The Iguratimod Effect on Lupus Nephritis (IGeLU)

Study Overview
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Brief Summary
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This study is a 52-week, randomized, open, active-controlled trial of patients with active diffused lupus nephritis, to assess the efficacy and safety of a novel chemical synthetic agent iguratimod. The subjects will randomly receive iguratimod or cyclophosphamide followed with azathioprine, both combined with steroids.

Official Title
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The Effect of Iguratimod on Active Lupus Nephritis, the IGeLU Study: a Randomized Controlled Trial

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Iguratimod
* Drug: Cyclophosphamide
* Drug: Azathioprine
* Drug: Steroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active lupus nephritis: Fulfill ACR classification criteria (2009) for SLE Proteinuria ≥1g/24h at screening Nephritis of class III, IV, V, III+IV or IV+V, confirmed by renal pathology within 90 days prior to screening Body weight ≥40kg SLE-2K score ≥8 Agreement of contraception Informed consent obtained Exclusion Criteria: Active severe SLE-driven renal disease or unstable renal disease at screening Active severe or unstable neuropsychiatric SLE Clinically significant active infection including ongoing and chronic infections History of receiving cyclophosphamide, azathioprine, tacrolimus , mycophenolate moetil or rituximab treatment with 90 days prior to screening History of human immunodeficiency virus (HIV) Confirmed Positive tests for hepatitis B or positive test for hepatitis C Active tuberculosis Live or attenuated vaccine within 4 weeks prior to screening Subjects with significant hematologic abnormalities Abnormal liver function test at screening (ALT, AST or total bilirubin over 2 fold of upper normal level History of peptic ulcer or GI bleeding; treatment with warfarin or other anticoagulants within last 14 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iguratimod<br>Patients will receive iguratimod over the whole follow-up, combined with steroids, as well as auxiliary treatment (such as vitamin D, gastrointestinal agents, blood pressure medications, if any) | Drug: Iguratimod<br>* 25mg twice a day, orally administrated<br>* Other names: Iremod (brand name);Drug: Steroids<br>* Prednisone, methylprednisolone or prednisonlone, once a day, orally administrated. Steroids should be 1mg/kg·d in the beginning four weeks, then tapered 5-10mg/d every two weeks till 30mg/d, then tapered 2.5-5mg/d every two weeks. After 24 weeks of follow-up, a patient should receive steroids no more than 10mg/d. Patients may receive temporal high dose of steroids (1mg/kg·d) because of symptoms outside of kidney, for no more than two weeks. All the dosage of steroids above is calculated by prednisone.<br>|
| Active Comparator: Cyc+AZA<br>Patients will receive cyclophosphamide in the first half of study (usually to 24 weeks), followed with azathioprine till the end of follow-up. Patients will also receive steroids as combinational therapy, as well as auxiliary treatment (such as vitamin D, gastrointestinal agents, blood pressure medications, if any) | Drug: Cyclophosphamide<br>* 1g/m², every 4 weeks, intravenous<br>Drug: Azathioprine<br>* 2mg/kg·d, once a day, orally administrated<br>Drug: Steroids<br>* Prednisone, methylprednisolone or prednisonlone, once a day, orally administrated. Steroids should be 1mg/kg·d in the beginning four weeks, then tapered 5-10mg/d every two weeks till 30mg/d, then tapered 2.5-5mg/d every two weeks. After 24 weeks of follow-up, a patient should receive steroids no more than 10mg/d. Patients may receive temporal high dose of steroids (1mg/kg·d) because of symptoms outside of kidney, for no more than two weeks. All the dosage of steroids above is calculated by prednisone.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| renal remission rate |  | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal remission rate |  | Week 24 | 
| Renal flare rate |  | Week 52 | 
| Number of participants with treatment-related adverse events | adverse events are assessed by CTCAE v4.0 | Week 52 | 
| SLEDAI-2K score | SLE SLE disease activity index (2000) | Week 52 | 
| BILAG score | British Isles lupus assessment group score | Week 52 | 
| PGA | Patient general assessment | Week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus, nephritis, iguratimod