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

Complement 5a and its receptor C5aR (CD88) is involved in the pathogenesis of
anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This is a randomized,
double-blind, placebo-controlled Phase 2 study to evaluate the safety and efficacy of the
C5aR inhibitor CCX168 in subjects with ANCA-associated vasculitis. The aim of this trial is
to test the safety and efficacy of two dose regimens of the complement C5a receptor CCX168
in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Inclusion Criteria:

- Clinical diagnosis of granulomatosis with polyangiitis (Wegener's), microscopic
polyangiitis or renal limited vasculitis

- Male and female subjects, aged at least 18 years, with new or relapsed AAV where
treatment with cyclophosphamide or rituximab would be required

- Use of adequate contraception during, and for at least the three months after, any
administration of study medication is required

- Positive indirect immunofluorescence (IIF) test for P-ANCA or C-ANCA, or positive
ELISA test for anti-proteinase-3 (PR3) or anti-myeloperoxidase (MPO) at screening

- Have at least one "major" item, or at least 3 other items, or at least 2 renal items
on the Birmingham Vasculitis Activity Score (BVAS) version 3

- Estimated glomerular filtration rate (eGFR) ≥ 20 mL per minute

Exclusion Criteria:

- Severe disease as determined by rapidly progressive glomerulonephritis, alveolar
hemorrhage, hemoptysis, rapid-onset mononeuritis multiplex or central nervous system
involvement

- Any other multi-system autoimmune disease

- Medical history of coagulopathy or bleeding disorder

- Received cyclophosphamide within 12 weeks prior to screening; if on azathioprine,
mycophenolate mofetil, or methotrexate at the time of screening, these drugs must be
withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1

- Received intravenous corticosteroids, >3000 mg methylprednisolone equivalent, within
12 weeks prior to screening

- Received an oral daily dose of a corticosteroid of more than 10 mg
prednisone-equivalent for more than 6 weeks continuously prior to the screening visit

- Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks
provided B cell reconstitution has occurred; received anti-tumor necrosis factor
(TNF) treatment, abatacept, alemtuzumab, intravenous immunoglobulin (IVIg),
belimumab, tocilizumab, or plasma exchange within 12 weeks prior to screening