RemiRit - Personalized immunosuppressive therapy with rituximab in the treatment of ANCA associated vasculitis - a randomized, multicenter clinical trial

Trial details

Who runs it

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Trial code

EU 2024-517881-40-00

Record updated

2024. november 24.

Original description

Part I - induction treatment: Comparison of the efficacy of combination treatment with rituximab (RTX) and cyclophosphamide (CYC) versus standard treatment with cyclophosphamide (CYC) in induction of complete remission of severe AAV, defined as BVAS/WG=0. Part II - maintenance treatment: To compare the efficacy of subcutaneous and intravenous rituximab (RTX) treatment in sustaining complete (BVAS/WG=0) or partial (BVAS/WG=1 or2) remission of AAV. Additional research objective: To evaluate genetic predisposition to disease development, disease course, and response to treatment.Read full original descriptionShow less

Part I - induction treatment: Comparison of the efficacy of combination treatment with rituximab (RTX) and cyclophosphamide (CYC) versus standard treatment with cyclophosphamide (CYC) in induction of complete remission of severe AAV, defined as BVAS/WG=0. Part II - maintenance treatment: To compare the efficacy of subcutaneous and intravenous rituximab (RTX) treatment in sustaining complete (BVAS/WG=0) or partial (BVAS/WG=1 or2) remission of AAV. Additional research objective: To evaluate genetic predisposition to disease development, disease course, and response to treatment.

Inclusion: Written informed consent of the patient to participate in the clinical trial; Consent to prophylactically intake of Entecavir in case of a positive total anti-Hbc result with HBsAg; Age ≥ 18 years; Diagnosis of AAV, including granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) as defined by the Chapel Hill Consensus Conference; New diagnosis or exacerbation of AAV; High AAV activity defined as ≥ 3 points on the BVAS/WG scale; Positive PR3-ANCA or MPO-ANCA at screening or within 30 days prior to screening; Discontinuation of current immunosuppressive and immunomodulatory agents, including mycophenolate mofetil, azathioprine, methotrexate and leflunomide, no later than the day of screening; Use of highly effective contraception by women of childbearing potential during the study and 12 months after the last administration of the investigational medicinal product; Use of high barrier contraception by men with female partners of childbearing potential throughout the study and 6 months after the last administration of an investigational medicinal product.

Exclusion: Limited form of disease that does not require treatment with cyclophosphamide; Abuse of drugs, alcohol or other intoxicating substances; Vaccination with live vaccines within 4 weeks prior to screening; History of hemorrhagic cystitis, bone marrow hypoplasia or malignancy during treatment with cyclophosphamide; Acute or chronic respiratory failure, not due to AAV; Documented history of antichimeric antibody formation after administration of monoclonal antibodies; Respiratory failure due to diffuse alveolar hemorrhage requiring mechanical ventilation; Diagnosis of disease associated with anti-glomerular basement membrane (anti-GBM) as defined by the Chapel Hill Consensus Conference; Active or history of cancer within the past 5 years, except for basal-cell carcinoma of the skin and carcinoma in situ of cervix in patients who have received radical treatment; Severe heart failure (New York Heart Association Class IV) or severe uncontrolled heart disease not due to AAV; Infections: a. Active and chronic viral, bacterial, fungal or parasitic infection b. Active or latent tuberculosis c. Active or chronic hepatitis B d. Active or chronic hepatitis C e. Diagnosed HIV infection; History of severe allergic reactions to human or chimeric monoclonal antibodies or mouse proteins; History of hypersensitivity to the active substance or any excipient of the investigational medicinal products (cyclophosphamide or rituximab); History of intolerance to any of the investigational medicinal products (cyclophosphamide or rituximab); History of allergy to drugs or other substances which, in the opinion of the Investigator is a contraindication to participation in the study; Acute or chronic liver disease, not due to AAV, which in the opinion of the Investigator is a contraindication to participation in the study; History or presence of other relevant diseases that, in the opinion of the Investigator may adversely affect the patient's participation in the study; Current history of urinary tract obstruction; Medications being taken: a. Rituximab and other drugs that cause B-lymphocyte depletion within 6 months prior to screening, b. Cyclophosphamide within 6 months prior to screening, except when oral cyclophosphamide is included up to 7 days prior to screening and discontinued no later than the day of screening, c. Infliximab within 3 months prior to screening, d. Adalimumab within 2 months prior to screening, e. Etanercept within 1 month prior to screening; Diagnosis of AAV with simultaneous presence of both MPO-ANCA and PR3-ANCA antibodies in serum; Screening findings: a. Leukopenia defined as a white blood cell (WBC) count below 4000/mm3, b. Neutropenia defined as a neutrophil count less than 1500/mm3, c. Thrombocytopenia defined as a platelet count (PLT) less than 100000/mm3, d. Hemoglobin (Hgb) less than 8.0 g/dl, e. AST or ALT elevations greater than 2.5 x GGN, not due to AAV, f. Severe immunoglobulin deficiency defined as IgG less than 400 mg/dL or IgA less than 10 mg/dL, g. Positive HBsAg, h. Positive anti-HCV result, i. Positive QuantiFERON-TB Gold test result, j. Positive anti-HIV 1 or anti-HIV 2; Positive pregnancy test performed among women of childbearing age at screening or Visit 1; Diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) as defined by the Chapel Hill Consensus Conference; Diagnosis of AAV limited to the kidney, without involvement of other organs; Pregnancy or planning a pregnancy during the study and 12 months after the study; Breastfeeding or planning to breastfeed during the study and 12 months after completion of the study; Participation in another clinical trial; Lack of patient compliance; Congenital or acquired immunodeficiency; Bone marrow aplasia.

EU CTIS 2024-517881-40-00