A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis (ADVOCATE)

• ClinicalTrials.gov Identifier: NCT02994927
• Recruitment Status: Completed
• First Posted: December 16, 2016
• Results First Posted: September 9, 2022
• Last Update Posted: January 29, 2024
• Sponsor: ChemoCentryx
• Information provided by (Responsible Party): ChemoCentryx

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: ANCA-Associated Vasculitis
• Interventions: Drug: Avacopan; Drug: Prednisone; Drug: Cyclophosphamide; Biological: Rituximab; Drug: Azathioprine
• Enrollment: 331

Participant Flow

Recruitment Details	A total of 143 study centers randomized at least 1 subject. The target enrollment was 300 subjects.
Pre-assignment Details	Screening details: Of 386 subjects screened, 331 were enrolled in the study and randomized to treatment. Reasons for subjects failing screening included not meeting inclusion/exclusion criteria, withdrawal by subject, adverse event (AE) and other.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo
Period Title: Overall Study
Started	165	166
Completed	150	151
Not Completed	15	15
Reason Not Completed
Withdrawal by parent/guardian	0	1
Did not meet eligibility criteria	0	1
Physician Decision	4	3
Death	4	2
Adverse Event	2	1
Withdrawal by Subject	3	6
Lost to Follow-up	2	1

Baseline Characteristics

Arm/Group Title		Prednisone Group	Avacopan Group	Total
Arm/Group Description		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo	Total of all reporting groups
Overall Number of Baseline Participants		164	166	330
Baseline Analysis Population Description		In the Prednisone group, one subject was randomized but withdrawn for not meeting disease criteria prior to dosing.
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Adolescents (12-17 years)	Number Analyzed	164 participants	166 participants	330 participants
		1 0.6%	2 1.2%	3 0.9%
Adults (18-50 years)	Number Analyzed	164 participants	166 participants	330 participants
		28 17.1%	30 18.1%	58 17.6%
Adults (51-64 years)	Number Analyzed	164 participants	166 participants	330 participants
		61 37.2%	48 28.9%	109 33.0%
Adults (65-75 years)	Number Analyzed	164 participants	166 participants	330 participants
		52 31.7%	62 37.3%	114 34.5%
Adults (>75 years)	Number Analyzed	164 participants	166 participants	330 participants
		22 13.4%	24 14.5%	46 13.9%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	164 participants	166 participants	330 participants
	Female	76 46.3%	68 41.0%	144 43.6%
	Male	88 53.7%	98 59.0%	186 56.4%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	164 participants	166 participants	330 participants
	Hispanic or Latino	5 3.0%	7 4.2%	12 3.6%
	Not Hispanic or Latino	157 95.7%	151 91.0%	308 93.3%
	Unknown or Not Reported	2 1.2%	8 4.8%	10 3.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	164 participants	166 participants	330 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	15 9.1%	17 10.2%	32 9.7%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 1.2%	3 1.8%	5 1.5%
	White	140 85.4%	138 83.1%	278 84.2%
	More than one race	1 0.6%	0 0.0%	1 0.3%
	Unknown or Not Reported	6 3.7%	8 4.8%	14 4.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Australia	Number Analyzed	164 participants	166 participants	330 participants
		4	10	14
Austria	Number Analyzed	164 participants	166 participants	330 participants
		3	3	6
Belgium	Number Analyzed	164 participants	166 participants	330 participants
		4	6	10
Canada	Number Analyzed	164 participants	166 participants	330 participants
		5	8	13
Czechia	Number Analyzed	164 participants	166 participants	330 participants
		7	2	9
Denmark	Number Analyzed	164 participants	166 participants	330 participants
		10	6	16
France	Number Analyzed	164 participants	166 participants	330 participants
		18	22	40
Germany	Number Analyzed	164 participants	166 participants	330 participants
		32	22	54
Italy	Number Analyzed	164 participants	166 participants	330 participants
		2	9	11
Japan	Number Analyzed	164 participants	166 participants	330 participants
		10	11	21
Netherlands	Number Analyzed	164 participants	166 participants	330 participants
		5	1	6
New Zealand	Number Analyzed	164 participants	166 participants	330 participants
		2	2	4
Ireland	Number Analyzed	164 participants	166 participants	330 participants
		4	4	8
Spain	Number Analyzed	164 participants	166 participants	330 participants
		7	8	15
Sweden	Number Analyzed	164 participants	166 participants	330 participants
		2	5	7
Switzerland	Number Analyzed	164 participants	166 participants	330 participants
		6	4	10
United Kingdom	Number Analyzed	164 participants	166 participants	330 participants
		23	17	40
United States	Number Analyzed	164 participants	166 participants	330 participants
		20	26	46
Geographic Region; Measure Type: Count of Participants; Unit of measure: Participants
North America	Number Analyzed	164 participants	166 participants	330 participants
		25 15.2%	34 20.5%	59 17.9%
Europe and Rest of World excluding Japan	Number Analyzed	164 participants	166 participants	330 participants
		129 78.7%	121 72.9%	250 75.8%
Japan	Number Analyzed	164 participants	166 participants	330 participants
		10 6.1%	11 6.6%	21 6.4%
ANCA-associated vasculitis Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
Newly diagnosed	Number Analyzed	164 participants	166 participants	330 participants
		114 69.5%	115 69.3%	229 69.4%
Relapsed	Number Analyzed	164 participants	166 participants	330 participants
		50 30.5%	51 30.7%	101 30.6%
		[1] Measure Description: ANCA=anti-neutrophil cytoplasmic autoantibody
ANCA Positivity [1]; Measure Type: Count of Participants; Unit of measure: Participants
Proteinase 3 (PR3)	Number Analyzed	164 participants	166 participants	330 participants
		70 42.7%	72 43.4%	142 43.0%
Myeloperoxidase (MPO)	Number Analyzed	164 participants	166 participants	330 participants
		94 57.3%	94 56.6%	188 57.0%
		[1] Measure Description: ANCA=anti-neutrophil cytoplasmic autoantibody
Standard of Care Treatment; Measure Type: Count of Participants; Unit of measure: Participants
Rituximab	Number Analyzed	164 participants	166 participants	330 participants
		107 65.2%	107 64.5%	214 64.8%
Intravenous (IV) Cyclophosphamide	Number Analyzed	164 participants	166 participants	330 participants
		51 31.1%	51 30.7%	102 30.9%
Oral Cyclophosphamide	Number Analyzed	164 participants	166 participants	330 participants
		6 3.7%	8 4.8%	14 4.2%
Type of ANCA-associated vasculitis [1]; Measure Type: Count of Participants; Unit of measure: Participants
Granulomatosis with polyangiitis (GPA)	Number Analyzed	164 participants	166 participants	330 participants
		90 54.9%	91 54.8%	181 54.8%
Microscopic polyangiitis (MPA)	Number Analyzed	164 participants	166 participants	330 participants
		74 45.1%	75 45.2%	149 45.2%
		[1] Measure Description: ANCA=anti-neutrophil cytoplasmic autoantibody
BVAS Entry Criteria [1]; Measure Type: Count of Participants; Unit of measure: Participants
One or more major item	Number Analyzed	164 participants	166 participants	330 participants
		102 62.2%	104 62.7%	206 62.4%
Three or more minor items	Number Analyzed	164 participants	166 participants	330 participants
		142 86.6%	146 88.0%	288 87.3%
Two renal items of proteinuria and hematuria	Number Analyzed	164 participants	166 participants	330 participants
		57 34.8%	60 36.1%	117 35.5%
		[1] Measure Description: BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health). * Subjects can appear in more than one category
BVAS Components [1]; Measure Type: Count of Participants; Unit of measure: Participants
General	Number Analyzed	164 participants	166 participants	330 participants
		114 69.5%	111 66.9%	225 68.2%
Cutaneous	Number Analyzed	164 participants	166 participants	330 participants
		23 14.0%	24 14.5%	47 14.2%
Mucous Membranes/Eyes	Number Analyzed	164 participants	166 participants	330 participants
		40 24.4%	26 15.7%	66 20.0%
Ear Nose and Throat	Number Analyzed	164 participants	166 participants	330 participants
		69 42.1%	75 45.2%	144 43.6%
Chest	Number Analyzed	164 participants	166 participants	330 participants
		71 43.3%	71 42.8%	142 43.0%
Cardiovascular	Number Analyzed	164 participants	166 participants	330 participants
		3 1.8%	6 3.6%	9 2.7%
Abdominal	Number Analyzed	164 participants	166 participants	330 participants
		1 0.6%	4 2.4%	5 1.5%
Renal + Other (RBC Casts and/or Glomerulonephritis)	Number Analyzed	164 participants	166 participants	330 participants
		134 81.7%	134 80.7%	268 81.2%
Nervous System	Number Analyzed	164 participants	166 participants	330 participants
		31 18.9%	38 22.9%	69 20.9%
		[1] Measure Description: BVAS=Birmingham Vasculitis Activity Score * Subjects can appear in more than one category
Age at screening; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	164 participants	166 participants	330 participants
		60.5 (14.50)	61.2 (14.56)	60.9 (14.51)
Age at diagnosis of ANCA-associated Vasculitis [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	164 participants	166 participants	330 participants
		59.4 (15.19)	59.8 (15.60)	59.6 (15.37)
		[1] Measure Description: ANCA=anti-neutrophil cytoplasmic autoantibody
Duration of ANCA-Associated Vasculitis [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	164 participants	166 participants	330 participants
		20.13 (40.473)	22.93 (52.464)	21.54 (46.840)
		[1] Measure Description: ANCA=anti-neutrophil cytoplasmic autoantibody
Body Weight; Mean (Standard Deviation); Unit of measure: Kilogram(s)
	Number Analyzed	164 participants	166 participants	330 participants
		77.71 (19.335)	76.43 (20.254)	77.07 (19.783)
BMI [1] [2]; Mean (Standard Deviation); Unit of measure: Kilogram(s)/square meter
	Number Analyzed	163 participants	165 participants	328 participants
		26.78 (5.212)	26.72 (5.997)	26.75 (5.612)
		[1] Measure Description: BMI=Body Mass Index; [2] Measure Analysis Population Description: Two subjects did not have a baseline BMI provided (one in each treatment group)
BVAS Score [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	164 participants	166 participants	330 participants
		16.2 (5.69)	16.3 (5.87)	16.2 (5.77)
		[1] Measure Description: BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).
VDI Score [1] [2]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	163 participants	165 participants	328 participants
		0.7 (1.39)	0.7 (1.54)	0.7 (1.47)
		[1] Measure Description: VDI=Vasculitis Damage Index; The VDI is comprised of 64 items of damage, grouped into 11 organ-based systems or categorizations. Damage is defined as the presence of non-healing scars and does not give any indication of current disease activity. Damage is also defined as having been present or currently present for at least 3 months. Completion of the form provides a numerical score, which ranges from 0 (best health) to 64 (worst health).; [2] Measure Analysis Population Description: Two subjects did not have a baseline VDI Score (one in each treatment group)

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Achieving Disease Remission at Week 26
Description	Disease remission at Week 26 was defined as: Achieving a BVAS of 0 as determined by the Adjudication Committee;; No administration of glucocorticoids given for ANCA-associated vasculitis within 4 weeks prior to Week 26;; No BVAS >0 during the 4 weeks prior to Week 26 (if collected for an unscheduled assessment).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description:	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed	164	166
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	70.1; (62.5 to 77.0)	72.3; (64.8 to 78.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prednisone Group, Avacopan Group
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	The proportion of subjects achieving disease remission at Week 26 and the two-sided 95% confidence intervals (CIs) for the difference in proportions was estimated for the comparison between the avacopan group and the prednisone group. For both the noninferiority and superiority tests, the one-sided P-values are presented. Statistical significance was claimed based on the one-sided type-I error of 0.025.
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Summary score test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Common difference in remission rates
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; -6.0 to 12.8
	Estimation Comments	Summary Score estimate of the common difference and Miettinen-Nurminen (score) confidence limits for the common difference

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Prednisone Group, Avacopan Group
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The proportion of subjects achieving disease remission at Week 26 and the two-sided 95% confidence intervals (CIs) for the difference in proportions was estimated for the comparison between the avacopan group and the prednisone group. For both the noninferiority and superiority tests, the one-sided P-values are presented. Statistical significance was claimed based on the one-sided type-I error of 0.025.
Statistical Test of Hypothesis	P-Value	= 0.2387
	Comments	[Not Specified]
	Method	Summary score test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Common difference in remission rates
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; -6.0 to 12.8
	Estimation Comments	Summary Score estimate of the common difference and Miettinen-Nurminen (score) confidence limits for the common difference

2. Primary Outcome

Title	Percentage of Subjects Achieving Sustained Disease Remission at Week 52
Description	Sustained remission at Week 52 was defined as: Disease remission at Week 26 as defined above;; Disease remission at Week 52 defined as a BVAS of 0 at Week 52 as determined by the Adjudication Committee and no administration of glucocorticoids for treatment of ANCA-associated vasculitis within 4 weeks prior to Week 52;; No disease relapse between Week 26 and Week 52 as determined by the Adjudication Committee.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description:	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed	164	166
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	54.9; (46.9 to 62.6)	65.7; (57.9 to 72.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prednisone Group, Avacopan Group
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	The proportion of subjects achieving sustained disease remission at Week 52, and the two-sided 95% confidence intervals (CIs) for the difference in proportions (avacopan minus prednisone) was estimated for the comparison between the avacopan group and the prednisone group. For both the noninferiority and superiority tests, the one-sided P-values are presented. Statistical significance was claimed based on the one-sided type-I error of 0.025.
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Summary score test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Common difference in remission rates
	Estimated Value	12.5
	Confidence Interval	(2-Sided) 95%; 2.6 to 22.3
	Estimation Comments	Summary Score estimate of the common difference and Miettinen-Nurminen (score) confidence limits for the common difference

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Prednisone Group, Avacopan Group
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The proportion of subjects achieving sustained disease remission at Week 52, and the two-sided 95% confidence intervals (CIs) for the difference in proportions (avacopan minus prednisone) was estimated for the comparison between the avacopan group and the prednisone group. For both the noninferiority and superiority tests, the one-sided P-values are presented. Statistical significance was claimed based on the one-sided type-I error of 0.025.
Statistical Test of Hypothesis	P-Value	= 0.0066
	Comments	[Not Specified]
	Method	Summary score test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Common difference in remission rates
	Estimated Value	12.5
	Confidence Interval	(2-Sided) 95%; 2.6 to 22.3
	Estimation Comments	Summary Score estimate of the common difference and Miettinen-Nurminen (score) confidence limits for the common difference

3. Secondary Outcome

Title	Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs
Description	AEs=Adverse events SAEs=Serious adverse events TEAE=Treatment-emergent adverse event
Time Frame	From day 1 throughout the study period (day 421/week 60)

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description:	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed	164	166
Measure Type: Number; Unit of Measure: Number
Number of subjects with at least one TEAE	161	164
Number of TEAEs	2139	1779
Number of subjects with SAEs	74	70
Number of SAEs	166	116
Subjects with TEAE leading to discontinuation	28	27

4. Secondary Outcome

Title	Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI
Description	GTI-CWS=Glucocorticoid Toxicity Index Cumulative Worsening Score; GTI-AIS=Glucocorticoid Toxicity Index Aggregate Improvement Score; The Glucocorticoid Toxicity Index (GTI) was developed to score glucocorticoid toxicity. The GTI includes: the Cumulative Worsening Score (CWS) that captures cumulative toxicity, both permanent and transient, over the course of time (serves as a cumulative record of toxicity); and the Aggregate Improvement Score that captures both improvement and worsening of toxicity over time (serves as a record of both improving and worsening toxicity). Both scores range from 0 (best health) to 100 (worst health).
Time Frame	Baseline, Week 13 and 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug. The number of subjects with data at the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		164	166
Least Squares Mean (Standard Error); Unit of Measure: Glucocorticoid Toxicity Index
GTI-CWS (Week 13)	Number Analyzed	161 participants	160 participants
		36.6 (3.41)	25.7 (3.40)
GTI-CWS (Week 26)	Number Analyzed	153 participants	154 participants
		56.6 (3.45)	39.7 (3.43)
GTI-AIS (Week 13)	Number Analyzed	161 participants	160 participants
		23.2 (3.46)	9.9 (3.45)
GTI-AIS (Week 26)	Number Analyzed	153 participants	154 participants
		23.4 (3.50)	11.2 (3.48)

5. Secondary Outcome

Title	Percentage of Participants With BVAS of 0 at Week 4, Regardless of Whether the Subjects Received Glucocorticoids During This Period of Time and Based on Assessment by the Blinded AC
Description	AC=Adjudication Committee; BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description:	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed	164	166
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	68.9; (61.2 to 75.9)	62.7; (54.8 to 70.0)

6. Secondary Outcome

Title	Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index
Description	SF-36v2: Measure of health- related quality of life (Medical Outcomes Survey Short Form-36 version 2) EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels The SF-36v2 component scores and the EQ-5D-5L VAS score range from 0 (worst health) to 100 (best health). The EQ-5D-5L Index Score ranges from 0 (worst health) to 1 (best health).
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug. The number of subjects with data at the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		150	154
Least Squares Mean (Standard Error); Unit of Measure: Change from baseline
SF-36v2: Physical Component Score (Week 26)	Number Analyzed	147 participants	153 participants
		1.344 (0.7432)	4.445 (0.7332)
SF-36v2: Physical Component Score (Week 52)	Number Analyzed	144 participants	147 participants
		2.626 (0.7505)	4.980 (0.7435)
SF-36v2: Physical Functioning (Week 26)	Number Analyzed	150 participants	153 participants
		1.88 (1.787)	7.31 (1.773)
SF-36v2: Physical Functioning (Week 52)	Number Analyzed	145 participants	149 participants
		4.82 (1.809)	9.55 (1.790)
SF-36v2: Role Physical (Week 26)	Number Analyzed	150 participants	154 participants
		7.52 (2.198)	16.78 (2.173)
SF-36v2: Role Physical (Week 52)	Number Analyzed	145 participants	150 participants
		12.27 (2.228)	17.12 (2.198)
SF-36v2: Bodily Pain (Week 26)	Number Analyzed	149 participants	154 participants
		9.82 (2.197)	14.75 (2.164)
SF-36v2: Bodily Pain (Week 52)	Number Analyzed	145 participants	150 participants
		11.87 (2.220)	16.12 (2.185)
SF-36v2: General Health Perception (Week 26)	Number Analyzed	148 participants	154 participants
		-2.89 (1.428)	3.12 (1.405)
SF-36v2: General Health Perception (Week 52)	Number Analyzed	145 participants	150 participants
		-0.17 (1.442)	5.84 (1.420)
SF-36v2: Mental Component Score (Week 26)	Number Analyzed	147 participants	154 participants
		3.271 (0.8403)	4.849 (0.8273)
SF-36v2: Mental Component Score (Week 52)	Number Analyzed	144 participants	148 participants
		4.694 (0.8491)	6.394 (0.8406)
SF-36v2: Mental Health (Week 26)	Number Analyzed	148 participants	154 participants
		6.84 (1.331)	8.29 (1.318)
SF-36v2: Mental Health (Week 52)	Number Analyzed	144 participants	148 participants
		9.66 (1.347)	10.89 (1.337)
SF-36v2: Role Emotional (Week 26)	Number Analyzed	150 participants	154 participants
		1.40 (2.183)	7.32 (2.158)
SF-36v2: Role Emotional (Week 52)	Number Analyzed	145 participants	150 participants
		4.14 (2.212)	9.38 (2.181)
SF-36v2: Social Functioning (Week 26)	Number Analyzed	147 participants	154 participants
		11.09 (2.037)	14.50 (2.002)
SF-36v2: Social Functioning (Week 52)	Number Analyzed	144 participants	149 participants
		13.56 (2.059)	18.06 (2.030)
SF-36v2: Vitality (Week 26)	Number Analyzed	148 participants	154 participants
		6.42 (1.751)	12.03 (1.727)
SF-36v2: Vitality (Week 52)	Number Analyzed	144 participants	148 participants
		10.48 (1.770)	14.36 (1.750)
EQ-5D-5L VAS Score (Week 26)	Number Analyzed	150 participants	153 participants
		5.5 (1.39)	9.1 (1.38)
EQ-5D-5L VAS Score (Week 52)	Number Analyzed	146 participants	149 participants
		7.1 (1.41)	13.0 (1.39)
EQ-5D-5L Index Score (Week 26)	Number Analyzed	146 participants	152 participants
		-0.0010 (0.01462)	0.0229 (0.01438)
EQ-5D-5L Index Score (Week 52)	Number Analyzed	145 participants	149 participants
		-0.0038 (0.01471)	0.0474 (0.01451)

7. Secondary Outcome

Title	Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving Remission at Week 26 in the Study
Description	The median time to relapse was not estimable because of small number of relapsed subjects. A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or; having achieved BVAS=0 at any time during the treatment period ANCA=anti-neutrophil cytoplasmic autoantibody; BVAS=Birmingham Vasculitis Activity Score; The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Subjects in the analysis population for the specified treatment group.

ITT Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description:	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed	115	120
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	12.2; (6.8 to 19.6)	7.5; (3.5 to 13.8)

8. Secondary Outcome

Title	Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving BVAS=0 at Any Time During the Treatment Period
Description	The median time to relapse was not estimable because of small number of relapsed subjects. A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or; having achieved BVAS=0 at any time during the treatment period The Birmingham Vasculitis Activity Score (BVAS) form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Subjects who achieved BVAS=0 during the 52 week treatment period.

ITT Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description:	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed	157	158
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	21.0; (14.9 to 28.2)	10.1; (5.9 to 15.9)

9. Secondary Outcome

Title	In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Change in eGFR From Baseline Over 52 Weeks
Description	Change from baseline in kidney function, as measured by eGFR (based on the MDRD equation), was measured in subjects with renal disease based on the BVAS renal component. eGFR=estimated glomerular filtration rate BVAS=Birmingham Vasculitis Activity Score MDRD=Modification of Diet in Renal Disease
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Subjects With Renal Disease at Baseline (based on BVAS).

ITT Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		127	121
Least Squares Mean (95% Confidence Interval); Unit of Measure: Change in eGFR (mL/min/1.73 m^2)
Week 26	Number Analyzed	127 participants	121 participants
		2.9; (0.9 to 4.9)	5.8; (3.7 to 7.8)
Week 52	Number Analyzed	125 participants	119 participants
		4.1; (2.1 to 6.1)	7.3; (5.2 to 9.4)

10. Secondary Outcome

Title	In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks
Description	BVAS=Birmingham Vasculitis Activity Score UACR=Urinary albumin:creatinine ratio
Time Frame	Baseline, Week 4, 26 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Subjects With Renal Disease (based on BVAS) and Albuminuria (UACR>=10 mg/g creatinine) at Baseline

ITT Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		124	121
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage change
Week 4	Number Analyzed	124 participants	121 participants
		0; (-16 to 19)	-40; (-50 to -28)
Week 26	Number Analyzed	118 participants	113 participants
		-70; (-75 to -65)	-63; (-69 to -56)
Week 52	Number Analyzed	114 participants	109 participants
		-77; (-81 to -72)	-74; (-78 to -69)

11. Secondary Outcome

Title	In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Percent Change in Urinary MCP-1:Creatinine Ratio From Baseline Over 52 Weeks
Description	BVAS=Birmingham Vasculitis Activity Score MCP-1=monocyte chemoattractant protein-1
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Subjects With Renal Disease at Baseline (based on BVAS).

ITT Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		117	106
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage change
Week 26	Number Analyzed	117 participants	106 participants
		-64; (-67 to -59)	-67; (-70 to -63)
Week 52	Number Analyzed	108 participants	106 participants
		-71; (-74 to -67)	-73; (-76 to -70)

12. Secondary Outcome

Title	Change in the VDI From Baseline Over 52 Weeks, Including the Week 26 and Week 52 Time Points
Description	VDI=Vasculitis Damage Index; The VDI is comprised of 64 items of damage, grouped into 11 organ-based systems or categorizations. Damage is defined as the presence of non-healing scars and does not give any indication of current disease activity. Damage is also defined as having been present or currently present for at least 3 months. Completion of the form provides a numerical score, which ranges from 0 (best health) to 64 (worst health).
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		155	161
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
Week 26	Number Analyzed	155 participants	161 participants
		0.97 (0.092)	1.06 (0.090)
Week 52	Number Analyzed	151 participants	150 participants
		1.15 (0.093)	1.17 (0.091)

13. Secondary Outcome

Title	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		151	147
Mean (Standard Error); Unit of Measure: 10^3 cells/μL
Leukocytes (Week 26)	Number Analyzed	151 participants	147 participants
		-5.69 (0.338)	-5.94 (0.387)
Leukocytes (Week 52)	Number Analyzed	149 participants	147 participants
		-5.54 (0.365)	-5.62 (0.395)
Neutrophils (Week 26)	Number Analyzed	148 participants	143 participants
		-5.10 (0.338)	-5.24 (0.380)
Neutrophils (Week 52)	Number Analyzed	147 participants	144 participants
		-4.89 (0.361)	-4.95 (0.372)
Lymphocytes (Week 26)	Number Analyzed	148 participants	143 participants
		-0.62 (0.090)	-0.84 (0.099)
Lymphocytes (Week 52)	Number Analyzed	147 participants	144 participants
		-0.67 (0.090)	-0.82 (0.100)

14. Secondary Outcome

Title	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		152	147
Mean (Standard Error); Unit of Measure: 10^9 cells/L
Eosinophils (Week 26)	Number Analyzed	148 participants	143 participants
		0.07 (0.016)	0.07 (0.018)
Eosinophils (Week 52)	Number Analyzed	147 participants	144 participants
		0.05 (0.013)	0.07 (0.019)
Basophils (Week 26)	Number Analyzed	148 participants	143 participants
		-0.01 (0.004)	-0.00 (0.004)
Basophils (Week 52)	Number Analyzed	147 participants	144 participants
		-0.01 (0.004)	-0.01 (0.004)
Monocytes (Week 26)	Number Analyzed	148 participants	143 participants
		0.01 (0.022)	-0.04 (0.024)
Monocytes (Week 52)	Number Analyzed	147 participants	144 participants
		0.01 (0.024)	-0.01 (0.026)
Platelets (Week 26)	Number Analyzed	152 participants	147 participants
		-73.9 (8.49)	-77.1 (9.30)
Platelets (Week 52)	Number Analyzed	149 participants	146 participants
		-75.5 (8.01)	-73.8 (9.31)

15. Secondary Outcome

Title	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		152	147
Mean (Standard Error); Unit of Measure: 10^12 cells/L
Erythrocytes (Week 26)	Number Analyzed	152 participants	147 participants
		0.226 (0.0450)	0.252 (0.0432)
Erythrocytes (Week 52)	Number Analyzed	149 participants	147 participants
		0.244 (0.0410)	0.279 (0.0432)

16. Secondary Outcome

Title	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		152	147
Mean (Standard Error); Unit of Measure: g/dL
Hemoglobin (Week 26)	Number Analyzed	152 participants	147 participants
		1.07 (0.129)	1.10 (0.120)
Hemoglobin (Week 52)	Number Analyzed	149 participants	147 participants
		1.20 (0.126)	1.27 (0.125)

17. Secondary Outcome

Title	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		152	147
Mean (Standard Error); Unit of Measure: percentage of red blood cells
Hematocrit (Week 26)	Number Analyzed	152 participants	147 participants
		2.6 (0.38)	2.7 (0.38)
Hematocrit (Week 52)	Number Analyzed	149 participants	147 participants
		3.0 (0.37)	3.2 (0.38)

18. Secondary Outcome

Title	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		154	150
Mean (Standard Error); Unit of Measure: U/L
Lactate Dehydrogenase (Week 26)	Number Analyzed	149 participants	145 participants
		2.3 (5.68)	-6.1 (5.40)
Lactate Dehydrogenase (Week 52)	Number Analyzed	146 participants	141 participants
		-8.6 (5.33)	-10.7 (4.80)
Alkaline Phosphatase (Week 26)	Number Analyzed	154 participants	150 participants
		-0.6 (2.47)	-3.9 (2.84)
Alkaline Phosphatase (Week 52)	Number Analyzed	152 participants	147 participants
		0.8 (1.77)	-4.0 (2.34)
Creatine Kinase (Week 26)	Number Analyzed	154 participants	150 participants
		47.6 (5.27)	76.8 (10.34)
Creatine Kinase (Week 52)	Number Analyzed	152 participants	147 participants
		57.6 (5.67)	76.3 (9.68)
Alanine Aminotransferase (Week 26)	Number Analyzed	154 participants	150 participants
		-6.8 (1.77)	-6.1 (1.54)
Alanine Aminotransferase (Week 52)	Number Analyzed	152 participants	147 participants
		-8.2 (1.57)	-7.2 (1.46)
Aspartate Aminotransferase (Week 26)	Number Analyzed	154 participants	150 participants
		1.9 (0.98)	2.5 (0.72)
Aspartate Aminotransferase (Week 52)	Number Analyzed	152 participants	147 participants
		0.5 (0.85)	2.0 (0.69)

19. Secondary Outcome

Title	Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		159	162
Mean (Standard Error); Unit of Measure: mg/dL
Creatinine (Week 26)	Number Analyzed	154 participants	150 participants
		-0.105 (0.0569)	-0.195 (0.0508)
Creatinine (Week 52)	Number Analyzed	152 participants	147 participants
		-0.200 (0.0416)	-0.244 (0.0627)
Urea Nitrogen (Week 26)	Number Analyzed	154 participants	150 participants
		-9.4 (1.16)	-11.0 (1.32)
Urea Nitrogen (Week 52)	Number Analyzed	152 participants	147 participants
		-7.8 (1.11)	-11.9 (1.32)
Protein (Week 26)	Number Analyzed	154 participants	150 participants
		50 (50)	220 (47)
Protein (Week 52)	Number Analyzed	152 participants	147 participants
		160 (48)	250 (41)
Cholesterol (Week 26)	Number Analyzed	154 participants	150 participants
		19.0 (4.27)	7.4 (3.99)
Cholesterol (Week 52)	Number Analyzed	152 participants	147 participants
		13.8 (4.28)	9.3 (4.05)
LDL Cholesterol (Week 26)	Number Analyzed	154 participants	152 participants
		22.7 (3.66)	12.0 (3.47)
LDL Cholesterol (Week 52)	Number Analyzed	159 participants	162 participants
		21.7 (3.48)	11.9 (3.41)
Bilirubin (Week 26)	Number Analyzed	154 participants	150 participants
		0.065 (0.0182)	0.078 (0.0250)
Bilirubin (Week 52)	Number Analyzed	152 participants	147 participants
		0.053 (0.0185)	0.057 (0.0201)

20. Secondary Outcome

Title	Change From Baseline in Vital Signs (1/5)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		154	154
Mean (Standard Error); Unit of Measure: mmHg
Systolic Blood Pressure (Week 26)	Number Analyzed	154 participants	154 participants
		-2.5 (1.70)	-2.6 (1.54)
Systolic Blood Pressure (Week 52)	Number Analyzed	151 participants	150 participants
		-2.4 (1.64)	-1.0 (1.60)
Diastolic Blood Pressure (Week 26)	Number Analyzed	154 participants	154 participants
		2.7 (0.98)	0.5 (0.92)
Diastolic Blood Pressure (Week 52)	Number Analyzed	151 participants	150 participants
		1.4 (1.01)	1.4 (1.00)

21. Secondary Outcome

Title	Change From Baseline in Vital Signs (2/5)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		152	154
Mean (Standard Error); Unit of Measure: beats/min
Pulse Rate (Week 26)	Number Analyzed	152 participants	154 participants
		2.2 (1.12)	0.9 (1.25)
Pulse Rate (Week 52)	Number Analyzed	151 participants	150 participants
		-1.3 (1.07)	-0.3 (1.21)

22. Secondary Outcome

Title	Change From Baseline in Vital Signs (3/5)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		152	151
Mean (Standard Error); Unit of Measure: degree Celsius
Temperature (Week 26)	Number Analyzed	152 participants	151 participants
		-0.03 (0.043)	-0.11 (0.046)
Temperature (Week 52)	Number Analyzed	148 participants	148 participants
		0.04 (0.044)	-0.11 (0.048)

23. Secondary Outcome

Title	Change From Baseline in Vital Signs (4/5)
Description	[Not Specified]
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		154	153
Mean (Standard Error); Unit of Measure: kilogram(s)
Weight (Week 26)	Number Analyzed	154 participants	153 participants
		3.33 (0.397)	1.93 (0.369)
Weight (Week 52)	Number Analyzed	151 participants	150 participants
		3.27 (0.477)	2.59 (0.487)

24. Secondary Outcome

Title	Change From Baseline in Vital Signs (5/5)
Description	BMI=Body Mass Index
Time Frame	Baseline, Week 26 and 52

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug. The number of subjects with data at baseline and the specified visit is reported.

Arm/Group Title		Prednisone Group	Avacopan Group
Arm/Group Description:		Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed		153	152
Mean (Standard Error); Unit of Measure: kilogram(s)/ square meter
BMI (Week 26)	Number Analyzed	153 participants	152 participants
		1.13 (0.135)	0.67 (0.132)
BMI (Week 52)	Number Analyzed	150 participants	149 participants
		1.12 (0.164)	0.94 (0.179)

25. Secondary Outcome

Title	Number of Subjects With Clinically Significant ECG Changes From Baseline
Description	Clinical significance was assessed by the individual reading of the ECGs ECG=Electrocardiogram
Time Frame	From day 1 throughout the study period (day 421/week 60)

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description:	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed	164	166
Measure Type: Count of Participants; Unit of Measure: Participants
	8 4.9%	12 7.2%

26. Secondary Outcome

Title	Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator
Description	AE=Adverse Event
Time Frame	From day 1 throughout the study period (day 421/week 60)

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description:	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed	164	166
Measure Type: Count of Participants; Unit of Measure: Participants
Relationship of avacopan/placebo to an AE	103 62.8%	100 60.2%
Relationship of glucocorticoid use to an AE	131 79.9%	107 64.5%
Relationship of cyclophosphamide IV use to an AE	30 18.3%	31 18.7%
Relationship of oral cyclophosphamide use to an AE	4 2.4%	8 4.8%
Relationship of rituximab use to an AE	61 37.2%	50 30.1%
Relationship of azathioprine use to an AE	35 21.3%	28 16.9%
Relationship of mycophenolate use to an AE	9 5.5%	6 3.6%

27. Secondary Outcome

Title	Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity
Description	WBC=White Blood Cell TEAE=Treatment-Emergent Adverse Event
Time Frame	From day 1 throughout the study period (day 421/week 60)

Outcome Measure Data

Analysis Population Description

Safety Population: The safety population included all subjects who were randomized and had received at least one dose of study drug.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description:	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed	164	166
Measure Type: Count of Participants; Unit of Measure: Participants
Any Treatment-Emergent Infection	124 75.6%	113 68.1%
Any Serious Treatment-Emergent Infection	25 15.2%	22 13.3%
Any Severe Treatment-Emergent Infection	10 6.1%	12 7.2%
Any Treatment-Emergent Infection Leading to Study Withdrawal	5 3.0%	4 2.4%
Any Treatment-Emergent Life-threatening Infection	2 1.2%	1 0.6%
Any Treatment-Emergent Infection Leading to Death	2 1.2%	1 0.6%
Any TEAE Associated with Hepatic Abnormalities	19 11.6%	22 13.3%
Any TEAE Associated with Low WBC Counts	39 23.8%	31 18.7%
Any TEAE Associated with hypersensitivity	70 42.7%	68 41.0%

28. Secondary Outcome

Title	Number of Subjects Experiencing a Relapse After Previously Achieving BVAS=0 During the Study
Description	BVAS=Birmingham Vasculitis Activity Score; A relapse was defined as occurrence of at least one major item in the BVAS, or three or more minor items in the BVAS, or one or two minor items in the BVAS recorded at two consecutive visits, after: having achieved remission at Week 26 (BVAS=0 and no glucocorticoids for ANCA-associated vasculitis within 4 weeks) or; having achieved BVAS=0 at any time during the treatment period The BVAS form is divided into 9 organ-based systems, with each section including symptoms/signs that are typical of that particular organ involvement in systemic vasculitis. The clinician only scores features believed to be due to active vasculitis. Completion of the form provides a numerical score, which ranges from 0 (best health) to 63 (worst health).
Time Frame	From day 1 throughout the study period (day 421/week 60)

Outcome Measure Data

Analysis Population Description

Intended-to-Treat (ITT) Population: The ITT Population included all subjects who were randomized in the study and who received at least one dose of blinded study drug.

Arm/Group Title	Prednisone Group	Avacopan Group
Arm/Group Description:	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone.	Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo.
Overall Number of Participants Analyzed	157	158
Measure Type: Count of Participants; Unit of Measure: Participants
	33 21.0%	16 10.1%

Adverse Events

Time Frame	From day 1 throughout the study period (day 421/week 60)
Adverse Event Reporting Description	An AE was considered treatment-emergent if the start date/time of the event was on or after the date/time of first dose of study drug through 56 days following the last dose administered during the randomized treatment period.
Arm/Group Title	Prednisone Group		Avacopan Group
Arm/Group Description	Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone. The safety population included all subjects who were randomized and had received at least one dose of study drug.		Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo. The safety population included all subjects who were randomized and had received at least one dose of study drug.
All-Cause Mortality
	Prednisone Group		Avacopan Group
	Affected / at Risk (%)		Affected / at Risk (%)
Total	4/164 (2.44%)		2/166 (1.20%)
Serious Adverse Events
	Prednisone Group		Avacopan Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/164 (45.12%)		70/166 (42.17%)
Blood and lymphatic system disorders
Agranulocytosis † 1	2/164 (1.22%)	2	1/166 (0.60%)	1
Lymphopenia † 1	3/164 (1.83%)	3	1/166 (0.60%)	1
Anaemia † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Neutropenia † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Thrombocytopenia † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Febrile neutropenia † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Bone marrow failure † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Bone marrow toxicity † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Granulomatous lymphadenitis † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Cardiac disorders
Angina pectoris † 1	0/164 (0.00%)	0	2/166 (1.20%)	2
Cardiac failure † 1	0/164 (0.00%)	0	2/166 (1.20%)	2
Acute myocardial infarction † 1	2/164 (1.22%)	2	1/166 (0.60%)	1
Atrioventricular block first degree † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Tachycardia † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Coronary artery disease † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Myocardial infarction † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Endocrine disorders
Adrenal insufficiency † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Eye disorders
Episcleritis † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Gastrointestinal disorders
Diarrhoea † 1	3/164 (1.83%)	3	0/166 (0.00%)	0
Large intestine polyp † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Vomiting † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Abdominal hernia † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Abdominal pain upper † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Gastrointestinal haemorrhage † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Inguinal hernia † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Intestinal obstruction † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Nausea † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Pancreatitis acute † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Vasculitis gastrointestinal † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Abdominal pain † 1	1/164 (0.61%)	2	0/166 (0.00%)	0
Duodenitis † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Enterocolitis † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Gastrointestinal disorder † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Rectal prolapse † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Small intestinal haemorrhage † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
General disorders
Pyrexia † 1	3/164 (1.83%)	3	2/166 (1.20%)	3
Oedema † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Oedema peripheral † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Asthenia † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Death † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Hernia † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Non-cardiac chest pain † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Systemic inflammatory response syndrome † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Hepatobiliary disorders
Hepatic function abnormal † 1	0/164 (0.00%)	0	2/166 (1.20%)	2
Cholelithiasis † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Drug-induced liver injury † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Hepatitis † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Hepatitis cholestatic † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Hepatocellular injury † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Immune system disorders
Drug hypersensitivity † 1	2/164 (1.22%)	3	2/166 (1.20%)	2
Anti-neutrophil cytoplasmic antibody positive vasculitis † 1	20/164 (12.20%)	25	12/166 (7.23%)	12
Infections and infestations
Pneumonia † 1	6/164 (3.66%)	6	8/166 (4.82%)	9
Urinary tract infection † 1	2/164 (1.22%)	2	3/166 (1.81%)	3
Device related infection † 1	0/164 (0.00%)	0	2/166 (1.20%)	2
Influenza † 1	1/164 (0.61%)	1	2/166 (1.20%)	2
Herpes zoster † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Infectious pleural effusion † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Pneumonia bacterial † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Respiratory syncytial virus infection † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Bronchitis † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Campylobacter gastroenteritis † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Hepatitis B † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Infective exacerbation of chronic obstructive airways disease † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Neutropenic sepsis † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Pneumonia haemophilus † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Post procedural sepsis † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Sepsis † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Urosepsis † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Aspergillus infection † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Bacteraemia † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Cryptococcosis † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Fungal infection † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Lower respiratory tract infection † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Meningitis † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Ophthalmic herpes simplex † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Parainfluenzae virus infection † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Pneumonia cytomegaloviral † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Respiratory tract infection viral † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Staphylococcal infection † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Subcutaneous abscess † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Injury, poisoning and procedural complications
Hip fracture † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Humerus fracture † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Infusion related reaction † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Multiple fractures † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Procedural pain † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Procedural vomiting † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Lumbar vertebral fracture † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Post procedural haematoma † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Investigations
Hepatic enzyme increased † 1	3/164 (1.83%)	3	2/166 (1.20%)	2
Blood creatinine increased † 1	2/164 (1.22%)	2	1/166 (0.60%)	1
Antineutrophil cytoplasmic antibody increased † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Aspartate aminotransferase increased † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Liver function test increased † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Alanine aminotransferase increased † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Lymphocyte count decreased † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Medical observation † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Transaminases increased † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Metabolism and nutrition disorders
Hyperglycaemia † 1	1/164 (0.61%)	1	2/166 (1.20%)	2
Dehydration † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Diabetic ketoacidosis † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Gout † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Hypoglycaemia † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Hyperkalaemia † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Hypokalaemia † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Osteonecrosis † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Polymyalgia rheumatica † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Chondrocalcinosis pyrophosphate † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Myalgia † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Basal cell carcinoma † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Pancreatic carcinoma metastatic † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Carcinoma in situ of skin † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Transitional cell carcinoma † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Nervous system disorders
Mononeuropathy multiplex † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Facial paralysis † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Cerebral infarction † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Hypoaesthesia † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Nervous system disorder † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Product Issues
Device malfunction † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Psychiatric disorders
Anxiety † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Depression † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Major depression † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Somatic symptom disorder † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	1/164 (0.61%)	2	3/166 (1.81%)	3
Glomerulonephritis † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
End stage renal disease † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Haematuria † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Renal impairment † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Chronic kidney disease † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary alveolar haemorrhage † 1	2/164 (1.22%)	2	1/166 (0.60%)	1
Epistaxis † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Pulmonary embolism † 1	3/164 (1.83%)	3	0/166 (0.00%)	0
Asthma † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Bronchopneumopathy † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Cough † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Dyspnoea exertional † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Interstitial lung disease † 1	1/164 (0.61%)	1	1/166 (0.60%)	1
Orthopnoea † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Pulmonary haemorrhage † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Laryngeal stenosis † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Nasal ulcer † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Pharyngeal ulceration † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Pneumomediastinum † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Pulmonary arterial hypertension † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Skin and subcutaneous tissue disorders
Angioedema † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Skin necrosis † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Purpura † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
Surgical and medical procedures
Arteriovenous fistula operation † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Vascular disorders
Granulomatosis with polyangiitis † 1	1/164 (0.61%)	1	5/166 (3.01%)	5
Microscopic polyangiitis † 1	2/164 (1.22%)	2	0/166 (0.00%)	0
Hypertension † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Thrombosis † 1	0/164 (0.00%)	0	1/166 (0.60%)	1
Deep vein thrombosis † 1	1/164 (0.61%)	1	0/166 (0.00%)	0
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Prednisone Group		Avacopan Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	161/164 (98.17%)		164/166 (98.80%)
Blood and lymphatic system disorders
Anaemia † 1	18/164 (10.98%)	19	13/166 (7.83%)	13
Leukopenia † 1	14/164 (8.54%)	20	12/166 (7.23%)	15
Increased tendency to bruise † 1	10/164 (6.10%)	11	7/166 (4.22%)	7
Lymphopenia † 1	18/164 (10.98%)	27	6/166 (3.61%)	7
Endocrine disorders
Cushingoid † 1	9/164 (5.49%)	9	3/166 (1.81%)	3
Gastrointestinal disorders
Nausea † 1	34/164 (20.73%)	46	39/166 (23.49%)	54
Diarrhoea † 1	24/164 (14.63%)	31	25/166 (15.06%)	33
Vomiting † 1	21/164 (12.80%)	27	25/166 (15.06%)	29
Abdominal pain upper † 1	10/164 (6.10%)	13	11/166 (6.63%)	12
Constipation † 1	11/164 (6.71%)	11	11/166 (6.63%)	11
Dyspepsia † 1	10/164 (6.10%)	12	5/166 (3.01%)	6
Rash † 1	13/164 (7.93%)	17	19/166 (11.45%)	26
Pruritus † 1	10/164 (6.10%)	11	10/166 (6.02%)	15
Alopecia † 1	12/164 (7.32%)	12	7/166 (4.22%)	7
General disorders
Oedema peripheral † 1	40/164 (24.39%)	56	35/166 (21.08%)	39
Fatigue † 1	15/164 (9.15%)	15	17/166 (10.24%)	19
Pyrexia † 1	19/164 (11.59%)	25	15/166 (9.04%)	18
Immune system disorders
Anti-neutrophil cytoplasmic antibody positive vasculitis † 1 [1]	34/164 (20.73%)	46	26/166 (15.66%)	30
Infections and infestations
Nasopharyngitis † 1	30/164 (18.29%)	46	25/166 (15.06%)	38
Upper respiratory tract infection † 1	24/164 (14.63%)	33	24/166 (14.46%)	28
Urinary tract infection † 1	23/164 (14.02%)	33	12/166 (7.23%)	19
Pneumonia † 1	11/164 (6.71%)	11	11/166 (6.63%)	12
Sinusitis † 1	12/164 (7.32%)	12	10/166 (6.02%)	10
Bronchitis † 1	10/164 (6.10%)	11	5/166 (3.01%)	7
Investigations
Weight increased † 1	17/164 (10.37%)	19	1/166 (0.60%)	1
Blood creatinine increased † 1	8/164 (4.88%)	10	10/166 (6.02%)	10
Metabolism and nutrition disorders
Hypercholesterolaemia † 1	20/164 (12.20%)	21	12/166 (7.23%)	13
Musculoskeletal and connective tissue disorders
Arthralgia † 1	36/164 (21.95%)	48	31/166 (18.67%)	42
Muscle spasms † 1	37/164 (22.56%)	47	18/166 (10.84%)	23
Back pain † 1	22/164 (13.41%)	22	16/166 (9.64%)	16
Myalgia † 1	22/164 (13.41%)	25	16/166 (9.64%)	17
Pain in extremity † 1	13/164 (7.93%)	13	13/166 (7.83%)	13
Nervous system disorders
Headache † 1	23/164 (14.02%)	30	34/166 (20.48%)	43
Dizziness † 1	10/164 (6.10%)	10	11/166 (6.63%)	14
Tremor † 1	10/164 (6.10%)	11	2/166 (1.20%)	2
Paraesthesia † 1	7/164 (4.27%)	8	9/166 (5.42%)	10
Psychiatric disorders
Insomnia † 1	25/164 (15.24%)	27	13/166 (7.83%)	13
Respiratory, thoracic and mediastinal disorders
Cough † 1	26/164 (15.85%)	29	26/166 (15.66%)	31
Epistaxis † 1	21/164 (12.80%)	30	14/166 (8.43%)	21
Dyspnoea † 1	11/164 (6.71%)	14	8/166 (4.82%)	11
Oropharyngeal pain † 1	12/164 (7.32%)	12	6/166 (3.61%)	7
Vascular disorders
Hypertension † 1	29/164 (17.68%)	31	30/166 (18.07%)	36
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment; [1] Worsening of vasculitis is reported as the Preferred Term of "anti-neutrophil cytoplasmic antibody-positive vasculitis".

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The PI shall provide Sponsor with an advance copy of any proposed publication or oral presentation at least 60 days prior to the planned date of submission or presentation and Sponsor shall have 60 days to review the proposed publication. Sponsor may request in writing, and the PI shall agree to, (a) the deletion of any Confidential Information, (b) any reasonable changes requested by Sponsor, or (c) a delay of such proposed submission for an additional period, not to exceed 90 days.

Results Point of Contact

• Name/Title: Clinical trial disclosure
• Organization: ChemoCentryx, Inc.
• Phone: 650.210.2900
• EMail: clinicaltrials@chemocentryx.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Harigai M, Kaname S, Tamura N, Dobashi H, Kubono S, Yoshida T. Efficacy and safety of avacopan in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: A subanalysis of a randomized Phase 3 study. Mod Rheumatol. 2023 Mar 2;33(2):338-345. doi: 10.1093/mr/roac037.

Soulsby WD. Journal Club Review of "Avacopan for the Treatment of ANCA-Associated Vasculitis". ACR Open Rheumatol. 2022 Jul;4(7):558-561. doi: 10.1002/acr2.11412. Epub 2022 Feb 15.

Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021 Feb 18;384(7):599-609. doi: 10.1056/NEJMoa2023386. Erratum In: N Engl J Med. 2024 Jan 25;390(4):388.

Merkel PA, Jayne DR, Wang C, Hillson J, Bekker P. Evaluation of the Safety and Efficacy of Avacopan, a C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Treated Concomitantly With Rituximab or Cyclophosphamide/Azathioprine: Protocol for a Randomized, Double-Blind, Active-Controlled, Phase 3 Trial. JMIR Res Protoc. 2020 Apr 7;9(4):e16664. doi: 10.2196/16664.

• Responsible Party: ChemoCentryx
• ClinicalTrials.gov Identifier: NCT02994927
• Other Study ID Numbers: CL010_168; ADVOCATE ( Other Identifier: ChemoCentryx )
• First Submitted: December 11, 2016
• First Posted: December 16, 2016
• Results First Submitted: May 19, 2022
• Results First Posted: September 9, 2022
• Last Update Posted: January 29, 2024