RITUXIMAB for ANCA-associated vasculitis (AAV)

Inclusion criteria

• {"criterion_text":"- Written informed consent of the patient to participate in the clinical trial."}
• {"criterion_text":"- Consent to prophylactically intake of Entecavir in case of a positive total anti-Hbc result with HBsAg."}
• {"criterion_text":"- Age ≥ 18 years."}
• {"criterion_text":"- Diagnosis of AAV, including granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) as defined by the Chapel Hill Consensus Conference."}
• {"criterion_text":"- New diagnosis or exacerbation of AAV."}
• {"criterion_text":"- High AAV activity defined as ≥ 3 points on the BVAS/WG scale."}
• {"criterion_text":"- Positive PR3-ANCA or MPO-ANCA at screening or within 30 days prior to screening."}
• {"criterion_text":"- Discontinuation of current immunosuppressive and immunomodulatory agents, including mycophenolate mofetil, azathioprine, methotrexate and leflunomide, no later than the day of screening."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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 criteria

• {"criterion_text":"- Diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) as defined by the Chapel Hill Consensus Conference."}
• {"criterion_text":"- Positive pregnancy test performed among women of childbearing age at screening or Visit 1."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Acute or chronic respiratory failure, not due to AAV."}
• {"criterion_text":"- Documented history of antichimeric antibody formation after administration of monoclonal antibodies."}
• {"criterion_text":"- Diagnosis of AAV limited to the kidney, without involvement of other organs."}
• {"criterion_text":"- Diagnosis of AAV with simultaneous presence of both MPO-ANCA and PR3-ANCA antibodies in serum."}
• {"criterion_text":"- Limited form of disease that does not require treatment with cyclophosphamide."}
• {"criterion_text":"- Respiratory failure due to diffuse alveolar hemorrhage requiring mechanical ventilation."}
• {"criterion_text":"- Diagnosis of disease associated with anti-glomerular basement membrane (anti-GBM) as defined by the Chapel Hill Consensus Conference."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Severe heart failure (New York Heart Association Class IV) or severe uncontrolled heart disease not due to AAV."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- History of severe allergic reactions to human or chimeric monoclonal antibodies or mouse proteins."}
• {"criterion_text":"- History of hypersensitivity to the active substance or any excipient of the investigational medicinal products (cyclophosphamide or rituximab)."}
• {"criterion_text":"- History of intolerance to any of the investigational medicinal products (cyclophosphamide or rituximab)."}
• {"criterion_text":"- History of allergy to drugs or other substances which, in the opinion of the Investigator is a contraindication to participation in the study."}
• {"criterion_text":"- Abuse of drugs, alcohol or other intoxicating substances."}
• {"criterion_text":"- Vaccination with live vaccines within 4 weeks prior to screening."}
• {"criterion_text":"- Pregnancy or planning a pregnancy during the study and 12 months after the study."}
• {"criterion_text":"- Breastfeeding or planning to breastfeed during the study and 12 months after completion of the study."}
• {"criterion_text":"- Participation in another clinical trial."}
• {"criterion_text":"- Acute or chronic liver disease, not due to AAV, which in the opinion of the Investigator is a contraindication to participation in the study."}
• {"criterion_text":"- Lack of patient compliance."}
• {"criterion_text":"- History or presence of other relevant diseases that, in the opinion of the Investigator may adversely affect the patient's participation in the study."}
• {"criterion_text":"- Congenital or acquired immunodeficiency."}
• {"criterion_text":"- Current history of urinary tract obstruction."}
• {"criterion_text":"- History of hemorrhagic cystitis, bone marrow hypoplasia or malignancy during treatment with cyclophosphamide."}
• {"criterion_text":"- Bone marrow aplasia."}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- Part I induction treatment: The occurrence of complete remission (defined as BVAS/WG=0 disease activity) at 26 weeks after enrollment to Part I. Part II - Maintenance treatment: The occurrence of a positive treatment effect defined as complete remission (BVAS/WG=0 disease activity) or partial remission (BVAS/WG=1 or BVAS/WG=2) at 104 weeks after randomization to Part II.","definition_or_measurement_approach":"Complete remission defined as BVAS/WG=0; partial remission defined as BVAS/WG=1 or BVAS/WG=2. Measurement timepoints: 26 weeks for Part I; 104 weeks after randomization for Part II."}

Secondary endpoints

• {"endpoint_text":"- Treatment response defined as a >50% reduction in BVAS/WG vasculitis activity from baseline at 26 weeks after enrollment in Part I.","definition_or_measurement_approach":">50% reduction in BVAS/WG from baseline at 26 weeks."}
• {"endpoint_text":"- The occurrence of serious adverse events at 26 weeks after enrollment in Part I.","definition_or_measurement_approach":"Occurrence of serious adverse events recorded up to 26 weeks after enrollment in Part I."}
• {"endpoint_text":"- The occurence of non-serious adverse events at 26 weeks after enrollment in Part I.","definition_or_measurement_approach":"Occurrence of non-serious adverse events recorded up to 26 weeks after enrollment in Part I."}
• {"endpoint_text":"- The occurence of organ damage (based on VDI) at 26 weeks after enrollment in Part I.","definition_or_measurement_approach":"Organ damage assessed by Vasculitis Damage Index (VDI) at 26 weeks after enrollment in Part I."}
• {"endpoint_text":"- Change at 13 and 26 weeks after enrollment in Part I from baseline: a. ANCA autoantibody titre, b. CD19+ lymphocyte count, c. Concentration of C5a component of complement, d. Creatinine concentration, e. eGFR.","definition_or_measurement_approach":"Laboratory measurements of ANCA titre, CD19+ counts, C5a concentration, creatinine, and eGFR at 13 and 26 weeks compared with baseline."}
• {"endpoint_text":"- The occurrence of a major relapse (defined as an increase in BVAS/WG score to ≥3 points, requiring reinitiation of remission-inducing treatment) at 26, 52, 78, and 104 weeks after randomization to Part II.","definition_or_measurement_approach":"Major relapse defined as BVAS/WG increase to ≥3 requiring reinitiation of remission-inducing treatment; assessed at 26, 52, 78, 104 weeks post-randomization to Part II."}
• {"endpoint_text":"- The occurrence of a minor relapse (defined as an increase in BVAS/WG score to 1-2 points, requiring only an increase in maintenance glucocorticosteroid dose) at 26, 52, 78, and 104 weeks after randomization to Part II.","definition_or_measurement_approach":"Minor relapse defined as BVAS/WG increase to 1-2 points requiring increase in maintenance steroid dose; assessed at specified timepoints."}
• {"endpoint_text":"- The occurrence of serious adverse events at 26, 52, 78, and 104 weeks after randomization to Part II.","definition_or_measurement_approach":"Occurrence of serious adverse events recorded at 26, 52, 78, and 104 weeks after randomization to Part II."}
• {"endpoint_text":"- The occurrence of non-serious adverse events at 26, 52, 78, and 104 weeks from randomization to Part II.","definition_or_measurement_approach":"Occurrence of non-serious adverse events recorded at 26, 52, 78, and 104 weeks after randomization to Part II."}
• {"endpoint_text":"- The occurrence of organ damage (based on VDI) at 26, 52, 78, and 104 weeks after randomization to Part II.","definition_or_measurement_approach":"Organ damage (VDI) assessed at 26, 52, 78, and 104 weeks after randomization to Part II."}
• {"endpoint_text":"- Change at 26, 52, 78, and 104 weeks after randomization to Part II from baseline: a. ANCA autoantibody titers, b. CD 19+ lymphocyte count, c. Concentration of C5a component of complement, d. Creatinine concentration, e. eGFR.","definition_or_measurement_approach":"Laboratory measurements of listed biomarkers at 26, 52, 78, 104 weeks compared with baseline."}
• {"endpoint_text":"- Change at 26, 52, 78, and 104 weeks after randomization to Part II from baseline in quality of life as measured by the SF-36 form.","definition_or_measurement_approach":"Quality of life assessed by SF-36 at 26, 52, 78, 104 weeks compared with baseline."}

Poland

Earliest CTIS Part Ii Submission Date

08-10-2024

Latest Decision Or Authorization Date

24-11-2024

Processing Time Days

47

Number Of Sites

6

Number Of Participants

130

Primary sponsor

Full Name

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Poland

Third parties

• {"country":"","full_name":"Agencja Badań Medycznych","duties_or_roles":"Source of monetary support","organisation_type":""}