Rituximab in Recurrent IgA Nephropathy

Phase 4

• Conditions: Recurrent IgA Nephropathy
• Interventions: Drug: Intravenous Rituximab; Drug: ACEI/ARB and corticosteroids

• Registration Number: NCT02571842
• Lead Sponsor: Chulalongkorn University

Brief Summary

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

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.

Study Timeline

• Study Start: 2012-01
• Status Verified: 2015-10
• Study First Submitted: 2015-10-06
• Study First Submitted QC: 2015-10-07
• Last Update Submitted: 2015-10-07
• Study First Posted: 2015-10-08
• Last Update Posted: 2015-10-08
• Primary Completion: 2016-12
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rituximab	Intravenous Rituximab	Drug: Rituximab •Rituximab 375 mg/m2 on treatment month 1, 2, 3, 4 Other Name: Mabthera
ACEI/ARB plus corticosteroids	ACEI/ARB and corticosteroids	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in allograft pathology following treatment	12 months	The difference of active and chronic score report by BANFF score, HAAS, Oxford criteria between pre-treatment and post-treatment

Trial Locations

Locations (1)

Chulalongkorn University; 🇹🇭 Bangkok, Thailand