A Randomized, Double-Blind, Active-Controlled, Phase 3 Study to Evaluate the Safety and Efficacy of CCX168 (Avacopan) in Patients with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis Treated Concomitantly with Rituximab or Cyclophosphamide/Azathioprine
- Conditions
- ANCA Associated Vasculitis10047066
- Registration Number
- NL-OMON45712
- Lead Sponsor
- Chemocentryx
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
1. Clinical diagnosis of granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis, consistent with Chapel-Hill Consensus Conference definitions
2. Aged at least 18 years, with newly-diagnosed or relapsed AAV where treatment with cyclophosphamide or rituximab is needed; where approved, adolescents (12-17 year old) may be enrolled
3. Positive test for anti-PR3 or anti-MPO (current or historic) antibodies
4. At least one major item, or at least 3 minor items, or at least the 2 renal items of proteinuria and hematuria in the BVAS
5. Estimated glomerular filtration rate *15 mL/minute/1.73 m2 (using the MDRD method for adults, and modified Schwartz equation for adolescents) at screening
6. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol; written Informed Consent should be obtained from the legal guardian in accordance with regional laws or regulations for patients 12 to 17 years of age
7. Judged by the Investigator to be fit for the study, based on medical history, physical examination (including electrocardiogram [ECG]), and clinical laboratory assessments.
1. Pregnant or breast-feeding
2. Alveolar hemorrhage requiring invasive pulmonary ventilation support anticipated to last beyond the screening period of the study
3. Any other known multi-system autoimmune disease including eosinophilic granulomatosis with polyangiitis (Churg-Strauss), systemic lupus erythematosus, IgA vasculitis (Henoch-Schönlein), rheumatoid vasculitis, Sjögren's syndrome, anti-glomerular basement membrane disease, or cryoglobulinemic vasculitis
4. Required dialysis or plasma exchange within 12 weeks prior to screening
5. Have had a kidney transplant
6. 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to screening; if on azathioprine, mycophenolate mofetil, or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1
7. Received intravenous glucocorticoids, >3000 mg methylprednisolone equivalent, within 4 weeks prior to screening
8. 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 the screening visit
9. 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 > 0.01x109/L); received anti-TNF treatment, abatacept, alemtuzumab, IVIg, belimumab, tocilizumab, or eculizumab within 12 weeks prior to screening
10. Currently taking a strong inducer of the cytochrome P450 3A4 (CYP3A4) enzyme, such as carbamazepine, phenobarbital, phenytoin, rifampin, or St. John*s wort
11. Any of the following within 12 weeks prior to screening: symptomatic congestive heart failure requiring prescription medication, unstable angina (unless successfully treated with stent or bypass surgery), clinically significant cardiac arrhythmia, myocardial infarction or stroke
12. History or presence of any form of cancer within the 5 years prior to screening, with the exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ such as cervical or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis
13. Evidence of tuberculosis based on interferon * release assay (IGRA), tuberculin purified protein derivative (PPD) skin test, or chest radiography (X rays or CT scan) done at screening or within 6 weeks prior to screening
14. HBV, HCV, or HIV viral screening test showing evidence of active or chronic prior viral infection done at screening or within 6 weeks prior to screening
15. Received a live vaccine within 4 weeks prior to screening
16. WBC count less than 3500/*L, or neutrophil count less than 1500/*L, or lymphocyte count less than 500/µL before start of dosing
17. Evidence of hepatic disease: AST, ALT, alkaline phosphatase, or bilirubin > 3 times the upper limit of normal before start of dosing
18. Clinically significant abnormal ECG during screening, e.g., QTcF greater than 450 msec
19. Known hypersensitivity to CCX168 or inactive ingredients of the CCX168 capsules (including gelatin, polyethylene glycol, or Cremophor), cyclophosphamide or its metabolites (for patients scheduled to receive cyclophosphamide), or known Type I hypersensitivity or anaphylactic reactions to murine proteins, Chinese Hamster Ovary cell proteins, or to any component of rituximab (for patients scheduled to receive rituximab), or any c
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoints are:<br /><br>1. The proportion of patients achieving disease remission at Week 26, defined<br /><br>as a BVAS score of 0 and not taking glucocorticoids for the treatment of AAV<br /><br>within 4 weeks prior to Week 26.<br /><br>2. The proportion of patients achieving sustained disease remission, defined as<br /><br>remission at Week 26 without relapse to Week 52 (BVAS of 0 and not taking<br /><br>glucocorticoids for the treatment of AAV within 4 weeks prior to Week 52). </p><br>
- Secondary Outcome Measures
Name Time Method