Replication of the NefIgArd Trial of TRF-budesonide in Primary IgAN

Currently, TRF-budesonide are the first specific treatment for IgA nephropathy that targets intestinal mucosal immunity. Results from part A of the Phase III clinical trial (NCT03643965) show that compared to the placebo group, the TRF-budesonide group significantly reduced proteinuria and hematuria, stabilized renal function, and lowered circulating Gd-IgA1 levels at 12 months. However, further real-world studies are needed to verify the efficiency and safety of this treatment for IgA nephropathy. Therefore, this replication trial of the part A of the Phase III clinical trial NefIgArd and evaluates the efficiency and safety of TRF-budesonide in treating IgA nephropathy based on existing observational data, aiming to complete real-world research to provide real-world evidence that can guide clinical practice for IgA nephropathy treatment.

Inclusion criteria

• Male or female patients aged ≥18 years;
• Primary IgA nephropathy confirmed by renal biopsy;
• Stable use of RAS blockers;
• 24-hour urine albumin quantitation ≥1g/day, or urine protein/creatinine ratio ≥0.8g/g (≥90 mg/mmol);
• eGFR ≥30 mL/min/1.73m².

Exclusion criteria

• Systemic diseases that may cause interstitial IgA deposition, including but not limited to anaphylactoid purpura, systemic lupus erythematosus, herpetic dermatitis, and ankylosing spondylitis;
• Patients who have received kidney transplants;
• Those with other glomerular diseases (such as C3 glomerular disease or diabetic nephropathy) and nephrotic syndrome;
• Patients with acute, chronic, or latent infectious diseases, including hepatitis, tuberculosis (TB), human immunodeficiency virus (HIV), and chronic urinary tract infections;
• Patients with cirrhosis or severe liver function impairment, as assessed by the investigator;
• Patients diagnosed with poorly controlled type 1 or type 2 diabetes;
• Patients with a history of unstable angina, grade III or IV congestive heart failure, and/or arrhythmia as assessed by the investigator;
• Patients with poorly controlled blood pressure with systolic or diastolic blood pressure ≥140mmHg or 90mmHg. At least one blood pressure measurement should be in the above range (based on up to three measurements, 1 minute apart, taken after resting in the supine position for at least 5 minutes);
• Patients diagnosed with malignancy within the last 5 years, with the exception of treated basal cell carcinoma of the skin, curably resected squamous cell carcinoma of the skin, polyps of the colon, or carcinoma in situ of the cervix;
• Patients with osteoporosis who are known to be at moderate or high risk. Chinese patients are defined according to the Asian Osteoporosis Self-Assessment Tool (OSTA) Index;
• Patients with known glaucoma, known history of cataract and/or cataract surgery that may interfere with study drug action or release (such as peptic ulcer disease, inflammatory bowel disease, and chronic diarrhea);
• Patients who are allergic to budesonide or any component of the investigational drug formulation;
• Patients who have previously had a severe adverse reaction to steroids;
• Patients with psychotic symptoms;
• Have received any systemic glucocorticoid therapy within 3 months prior to medication;
• Received immunosuppressants or biologics within 3 months prior to medication;
• Patients taking potent inhibitors of the cytochrome P450 3A4 enzyme (CYP3A4);
• Current or former (within the last 2 years) alcohol or drug abuse;
• Patients who are unwilling or unable to meet program requirements;
• Life expectancy <5 years;
• Women who are pregnant, nursing, or unwilling to use contraception during treatment.