Clinical Study of Rituximab Combined With Corticosteroids or Rituximab Monotherapy in the Treatment of Primary Membranous Nephropathy

NCT05514015 | Recruiting Phase 4 DMC

• 1 other identifier: HLK-202302
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

This was a prospective, randomized, multicenter clinical trial. Seventy-eight patients with primary membranous nephropathy (PMN) were randomly divided into intervention or control group. Intervention group was given rituximab combined with corticosteroids in induction therapy and the control group was given rituximab monotherapy. After 6 months, patients who had decreased 24h urinary protein by \> 25% but did not achieve CR were given rituximab maintenance therapy. The complete response rate at 12 months was measured.

Conditions

Primary Membranous Nephropathy

Keywords

rituximab; Primary membranous nephropathy; rituximab combined with corticosteroids; safety; remission

Outcome Measures

Primary Outcomes (1)

• The complete response rate at 12 months;

  The complete response rate at 12 months;

  12 months

Secondary Outcomes (8)

• Response rates at 6, 12, 18 and 24 months (including the proportion of participants with complete response and partial response);

  24 months

• Median remission time;

  24 months

• Proportion of patients without recurrence at 12, 18 and 24 months;

  24 months

• Median non-recurrence time;

  24 months

• Cumulative dose of glucocorticoids;

  24 months

Study Arms (2)

Intervention arm

EXPERIMENTAL

rituximab combined with corticosteroids treatment group

Drug: rituximab combined with corticosteroids

Control arm

ACTIVE COMPARATOR

Rituximab monotherapy treatment

Drug: rituximab

Interventions

rituximab combined with corticosteroids DRUG

Induction therapy: Rituximab intravenous infusion of 1g, d1, d15, combined with glucocorticoid therapy, oral prednisolone, initial dose of 0.5mg/(kg·d), once a day, after 8 weeks of treatment, reduce by 5mg every 4 weeks until 0.25mg/kg, this dose was maintained for 8 weeks, and then reduced by 2.5mg every 4 weeks, until 5-10mg is maintained, and the total course of treatment was about one year or so;

Also known as: Intervention arm

Intervention arm

rituximab DRUG

Control group (treated with Rituximab monotherapy treatment) :Rituximab intravenous infusion of 1g, d1, d15

Also known as: Control arm

Control arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 18-75 years;
• Patients diagnosed as primary membranous nephropathy (PMN) by renal biopsy;
• After treatment with ACE inhibitors or ARBs for at least 3 months, the following two points were met (unless intolerance to ACE inhibitors or ARBs, contraindications, hypotension that may cause side effects, or the investigator judged that the patient was not suitable for RAS inhibitors):
• (1) Those who have an average 24-hour urine protein ≥ 3.5g twice a week, or an average 24-hour urine protein ≥ 5g twice in 14 days, the requirement of RASi for at least 3 months is not required (2) Blood pressure≤ 130/80mmHg, 4. Glomerular filtration rate (eGFR) ≥30mL/min/1.73m2 (calculated according to the CKD-EPI formula) 5. If female, must be postmenopausal or postoperatively infertile or on medical contraception (considering the potential risk of thromboembolism in patients with kidney disease); 6. Subjects voluntarily signed the informed consent form;

You may not qualify if:

• Patients with type 1 diabetes mellitus or type 2 diabetes mellitus complicated with diabetic nephropathy. Patients with a recent history of steroid-induced diabetes were eligible if renal biopsies show no evidence of secondary diabetic nephropathy within 6 months before the screening period
• Patients with secondary membranous nephropathy (such as hepatitis B and C, systemic lupus erythematosus, drug therapy, malignant tumors and other secondary causes);
• Previous treatment with rituximab, steroids, alkylating agents, calcineurin inhibitors, synthetic ACTH, mycophenolate (MMF), and azathioprine;
• Receipt of any other study medication (within the last month);
• Suspected or known allergy or immune reaction to rituximab, corticosteroids or any of their components (including excipients);
• Active infection, such as active hepatitis B or hepatitis C, tuberculosis (evidence of active tuberculosis infection within 1 year), or human immunodeficiency virus HIV infection (positive for anti-HIV antibodies), etc.
• A history of immunodeficiency, including other acquired or congenital immunodeficiency diseases, or organ transplantation;
• Females with a positive pregnancy screening test or lactating or planning to become pregnant in the next 24 months. Female or male patients who were unwilling to use contraceptive methods throughout the study;
• A history of mental illness;
• Laboratory tests that meet the following criteria need to be excluded:

Sponsors & Collaborators

• First Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

Wei Chen

Guangzhou, Guangdong, 510080, China

RECRUITING

Related Publications (13)

• Cai Q, Hendricks AR. Membranous nephropathy: A ten-year journey of discoveries. Semin Diagn Pathol. 2020 May;37(3):116-120. doi: 10.1053/j.semdp.2020.01.001. Epub 2020 Jan 29.

  PMID: 32061439 BACKGROUND

• Pathological features and diagnosis of membranous nephropathy

  BACKGROUND

• Dahan K. [Membranous nephropathy: Diagnosis, new insights in pathophysiology, and therapeutic approach]. Rev Med Interne. 2016 Oct;37(10):674-679. doi: 10.1016/j.revmed.2016.02.003. Epub 2016 May 25. French.

  PMID: 27236434 BACKGROUND

• Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB, Salant DJ. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009 Jul 2;361(1):11-21. doi: 10.1056/NEJMoa0810457.

  PMID: 19571279 BACKGROUND

• Ruggenenti P, Debiec H, Ruggiero B, Chianca A, Pelle T, Gaspari F, Suardi F, Gagliardini E, Orisio S, Benigni A, Ronco P, Remuzzi G. Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous Nephropathy. J Am Soc Nephrol. 2015 Oct;26(10):2545-58. doi: 10.1681/ASN.2014070640. Epub 2015 Mar 24.

  PMID: 25804280 BACKGROUND

• Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021. No abstract available.

  PMID: 34556256 BACKGROUND

• Expert consensus on the use of rituximab in glomerulonephritis

  BACKGROUND

• Expert Group on Biologics Treatment of Immune Glomerular Diseases. Chinese Expert Consensus on Biologics for the Treatment of Immune Glomerular Diseases.

  BACKGROUND

• Nephrology Expert Panel of the Peking University Health Science Center. [Expert consensus on the application of rituximab in the treatment of membranous nephropathy]. Zhonghua Nei Ke Za Zhi. 2022 Mar 1;61(3):282-290. doi: 10.3760/cma.j.cn112138-20210927-00660. Chinese.

  PMID: 35263969 BACKGROUND

• Fervenza FC, Appel GB, Barbour SJ, Rovin BH, Lafayette RA, Aslam N, Jefferson JA, Gipson PE, Rizk DV, Sedor JR, Simon JF, McCarthy ET, Brenchley P, Sethi S, Avila-Casado C, Beanlands H, Lieske JC, Philibert D, Li T, Thomas LF, Green DF, Juncos LA, Beara-Lasic L, Blumenthal SS, Sussman AN, Erickson SB, Hladunewich M, Canetta PA, Hebert LA, Leung N, Radhakrishnan J, Reich HN, Parikh SV, Gipson DS, Lee DK, da Costa BR, Juni P, Cattran DC; MENTOR Investigators. Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. N Engl J Med. 2019 Jul 4;381(1):36-46. doi: 10.1056/NEJMoa1814427.

  PMID: 31269364 BACKGROUND

• Scolari F, Delbarba E, Santoro D, Gesualdo L, Pani A, Dallera N, Mani LY, Santostefano M, Feriozzi S, Quaglia M, Boscutti G, Ferrantelli A, Marcantoni C, Passerini P, Magistroni R, Alberici F, Ghiggeri GM, Ponticelli C, Ravani P; RI-CYCLO Investigators. Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial. J Am Soc Nephrol. 2021 Apr;32(4):972-982. doi: 10.1681/ASN.2020071091. Epub 2021 Mar 1.

  PMID: 33649098 BACKGROUND

• Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32. doi: 10.1056/NEJMoa0909905.

  PMID: 20647199 BACKGROUND

• Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G; LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012 Apr;64(4):1215-26. doi: 10.1002/art.34359. Epub 2012 Jan 9.

  PMID: 22231479 BACKGROUND

MeSH Terms

Interventions

Adrenal Cortex Hormones; Rituximab

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Wei Chen

CONTACT

8602087769673; chenwei99@mail.sysu.edu.cn

Qiong Wen

CONTACT

8602087769673; wenqiong@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 14, 2022
• First Posted: August 24, 2022
• Study Start: March 29, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)