A Multicentered, Single-group Phase 2, Exploratory, Open-label Study to Investigate Safety and Effect of Sparsentan in Combination With SGLT2 Inhibition in the Treatment of Adult Participants With Immunoglobulin A Nephropathy (IgAN)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Change in Urine Albumin-creatinine Ratio (UA/C) at Week 24
研究概览
简要总结
This was a 28-week, open-label, multicenter, single-group Phase 2 exploratory study to determine the safety and effect of sparsentan in participants with IgAN who are at risk of disease progression to kidney failure despite being on both stable RAASi and SGLT2 inhibitor treatment for at least 12 weeks prior to study entry
详细描述
This was a 28-week, open-label, multicenter, single-group Phase 2 exploratory study to determine the safety and effect of sparsentan in participants with Immunoglobulin A Nephropathy (IgAN) who are at risk of disease progression to kidney failure (KF) despite being on both stable renin angiotensin aldosterone system inhibitor (RAASi) and sodium glucose cotransporter-2 (SGLT2) inhibitor treatment for at least 12 weeks prior to study entry.
Participants who provided written informed consent were assessed for eligibility and underwent baseline evaluations including clinical laboratory tests. Per the eligibility criteria, all participants were required to be on a stable dose(s) of angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) and on a stable dose of a SGLT2 inhibitor at screening and continued their stable treatments through the screening period. Eligible participants discontinued ACEI and/or ARB therapy the day before the Day 1 visit and remained on stable SGLT2 inhibitor dosing for the duration of the study.
Study intervention was administered daily for a treatment period of 24 weeks with study visits conducted at weeks 2-, 4-, 12-, and 24- following Day 1. Following the 24-week treatment period, study intervention was discontinued for 4 weeks and standard of care RAASi treatment resumed, with a safety visit at Week 28.
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
- •Aged ≥18 years at the time of signing the informed consent.
- •Biopsy-proven IgAN. The biopsy may have been performed at any time in the past.
- •UA/C ≥0.3 g/g at screening
- •An eGFR value of ≥25 mL/min/1.73m^2 at screening.
- •On a stable dose of an SGLT2 inhibitor for at least 12 weeks prior to screening.
- •On a stable dose of ACEI and/or ARB therapy for at least 12 weeks prior to screening that is:
- •The participant's maximum tolerated dose (MTD), and
- •at least one half of the maximum labeled dose (MLD)
- •Systolic BP must be ≤160 mmHg, and diastolic BP must be ≤110 mmHg at screening.
- •For participants receiving chronic low dose systemic corticosteroids (defined as ≤10 mg/day prednisone or equivalent), or an enteric formulation of budesonide and/or a mineralocorticoid receptor antagonist (MRA), the dosage must be stable for ≥12 weeks prior to screening.
排除标准
- •IgAN secondary to another condition or immunoglobulin A (IgA) vasculitis.
- •Undergone any organ transplant, with the exception of corneal transplants.
- •Documented history of heart failure.
- •Taking high dose (defined as >10 mg/day prednisone) or other any systemic immunosuppressive medications within 12 weeks of prior to screening.
- •Has clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (hospitalization for myocardial infarction unstable angina, new onset of angina with positive functional tests, coronary angiogram revealing stenosis, or a coronary revascularization procedure) within 3 months prior to screening.
- •Has jaundice, hepatitis, or known hepatobiliary disease (excluding asymptomatic cholelithiasis), or ALT and/or AST >2 times the ULN range at screening.
- •Has a history of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years.
- •Has a history of serious side effect or allergic response to any AngII antagonist, ERA or sparsentan, or has a hypersensitivity to any of the excipients in the study intervention.
- •Requires any of the prohibited concomitant medications.
- •Treatment with sparsentan within 12 weeks prior to screening
- •Has participated in a study of another investigational product within 28 days prior to screening or plans to participate in such a study during the course of this study.
- •Has a screening hematocrit value <27% (0.27 Volume/Volume) or hemoglobin value <9 g/dL (90 g/L).
- •Has a screening potassium value of >5.5 mEq/L (5.5 mmol/L).
- •Is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
- •The participant, in the opinion of the Investigator, is unable to adhere to the requirements of the study, including the ability to swallow the study intervention capsules whole.
研究组 & 干预措施
sparsentan
Sparsentan will be administered daily as a 200-mg oral tablet. The goal is to titrate from the initial dose of 200 mg (Day 1) to the target dose of 400 mg at Week 2.
干预措施: Sparsentan (Drug)
结局指标
主要结局
Change in Urine Albumin-creatinine Ratio (UA/C) at Week 24
时间窗: Week 24
The change from baseline in UA/C at Week 24 based on first morning void (FMV) samples
次要结局
- Estimated Glomerular Filtration Rate (eGFR)(Week 24)
- UA/C <0.2 g/g at Week 24(Week 24)
- 30% Reduction From Baseline in UA/C at Week 24(Week 24)
- Change in Urine Protein-to-creatinine Ratio (UP/C) at Week 24(Week 24)
- Change in Diastolic Blood Pressure (BP)(Week 24)
- 50% Reduction From Baseline in UA/C at Week 24(Week 24)
- Systolic Blood Pressure (BP) at Week 24(Week 24)