Blinatumomab for CNI-Resistant/Intolerant SRNS in Children

NCT ID: NCT06607991

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-19
• Study Completion Date: 2027-09-18

Brief Summary

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.

Detailed Description

Nephrotic syndrome (NS) in children is characterized by excessive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Approximately 15-20% of pediatric NS cases are classified as steroid-resistant nephrotic syndrome (SRNS), a condition associated with poor prognosis and limited response to standard therapies. Calcineurin inhibitors (CNIs) are frequently used as first-line immunosuppressants in SRNS; however, a subset of patients demonstrate resistance to or intolerance of CNIs. Moreover, a proportion of patients may be refractory to multiple classes of immunosuppressive agents, including biologics, posing a significant therapeutic challenge.

This exploratory, single-center, open-label clinical trial is designed to evaluate the safety and efficacy of Blinatumomab-a bispecific T-cell engager targeting CD19-positive B cells-in pediatric patients with CNI-resistant or multidrug-resistant SRNS. Eligible participants will include children aged 2 to 17 years who have either not responded to adequate CNI therapy or have failed to achieve remission despite treatment with at least two classes of immunosuppressive agents (including CNIs and biologics).

A total of 6 patients will be enrolled and administered two short courses of low-dose Blinatumomab intravenously, each lasting 5 days. The primary efficacy outcome will be the rate of complete or partial remission of proteinuria. Secondary outcomes will include safety and tolerability assessments, changes in immunologic markers, and renal function monitoring. By selectively depleting CD19-positive B cells, Blinatumomab may modulate aberrant immune activation that underlies treatment-resistant SRNS.

This study seeks to generate preliminary data on the potential therapeutic role of Blinatumomab in this difficult-to-treat pediatric population, with the ultimate goal of identifying a novel immunomodulatory approach for SRNS patients with limited treatment options.

Conditions

CNI-resistant Steriod Resistant Nephrotic Syndrome; CNI-intolerent; Steriod Resistant Nephrotic Syndrome; Multidrug Resistant Nephrotic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Blinatumomab Treatment

Group Type: EXPERIMENTAL

Blinatumomab Treatment

Intervention Type: DRUG

Blinatumomab treatment for CNI-resistant/Intolerant pediatric steriod-resistant nephrotic syndrome Patients will receive two 5-day cycles of Blinatumomab (5 µg/m²/day, maximum dose 9 µg/day), administered intravenously. The second cycle will begin on the first day of the third week following the first cycle.

Interventions

Blinatumomab Treatment

Blinatumomab treatment for CNI-resistant/Intolerant pediatric steriod-resistant nephrotic syndrome Patients will receive two 5-day cycles of Blinatumomab (5 µg/m²/day, maximum dose 9 µg/day), administered intravenously. The second cycle will begin on the first day of the third week following the first cycle.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Children's Hospital of Zhejiang University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Mao Jianhua

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jianhua Mao, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Children&#39;s Hospital, Zhejiang University School of Medicine

Locations

Children&#39;s Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jianhua Mao, PhD, MD

Role: CONTACT

maojh88@zju.edu.cn

13516819071

Xiaojing Zhang, MD

Role: CONTACT

6510007@zju.edu.cn

15867172808

Facility Contacts

Jianhua Mao, PhD, MD

Role: primary

maojh88@zju.edu.cn

86+13616819071

Other Identifiers

2024-IRB-0241-P-01

Identifier Type: -

Identifier Source: org_study_id