ANCA-associated vasculitis
Conditions
Interventions
The study is designed as an open-label, 1:1 randomized, prospective study between RTX with cyclophosphamide and RTX alone. The duration of the study is 104 weeks during which AAV patients will be eval
Sponsors
LUMC
Eligibility
Inclusion criteria
Inclusion criteria: 4.1. Inclusion criteria Subjects enrolled in the study must meet the following inclusion criteria: 1) Clinical diagnosis of granulomatosis with polyangiitis (GPA) or microscopic Polyangiitis (MPA), consistent with Chapel-Hill Consensus Conference definitions26 2) 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 3) Positive test for anti-PR3 or anti-MPO (current or historic) 4) Willing and able to give written Informed Consent and to comply with the requirements of the study protocol
Exclusion criteria
Exclusion criteria: 4.2. Exclusion criteria Subjects will be excluded from participation if they meet any of the following exclusion criteria: 1) Pregnant or breast-feeding 2) Active pregnancy, as proven by a positive urine beta-HCG test or a positive serum beta-HCG 3) Significant hypogammaglobulinemia (IgG 3 times the upper limit of normal before start of dosing 11) Have any other clinically significant abnormal laboratory value in the opinion of the investigator 12) Required dialysis or plasma exchange within 12 weeks prior to screening 13) Received intravenous glucocorticoids, >3000mg methylprednisolone equivalent, within 4 weeks prior to screening 14) Immunization with a live vaccine 1 month before screening 15) 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. 16) Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| In this randomized study the primary objective is to prove the superiority of combination treatment RTX with cyclophosphamide to achieve a state of durable immunological remission in AAV patients as compared to RTX alone. The primary objective is to assess the number of patients that reach a ANCA negative test within 24 weeks of therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives are: - time to a ANCA negative test - Percentage of patients that have ANCA return during follow-up - number of Rituximab infusions as maintenance therapy - duration of B-cell depletion - composition of the memory B-cell and plasma cell compartment before and after treatment - to investigate whether MRA is associated with disease flares - to investigate whether MRA is associated with (a shorter) time to a disease flares - to investigate whether the presence or absence of MRA after RTX can guide a personalized treatment - to assess the safety parameters of each treatment arm including adverse events according to WHO toxicity criteria, time to immune reconstitution and recording of infectious events | — |
Contacts
Public ContactLaura van Dam
LUMC
Outcome results
None listed