Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy

Study Overview
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Brief Summary
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The overall aim of the study is to evaluate the efficacy, safety, and tolerability of Nefecon 16 mg per day in the treatment of patients with primary IgAN (Immunoglobulin A nephropathy) at risk of progressing to end-stage renal disease (ESRD), despite maximum tolerated treatment with renin-angiotensin system (RAS) blockade using angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type I receptor blockers (ARBs).

Detailed Description
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This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy, safety, and tolerability of oral Nefecon compared to matching placebo in patients with primary IgAN on a background of optimized RAS inhibitor therapy. The study will consist of 2 parts, Part A and Part B. Part A will include a 9 month blinded Treatment Period, and a 3-month Follow up Period. Part B of the study will consist of a 12-month observational Follow up Period; no study drug will be administered during Part B. Part A and B will be blinded. Safety will be monitored by an independent Data Safety Monitoring Board.

Official Title
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A Randomized, Double-blind, Placebo Controlled Study to Evaluate Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy at Risk of Progressing to End-stage Renal Disease (NefIgArd)

Conditions
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Primary IgA Nephropathy

Intervention / Treatment
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* Drug: Nefecon
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male patients ≥18 years Biopsy-verified IgA nephropathy Stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) at the maximum allowed dose or Maximum Tolerated Dose (MTD) according to the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) guidelines Urine protein creatinine ratio ≥1 g/24hr eGFR ≥35 mL/min per 1.73 m2 and ≤90 mL/min per 1.73 m2 using the Chronic Kidney Diseae Epidemiology Collaboration (CKD-EPI) formula Willing and able to give informed consent Exclusion Criteria: Systemic diseases that may cause mesangial IgA deposition. Patients who have undergone a kidney transplant. Patients with acute or chronic infectious disease including hepatitis, tuberculosis, human immunodeficiency virus (HIV), and chronic urinary tract infections. Patients with liver cirrhosis, as assessed by the Investigator. Patients with a diagnosis of type 1 or type 2 diabetes mellitus which is poorly controlled. Patients with history of unstable angina, class III or IV congestive heart failure, and/or clinically significant arrhythmia, as judged by the Investigator; Patients with unacceptable blood pressure control defined as a blood pressure consistently above national guidelines for proteinuric renal disease, as assessed by the Investigator Patients with diagnosed malignancy within the past 5 years.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nefecon<br>Nefecon 16 mg once daily by mouth for 9 months. | Drug: Nefecon<br>* Nefecon 16 mg for daily administration by mouth for 9 months.<br>* Other names: Budesonide modified released capsule;|
| Placebo Comparator: Placebo oral capsule<br>Placebo oral capsule once daily by mouth for 9 months. | Drug: Placebo oral capsule<br>* Placebo capsules for daily administration by mouth for 9 months.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Proteinuria, measured as Urine Protein to creatinine ratio (UPCR). | The primary outcome measure is UPCR (based on 24-hour urine collections) at 9 months following the first dose of study drug compared to baseline | 9 months | 
| Renal function measured as estimated glomerular filtration rate (eGFR) | Based on eGFR measure compared to baseline calculated using the CKD-EPI formula | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of treatment-emergent adverse events. | Adverse event data collection | From enrollment and up to 2 years | 
| Renal function | Renal function measured as eGFR using the CKD-EPI formula | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgA Nephropathy