Membranous Nephropathy
Conditions
Interventions
Initial Cohort:Initial Treatment Administration: Patients will receive standard-dose Zebutonumab therapy, specifically 1000 mg, administered intravenously at Week 0 and Week 2.
Treatment Adjustment Ba
otherwise, an additional treatment course (Zebutonumab 1000 mg, administered intravenously at Week 24) will be continued.
The study will continue to observe until Week 52, with five follow-up visits d
Immunosuppressive Treatment Failure Cohort:Initial Treatment Administration: Patients will receive standard-dose Zebutonuma
Sponsors
The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria to be enrolled in this study: (1) Age between 18 and 75 years; (2) Diagnosed with primary membranous nephropathy through kidney biopsy within the past 5 years; (3) Positive PLA2R antibody as indicated by serological or histopathological testing; (4) Urine protein > 3.5 g based on the average of two 24-hour urine samples collected within 14 days; (5) If receiving non-immunosuppressive anti-proteinuria treatment, the dosage must be stable within 2 weeks prior to screening or since the start of treatment; (6) If receiving immunosuppressive therapy, the treatment must be discontinued within 2 weeks prior to screening; if it is corticosteroid medication, the dosage should be gradually reduced during the study; (7) 24-hour creatinine clearance >= 40 mL/min/1.73m², or estimated glomerular filtration rate (eGFR) >= 40 mL/min/1.73m² when receiving ACEi/ARB treatment; (8) Assessed by the investigator as suitable to receive Zebutonumab, including: Cohort 1: Newly diagnosed membranous nephropathy patients who have not previously received immunosuppressive treatment: diagnosis of membranous nephropathy = 3 months without remission, or patients receiving rituximab treatment for >= 6 months without remission; or patients unable to tolerate adverse reactions from CNI drugs and/or corticosteroids combined with cyclophosphamide; or MN patients who have relapsed after remission following treatment with CNI drugs and/or corticosteroids combined with cyclophosphamide and/or rituximab. (9) Patients must understand the purpose and procedures of this trial and voluntarily sign a written informed consent form.
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria shall be excluded from this study: (1) Patients with secondary membranous nephropathy (e.g., due to malignancy, systemic infections, systemic autoimmune diseases, medications, etc.); (2) Patients with type I or type II diabetes; (3) Positive screening for hepatitis C antibody; positive HIV serology; (4) Positive serological tests for hepatitis B during screening: a. Hepatitis B surface antigen (HBsAg); b. Hepatitis B core antibody (HBcAb) and Hepatitis B virus (HBV) DNA above the lower limit of quantification (LLOQ) during screening. Patients who are HBsAg negative, HBcAb positive, and have HBV DNA levels below LLOQ are eligible for this study, but must be monitored for HBV DNA every 3 months for up to 6 months after the last dose; (5) Patients who have experienced a significant infection or active infection within the last 3 months; (6) Any of the following conditions: a. History of active tuberculosis; b. Active tuberculosis symptoms or signs discovered during screening; c. Signs of active tuberculosis infection on chest imaging during screening or within the 12 weeks prior to screening; d. Recent close contact with a patient with active tuberculosis, requiring referral to a tuberculosis specialist for assessment; if necessary, appropriate latent tuberculosis treatment may be provided, and inclusion is allowed after completing appropriate latent tuberculosis treatment; e. Patients with positive T-SPOT results during screening require comprehensive evaluation to exclude active tuberculosis; those diagnosed with latent TB must complete latent tuberculosis treatment before receiving the investigational drug. (7) Severe renal impairment, including those requiring dialysis or other renal replacement therapy; (8) Receipt of live vaccines within 4 weeks prior to screening or during screening, major surgery (excluding diagnostic procedures), or participation in other clinical trials; (9) Pregnant or breastfeeding women; (10) Participants unwilling to comply with scientifically acceptable contraceptive methods throughout the study; (11) Patients with any contraindications specified in the Zebutonumab prescribing information; (12) Any other condition that the investigator deems inappropriate for participation in this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 24-hour urinary protein;Estimated Glomerular Filtration Rate;Anti PLA2R antibody;B cell level examination;Creatinine clearance rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Urine pregnancy examination;HIV testing;HBV testing;HCV testing;Vital sign examination;Physical examination;Electrocardiogram;T-SPOT detection;Chest X-ray;Height;Weight;Body surface area;Blood routine and C reactive protein;Blood biochemistry test;Urinalysis; | — |
Countries
China
Contacts
Public ContactQiang He
The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)
Outcome results
None listed