Zuberitamab in the First Episode of Paediatric Nephrotic Syndrome

NCT07765914 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: HiFIRPedINS
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 9

Brief Summary

The goal of this clinical trial is to learn whether adding Zuberitamab to standard corticosteroid therapy can help prevent relapse in children and adolescents aged 1 to 18 years with newly diagnosed steroid-sensitive nephrotic syndrome (SSNS). It will also learn about the safety of Zuberitamab. The main questions it aims to answer are:

• Does Zuberitamab plus standard corticosteroid therapy prolong the time to first relapse compared with standard corticosteroid therapy alone?
• What medical problems do participants experience during treatment? Researchers will compare Zuberitamab plus standard corticosteroid therapy to standard corticosteroid therapy alone to see whether adding Zuberitamab improves disease control. Participants will:
• Receive standard corticosteroid treatment for approximately 12 weeks, with or without a single intravenous infusion of Zuberitamab after achieving remission
• Take preventive antibiotics if they are in the Zuberitamab group
• Test their urine daily at home using dipsticks and record results in a diary
• Visit the clinic for regular checkups and blood and urine tests during follow-up for up to 12 months

Conditions

Nephrotic Syndrome

Keywords

Anti-CD20 Monoclonal Antibody, Randomised Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Relapse-free survival time within 12 months after randomization

  Time from randomization to the first confirmed disease relapse during the 12-month follow-up period. Participants without relapse will be censored at the date of the last available assessment. Relapse is defined according to the 2023 International Pediatric Nephrology Association (IPNA) criteria as urine dipstick protein ≥3+ (≥300 mg/dL) or urine protein-to-creatinine ratio (UPCR) ≥200 mg/mmol (≥2 mg/mg) on a spot urine sample for three consecutive days, with or without edema, in a participant who previously achieved complete remission.

  From randomization until first relapse or 12 months after randomization, whichever occurs first.

Secondary Outcomes (28)

• Relapse-Free Survival Rate at 12 Months Post-Randomization

  12 months post-randomization.

• Relapse-Free Survival Rate at 6 Months Post-Randomization

  6 months post-randomization.

• Cumulative Steroid Dose at 12 Months Post-Randomization

  12 months post-randomization.

• Change From Baseline in Serum Creatinine (Renal Function) at 12 Months

  From baseline to 12 months post-randomization.

• Change From Baseline in Serum Creatinine at the Time of Relapse

  From baseline to the date of documented disease relapse (up to 12 months).

Study Arms (2)

Zuberitamab + Standard corticosteroid treatment

EXPERIMENTAL

Zuberitamab plus standard corticosteroid treatment: Zuberitamab 375 mg/m2 (max 500 mg) as a single IV dose after remission. Premedication 30 min prior includes oral antipyretic and antihistamine and IV methylprednisolone 1.6 mg/kg (max 48 mg); oral steroid withheld on infusion day. Standard corticosteroid treatment consists of oral prednisone/prednisolone per protocol taper. TMP-SMZ prophylaxis (TMP 3 mg/kg on alternate days, max SMZ 960 mg) is administered until CD19 recovery. Relapse is managed per protocol with corticosteroid re-induction and possible repeat zuberitamab after remission. Permitted and prohibited concomitant medications are the same as in the comparator arm.

Biological: Zuberitamab; Drug: standard corticosteroid treatment

Standard corticosteroid treatment Only

ACTIVE COMPARATOR

Standard corticosteroid treatment: oral prednisone/prednisolone 2 mg/kg/day (max 60 mg) for 6 weeks, followed by 1.5 mg/kg (max 40 mg) on alternate days for 6 weeks, then discontinue. No zuberitamab, TMP-SMZ prophylaxis, or infusion premedication is given during initial treatment. Relapse is managed per protocol with corticosteroid re-induction; participants may receive zuberitamab after remission is re-achieved according to predefined criteria. Permitted concomitant medications include antihypertensives, calcium supplementation, anti-infective agents, antihistamines, anticoagulants, IVIG, hepatoprotective agents, glucose-lowering medications, and ophthalmic treatments. Prohibited therapies include other immunosuppressants (rituximab, CNIs, MMF, cyclophosphamide, plasma exchange) and Chinese herbal medicines for nephrotic syndrome (e.g., Huangkui, Huaiqihuang, Tripterygium). Live vaccines are prohibited during B-cell depletion.

Drug: standard corticosteroid treatment

Interventions

Zuberitamab BIOLOGICAL

Zuberitamab is administered as a single intravenous infusion at a dose of 375 mg/m² (maximum 500 mg) following achievement of steroid-sensitive remission. To reduce the risk of infusion-related reactions, premedication is administered approximately 30 minutes before infusion and may include: * Acetaminophen or ibuprofen; * Cetirizine, cyproheptadine, loratadine, or equivalent antihistamines; * Intravenous methylprednisolone 1.6 mg/kg (maximum 48 mg). Participants receiving zuberitamab also receive prophylactic trimethoprim-sulfamethoxazole (TMP 3 mg/kg every other day; maximum SMZ dose 960 mg every other day) until B-cell recovery. Infusion-related reactions are managed according to protocol-defined procedures, including infusion rate reduction, temporary interruption, permanent discontinuation when clinically indicated, and appropriate supportive therapy.

Also known as: Zuberitamab (BioRay Biopharmaceutical Co., Ltd.)

Zuberitamab + Standard corticosteroid treatment

standard corticosteroid treatment DRUG

standard corticosteroid treatment administered orally to treat steroid-sensitive nephrotic syndrome: 6 weeks at 2 mg/kg (max 60 mg/day), then alternate day steroid 1.5 mg/kg (max 40 mg on alternate days) for 6 weeks.

Also known as: prednisolone/prednisone

Standard corticosteroid treatment Only; Zuberitamab + Standard corticosteroid treatment

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Newly diagnosed steroid-sensitive nephrotic syndrome (SSNS) according to the 2023 IPNA criteria, who achieved complete remission after steroid induction therapy prior to study entry, defined as UPCR (based on first morning void or 24 h urine sample) \<= 20 mg/mmol (0.2 mg/mg), or negative or trace dipstick on three or more consecutive days.
• An estimated glomerular filtration rate \>= 90 mL/min/ 1.73 m2 at study entry.
• Peripheral blood CD20+ (detected as CD19+) cells \>= 1% of total lymphocytes.
• No use of other immunosuppressants within 3 months prior to study entry, other than steroids for nephrotic syndrome.

You may not qualify if:

• Known etiology including congenital nephrotic syndrome, IgA nephropathy, Henoch-Schönlein purpura nephritis, lupus nephritis, or other secondary nephrotic syndromes.
• Patients exhibiting any of the following abnormal clinical laboratory values: leukopenia (white blood cells \<= 3.0 × 10\^9/L), absolute neutrophil count \< 1.5 × 10\^9/L; moderate to severe anemia (hemoglobin \< 9.0 g/dL); thrombocytopenia (platelet count \< 100 × 10\^12/L); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal; positive for any autoimmune markers (ANA, ENA, ANCA, etc.) or decreased complement C3 levels.
• Evidence of the following infections: severe or opportunistic infection within the previous 6 months (active tuberculosis or history of tuberculosis or suspected tuberculosis; chronic active infections such as EBV, CMV; active hepatitis B presentation or history, or hepatitis C or hepatitis B virus carrier; HIV infection; or other active viral infections).
• Receipt of live vaccine within one month prior to study entry.
• History of previous use of biological agents.
• Current examination suggestive of heart failure, severe arrhythmia, angina pectoris (CTCAE Grade 4), or uncontrolled blood pressure.
• Severe diseases of vital organs such as the brain or liver, or suffering from hematological or endocrine system disorders.
• Diagnosis of co-existing autoimmune diseases, primary immunodeficiency, or malignancy.
• History of organ transplantation (excluding cornea and hair transplants).
• Known allergy to methylprednisolone, Zuberitamab injection active ingredients or any excipients, sulfamethoxazole (or a contraindication to this drug due to G6PD deficiency).
• Investigator's judgment that the patient is unsuitable for participation in this study (e.g., patient is highly likely to be lost to follow-up or provide false results, such as alcohol dependence or psychiatric illness).

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead
• Guiyang Maternal and Child Health Care Hospital: collaborator
• Wuhan Children's Hospital: collaborator
• Shanghai Children's Medical Center: collaborator
• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Shanghai Children's Hospital: collaborator
• Wuxi Women's & Children's Hospital: collaborator
• Xiamen Maternity & Child Care Hospital: collaborator
• Second Xiangya Hospital of Central South University: collaborator

Study Sites (9)

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Location

Second Xiangya Hospital of Central South University

Changsha, China

Location

Guiyang Maternal and Child Health Care Hospital

Guiyang, China

Location

Shanghai Children's Hospital

Shanghai, China

Location

Shanghai Children's Medical Center

Shanghai, China

Location

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, China

Location

Wuhan Children's Hospital

Wuhan, China

Location

Wuxi Women's & Children's Hospital

Wuxi, China

Location

Xiamen Maternity & Child Care Hospital

Xiamen, China

Location

Related Publications (2)

• Su X, Wu B, Tie X, Guo X, Feng R, Qiao X, Wang L. Obinutuzumab as Initial or Second-Line Therapy in Patients With Primary Membranous Nephropathy. Kidney Int Rep. 2024 May 13;9(8):2386-2398. doi: 10.1016/j.ekir.2024.05.004. eCollection 2024 Aug.

  PMID: 39156138 BACKGROUND

• Liu J, Deng F, Wang X, Liu C, Sun S, Zhang R, Zhang A, Jiang X, Yan W, Dou Y, Zhang Y, Xie L, Qian B, Shen Q, Xu H. Early Rituximab as an Add-On Therapy in Children With the Initial Episode of Nephrotic Syndrome. Kidney Int Rep. 2024 Feb 16;9(5):1220-1227. doi: 10.1016/j.ekir.2024.02.1395. eCollection 2024 May.

  PMID: 38707815 RESULT

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

Long-Term Synaptic Depression; Prednisolone; Prednisone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Neuronal Plasticity; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Study Officials

• Hong Xu

  Children's Hospital of Fudan University

  PRINCIPAL INVESTIGATOR

• Qian Shen

  Children's Hospital of Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jialu Liu

CONTACT

8602164932827; jialuliu10@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: August 14, 2026
• Study Start (Estimated): August 20, 2026
• Primary Completion (Estimated): August 20, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)