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

Complement 5a and its receptor C5aR (CD88) are involved in the pathogenesis of
anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

This is a randomized, double-blind, active-controlled Phase 3 study to evaluate the safety
and efficacy of the orally-administered, selective C5aR inhibitor CCX168 (avacopan) in
inducing and sustaining remission in patients with anti-neutrophil cytoplasmic antibody
(ANCA)-associated vasculitis (AAV) treated concomitantly with Rituximab or
Cyclophosphamide/Azathioprine.

Inclusion Criteria:

- Clinical diagnosis of granulomatosis with polyangiitis (Wegener's) or microscopic
polyangiitis

- Male and female subjects, aged at least 18 years, with newly-diagnosed or relapsed AAV
where treatment with cyclophosphamide or rituximab is needed; where approved by
Regulatory Agencies, adolescents (12-17 year old) may be enrolled

- Use of adequate contraception

- Positive test for anti-PR3 or anti-MPO

- At least 1 major item, or at least 3 non-major items, or at least the 2 renal items of
proteinuria and hematuria on BVAS

- Estimated glomerular filtration rate ≥15 mL/minute/1.73 m^2 at screening

Exclusion Criteria:

- Pregnant or breast-feeding

- Alveolar hemorrhage requiring pulmonary ventilation support at screening

- Any other known multi-system autoimmune disease

- Required dialysis or plasma exchange within 12 weeks prior to screening

- Have a kidney transplant

- 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withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1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 glucocorticoids, >3000 mg methylprednisolone equivalent, within 4
weeks prior to screening

- Have been taking an oral daily dose of a glucocorticoid of more than 10 mg
prednisone-equivalent for more than 6 weeks continuously prior to screening

- Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks
provided B cell reconstitution has occurred (i.e., CD19 count > 0.01x10^9/L); received
anti-TNF treatment, abatacept, alemtuzumab, IVIg, belimumab, tocilizumab, or
eculizumab within 12 weeks prior to screening

- For patients scheduled to receive cyclophosphamide treatment, urinary outflow
obstruction, active infection (especially varicella zoster infection), or platelet
count <50,000/μL before start of dosing

- Participated previously in a CCX168 study