Mechanistic Evaluation of Atrasentan in Patients With IgA Nephropathy (IgAN)

This multicenter, single-arm, open-label Phase 4 pilot study evaluates the effects of atrasentan added to optimized supportive care on kidney structure and function in adults with biopsy-confirmed IgA nephropathy. Approximately 20 participants will receive atrasentan 0.75 mg orally once daily for 52 weeks. Kidney multiparametric MRI is performed at baseline, 6 months, and 12 months, with blood and urine biomarker assessments throughout treatment. An optional nested cohort of up to 5 participants undergoes native kidney biopsy at baseline and 12 months.

Inclusion Criteria: 1. Signed informed consent. 2. Male or female ≥18 years with biopsy-confirmed IgAN; eGFR ≥30 mL/min/1.73 m² for main cohort; \>40 mL/min/1.73 m² for optional biopsy cohort. 3. Screening UPCR ≥0.5 g/g measured by first morning void. 4. Maximally tolerated or locally approved maximal ACEi/ARB dose before enrollment; diuretics, other antihypertensives and SGLT2i, if used, stabilized for at least 90 days before baseline. 5. WOCBP and sexually active participants must comply with protocol contraception requirements. Exclusion Criteria: 1. Hypersensitivity to study treatment/excipients or similar drug classes. 2. CKD primarily attributable to non-IgAN etiology. 3. Suspected RPGN or IgA vasculitis. 4. Nephrotic syndrome. 5. BNP \>200 pg/mL or NT-proBNP \>450 pg/mL at screening. 6. Platelets \2 weeks in prior 3 months or rituximab within 6 months. 9. Confirmed BP \>150/95 mmHg based on mean of 3 screening measurements. 10. Heart failure/fluid overload. 11. Significant liver disease or transaminases/bilirubin \>2× ULN. 12. Hemoglobin \