Inclusion Criteria

Each patient must meet the following criteria to be enrolled in this study.

1. Subjects aged 18 or greater.
2. Fulfillment of the definitions of the Second Chapel Hill Consensus Conference for ANCA-associated vasculitis (either granulomatosis with polyangiitis or microscopic polyangiitis).
1. Positivity for ANCA, directed against proteinase-3 (PR3)
2. 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 need for rituximab therapy as per investigator.
3. Minimum BVAS/WG of 3
4. Relapsing patients must have B cells detectable in the peripheral blood.
5. 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.
6. Female subjects of childbearing potential and 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 medications.  Male and female patients must agree to not donate sperm or eggs, respectively, 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 one 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

Patients who present any of the following criteria will be excluded from the study.

1. Diagnosis with eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) as defined by the Chapel Hill Consensus Conference.
2. Non-severe AAV, defined as disease that does not justify treatment with both B cell depletion and a four-month glucocorticoid taper.
3. 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 deepspace 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
• 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 antiglomerular 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 COVID19 infection.
• Uncontrolled disease: evidence of glucocorticoid dependant disease such as asthma requiring consistently greater than 10 mg of prednisone for disease control which might affect endpoint assessment or other uncontrolled disease, including drug and alcohol abuse, that could interfere with participation in the trial according to the protocol.

4. Diagnosis of human anti-chimeric antibodies (HACA) formation.
5. Positive pregnancy test
6. Use of prohibited medications: They have used any of the prohibited medication listed in Section 5.7.1.
7. Plasma exchange: They have been treated with plasma exchange within the 3 months preceding the screening visit.
8. History of intolerance to rituximab or other chimeric monoclonal antibodies (e.g., infliximab).
9. Recent vaccination: They have had a live vaccine fewer than 4 weeks before randomization.

• The following medications are prohibited:

• Cyclophosphamide - prohibited within three months prior to baseline (Visit 2)
• IVIg (for the purpose of treating AAV) - prohibited within one month of baseline
• Plasma exchange - prohibited within one month of baseline
• Avacopan is not allowed as adjunct therapy for remission induction or maintenance
• Other biologic disease-modifying anti-rheumatic drugs (DMARDs) must be stopped one month before baseline or for five half-lives, whichever is longer.  Examples of DMARDs are:

• Examples of Biologic DMARDs

  Generic Name - Trade Name

  Abatacept - Orencia

  Adalimumab - Humira

  Anakinra - Kineret

  Certolizumab - Cimzia

  Etanercept - Enbrel

  Golimumab - Simponi

  Infliximab - Remicade

  Rituximab - Rituxan

  Tocilizumab - Actemra

  Patients taking methotrexate, azathioprine, mycophenolate mofetil, or leflunomide at the time of screening must stop these medications before the baseline visit.

• 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 before randomization.

Eligibility last updated 1/17/22. Questions regarding updates should be directed to the study team contact.