The Effect of Nefecon® in Patients With Primary IgA Nephropathy at Risk of Developing End-stage Renal Disease

Study Overview
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Brief Summary
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The objective of the study is to evaluate efficacy and safety of two different doses of NEFECON in the treatment of patients with primary IgA nephropathy (IgAN) at risk of developing end-stage renal disease, under rigorous blood pressure control with an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin II receptor I blocker (ARB).

Detailed Description
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NEFECON is an add-on treatment to other medications for nephropathy symptoms and kidney function, including ACEI and/or ARBs. Rigorous blood pressure control will be achieved over a 6-month Run-in Phase in which ACEI and/or ARB will be dosed to target a blood pressure of <130/80 mm Hg and UPCR <0.5 g/g. Patients who complete the Run-in Phase, and despite optimized ACEI and/or ARB therapy, have a UPCR ≥0.5 g/g OR urine protein ≥0.75 g/24hr will be eligible for randomization and entry into the treatment phase of the trial. Patients will remain on their ACEI and/or ARB dosing regimen for the duration of the trial. Patients entering the treatment phase will be administered NEFECON (8 mg/day OR 16 mg/day) OR placebo for a phase of 9 months. A 3-month follow-up phase will follow on from the treatment phase, of which the first 2 weeks will be used to taper the dose of those patients that received 16 mg/day dosing to 8 mg/day, with the placebo and 8 mg/day groups receiving placebo to retain blinding.

Official Title
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A Multicentre, Interventional Treatment, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Two Different Doses of Nefecon in Primary IgA Nephropathy Patients at Risk of End-stage Renal Disease

Conditions
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Primary IgA Nephropathy

Intervention / Treatment
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* Drug: NEFECON
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Screening Inclusion Criteria: Female or male patients ≥18 years Biopsy-verified IgA nephropathy Urine protein creatinine ratio ≥0.5 g/g OR urine protein ≥0.75 g/24hr Estimated GFR (using the CKD-EPI formula) OR measured GFR ≥50 mL/min per 1.73 m2 OR ≥45 mL/min per 1.73m2 for patients on a maximum recommended or maximum tolerated dose of an ACEI and/or ARB Willing to change antihypertensive medication regimen if applicable Willing and able to give informed consent Screening Exclusion Criteria: Secondary forms of IgA nephropathy as defined by the treating physician (for example, Henoch-Schönlein purpura patients and those with associated alcoholic cirrhosis) Presence of crescent formation in ≥50% of glomeruli assessed on renal biopsy Kidney transplanted patients 4. Severe gastrointestinal disorders (including peptic ulcer disease and inflammatory bowel disease) which may impair drug effect, or other conditions which could modify the effect of the trial drug as judged by the Investigator Patients currently treated with systemic immunosuppressive or systemic corticosteroid drugs (excluding topical or nasal steroids) or have been previously treated for more than one week within the last 24 months. Patients currently treated chronically (daily dosing) with inhaled corticosteroid drugs or have previously been treated chronically for more than one month within the last 12 months Patients previously treated with immunosuppressive or systemic corticosteroids for the treatment of IgA nephropathy Patients unable to take oral medication or intolerant to budesonide or other corticosteroid preparations Patients with known allergy or intolerance to ACEI, ARB or to any component of the trial drug formulation Patients with acute or chronic infectious disease incl. hepatitis, HIV positive patients and patients with chronic urinary tract infections Severe liver disease according to the discretion of the Investigator Patients with Type 1 or 2 diabetes Patients with uncontrolled cardiovascular disease as judged by the Investigator Patients with current malignancy or history of malignancy during the last three years For women only; pregnant or breast feeding or unwilling to use adequate contraception during the trial (only women of child bearing potential) Randomization Inclusion Criteria: Completion of the Run-in Phase Urine protein creatinine ratio ≥0.5 g/g OR urine protein ≥0.75 g/24hr eGFR ≥45 mL/min per 1.73 m2 using CKD-EPI formula OR measured GFR ≥45 mL/min per 1.73 m2 Randomization Exclusion Criteria: Unacceptable blood pressure defined as a systolic value >160 mm Hg or diastolic >100 mm Hg eGFR (CKD-EPI) loss >30% over the entire duration of the Run-in Phase For women only; pregnant or breast feeding or unwilling to use adequate contraception during the trial (only women of child bearing potential)

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEFECON 8 mg/day<br>NEFECON 8 mg/day (2 active + 2 placebo capsules daily) for 9 months | Drug: NEFECON<br>* All patients will receive a maximum recommended daily dose of an ACEI and/or ARB (or maximum tolerated dose not exceeding the maximum recommended daily dose) for the duration of the treatment and follow-up phases.<br>* Other names: Budesonide modified-released capsules (4 mg/capsule);|
| Experimental: NEFECON 16 mg/day<br>NEFECON 16 mg/day (4 active capsules daily) for 9 months | Drug: NEFECON<br>* All patients will receive a maximum recommended daily dose of an ACEI and/or ARB (or maximum tolerated dose not exceeding the maximum recommended daily dose) for the duration of the treatment and follow-up phases.<br>* Other names: Budesonide modified-released capsules (4 mg/capsule);|
| Placebo Comparator: Placebo<br>Placebo (4 placebo capsules daily) for 9 months | Other: Placebo<br>* All patients will receive a maximum recommended daily dose of an ACEI and/or ARB (or maximum tolerated dose not exceeding the maximum recommended daily dose) for the duration of the treatment and follow-up phases.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urine protein creatinine ratio |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urine albumin creatinine ratio |  | 9 months | 
| Change from baseline in 24 hour albuminuria |  | 9 months | 
| Change from baseline in estimated GFR |  | 9 months | 

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