Rituximab Combined With Cyclosporine Versus Rituximab Alone in the Treatment of iMN

NCT04743739 | Terminated Phase 3

• 1 other identifier: iMN RTX plus CsA
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 7

Brief Summary

The primary objective of this study is to determine whether or not cyclosporine (CsA) combined with RTX is more effective than RTX alone in the treatment of idiopathic membranous nephropathy (iMN).

Conditions

Idiopathic Membranous Nephropathy

Keywords

Rituximab; cyclosporine; idiopathic membranous nephropathy

Outcome Measures

Primary Outcomes (1)

• complete remission (CR) or partial remission (PR) at 24 month

  complete or partial remission at 24 month. complete remission is defined as urine protein≤0.5g/24h and serum albumin≥3.5g/dl. Partial remission is defined as reduction in baseline urine protein ≥50% plus urine protein≤3.5g/24h but \>0.5g/24h

  24 months after randomization

Secondary Outcomes (10)

• complete remission (CR) or partial remission (PR) on 6 month, 12 month, 18 month

  6, 12, 18 months after randomization

• complete remission (CR) on 6, 12, 18, 24 month

  6, 12, 18, 24 months after randomization

• Time to complete remission (CR) or partial remission (PR)

  from date of randomization until the date of first remission, assessed up to 24 months

• Change of estimated glomerular filtration rate (eGFR)

  24 months

• Serum creatinine increase≥50 percent from baseline

  24 months

Study Arms (2)

Rituximab monotherapy

ACTIVE COMPARATOR

Rituximab 1000mg I.V. on Days 1 and 181, and will be retreated or not on Days 15 and 195 according to the CD19+ B cells count.

Drug: Rituximab

Rituximab combined with cyclosporine

EXPERIMENTAL

Rituximab 1000mg I.V. on Days 1 and 181, and will be retreated or not on Days 15 and 195 according to CD19+ B cells count. cyclosporine (CsA) will be started at a dose of 3mg/kg/day p.o. divided into 2 equal doses given at 12 hour intervals. Doses of CsA will be adjusted according to the blood levels of CsA. CsA will be tapered after 6 months and discontinued over a 3 month period.

Drug: Rituximab; Drug: cyclosporine

Interventions

Rituximab DRUG

Rituximab 1000mg, I.V. on Days 1 and 181, and will be retreated or not at Days 15 and 195 according to the CD19+ B cell count.

Also known as: CD20 antibody

Rituximab combined with cyclosporine; Rituximab monotherapy

cyclosporine DRUG

cyclosporine (CsA) will be started at a dose of 3mg/kg/d and adjusted according to the blood levels of the CsA. CsA will be tapered after 6 months and discontinued over a three month period.

Also known as: CsA

Rituximab combined with cyclosporine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• idiopathic MN with or without diagnostic biopsy
• Female, must be post-menopausal, sterile or have effective method of contraception
• must be off steroid or mycophenolate mofetil for \>1 month and alkylating agents for \> 6 months
• Angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for ≥3 months prior to randomization with controlled blood pressure or if patients is intolerant to ACEI/ARB
• proteinuria ≥4g/24h using the average from two 24-hour urine samples collected within 2 weeks of each other, and decreased ≤50% from baseline.
• estimated glomerular filtration rate (eGFR) ≥40ml/min/1.73m2

You may not qualify if:

• presence of active infection or a secondary cause of MN
• diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy.
• pregnancy or breast feeding
• history of resistance to CsA or other calcineurin inhibitors(CNI), RTX or alkylating agents.
• Patients who previously achieved remission after treatment of CNI, RTX or alkylating agents but relapsed off CNI after 3 months, or relapsed off RTX or alkylating agents after 6 months, are eligible.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Beijing Tongren Hospital: collaborator
• Chinese Academy of Medical Sciences, Fuwai Hospital: collaborator
• The Luhe Teaching Hospital of the Capital Medical University: collaborator
• The Seventh Affiliated Hospital of Sun Yat-sen University: collaborator
• First Affiliated Hospital of Xinjiang Medical University: collaborator
• Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.: collaborator

Study Sites (7)

Fuwai Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100037, China

Location

Beijing Tongren Hospital， Capital Medical University

Beijing, Beijing Municipality, 100730, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Beijing Luhe Hospital, Capital Medical University

Beijing, Beijing Municipality, 101149, China

Location

Nanyang Nanshi Hospital, Henan University

Nanyang, Henan, 473065, China

Location

The Seventh Affiliated Hospital, Sun Yat-sen University

Shenzhen, Shenzhen, China

Location

The First Affiliated Hospital of Xinjiang Medical University

Ürümqi, Xinjiang, 830054, China

Location

Related Publications (10)

• Polanco N, Gutierrez E, Covarsi A, Ariza F, Carreno A, Vigil A, Baltar J, Fernandez-Fresnedo G, Martin C, Pons S, Lorenzo D, Bernis C, Arrizabalaga P, Fernandez-Juarez G, Barrio V, Sierra M, Castellanos I, Espinosa M, Rivera F, Oliet A, Fernandez-Vega F, Praga M; Grupo de Estudio de las Enfermedades Glomerulares de la Sociedad Espanola de Nefrologia. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol. 2010 Apr;21(4):697-704. doi: 10.1681/ASN.2009080861. Epub 2010 Jan 28.

  PMID: 20110379 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

• Schreiber SL, Crabtree GR. The mechanism of action of cyclosporin A and FK506. Immunol Today. 1992 Apr;13(4):136-42. doi: 10.1016/0167-5699(92)90111-J.

  PMID: 1374612 BACKGROUND

• Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, Reiser J, Mundel P. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med. 2008 Sep;14(9):931-8. doi: 10.1038/nm.1857.

  PMID: 18724379 BACKGROUND

• Cattran DC, Alexopoulos E, Heering P, Hoyer PF, Johnston A, Meyrier A, Ponticelli C, Saito T, Choukroun G, Nachman P, Praga M, Yoshikawa N. Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : workshop recommendations. Kidney Int. 2007 Dec;72(12):1429-47. doi: 10.1038/sj.ki.5002553. Epub 2007 Sep 26.

  PMID: 17898700 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

• van den Brand JAJG, Ruggenenti P, Chianca A, Hofstra JM, Perna A, Ruggiero B, Wetzels JFM, Remuzzi G. Safety of Rituximab Compared with Steroids and Cyclophosphamide for Idiopathic Membranous Nephropathy. J Am Soc Nephrol. 2017 Sep;28(9):2729-2737. doi: 10.1681/ASN.2016091022. Epub 2017 May 9.

  PMID: 28487395 BACKGROUND

• Segarra A, Praga M, Ramos N, Polanco N, Cargol I, Gutierrez-Solis E, Gomez MR, Montoro B, Camps J. Successful treatment of membranous glomerulonephritis with rituximab in calcineurin inhibitor-dependent patients. Clin J Am Soc Nephrol. 2009 Jun;4(6):1083-8. doi: 10.2215/CJN.06041108. Epub 2009 May 28.

  PMID: 19478097 BACKGROUND

• Waldman M, Beck LH Jr, Braun M, Wilkins K, Balow JE, Austin HA 3rd. Membranous nephropathy: Pilot study of a novel regimen combining cyclosporine and Rituximab. Kidney Int Rep. 2016 Jul;1(2):73-84. doi: 10.1016/j.ekir.2016.05.002. Epub 2016 Jun 11.

  PMID: 27942609 BACKGROUND

• Fernandez-Juarez G, Rojas-Rivera J, Logt AV, Justino J, Sevillano A, Caravaca-Fontan F, Avila A, Rabasco C, Cabello V, Varela A, Diez M, Martin-Reyes G, Diezhandino MG, Quintana LF, Agraz I, Gomez-Martino JR, Cao M, Rodriguez-Moreno A, Rivas B, Galeano C, Bonet J, Romera A, Shabaka A, Plaisier E, Espinosa M, Egido J, Segarra A, Lambeau G, Ronco P, Wetzels J, Praga M; STARMEN Investigators. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy. Kidney Int. 2021 Apr;99(4):986-998. doi: 10.1016/j.kint.2020.10.014. Epub 2020 Nov 7.

  PMID: 33166580 BACKGROUND

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Interventions

Rituximab; Cyclosporine

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides

Study Officials

• Yan Qin, Doctor

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2021
• First Posted: February 8, 2021
• Study Start: April 14, 2021
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2024
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (7)