Blinatumomab for CNI-Resistant/Intolerant SRNS in Children

NCT06607991 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 2024-IRB-0241-P-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

CNI-resistant SRNS; children; Blinatumomab; Multidrug resistant steroid resistant nephrotic syndrome; steroid resistant nephrotic syndrome

Outcome Measures

Primary Outcomes (1)

• Effectiveness and safety of Blinatumomab

  Effectiveness: The primary endpoint is the proportion of patients achieving complete or partial remission within 24 weeks of treatment. Complete remission is defined as a urinary protein/creatinine ratio (UPCR) ≤ 200 mg/g for three consecutive days, while partial remission is defined as a ≥ 50% reduction in proteinuria from baseline with a UPCR between 200 and 2000 mg/g. Safety: Adverse events (AEs) and serious adverse events (SAEs) will be monitored and classified according to the CTCAE v5.0. This includes events such as cytokine release syndrome, fever, headache, and potential neurotoxicity.

  with 24 weeks of Blinatumomab treatment

Secondary Outcomes (1)

• long-term efficacy of Blinatumomab and Immunological Markers

  with 52 weeks of Blinatumomab

Study Arms (1)

Blinatumomab Treatment

EXPERIMENTAL

Drug: Blinatumomab Treatment

Interventions

Blinatumomab Treatment 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.

Blinatumomab Treatment

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:
• \) 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.
• \. Renal biopsy performed prior to screening confirms a diagnosis of minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS).
• \. 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.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from the study:
• eGFR \&lt; 60 mL/min/1.73 m² (using the modified Bedside Schwartz formula);
• Stroke or seizure within 6 months prior to screening, or other active central nervous system disorders;
• Genetic nephropathy confirmed by genetic testing;
• Renal biopsy confirming IgA nephropathy, membranous nephropathy, or membranoproliferative glomerulonephritis;
• 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;
• 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;
• 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);
• Subjects with tumors or other life-threatening diseases prior to screening;
• Positive blood pregnancy test;
• Participation in other clinical trials within 1 month prior to enrollment;
• Received rituximab or cyclophosphamide therapy within the past 3 months;
• Any other condition deemed by the investigator to be unsuitable for participation;
• Vaccination with live vaccines within 4 weeks prior to screening.

Sponsors & Collaborators

• The Children's Hospital of Zhejiang University School of Medicine: lead

Study Sites (1)

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

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Conditions

Nephrotic Syndrome

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Jianhua Mao, PhD, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianhua Mao, PhD, MD

CONTACT

13516819071; maojh88@zju.edu.cn

Xiaojing Zhang, MD

CONTACT

15867172808; 6510007@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 18, 2024
• First Posted: September 23, 2024
• Study Start: September 19, 2024
• Primary Completion (Estimated): September 19, 2026
• Study Completion (Estimated): September 18, 2027
• Last Updated: August 6, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)