A Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With ANCA-Associated Vasculitis

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

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).

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)

Percent change in Burmingham 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.

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

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

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

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

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

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

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

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

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

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).

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).

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).