 0 = <10%, 1 = 10-25%, 
2 = 26-50%, 3 = >50% involvement. For vascular disease, a score of 0 will be assigned if intimal 
thickening is < thickness of media and 1 if intimal thickening is ≥ thickness of media. The C3G 
Histologic Index for disease chronicity can assume a score from 0-10.The primary endpoint is 
based on the percent change from baseline in the C3G Histologic Index for disease activity. 
Percent change from baseline in C3G Histologic Index for disease chronicity will be a secondary 
endpoint. 
Electron microscopy will be performed to evaluate the treatment effect of avacopan on electron 
microscopic features of the disease such as dense deposits. 
Immunohistochemistry evaluation will be performed by the central pathologist to evaluate the 
treatment effect of avacopan on specific immune cell populations such as total leukocytes, 
macrophages, neutrophils, etc. 
7.1.2. 
Urinary Measurements 
A clean catch midstream urine sample needs to be collected at the clinic according to instructions 
provided separately. The urine samples will be sent to the central laboratory for analysis. The 
following analyses will be performed according to the Time and Events Table: 
• Urinalysis including blood, protein, and nitrites; if positive for blood, protein, or nitrites, a 
microscopic assessment for RBC casts and RBC count will be performed; 
• Quantitative albumin, protein and creatinine measurements to calculate the urinary 
albumin:creatinine ratio (UACR) and protein:creatinine ratio (UPCR); 
• Quantitative MCP-1 measurements to calculate the MCP-1:creatinine ratio; 
• Other urinary markers related to inflammation and the complement system may also be 
measured. 


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Microscopic review is triggered if a urinary dipstick test is positive for blood, nitrite, or protein. 
When microscopy is performed, hematuria will be categorized as follows: None, Occasional 
(Occ), 1 - 2, 3 - 5, 6 - 9, 10 - 15, 16 - 29, 30 - 49, 50 - 75, and >75 RBCs per high power field. 
Proteinuria will be assessed by measuring the protein and creatinine concentrations and 
calculating the UPCR. Results will be expressed as mg protein/g creatinine. 
Albuminuria will be assessed by measuring the albumin and creatinine concentrations and 
calculating the UACR. Results will be expressed as mg albumin/g creatinine. 
Urine MCP-1 will be measured by specific ELISA assay. Urine MCP-1 levels will be 
standardized to urine creatinine and expressed as pg MCP-1/mg creatinine. 
Other inflammation and complement markers will be measured using validated assay 
methodology. 
7.1.3. 
Estimated Glomerular Filtration Rate 
For adults (aged 18 years or older), estimated glomerular filtration rate (eGFR) will be calculated 
from serum creatinine measurements at all applicable study visits using the Chronic Kidney 
Disease-Epidemiology Collaboration study (CKD-EPI) equation according to Table 3 (Levey et 
al., 2009). 
Table 3: 
CKD-EPI Equation Based on Race and Gender 
Race and Sex 
Serum 
Creatinine, 
µmol/L (mg/dL) 
Equation 
Black 
 
 
Female 
≤62 (≤0.7) 
GFR = 166 x (serum creatinine/0.7)-0.329 x (0.993)Age 
 
>62 (>0.7) 
GFR = 166 x (serum creatinine /0.7)-1.209 x (0.993)Age 
Male 
≤80 (≤0.9) 
GFR = 163 x (serum creatinine /0.9)-0.411 x (0.993)Age 
 
>80 (>0.9) 
GFR = 163 x (serum creatinine /0.9)-1.209 x (0.993)Age 
White or Other 
 
 
Female 
≤62 (≤0.7) 
GFR = 144 x (serum creatinine /0.7)-0.329 x (0.993)Age 
 
>62 (>0.7) 
GFR = 144 x (serum creatinine /0.7)-1.209 x (0.993)Age 
Male 
≤80 (≤0.9) 
GFR = 141 x (serum creatinine /0.9)-0.411 x (0.993)Age 
 
>80 (>0.9) 
GFR = 141 x (serum creatinine /0.9)-1.209 x (0.993)Age 
Source: Levey et al., 2009 
The CKD-EPI equation is not optimal for evaluation of the eGFR in children (Selistre et al., 
2016). The modified Schwartz equation has been developed to calculate the eGFR in children 
(Schwartz et al., 2009). The equation is as follows: 
eGFR = (0.413 x Height [in cm]) / Serum creatinine (in mg/dL) 
The revised Schwartz equation will be used to calculate eGFR in adolescents (12 to 17 years old) 
enrolled in this study. 


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Serum creatinine (and eGFR) measurements will be made according to the Time and Events 
Table. Change and percent change from baseline in eGFR will be calculated and will be assessed 
as a secondary endpoint in the study. 
7.1.4. 
Health-Related Quality of Life Assessments 
The SF-36 v2 and EQ-5D-5L will be completed by study patients at visits specified in the 
Time and Events Table to measure changes from baseline in health-related quality of life. Proven 
translations will be used for non-English speaking patients whenever possible. An administrator 
will facilitate completion of the questionnaires by the patients, but will not complete the forms 
for the patients. The administrator will establish a rapport with the patient, emphasize the 
importance of completing the form, and serve to answer questions and address concerns. The 
questionnaires should be completed by patients before seeing the Investigator at the visit. 
7.2. 
Safety Assessments 
7.2.1. 
Physical Examinations, Vital Signs and 12-lead ECGs 
A complete physical examination (including evaluation of general appearance/mental status, 
head, eyes, ears, nose, throat, and the following body systems: dermatologic, cardiovascular, 
respiratory, gastrointestinal, musculoskeletal and neurologic) will be performed at visits 
indicated in the Time and Events Table. Findings must be recorded in the source documents. 
Any new or worsening findings upon physical examination need to be recorded as adverse 
events. 
Body weight will be measured as part of the physical examinations. Height needs to be recorded 
at screening only, except for adolescents (12 to 17 years old) in whom height will also be 
included as part of all physical examinations. BMI will be calculated in the EDC from the body 
weight and height measurements. 
Vital signs will be measured during screening and on each scheduled study day as indicated in 
the Time and Events Table. Sitting blood pressure, pulse rate, and body temperature will be 
measured. All vital signs assessments will be performed after the patient has rested for at least 
three minutes. 
12-lead ECGs will be performed at visits indicated in the Time and Events Table. Findings must 
be recorded in the source documents. The ECG will be performed after the patient has rested for 
three minutes in a supine position. Abnormal and clinically significant changes in ECG per 
Investigator’s assessment compared to baseline screening need to be recorded as adverse events. 
7.2.2. 
Clinical Safety Laboratory Assessments 
The following tests will be performed via Central Laboratory at the visits identified in the Time 
and Events Table. 
• Hematology: hemoglobin, hematocrit, RBC count, WBC count with differential, platelet 
count, mean cell hemoglobin, mean cell hemoglobin concentration, mean corpuscular 
volume; 


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• Serum Chemistry: liver panel (total and fractionated bilirubin, lactate dehydrogenase, 
aspartate aminotransferase, alanine aminotransferase), renal panel (blood urea nitrogen, 
creatinine), creatine phosphokinase (CPK), albumin, sodium, potassium, magnesium, 
bicarbonate, chloride, calcium, inorganic phosphorus, glucose, total protein, alkaline 
phosphatase, total cholesterol, uric acid, serum amylase, and serum lipase; 
• Coagulation: PT and INR if retest is performed because of ALT and/or AST >3x ULN; 
• Urinalysis: at the central laboratory, nitrite, blood, and protein, will be tested. If positive, 
microscopy will be performed; 
• Virology (measured only at screening and may be measured at the local laboratory): hepatitis 
B surface antigen, hepatitis C antibodies, HIV 1 and 2 antibodies; virology tests done within 
6 weeks prior to screening are acceptable for eligibility assessment. Results from prior tests 
performed at the local laboratory must be recorded in the EDC system; 
• TB screen: only one of the following is needed: interferon γ release assay (IGRA), tuberculin 
purified protein derivative (PPD) skin test, or chest radiograms (X rays or CT scan); chest 
radiography done within 6 weeks prior to screening is allowed for eligibility assessment. 
7.2.3. 
Complement Panel 
The following panel will be measured in all patients based on recommendations from a 
consensus panel (Pickering et al., 2013): 
• Plasma C3a, C5a, C5b-9, and C5; 
• Serum C3 and C4; 
• Serum C3 nephritic factor; 
• Plasma complement factor H and factor B; 
• Serum factor H auto-antibody; 
• Serum paraprotein detection; 
• CFHR5 mutation 
Results from tests performed within 4 weeks prior to screening will be allowed for the study. For 
CFHR5 mutation, results from tests performed any time in the past will be allowed. If these tests 
have not been performed previously in a patient, samples need to be collected prior to Day 1 for 
measurement either at the local laboratory (if capabilities exist) or at the central laboratory. 
Results from these tests do not need to be available prior to start of dosing on Day 1, except for 
C5b-9 which is needed for eligibility assessment. Results from tests performed at the local 
laboratories need to be recorded in the EDC. 
7.2.4. 
Adverse Events 
An adverse event (AE) is defined as any untoward medical occurrence associated with the use of 
a drug in humans, whether or not considered drug related. An adverse event could therefore be 
any unfavorable and/or unintended sign (including abnormal laboratory findings), symptom, or 
disease temporally associated with the use of the drug, whether or not considered related to the 
drug. This definition includes intercurrent illnesses or injuries, and exacerbation of pre-existing 
conditions. 


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An unexpected adverse event is an adverse event that is not identified in nature, severity, or 
frequency in the current Investigator’s Brochure, or that is of greater severity than expected 
based on the information in the Reference Safety Information listing within the Investigator’s 
Brochure. 
All adverse events occurring in patients who have been randomized to treatment will be recorded 
in the EDC system and will be reported in accordance with regulatory requirements. Adverse 
events reported prior to commencement of administration of blinded study medication will be 
considered pre-treatment events and will also be captured. 
All adverse events will be monitored until resolution or, if the adverse event is determined to be 
chronic, until a cause is identified. If an adverse event remains unresolved at the conclusion of 
the study, a clinical assessment will be made by the Investigator and the Sponsor’s Medical 
Monitor to determine whether continued follow-up of the adverse event is warranted. 
7.2.4.1. 
Adverse Event Severity Assessment 
The severity of each adverse event will be determined by the Investigator using the following 
scale: 
• Mild (Grade 1): no limitation of usual activities 
• Moderate (Grade 2): some limitation of usual activities  
• Severe (Grade 3): inability to carry out usual activities 
• Life-threatening (Grade 4): an immediate risk of death 
• Death (Grade 5) 
It is not necessary to utilize Common Terminology Criteria for Adverse Events (CTCAE) 
grading for clinical events. However, in terms of lab values, the lab CTCAE criteria may be used 
for severity assessment. If there is a clinical AE that is related to a lab abnormality, the AE 
should be reported as the clinical event, where possible. 
7.2.4.2. 
Causality Assessment 
The relationship of avacopan/placebo to an adverse event will be determined by the Investigator 
and Sponsor based on the following definitions: 
• Probably Not Related: the adverse event was more likely explained by causes other than 
avacopan/placebo. 
• Possibly Related: there is evidence for a reasonable possibility that avacopan/placebo 
administration caused the adverse event. 
7.2.4.3. 
Serious Adverse Events 
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose: 
• Results in death; 
• Is life-threatening (i.e., the patient was, in the opinion of the Investigator, at immediate risk 
of death from the event as it occurred); 
• Requires or prolongs hospitalization; 


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• Results in persistent or significant disability or incapacity; 
• Is a congenital anomaly or birth defect; 
• Is an important and significant medical event that, based on appropriate medical judgment, 
may jeopardize the patient and/or may require medical or surgical intervention to prevent one 
of the other outcomes defining serious. 
Elective surgery already known during screening to occur in the course of the study, and elective 
hospitalizations for convenience of the patient which are clearly unrelated to any medical 
condition and agreed upon between the Investigator and the patient prior to randomization, will 
not have to be reported as SAEs. 
7.2.4.4. 
Infections 
For medically important infections, the organism(s) involved in the infection needs to be 
determined whenever possible. As a selective C5aR antagonist, avacopan does not appear to 
affect formation of the C5b-9 membrane attack complex, a defense mechanism against infection 
by encapsulated bacteria such as Neisseria meningitidis. Nevertheless, any such events need to 
be clearly documented in the EDC and all local and national vaccination recommendations 
should be followed. 
7.2.4.5. 
SARs and SUSARs 
A serious adverse reaction (SAR) is defined as an SAE for which there is at least a reasonable 
possibility that the study drug (avacopan or placebo) caused the event. 
A suspected unexpected serious adverse reaction (SUSAR) is defined as an SAE for which there 
is at least a reasonable possibility that the study drug caused the event, and the SAE is 
”unexpected”, i.e., not described in terms of nature, severity, or frequency in the Reference 
Safety Information within the current Investigator’s Brochure. 
“Reasonable possibility” means that there is evidence to suggest a causal relationship between 
the study drug and the adverse event. Within the reporting requirements, the following examples 
illustrate the types of evidence that would suggest a causal relationship: 
• A single occurrence of an event that is uncommon and known to be strongly associated 
with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson Syndrome); 
• One or more occurrences of an event that is not commonly associated with drug 
exposure, but is otherwise uncommon in the population exposed to the drug (e.g., tendon 
rupture); 
• An aggregate analysis of specific events observed in a clinical trial (such as known 
consequences of the underlying disease or condition under investigation or other events 
that commonly occur in the study population independent of drug therapy) that indicates 
those events occur more frequently in the drug treatment group than in a concurrent or 
historical control group. 
Events related to the underlying disease, such as relapses or worsening of disease will not be 
considered as SUSARs, unless there is a reasonable possibility that avacopan use was associated 
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7.2.4.6. 
Laboratory Abnormalities 
Safety laboratory tests are performed frequently over the course of the study. Laboratory reports 
with abnormal findings will be reviewed by the Investigator. The Medical Monitor will review 
notably abnormal laboratory results according to the Safety Monitoring Plan. 
Please see Section 4.4 for guidance on laboratory abnormalities (white blood cell count, 
neutrophil count, lymphocyte count, AST or ALT and other lab abnormalities of impaired liver 
function or hepatic toxicity, CPK increase, creatinine or proteinuria increases) that would prompt 
pausing or permanently discontinuing study drug (avacopan or placebo). 
7.2.4.7. 
Pregnancies 
If a patient becomes pregnant during the study or within the safety follow up period defined in 
the protocol, the investigator is to stop dosing with study drug(s) (avacopan or placebo) 
immediately and the patient should be withdrawn from the study. Early termination procedures 
should be implemented at that time. 
A pregnancy is not considered to be an AE or SAE; however, i must be reported to 
Clinical Safety within 24 hours of knowledge of the event.
Clinical Safety wil  then 
provide the investigator/site the Exposure In Utero (EIU) form for completion. The 
investigator/site must complete the EIU form and fax/email it back to 
Clinical Safety. 
If the female partner of a male patient becomes pregnant while the patient is receiving study drug 
or within the safety follow up period defined in the protocol, the investigator should notify 
Clinical Safety as described above. 
The pregnancy should be followed until the outcome of the pregnancy, whenever possible. Once 
the outcome of the pregnancy is known, the EIU form should be complete follow-up form and 
faxed/emailed to
Clinical Safety. If the outcome of the pregnancy meets the criteria for 
immediate classifica on as an SAE, (i.e. postpartum complication, spontaneous abortion, 
stillbirth, neonatal death, or congenital anomaly) the investigator should follow the procedures 
for reporting an SAE. 
7.2.5. 
Special Situation Reporting 
Special situation reports include reports of overdose, misuse and abuse of the IMP: 
• Overdose: Refers to the administration of a quantity of a medicinal product given per 
administration or cumulatively (accidentally or intentionally), which is above the 
maximum recommended dose according to the protocol. Clinical judgment should always 
be applied. In cases of a discrepancy in the drug accountability, overdose will be 
established only when it is clear that the patient has taken excess dose(s) or the 
Investigator has reason to suspect that the patient has taken additional dose(s). 
• Misuse: Refers to situations where the medicinal product is intentionally and 
inappropriately used in a way that is not in accordance with the protocol instructions or 
local prescribing information and may be accompanied by harmful physical and/or 
psychological effects. 


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• Abuse: Is defined as persistent or sporadic, intentional excessive use of a medicinal 
product which is accompanied by harmful physical or psychological effects. 
• Medication Error: Medication error is any unintentional error in the prescribing, 
dispensing or administration of a medicinal product by a healthcare professional, patient 
or consumer, respectively. The administration or consumption of the unassigned 
treatment and administration of an expired product are always reportable as medication 
errors, cases of patients missing doses of investigational product are not considered 
reportable as medication error. 
All spec al situation reports must be reported on the special situations report form and forwarded 
to 
Clinical Safety within 24 hours. 
All adverse events (AEs) associated with these special situation reports should be reported as 
AEs or SAEs at the same time using the AE eCRF and/or the SAE report form. Details of the 
symptoms and signs, clinical management and outcome will be reported, when available. 
7.2.6. 
Serious Adverse Event Reporting 
Any serious adverse event occurring from screening through the end of the follow-up period, 
whe her or not considered study related, will be reported immediately (within 24 hours) to the 
 Clinical Safety team. Patients who terminate early from the trial will have SAEs 
reco ded at follow-up visits or at least 30 days after last study drug (avacopan or placebo) 
administration. Reporting is done by completing the SAE form in the EDC system. If it is not 
possible to access the EDC system, the Investigator will send an email to the 
 clinical 
safety mailbox (see information below) or call their regional SAE hotline and fa
he completed 
SAE report form within 24 hours of awareness. When access to the EDC system is resumed, the 
SAE information should be entered as soon as possible. Contact details are as follows: 
SAE hotline – USA: 
Telephone:
Facsimile: 
e-mail: 
 
SAE hotline – Europe: 
Telephone: 
 
Fax: 
e-mail: 
 
Any medication or other therapeutic measures used to treat the event, in addition to the outcome 
of the adverse event, will be recorded in the EDC system. 
 


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Follow-Up Reports 
The Investigator must continue to follow the patient until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
patient dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation (e.g., 
patient discharge summary or autopsy reports) to
Clinical Safety via fax or e-mail. If it 
is not possible to access the EDC system, refer to th  pr cedures outlined above for initial 
reporting of SAEs. 
The Sponsor or its representatives will report all SUSARs to national health authorities and 
central ethics committees in an expedited manner in accordance with Clinical Trial Directive, 
Articles 16 and 17, ICH Guideline E2A and ENTR CT3 on the reporting of all SUSARs. 
Investigators will forward any safety communication as applicable to their local ethics 
committees. 
7.3. 
Pharmacokinetic Assessments 
Concentrations of avacopan (and its metabolite CCX168-M1) will be determined in plasma 
according to the schedule in the Time and Events Table, using a validated analytical method. The 
samples on Day 1 will be collected prior to the first dose of avacopan/placebo on that day. Only 
for patients 12 to 17 years of age, samples will also be taken at Hours 0.5, 1, 2, 3, 4, and 6 
following the first dose of avacopan/placebo on Day 1 and following the morning dose of 
avacopan on Day 183 (Week 26). The Day 183 morning dose for these adolescent patients 
should be taken in the clinic, not at home. The blood samples collected on the other study days 
will be single time point samples and do not need to be collected prior to the avacopan/placebo 
dose on those days. However, the date and time of the last dose of avacopan/placebo (or 
avacopan in the open-label portion of the study) prior to the sample collections must be recorded 
in the EDC system.  
On the day of the Week 52 visit, the patient should not take the dose, either at home or in the 
clinic. Two days before this visit, the patient should be reminded of such through a telephone 
call. The time of the last dose in the prior evening should be recorded. PK sampling from 
Week 52 onward (four samples total collected on Week 52, Week 54, Week 57, and on the 
follow-up visit, Week 60) is for terminal PK evaluation.  
Total plasma concentrations of avacopan (and its metabolite CCX168-M1) will be determined 
using validated analytical methods. Plasma samples collected for PK analysis may also be used 
to measure cytokines, complement fragments, or other markers associated with AAV. 
7.4. 
Pharmacodynamic Assessments 
Blood samples will be collected according to the schedule in the Time and Events Table for PD 
marker measurements in plasma and serum, which may include, for example, cystatin C, 
complement components, and inflammatory cytokine and chemokine levels. Blood samples 
collected will be used for lymphocyte subset counts including B cells, T cells, and natural killer 
cells. The complete blood cell (CBC) count results from the hematology samples will also be 


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included in the PD assessments. The PK plasma samples may also be used for PD marker 
measurements. 
Urine samples will be collected according to the schedule in the Time and Events Table for 
biomarker assessments including, for example, soluble CD163, complement fragments, and 
inflammatory cytokine and chemokine levels. 
7.5. 
Study Completion and Withdrawal 
The Week 60 visit will be the last Study Day for all patients. Procedures for this day will be 
completed per the Time and Events Table. Each patient’s condition will be evaluated by the 
Investigator at the end of the clinical trial and appropriate standard of care medical treatment will 
be provided to all patients as needed. For early withdrawals from the study, the procedures for 
the Early Termination visit will be performed, when possible (see Section 6.23). 
The clinical trial will be terminated early if there is a safety concern that cannot be addressed by 
a modification of the protocol. 
7.6. 
Data Monitoring Committee 
In addition to continuous safety monitoring by the Medical Monitor and clinical staff, an external 
Data Monitoring Committee (DMC) will monitor the safety of patients over the course of the 
study. The DMC will consist of external physicians and a biostatistician. At least one of the 
DMC members will be a pediatric nephrologist. A DMC charter will be developed before start of 
the study and the DMC will function according to the charter. 
It is anticipated that the DMC will have regular meetings, once every 3 to 6 months, depending 
on study enrollment rate. Ad hoc meetings may be scheduled if unanticipated safety events 
occur. After review of data at each meeting, the DMC will make recommendations about further 
conduct of the study. 
8. 
STATISTICAL METHODS 
Details of the statistical analysis will be provided in a separate statistical analysis plan (SAP), 
which will be written, finalized, and approved prior to database lock and will be included in the 
Clinical Study Report (CSR) for this protocol. The SAP will supersede the statistical analysis 
methods described in this clinical protocol. Any major deviations from the protocol will be 
documented and described in the final report. If changes to principal features stated in the 
protocol are required, these will be documented in a protocol amendment. The final SAP will 
take into account any amendment to the protocol. Data analysis and writing of a CSR for all 
study data will be performed by the designated CRO in accordance with its SOPs. Analysis of 
PK and PD data, and writing of PK and PD reports will be performed by designated PK and PD 
teams in accordance with their standard operating procedures. 


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8.1. 
Patient Populations 
8.1.1. 
Intent-to-Treat Population 
For the purposes of data analysis, the ITT Population will include all patients who have provided 
written Informed Consent/Assent and are randomized in the study. 
8.1.2. 
Per Protocol Population 
The Per Protocol (PP) population will consist of all randomized patients who receive at least one 
dose of study drug and do not have protocol deviations that could significantly affect the 
interpretation of the results for the primary endpoints. Patients’ inclusion/exclusion from the PP 
population will be determined and documented prior to the database lock and unblinding. 
8.1.3. 
Safety Population 
The safety population will include all patients who are randomized and have received at least one 
dose of study drug. 
8.2. 
Target Patient Population 
8.2.1. 
C5b-9 Elevated Stratum 
This population includes all patients enrolled under the C5b-9 elevated stratum, and is the 
primary target population for analysis. 
8.2.2. 
C5b-9 Non-Elevated Stratum 
This population includes all patients enrolled under the C5b-9 non-elevated stratum. This is the 
secondary target population for analysis. 
8.2.3. 
Exploratory Population 
The two strata combined will be considered the exploratory population. 
8.3. 
Efficacy Endpoints 
8.3.1. 
Primary Endpoint 
The primary efficacy endpoint is the percent change from baseline to Week 26 in the C3G 
Histologic Index for disease activity. 
8.3.2. 
Secondary and Other Endpoints 
Secondary efficacy endpoints include: 
1. The proportion of patients who have a histologic response, defined as a decrease 
(improvement) in the C3G Histologic Index for disease activity of at least 35% from 
baseline to Week 26 (see Section 8.8 for basis of selection of 35% threshold); 
2. The percent change from baseline in the C3G Histologic Index for disease chronicity 
over the placebo-controlled 26-week treatment period. 


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Other efficacy endpoints include: 
1. The change and percent change from baseline in eGFR over the placebo-controlled 
26-week treatment period; 
2. The percent change from baseline in UPCR over the placebo-controlled 26-week 
treatment period; 
3. The percent change from baseline in urinary MCP-1:creatinine ratio over the placebo-
controlled 26-week treatment period; 
4. Change from baseline in EQ-5D-5L (visual analogue scale and index) and SF-36 v2 
(domains and component scores) over the placebo-controlled 26-week treatment period. 
8.4. 
Safety Endpoints 
Safety endpoints include: 
1. Patient incidence of treatment-emergent serious adverse events, adverse events, and 
withdrawals due to adverse events; 
2. Change from baseline and shifts from baseline in all safety laboratory parameters; 
3. Change from baseline in vital signs. 
8.5. 
Pharmacokinetic Endpoints 
Avacopan (and its metabolite CCX168-M1) plasma concentration results for both C5b-9 level 
strata combined will be used to calculate trough plasma concentrations (Cmin) over the course of 
the clinical trial. When possible, the terminal elimination half-life will also be calculated. 
The Cmax, Tmax, and AUC0-6hr will be determined for patients 12 to 17 years old based on 
avacopan and metabolite plasma concentration data on Day 1 and on Day 183 (Week 26). 
8.6. 
Exploratory Pharmacodynamic Endpoints 
The following PD endpoints may be assessed: 
1. Change and percent change from baseline in plasma biomarkers such as inflammatory 
cytokine and chemokine levels; 
2. Change and percent change from baseline in urine biomarkers such as urinary 
sCD163:creatinine ratio, inflammatory cytokine and chemokine levels; 
3. Change from baseline in CBC count (especially WBCs, neutrophils, and lymphocytes) 
and lymphocyte subset counts including B cells, T cells, and natural killer cells; 
4. The relationship between PK parameters and renal function based on eGFR will be 
evaluated. The data may also be used to evaluate the PK/PD relationship of avacopan 
treatment for both C5b-9 level strata separately as well as combined. To this end, the 
change and/or percent change from baseline in the C3G Histologic Index, UPCR, eGFR, 
urinary MCP-1:creatinine ratio, and other biomarkers may be used as PD markers. 


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8.7. 
Statistical Analysis Methodology 
A statistical analysis plan (SAP).with specific details of all the planned analyses and sensitivity 
analyses will be generated and approved before unblinding the data for analysis. 
All statistical testing will be two-sided, with the Type I error rate at α = 0.05. 
The efficacy analyses for the efficacy endpoints will be performed in the ITT and PP 
populations, with the ITT analysis being the primary analysis. 
The earliest timepoint at which the primary analysis of the efficacy endpoints can be conducted 
is when all patients in the elevated stratum have completed at least the Week 26 study visit. 
Additionally, enrollment for the stratum with C5b-9 levels ≤244 ng/ml could terminate early, if 
patient enrollment in the other stratum (C5b-9 level >244 ng/mL) reaches target enrollment first. 
Further, both strata can be analyzed separately and independently. The stratum with elevated 
levels (primary population) will be analyzed first should the stratum with C5b-9 ≤244ng/ml 
(secondary population) continue a blinded follow up – further details will be provided in the 
SAP. 
For efficacy analysis, to control for the Type I error rate, a gate-keeping procedure will be 
applied for the analysis of the primary efficacy endpoint (percent change in C3G Histologic 
Index for disease activity). The primary endpoint will be tested in the elevated C5b-9 stratum 
first with a two-sided α = 0.05. If this test reaches statistical significance, then the primary 
endpoint will be tested in the non-elevated C5b-9 stratum with a two-sided α = 0.05. If the test in 
the elevated stratum fails to reach statistical significance, then the test in the non-elevated C5b-9 
stratum will not be performed and only performed as an exploratory analysis. The statistical 
analysis for the secondary endpoint (C3G Histologic Index for disease chronicity) will be tested 
at a 0.05 α-level only if the primary endpoint in the same stratum reaches statistical significance.  
Another analysis will be performed when all patients have completed the study after week 60. 
Individual patient group assignment will remain blinded to investigators and patients until after 
the analysis of the data from the second analysis in order to maintain study integrity. 
Baseline is defined as the last value prior to start of dosing with study medication (typically the 
Day 1 pre-dose value). 
8.7.1. 
Patient Disposition 
The number of patients who were screened, who screen failed (by reason), who were 
randomized, who completed Week 26, Week 52, and Week 60 of the study, who withdrew early 
from the study, along with the reasons for withdrawal, will be presented by treatment group. 
8.7.2. 
Demographics and Baseline Characteristics 
All patient baseline characteristics and demographic data (age, sex, race, ethnicity, weight, 
height, body mass index, viral test results, C3G disease type and duration [from time of first 
diagnosis based on renal biopsy], eGFR, proteinuria [UPCR], complement marker levels, urinary 
MCP-1:creatinine ratio, physical examination abnormalities, medical history, previous [within 6 
months of screening] and concomitant medications [including other treatments for C3G] at study 
entry) will be listed by study center and patient number, and will also be summarized. 


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8.7.3. 
Prior and Concomitant Medications 
All medications will be coded using the World Health Organization Drug Dictionary (WHODD). 
All prior (within 12 months of screening for C3G medications, and within 6 months of screening 
for all other medications) and concomitant medications (including C3G medication) will be 
listed and summarized by WHODD Anatomic Therapeutic Chemistry (ATC) classification and 
preferred term. 
8.7.4. 
Study Drug Exposure and Compliance 
Patient drug exposure will be calculated comparing the study drug dispensing and return records, 
as well as avacopan plasma concentrations over the course of the study. The study drug exposure 
(duration, total dose, and average daily dose) and compliance will be summarized for the double-
blind and active treatment periods separately. Individual patient data listing will also be 
provided. 
8.7.5. 
Efficacy Analyses 
Summary statistics will be calculated for each of the efficacy endpoints. For categorical 
endpoints, numbers and percentages, and 95% confidence intervals will be calculated. For 
continuous variables, numbers, means, medians, minimum, maximum, standard deviations, and 
standard error of means, and 95% confidence intervals will be calculated. Geometric means will 
be calculated for UPCR and urinary MCP-1:creatinine, and other data that are not normally 
distributed.  
Results will be presented by treatment group. Results will be presented by stratum for C3GN vs. 
DDD and renal transplant vs. no renal transplant. Data will also be presented by geographic 
distribution (North America vs. Rest of World), sex, age group (including a separate analysis in 
12-17 year old patients), race, and ethnicity for at least the primary endpoint. 
The overall efficacy hypothesis in this study is that avacopan treatment will be effective in 
treatment of patients with C3G based on improvement in renal histology (C3G histologic index 
of activity).  
The primary efficacy endpoint is the percent change from baseline to Week 26 in the C3G 
Histologic Index for disease activity. 
• The null hypothesis (H0) is that the avacopan group is not different from the placebo group 
when comparing the percent change from baseline to Week 26 in the C3G Histologic Index 
for disease activity. 
• The alternative hypothesis (H1) is that the avacopan group is superior to the placebo group 
when comparing the percent change from baseline to Week 26 in the C3G Histologic Index 
for disease activity. 
Avacopan and placebo groups will be compared by ANCOVA with treatment group as factor 
and baseline C3G Histologic Index for disease activity as covariate. A point estimate and 
corresponding 95% confidence interval will be estimated for the treatment main effect. The 
heterogeneity of the treatment effect across disease diagnoses and renal transplant strata will be 
investigated through subgroup analyses. If data are not normally distributed, in addition to the 
ANCOVA for the percent change in C3G Histologic Index for disease activity and chronicity, 


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the Cochran-Mantel-Haenszel (CMH) test will be applied to the percent change results and 
ANCOVA will be applied to the change in C3G Histologic Index disease activity and chronicity 
scores. 
The treatment effect based on the baseline complement profile of patients will also be 
investigated. 
Data from patients who are treatment failures, i.e., requiring treatment rescue measures such as 
high dose glucocorticoids during the treatment period, will be excluded from efficacy analysis 
after the point of rescue treatment. 
Since the placebo group will receive avacopan during the second 26 weeks of the study, the 
change from Week 26 to Week 52 in the C3G Histologic Index for activity in the placebo control 
group will be compared to the change from baseline to Week 26 in this group. This analysis will 
be done by the paired t-test. Point estimates and corresponding 95% confidence intervals will be 
estimated for the difference between the second 26 weeks (avacopan treatment) and the first 26 
weeks (placebo treatment). 
The change from baseline to Week 52 in the C3G Histologic Index in the avacopan group will 
also be compared to the change from baseline to Week 26 in placebo control group using similar 
methodology as described for the primary efficacy endpoint. 
Continuous variables, including eGFR, UPCR, urinary MCP-1:creatinine ratio, EQ-5D-5L, and 
SF-36 v2 will be analyzed using a mixed effects model for repeated measures (MMRM) with 
treatment group, visit, and treatment-by-visit interaction as factors, and baseline as covariate. 
Patients will be considered as repeated measure units over visits. The interaction term may be 
dropped if it is not significant at α = 0.25 level. Point estimates and corresponding 95% 
confidence intervals will be estimated for the difference between the avacopan group and the 
control group at Week 26 using simple contrast from the model. 
Similar to the primary endpoint, the second 26 weeks will be compared to the first 26 weeks for 
the placebo group. Changes in the efficacy parameters across 52 weeks will also be assessed. 
Change and percent change in the efficacy parameters during the 8-week follow-up period will 
also be assessed to determine the off-treatment effect. 
Change from baseline in individual components of the C3G Histologic Index activity and 
chronicity indices as well as glomerular leukocytes and leukocyte subsets based on 
immunohistochemistry will be summarized and, where appropriate, analyzed using similar 
methodologies as describe above. 
The secondary endpoint of the proportion of patients who have a histologic response will be 
analyzed by the CMH chi-square test. Data from patients who are treatment failures, i.e., require 
rescue medication, will be summarized. 
The primary efficacy analysis will be based on the intent-to-treat (ITT) population, defined as all 
patients who are randomized. 
8.7.6. 
Handling of Missing Data 
If data are missing after all efforts made to collect post-baseline C3G Histologic Index data, 
missing data will be imputed using the last observation carried forward (LOCF) method. This 


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method may impute Week 26 missing data with the baseline value if there are no unscheduled 
data from visits prior to the missing time point. Multiple-imputation using Markov Chain Monte 
Carlo (MCMC) or other statistical method may also be performed. 
8.7.7. 
Covariates and Subgroups 
The analysis of the efficacy endpoints may be adjusted by the following variables in the form of 
covariate analysis, stratified analysis, and/or subgroup analysis: 
• Randomization stratification variables, i.e. C3GN or DDD and Having received a renal 
transplant or not 
• Sex 
• BMI 
• Age at diagnosis of C3G 
• Age at study entry; a subgroup analysis will be performed in 12 to 17 year-old patients, if 
feasible. 
• Duration of C3G 
• Patient’s age, race, and ethnicity (if plausible) 
• Baseline C3G Histologic Index for disease activity 
• Baseline C3G Histologic Index for disease chronicity 
• Baseline eGFR 
• Baseline UPCR 
• Baseline urinary MCP-1:creatinine ratio 
• Baseline C5b-9, C5a, and C3a 
• Geographic distribution (North America vs. Rest of World) 
8.7.8. 
Safety Analyses 
All clinical safety and tolerability data will be listed by treatment group and by patients and will 
be summarized by treatment group. 
All reported adverse events will be coded using MedDRA and listed by System Organ Class, 
preferred term, and verbatim term. 
Treatment-emergent adverse events will be listed and summarized by System Organ Class and 
Preferred Term, by relatedness, by maximum severity and by treatment group. 
Serious adverse events and adverse events leading to study withdrawal will be summarized by 
treatment group. This will include serious infections. 
Individual vital signs and change from baseline in vital signs will be listed by treatment group, 
patient, and study visit, and summarized by treatment group. 


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Laboratory data (actual values and change from baseline) will be listed by treatment group, 
patient and study visit. Abnormal laboratory values will be flagged. Laboratory data will also be 
summarized by treatment group and study visit. Shift tables will be generated for shifts in 
laboratory parameters by study visit. 
8.7.9. 
Pharmacokinetic and Exploratory Pharmacodynamic Marker Analysis 
Individual plasma concentrations of avacopan and its significant metabolite CCX168-M1 will be 
listed, plotted, and summarized descriptively and graphically. When possible, the mean steady 
state trough concentrations and the terminal elimination half-life will be calculated. PK 
parameters such as Cmax, Tmax, and AUC0-6hr will be calculated in adolescents for avacopan and 
metabolite CCX168-M1 based on plasma concentrations for samples collected on Day 1 and on 
Day 183. 
Plasma and urinary PD markers will be summarized and may be analyzed using methods 
analogous to the efficacy parameters. 
The relationship between PK parameters and renal function based on eGFR will also be 
evaluated. The data may also be used to evaluate the PK/PD relationship of avacopan treatment. 
To this end, the change and/or percent change from baseline in C3G Histologic Index for disease 
activity, C3G Histologic Index for disease chronicity, eGFR, UPCR, urinary MCP-1:creatinine 
ratio, or other biomarkers may be used as PD markers. 
8.8. 
Sample Size Justification 
A sample size of 22 patients per treatment group (avacopan and placebo, respectively) in each of 
the C5b-9 level strata is based on the between-treatment difference of -35% in the C3G 
Histologic Index for activity at Week 26, standard deviation (SD) 34%, power 90%, and 2-sided 
α = 0.05. 
The sample size of 22 per group also provides approximately 90% power to detect a delta 
of -35% in the C3G Histologic Index for activity between the percent change from baseline in 
the first 26 weeks and in the second 26 weeks, assuming an SD of 34% for each change. 
The mean treatment effect size of 35% is considered reasonable based of the following: 
• Of the 5 patients with histologic data in the study by Herlitz et al., 2012 with eculizumab, an 
anti-C5 antibody, 2 patients had a 67% decrease (improvement) in histologic score, 1 had a 
43% decrease, and 2 had no change from baseline; the mean decrease for the 5 patients was 
35%; 
• An improvement in the histologic score of at least 35% is considered clinically meaningful 
by clinical and histology experts; 
• The SD for the percent change from baseline in C3G Histologic Index of activity was 34% in 
the Herlitz study; a change of 35% of greater will be above the observed variance for this 
parameter. 


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8.9. 
Interim Analysis 
Safety data from the study will be summarized for review by the DMC at various points over the 
course of the study (see Section 7.6). The DMC charter will include details of these reviews. 
No Type I error adjustment will be made based on the DMC review of the data, since these 
reviews will focus on safety assessment. 
The earliest timepoint at which the primary analysis can be performed is when all patients in the 
primary population have completed at least the Week 26 visit. Another analysis will be 
performed when all patients have completed the full study. No Type I error adjustment will be 
made for the second analysis since the endpoints for the second analysis are different from the 
first analysis. 
8.10. 
Protocol Deviations 
Significant protocol deviations will be listed and summarized by deviation category. The effect 
of significant protocol deviations on the safety and efficacy outcomes will be assessed by 
conducting sensitivity analyses excluding patients and/or study visits with significant protocol 
deviations. This will be determined and documented before unblinding the study. 
The Sponsor will assess any protocol deviation and decide whether any of these should be 
reported to Competent Authorities (CAs) as a serious breach of GCP and the protocol. Protocol 
waivers are not acceptable. 
9. 
STUDY COMPLETION AND TERMINATION 
9.1. 
Study Completion 
A patient has completed the study when s/he has completed the study procedures per protocol. 
9.2. 
Study Termination 
The end of study is defined as the last study visit of the last clinical trial patient. 
The study will be terminated early if there is an insurmountable safety concern. This will be 
determined in conjunction with the DMC. In this case, the Investigators, CAs, and IRB/EC will 
be notified expeditiously and appropriate measures taken to safeguard the study patients. 
10. 
REGULATORY AND ADMINISTRATIVE REQUIREMENTS 
10.1. 
Investigator Responsibilities 
Prior to trial initiation, the Investigator will provide the Sponsor with a fully executed and signed 
FDA Form 1572, a Financial Disclosure Form, and a curriculum vitae. Financial Disclosure 
Forms also will be completed for all Sub-Investigators listed on the Form 1572 who will be 
involved directly in the treatment or evaluation of research patients in this trial. 


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The study will be conducted in accordance with the Declaration of Helsinki (amended by the 
59th World Medical Association General Assembly, October 2008) and Good Clinical Practices 
(GCP) according to International Conference on Harmonisation (ICH) guidelines. Specifically, 
the study is based on adequately performed laboratory and animal experimentation; the study 
will be conducted under a protocol reviewed by a properly constituted IRB/EC; the study will be 
conducted by scientifically and medically qualified persons; the benefits of the study are in 
proportion to the risks; the rights and welfare of the patients will be respected; and each patient 
or his/her legal guardian will give his/her written Informed Consent/Assent before any protocol-
specific tests or evaluations are performed. 
10.2. 
Institutional Review Board or Ethics Committee 
Prior to initiating the study, the Investigator will obtain written confirmation from the IRB/EC 
that the IRB/EC was properly constituted and met the definition of all United States Code of 
Federal Regulations Title 21, Section 312.3(b) and Part 56, and/or the applicable local, regional 
or national Regulatory requirements. A copy of the confirmation will be provided to the Sponsor. 
The Principal Investigator will provide the IRB/EC with all appropriate materials, including the 
protocol and Informed Consent/Assent documents. The trial will not be initiated until IRB/EC 
approval of the protocol, the Informed Consent/Assent document, and all recruiting materials are 
obtained in writing by the Investigator and copies are received by the Sponsor. Appropriate 
reports on the progress of the study will be made to the IRB/EC and the Sponsor by the Principal 
Investigator in accordance with applicable governmental regulations and in agreement with the 
policy established by the Sponsor. 
10.3. 
Informed Consent/Assent 
A properly executed, written, and appropriately explained Informed Consent Form, or Assent 
Form (where relevant), in compliance with the Declaration of Helsinki, ICH GCP, and US Code 
of Federal Regulations for Protection of Human Patients (21 CFR 50.25[a,b], CFR 50.27, and 
CFR Part 46, Subpart A), will be signed by each patient or his/her legal guardian prior to 
entering the trial. Either the Investigator or the Investigator’s designee will obtain the consent of 
the study patient. The patient will be provided as much time as necessary to review the 
document, to inquire about details of the trial, and to decide whether or not to participate in the 
study. The Informed Consent/Assent will be signed and dated by the study patient/legal guardian 
and by the person who conducted the Informed Consent discussion. The Investigator will provide 
a copy of the signed Informed Consent/Assent Form to each patient and will maintain the 
original in the patient’s record file. 
10.4. 
Protocol Modifications 
Only the Sponsor may modify the protocol. The only exception is when the Investigator 
considers that a patient’s safety would be compromised without immediate action. In this 
circumstance, immediate approval of the chairperson of the IRB/EC must be sought, and the 
Investigator should inform the Sponsor’s Medical Monitor and the full IRB/EC within five 
working days after the emergency occurred. 
All other amendments that have an impact on patient risk or the study objectives, and/or that 
require revision of the Informed Consent/Assent Form, must receive approval from the IRB/EC 


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prior to their implementation, except when the changes involve only logistical or administrative 
aspects of the trial. The IRB/EC must be notified of changes that are made to study contact 
personnel, but IRB/EC review or approval of these changes is not required. If protocol 
amendments are substantial and are likely to have an impact on the safety of the trial patients or 
to change the interpretation of the scientific documents in support of the conduct of the trial, or if 
they are otherwise significant, the sponsor shall notify the FDA and other CAs concerned of the 
reasons for, and content of, these amendments according to the European Directive “Detailed 
guidance on the request to the CAs for authorization of a clinical trial on a medical products for 
human use, the notification of substantial amendments and the declaration of the end of trial 
(CT-1)(2010/C 82/01)” and other regulatory guidance. In case of a substantial amendment to the 
protocol, approval will be sought from CAs before implementation. 
10.5. 
Regulatory Aspects 
Before the study is conducted, the protocol will be submitted to the country-specific 
CA/regulatory agency for review and approval. The study will not commence until written 
approval has been obtained from the CA. 
All regulatory documentation including regulatory submissions, 1572 forms, and correspondence 
regarding this study will be kept by the Sponsor. The CRO that will conduct the study on behalf 
of the Sponsor will maintain all study documentation according to their SOPs. Clinical trial 
related documents will be archived for the longest of: 
1. 10 years according to national Swedish and EU regulations (LVFS 2003:3), or  
2. For 2 years following the date a full marketing application is approved, or  
3. For 2 years after the FDA is notified that the IND is discontinued if there is no marketing 
application. 
10.6. 
Patient Identification Register 
The Investigator agrees to complete a patient identification register, which will be used for the 
purpose of long term follow-up, if needed. This form will be treated as confidential, and will be 
filed by the Investigator in a secure locked place. Otherwise, all reports and communications 
relating to the study will identify participants by initials and/or assigned number only. 
10.7. 
Record Retention 
The Investigator must retain all study records required by the Sponsor and by the applicable 
regulations in a secure and safe facility. The Investigator must consult a Sponsor CRA before 
disposal of any study records, and must notify the Sponsor of any change in the location, 
disposition, or custody of the study files. Clinical trial related documents will be archived for the 
longest of: 
1. 10 years according to national Swedish and EU regulations (LVFS 2003:3), or 
2. For 2 years following the date a full marketing application is approved, or 
3. For 2 years after the FDA is notified that the IND is discontinued if there is no marketing 
application. 


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10.8. 
Case Report Form Completion 
Electronic Case Report Forms (CRFs) will be generated for each patient. The electronic data 
capture (EDC) system will comply with CFR 21 Part 11. 
Participants will not be identified in the EDC by name or initials and birth date. Only the 
Investigator or his/her designated representative will enter data into the EDC. It is the policy of 
the Sponsor that study data must be verifiable to the source data, which necessitates access to all 
original recordings, laboratory reports, and patients’ records. The Investigator must therefore 
agree to allow access to patients’ records, and source data must be made available for all study 
data. Each patient (or their legal representative) must also allow access to their medical records; 
they will be informed of this requirement and will indicate their agreement when giving 
Informed Consent/Assent. Upon completion of the study, electronic copies of the CRFs will be 
provided to the Investigators and should be included as part of his/her study files and retained as 
per FDA or local regulations. 
10.9. 
Monitoring 
At intervals during the study, as well as after the completion of patient enrollment at the study 
center, the study center will be monitored by a CRA for compliance, which will include ensuring 
that accurate and complete data are promptly recorded in EDC, and reviewing source 
documentation and drug accountability records. The study will be conducted according to the 
principles of GCP as accepted in the United States and according to CPMP/ICH/135/95. 
10.10. 
On-site Visits and Audits 
The Sponsor’s representatives will visit the study center prior to initiation of the study to review 
with the center personnel information regarding the investigational agent, protocol requirements, 
monitoring requirements, and reporting of serious adverse events. 
In certain circumstances, a secondary audit may be conducted by members of a Quality 
Assurance group designated by the Sponsor. The Investigator will be informed if this is to take 
place and advised as to the nature of the audit. Representatives of the Food and Drug 
Administration (FDA) and/or representatives of other regulatory authorities may also conduct an 
audit of the study. If informed of such an audit, the Investigator should notify the Sponsor 
immediately. 
10.11. 
Study Registration, Use of Information and Publication 
The study will be registered in clinicaltrials.gov and other country-specific registries, as required, 
prior to initiation. 
It is understood by the Investigator that the information generated in this study will be used by 
the Sponsor in connection with the development of the product and therefore may be disclosed to 
government agencies in various countries. To allow for the use of information derived from the 
study, it is understood that the Investigator is obliged to provide the Sponsor with complete test 
results, all study data, and access to all study records. 
The Sponsor recognizes the importance of communicating study data and will disclose or publish 
the results in a suitable form regardless of outcome. The Sponsor will post the clinical trial 


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information on appropriate registries, e.g., clinicaltrials.gov prior to enrollment of the first 
patients, and publish the results of this study in scientific journals, at seminars or conferences, 
and/or in other manner(s) it so chooses. Results from this study shall not be made available to 
any third party by the investigating team without the express permission of the Sponsor. 


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11. 
REFERENCES 
1. Bekker P, et al. Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a 
Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on 
Preclinical Evaluation and Randomized Phase 1 Clinical Study. PLoS One. 2016; 11(10): 
e0164646.  
2. Bomback AS, et al. Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin J Am 
Soc Nephrol. 2012; 7(5):748–756.  
3. Bomback AS, et al. C3 glomerulonephritis and dense deposit disease share a similar disease 
course in a large United States cohort of patients with C3 glomerulopathy. Kidney Int. 2018.  
4. Food and Drug Administration (FDA), July 2009 Guidance for Industry.  Drug-induced liver 
injury: premarketing clinical evaluation.   
5. Herlitz LC, et al. Pathology after eculizumab in Dense Deposit Disease and C3 GN. J Am Soc 
Nephrol. 2012; 23(7):1229–1237.  
6. Hou J, et al. Toward a working definition of C3 glomerulopathy by immunofluorescence. Kidney 
Int. 2014; 85(2):450–456.  
7. Jayne DRW, et al. Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated 
Vasculitis. J Am Soc Nephrol. 2017; 28(9):2756–2767.  
8. Johnson TN, et al. Prediction of the clearance of eleven drugs and associated variability in 
neonates, infants and children. Clin Pharmacokinet. 2006; 45(9):931–956. 
9. Levey AS, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 
150(9):604–612. 
10. Momper JD, et al. Adolescent dosing and labeling since the Food and Drug Administration 
Amendments Act of 2007. JAMA Pediatr. 2013; 167(10):926–932.  
11. Pickering MC, et al. Uncontrolled C3 activation causes membranoproliferative 
glomerulonephritis in mice deficient in complement factor H. Nat Genet. 2002; 31(4):424–428. 
12. Pickering MC, et al. Prevention of C5 activation ameliorates spontaneous and experimental 
glomerulonephritis in factor H-deficient mice. Proc Natl Acad Sci USA. 2006; 103(25):9649–
9654. 
13. Pickering MC, et al. C3 glomerulopathy: consensus report. Kidney Int. 2013; 84(6):1079–1089.  
14. Schwartz GJ, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 
2009; 20(3):629–637.  
15. Selistre L, et al. Comparison of the Schwartz and CKD-EPI Equations for Estimating Glomerular 
Filtration Rate in Children, Adolescents, and Adults: A Retrospective Cross-Sectional Study 
PLoS Med. 2016; 13(3): e1001979.  
16. Sethi S, et al. Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic 
Classification, Diagnosis, and Reporting of GN. J Am Soc Nephrol. 2016; 27(5):1278–1287. 
17. Xiao H, et al. C5a receptor (CD88) blockade protects against MPO-ANCA GN. J Am Soc 
Nephrol. 2014; 25(2):225–231.   


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12. 
APPENDICES 
12.1. 
Statement of Obligations of Sponsor, Monitor, and Clinical 
Investigator 
Sponsor and Monitor 
If the Sponsor is not familiar with the study site, the Sponsor or its designated representative, 
will: 
A. Conduct a pre-study visit to: 
1. Establish the acceptability of the facility, the recruitment potential and the standard of patient 
care at this site, and record this in a written report. 
2. Discuss the proposed clinical trial with the Investigator, review the CRF requirements, and 
supply the Investigator’s Brochure and the draft protocol for review and approval. 
3. Discuss with the Investigator FDA and other regulatory requirements with respect to 
Informed Consent/Assent, CA and IRB/EC approval of the trial, the protocol, protocol 
amendments, and Informed Consent/Assent changes. 
B. Conduct periodic site visits to: 
1. Assure adherence to the protocol. 
2. Review CRFs and medical records for accuracy and completeness of information. 
3. Examine pharmacy records for documentation of quantity and date of receipt of 
investigational supplies, dispensation and accountability data for administration to each 
patient, loss of materials, contamination, and unused supplies. 
4. Record and report observations on the progress of the trial and continued acceptability of the 
facilities in a Site Visit Report. 
5. Review Investigator files for required documents, e.g., protocols, protocol amendments, CA 
and EC approvals (protocols, amendments, Informed Consent/Assent, etc.), EC charter and 
membership, and communications between the EC and the Investigator.  
Clinical Investigator 
A. EC 
The Investigator must assure the monitor that the EC: 
1. Meets FDA regulations as defined in 21 CFR Part 56 and other applicable ICH and GCP 
requirements. 
2. Has authority delegated by the parent institution and found in EC by-laws, operation 
guidelines, or charter to approve or disapprove clinical trials and protocols, including 
Informed Consent/Assent Forms and other documents (protocol amendments, information to 
be supplied to patients concerning Informed Consent/Assent, etc.). 


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3. Complies with proper personnel makeup of an EC and maintains an active up-to-date roster 
of all EC members participating in the meetings. 
4. Convenes meetings using acceptable rules of order for making decisions, recording such 
decisions, and implementing them. 
5. Files contain (a) documentation of its decisions such as are found in EC minutes and 
correspondence, (b) written guidelines or by-laws governing EC functions, (c) protocols, 
(d) protocol information to be supplied to the patient, (e) correspondence between the EC and 
the Investigator (Informed Consent/Assent Form changes, protocol amendments, etc.). 
B. Informed Consent/Assent of Human Patients 
The Principal Investigator must assure the monitor that the Informed Consent/Assent Form: 
1. Meets FDA regulations as defined in 21 CFR Part 50 Informed Consent, and other applicable 
ICH and GCP requirements. 
2. Has been approved by the EC, including, when required, information to be given to the 
patient regarding the trial in which s/he is enrolled. 
a. The Informed Consent/Assent Form includes the Basic Elements and any Additional 
Elements necessary. 
b. The patient and a study center representative sign the Informed Consent/Assent Form and 
the patient is given a copy. 
C. Storage and Dispensing of Study Supplies 
The Investigator (or pharmacist or pharmacy technician) must demonstrate to the Monitor that: 
1. Adequate and accurate written records show receipt and disposition of all study supplies, 
including dates, serial or lot numbers, quantities received, and each quantity dispensed, 
administered, or used, with identification of each patient. 
2. Purpose and reasons are given in written records for study material disposal, e.g., the amount 
contaminated, broken, or lost, and the quantity returned to the Sponsor. 
D. Case Report Forms 
The Investigator must assure the Monitor that: 
1. Case report forms, when complete, accurately reflect the medical records on each patient. 
2. Case report forms and medical records will be accessible to the Monitor or FDA and other 
regulatory inspectors during site visits. 
E. Files and Records 
The Investigator must assure the quality, integrity, and content of his or her files that will be 
inspected by the Monitor and regulatory inspectors. The files must contain, at a minimum: 
1. Correspondence between the EC and the Investigator. 


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2. The following documents: 
a. EC-approved protocols. 
b. EC-approved protocol amendments. 
c. EC-approved Informed Consent/Assent Form and information supplied to the patient. 
d. EC charter, membership, and qualifications. 
3. Clinical supplies: 
a. Record of receipt, date and quantity, and batch or lot number. 
b. Disposition dates and quantity administered to each patient. 
c. Inventory records. 
Clinical trial related documents will be archived for the longest of: 
1. 10 years according to national Swedish and EU regulations (LVFS 2003:3), or 
2. For 2 years following the date a full marketing application is approved, or 
3. For 2 years after the FDA is notified that the IND is discontinued if there is no marketing 
application. 
12.2. 
Informed Consent/Assent Form 
In seeking Informed Consent/Assent, the following information shall be provided to each 
patient/legal guardian, where relevant: 
A statement that the study involves research, an explanation of the purposes of the research and 
the expected duration of the patient's participation, a description of the procedures to be 
followed, and identification of any procedures which are experimental. 
A description of any reasonably foreseeable risks or discomforts to the patient. 
A description of any benefits to the patient or to others that may reasonably be expected from the 
research. 
A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be 
advantageous to the patient. 
A statement describing the extent, if any, to which confidentiality of records identifying the 
patient will be maintained and that notes the possibility that the Food and Drug Administration 
or other regulatory agency may inspect the records. 
For research involving more than minimal risk, an explanation as to whether any compensation 
and as to whether any medical treatments are available if injury occurs and, if so, what they 
consist of, or where further information may be obtained. 
An explanation of who to contact for answers to pertinent questions about the research and 
research patients' rights, and who to contact in the event of a research related injury to the 
patient. 
A statement that participation is voluntary, that refusal to participate will involve no penalty or 
loss of benefits to which the patient is otherwise entitled, and that the patient may discontinue 
participation at any time without penalty or loss of benefits to which the patient is otherwise 
entitled. 


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12.2.1. 
ADDITIONAL ELEMENTS OF INFORMED CONSENT 
1. A statement that the particular treatment or procedure may involve risks to the patient (or to 
the embryo or fetus if the patient is or may become pregnant) which are currently 
unforeseeable. 
2. Anticipated circumstances under which the patient’s participation may be terminated by the 
Investigator without regard to the patient’s consent. 
3. Any additional costs to the patient that may result from participation in the research. 
4. The consequences of a patient’s decision to withdraw from the research and procedures for 
orderly termination of participation by the patient. 
5. A statement that significant new findings developed during the course of the research which 
may relate to the patient’s willingness to continue participation will be provided to the 
patient. 
6. The approximate number of patients involved in the study. 
12.3. 
Benefit-Risk Assessment 
12.3.1. 
Nonclinical Evaluation 
Single dose and repeat dose toxicology, safety pharmacology, and genotoxicity studies have been 
conducted with avacopan. General toxicity studies of up to 26-week duration in rats and 44-week 
duration in cynomolgus monkeys have been conducted at avacopan doses up to 200 and 
45 mg/kg/day, respectively, significantly higher than the highest human daily dose of 30 mg 
twice daily (BID) being tested in patients with C3G and other indications. 
Based on in vivo safety pharmacology studies, which included neuropharmacology, pulmonary, 
and renal safety studies in rats, and a cardiovascular safety study in conscious telemetered 
cynomolgus monkeys, there was no evidence of toxicity of avacopan. No evidence of 
electrocardiographic alterations was seen in the monkey 4-week, 20-week, or 44-week studies or 
in in vitro cardiovascular safety studies (IC50 values for hERG inhibition was determined to be 
>2.3 µM for avacopan and >3.0 µM for its metabolite avacopan-M1, the limit of solubility for 
both compounds). A safety margin for avacopan and its metabolite CCX168-M1 of at least 
3,500-fold relative to expected steady state human unbound maximum plasma is projected. 
Protein binding, red blood cell partitioning, hepatocyte metabolism, cytochrome P450 inhibition 
and induction, Caco-2 permeability and genotoxicity studies, including in vitro bacterial 
mutagenicity (Ames test) and in vitro mammalian cell mutagenicity (mouse lymphoma) studies, 
in vivo bone marrow rat micronucleus and in silico mutagenicity evaluation of starting materials, 
intermediates and chemical impurities utilized and formed during the synthesis of avacopan were 
also conducted; none of these studies identified any safety concerns or significant potential for 
drug-drug interactions. In an acute toxicology study, single doses of avacopan up to 100 mg/kg 
in rats produced no remarkable effects. No effects on IgG and IgM antibody production in rats or 
monkeys were noted following immunization with keyhole limpet hemocyanin antigen. 
Immunophenotypic analyses performed in the 44-week monkey study did not reveal any 
avacopan-related effects. No phototoxicity potential was observed for avacopan in the in vitro 
3T3 assay. 


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Avacopan was well tolerated in studies up to 26 and 44 weeks in rats and cynomolgus monkeys, 
respectively, up to the highest doses tested (200 mg/kg/day in rats and 45 mg/kg/day in 
cynomolgus monkeys). These doses provide an exposure margin of ~19-fold and ~6-fold, 
respectively, compared to the avacopan 30 mg twice daily therapeutic dose in humans. There 
were no significant toxicological findings of concern in these chronic studies or the preceding 
sub-chronic studies. Metabolite CCX168-M1 (which has been identified in humans) was present 
in samples collected in the rat 13- and 26-week and the monkey 20- and 44-week studies at 
relatively high levels indicating that this metabolite has been qualified. 
No avacopan-related effects were observed upon pregnancy or embryo-fetal development in 
studies at doses up to 1000 mg/kg and 200 mg/kg in hamsters and rabbits, respectively. No 
evidence of histopathological alterations to the male or female reproductive system was seen in 
rats or monkeys in toxicology studies. 
In summary, no safety findings in toxicology studies in rats, cynomolgus monkeys, rabbits and 
hamsters have been observed that would preclude dosing to humans at the 30 mg twice daily 
dose in this clinical trial. 
12.3.2. 
Clinical Evaluation 
Five Phase 1 studies and four Phase 2 studies with avacopan have previously been completed. A 
Phase 3 study in patients with AAV previously completed enrollment but follow up is ongoing 
and the study remains blinded. A total of 182 healthy volunteers participated in the five Phase 1 
studies; 153 of these patients received avacopan at doses ranging from 1 mg up to 100 mg 
(CL001_168, CL004_168, CL007_168, CL008_168, and Japanese Phase 1 study CCX1101). 
Avacopan was generally well tolerated in these studies. 
The most frequently reported adverse events in patients receiving avacopan in Phase 1 clinical 
studies were headache (14.6% vs. 14.3% for placebo), diarrhea (6.7% vs. 7.1% for placebo), 
dizziness (4.5% vs. 0% for placebo), upper respiratory tract infection (4.5% vs. 0% for placebo), 
nausea (3.4% vs. 0% for placebo), oropharyngeal pain (3.4% vs. 7.1% for placebo), and 
decreased WBC count (3.4% vs. 0% for placebo). All other adverse events occurred at an 
incidence less than 3%. 
In addition, two Phase 2 clinical trials (CL002_168 and CL003_168) have been conducted in 
109 patients with AAV; 73 of these were randomized to receive avacopan in these trials. A total 
of 60 patients received 30 mg avacopan twice daily and 13 patients received 10 mg avacopan 
twice daily for 12 weeks. 
No deaths were observed in the Phase 2 AAV studies. As anticipated, since all patients received 
rituximab or cyclophosphamide, and most also received glucocorticoids, serious infections were 
the most common serious adverse event. The incidence of serious infections was similar in 
patients receiving avacopan compared to the control group. Vasculitis or renal vasculitis 
(worsening) was also reported at a similar incidence in the two groups. 
The most commonly reported treatment-emergent adverse events in patients with AAV receiving 
avacopan in studies CL002_168 and CL003_168 combined were hypertension (17.8% vs. 16.7% 
in the control group), nausea (17.8% vs. 19.4% in the control group), vomiting (13.7% vs. 0.0% 
in the control group), headache (11.0% vs. 11.1% in the control group), nasopharyngitis (11.0% 
vs. 8.3% in the control group), peripheral edema (9.6% vs. 11.1% in the control group), 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 98 of 100 
arthralgia (8.2% vs. 2.8% in the control group), and diarrhea (8.2% vs. 2.8% in the control 
group). Grade 3 lymphopenia has been observed in more patients receiving avacopan plus 
cyclophosphamide or rituximab compared to cyclophosphamide or rituximab alone. This 
lymphopenia occurred within the first 2 weeks of treatment, and was not progressive with 
continued treatment. 
Avacopan did not show evidence of pro-arrhythmic potential in an intensive ECG study 
(CL007_168). 
Caution should be exercised when avacopan is given with potent CYP3A4 inhibitors such as 
itraconazole, since the avacopan plasma exposure may increase approximately two-fold. 
Avacopan has shown evidence of efficacy in Phase 2 study CL002_168 based on BVAS, quality 
of life measurements, renal response, urinary albuminuria, and urinary MCP-1:creatinine results. 
This efficacy was demonstrated across a number of relevant immunological and clinical 
subgroups, i.e., patients with MPO ANCA-positive disease vs. PR3 ANCA-positive disease, 
newly diagnosed vs. relapsing patients, and in patients on cyclophosphamide vs. those on 
rituximab. Avacopan was able to safely replace the use of oral prednisone with the same or 
greater efficacy based on results from this study. 
It is of note that avacopan as a selective C5aR blocker does not appear to affect the formation of 
C5b and the membrane attack complex (MAC) or terminal complement complex (TCC) which is 
needed to protect against Neisseria infections. Nevertheless, all local and national vaccination 
protocols should be followed and investigators should be vigilant in reporting all infections 
occurring during clinical trials and should attempt to identify the organisms involved in all 
infections. 
In an ongoing Phase 3 study of avacopan and background therapy of cyclophosphamide followed 
by azathioprine, or in combination with rituximab in patients with AAV (ADVOCATE, 
CL010_168), review of safety data by the Data Monitoring Committee (DMC) for that study 
have commented on a potential risk of 
 and 
, and a potential risk of 
 after the
 unblinded review of safety data from 
enrolled patients. 
The Reference Safety Informa on section of the Investigator’s Brochure has been updated to 
include the potential risk of 
, 
 and 
, and to state that general 
gastrointestinal adverse events (e g. nausea, diarrhea) as previousl observed in Phase 2 AAV 
studies have been observed in the ongoing Phase 3 CL010_168 study at approximately the same 
frequency and severity. 
Based on DMC review of safety data from all completed and ongoing studies of avacopan, the 
frequency of monitoring of hematology has been increased to monthly and rules for pausing 
administration of blinded study drug have been modified. These changes to the protocol were 
based on observations of 
 in this blinded study in a patient 
with C3 glomerulopathy (CL011_168) and 
 in the ongoing and blinded Phase 3 
study of avacopan in patients with AAV (ADVOCATE  CL010_168). In all reported cases, 
patients were receiving multiple immunosuppressants (e.g., cyclophosphamide, rituximab, 
mycophenolate mofetil, others) in addition to study medication. Therefore a causal relationship 
with study medication is not clear. 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 99 of 100 
12.3.3. 
Pediatric Testing 
There is currently no approved therapy for C3G in adults or juveniles. 
Avacopan appears to be generally well tolerated and safe in adults with ANCA-associated 
vasculitis who have been included in clinical trials. There are no data currently available on the 
efficacy and safety of avacopan in patients younger than 18 years of age. However, avacopan has 
been well tolerated at supra-therapeutic doses in young animals (rats and cynomolgus monkeys) 
in long term toxicology studies, and at doses up to 100 mg twice daily in adults. Therefore, it is 
reasonable to postulate that avacopan may be well tolerated in younger patients. 
The current therapies that are used to treat C3G in children have significant safety concerns. 
Glucocorticoids increase the risk of infection, new onset diabetes and hypertension, acne and 
Cushingoid changes, psychiatric disorders, glaucoma, cataracts, and peptic ulceration. It may 
negatively impact growth, immunity, and adrenal function. Broad immunosuppressive drugs are 
associated with increased risk of infection. 
Avacopan is a highly selective inhibitor of the terminal effector of the complement cascade, C5a, 
by blocking the binding of C5a to its receptor, C5aR. It does not block other parts of the 
complement pathway, e.g., formation of the terminal complement complex, C5b-9, C3a, C3b, or 
other parts of the immune system. It is not known at this time whether the efficacy and safety 
profile of avacopan would be different in children compared to adults. However, it is anticipated 
that the mechanism of action of avacopan would also apply to C3G in children. There is also no 
evidence from the animal toxicology studies in young growing animals that avacopan affects 
growth and organ maturation. 
Avacopan is orally administered, which makes it convenient for use in children. 
Avacopan has shown evidence of efficacy in adults in Phase 2 studies in adults with AAV 
(CL002_168 and CL003_168) based on the BVAS, quality of life, and other markers such as 
albuminuria. 
The PK profile of avacopan in children is not known. However, since avacopan is cleared from 
the body primarily through hepatic metabolism mediated by CYP3A4, which is known to mature 
in children well before the age of 12 (Johnson et al., 2006), it can be scientifically justified to 
adjust the avacopan dose for 12 to 17 year old children based on body weight. This methodology 
is proposed in this clinical trial. In a recent study of 126 unique products with pediatric studies 
by FDA scientists (Momper et al., 2013), allometric scaling using body weight was found to 
predict adolescent drug clearance well, with an overall mean absolute percentage error of 17.0%. 
By taking this approach, a 40 kg adolescent would need a 2/3 dose relative to a 70 kg adult to 
produce similar drug exposure. In this study (CL011_168), a conservative approach will be 
followed with an adolescent <40 kg by beginning with a dose that is 1/3 of the adult dose (i.e., 
10 mg instead of 30 mg avacopan twice daily); the dose may be adjusted based on the Day 1 
avacopan plasma concentrations. Linear pharmacokinetics is assumed for this approach based on 
the approximate dose linearity in AUC observed between 10 mg and 30 mg in adult AAV 
patients in study CL003_168 (153 ± 86.7 and 525 ± 276 ng•hr/mL for 10 mg and 30 mg 
avacopan, respectively). 
The level of discomfort and the risk threshold for adolescent participation in this study have been 
carefully considered, and measures taken to monitor patients closely during the study: 


CCX168 (avacopan) 
 
Protocol CL011_168 
 
 
Amendment 4.0 
ChemoCentryx, Inc. 
CONFIDENTIAL 
Page 100 of 100 
• Based on all available data, there is no evidence of a negative effect of avacopan on growth 
and maturation of all relevant organ systems. 
• All patients will be monitored closely over the course of the study by the study center 
personnel, study monitors, as well as an external data monitoring committee for any 
untoward effects. 
• The protocol provides stopping rules for significant laboratory abnormalities, such as hepatic 
enzyme elevations and WBC, neutrophil, and lymphocyte count decreases (Section 4.4). 
• Patients will be seen frequently over the course of the study, with a particularly high 
frequency in the first 4 weeks of treatment.  
• Adolescents will be kept for at least 6 hours at the clinic. During this time, patients will be 
monitored for any adverse effects, and plasma samples will be taken to measure the levels of 
avacopan, and to adjust the dose of avacopan if the plasma levels are too high or low 
(Section 3.3). 
In summary, there are a number of potential benefits of testing avacopan in adolescent patients 
with C3G in this study. For example, there are no currently approved medications for C3G in 
juveniles and it has been demonstrated that complement biology is involved in C3G. Further, as 
avacopan is an orally administered selective inhibitor of C5aR it carries potential safety and 
efficacy advantages of avacopan compared to other non-oral and/or non-approved therapies such 
as glucocorticoids and other immunosuppressants that may be used. Given the favorable safety 
profile that has been demonstrated with avacopan to date in conjunction with a prudent dose 
adjustment for adolescents based on plasma drug exposure these benefits outweigh the potential 
risk and would justify the testing in adolescent patients. 
12.3.4. 
Summary Benefit-Risk Statement 
Based on the nonclinical and clinical study results, the potential benefits of testing avacopan in 
patients with C3G outweigh the potential risks. 
Patients participating in clinical trials must be closely monitored for any adverse events, and 
laboratory, physical examination, or vital signs abnormalities. WBC and differential counts, and 
liver enzyme values must be monitored over the course of the studies. 
As with all investigational compounds, the potential exists for unanticipated serious or life-
threatening toxicities or adverse events not predicted by the animal toxicology or clinical studies 
conducted to date. Investigators should exercise vigilance in the monitoring of patients involved 
in this clinical trial with avacopan. 

SAP_001.pdf: 


SIGNATURE PAGE 
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the 
Safety and Efficacy of Avacopan (CCX168) in Patients with C3 Glomerulopathy 
Protocol Number: CLOl 1 168 
We, the undersigned, have reviewed and approve this Statistical Analysis Plan. 
Signature 
Project Statistician 
Senior Vice President, Clinical Development 
Che<~. 
Executive Director of Biostatistics 
ChemoCentryx, Inc. 
Medical Monitor 
Statistical Analysis Plan 
Version Number: 1.0 
Page2 
Date 
13-Nov-2020 
13-Nov-2020 
13-Nov-2020 
Protocol Number: CL0l 1 168 
Version Date: 05 Nov 2020 


SIGNATURE PAGE 
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the 
Safety and Efficacy of Avacopan (CCX168) in Patients with C3 Glomerulopathy 
Protocol Number: CLOI 1_168 
We, the undersigned, have reviewed and approve this Statistical Analysis Plan. 
Signature 
Project Statistician 
::::
Senior 
President Clinical Development 
ChemoCentryx, Inc. 
Executive Director of Biostatistics 
ChemoCentryx, Inc. 
Med cal Monitor 
Statistical Analysis Plan 
Version Number: 1.0 
Page 2 
Date 
Protocol Number: CLOl 1_168 
Version Date: 05 Nov 2020 














2.1.1
Primary Objective 
2.1.2
Secondary Objectives 
2.1.3
Exploratory Objectives 
2.2.1
Overview 


2.2.2
Stratification 
2.2.3
Randomization and Blinding 


2.2.4
Screening Period (Up to 6 Weeks)


2.2.5
26-Week Double-blind Placebo-Controlled Treatment Period A 
2.2.6
26-Week Avacopan Treatment Period B


2.2.7
8-Week Off Treatment Follow-up Period 
2.3.1
Primary Efficacy Endpoint 
2.3.2
Secondary Efficacy Endpoints 
2.3.3
Other Efficacy Endpoints 
2.3.4
Efficacy Assessments 


C3G Histologic Index for Disease Activity 
C3G Histologic Index for Disease Chronicity 


eGFR


2.3.5
Pharmacokinetic Assessments 
2.3.6
Pharmacodynamic Assessments 


2.3.7
Safety Endpoints 






3.1.1
Study Day 
3.1.2
Analysis Visits for Efficacy 


3.1.3
Definition of Baseline
3.1.4
Handling of Missing Data 
3.1.5
Other Data Handling Approaches 
3.1.6
Summary Statistics 


3.1.7
Evaluation of Site Effect 
3.1.8
Adjustments for Potential Impact of COVID-19 
3.2.1
Randomized Population 
3.2.2
Intent-to-Treat Population 
3.2.3
Safety Population 


3.2.4
Per Protocol Population 


3.2.5
C5b-9 Patient Populations 


4.4.1
Non-Study Supplied Treatments for C3G 




**********************************************************************************
Note:  TRT01PN = Randomized Treatment Group (1 = Placebo, 2 = Avacopan) 
       PCHG = Percent Change from Baseline 


       BLIndex = Baseline C3G Histologic Index for disease activity 
**********************************************************************************
proc mixed data=C3GData; 
 
class TRT01PN; 
 
model PCHG= TRT01PN BLIndex / solution cl outp=resid ddfm=kr; 
 
LSMEANS TRT01PN / cl diff alpha=0.05;  
 
ODS output LSMeans=lsmean  
                  Diffs=lsmdiff; 
run;
5.2.1
Primary Analysis 


5.2.2
Secondary Analysis 


**********************************************************************************
Note:
      BL_W26 = Percent Change from Baseline to Week 26 in the C3G Histologic Index for 
                activity in the randomized placebo or avacopan group 
      W26_W52 = Percent Change from Week 26 to Week 52 in the C3G Histologic Index for 
                 activity in the randomized placebo or avacopan group 
      BLIndex = Baseline C3G Histologic Index for disease activity 
**********************************************************************************
proc ttest data=C3G_pair; 
 
paired BL_W26 * WK26_W52; 
 
ODS output Statistics=S_ttest ttests=T_ttest; 
run;
5.2.3
Sensitivity Analysis 


5.2.4
Completer Analysis 
5.2.5
Individual Components of C3G Histological Index Activity 
5.2.6
Per-Protocol Analyses 


5.3.1
Percent change from baseline in UPCR during the 26 Week placebo-controlled 
treatment period 
**********************************************************************************
Note:
TRT01AN = randomized treatment group (numeric): 1=Placebo, 2=Avacopan 
VISITN = Visit Number
LR2BASE = Ratio of Visit Value to Baseline Value (log-transformed)
LBASE = Baseline value of response (log transformed) 
proc mixed data=lablog;
class SUBJID VISITN TRT01AN(ref='1');
model LR2BASE = TRT01AN VISITN TRT01AN*VISITN LBASE/ 
solution cl ddfm=kr;
Repeated VISITN / TYPE=TOEP sub=SUBJID;
**use AR(1) if no convergence, then CS;
lsmeans VISITN*TRT01AN / alpha=0.05 cl pdiff slice=VISITN;
ods output LSMeans=LSM 


           Diffs=DiffLSM; 
run;


5.3.2
Change and Percent change from baseline in eGFR during the 26 Week placebo-
controlled treatment period 
5.3.3
Change from baseline in the C3G Histological Index for disease chronicity during the 
26 Week placebo-controlled treatment period 


5.3.4
Proportion of subjects who have a histological response 
**********************************************************************************
Note:  TRT01PN = Randomized Treatment Group (1 = Placebo, 2 = Avacopan) 
       RESPONSE = Histological Response (1=Yes, 0=No)
proc freq data=HISTRESP; 
   tables TRT01PN*RESPONSE/out=counts outpct cmh; 
   ods output CMH=pvalue; 
run;
**********************************************************************************


5.3.5
Change from baseline in urinary MCP-1:creatinine ratio during the 26 Week placebo-
controlled treatment period 
5.3.6
SF-36 v2 and EQ-5D-5L VAS and Index - Change from Baseline during the 26 Week 
placebo-controlled treatment period 


Percent Compliance = 100 × number of capsules taken / (6 × number of days in the specified 
period).


100 × number of capsules taken / (2 × number of days in the specified period).












12.1.1 EQ-5D-5L
12.2.1 Incomplete Adverse Event Start Date: 
Missing day and month 


Missing day only 
Missing day, month, and year 
12.2.2 Incomplete AE Stop Date: 
Missing day and month 
Missing day only 


12.2.1 Incomplete Start/Stop Dates for Prior/Concomitant Medications/Procedures 


**********************************************************************************
Note:
      W26 = Week 26 continuous result 
      BL = Baseline continuous result 
      DISTYPE  = Disease Type (C3GN or DDD) 
      RENTRANS = Renal Transplant Status (Y/N)
      TRT01PN = Treatment Group (Placebo/Avacopan) 
**********************************************************************************
**********************************************************************************
**********************************************************************************
/* Imputation at Week 26 */ 
Proc MI Data= num_org Seed= Seedno nimpute= 100
minimum= . . . 0
maximum= . . . 100
Out= mum_mi26; 
     
by TRT01PN; 
     
class DISTYPE RENTRANS; 
     
var DISTYPE RENTRANS BL W26; 
     
monotone reg(W26/details) ;  
Run;
/* Note: In the code above, remove minimum and maximum when imputed value is out of 
range; replace percentage <0 to be 0 and replace percentage >100 to be 100 for imputed 
values */ 
proc sort data= mum_mi26; 
by _imputation_ TRT01PN; 
run;


/* Imputation at Week 52 */ 
Proc MI Data= mum_mi26 Seed= Seedno nimpute= 1
minimum= . . . . 0
maximum= . . . . 100
Out= mum_mi52; 
     
by _imputation_ TRT01PN; 
     
class DISTYPE RENTRANS; 
     
var DISTYPE RENTRANS BL W26 W52; 
     
monotone reg(W52/details) ;  
Run;
/* Note:  In the code above, if the model is not able to be fit, remove Renal 
Transplant Status (RENTRANS) */ 
**********************************************************************************
**********************************************************************************
/* Imputation at Week 26 */ 
Proc MI Data= cat_org Seed= Seedno nimpute=100
out= cat_mi26; 
    
by TRT01PN;  
class DISTYPE RENTRANS BL; 
var DISTYPE RENTRANS BL; 
monotone logistic(W26= DISTYPE RENTRANS BL/ Details Likelihood=AUGMENT) ;
run;
proc sort data= cat_mi26; 
by _imputation_ TRT01PN; 
run;
/* Imputation at Week 52 */ 
Proc MI Data= cat_mi26 Seed= Seedno nimpute=1
out= cat_mi52; 
    
by _imputation_ TRT01PN; 
 
class DISTYPE RENTRANS BL W26 W52; 
var DISTYPE RENTRANS BL W26 W52; 
monotone logistic(W52= DISTYPE RENTRANS BL W26/ Details Likelihood=AUGMENT) ;
fcs logistic(W52= DISTYPE RENTRANS BL W26/ Details Likelihood=AUGMENT) ;
run;
**********************************************************************************
If there are no patients randomized to Avacopan with missing data at Week 26 in 
observed dataset, 100 datasets will be created from observed dataset to combine with 
the 100 imputed datasets from the Placebo group; similarly, for no missing in Placebo 
group.
**********************************************************************************


**********************************************************************************
Note:
      EFFI = Imputed efficacy analysis dataset 
      AVAL = Variable analyzed
      Imputation = Imputed number 
      TRT01PN = Treatment Group (Placebo/Avacopan) 
**********************************************************************************
*** Proc Univariate to generate sample means and standard errors for the variables in 
each imputed data set 
Proc Univariate Data= EFFI; 
 
By _Imputation_; 
 
Class TRT01PN; 
 
Var AVAL; 
 
Output Out= SumStat_MI 
 
 
Mean= AVAL 
 
 
Stderr= SAVAL; 
Run;
Proc sort data= SumStat_MI; By TRT01PN; Run; 
*** Proc MIANALYZE; 
PROC MIANALYZE DATA = SumStatMI; 
 
By TRT01PN; 
 
Modeleffects AVAL; 
 
Stderr SAVAL; 
 
ODS Output 
 
 
ParameterEstimates = SumStat_Mian; 
RUN;
Note: If variables not requested imputation, the above procedure won’t be appropriate. 
Using PROC MEANS to summary one single imputation to get summary statistics.


**********************************************************************************
Note:
      EFFI = Imputed efficacy analysis dataset 
      Response = CHG/PCHG
      CHG = Change from baseline in C3G Disease Activity or Chronicity 
      PCHG = Percent change from baseline in C3G Disease Activity or Chronicity
      Base = Baseline value 
      TRT01PN = Treatment Group (Placebo/Avacopan) 
**********************************************************************************
***  Perform ANCOVA; 
PROC MIXED DATA= EFFI; 
 
By _Imputation_; 
 
Class TRT01AN(ref='1');
 
Model Response = TRT01AN Base / solution cl ddfm = KR  
 
 
 
 
 
 
   residual OUTP = ano_res ; 
* studentized residual ; 
 
Lsmeans TRT01AN / Alpha=0.05 cl diff ; 
 
ODS Output LSMEANS = ano_lsm 
 
 
 
   Diffs = ano_diff; 
RUN;
*** Combine result; 
PROC MIANALYZE DATA = ano_lsm; 
 
By TRT01AN; 
 
Modeleffects Estimate; 
 
Stderr; 
 
ODS Output 
 
 
ParameterEstimates = miana_lsm; 
RUN;
PROC MIANALYZE DATA = ano_diff; 
 
By TRT01AN; 
 
Modeleffects Estimate; 
 
Stderr; 
 
ODS Output 
 
 
ParameterEstimates = miana_diff; 
RUN;
*** Normality Test; 
PROC UNIVARIATE DATA = ano_res Normaltest; 
 
Class _Imputation_; 
 
Var StudentResid; 
 
ODS Output 
 
 
TestsForNormality = res_SW (Where=(Test="Shapiro-Wilk"));
Run;
*** Select the minimum P-value from Shapiro-Wilk test among all imputation; 


**********************************************************************************
Note:
       EFFI = Efficacy Analysis Dataset with multiple imputation
       Response = categorical variable of interest in analysis
       DISTYPE  = Disease Type (C3GN or DDD) 
       RENTRANS = Renal Transplant Status (Y/N)
       TRT01PN = Treatment Group (Placebo/Avacopan) 
**********************************************************************************
*** Van Elteren's Test by each Imputation; 
Proc Freq Data= EFFI; 
 
By _Imputation_; 
 
Table DISTYPE*RENTRANS*TRT01PN*Response / CMH Scores= modridit; 
 
Ods Output 
 
 
CMH= cmh_RMS (Where=(AltHypothesis="Row Mean Scores Differ")); 
Run;
*** Apply Wilson-Hilferty transformation to the CMH statistic and standardize the 
resulting normal variable; 
DATA cmh_wh; 
 
SET cmh_RMS; 
 
cmh_value_wh = ((VALUE/DF)**(1/3) - (1-2/(9*DF)))/SQRT(2/(9*DF)); 
 
cmh_sterr_wh = 1.0; 
RUN;
*** Proc MIANALYZE; 
PROC MIANALYZE DATA = cmh_wh; 
 
Modeleffects cmh_value_wh; 
 
Stderr cmh_sterr_wh; 
 
ODS Output 
 
 
ParameterEstimates = cmh_miana; 
RUN;


**********************************************************************************
Note:
      W26 = Week 26 result 
      BL = Baseline result 
      DISTYPE  = Disease Type (C3GN or DDD) 
      RENTRANS = Renal Transplant Status (Y/N)
      TRT01PN = Treatment Group (Placebo/Avacopan) 
**********************************************************************************
**********************************************************************************
**********************************************************************************
*** Imputation at Week 26, Continuous variable; 
Proc MI Data= ERT (Where=(PARAMCD=" ")) Seed= ##### Nimpute= 100
 
Minimum= . . . 0  
 
Maximum= . . . 100 
 
OUT= PMMnum_IM26; 
     
Class TRT01PN DISTYPE RENTRANS; 
 
Var DISTYPE RENTRANS BL W26; 
     
Monotone Reg(W26/Details) ;  
 
MNAR Model(W26/ modelobs=(TRT01PN='1')) ; 
 Run; 
**********************************************************************************
**********************************************************************************
*** Week 26, Classification variable; 
Proc MI Data= ERT (Where=(PARAMCD=" ")) Seed= ##### Nimpute= 100
 
OUT= PMMcat_IM26; 
     
Class DISTYPE RENTRANS TRT01PN BL W26; 
 
Var DISTYPE RENTRANS TRT01PN BL W26; 
     
Monotone Logistic(W26= DISTYPE RENTRANS TRT01AN BL / Details 
likelihood=AUGMENT);
 
MNAR Model(W26/ modelobs=(TRT01PN='1')) ; 
 Run;