Nephrotic SyndromePhase 3NCT07765914
Zuberitamab in the First Episode of Paediatric Nephrotic Syndrome
A Phase 3 study testing Zuberitamab and standard corticosteroid treatment in people with Nephrotic Syndrome, run by Children's Hospital of Fudan University at 9 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Nephrotic Syndrome
- What is being tested?
- Zuberitamab and standard corticosteroid treatment
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 9 sitesChina
- Study dates
- 20 Aug 2026to 31 Dec 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
China9 sites
Second Xiangya Hospital of Central South University
Changsha
Guiyang Maternal and Child Health Care Hospital
Guiyang
Yuhong Li
Children's Hospital of Fudan University
Shanghai, Shanghai Municipality
Hong Xu
Shanghai Children's Hospital
Shanghai
Shanghai Children's Medical Center
Shanghai
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai
Wuhan Children's Hospital
Wuhan
Wuxi Women's & Children's Hospital
Wuxi
Xiamen Maternity & Child Care Hospital
Xiamen
About this study
Official title: 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:
Read more
- 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
Read the detailed description
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.
- Conditions
- Nephrotic Syndrome
- Being tested
- Zuberitamab, standard corticosteroid treatment
- Keywords
- Anti-CD20 Monoclonal Antibody, Randomised Controlled Trial
- Medical subject headings
- Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZuberitamabBiological
Also called Zuberitamab (BioRay Biopharmaceutical Co., Ltd.)
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.
standard corticosteroid treatmentDrug
Also called prednisolone/prednisone
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: standard corticosteroid treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The proportion of participants who remain free from disease relapse at 12 months after randomization.
Measured: 12 months post-randomization.
Relapse-Free Survival Rate at 6 Months Post-Randomization
The proportion of participants who remain free from disease relapse at 6 months after randomization.
Measured: 6 months post-randomization.
Cumulative Steroid Dose at 12 Months Post-Randomization
The total amount of steroid medication (prednisolone) taken by participants from randomization until 12 months.
Measured: 12 months post-randomization.
Change From Baseline in Serum Creatinine (Renal Function) at 12 Months
Change from baseline in serum creatinine levels to assess renal function.
Measured: From baseline to 12 months post-randomization.
Change From Baseline in Serum Creatinine at the Time of Relapse
Change from baseline in serum creatinine levels measured at the acute phase of disease relapse.
Measured: 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
Change from baseline in eGFR, calculated using an appropriate pediatric formula (e.g., the modified Schwartz formula), to assess renal function.
Measured: From baseline to 12 months post-randomization
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at the Time of Relapse
Change from baseline in eGFR at the acute phase of disease relapse.
Measured: 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
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).
Measured: From baseline to 12 months post-randomization
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Scores at the Time of Relapse
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.
Measured: 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
Change from baseline in systolic blood pressure, expressed as Z-scores relative to age-, sex-, and height-specific normative data.
Measured: From baseline to 12 months post-randomization
Change From Baseline in systolic Blood Pressure Z-scores at the Time of Relapse
Change from baseline in systolic blood pressure, expressed as Z-scores relative to age-, sex-, and height-specific normative data.
Measured: 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
Change from baseline in diastolic blood pressure, expressed as Z-scores relative to age-, sex-, and height-specific normative data.
Measured: From baseline to 12 months post-randomization
Change From Baseline in diastolic Blood Pressure Z-scores at the Time of Relapse
Change from baseline in diastolic blood pressure, expressed as Z-scores relative to age-, sex-, and height-specific normative data.
Measured: From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in Height Z-scores at 12 Months
Change from baseline in height, expressed as Z-scores relative to age- and sex-specific normative growth charts.
Measured: From baseline to 12 months post-randomization
Change From Baseline in Height Z-scores at the Time of Relapse
Change from baseline in height Z-scores at the acute phase of disease relapse.
Measured: From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in Weight Z-scores at 12 Months
Change from baseline in weight, expressed as Z-scores relative to age- and sex-specific normative growth charts.
Measured: From baseline to 12 months post-randomization
Change From Baseline in Weight Z-scores at the Time of Relapse
Change from baseline in weight Z-scores at the acute phase of disease relapse.
Measured: From baseline to the date of documented disease relapse (up to 12 months)
Change From Baseline in Laboratory Blood Parameters (Hemoglobin) at 12 Months
Change from baseline in hemoglobin levels.
Measured: From baseline to 12 months post-randomization
Change From Baseline in Laboratory Blood Parameters (Hemoglobin Levels) at the Time of Relapse
Change from baseline in hemoglobin levels at the acute phase of disease relapse.
Measured: 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
Change from baseline in serum albumin levels.
Measured: From baseline to 12 months post-randomization
Change From Baseline in Laboratory Blood Parameters (Serum Albumin) at the Time of Relapse
Change from baseline in serum albumin levels at the acute phase of disease relapse.
Measured: 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
Measurement of total cholesterol concentration in blood.
Measured: From baseline to 12 months post-randomization
Change From Baseline in Laboratory Blood Parameters (Total Cholesterol) at the Time of Relapse
Change from baseline in total cholesterol levels at the acute phase of disease relapse.
Measured: From baseline to the date of documented disease relapse (up to 12 months)
Time to CD19+ B-Cell Recovery
The time from CD19+ cell depletion until the first detection of CD19+ cells exceeding 1% of total CD45+ lymphocytes.
Measured: From baseline to 12 months post-randomization
T-cell Immunophenotyping
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.
Measured: Baseline, 1 month, 3 months, 6 months and 12 months after randomization.
B-cell Immunophenotyping
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.
Measured: Baseline, 1 month, 3 months, 6 months and 12 months after randomization.
Cytokine Profiling
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.
Measured: Baseline, 1 month, 3 months, 6 months and 12 months after randomization.
Incidence and Severity of Adverse Events (AEs)
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.
Measured: From randomization through study completion, up to 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2026
- Study start20 Aug 2026 (estimated)
- Primary completion20 Aug 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Nephrotic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- Guiyang Maternal and Child Health Care Hospital, Wuhan Children's Hospital, Shanghai Children's Medical Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Children's Hospital, Wuxi Women's & Children's Hospital, Xiamen Maternity & Child Care Hospital, Second Xiangya Hospital of Central South University
- Responsible party
- Sponsor
- Investigators
- Hong Xu, Principal investigator, Children's Hospital of Fudan UniversityQian Shen, Principal investigator, Children's Hospital of Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07765914
- Sponsor's protocol ID
- HiFIRPedINS
- Status last verified
- May 2026
- First submitted
- 8 Jun 2026
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39156138Liu 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.
PubMed 38707815