Mycophenolate Mofetil in Patients With Progressive Idiopathic Membranous Nephropathy

Glomerulonephritis, Membranous Clinical Trial

— MMFPRIMER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01282073
• Other study ID #: MMFPRIMER
• Status: Recruiting
• Phase: Phase 3
• First received: January 19, 2011
• Last updated: April 9, 2015
• Start date: March 2011
• Est. completion date: July 2017

Study information

• Verified date: April 2015
• Source: Kyungpook National University
• Contact: Hee-Yeon Jung, MD
• Phone: +82-10-2536-4106
• Email: 83mayring[@]hanmail.net
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glomerulonephritis
• Glomerulonephritis, Membranous
• Kidney Diseases

Intervention

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
• 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

Locations

Country	Name	City	State
Korea, Republic of	Dong-A University Medical Center	Busan
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Daegu Fatima Hospital	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam University Medical Center	Daegu
Korea, Republic of	Boramae Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan

Sponsors (2)

Lead Sponsor	Collaborator
Kyungpook National University	Hanmi Pharmaceutical Company Limited

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Proteinuria	The change of proteinuria from baseline to 48 week after treatment	at 48 week after treatment	No
Secondary	Side effects	Any undesired effects of interventional drugs	For 48 weeks after treatment	Yes