Rituximab in Recurrent IgA Nephropathy

Study Overview
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Brief Summary
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Currently, the treatment options of recurrent IgA nephropathy (IgAN) are conflicting and largely based on expert opinions. Consequently, the recent KDIGO clinical practice guideline for the care of kidney transplant recipients has concluded that there are no definite strategies for prevention and treatment. However, recurrent IgAN in the transplanted kidney is common and may contribute to graft loss, in particular, if cresentic formation, extra- or endocapillary proliferation were presented in kidney pathology. Herein, the investigators assume that rituximab, anti-CD20 Ab agent, can reduce circulating IgA with subsequently decrease rate of polymeric forms of IgA deposition in glomerular capillaries. Therefore, the investigators speculate that rituximab may have potential effect to reduce circulating polymeric forms of IgA and slow progression of recurrent IgAN.

Detailed Description
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Hypothesis: In kidney transplant recipients with active endocapillary proliferation pathology of recurrent IgAN, an intravenous infusion of 375mg/m2 of rituximab on 4 consecutive monthly dose is superior to conventional therapy in reducing 24-hour proteinuria, and slowing progression of recurrent IgAN.

Official Title
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A Randomized, Prospective, Open-Label Study of Rituximab in the Treatment of Recurrent IgA Nephropathy With Active Endocapillary Proliferation Pathology

Conditions
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Recurrent IgA Nephropathy

Intervention / Treatment
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* Drug: Intravenous Rituximab
* Drug: ACEI/ARB and corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any kidney transplant recipients between the age of 18 and 70 years of age and able to give informed consent GFR by 24h Creatinine Clearance (CrCl) >30 ml/min/1.73m² Biopsy proven recurrent IgA nephropathy with endocapillary proliferation pattern Exclusion Criteria: Clinical and histologic evidence of IgA combination with other forms of glomerulonephritis Clinical evidence of cirrhosis, chronic active liver disease or known infection with hepatitis B, C or HIV 24h CrCl <30 ml/min/1.73m² at the time of screening Active systemic infection or history of serious infection within one month of entry Positive pregnancy test or breast feeding at time of study entry Patients receiving >6 months therapy with oral prednisone >5mg/day or glucocorticoid equivalent Live vaccine within 28 days of study enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Rituximab<br>Drug: Rituximab •Rituximab 375 mg/m2 on treatment month 1, 2, 3, 4 Other Name: Mabthera | Drug: Intravenous Rituximab<br>* - 375 mg/m2 rituximab be prescribed 4 consecutive monthly<br>* Other names: Mabthera;|
| Active Comparator: ACEI/ARB plus corticosteroids<br>Drug: ACEI/ARB An ACEI and /or ARBs will be used to achieve proteinuria reduction and a blood pressure goal of <130/80 mmHg. Patients not attaining the target blood pressure with an ACEI or ARB alone should be treated with the combination of ACEI + ARB Corticosteroids will be used as prednisolone 0.5 mg/kg/day with gradually taper off in 6-8 weeks to 5mg/day daily Other Name: Enalapril, Lorsartan, Prednisolone | Drug: ACEI/ARB and corticosteroids<br>* ACEI or ARB will be prescribed as high as tolerable dose. Prednisolone will be prescribed starting as 0.5 mg/kg/day then taper off to 5 mg/day within 6-8 weeks<br>* Other names: Enalapril, Lorsartan, Prednisolone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate | Percentage of patients in each group achieving complete or partial response determined by proteinuria and 24-hour creatinine clearance | 12 months | 
| Incidence of all adverse events | The incidence of adverse events such as serious infection, allergy, fever, headache, etc. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in allograft pathology following treatment | The difference of active and chronic score report by BANFF score, HAAS, Oxford criteria between pre-treatment and post-treatment | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent IgA nephropathy, Rituximab