Leflunomide Plus Low Dose Corticosteroid in Immunoglobulin A (IgA) Nephropathy With Renal Insufficiency

A Randomized, Controlled Trial to Evaluate Leflunomide Plus Low Dose Corticosteroid Therapy in Progressive IgA Nephropathy With Renal Insufficiency

IgA nephropathy is the most common primary glomerulonephritis in the world. Because of the poor treatment effect in advanced patients, it is still the main cause of maintenance dialysis. Current immunosuppressive therapy is still controversial, especially to those progressive IgA nephropathy with eGFR<50ml/min. Leflunomide is widely used in the treatment of rheumatic diseases, such as rheumatoid arthritis and lupus nephritis, it's serum concentration will not be affected by renal function, and it also has antiviral effect. There are two randomized controlled trials and a retrospective study suggesting that leflunomide combined with glucocorticoids can effectively control urinary protein compared with glucocorticoids or conservative treatment, but these three studies are not specifically targeted at patients with estimated Glomerular Filtration Rate(eGFR) < 50ml/min.

Investigators will perform a prospective, open-label, randomized, controlled trial to evaluate the efficacy and safety of leflunomide and low dose glucocorticoids therapy in progressive IgA nephropathy with eGFR<50ml/min

Study Overview

• Status: Unknown
• Conditions: Renal Insufficiency, Chronic; Glomerulonephritis, IGA
• Intervention / Treatment: Drug: Leflunomide 20 mg+prednisone 0.5mg/kg/d

Detailed Description

all the participants enrolled in the study will be randomly assigned in a 1:1 ratio, the experimental group will receive leflunomide + low dose glucocorticoids therapy on the basis of conservative treatment, while the control group receive conservative treatment only. Conservative treatment is defined as the treatment of delaying the progress of renal function, including low-protein diet supplemented with ketoacid therapy, Renin Angiotensin system (RAS) inhibitor, blood pressure control, lipid-regulating therapy and antiplatelet aggregation therapy. The course of treatment will last one year, then the leflunomide+glucocorticoids group will continue the conservative treatment. Participants will be follow-up at least 98 weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Xu Yi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 14 to 65 years old participants, No restrictions on gender or race
• Diagnosis of primary IgA nephropathy
• Renal biopsy within 6 months before screening. Renal pathology shows diffuse IgA deposition in the Mesangial area and dense deposition in the Mesangial area under electron microscope. glomeruli more than 8
• persistent proteinuria ≥ 1 g/24 hr (or urine protein/creatinine ratio ≥ 1.0 mg/g), eGFR at 25-50 ml/min/1.73 m2 (calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula)
• signed written consent; patients under 18 years old need to have legal guardians to sign informed consent at the same time

Exclusion Criteria:

• Secondary IgA nephropathy (such as lupus nephritis, Henoch-Schönlein purpura, hepatitis B associated glomerulonephritis, hepatitis C associated glomerulonephritis, liver cirrhosis and other autoimmune diseases)
• eGFR < 25 ml/min/1.73m2 or eGFR > 50 ml/min/1.73m2 (calculated by CKD-EPI formula)
• Special types of IgA nephropathy need to be excluded, such as crescent IgA glomerulonephritis (defined as the presence of crescents in over 50% of the glomeruli), or minimal lesions with IgA deposition
• Acute kidney injury within 3 months before screening
• Received immunosuppressive therapy within 3 months before screening
• Patients who had acute or chronic infections that need treatment, and the researchers judged that they were not suitable for inclusion in the study
• Pregnancy, lactation or unreliable birth control
• Dialysis treatment before screening
• Allergic or taboo to planned drugs (such as leflunomide, glucocorticoids, etc.)
• Severe acute or chronic diseases that the researchers believe may bring an excessive risk to the subjects
• A history of malignant tumors within 5 years, with the exception of carcinoma in situ and papillary thyroid carcinoma which have been adequately treated
• Participated in other clinical trials and / or used other research drugs within 4 weeks prior to screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: leflunomide + low dose glucocorticoids therapy group; the experimental group will receive leflunomide + low dose glucocorticoids therapy on the basis of conservative treatment, while the control group receive conservative treatment	Drug: Leflunomide 20 mg+prednisone 0.5mg/kg/d; Leflunomide plus low dose glucocorticoids to have the immunosuppressive therapy to those progressive IgA nephropathy with eGFR<50ml/min; Other Names: Arava
No Intervention: Basic conservative treatment group; the basic conservative treatment group is the delaying the progress of renal function, including low-protein diet supplemented with ketoacid therapy, RAS inhibitor, blood pressure control, lipid-regulating therapy and antiplatelet aggregation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
renal survival rate	50% increase in serum creatinine compared with the baseline level or End Stage Renal Disease(ESRD)	at least 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proteinuria	changes in proteinuria compared to the baseline	at least 96 weeks
eGFR	extent of eGFR decline compared with the baseline and annual decline rate	at least 96 weeks
complete remission rate	Complete Remission (CR): proteinuria < 1.0g / 24hr, Scr stable (Scr increase ≤ 15% baseline level)	at least 96 weeks
partial remission rate	Partial Remission (PR): proteinuria in 1.0-3.5g/24hr range and decrease more than 50%, Scr stable (Scr increased ≤ 15% baseline level)	at least 96 weeks
no response rate	No Response (NR)：proteinuria > 3.5g/24hr or decrease less than 50% of baseline , with or without deterioration of renal function	at least 96 weeks

Collaborators and Investigators

• Sponsor: Shenzhen Second People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2019
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): May 31, 2022

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 11, 2019
• First Posted (Actual): July 16, 2019

Study Record Updates

• Last Update Posted (Actual): February 18, 2020
• Last Update Submitted That Met QC Criteria: February 14, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Renal Insufficiency, Chronic; Glucocorticoids; Conservative Treatment; Leflunomide; Glomerulonephritis, IGA
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Nephritis; Renal Insufficiency, Chronic; Renal Insufficiency; Glomerulonephritis; Glomerulonephritis, IGA; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Leflunomide
• Other Study ID Numbers: 20193357002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No