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

Phase 4Not Yet RecruitingNCT07820995

University of Illinois at Chicago20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

IgA Nephropathy (IgAN)Immunoglobulin A Nephropathy (IgAN)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 \<80,000/µL. 7. Organ transplant history other than corneal transplant. 8. Systemic immunosuppressants \>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 \<9 g/dL or transfusion for anemia within 3 months. 13. Malignancy unless protocol-defined exception. 14. Pregnancy/breastfeeding or intent to become pregnant. 15. Male intent to father a child/donate sperm during study and 1 month after. 16. Recent investigational/approved IgAN treatment per protocol washout. 17. Clinically significant unstable/uncontrolled medical disorder that may confound results or add risk. 18. Alcohol/illicit drug-related disorder within 3 years. 19. WOCBP not using highly effective contraception; sexually active males unwilling to use condoms. 20. Prohibited therapies. 21. MRI contraindications. 22. Optional biopsy cohort exclusion if biopsy risk is unacceptably high.

Outcomes

Primary Outcomes

Proportion of participants achieving improvement in at least one component of the composite kidney mpMRI endpoint at Month 6

The proportion of participants with improvement from baseline at Month 6 in at least one of: ≥5% decrease in cortical native T1 mapping time; ≥5% increase in cortical apparent diffusion coefficient (ADC); or ≥10% increase in phase-contrast-derived renal artery blood flow.

Time frame: Baseline to Month 6 (Week 26)

Secondary Outcomes

Percent change from baseline in urinary KIM-1 and MCP-1 over 6 months

Percent change from baseline in urine biomarkers Kidney Injury Molecule-1 (KIM-1) and Monocyte Chemoattractant Protein-1 (MCP-1), assessed individually and/or as a composite.

Time frame: Baseline through Month 6

Central Contacts

Kimberly Silva, MPH

CONTACT

312-996-0185 ksilva4@uic.edu

Natalie Meza, MPH