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

Inclusion criteria

• Signed informed consent.
• 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.
• Screening UPCR ≥0.5 g/g measured by first morning void.
• 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.
• WOCBP and sexually active participants must comply with protocol contraception requirements.

Exclusion criteria

• Hypersensitivity to study treatment/excipients or similar drug classes.
• CKD primarily attributable to non-IgAN etiology.
• Suspected RPGN or IgA vasculitis.
• Nephrotic syndrome.
• BNP >200 pg/mL or NT-proBNP >450 pg/mL at screening.
• Platelets <80,000/µL.
• Organ transplant history other than corneal transplant.
• Systemic immunosuppressants >2 weeks in prior 3 months or rituximab within 6 months.
• Confirmed BP >150/95 mmHg based on mean of 3 screening measurements.
• Heart failure/fluid overload.
• Significant liver disease or transaminases/bilirubin >2× ULN.
• Hemoglobin <9 g/dL or transfusion for anemia within 3 months.
• Malignancy unless protocol-defined exception.
• Pregnancy/breastfeeding or intent to become pregnant.
• Male intent to father a child/donate sperm during study and 1 month after.
• Recent investigational/approved IgAN treatment per protocol washout.
• Clinically significant unstable/uncontrolled medical disorder that may confound results or add risk.
• Alcohol/illicit drug-related disorder within 3 years.
• WOCBP not using highly effective contraception; sexually active males unwilling to use condoms.
• Prohibited therapies.
• MRI contraindications.
• Optional biopsy cohort exclusion if biopsy risk is unacceptably high.