A Multicenter, Single Arm, Open Label, Pilot Study to Assess the Effect of Atrasentan Alongside Supportive Care on Structural and Functional Changes in Kidneys of Adult Patients With IgA Nephropathy (IgAN)
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Proportion of participants achieving improvement in at least one component of the composite kidney mpMRI endpoint at Month 6
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Atrasentan
Adults with biopsy-confirmed IgAN receive atrasentan 0.75 mg orally once daily for 52 weeks in addition to optimized supportive care. The optional repeat-biopsy cohort is nested within this arm and is not a separate randomized arm.
干预措施: atrasentan (Drug)
结局指标
主要结局
Proportion of participants achieving improvement in at least one component of the composite kidney mpMRI endpoint at Month 6
时间窗: 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.
次要结局
- Percent change from baseline in urinary KIM-1 and MCP-1 over 6 months(Baseline through Month 6)