Please select the eligibility criteria that correspond to the clinical trial below.
Title: 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
Brief Summary: 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).


Options:
A: Inclusion Criteria:

* Patients with IgA nephropathy confirmed by renal biopsy
* Serum creatinine measurement ≤1.5mg/ml or MDRD estimated GFR ≥ 45ml/min/1.73m2 (MDRD: Modification of Diet in Renal Disorder)
* UACR level between 0.3 and 3.0
* Blood pressure measurements \< 130/80mmHg

Exclusion Criteria:

* Use of immunosuppressants for more than two weeks within last one month
* Concomitant use of ACE inhibitor, ARB, steroids or immunosuppressant, NDHP-CCB, diuretics, omega-3 fatty acids and its analogue \& additional dietary to treat igA nephropathy (ACE: Angiotensin Converting Enzyme, ARB: Angiotensin Receptor Blocker, NDHP-CCB: Non-dihydropyridine-type Calcium Channel Blocker
* Pregnant or breast-feeding patients. Patients who plan to bear children or breast-feed during the study and within 6 month after completion of study
* Hypersensitivity to the investigational drug or macrolide agents
* Use of potassium-sparing diuretics
* Persistence of liver function abnormality more than 1 month or presence of acute active hepatitis
* Other investigational drug within last 30 days
B: Screening Inclusion Criteria:

1. Female or male patients ≥18 years
2. Biopsy-verified IgA nephropathy
3. Urine protein creatinine ratio ≥0.5 g/g OR urine protein ≥0.75 g/24hr
4. 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
5. Willing to change antihypertensive medication regimen if applicable
6. Willing and able to give informed consent

Screening Exclusion Criteria:

1. Secondary forms of IgA nephropathy as defined by the treating physician (for example, Henoch-Schönlein purpura patients and those with associated alcoholic cirrhosis)
2. Presence of crescent formation in ≥50% of glomeruli assessed on renal biopsy
3. 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
4. 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.
5. 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
6. Patients previously treated with immunosuppressive or systemic corticosteroids for the treatment of IgA nephropathy
7. Patients unable to take oral medication or intolerant to budesonide or other corticosteroid preparations
8. Patients with known allergy or intolerance to ACEI, ARB or to any component of the trial drug formulation
9. Patients with acute or chronic infectious disease incl. hepatitis, HIV positive patients and patients with chronic urinary tract infections
10. Severe liver disease according to the discretion of the Investigator
11. Patients with Type 1 or 2 diabetes
12. Patients with uncontrolled cardiovascular disease as judged by the Investigator
13. Patients with current malignancy or history of malignancy during the last three years
14. 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:

1. Completion of the Run-in Phase
2. Urine protein creatinine ratio ≥0.5 g/g OR urine protein ≥0.75 g/24hr
3. 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:

1. Unacceptable blood pressure defined as a systolic value \>160 mm Hg or diastolic \>100 mm Hg
2. eGFR (CKD-EPI) loss \>30% over the entire duration of the Run-in Phase
3. For women only; pregnant or breast feeding or unwilling to use adequate contraception during the trial (only women of child bearing potential)
C: Inclusion Criteria:

* Male or female patients from 18-70 years with histologically proven primary IgAN with typical mesangioproliferative features. Diagnosis has to be made by a neuropathologist.
* Proteinuria above 0.75 g/day within 12 weeks prior to or at the first visit in the run-in phase (month -6)and presence of at least one further risk factor for the development of end stage renal disease

  1. arterial hypertension, defined as ambulatory blood pressure \>140/90 mm Hg or the use of antihypertensive medication or
  2. impaired renal function, defined as creatinine clearance or estimated GFR \<90 ml/min.

Exclusion Criteria:

* Known allergy or intolerance to study medication (except in case of ACE-inhibitor, in which case a change to an angiotensin receptor blocker is possible).
* Women who are pregnant or breastfeeding and women without sufficient contraception.
* Any prior immunosuppressive therapy.
* Variants of primary IgAN (e.g. rapidly progressive IgAN with crescents in \>50% of glomeruli or minimal change GN with glomerular IgA deposits).
* Significant liver dysfunction (more than three fold increased GPT compared to norm)
* Contraindication for immunosuppressive therapy, like

  * acute or chronic infectious disease incl. hepatitis and HIV positive patients
  * any malignancy
  * leukocytopenia, thrombocytopenia or known allergy against prednisolone, cyclophosphamide or azathioprine
  * active intestinal bleeding, active gastric or duodenal ulcer
  * Need of permanent immunosuppression, (e.g. transplanted patients, steroid-dependent inflammatory diseases)
* Secondary IgAN or diseases associated with glomerular deposits of IgA.
* Additional other chronic renal disease.
* Creatinine clearance below 30 ml/min (mean of 3 measurements).
* Alcohol or drug abuse
* Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
* Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
* Participation in a parallel clinical trial or participation in another clinical trial within the last 3 months.
* Subjects who are in any state of dependency to the sponsor or the investigators.
* Employees of the sponsor or the investigators.
* Subjects who have been committed to an institution by legal or regulatory order.
D: Inclusion Criteria:

1. underwent renal biopsy within 1 year before start fo trial;
2. 24 hour urinary protein excretion ranged between 1 to 7 g/d;
3. eGFR, evaluated by MDRD formula, should be higher than 30 ml/min

Exclusion Criteria:

1. crescentic glomerulonephritis;
2. steroid therapy subjected within 1 year before trial;
3. malignant hypertension(DBP\> 130 mmHg and/or SBP\> 220mmHg), resistant to anti-hypertensive agents;
4. urinary protein excretion decrease below 1 g/l after run-in period;
5. Myocardial infarction or cerebrovascular accident in 6 months preceding the trial;
6. renovascular disease;
7. diabetes mellitus;
8. Malignancy, severe liver disease, refractory infection;
9. peptic ulcer in active disease phase;
10. pregnancy;
11. other contraindication to the use of ACEi/ ARB or corticosteroid;
12. alcohol abuse or drug addiction

Answer: B