Using Blinatumomab to treat children with resistant nephrotic syndrome

Study of Blinatumomab for the Treatment of Calcineurin Inhibitor-Resistant or Intolerant Steriod-Resistant Nephrotic Syndrome in Pediatric Patients

This study is testing if a new drug called Blinatumomab can help children with tough-to-treat nephrotic syndrome feel better by reducing protein in their urine.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 2 Years to 17 Years
• Sex: All
• Sponsor: The Children's Hospital of Zhejiang University School of Medicine (other)
• Drugs / interventions: ofatumumab, obinutuzumab, rituximab, methotrexate, cyclophosphamide, Blinatumomab
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06607991 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of Blinatumomab in children suffering from calcineurin inhibitor (CNI)-resistant or intolerant, steroid-resistant nephrotic syndrome (SRNS). The study involves administering two short courses of low-dose Blinatumomab intravenously to pediatric patients aged 2 to 17 who have not responded to CNI treatments or cannot tolerate them. The primary goal is to assess the reduction of proteinuria and the induction of remission, potentially providing a new treatment option for these patients. The study will also monitor safety and immune responses to the treatment.

Who should consider this trial

Good fit: Ideal candidates are children aged 2 to 17 with steroid-resistant nephrotic syndrome who are either resistant to or intolerant of calcineurin inhibitors.

Not a fit: Patients who do not meet the age criteria or have not been diagnosed with steroid-resistant nephrotic syndrome will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for children with limited alternatives for managing their nephrotic syndrome.

How similar studies have performed: While the use of Blinatumomab in this specific context is novel, similar approaches targeting immune dysfunction have shown promise in other studies.

Eligibility criteria

\- Inclusion Criteria:

Subjects must meet all of the following criteria to be included in the study:

1.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:

1. Have received an adequate dose of calcineurin inhibitors (CNIs) for more than 6 months without achieving at least partial remission.
2. 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:

1. Conventional immunosuppressive agents: cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide
2. 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.

-Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from the study:

1. eGFR \&lt; 60 mL/min/1.73 m² (using the modified Bedside Schwartz formula);
2. Stroke or seizure within 6 months prior to screening, or other active central nervous system disorders;
3. Genetic nephropathy confirmed by genetic testing;
4. Renal biopsy confirming IgA nephropathy, membranous nephropathy, or membranoproliferative glomerulonephritis;
5. Severe congenital heart disease or history of acute myocardial infarction within 6 months, or severe arrhythmias (e.g., frequent multifocal ventricular or supraventricular tachycardia, ventricular tachycardia), or moderate to large pericardial effusion, severe myocarditis, or unstable vital signs requiring vasopressors to maintain blood pressure;
6. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with hepatitis B virus (HBV) DNA levels above the normal range; positive for hepatitis C virus (HCV) antibodies with HCV RNA levels above the normal range; or positive for human immunodeficiency virus (HIV) antibodies, syphilis, or cytomegalovirus (CMV) DNA;
7. Abnormal laboratory values prior to screening: moderate to severe neutropenia (≤1.0×10⁹/L); moderate to severe anemia (hemoglobin ≤90 g/L); thrombocytopenia (≤75×10⁹/L); or liver dysfunction (ALT, AST, or bilirubin greater than 2.5 times the upper limit of normal and persisting for 2 weeks);
8. Subjects with tumors or other life-threatening diseases prior to screening;
9. Positive blood pregnancy test;
10. Participation in other clinical trials within 1 month prior to enrollment;
11. Received rituximab or cyclophosphamide therapy within the past 3 months;
12. Any other condition deemed by the investigator to be unsuitable for participation;
13. Vaccination with live vaccines within 4 weeks prior to screening.

Where this trial is running

Hangzhou, Zhejiang

• Children's Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Principal investigator: Jianhua Mao, PhD, MD — Children's Hospital, Zhejiang University School of Medicine
• Study coordinator: Jianhua Mao, PhD, MD

Conditions: CNI-resistant Steriod Resistant Nephrotic Syndrome, CNI-intolerent, Steriod Resistant Nephrotic Syndrome, Multidrug Resistant Nephrotic Syndrome, CNI-resistant SRNS, children, Blinatumomab, Multidrug resistant steroid resistant nephrotic syndrome