CYCLOPHOSPHAMIDE for ANCA-associated vasculitis

Inclusion criteria

• {"criterion_text":"- Clinical diagnosis of granulomatosis with polyangiitis (GPA) or microscopic Polyangiitis (MPA), consistent with Chapel-Hill Consensus Conference definitions\n- 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\n- Positive test for anti-PR3 or anti-MPO (current or historic)\n- Willing and able to give written Informed Consent and to comply with the requirements of the study protocol"}

Exclusion criteria

• {"criterion_text":"- Pregnant or breast-feeding\n- Required dialysis or plasma exchange within 12 weeks prior to screening\n- Received intravenous glucocorticoids, >3000mg methylprednisolone equivalent, within 4 weeks prior to screening\n- Immunization with a live vaccine 1 month before screening\n- 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\n- Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies\n- Active pregnancy, as proven by a positive urine beta-HCG test or a positive serum beta-HCG\n- Significant hypogammaglobulinemia (IgG < 4.0 g/L) or an IgA deficiency (IgA < 0.1 g/L)\n- 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\n- Have a history of a primary immunodeficiency\n- Have a significant infection history that in the opinion of the investigator would make the candidate unsuitable for the study\n- Have a neutrophil count of < 1.5x10E9/L\n- Evidence of hepatic disease: AST, ALT, alkaline phosphatase, or bilirubin > 3 times the upper limit of normal before start of dosing\n- Have any other clinically significant abnormal laboratory value in the opinion of the investigator"}

Primary endpoints

• {"endpoint_text":"- Compare the number of RTX retreatment infusions needed to maintain clinical remission over 2 years, based on B-cell status and ANCA status, in both arms","definition_or_measurement_approach":"Number of RTX retreatment infusions over 2 years; comparison stratified/assessed based on B-cell status and ANCA status as recorded during follow-up."}

Secondary endpoints

• {"endpoint_text":"- Assess the time to an ANCA negative test by using a high-quality ELISA measuring ANCAs. A negative test is defined as below the detection level","definition_or_measurement_approach":"Time to first negative ANCA result measured by high-quality ELISA; negative defined as below the assay detection level."}
• {"endpoint_text":"- Assess the time to ANCA return defined as seroconversion to positive on at least 2 consecutive visits (the time of the first is then representative time of seroconversion) OR a doubling of the ANCA serum levels PR3 or MPO ELISA test compared to a previously achieved nadir","definition_or_measurement_approach":"Time to seroconversion to positive on ≥2 consecutive visits (time of first positive is time of seroconversion) OR doubling of PR3 or MPO ELISA compared to prior nadir."}
• {"endpoint_text":"- Duration of B-cell depletion defined as time taken to detect a repopulation of B-cells above the detection limit of standard flowcytometry (i.e. > 1x10^6 cells/L)","definition_or_measurement_approach":"Time from depletion to repopulation defined as B-cells >1x10^6 cells/L by standard flow cytometry."}
• {"endpoint_text":"- To assess the safety parameters of each treatment arm including adverse events according to WHO toxicity criteria and recording of infectious events","definition_or_measurement_approach":"Safety assessed by recording adverse events graded per WHO toxicity criteria and documenting infectious events."}
• {"endpoint_text":"- To assess quality of life by patient related outcome scores (AAV-PRO and SNOT22)","definition_or_measurement_approach":"Quality of life measured using AAV-PRO and SNOT22 patient-reported outcome instruments."}
• {"endpoint_text":"- To assess clinical disease activity of each treatment arm as described in section 7.2.3 of the protocol","definition_or_measurement_approach":"Clinical disease activity assessed per protocol section 7.2.3 (specific disease-activity instrument and schedule referenced in protocol)."}

Netherlands

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

11-08-2025

Processing Time Days

355

Number Of Sites

8

Number Of Participants

100

Primary sponsor

Full Name

Academisch Ziekenhuis Leiden

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands