Rituximab for ANCA-associated vasculitis|Granulomatosis with polyangiitis|Microscopic polyangiitis

Inclusion criteria

• {"criterion_text":"- Informed consent given by patient according to national regulations\n- AAV [granulomatosis with polyangiitis or microscopic polyangiitis], according to the definitions of the Chapel Hill Consensus Conference\n- Current or history of PR3/MPO-ANCA positivity by ELISA\n- A stable remission (BVAS =0) for the last 24 months\n- Has received a minimum of 24 months of RTX maintenance therapy and last dose minimum 6 months prior to screening. A Rituximab dose of 500 mg or 1000 mg 6 months before inclusion will be accepted\n- Females of childbearing potential must agree to avoid pregnancy during treatment with RTX during 12 months after discontinuation of RTX. They also must have a negative urine or serum pregnancy test at the screening visit. Adequate contraception methods must be followed according to clinical routine for these patients"}

Exclusion criteria

• {"criterion_text":"- Significantly abnormal eGFR at screening (≤15 eGFR ml/min/1.73m2)\n- Hypogammaglobulinemia, IgG <3 g/L\n- History of malignancy within the past five years or any evidence of persistent malignancy. Fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ which has been treated or excised in a curative procedure is allowed\n- Females who are lactating or pregnant at screening (verified with a negative urine or serum pregnancy test at screening visit).\n- Medical, psychiatric, cognitive, or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study\n- Participant in another clinical trial with therapeutic intervention or use of any other investigational agent\n- Previous therapy with any of the following: - any biological B cell depleting agent other than rituximab during the last 6 months (i.e Obinutuzumab, Belimumab) - IVIg, infliximab, etanercept, adalimumab, abatacept or plasma exchange in past 3 months - any investigational agent within 28 days of screening, or 5 half-lives of the investigational drug (whichever is longer)\n- Ongoing therapy with any of the following. - disease modifying therapy related for AAV such as methotrexate, azathioprine, and mycophenolate mofetil or glucocorticoid >5 mg daily\n- Recurrent AAV relapses less than 6 months off immunosuppressive medication\n- Significant or uncontrolled medical disease not related to AAV, which in the investigator’s opinion would preclude patient participation\n- Presence of another multisystem autoimmune disease, including Churg Strauss syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic vasculitis\n- History of severe allergic or anaphylactic reactions to humanized or murine chimeric monoclonal antibodies\n- Past or current history of hepatitis B virus, current active hepatitis C\n- Bone marrow suppression as evidenced by a total white count < 3.0 x109/l and/or neutropenia neutrophil count < 1.5 × 109"}

Primary endpoints

• {"endpoint_text":"- Disease relapse rate, from randomization to relapse","definition_or_measurement_approach":"Relapse rate measured from randomization to relapse; primary objective is to study relapse rate after discontinuation vs maintenance in AAV patients in stable remission. Follow-up period referenced up to 36 months."}

Secondary endpoints

• {"endpoint_text":"- Time to relapse (either minor or major)","definition_or_measurement_approach":"Time from randomization to first relapse (minor or major)."}
• {"endpoint_text":"- Proportion of patients who maintain AAV remission at 24 and 36 months.","definition_or_measurement_approach":"Proportion maintaining remission at specified timepoints (24 and 36 months) post-randomization."}
• {"endpoint_text":"- Serological response during study (ANCA positivity vs negativity)","definition_or_measurement_approach":"ANCA serostatus monitored during study; comparisons of positivity vs negativity over time."}
• {"endpoint_text":"- Loss of kidney function (eGFR slope from randomization+ fixed points at 12, 24, and 36 months)","definition_or_measurement_approach":"eGFR slope assessed from randomization with measurements at 12, 24, and 36 months."}
• {"endpoint_text":"- Start of kidney replacement therapy","definition_or_measurement_approach":"Initiation of kidney replacement therapy recorded as event."}
• {"endpoint_text":"- Duration (number of months) and doses of RTX treatment prior to randomization","definition_or_measurement_approach":"Recording prior RTX exposure in months and doses before randomization."}
• {"endpoint_text":"- Duration (number of months) of GC exposure prior to randomization","definition_or_measurement_approach":"Recording cumulative months of glucocorticoid exposure prior to randomization."}
• {"endpoint_text":"- Cumulative GC exposure from randomization to end of study end of study or relapse whichever comes first","definition_or_measurement_approach":"Cumulative glucocorticoid exposure from randomization until end of study or relapse, whichever occurs first."}
• {"endpoint_text":"- Cumulative accrual of damage measured by the Vasculitis Damage Index (VDI) scale","definition_or_measurement_approach":"VDI scores collected over time to assess cumulative damage accrual."}
• {"endpoint_text":"- Health-related quality of life measurements","definition_or_measurement_approach":"Assessment using validated QOL instruments (e.g., RAND-36, EQ-5D, HADS, AAV-PRO); compare between groups."}
• {"endpoint_text":"- Serious adverse event rate","definition_or_measurement_approach":"Rate and proportion of serious adverse events (SAEs) captured during study."}
• {"endpoint_text":"- Frequency of AEs of special interest (AESI)","definition_or_measurement_approach":"Frequency counts of prespecified AEs of special interest."}
• {"endpoint_text":"- Health economics","definition_or_measurement_approach":"Health economic analyses including QALY assessment, costs, and complications derived from validated instruments and cost data."}

Sweden

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

20-06-2024

Processing Time Days

22

Number Of Sites

13

Number Of Participants

86

Primary sponsor

Full Name

Region Oestergoetland

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"Sponsor duties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}