Mycophenolate Mofetil (MMF) in Patients With IgA Nephropathy (IgAN)

Official Title: “A Prospective, Multicenter, Randomized Controlled Trial of Mycophenolate Mofetil (MMF) in Patients With IgA Nephropathy (IgAN)”

A multi-center, randomized, controlled clinical trial to evaluate the short-term and long-term efficacy and safety of mycophenolate mofetil (MMF) in reducing proteinuria and preserving renal function in patients with IgAN who have pre-treated (and continue to be treated) with angiotensin II receptor blockers (ARB), compared to the corticosteroids.

There are four phases of study for each subject. Phase 1 the screening phase. During this phase each potential subject will be evaluated to determine if he/she is eligible for the study.

Phase 2 the ARB lead-in phase will last for three months. Phase 3 the intervention phase.

Each subject will be randomly received 12 months treatment with the study drugs (MMF, prednisone or MMF plus prednisone) Phase 4 following-up phase. All the patients will be followed by 3 years after study drug stopped.

Intervention(s) in this Clinical Trial

• Drug: irbesartan
  • In the ARB lead-in phase, each subject will be on a strict sodium-restricted diet ( < 5 g NaCl/day), and then given a stable dose (150mg ~ 300mg/day) of irbesartan (Aprovel) for 3 months until reaching the target blood pressure (BP) level of ≤ 125/75 mmHg. Patients will continue ARB treatment in the drug treatment phase and at lease 3 years in the follow-up phase.
• Drug: methylprednisolone (MP) or prednisone (pred)
  • Patients will take oral Pred ( 0.5 mg/kg/d) on alternate days, and on the first, third and fifth months of the drug treatment phase, patients will be given intravenous pulse therapy with methylprednisolone ( 0.5 g/day) for 3 successive days. And after 6 months, Pred should be tapered to be stopped until the end of the 12-month course of treatment.
• Drug: mycophenolate mofetil (MMF)
  • Patients will take MMF 1.0g bid (wt ≥ 50kg) or 0.75g bid (wt ＜ 50kg) for the first 6-month of drug treatment phase, then to 0.5 bid (wt ≥ 50kg) for the remaining 6-month.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Pred Group: Prednisone treatment
• Active Comparator: 2
  • MMF Group: MMF treatment
• Active Comparator: 3
  • Pred plus MMF Group: Prednisone plus MMF treatment

Primary Measures

• Remission of proteinuria (complete or partial)
  • Time Frame: every 3 month for 4.3 years（including 3 months ARB leading-in phase， 1 years' treatment phase and 3 years' follow-up）
    Safety Issue?: Yes

Secondary Measures

• Deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine (SCr) levels, or a 25% decline from baseline eGFR levels, or onset of end-stage renal disease or dialysis treatment, or kidney transplantation)
  • Time Frame: every 6 month for 4.3 years（including 3 months ARB leading-in phase， 1 years' treatment phase and 3 years' follow-up）
    Safety Issue?: Yes

Inclusion Criteria:

• Willingness to sign an informed consent
• Age:14~60 years, regardless of gender
• Clinical evaluation and renal biopsy diagnostic for IgAN, excluded secondary IgAN.
• Renal histological criteria should be defined by Lee's glomerular grading system.
• 1 g/day <= proteinuria < 3.5 g/day, or UPr/Cr ratio ≥ 0.6 (male) or ≥ 0.8 (female) when taking ARB
• eGFR ≥ 40 mL/min/1.73 m2

Exclusion Criteria:

• Inability or unwillingness to sign the informed consent
• Inability or unwillingness to meet the scheme demands raised by the investigators
• Rapidly progressive nephritic syndrome and acute renal failure, including rapidly progressive IgAN ( IgAN with rapid decline in renal function characterized histologically by necrotizing vasculitis and crescent formation≥30%) necessitating the use of other immunosuppressive agents.
• Secondary IgAN such as systemic lupus erythematosus, Henoch-Schonlein purpuric nephritis and hepatitis B -associated nephritis
• est GFR < 40 mL/min/1.73m2
• Malignant hypertension that is difficult to be controlled by oral drugs
• Cirrhosis, chronic active liver disease.
• History of significant gastrointestinal disorders (e.g. severe chronic diarrhea or active peptic ulcer disease.)
• Any Active systemic infection or history of serious infection within one month of entry or known infection with HIV, hepatitis B, or hepatitis C.
• Other major organ system disease (e.g. serious cardiovascular diseases including congestive heart failure , chronic obstructive pulmonary disease, asthma requiring oral steroid treatment or central nervous system diseases)
• Malignant tumors (except fully cured basal cell carcinoma)
• Absolute neutrophil count ＜ 1500／mm3, absolute platelet count ＜75000／mm3 or hematocrit (Hct) <28% (anemic subjects may be reevaluated after the anemia has been treated.)
• Known allergy, contraindication or intolerance to the MMF, corticosteroids or ACEI/ARB.
• Pregnancy or breast feeding at the time of entry or unwillingness to comply with measures for contraception
• Current exposure to MMF or azathioprine. In case of current treatment with oral steroid or ACEI/ARB, entry is permitted after corticosteroids or ACEI/ARB are stopped for 2 weeks.
• Current or recent (within 30 days) exposure to any other investigational drugs

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 14 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Sun Yat-sen University Other

Overall Clinical Trial Officials and Contacts

Xueqing Yu, MD Principal Investigator Department of Nephrology, 1st Affiliated Hospital, Sun Yat-Sen University  

Overall Contact: Xueqing Yu, MD 8620-87766335 yuxq@mail.sysu.edu.cn

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00657059

Study ID Number: SYSU-PRGIgAN-001

ClinicalTrials.gov Identifier: NCT00657059

Health Authority: China: State Food and Drug Administration