Mycophenolate Mofetil in Patients With Progressive Idiopathic Membranous Nephropathy (MMFPRIMER)

A Randomized Controlled Multi-center Trial of Mycophenolate Mofetil for the Patient With High Risk Membranous Nephropathy

Cyclosporin decreases proteinuria and improve renal function in patients with idiopathic membranous nephropathy, but has a risk of side effects such as nephrotoxicity. The investigators plan to the study to evaluate whether mycophenolate mofetil (MMF) could be a reasonable alternative with fewer side effect.

Study Overview

• Status: Completed
• Conditions: Glomerulonephritis, Membranous
• Intervention / Treatment: Drug: Mycophenolate mofetil, low dose steroid; Drug: Cyclosporin, low dose steroid

Detailed Description

Idiopathic membranous nephropathy is most common cause of glomerulonephritis in adults. Persistent high grade proteinuria or progressively decrease of renal function is a risk factor for end stage renal disease in idiopathic membranous nephropathy. It has been reported that cyclosporin in patients with idiopathic membranous nephropathy decreases proteinuria and improve renal function. Mycophenolate mofetil is a recently developed immunosuppressive agent with fewer side effect than cyclosporin. In this study patients with high risk group of progressive idiopathic membranous nephropathy will be treated with mycophenolate mofetil and low dose prednisone. The outcome will be compared to controls treated with cyclosporin and low dose prednisone.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Korea
  • Busan, South Korea, 602-715
    • Dong-A University Medical Center
  • Busan, South Korea
    • Inje University Haeundae Paik Hospital
  • Daegu, South Korea, 700-721
    • Kyungpook National University Hospital
  • Daegu, South Korea, 701-600
    • Daegu Fatima Hospital
  • Daegu, South Korea, 705-717
    • Yeungnam University Medical Center
  • Seoul, South Korea, 110-799
    • Seoul National University Hospital
  • Seoul, South Korea, 120-752
    • Yonsei University Hospital
  • Seoul, South Korea, 156-707
    • Boramae Medical Center
  • Ulsan, South Korea, 682-714
    • Ulsan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with idiopathic membranous nephropathy
2. The duration of disease is less than twelve months
3. Patients with persistent proteinuria more than 8 grams per day
4. Patients who provided informed consent

5. The cases that satisfy more than three of following items even if proteinuria is less than 8 grams per day:

   • eGFR < 60 ml/min/1.73m2
   • Hypertension (BP above 140/90mmHg or BP above 120/80 in patients taking anti-hypertensive agents)
   • 24 hours urine protein or spot urine protein/creatinine ratio > 5.0 g/day
   • Serum albumin (g/dL) < 3.0
   • Selectivity index > 0.2

Exclusion Criteria:

1. Severe digestive organ disease
2. Allergy history to clinical trial medication and acute or chronic allergy for 4 weeks recently.
3. Clinical history of treatment with other immunosuppressive medication
4. Probability of pregnancy, breast feeding woman
5. Uncontrolled hypertension (more than 160/100mmHg)
6. Uncontrolled systemic disease
7. Drug addiction or alcoholics within 6 months
8. eGFR is less than 30ml/min at screening
9. Abnormal liver function test (more than 3 times above compared with normal value)
10. Absolute neutrophil count <1,500/mm3 or leukocyte <2,500/mm3 or platelets <100,000/mm3
11. Secondary membranous nephropathy
12. Expected life expectancy is less than 1 year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mycophenolate mofetil, low dose steroid	Drug: Mycophenolate mofetil, low dose steroid; Mycophenolate Mofetil: Myconol capsule 250mg, Myconol 500 mg bid per day (less than 50kg), 750 ~ 1000 mg bid per day (more than 50kg) Steroid: Methylprednisone 4mg tablet or Prednisolone 5mg tablet or Deflazacort 6mg tablet. Prednisolone dose: 0.15mg/kg up to a maximum dose of 15mg/day Duration: 48 weeks; Other Names: Myconol, MMF
Active Comparator: Cyclosporin, low dose steroid	Drug: Cyclosporin, low dose steroid; Cyclosporin: Implanta soft cap (cyclosporin microemulsion) 25mg/100mg, starting dose of 4mg/kg per day and titrate according to investigator's decision based on cyclosporin trough level (100±50 ng/ml) Steroid: same dosage with active comparator goup Duration: 48 weeks; Other Names: Implanta soft capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Complete Remission	Complete remission: Reduction in proteinuria to 200 mg per day with stable serum albumin with more than 3.5 g/dL	at 48 week after treatment
Percentage of Partial Remission	Partial remission: Reduction in proteinuria to greater than 50 percent of initial values or absolute values of proteinuria between 200 mg and 3.5 g per day	at 48 week after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse	A relapse is return of proteinuria to approximately 3.5g/day in patients who had previously undergone a complete or partial remission	For 48 weeks after treatment
Proteinuria	The change of proteinuria from baseline to 48 week after treatment	at 48 week after treatment
Estimated Glomerular Filtration Rate (eGFR)	The change of eGFR mesured by Modification of Diet in Renal Disease (MDRD) study equation from baseline to 1 year after treatment	at 48 week after treatment
Side Effects	Any undesired effects of interventional drugs	For 48 weeks after treatment

Collaborators and Investigators

• Sponsor: Kyungpook National University Hospital
• Collaborators: Hanmi Pharmaceutical Company Limited
• Investigators: Principal Investigator: Sun-Hee Park, MD, Kyungpook National University Hospital

Publications and helpful links

General Publications

• von Groote TC, Williams G, Au EH, Chen Y, Mathew AT, Hodson EM, Tunnicliffe DJ. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293. doi: 10.1002/14651858.CD004293.pub4.
• Choi JY, Kim DK, Kim YW, Yoo TH, Lee JP, Chung HC, Cho KH, An WS, Lee DH, Jung HY, Cho JH, Kim CD, Kim YL, Park SH. The Effect of Mycophenolate Mofetil versus Cyclosporine as Combination Therapy with Low Dose Corticosteroids in High-risk Patients with Idiopathic Membranous Nephropathy: a Multicenter Randomized Trial. J Korean Med Sci. 2018 Feb 26;33(9):e74. doi: 10.3346/jkms.2018.33.e74.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: January 19, 2011
• First Submitted That Met QC Criteria: January 21, 2011
• First Posted (Estimated): January 24, 2011

Study Record Updates

• Last Update Posted (Estimated): August 27, 2025
• Last Update Submitted That Met QC Criteria: August 10, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Proteinuria; Renal function; Mycophenolate mofetil; Idiopathic membranous nephropathy
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Urination Disorders; Urological Manifestations; Glomerulonephritis; Nephritis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Proteinuria; Glomerulonephritis, Membranous; Peptides; Amino Acids, Peptides, and Proteins; Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Polycyclic Compounds; Fused-Ring Compounds; Macrocyclic Compounds; Peptides, Cyclic; Caproates; Cyclosporins; Mycophenolic Acid; Cyclosporine; Steroids
• Other Study ID Numbers: MMFPRIMER