Clinical trial to evaluate the safety and efficacy of CCX168 in ANCA-associated vasculitis (AAV)
- Conditions
- ANCA-associated vasculitis (AAV)Circulatory System
- Registration Number
- ISRCTN19848432
- Lead Sponsor
- ChemoCentryx, Inc. (USA)
- Brief Summary
2016 results presented at ACR/ARHP 2016: https://acrabstracts.org/abstract/a-randomized-clinical-trial-of-ccx168-an-orally-administered-c5ar-inhibitor-for-treatment-of-patients-with-anca-associated-vasculitis/ (added 15/04/2019) 2020 results in https://pubmed.ncbi.nlm.nih.gov/33128347/ (added 19/04/2021)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 42
1. Male or female subjects 18 years and older, with new or relapsed AAV
2. Clinical diagnosis of granulomatosis with polyangiitis (Wegener?s), microscopic polyangiitis or renal limited vasculitis
3. Female subjects of childbearing potential, and male subjects with partners of childbearing potential may participate in the study if adequate contraception is used
4. 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
5. Have at least one 'major' item, or at least three other items, or at least two renal items on the Birmingham Vasculitis Activity Score (BVAS) version 3
6. Estimated glomerular filtration rate (eGFR) = 20 mL per minute
1. Severe disease as determined by rapidly progressive glomerulonephritis or alveolar hemorrhage
2. Any other multi-system autoimmune disease
3. Medical history of coagulopathy or bleeding disorder
4. Received cyclophosphamide with 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to screening; if on azathioprine, mycophenolate mofetil, or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1
5. Received intravenous corticosteroids, >3000 mg methylprednisolone equivalent, within 12 weeks prior to screening
6. 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
7. 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
8. Symptomatic congestive heart failure requiring prescription medication, peripheral edema of cardiac origin, poorly-controlled hypertension, history of unstable angina, myocardial infarction or stroke within 6 months prior to screening
9. History or presence of any form of cancer within the 5 years prior to screening
10. Evidence of tuberculosis based on chest X rays
11. Positive HBV, HCV, or HIV viral screening test
12. Any infection requiring antibiotic treatment within 4 weeks prior to screening
13. Received a live vaccine within 4 weeks prior to screening
14. WBC count less than 4000/µL, or neutrophil count less than 2000/µL, or lymphocyte count less than 1000/µL
15. Hemoglobin less than 9 g/dL at screening
16. Evidence of hepatic disease
17. Prothrombin time (PT) or partial thromboplastin time (PTT) above the normal reference limit
18. Clinically significant abnormal ECG during screening
19. Participated in any clinical study of an investigational product within 30 days prior to screening
20. History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety and efficacy of CCX168 in subjects with AAV on SOC cyclophosphamide or rituximab plus corticosteroid treatment. Efficacy is evaluated based on the Birmingham Vasculitis Activity Score (BVAS). BVAS assessments will be made on Days 1, 29, 85, 113, and 169.
- Secondary Outcome Measures
Name Time Method <br> 1. Efficacy of CCX168 compared to SOC based on changes in eGFR, Hematuria and Albuminuria will be assessed on Days 1, 2, 8, 15, 22, 29, 43, 57, 71, 85, 99, 113, 141, and 169.<br> 2. Assessment of changes in renal inflammatory activity based on MCP-1:creatinine ratio and serum C-reactive protein concentrations with CCX168 compared to SOC will be completed on Days 1 (prior to dosing), 8, 15, 29, 57, 85, 113, and 169.<br> 3. Assessment of health-related quality-of-life changes based on SF-36v2 and EQ-5D-5L with CCX168 compared to SOC will completed on Days 1, 29, 85, and 169.<br> 4. Assessment of changes in VDI with CCX168 compared to SOC, made on Days 1, 85, and 169.<br> 5. Assessment of changes in ANCA (anti-PR3 and anti-MPO) with CCX168 compared to SOC will be made on Days 1 (prior to dosing), 29, 85, 113, and 169.<br>