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Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX168 in Subjects with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis on Background Cyclophosphamide or Rituximab Treatment

Summary
EudraCT number	2011-001222-15
Trial protocol	BE GB CZ SE DE NL HU PL AT IE FR
Global end of trial date	18 Jan 2016

Results information
Results version number	v1(current)
This version publication date	12 Aug 2023
First version publication date	12 Aug 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CL002_168

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

ChemoCentryx, Inc.

Sponsor organisation address

850 Maude Avenue, Mountain View, California, United States, 94043

Public contact

Clinical trial disclosure, ChemoCentryx, Inc., +1 650-210-2900, clinicaltrials@chemocentryx.com

Scientific contact

Clinical trial disclosure, ChemoCentryx, Inc., +1 650-210-2900, clinicaltrials@chemocentryx.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

13 Apr 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

18 Jan 2016

Global end of trial reached?

Yes

Global end of trial date

18 Jan 2016

Was the trial ended prematurely?

Main objective of the trial

The primary safety objective of this study was to evaluate the safety and tolerability of CCX168 in subjects with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) on background cyclophosphamide or rituximab treatment. The primary efficacy objective was to evaluate the efficacy of CCX168 based on the Birmingham Vasculitis Activity Score (BVAS) version 3.

Protection of trial subjects

The study was conducted in accordance with the Declaration of Helsinki and with all applicable laws and regulations of the locale and country where the study was conducted, and in compliance with Good Clinical Practice Guidelines. Only subjects that met all the study inclusion and none of the exclusion criteria were entered in the study. The rationale of the study, procedural details, and investigational goals were explained to each subject, along with potential risks and benefits. Each subject was assured of his/her right to withdraw from the study at any time. An external data monitoring committee (DMC) reviewed safety data, including rescue glucocorticoid use over the course of the study, and advised the Sponsor regarding progression from each step to the next in the study.

Background therapy

Standard therapy for AAV includes cyclophosphamide or rituximab and oral glucocorticoids, tapered over a period of time. IV Cyclophosphamide was used throughout the study as background treatment. Subjects with prior rituximab treatment received rituximab throughout.

Evidence for comparator

Actual start date of recruitment

27 Sep 2011

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

3 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 4

Country: Number of subjects enrolled

Poland: 2

Country: Number of subjects enrolled

Sweden: 11

Country: Number of subjects enrolled

United Kingdom: 14

Country: Number of subjects enrolled

Austria: 2

Country: Number of subjects enrolled

Belgium: 9

Country: Number of subjects enrolled

Czech Republic: 5

Country: Number of subjects enrolled

France: 4

Country: Number of subjects enrolled

Germany: 13

Country: Number of subjects enrolled

Hungary: 3

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

The Screening period must not have exceeded 14 days prior to Study Day 1 (the first day of dosing).

Period 1 title

Period 1 (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer

Are arms mutually exclusive

Yes

Placebo BID Plus 60 mg Prednisone

Arm description

Placebo plus a full dose of oral glucocorticoids

Arm type

Placebo

Investigational medicinal product name

CCX168 Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Three placebo capsules in the morning and three placebo capsules in the evening. Duration: Daily for 84 consecutive days.

Investigational medicinal product name

Prednisone

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Prednisone dosage equivalent to 60 mg orally per day if body weight ≥ 55 kg, or equivalent to 45 mg orally per day if body weight <55 kg. Duration: Starting Day 1 with a tapered dose per protocol-specified schedule.

CCX168 30 mg BID Plus 20 mg Prednisone

Arm description

30 mg CCX168, plus two-thirds reduced dose of oral glucocorticoids.

Arm type

Experimental

Investigational medicinal product name

Prednisone

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Prednisone dosage: 20 mg orally per day if body weight >55 kg, or 15 mg orally per day if body weight <55 kg Duration: Starting Day 1 with a tapered dose per protocol-specified schedule.

Investigational medicinal product name

CCX168

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Three 10 mg CCX168 capsules in the morning and three 10 mg capsules in the evening, approximately 12 hours following the morning dose. Duration: Daily for 84 consecutive days.

Investigational medicinal product name

Prednisone-matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Dosage: equivalent to 40 mg orally per day is body weight > 55kg or equivalent to 30 mg orally per day if body weight <55 kg. Duration: Starting Day 1 with a tapered dose per protocol-specified schedule.

CCX168 30 mg BID Without Prednisone

Arm description

30 mg of CCX168

Arm type

Experimental

Investigational medicinal product name

CCX168

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Three 10 mg CCX168 capsules in the morning and three 10 mg capsules in the evening, approximately 12 hours following the morning dose. Duration: Daily for 84 consecutive days.

Investigational medicinal product name

Prednisone-matching placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Equivalent to 60 mg orally per day if body weight >55 kg, or equivalent to 45 mg orally per day if body weight <55 kg. Duration: Starting Day 1 with a tapered dose per protocol-specified schedule.

Number of subjects in period 1	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Started	23	22	22
Completed	18	19	18
Not completed	5	3	4
Consent withdrawn by subject	3	-	1
Physician decision	-	-	1
Adverse event, non-fatal	2	2	2
Rescue medication	-	1	-

Baseline characteristics

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Reporting group title

Placebo BID Plus 60 mg Prednisone

Reporting group description

Placebo plus a full dose of oral glucocorticoids

Reporting group title

CCX168 30 mg BID Plus 20 mg Prednisone

Reporting group description

30 mg CCX168, plus two-thirds reduced dose of oral glucocorticoids.

Reporting group title

CCX168 30 mg BID Without Prednisone

Reporting group description

30 mg of CCX168

Reporting group values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone	Total
Number of subjects	23	22	22	67
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	13	16	15	44
From 65-84 years	10	6	7	23
85 years and over	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	59.1 ± 14.0	57.0 ± 14.2	57.4 ± 14.0	-
Gender categorical
Units: Subjects
Female	6	8	6	20
Male	17	14	16	47
Ethnicity (NIH/ OMB)
Units: Subjects
Not Hispanic or Latino	23	22	22	67
Race (NIH/OMB)
Units: Subjects
White	23	22	22	67
Smoking Status
Units: Subjects
Current Smoker	3	2	4	9
Past Smoker	11	6	8	25
Never Smoked	9	14	10	33
ANCA disease status
ANCA = anti-neutrophil cytoplasmic antibody
Units: Subjects
Newly diagnosed	18	15	16	49
Relapsed	5	7	6	18
Background treatment
Units: Subjects
Rituximab	3	5	5	13
Cyclophosphamide	20	17	17	54
Type of AAV
AAV= ANCA-associated vasculitis; GPA = granulomatosis with polyangitis (Wegener's)
Units: Subjects
GPA	10	11	12	33
Microscopic polyangiitis	10	9	9	28
Renal-limited vasculitis	2	2	1	5
Unknown	1	0	0	1
ANCA status categorical
ANCA = anti-neutrophil cytoplasmic antibody; MPO=myeloperoxidase; PR3=proteinase 3
Units: Subjects
Anti-MPO positive	10	12	13	35
Anti-PR3 positive	11	10	8	29
Both anti-MPO positive and anti- PR3 positive	1	0	0	1
ANCA equivocal	0	0	1	1
ANCA negative	1	0	0	1
Urinary red blood cells
Units of measure: per hpf; HPF= high power field
Units: Subjects
30-49	6	4	2	12
50-75	5	4	3	12
>75	3	5	3	11
No data available	9	9	14	32
BMI
BMI = Body Mass Index 21 Subjects for CCX168 30 mg BID Plus 20 mg Prednisone and CCX168 30 mg BID Without Prednisone arms.
Units: kg/m²
arithmetic mean (standard deviation)	27.3 ± 7.09	24.9 ± 4.05	26.5 ± 4.66	-
BVAS total score
BVAS = Birmingham Vasculitis Activity Score
Units: units on a scale
arithmetic mean (standard deviation)	13.2 ± 5.80	14.3 ± 5.98	13.8 ± 6.38	-
VDI score
VDI=Vasculitis Damage Index
Units: units on a scale
arithmetic mean (standard deviation)	1.2 ± 1.35	0.9 ± 1.46	0.5 ± 1.19	-
Glomerular filtration rate (MDRD)
MDRD=Modification of Diet in Renal Disease 22 participants for Placebo BID Plus 60 mg Prednisone arm.
Units: mL/min/1.73 m²
arithmetic mean (standard deviation)	47.6 ± 15.08	52.5 ± 26.70	54.7 ± 19.64	-
Albumin: creatinine ratio
21 participants for CCX168 30 mg BID Without Prednisone arm. 22 participants for Placebo BID Plus 60 mg Prednisone arm.
Units: mg/g
geometric mean (full range (min-max))	353.9 (28 to 5962)	278.6 (24 to 2459)	283.4 (25 to 3051)	-
Urinary MCP-1: creatinine ratio
MCP-1 = Monocyte chemoattractant protein 1
Units: pg/mg creatinine
geometric mean (full range (min-max))	825.9 (171.2 to 2549.2)	1266.1 (360.8 to 7290.5)	846.4 (107.2 to 6075.7)	-
ANCA- associated vasculitis disease duration at screening
ANCA = anti-neutrophil cytoplasmic antibody 21 participants for CCX168 30 mg BID Without Prednisone arm
Units: months
median (full range (min-max))	0.0 (0 to 162)	0.0 (0 to 61)	1.0 (0 to 108)	-

End points

Top of page

Reporting group title

Placebo BID Plus 60 mg Prednisone

Reporting group description

Placebo plus a full dose of oral glucocorticoids

Reporting group title

CCX168 30 mg BID Plus 20 mg Prednisone

Reporting group description

30 mg CCX168, plus two-thirds reduced dose of oral glucocorticoids.

Reporting group title

CCX168 30 mg BID Without Prednisone

Reporting group description

30 mg of CCX168

Primary: Proportion of subjects achieving disease response at Day 85

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End point title

Proportion of subjects achieving disease response at Day 85

End point description

Disease response is defined as BVAS percentage reduction from baseline of at least 50% plus no worsening in any body system component.

End point type

Primary

End point timeframe

Baseline to day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	20	22	21
Units: Participants	14	19	17

Analysis of Clinical Response Based on BVAS Score

Statistical analysis description

BVAS = Birmingham Vasculitis Activity Score; ITT = Intent-to-Treat The proportion of subjects with a clinical response, defined as BVAS decrease from baseline of at least 50%, and no worsening in any body system component, after 12 weeks of treatment (at Day 85) for the ITT Population.

Comparison groups

Placebo BID Plus 60 mg Prednisone v CCX168 30 mg BID Plus 20 mg Prednisone

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

P-value

= 0.0019

Method

Noninferiority test for risk difference

Confidence interval

level

90%

sides

2-sided

lower limit

-4.3

upper limit

37.1

Notes
[1] - Based on a non-inferiority margin of 20.0%.

Analysis of Clinical Response Based on BVAS Score

Statistical analysis description

Comparison groups

Placebo BID Plus 60 mg Prednisone v CCX168 30 mg BID Without Prednisone

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

P-value

= 0.0102

Method

Noninferiority test for risk difference

Parameter type

Noninferiority test for risk difference

Confidence interval

level

90%

sides

2-sided

lower limit

-11

upper limit

32.9

Notes
[2] - Based on a non-inferiority margin of 20.0%.

Secondary: Proportion of Patients Achieving Renal Response at Day 85

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End point title

Proportion of Patients Achieving Renal Response at Day 85

End point description

Renal response, assessed in patients with hematuria and albuminuria at baseline, and defined as an improvement in renal parameters, i.e., an increase from baseline to Day 85 in eGFR (Estimated glomerular filtration rate), MDRD (Modification of Diet in Renal Disease), serum creatinine equation, a decrease from baseline to Day 85 in haematuria (central laboratory microscopic count of urinary red blood cells), decrease from baseline to Day 85 in albuminuria count (first morning UACR (urinary albumin:creatinine ratio).

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	20	18	18
Units: Participants	8	10	6

No statistical analyses for this end point

Secondary: Proportion of Subjects Achieving Disease Remission at Day 85

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End point title

Proportion of Subjects Achieving Disease Remission at Day 85

End point description

Disease remission is defined as BVAS (Birmingham Vasculitis Activity Score) of 0 or 1 plus no worsening in eGFR (Estimated glomerular filtration rate) and urinary RBC (Red Blood cell) count <10/high power field (hpf)

End point type

Secondary

End point timeframe

Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	20	22	21
Units: Participants	7	6	4

No statistical analyses for this end point

Secondary: Percent Change From Baseline to Day 85 in BVAS

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End point title

Percent Change From Baseline to Day 85 in BVAS

End point description

Percent change in Birmingham Vasculitis Index Score (BVAS) at week 12, higher percentage change indicates worse outcome 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). A negative percentage change indicated improvement in health.

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	19	20	19
Units: percentage change from baseline
arithmetic mean (standard deviation)	-56.45 ± 62.100	-79.05 ± 23.005	-73.01 ± 29.464

No statistical analyses for this end point

Secondary: Change From Baseline to Day 85 in eGFR

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End point title

Change From Baseline to Day 85 in eGFR

End point description

eGFR (Estimated glomerular filtration rate) based on the MDRD (Modification of Diet in Renal Disease) formula using serum creatinine

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	20	22	21
Units: Change in eGFR ml/min/1.73 m²
arithmetic mean (standard deviation)	5.55 ± 10.211	6.00 ± 10.469	0.79 ± 9.549

No statistical analyses for this end point

Secondary: Percent Change From Baseline to Day 85 in eGFR

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End point title

Percent Change From Baseline to Day 85 in eGFR

End point description

eGFR (Estimated glomerular filtration rate) based on the MDRD (Modification of Diet in Renal Disease) formula using serum creatinine

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	20	21	19
Units: Percentage change
arithmetic mean (standard deviation)	15.36 ± 23.685	19.91 ± 23.034	0.92 ± 20.562

No statistical analyses for this end point

Secondary: Proportion of Subjects Achieving Urinary RBC Count <=5/Hpf at Any Time During the 84-day Treatment Period

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End point title

Proportion of Subjects Achieving Urinary RBC Count <=5/Hpf at Any Time During the 84-day Treatment Period

End point description

In subjects with baseline hematuria >5 RBCs/hpf (Red Blood Cell/High Power Field)

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	19	18	18
Units: Participants	15	11	11

No statistical analyses for this end point

Secondary: Time to First Achieving Urinary RBC Count <=5/Hpf at Any Point During the 84-day Treatment Period

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End point title

Time to First Achieving Urinary RBC Count <=5/Hpf at Any Point During the 84-day Treatment Period

End point description

In subjects with baseline hematuria <=5 RBCs/hpf (Red Blood Cell/High Power Field) *Most of the 75th quantiles were non-estimable due to small sample size. Therefore, the inter-quartile range (IQR) is non-estimable. Days of first occurrence to urinary RBC <5=/HPF is as follows: Placebo: median 69.0, 25th percentile 28.0, 75th percentile 84.0 CCX168 30 mg BID plus 20 mg prednisone: median 69.0, 25th percentile 28.0, 75th percentile non-estimable CCX168 30 mg BID without prednisone: median 42.0, 25th percentile 7.0, 75th percentile non-estimable

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	0 ^[3]	0 ^[4]	0 ^[5]
Units: Participants

Notes
[3] - No data displayed because Outcome Measure has zero total participants analysed.
[4] - No data displayed because Outcome Measure has zero total participants analysed.
[5] - No data displayed because Outcome Measure has zero total participants analysed.

No statistical analyses for this end point

Secondary: Proportion of Subjects Achieving Urinary RBC Count <30/Hpf at Any Time During the 84-day Treatment Period

Top of page

End point title

Proportion of Subjects Achieving Urinary RBC Count <30/Hpf at Any Time During the 84-day Treatment Period

End point description

In subjects with baseline hematuria >=30 RBCs/hpf,(Red Blood Cell/High Power Field)

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	12	13	7
Units: Participants	11	13	5

No statistical analyses for this end point

Secondary: Time to First Achieving Urinary RBC Count <=30/Hpf at Any Point During the 84-day Treatment Period

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End point title

Time to First Achieving Urinary RBC Count <=30/Hpf at Any Point During the 84-day Treatment Period

End point description

In subjects with baseline hematuria <=30 RBCs/hpf (Red Blood Cell/High Power Field) Most of the 75th quantiles were non-estimable due to small sample size. Therefore, the inter-quartile range (IQR) is non estimable. Days of first occurrence to urinary RBC <30/HPF is as follows: Placebo: median 10.5, 25th percentile 1.0, 75th percentile 35.0 CCX168 30 mg BID plus 20 mg prednisone: median 21.0, 25th percentile 7.0, 75th percentile 42.0 CCX168 30 mg BID without prednisone: median 42.0, 25th percentile 1.0, 75th percentile non estimable

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	0 ^[6]	0 ^[7]	0 ^[8]
Units: Participants

Notes
[6] - No data displayed because Outcome Measure has zero total participants analysed.
[7] - No data displayed because Outcome Measure has zero total participants analysed.
[8] - No data displayed because Outcome Measure has zero total participants analysed.

No statistical analyses for this end point

Secondary: Percent Change From Baseline to Day 85 in Urinary RBC Count

Top of page

End point title

Percent Change From Baseline to Day 85 in Urinary RBC Count

End point description

In subjects with hematuria at baseline, RBC (Red Blood Cell)

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	20	19	17
Units: Percentage change
arithmetic mean (full range (min-max))	-72.37 (-99.4 to 66.7)	1.63 (-99.7 to 1150.0)	-21.26 (-99.4 to 368.8)

No statistical analyses for this end point

Secondary: Percent Change From Baseline to Day 85 in UACR

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End point title

Percent Change From Baseline to Day 85 in UACR

End point description

In subjects with albuminuria at baseline UACR (urinary albumin:creatinine ratio)

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	20	20	18
Units: Percentage change
arithmetic mean (full range (min-max))	-3.10 (-71.1 to 131.7)	-34.18 (-89.2 to 173.1)	-15.21 (-85.9 to 360.3)

No statistical analyses for this end point

Secondary: Percent Change From Baseline to Day 85 in Urinary MCP-1:Creatinine Ratio

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End point title

Percent Change From Baseline to Day 85 in Urinary MCP-1:Creatinine Ratio

End point description

Urinary Monocyte Chemoattractant Protein-1 (MCP-1):creatinine ratio

End point type

Secondary

End point timeframe

Baseline Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	20	20	19
Units: percentage change from baseline
arithmetic mean (full range (min-max))	-37.57 (-72.7 to 41.0)	-59.29 (-93.6 to 60.1)	-39.44 (-90.7 to 59.0)

No statistical analyses for this end point

Secondary: Proportion of Subjects Requiring Rescue IV or Oral Glucocorticoid Treatment

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End point title

Proportion of Subjects Requiring Rescue IV or Oral Glucocorticoid Treatment

End point description

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	11	9	8
Units: Participants	0	3	1

No statistical analyses for this end point

Secondary: Change From Baseline to Day 85 in the Vasculitis Damage Index

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End point title

Change From Baseline to Day 85 in the Vasculitis Damage Index

End point 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).

End point type

Secondary

End point timeframe

Baseline to Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	20	20	19
Units: score on a scale
arithmetic mean (standard deviation)	0.7 ± 0.81	0.3 ± 0.57	0.2 ± 0.54

No statistical analyses for this end point

Secondary: Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the SF-36 v2

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End point title

Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the SF-36 v2

End point description

SF-36v2: Medical Outcomes Survey Short Form-36 version 2. SF-36v2 measures each of the following eight health domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Scores on each item are summed and averaged. The SF-36v2 component domain scores range from 0 (worst health) to 100 (best health). Number of subjects with data at baseline and the specified visit are specified. *14 subjects for SF-36 Role Physical (Day 29), SF-36 Social Functioning (Day 29), SF-36 Reported Health Transition (Day 29), SF-36 Physical Functioning (Day 29) and SF-36 Role-Emotional (Day 29). 12 Subjects for SF-36 Physical Component Summary (Day 29) and SF-36 Mental Health Summary (Day 29). 13 Subjects for the rest of the categories.

End point type

Secondary

End point timeframe

Baseline, Day 29 & Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	10 ^[9]	14 ^[10]	8 ^[11]
Units: Change from baseline score on a scale
arithmetic mean (standard error)
SF-36 Role Physical (Day 29)	9.7 ± 10.73	13.8 ± 7.61	8.6 ± 6.02
SF-36 Role Physical (Day 85)	13.7 ± 11.06	36.1 ± 9.28	16.1 ± 9.24
SF-36 Bodily pain (Day 29)	3.1 ± 10.63	17.3 ± 8.42	5.1 ± 16.75
SF-36 Bodily pain (Day 85)	12.8 ± 7.36	21.7 ± 9.54	14.0 ± 9.30
SF-36 General Health Perceptions (Day 29)	2.5 ± 8.26	3.7 ± 4.60	-13.7 ± 10.21
SF-36 General Health Perceptions (Day 85)	5.7 ± 6.05	2.3 ± 3.93	-1.5 ± 5.51
SF-36 Vitality (Day 29)	7.63 ± 6.403	12.98 ± 7.400	-0.78 ± 3.630
SF-36 Vitality (Day 85)	4.36 ± 6.457	22.28 ± 7.541	10.71 ± 5.893
SF-36 Social Functioning (Day 29)	-2.8 ± 11.74	24.1 ± 6.07	-7.8 ± 6.22
SF-36 Social Functioning (Day 85)	6.3 ± 9.90	35.6 ± 6.91	5.4 ± 3.72
SF-36 Mental Health (Day 29)	1.7 ± 2.20	10.8 ± 3.71	-8.1 ± 6.88
SF-36 Mental Health (Day 85)	-1.0 ± 4.88	16.5 ± 4.65	2.1 ± 4.86
SF-36 Reported Health Transition (Day 29)	0.2 ± 0.22	-0.6 ± 0.41	0.3 ± 0.31
SF-36 Reported Health Transition (Day 85)	0.0 ± 0.37	-1.2 ± 0.48	-0.4 ± 0.48
SF-36 Physical Functioning (Day 29)	5.0 ± 6.18	7.0 ± 6.90	8.2 ± 11.46
SF-36 Physical Functioning (Day 85)	5.2 ± 7.00	13.5 ± 7.73	11.4 ± 8.43
SF-36 Role-Emotional (Day 29)	1.9 ± 9.08	20.3 ± 8.04	-1.1 ± 8.97
SF-36 Role-Emotional (Day 85)	0.0 ± 10.98	21.8 ± 9.42	10.7 ± 8.27
SF-36 Physical Component Summary (Day 29)	2.693 ± 3.436	4.074 ± 2.601	2.826 ± 4.526
SF-36 Physical Component Summary (Day 85)	5.383 ± 2.694	6.744 ± 3.132	4.863 ± 2.415
SF-36 Mental Health Summary (Day 29)	0.303 ± 3.120	10.855 ± 3.244	-4.760 ± 3.266
SF-36 Mental Health Summary (Day 85)	-0.766 ± 3.888	11.779 ± 3.428	2.197 ± 1.066

Notes
[9] - 9 Subjects for all categories for Day 29 10 Subjects for all categories for Day 85
[10] - *see description for more details
[11] - 8 Subjects for all categories for Day 29 7 Subjects for all categories for Day 85

No statistical analyses for this end point

Secondary: Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the EQ-5D-5L

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End point title

Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the EQ-5D-5L

End point description

EQ-5D-5L: EuroQuality of Life-5 Domains-5 Levels. The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The answers given can be converted into an Index Score ranging from 0 for death to 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst imaginable health) to 100 (the best imaginable health). Number of subjects with data at baseline and the specified visit are specified.

End point type

Secondary

End point timeframe

Baseline, Day 29 and Day 85

End point values	Placebo BID Plus 60 mg Prednisone	CCX168 30 mg BID Plus 20 mg Prednisone	CCX168 30 mg BID Without Prednisone
Number of subjects analysed	9	13	9 ^[12]
Units: Change from baseline score on a scale
arithmetic mean (standard deviation)
VAS Score (Day 29)	-2.4 ± 10.61	6.5 ± 17.96	4.5 ± 12.62
VAS Score (Day 85)	-3.3 ± 13.23	11.8 ± 17.61	4.0 ± 4.69
Index Score (Day 29)	-0.044 ± 0.1597	0.034 ± 0.1111	-0.057 ± 0.0952
Index Score (Day 85)	-0.043 ± 0.1718	0.067 ± 0.1314	-0.047 ± 0.0721

Notes
[12] - 8 Subjects for Vas Score and Index Score (Day 29) 7 Subjects for Vas Score and Index Score (Day 85)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

168 Day Treatment Period

Adverse event reporting additional description

An adverse event is considered treatment-emergent if the start date of the event is on or after administration of the first dose of study medication

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.0

Reporting group title

CCX168 + No Prednisone

Reporting group description

The Safety Population included all subjects who were randomized and had received at least 1 dose of study medication.

Reporting group title

Placebo + Full Dose Prednisone

Reporting group description

The Safety Population included all subjects who were randomized and had received at least 1 dose of study medication.

Reporting group title

CCX168 + Low Dose Prednisone

Reporting group description

The Safety Population included all subjects who were randomized and had received at least 1 dose of study medication.

Serious adverse events	CCX168 + No Prednisone	Placebo + Full Dose Prednisone	CCX168 + Low Dose Prednisone
Total subjects affected by serious adverse events
subjects affected / exposed	10 / 22 (45.45%)	5 / 23 (21.74%)	8 / 22 (36.36%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Investigations
Hepatic enzyme increased
subjects affected / exposed	1 / 22 (4.55%)	0 / 23 (0.00%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatic enzymes increased
subjects affected / exposed	1 / 22 (4.55%)	0 / 23 (0.00%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
C-reactive protein increased
subjects affected / exposed	1 / 22 (4.55%)	0 / 23 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Lumbar vertebral fracture
subjects affected / exposed	0 / 22 (0.00%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Vasculitis
subjects affected / exposed	2 / 22 (9.09%)	1 / 23 (4.35%)	2 / 22 (9.09%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Microscopic polyangiitis
subjects affected / exposed	1 / 22 (4.55%)	0 / 23 (0.00%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 22 (0.00%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 22 (0.00%)	0 / 23 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Ocular Hyperaemia
subjects affected / exposed	0 / 22 (0.00%)	0 / 23 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pleurisy
subjects affected / exposed	0 / 22 (0.00%)	0 / 23 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 22 (4.55%)	0 / 23 (0.00%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 22 (0.00%)	0 / 23 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	1 / 22 (4.55%)	0 / 23 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal vasculitis
subjects affected / exposed	1 / 22 (4.55%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
subjects affected / exposed	0 / 22 (0.00%)	0 / 23 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 22 (0.00%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Respiratory tract infection
subjects affected / exposed	2 / 22 (9.09%)	0 / 23 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	1 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile infection
subjects affected / exposed	0 / 22 (0.00%)	0 / 23 (0.00%)	1 / 22 (4.55%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 22 (0.00%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lung infection
subjects affected / exposed	1 / 22 (4.55%)	0 / 23 (0.00%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 22 (0.00%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	CCX168 + No Prednisone	Placebo + Full Dose Prednisone	CCX168 + Low Dose Prednisone
Total subjects affected by non serious adverse events
subjects affected / exposed	21 / 22 (95.45%)	21 / 23 (91.30%)	21 / 22 (95.45%)
Vascular disorders
Hypertension
subjects affected / exposed	6 / 22 (27.27%)	2 / 23 (8.70%)	2 / 22 (9.09%)
occurrences all number	6	2	2
Deep vein thrombosis
subjects affected / exposed	0 / 22 (0.00%)	2 / 23 (8.70%)	1 / 22 (4.55%)
occurrences all number	0	2	1
Vasculitis
subjects affected / exposed	2 / 22 (9.09%)	2 / 23 (8.70%)	3 / 22 (13.64%)
occurrences all number	2	2	3
General disorders and administration site conditions
Chills
subjects affected / exposed	3 / 22 (13.64%)	0 / 23 (0.00%)	1 / 22 (4.55%)
occurrences all number	3	0	1
Fatigue
subjects affected / exposed	4 / 22 (18.18%)	3 / 23 (13.04%)	0 / 22 (0.00%)
occurrences all number	4	3	0
Oedema peripheral
subjects affected / exposed	2 / 22 (9.09%)	5 / 23 (21.74%)	1 / 22 (4.55%)
occurrences all number	2	5	1
Pyrexia
subjects affected / exposed	2 / 22 (9.09%)	3 / 23 (13.04%)	0 / 22 (0.00%)
occurrences all number	2	3	0
Asthenia
subjects affected / exposed	2 / 22 (9.09%)	0 / 23 (0.00%)	0 / 22 (0.00%)
occurrences all number	2	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 22 (9.09%)	2 / 23 (8.70%)	3 / 22 (13.64%)
occurrences all number	2	2	3
Epistaxis
subjects affected / exposed	3 / 22 (13.64%)	2 / 23 (8.70%)	4 / 22 (18.18%)
occurrences all number	3	2	4
Dyspnoea exertional
subjects affected / exposed	0 / 22 (0.00%)	2 / 23 (8.70%)	2 / 22 (9.09%)
occurrences all number	0	2	2
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 22 (0.00%)	3 / 23 (13.04%)	0 / 22 (0.00%)
occurrences all number	0	3	0
Insomnia
subjects affected / exposed	1 / 22 (4.55%)	1 / 23 (4.35%)	2 / 22 (9.09%)
occurrences all number	1	1	2
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 22 (9.09%)	1 / 23 (4.35%)	1 / 22 (4.55%)
occurrences all number	2	1	1
Blood creatinine increased
subjects affected / exposed	1 / 22 (4.55%)	2 / 23 (8.70%)	1 / 22 (4.55%)
occurrences all number	1	2	1
Breath sounds abnormal
subjects affected / exposed	0 / 22 (0.00%)	2 / 23 (8.70%)	1 / 22 (4.55%)
occurrences all number	0	2	1
Nervous system disorders
Headache
subjects affected / exposed	4 / 22 (18.18%)	3 / 23 (13.04%)	3 / 22 (13.64%)
occurrences all number	4	3	3
Paraesthesia
subjects affected / exposed	1 / 22 (4.55%)	3 / 23 (13.04%)	3 / 22 (13.64%)
occurrences all number	1	3	3
Dizziness
subjects affected / exposed	0 / 22 (0.00%)	2 / 23 (8.70%)	0 / 22 (0.00%)
occurrences all number	0	2	0
Tremor
subjects affected / exposed	0 / 22 (0.00%)	2 / 23 (8.70%)	0 / 22 (0.00%)
occurrences all number	0	2	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 22 (0.00%)	2 / 23 (8.70%)	1 / 22 (4.55%)
occurrences all number	0	2	1
Gastrointestinal disorders
Nausea
subjects affected / exposed	5 / 22 (22.73%)	6 / 23 (26.09%)	7 / 22 (31.82%)
occurrences all number	5	6	7
Vomiting
subjects affected / exposed	5 / 22 (22.73%)	1 / 23 (4.35%)	4 / 22 (18.18%)
occurrences all number	5	1	4
Constipation
subjects affected / exposed	2 / 22 (9.09%)	3 / 23 (13.04%)	5 / 22 (22.73%)
occurrences all number	2	3	5
Diarrhoea
subjects affected / exposed	3 / 22 (13.64%)	3 / 23 (13.04%)	3 / 22 (13.64%)
occurrences all number	3	3	3
Abdominal pain upper
subjects affected / exposed	2 / 22 (9.09%)	2 / 23 (8.70%)	1 / 22 (4.55%)
occurrences all number	2	2	1
Abdominal discomfort
subjects affected / exposed	0 / 22 (0.00%)	1 / 23 (4.35%)	2 / 22 (9.09%)
occurrences all number	0	1	4
Abdominal pain
subjects affected / exposed	0 / 22 (0.00%)	2 / 23 (8.70%)	0 / 22 (0.00%)
occurrences all number	0	2	0
Dyspepsia
subjects affected / exposed	1 / 22 (4.55%)	2 / 23 (8.70%)	2 / 22 (9.09%)
occurrences all number	1	2	2
Skin and subcutaneous tissue disorders
Purpura
subjects affected / exposed	3 / 22 (13.64%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences all number	3	1	0
Rash
subjects affected / exposed	3 / 22 (13.64%)	1 / 23 (4.35%)	1 / 22 (4.55%)
occurrences all number	3	1	1
Hyperhidrosis
subjects affected / exposed	1 / 22 (4.55%)	2 / 23 (8.70%)	0 / 22 (0.00%)
occurrences all number	1	2	0
Erythema
subjects affected / exposed	0 / 22 (0.00%)	2 / 23 (8.70%)	0 / 22 (0.00%)
occurrences all number	0	2	0
Renal and urinary disorders
Nocturia
subjects affected / exposed	0 / 22 (0.00%)	1 / 23 (4.35%)	3 / 22 (13.64%)
occurrences all number	0	1	3
Renal vasculitis
subjects affected / exposed	1 / 22 (4.55%)	2 / 23 (8.70%)	1 / 22 (4.55%)
occurrences all number	1	2	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	5 / 22 (22.73%)	2 / 23 (8.70%)	3 / 22 (13.64%)
occurrences all number	5	2	3
Muscle spasms
subjects affected / exposed	1 / 22 (4.55%)	5 / 23 (21.74%)	1 / 22 (4.55%)
occurrences all number	1	5	1
Neck pain
subjects affected / exposed	2 / 22 (9.09%)	0 / 23 (0.00%)	0 / 22 (0.00%)
occurrences all number	2	0	0
Back pain
subjects affected / exposed	1 / 22 (4.55%)	5 / 23 (21.74%)	1 / 22 (4.55%)
occurrences all number	1	5	1
Pain in extremity
subjects affected / exposed	1 / 22 (4.55%)	0 / 23 (0.00%)	2 / 22 (9.09%)
occurrences all number	1	0	2
Musculoskeletal chest pain
subjects affected / exposed	1 / 22 (4.55%)	0 / 23 (0.00%)	2 / 22 (9.09%)
occurrences all number	1	0	2
Infections and infestations
Nasopharyngitis
subjects affected / exposed	5 / 22 (22.73%)	5 / 23 (21.74%)	4 / 22 (18.18%)
occurrences all number	5	5	4
Rhinitis
subjects affected / exposed	2 / 22 (9.09%)	1 / 23 (4.35%)	2 / 22 (9.09%)
occurrences all number	2	1	2
Viral upper respiratory tract infection
subjects affected / exposed	1 / 22 (4.55%)	0 / 23 (0.00%)	2 / 22 (9.09%)
occurrences all number	1	0	2
Bronchitis
subjects affected / exposed	2 / 22 (9.09%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences all number	2	1	0
Oral herpes
subjects affected / exposed	3 / 22 (13.64%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences all number	3	1	0
Respiratory tract infection
subjects affected / exposed	2 / 22 (9.09%)	0 / 23 (0.00%)	2 / 22 (9.09%)
occurrences all number	2	0	2
Upper respiratory tract infection
subjects affected / exposed	0 / 22 (0.00%)	0 / 23 (0.00%)	2 / 22 (9.09%)
occurrences all number	0	0	2
Viral infection
subjects affected / exposed	0 / 22 (0.00%)	2 / 23 (8.70%)	0 / 22 (0.00%)
occurrences all number	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 22 (0.00%)	0 / 23 (0.00%)	3 / 22 (13.64%)
occurrences all number	0	0	3
Hypercholesterolaemia
subjects affected / exposed	2 / 22 (9.09%)	1 / 23 (4.35%)	0 / 22 (0.00%)
occurrences all number	2	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

23 Apr 2012

Changes made to the protocol included the following: - Laboratory results from the local laboratories obtained within 72 hours of Screening were acceptable in order to avoid unnecessary blood draws - A number of inclusion and exclusion criteria were clarified based on questions from the Investigators - Subjects were permitted to take immunosuppressive treatment, including azathioprine, mycophenolate mofetil, or methotrexate during the 84-day follow-up period, but not during the 84-day treatment period (the rationale was that it was consistent with standard practice at certain study centers) - Data from subjects receiving placebo in all 3 steps could have been combined, irrespective of the study step - A statement was included regarding subject care at the end of the study - A statement was included regarding review of substantial protocol Amendments by the Competent Authorities according to European Directive (CT-1)(2010/C 82/01) - A statement was included regarding archival of clinical study related documents for a period of 10 years according to European Union regulations (LVFS 2003:3) - A statement was included regarding implementation of the study according to Good Clinical Practice as per CPMP/ICH/135/95.

14 Mar 2013

The main changes that Amendment 2.0 made to the protocol included the following: - The inclusion criteria for the protocol were amended to change the upper age limit from 75 years to 80 years, and the lower limit of eGFR from 30 mL/min/1.73 m2 to 25 mL/min/1.73 m2; - Wording was added to indicate that oral glucocorticoid rescue treatment could be used instead of IV glucocorticoid rescue treatment at the discretion of the Investigator - Wording was added to indicate that data from Steps 1 and 2 could be combined depending on the study course - The study period was changed from 18 months to 30 months to reflect the study duration estimation at the time

30 May 2014

-Protocol modified to show that subjects with AAV with or without renal disease were eligible for the study; rituximab allowed instead of cyclophosphamide as background treatment -Study period changed to 60 months -Clinical study objectives revised to indicate the primary efficacy objective and priority order of secondary objectives -Step 3 of the study modified to include the Step 1 CCX168 group in addition to the Step 2 CCX168 group and the standard of care control group -Stratification for MPO and PR3 ANCA and cyclophosphamide or rituximab background treatment were added -Treatment during 84-day follow-up period standardized so that all subjects in the cyclophosphamide stratum received oral azathioprine, starting on Day 99 continuing through Day 168, and all subjects in the rituximab stratum did not receive any additional treatment during the 84-day follow-up period -SF-36 v2 and EQ-5D-5L added to measure changes in health related QoL -Inclusion and exclusion criteria modified to update disease nomenclature (eosinophilic granulomatosis with polyangiitis [Churg Strauss] and IgA vasculitis [Henoch-Schönlein purpura], to be consistent with inclusion of subjects with non-renal AAV, to include elderly subjects, subjects with eGFR ≥20 mL/min/1.73 m2, hemoglobin ≥9 g/dL, liver enzymes not more than 3 x upper limit of normal, to allow up to 3000 mg of IV methylprednisolone prior to Screening, to exclude subjects who had received belimumab or tocilizumab within 12 weeks prior to Screening and subjects with a low lymphocyte count -Plasma sample collection for PD marker and saliva sample for polymorphism assessments added -Safety endpoint added to more precisely evaluate adverse events potentially associated with glucocorticoid use -Efficacy endpoints and statistical analysis methodology sections updated -Sample size estimation section revised -Trough plasma concentration added as a PK parameter -Potential measurements of rituximab plasma added

18 Sep 2015

Changes made to the protocol included the following: - The statistical methodology section was revised to indicate that the difference in proportions of subjects achieving the categorical endpoints were to be used instead of the odds ratio; an MMRM analysis for continuous variables was added - The study schema was corrected to indicate that the Step 3 enrollment target was 36 subjects, not 180 - Wording was revised to consolidate previous country-specific Amendments - Wording was added regarding stopping criteria for CCX168/placebo dosing of the protocol regarding WBC and neutrophil counts: If a subject developed Grade 2 or worse leukopenia or an ANC <1x109/L, dosing with CCX168 or placebo was to be ceased in such a subject. Study medication might be resumed only if WBC and absolute neutrophil count both exceeded the lower limit of the respective normal range, the Investigator deemed resumption to be appropriate, and the WBC and ANC were monitored closely thereafter. This recommendation was based on findings of leukopenia/neutropenia in 2 cases in another study in subjects with AAV (study CL003_168).

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

This study is relatively small and the treatment duration was short.

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Clinical trials

Clinical Trial Results: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX168 in Subjects with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis on Background Cyclophosphamide or Rituximab Treatment

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Proportion of subjects achieving disease response at Day 85

Primary: Proportion of subjects achieving disease response at Day 85

Secondary: Proportion of Patients Achieving Renal Response at Day 85

Secondary: Proportion of Patients Achieving Renal Response at Day 85

Secondary: Proportion of Subjects Achieving Disease Remission at Day 85

Secondary: Proportion of Subjects Achieving Disease Remission at Day 85

Secondary: Percent Change From Baseline to Day 85 in BVAS

Secondary: Percent Change From Baseline to Day 85 in BVAS

Secondary: Change From Baseline to Day 85 in eGFR

Secondary: Change From Baseline to Day 85 in eGFR

Secondary: Percent Change From Baseline to Day 85 in eGFR

Secondary: Percent Change From Baseline to Day 85 in eGFR

Secondary: Proportion of Subjects Achieving Urinary RBC Count <=5/Hpf at Any Time During the 84-day Treatment Period

Secondary: Proportion of Subjects Achieving Urinary RBC Count <=5/Hpf at Any Time During the 84-day Treatment Period

Secondary: Time to First Achieving Urinary RBC Count <=5/Hpf at Any Point During the 84-day Treatment Period

Secondary: Time to First Achieving Urinary RBC Count <=5/Hpf at Any Point During the 84-day Treatment Period

Secondary: Proportion of Subjects Achieving Urinary RBC Count <30/Hpf at Any Time During the 84-day Treatment Period

Secondary: Proportion of Subjects Achieving Urinary RBC Count <30/Hpf at Any Time During the 84-day Treatment Period

Secondary: Time to First Achieving Urinary RBC Count <=30/Hpf at Any Point During the 84-day Treatment Period

Secondary: Time to First Achieving Urinary RBC Count <=30/Hpf at Any Point During the 84-day Treatment Period

Secondary: Percent Change From Baseline to Day 85 in Urinary RBC Count

Secondary: Percent Change From Baseline to Day 85 in Urinary RBC Count

Secondary: Percent Change From Baseline to Day 85 in UACR

Secondary: Percent Change From Baseline to Day 85 in UACR

Secondary: Percent Change From Baseline to Day 85 in Urinary MCP-1:Creatinine Ratio

Secondary: Percent Change From Baseline to Day 85 in Urinary MCP-1:Creatinine Ratio

Secondary: Proportion of Subjects Requiring Rescue IV or Oral Glucocorticoid Treatment

Secondary: Proportion of Subjects Requiring Rescue IV or Oral Glucocorticoid Treatment

Secondary: Change From Baseline to Day 85 in the Vasculitis Damage Index

Secondary: Change From Baseline to Day 85 in the Vasculitis Damage Index

Secondary: Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the SF-36 v2

Secondary: Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the SF-36 v2

Secondary: Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the EQ-5D-5L

Secondary: Change From Baseline to Day 85 in Health-related Quality of Life as Measured by the EQ-5D-5L

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX168 in Subjects with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis on Background Cyclophosphamide or Rituximab Treatment