Study of Rituximab Monotherapy on Children With New-onset Nephrotic Syndrome: A Randomized Controlled Trial

NCT05734794 | Recruiting Phase 3

• 1 other identifier: STORM
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective is to evaluate the effectiveness of Rituximab monotherapy versus steroid therapy on children with new-onset nephrotic syndrome within the 52-week follow-up.

Conditions

Nephrotic Syndrome in Children; Rituximab

Keywords

Rituximab; Glucocorticosteroids

Outcome Measures

Primary Outcomes (1)

• Recurrence-free survival time(day) after first complete remission

  The time from complete remission to the first relapse during the whole 52-week follow-up in patients who achieve complete remission within 6 weeks. In order to evaluate the remission, all the participants will document their proteinuria. Relapse is defined by first-morning urine dipstick ≥3+ on three or more consecutive days, 24-h PCR≥2.0g/g, or 24-h urine protein ≥ 50mg/kg, with or without edema after complete remission(KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases). Complete remission is defined by the first morning or 24h PCR ≤ 0.2g/g (or negative or trace dipstick) on three or more consecutive occasions(KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases).

  From complete remission to 52 weeks

Secondary Outcomes (5)

• Complete remission of nephrotic syndrome

  From admission day to 6 weeks

• Inefficiency of nephrotic syndrome

  From admission day to 6 weeks

• The time(day) to first complete remission

  From admission day to 6 weeks

• Relapse of nephrotic syndrome

  From admission day to 52 weeks

• Cumulative prednisone dosage of each individual (milligrams per kilogram per year)

  From admission day to 52 weeks

Study Arms (2)

Rituximab Group

EXPERIMENTAL

Rituximab dose: 4 doses of 375 mg/m2 rituximab at 1-week intervals( within +7 days).

Drug: Rituximab

Steroid Group

ACTIVE COMPARATOR

Daily oral prednisone/prednisolone 2 mg/kg/d (maximum 60 mg/d) for 6 weeks followed by alternate day prednisone/prednisolone, 1.5 mg/kg (maximum of 50 mg), for other 6 weeks.

Drug: Steroid

Interventions

Rituximab DRUG

Rituximab dose: 4 doses of 375 mg/m2 rituximab at 1-week intervals( within +7 days), associated with trimethoprim-sulfamethoxazole(25-50 mg/kg/day orally twice per day, 3 days per week. If the patient is not allergic) for three months from the first rituximab dosing date(Day 1). Four doses of rituximab are necessary whether the patient achieves complete remission.

Rituximab Group

Steroid DRUG

Daily oral prednisone/prednisolone 2 mg/kg/d (maximum 60 mg/d) for 6 weeks followed by alternate day prednisone/prednisolone, 1.5 mg/kg (maximum of 50 mg), for other 6 weeks. Vitamin D and calcium(adjusted according to the blood calcium level) were administered for three months.

Steroid Group

Eligibility Criteria

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

You may qualify if:

• New-onset idiopathic nephrotic syndrome
• Glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry.

You may not qualify if:

• Glomerular hematuria: Urine red blood cell counts≥ 10/high power field(HP), ≥ 3 times within 2 weeks;
• Continuous hypocomplementaemia(\< 0.9g/L) ;
• Repeated or persistent Hypertension(systolic and/or diastolic blood pressures measured greater than the 95th percent of blood pressure in children matching sex, age and height ≥3 different time points)
• Diagnosis of secondary NS, such as secondary to Systemic Lupus Erythematosus, Immunoglobulin A Vasculitis(IgAV), diabetes, Hepatitis B virus(HBV) infection, etc.
• Complicated with other kidney diseases, such as multiple renal cysts, ANCA vasculitis, urinary system abnormalities, etc;
• With a family history of nephrotic syndrome, chronic glomerulonephritis, uremia, or other kidney diseases;
• Other monogenic genetic diseases known as the effect the condition of nephrotic syndromes, such as Wilms' tumor 1(WT1), NPHS2, LAMB2, PLCE1, etc.
• Congenital or acquired immunodeficiency, or patients with active tuberculosis, active Epstein-Barr virus and cytomegalovirus(CMV), acute hepatitis B, hepatitis C, HIV infection, deep fungal infection or other active infections.
• Laboratory indicators were abnormal, such as moderate or severe neutropenia(≤1000/μL)， moderate or severe anemia(hemoglobin\<9.0g/dL), Thrombocytopenia (platelet count\<100\* 10\^12/L) or with abnormal hepatic function (Alaninetransaminase(ALT), aspartate Aminotransferase(AST) or bilirubin \>2.5\*upper limit of normal value and continue to increase for 2 weeks);
• Steroid or immunosuppressive medicine for other diseases within 3 months, such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, tripterygium wilfordii, etc.
• With tumor, severe cardiac failure, severe hepatologic diseases, hematological diseases, or other severe system diseases.
• Patients who are known to be allergic to rituximab;
• History of transplantation, excluding cornea or hair transplantation;
• The attenuated live vaccine was inoculated within 1 month before enrollment;
• Patients who participated in other clinical trials within three months before enrollment;

Sponsors & Collaborators

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

Study Sites (1)

Children's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

Related Publications (11)

• Veltkamp F, Rensma LR, Bouts AHM; LEARNS consortium. Incidence and Relapse of Idiopathic Nephrotic Syndrome: Meta-analysis. Pediatrics. 2021 Jul;148(1):e2020029249. doi: 10.1542/peds.2020-029249. Epub 2021 Jun 30.

  PMID: 34193618 BACKGROUND

• Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003 Aug 23;362(9384):629-39. doi: 10.1016/S0140-6736(03)14184-0.

  PMID: 12944064 BACKGROUND

• Filler G, Young E, Geier P, Carpenter B, Drukker A, Feber J. Is there really an increase in non-minimal change nephrotic syndrome in children? Am J Kidney Dis. 2003 Dec;42(6):1107-13. doi: 10.1053/j.ajkd.2003.08.010.

  PMID: 14655180 BACKGROUND

• Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr. Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol. 1997 May;8(5):769-76. doi: 10.1681/ASN.V85769.

  PMID: 9176846 BACKGROUND

• Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. Lancet. 2018 Jul 7;392(10141):61-74. doi: 10.1016/S0140-6736(18)30536-1. Epub 2018 Jun 14.

  PMID: 29910038 BACKGROUND

• Ye Q, Mao JH. [Immunologic pathogenesis of idiopathic nephrotic syndrome in children: the present and future]. Zhonghua Er Ke Za Zhi. 2020 Sep 2;58(9):705-707. doi: 10.3760/cma.j.cn112140-20200626-00664. Chinese.

  PMID: 32872709 BACKGROUND

• Iijima K, Sako M, Nozu K. Rituximab for nephrotic syndrome in children. Clin Exp Nephrol. 2017 Apr;21(2):193-202. doi: 10.1007/s10157-016-1313-5. Epub 2016 Jul 15.

  PMID: 27422620 BACKGROUND

• Sinha A, Bagga A. Rituximab therapy in nephrotic syndrome: implications for patients' management. Nat Rev Nephrol. 2013 Mar;9(3):154-69. doi: 10.1038/nrneph.2012.289. Epub 2013 Jan 22.

  PMID: 23338210 BACKGROUND

• Ravani P, Ponticelli A, Siciliano C, Fornoni A, Magnasco A, Sica F, Bodria M, Caridi G, Wei C, Belingheri M, Ghio L, Merscher-Gomez S, Edefonti A, Pasini A, Montini G, Murtas C, Wang X, Muruve D, Vaglio A, Martorana D, Pani A, Scolari F, Reiser J, Ghiggeri GM. Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome. Kidney Int. 2013 Nov;84(5):1025-33. doi: 10.1038/ki.2013.211. Epub 2013 Jun 5.

  PMID: 23739238 BACKGROUND

• Chan EY, Yu ELM, Angeletti A, Arslan Z, Basu B, Boyer O, Chan CY, Colucci M, Dorval G, Dossier C, Drovandi S, Ghiggeri GM, Gipson DS, Hamada R, Hogan J, Ishikura K, Kamei K, Kemper MJ, Ma AL, Parekh RS, Radhakrishnan S, Saini P, Shen Q, Sinha R, Subun C, Teo S, Vivarelli M, Webb H, Xu H, Yap HK, Tullus K. Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study. J Am Soc Nephrol. 2022 Jun;33(6):1193-1207. doi: 10.1681/ASN.2021111472. Epub 2022 Mar 30.

  PMID: 35354600 BACKGROUND

• Fenoglio R, Sciascia S, Beltrame G, Mesiano P, Ferro M, Quattrocchio G, Menegatti E, Roccatello D. Rituximab as a front-line therapy for adult-onset minimal change disease with nephrotic syndrome. Oncotarget. 2018 Jun 22;9(48):28799-28804. doi: 10.18632/oncotarget.25612. eCollection 2018 Jun 22.

  PMID: 29989000 BACKGROUND

MeSH Terms

Interventions

Rituximab; Steroids

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Jianhua Mao, PHD.MD

CONTACT

86057186670015; maojh88@zju.edu.cn

Fei Liu

CONTACT

alexdevin@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Dean

Study Record Dates

• First Submitted: November 20, 2022
• First Posted: February 21, 2023
• Study Start: February 9, 2023
• Primary Completion: December 25, 2025
• Study Completion (Estimated): July 30, 2026
• Last Updated: August 25, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)