A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of the Safety and Efficacy of OMS721 in Patients With Immunoglobulin A (IgA) Nephropathy (ARTEMIS - IGAN)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 360
- 试验地点
- 2
- 主要终点
- Percent Change in 24-hour UPE in g/Day Compared to Baseline
研究概览
简要总结
The primary objective of this study is to evaluate the effect of OMS721 on 24-hour urine protein excretion (UPE) in IgA nephropathy (IgAN) patients with high baseline proteinuria (high-risk proteinuria group; 24-hour UPE ≥ 2 g/day) assessed at 36 weeks from baseline.
详细描述
This is a Phase 3, double-blind, randomized, placebo-controlled, study in patients aged 18 years and above with a biopsy-confirmed diagnosis of IgAN and with 24-hour UPE that is > 1 g/day. The purpose of this study is to evaluate the efficacy and safety of narsoplimab (OMS721) compared to placebo on proteinuria and whether narsoplimab has the ability to slow disease progression in primary IgAN patients. The primary objective of the study is to evaluate proteinuria reduction as assessed by 24-hour UPE at 36 weeks from baseline. The trial will continue beyond 36 weeks in a blinded fashion to provide confirmatory evidence of long-term efficacy based on the annualized slope of eGFR over 24 months. The trial will enroll approximately 450 patients with 225 patients per arm, all having biopsy-proven IgAN with eGFR≥30 mL/min/1.73m^2 and 24 hour UPE >1g/day. The study duration for each patient is expected to last approximately 112 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age 18 years or older at the onset of Screening
- •Biopsy confirmed diagnosis of IgAN within 8 years prior to Screening or Run-in Visit 1
- •Documented history of proteinuria of > 1 g/day within 6 months prior to Screening or uPCR > 0.75 by spot urine at Screening
- •Mean of two proteinuria measurements > 1 g/day at baseline
- •Estimated glomerular filtration rate of ≥ 30 mL/min/1.73 m² at Screening and baseline
排除标准
- •Treatment with immunosuppressants (e.g., azathioprine or cyclophosphamide), Chinese traditional medicine with immunosuppressive function, cytotoxic drugs, or eculizumab within 8 weeks prior to Screening, unless such treatment is given for indications other than IgA.
- •Treatment with systemic corticosteroids within 8 weeks prior to Screening
- •Uncontrolled BP, a systolic BP of > 150 mmHg and a diastolic BP of > 100 mmHg at rest despite the combination of two or more anti-hypertensives including ACE inhibitors, ARBs, or direct renin inhibitors
- •Female patients who are pregnant, breast feeding, or planning to become pregnant up through 12 weeks after the last dose of study drug, including possible retreatments. Males who are planning to father children up through 12 weeks after the last dose of study drug, including possible retreatments
- •Clinical or biological evidence of Type 1 diabetes mellitus (DM), or poorly controlled DM with hemoglobin A1c > 7.5 or with evidence of diabetic nephropathy on biopsy, systemic lupus erythematosus, IgA vasculitis (Henoch-Schonlein purpura), secondary IgAN, or other renal disease during Screening and Run-In
- •Presence of significant morbidity or other major illness or disease that may confound the interpretation of the clinical trial results or may result in death within 2 years of Screening
- •History of renal transplantation
- •Have a known hypersensitivity to any constituent of the investigational product
- •Rapidly progressive glomerulonephritis, defined as a fall in eGFR of > 30 mL/min/1.73 m^2 within 24 weeks or > 15 mL/min/1.73 m^2 within 12 weeks prior to Screening
- •Significant abnormalities in clinical laboratory values
- •History of human immunodeficiency virus (HIV), evidence of immune suppression, active hepatitis C virus (HCV) infection (patients with positive anti-HCV antibody but a non-detected HCV RNA PCR can enroll), hepatitis B virus (HBV) infection (patients with positive HBsAg are excluded; for patients with isolated positive anti-HBc antibody, HBV DNA test by PCR must be non-detectable to enroll).
- •Diagnosis of a malignancy except for adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer from which the patient has been disease-free for ≥ 5 years
- •Have received any other investigational drug or device or experimental procedures within 30 days of the Screening Visit (SV) or within 5 times the plasma half-life of the administered experimental drug, whichever is longer
- •Initiation or change in dosing of sodium glucose co-transporter 2 inhibitors (SGLT2i) during Screening and Run-In Periods. However, a stable dose regimen established at least 8 weeks prior to screening is acceptable
- •Treatment with Tarpeyo™ (budesonide) or other approved treatments for IgAN within 6 months prior to screening. Treatment with Tarpeyo is not allowed during Screening and Run-In Periods
- •Treatment with Kerendia® (finerenone) within 6 months prior to screening. Treatment with Kerendia is not allowed during Screening and Run-In Periods
- •Initiation of treatment with Filspari™ (sparsentan), a dual Endothelin Angiotensin Receptor Antagonist (dEARA) or similar medication within three months prior to screening. A stable dose initiated at minimum 3 months before screening is acceptable and will take the place of ACEi/ARB as background therapy
研究组 & 干预措施
OMS721
Administration of OMS721
干预措施: OMS721 (Biological)
Placebo
Administration of Vehicle (D5W or Saline Solution)
干预措施: Vehicle (D5W or saline) (Other)
结局指标
主要结局
Percent Change in 24-hour UPE in g/Day Compared to Baseline
时间窗: 36 Weeks
The Primary Endpoint of this Study is the Percent Change from Baseline in Log-transformed 24-hour UPE in g/Day at 36 Weeks in Patients with High Baseline Proteinuria (High-risk Proteinuria Group; 24-hour UPE ≥ 2 g/day.
次要结局
- Change in Annualized eGFR Compared to Baseline.(96 Weeks)
- Change in Annualized eGFR Compared to Baseline in All Patients.(96 Weeks)
- Change in 24-hour UPE in g/Day Compared to Baseline in All Patients(36 Weeks)
- Change in 24-hour UPE in g/Day Between 36 Weeks and 48 Weeks.(36 weeks and 48 weeks)
- Change in 24-hour UPE in g/Day Between 36 Weeks and 72 Weeks in Patients With >= 2 g/Day UPE at Baseline (High-risk Proteinuria Group).(36 weeks and 72 weeks)
- Change in 24-hour UPE in g/Day Between 36 Weeks and 48 Weeks in All Patients(36 weeks and 48 weeks)
- Change in 24-hour UPE in g/Day Between 36 Weeks and 72 Weeks in All Patients(36 weeks and 72 weeks)
- Safety and Tolerability of Narsoplimab for the Treatment of IgAN as Assessed by AEs, Vital Signs, Clinical Laboratory Tests, and ECGs(Week 112)