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

Summary

The primary objective is to evaluate the efficacy of CCX168 (avacopan) to induce and sustain remission in patients with active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), when used in combination with cyclophosphamide followed by azathioprine, or in combination with rituximab.

Timeline

Start

2017-03-15

Primary completion

2019-09-07

Completion

2019-11-01

Outcome

Met primary endpoint

registry analysis (non-inferiority test); Prednisone Group vs Avacopan Group; p < 0.0001; Common difference in remission rates 3.4 (95% CI -6.0 to 12.8); Summary score test NCT02994927 ↗

registry analysis (superiority test); Prednisone Group vs Avacopan Group; p = 0.0066; Common difference in remission rates 12.5 (95% CI 2.6 to 22.3); Summary score test NCT02994927 ↗

Publications

• Geetha D, Neumann T, Karras A, Cid MC, Merkel PA, Bray S, Bozeman AM, Jayne DRW; Members of the ADVOCATE Study Group. Efficacy and safety of avacopan for treatment of patients with ANCA-associated vasculitis receiving cyclophosphamide. RMD Open. 2025 Oct 5;11(4):e005743. doi: 10.1136/rmdopen-2025-005743.
• Geetha D, Dua A, Yue H, Springer J, Salvarani C, Jayne D, Merkel P; ADVOCATE Study Group. Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial. Ann Rheum Dis. 2024 Jan 11;83(2):223-232. doi: 10.1136/ard-2023-224816.
• Soulsby WD. Journal Club Review of "Avacopan for the Treatment of ANCA-Associated Vasculitis". ACR Open Rheumatol. 2022 Jul;4(7):558-561. doi: 10.1002/acr2.11412. Epub 2022 Feb 15.
• Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021 Feb 18;384(7):599-609. doi: 10.1056/NEJMoa2023386.
• Merkel PA, Jayne DR, Wang C, Hillson J, Bekker P. Evaluation of the Safety and Efficacy of Avacopan, a C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Treated Concomitantly With Rituximab or Cyclophosphamide/Azathioprine: Protocol for a Randomized, Double-Blind, Active-Controlled, Phase 3 Trial. JMIR Res Protoc. 2020 Apr 7;9(4):e16664. doi: 10.2196/16664.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Avacopan	Small molecule	30 mg	Oral
Comparator	Prednisone	Other / unclassified	30 mg	Oral
Comparator	Prednisone	Other / unclassified	45 mg	Oral
Comparator	Prednisone	Other / unclassified	60 mg	Oral
Background	Azathioprine	Small molecule	—	Oral
Background	Cyclophosphamide	Other / unclassified	—	Oral
Background	Rituximab	Monoclonal antibody	—	Intravenous

Indications