IgA Nephropathy (IgAN), Immunoglobulin A Nephropathy (IgAN)
Conditions
Keywords
IgA nephropathy, atrasentan, multiparametric MRI, MRI, biomarkers, kidney injury, mechanistic, fibrosis, renal blood flow, kidney biopsy, histopathology
Brief summary
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.
Interventions
DRUGatrasentan
Atrasentan 0.75 mg oral tablet once daily for 52 weeks, added to optimized supportive care.
Sponsors
University of Illinois at Chicago
Novartis
University of Michigan
Endeavor Health
University of North Carolina, Chapel Hill
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving improvement in at least one component of the composite kidney mpMRI endpoint at Month 6 | Baseline to Month 6 (Week 26) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent change from baseline in urinary KIM-1 and MCP-1 over 6 months | Baseline through Month 6 | 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. |
Countries
United States
Contacts
CONTACTKimberly Silva, MPH
CONTACTNatalie Meza, MPH
PRINCIPAL_INVESTIGATORAnand Srivastava, MD, MPH
University of Illinois at Chicago
Outcome results
None listed