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Zuberitamab in the First Episode of Paediatric Nephrotic Syndrome

11. srpna 2026 aktualizováno: Children's Hospital of Fudan University

Efficacy and Safety of Single-dose Zuberitamab in the Initial Episode of Paediatric Steroid-sensitive Nephrotic Syndrome: A Multicenter Randomized Controlled Trial

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

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

Primary nephrotic syndrome (PNS) is the most common glomerular disease in children. Although 80-90% of affected children achieve complete remission after initial corticosteroid therapy and are classified as having steroid-sensitive nephrotic syndrome (SSNS), most experience disease relapse within the first year after onset. Approximately half subsequently develop frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS), requiring prolonged exposure to corticosteroids and additional immunosuppressive agents. Recurrent relapses and long-term immunosuppressive treatment are associated with substantial morbidity, including infection, impaired growth and development, metabolic complications, nephrotoxicity, and reduced quality of life.

B-cell depletion therapy has emerged as an effective strategy for relapsing nephrotic syndrome. Rituximab, an anti-CD20 monoclonal antibody, has demonstrated the ability to reduce relapse rates and maintain remission in children with FRNS/SDNS, even after withdrawal of corticosteroids and other immunosuppressive agents. Based on accumulating evidence, rituximab has been incorporated into international treatment guidelines. Building upon extensive clinical experience with rituximab, our group initiated an investigator-sponsored multicenter study evaluating early rituximab treatment in children with newly diagnosed SSNS. Long-term follow-up from this study suggested potential benefits in preventing relapse and demonstrated an acceptable safety profile.

Zuberitamab is a next-generation anti-CD20 monoclonal antibody developed through molecular engineering of rituximab. Compared with rituximab, preclinical studies have demonstrated enhanced antibody-dependent cellular cytotoxicity (ADCC), a larger steady-state volume of distribution, and more sustained B-cell depletion. Zuberitamab was approved in China in 2023 for the treatment of CD20-positive diffuse large B-cell lymphoma. In addition, its use in kidney diseases has been reported in retrospective cohort studies and other early clinical experiences, including patients with membranous nephropathy. However, evidence regarding its efficacy and safety in glomerular diseases, particularly in paediatric nephrotic syndrome, remains limited.

Current treatment strategies for childhood nephrotic syndrome primarily focus on managing relapses after they occur rather than preventing them during the early phase of disease. Whether early intervention with a potent anti-CD20 monoclonal antibody can modify the disease course and reduce future relapses remains uncertain. This study is designed to evaluate the efficacy and safety of early Zuberitamab administration in combination with standard corticosteroid therapy in children with newly diagnosed steroid-sensitive nephrotic syndrome.

This is a multicenter, open-label, randomized controlled trial conducted across nine pediatric nephrology centers in China. Children with newly diagnosed steroid-sensitive nephrotic syndrome (SSNS) who achieve remission following standard corticosteroid treatment will be randomized at weeks 4-5 after remission to receive either Zuberitamab plus standard corticosteroid treatment or standard corticosteroid treatment alone. Participants will be followed prospectively for up to 12 months to assess disease relapse, cumulative corticosteroid exposure, safety outcomes, kidney function, and health-related quality of life.

The study aims to determine whether early addition of Zuberitamab at weeks 4-5 after remission, compared with standard corticosteroid treatment alone, can prolong time to first relapse within 12 months.

Typ studie

Intervenční

Zápis (Odhadovaný)

120

Fáze

  • Fáze 3

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

Studijní místa

  • Čína
      • Changsha, Čína
        • Second Xiangya Hospital of Central South University
      • Guiyang, Čína
        • Guiyang Maternal and Child Health Care Hospital
        • Kontakt:
          • Yuhong Li
      • Shanghai, Čína
        • Shanghai Children's Medical Center
      • Shanghai, Čína
        • Shanghai Children's Hospital
      • Shanghai, Čína
        • Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
      • Wuhan, Čína
        • Wuhan Children's Hospital
      • Wuxi, Čína
        • Wuxi Women's & Children's Hospital
      • Xiamen, Čína
        • Xiamen Maternity & Child Care Hospital
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, Čína
        • Children's Hospital of Fudan University
        • Kontakt:
          • Hong Xu

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dítě
  • Dospělý

Přijímá zdravé dobrovolníky

Ne

Popis

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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).

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Singl

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Zuberitamab + Standard corticosteroid treatment
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.
Biologický: Zuberitamab

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.

Ostatní jména:
  • Zuberitamab (BioRay Biopharmaceutical Co., Ltd.)
Lék: standard corticosteroid treatment
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.
Ostatní jména:
  • prednisolon/prednison
Aktivní komparátor: Standard corticosteroid treatment Only
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.
Lék: standard corticosteroid treatment
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.
Ostatní jména:
  • prednisolon/prednison

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Relapse-free survival time within 12 months after randomization
Časové okno: From randomization until first relapse or 12 months after randomization, whichever occurs first.
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.

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Relapse-Free Survival Rate at 12 Months Post-Randomization
Časové okno: 12 months post-randomization.
The proportion of participants who remain free from disease relapse at 12 months after randomization.
12 months post-randomization.
Relapse-Free Survival Rate at 6 Months Post-Randomization
Časové okno: 6 months post-randomization.
The proportion of participants who remain free from disease relapse at 6 months after randomization.
6 months post-randomization.
Cumulative Steroid Dose at 12 Months Post-Randomization
Časové okno: 12 months post-randomization.
The total amount of steroid medication (prednisolone) taken by participants from randomization until 12 months.
12 months post-randomization.
Change From Baseline in Serum Creatinine (Renal Function) at 12 Months
Časové okno: From baseline to 12 months post-randomization.
Change from baseline in serum creatinine levels to assess renal function.
From baseline to 12 months post-randomization.
Change From Baseline in Serum Creatinine at the Time of Relapse
Časové okno: From baseline to the date of documented disease relapse (up to 12 months).
Change from baseline in serum creatinine levels measured at the acute phase of disease relapse.
From baseline to the date of documented disease relapse (up to 12 months).
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at 12 Months
Časové okno: From baseline to 12 months post-randomization
Change from baseline in eGFR, calculated using an appropriate pediatric formula (e.g., the modified Schwartz formula), to assess renal function.
From baseline to 12 months post-randomization
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at the Time of Relapse
Časové okno: From baseline to the date of documented disease relapse (up to 12 months)
Change from baseline in eGFR at the acute phase of disease relapse.
From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Scores at 12 Months
Časové okno: From baseline to 12 months post-randomization
Change from baseline in total and domain-specific scores (physical, emotional, social, and school functioning) using the PedsQL 4.0 Chinese Standard Version (30-day recall) and PedsQL Infant scales (13-24 months). Scores range from 0 to 100, with higher scores indicating better quality of life. Includes child self-report (ages 5-18) and parent proxy (ages 2-18 and infants).
From baseline to 12 months post-randomization
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Scores at the Time of Relapse
Časové okno: From baseline to the date of documented disease relapse (up to 12 months)
Change from baseline in PedsQL total and domain scores measured at the time of disease relapse. Scores range from 0 to 100, with higher scores indicating better quality of life.
From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in Systolic Blood Pressure Z-scores at 12 Months
Časové okno: From baseline to 12 months post-randomization
Change from baseline in systolic blood pressure, expressed as Z-scores relative to age-, sex-, and height-specific normative data.
From baseline to 12 months post-randomization
Change From Baseline in systolic Blood Pressure Z-scores at the Time of Relapse
Časové okno: From baseline to the date of documented disease relapse (up to 12 months)
Change from baseline in systolic blood pressure, expressed as Z-scores relative to age-, sex-, and height-specific normative data.
From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in diastolic Blood Pressure Z-scores at 12 Months
Časové okno: From baseline to 12 months post-randomization
Change from baseline in diastolic blood pressure, expressed as Z-scores relative to age-, sex-, and height-specific normative data.
From baseline to 12 months post-randomization
Change From Baseline in diastolic Blood Pressure Z-scores at the Time of Relapse
Časové okno: From baseline to the date of documented disease relapse (up to 12 months)
Change from baseline in diastolic blood pressure, expressed as Z-scores relative to age-, sex-, and height-specific normative data.
From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in Height Z-scores at 12 Months
Časové okno: From baseline to 12 months post-randomization
Change from baseline in height, expressed as Z-scores relative to age- and sex-specific normative growth charts.
From baseline to 12 months post-randomization
Change From Baseline in Height Z-scores at the Time of Relapse
Časové okno: From baseline to the date of documented disease relapse (up to 12 months)
Change from baseline in height Z-scores at the acute phase of disease relapse.
From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in Weight Z-scores at 12 Months
Časové okno: From baseline to 12 months post-randomization
Change from baseline in weight, expressed as Z-scores relative to age- and sex-specific normative growth charts.
From baseline to 12 months post-randomization
Change From Baseline in Weight Z-scores at the Time of Relapse
Časové okno: From baseline to the date of documented disease relapse (up to 12 months)
Change from baseline in weight Z-scores at the acute phase of disease relapse.
From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in Laboratory Blood Parameters (Hemoglobin) at 12 Months
Časové okno: From baseline to 12 months post-randomization
Change from baseline in hemoglobin levels.
From baseline to 12 months post-randomization
Change From Baseline in Laboratory Blood Parameters (Hemoglobin Levels) at the Time of Relapse
Časové okno: From baseline to the date of documented disease relapse (up to 12 months)
Change from baseline in hemoglobin levels at the acute phase of disease relapse.
From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in Laboratory Blood Parameters (Serum Albumin) at 12 Months
Časové okno: From baseline to 12 months post-randomization
Change from baseline in serum albumin levels.
From baseline to 12 months post-randomization
Change From Baseline in Laboratory Blood Parameters (Serum Albumin) at the Time of Relapse
Časové okno: From baseline to the date of documented disease relapse (up to 12 months)
Change from baseline in serum albumin levels at the acute phase of disease relapse.
From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in Laboratory Blood Parameters (Total Cholesterol) at 12 Months
Časové okno: From baseline to 12 months post-randomization
Measurement of total cholesterol concentration in blood.
From baseline to 12 months post-randomization
Change From Baseline in Laboratory Blood Parameters (Total Cholesterol) at the Time of Relapse
Časové okno: From baseline to the date of documented disease relapse (up to 12 months)
Change from baseline in total cholesterol levels at the acute phase of disease relapse.
From baseline to the date of documented disease relapse (up to 12 months)
Time to CD19+ B-Cell Recovery
Časové okno: From baseline to 12 months post-randomization
The time from CD19+ cell depletion until the first detection of CD19+ cells exceeding 1% of total CD45+ lymphocytes.
From baseline to 12 months post-randomization
T-cell Immunophenotyping
Časové okno: Baseline, 1 month, 3 months, 6 months and 12 months after randomization.
Longitudinal assessment of peripheral blood T-cell subsets, including absolute counts and relative proportions of naïve T cells, central memory T cells, effector memory T cells, regulatory T cells, and other predefined T-cell populations measured by flow cytometry.
Baseline, 1 month, 3 months, 6 months and 12 months after randomization.
B-cell Immunophenotyping
Časové okno: Baseline, 1 month, 3 months, 6 months and 12 months after randomization.
Longitudinal assessment of peripheral blood B-cell subsets, including absolute counts and relative proportions of naïve B cells, memory B cells, switched memory B cells, plasmablasts, CD19+ B cells, and other predefined B-cell populations measured by flow cytometry.
Baseline, 1 month, 3 months, 6 months and 12 months after randomization.
Cytokine Profiling
Časové okno: Baseline, 1 month, 3 months, 6 months and 12 months after randomization.
Longitudinal assessment of serum cytokine and chemokine concentrations associated with immune regulation and relapse risk, including but not limited to IL-7, IL-9, IL-15, VEGF, TGF-β3, RANTES, IL-10, IL-6, IFN-γ, and IL-4.
Baseline, 1 month, 3 months, 6 months and 12 months after randomization.
Incidence and Severity of Adverse Events (AEs)
Časové okno: From randomization through study completion, up to 12 months.
Monitoring and recording of the frequency and severity of adverse events, including infusion-related reactions (e.g., nausea, rash, fever, chills, bronchospasm, hypertension, hypotension), infections (e.g., respiratory, HBV reactivation, VZV, Pneumocystis carinii pneumonia), cardiac events (e.g., fulminant myocarditis, heart failure), interstitial lung disease, inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease), and abnormal laboratory findings (e.g., neutropenia, persistent hypogammaglobulinemia, elevated transaminases). Adverse events are graded according to NCI-CTCAE v5.0.
From randomization through study completion, up to 12 months.

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Children's Hospital of Fudan University

Spolupracovníci

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

Vyšetřovatelé

  • Vrchní vyšetřovatel: Hong Xu, Children's Hospital of Fudan University
  • Vrchní vyšetřovatel: Qian Shen, Children's Hospital of Fudan University

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

20. srpna 2026

Primární dokončení (Odhadovaný)

20. srpna 2028

Dokončení studie (Odhadovaný)

31. prosince 2028

Termíny zápisu do studia

První předloženo

8. června 2026

První předloženo, které splnilo kritéria kontroly kvality

11. srpna 2026

První zveřejněno (Aktuální)

14. srpna 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

14. srpna 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

11. srpna 2026

Naposledy ověřeno

1. května 2026

Více informací

Termíny související s touto studií

Klíčová slova

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NE

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