Inclusion Criteria:
* Fulfillment of the definitions of the Second Chapel Hill Consensus Conference for ANCA-associated vasculitis (either granulomatosis with polyangiitis or microscopic polyangiitis).
* Positivity for ANCA, directed against proteinase-3 (PR3)
* Severe newly-diagnosed disease or severe relapsing disease. Severe relapsing disease is defined as at least one major BVAS/WG item or a score ≥ 3 and the investigator deems standard treatment for severe disease is necessary.
* Minimum BVAS/WG of 3
* Relapsing patients must have B cells detectable in the peripheral blood.
* Patients must have completed COVID19 vaccination (including booster if eligible) at least 4 weeks prior to enrollment with a positive spike protein antibody test result. Patients who have recovered from COVID19 prior to screening with a positive spike protein antibody test result but have not been vaccinated are also eligible.
* Female subjects of childbearing potential who are not sterile must agree to use an acceptable method of contraception for 18 months after the last dose of infusion medication. Male subjects who are not sterile whose female partners are of childbearing potential must agree to use an acceptable method of contraception for 180 days after the last dose of infusion medication.
* Females of childbearing potential include any female who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (to be considered postmenopausal, the patient must have had amenorrhea for \>12 consecutive months).
* Acceptable methods of contraception include the use of at least two of the following: 1) intrauterine device; 2) hormonal contraceptives for at least 30 days prior to first dose infusion (oral, injectable, implant or ring); 3) barrier contraceptives (condom or diaphragm) with spermicide; or 4) abstinence.
Exclusion Criteria:
* Diagnosis with eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) as defined by the Chapel Hill Consensus Conference.
* Positive serum assays for ANCA directed against myeloperoxidase (MPO-ANCA)
* Non-severe AAV, defined as disease that does not justify treatment with both B cell depletion and a four-month glucocorticoid taper.
* Any of the co-morbidities:
* Allergies: a history of severe allergic reactions to human or chimeric monoclonal antibodies or murine protein.
* Infection (systemic): an active systemic infection at screening visit
* Infection (deep space): have been diagnosed as having a deep-space infection, such as osteomyelitis, septic arthritis, or pneumonia complicated by empyema or lung abscesses, within 6 months prior to the screening visit
* Infection (blood borne): active hepatitis B or active hepatitis C or a documented history of HIV, hepatitis B, or hepatitis C
* Infection (history): History of recurrent significant infection or history of recurrent bacterial infections
* Liver disease: acute or chronic liver disease that is deemed sufficiently severe to impair their ability to participate in the trial.
* Renal disease: a history of documented anti-glomerular basement membrane disease (anti-GBM disease).
* Malignancy: Active or history of malignancy in the last 5 years. Individuals with squamous cell or basal cell skin carcinomas and individuals with cervical carcinoma in situ may be enrolled if they have received curative surgical treatment.
* Active COVID-19 infection.
* Uncontrolled disease: evidence of glucocorticoid dependent disease (such as asthma, COPD, psoriasis or IBD, etc.) requiring consistently greater than 10 mg of prednisone for disease control which might affect endpoint assessment or,
* Other uncontrolled diseases, including any uncontrolled psychiatric disorders, drug and alcohol abuse, that could interfere with participation in the trial according to the protocol.
* Diagnosis of human anti-chimeric antibodies (HACA) formation.
* Subjects who are premenopausal and are:
* Pregnant on the basis of a serum pregnancy test,
* Breastfeeding, or
* Do not agree to use effective method(s) of contraception
* Use of prohibited medications: They have used any of the prohibited medication listed in Section 5.9.1.
* Plasma exchange: They have been treated with plasma exchange within the 3 months preceding the screening visit.
* History of intolerance to rituximab or other chimeric monoclonal antibodies (e.g., infliximab).
* Recent vaccination: They have had a live vaccine fewer than 4 weeks (28 days) before or during randomization (vaccination with live vaccine through the end of study participation is contraindicated).
* Daily use of non-steroidal anti-inflammatory drugs (NSAIDs)
* Exclusion criteria related to laboratory parameters:
* Bone marrow suppression as evidenced by a total white count \< 4 x10 /l, hemoglobin \< 7 gm/dl or platelet count \< 100,000/μl
* Aspartate aminotransferase or alanine aminotransferase or amylase \> 2.5 times the upper limit of normal, unless attributed to vasculitis
