Clinical Trial to Evaluate Safety and Efficacy of CCX168 in ANCA-Associated Vasculitis

This is a safety study to assess the overall rates of treatment-emergent adverse events (TEAEs) across all study arms.

Proportion of Patients achieving 50% reduction in the Birmingham Vasculitis Activity Score [BVAS] at Day 85 and no worsening in any body system component at day 85

Proportion of subjects achieving disease remission based on Birmingham Vasculitis Activity Score (BVAS) defined as 0 at Day 85.

Proportion of subjects achieving early disease remission based on Birmingham Vasculitis Activity Score (BVAS) score of 0 at Days 29 and 85.

The Birmingham Vasculitis Activity (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.

Renal responses among patients (who had hematuria or albuminuria at baseline determined secondary to ANCA-associated vasculitis) were defined as improvement in the following parameters of renal vasculitis: (1) increase from baseline to day 85 in eGFR [Modification of Diet in Renal Disease (MDRD equation)], (2) decrease from baseline to day 85 in hematuria (microscopic count of urinary red blood cells [RBC]), and (3) decrease from baseline to day 85 in albuminuria (first morning urinary albumin:creatinine ratio).

Mean Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula, for patients with renal disease at baseline.

Mean Percentage Change in Estimated Glomerular Filtration Rate based on modification of diet in renal disease formula.

Mean Percent Change of Urinary Red Blood Cells (UBC) in Patients in Hematuria at Baseline.

Mean Percent Change of Urinary Albumin:Creatinine Ratio in Patients with Albuminuria at Baseline

Mean Percent Change of Urinary monocyte chemoattractant protein (MCP-1:creatinine) ratio from Baseline

The Vasculitis Damage Index (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)

Change from Baseline to Day 85 in Health-Related Quality-Of-Life as Measured by the Short Form-36 (SF-36v2) 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).

Mean Change from baseline to Day 85 in health-related quality-of-life as measured by the Euro Quality-of-Life-5 Domains-5 Levels (EQ-5D-5L).

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).

Proportion of subjects requiring rescue glucocorticoid treatment from Baseline to Day 85