Study of Blinatumomab for the Treatment of Calcineurin Inhibitor-Resistant or Intolerant Steriod-Resistant Nephrotic Syndrome in Pediatric Patients
This exploratory clinical trial aims to evaluate the efficacy and safety of Blinatumomab in treating children with calcineurin inhibitor (CNI)-resistant or multidrug-resistant steroid-resistant nephrotic syndrome (SRNS). Eligible participants include pediatric patients aged 2 to 17 years who have either failed to respond to adequate CNI therapy or are resistant to at least two classes of immunosuppressants, including CNIs and biologics. A short course of low-dose Blinatumomab will be administered in an open-label, single-arm, self-controlled trial design. The study seeks to determine whether Blinatumomab can reduce proteinuria and induce clinical remission in this difficult-to-treat population, offering a potential new therapeutic option for children with limited response to conventional therapies.
‣ Subjects must meet all of the following criteria to be included in the study:
• Age between 2 and 17 years, regardless of gender. 2.Meet the 2021 KDIGO definition of steroid-resistant nephrotic syndrome (SRNS), and fulfill either of the following:
⁃ Have received an adequate dose of calcineurin inhibitors (CNIs) for more than 6 months without achieving at least partial remission.
⁃ Or have contraindications to CNI use, including:
‣ 1\) Significant renal impairment, defined as estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m², or presence of acute kidney injury at the time of diagnosis; 2) Renal biopsy showing prominent acute or chronic tubular injury, such as tubular atrophy or interstitial fibrosis involving more than 50% of the sampled tissue; 3) Elevated urinary markers (β2-microglobulin, α1-microglobulin, or retinol-binding protein) exceeding three times the upper limit of normal; 4) Abnormal glucose tolerance; 5) Severe uncontrolled hypertension, defined as systolic and/or diastolic blood pressure ≥ the 95th percentile + 12 mmHg for age, sex, and height, or ≥ 140/90 mmHg; 6) Concomitant use of medications known to have significant interactions with CNIs, leading to increased toxicity or reduced efficacy; 7) Known allergy or hypersensitivity to CNIs or any of their components. (3) Or have demonstrated inadequate response or disease relapse after treatment with at least two immunosuppressive agents, including CNIs and at least one of the following:
⁃ Conventional immunosuppressive agents: cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide
⁃ Biologic agents: abatacept, ofatumumab, obinutuzumab, rituximab Inadequate response is defined as failure to achieve complete remission after 12 months of therapy or relapse following initial response.
‣ 3\. Renal biopsy performed prior to screening confirms a diagnosis of minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS).
‣ 4\. The subject and/or their legal guardian must provide written informed consent, indicating understanding of the study's purpose and procedures, with the right to withdraw consent at any time without affecting the subject's future medical care.