Tests approved drugs with standard care in adults with IgA nephropathy

Who can take part

• Must be able to provide a written informed consent form, which must be obtained before the initiation of study assessments
• Adults between 18-65 years of age
• Males or Females
• Diagnosis of primary IgAN as demonstrated by renal biopsy of any vintage if eGFR ≥45 mL/min/1.73 m2 or within the last ten years if eGFR <45 mL/min/1.73 m2. If diabetic, the biopsy vintage should be less than five years
• eGFR ≥20 mL/min/1.73 m2 at screening, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
• Total urine protein excretion ≥1 g per 24-hour or UPCR ≥ 0.75 g/g from an adequately measured 24-hour urine sample (24HUP) during the Screening Period
• Patient on the maximum labelled or tolerated dose of ACEi or ARB AND 10mg/d of Dapagliflozin (SGLT2i) for at least 12 weeks at screening and from screening to study Day 1
• Systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mmHg at randomisation. Other anti-hypertensives can be optimised during the screening period to achieve the BP goal
• A female is eligible if she is not pregnant and consents to avoid pregnancy during the study duration

Who cannot take part

• Concomitant kidney disease in addition to IgAN in kidney biopsy (e.g., diabetic nephropathy, primary focal segmental glomerulosclerosis, membranous nephropathy, C3 glomerulopathy, lupus nephritis)
• Concomitant co-morbidities like systemic autoimmune disorders, chronic active infections like tuberculosis, hepatitis B, hepatitis C and human immunodeficiency virus infection, chronic liver disease, and chronic obstructive pulmonary disease
• Renal or other organ transplantation before, or expected during, the study, except for corneal transplants
• Prohibited medications:; Participants who received oral steroids over two weeks within 12 weeks before screening; Immunosuppressive medications (e.g., MMF, azathioprine, cyclophosphamide, hydroxychloroquine) for treating IgAN within 12 weeks before screening; Use of B-cell-directed biologic therapies, including belimumab, rituximab, and ocrelizumab, within six months before screening; Use of other biologics (e.g., anti-TNF, abatacept, anti-IL-6) and investigational biologics within the last four weeks or five half-lives, whichever is longer, before the screening; Use of traditional medications and/or Ayurvedic medications within 12 weeks before screening; Use of endothelin receptor antagonists/ oral spironolactone or oral finerenone/ GLP-1 agonists/ hydroxychloroquine within 12 weeks before screening
• Active clinically significant viral, bacterial, or fungal infection or any major episode of infection requiring hospitalisation or treatment with parenteral anti-infectives within four weeks before or during the Screening Visit
• Major surgery within six weeks before the Screening Visit
• IgAN secondary to another condition (e.g., liver cirrhosis) or other causes of mesangial IgA deposition such as systemic lupus erythematosus (SLE), dermatitis herpetiformis, ankylosing spondylitis, etc. IgA vasculitis (i.e., Henoch-Schonlein purpura) with biopsy-proven mesangial IgA deposition and no active skin vasculitis for the last year can be included
• History or diagnosis of demyelinating diseases such as multiple sclerosis or optic neuritis
• Patients with a history of unstable angina, Class III and IV congestive heart failure, and clinically significant arrhythmia, as judged by the Investigator
• History of malignancy within the past five years before Screening (except for adequately treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or cervical carcinoma in situ, with no evidence of recurrence)
• Known hypersensitivity to any of the interventions
• Clinically significant history of alcohol or drug abuse in the one year before the Screening Visit as per the Investigator's opinion
• Evidence of nephrotic syndrome at screening (serum albumin <3g/dL AND UPCR >3.5 g/g)
• Evidence of rapidly progressive glomerulonephritis defined as loss of ≥ 50% of eGFR in three months before screening
• Uncontrolled diabetes as defined by HbA1c > 8% at screening
• Female patients planning pregnancy
• Morbid obesity defined as BMI ≥ 40 kg/m2 at screening
• Unwillingness or lack of capacity to follow all study procedures