Different Immunosuppressive Treatment in iMN

NCT04745728 | Recruiting Phase 3

• 1 other identifier: iMN cohort
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to compare the 24 month remission of different immunosuppressive therapies in the treatment of idiopathic membranous nephropathy (iMN)

Conditions

Idiopathic Membranous Nephropathy

Outcome Measures

Primary Outcomes (1)

• complete or partial remission on 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 urine protein≥50% plus urine protein ≤3.5g/24h but \>0.5g/24h

  24 months

Secondary Outcomes (9)

• complete or partial remission on 6, 12 and 18 month

  6, 12 and 18 months

• complete remission on 6, 12, 18 and 24 month

  6, 12, 18 and 24 months

• time to complete or partial remission

  from date of treatment until the date of first documented remission, 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)

cyclophosphamide and prednisone

ACTIVE COMPARATOR

Prednisone will be given at 1mg/kg/d p.o. and will be tapered after 2 months and discontinued over a 6-12 month period. Cyclophosphamide will be given at 1-2mg/kg/d p.o. with a target accumulated dose of 12g. Azathioprine or mycophenolate mofetil are optional which could be given for a short period of time (\<6 months）after discontinuation of cyclophosphamide if patients do not remit at 6 month.

Drug: Prednisone; Drug: Cyclophosphamide

Rituximab

ACTIVE COMPARATOR

Rituximab 1000mg I.V. on Day1 and at 6 month. After 6 months, in patients with response but without complete remission, Rituximab could be stopped or repeated with a 6 month-interval (12 month, 18 month, 24 month) until complete remission. Rituximab 1000mg I.V. will be given on the 15th day after each Rituximab infusion if CD19+ B cell count\>5/ul on the 15th day. Calcineurin inhibitors (CNI) are optional but should be tapered after 6 months and discontinued after 9 months.

Drug: Rituximab

Interventions

Rituximab DRUG

1000mg I.V. on D1 and at 6 month. After 6 month, in patients with response but not complete remission, Rituximab could be stopped or repeated with a 6 month-interval (12 month, 18 month, 24 month) until complete remission. Rituximab 1000mg I.V. will be repeated on the 15th day of each Rituximab infusion if CD19+ B cell count\>5/ul.

Also known as: CD20 antibody

Rituximab

Prednisone DRUG

1mg/kg/d p.o.which will be tapered after 2 months and discontinued over a 6-12 month period.

cyclophosphamide and prednisone

Cyclophosphamide DRUG

1-2mg/kg/d p.o. with a target accumulated dose of 12g.

Also known as: CTX

cyclophosphamide and prednisone

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 membranous nephropathy
• Female, must be post-menopausal, sterile or have effective contraception
• must be off steroid or mycophenolate mofetil for \>1 month and alkylating agents for or RTX\> 6 months
• Angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for ≥ 3 months with controlled blood pressure prior to beginning of immunosuppressive therapy or if patients are intolerant to ACEI/ARB.
• proteinuria ≥4g/24h and decreased ≤ 50% from baseline

You may not qualify if:

• presence of active infection or a secondary cause of membranous nephropathy
• proteinuria associated with diabetic nephropathy
• pregnancy or breast feeding
• history of resistance to rituximab or alkylating agents or corticosteroid
• Patients who previously achieved remission after treatment of rituximab or alkylating agents but relapsed off rituximab or alkylating agents after 6 months are eligible.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (6)

• 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

• Dahan K, Debiec H, Plaisier E, Cachanado M, Rousseau A, Wakselman L, Michel PA, Mihout F, Dussol B, Matignon M, Mousson C, Simon T, Ronco P; GEMRITUX Study Group. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up. J Am Soc Nephrol. 2017 Jan;28(1):348-358. doi: 10.1681/ASN.2016040449. Epub 2016 Jun 27.

  PMID: 27352623 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

• 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

• Dahan K, Johannet C, Esteve E, Plaisier E, Debiec H, Ronco P. Retreatment with rituximab for membranous nephropathy with persistently elevated titers of anti-phospholipase A2 receptor antibody. Kidney Int. 2019 Jan;95(1):233-234. doi: 10.1016/j.kint.2018.08.045. No abstract available.

  PMID: 30606419 BACKGROUND

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Interventions

Prednisone; Cyclophosphamide; Rituximab

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)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Yan Qin

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sanxi Ai

CONTACT

18811054896; sanxiai@163.com

Yan Qin

CONTACT

qinyanbeijing@126.com

Study Design

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

Study Record Dates

• First Submitted: February 4, 2021
• First Posted: February 9, 2021
• Study Start: April 14, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

CN (1)