Evaluating, clinical and immunological effects of rituximab with cyclophosphamide compared to rituximab alone in AAV patients

Prior treatment

• Required dialysis or plasma exchange within 12 weeks prior to screening
• Received intravenous glucocorticoids, >3000mg methylprednisolone equivalent, within 4 weeks prior to screening
• Immunization with a live vaccine 1 month before screening
• Active infection not compatible with start of remission-induction therapy in the opinion of the treating physician and/or investigator, e.g.: - Serological evidence of viral hepatitis defined as: patients positive for HbsAg test or HBcAb or a positive hepatitis C antibody not treated with antiviral medication - Have a historically positive HIV test or test positive at screening for HIV

Other illness

• History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the patient at unacceptable risk for study participation
• Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies
• Have a history of a primary immunodeficiency
• Have a significant infection history that in the opinion of the investigator would make the candidate unsuitable for the study

Lab values

• Active pregnancy, as proven by a positive urine beta-HCG test or a positive serum beta-HCG
• Significant hypogammaglobulinemia (IgG < 4.0 g/L) or an IgA deficiency (IgA < 0.1 g/L)
• Have a neutrophil count of < 1.5x10E9/L
• Evidence of hepatic disease: AST, ALT, alkaline phosphatase, or bilirubin > 3 times the upper limit of normal before start of dosing
• Have any other clinically significant abnormal laboratory value in the opinion of the investigator

Other

• Pregnant or breast-feeding

• Clinical diagnosis of granulomatosis with polyangiitis (GPA) or microscopic Polyangiitis (MPA), consistent with Chapel-Hill Consensus Conference definitions
• Aged at least 18 years, with newly-diagnosed or relapsed AAV with ‘generalised disease’, defined as involvement of at least one major organ (e.g. kidney, lung, heart, peripheral or central nervous system), requiring induction treatment with cyclophosphamide or rituximab
• Positive test for anti-PR3 or anti-MPO (current or historic)
• Willing and able to give written Informed Consent and to comply with the requirements of the study protocol