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
- 招募中
- 入组人数
- 450
- 试验地点
- 10
- 主要终点
- 1.Change from baseline in 24-hour urine protein excretion (UPE) in g/day at 36 weeks from beginning of treatment [ Time Frame: 36 Weeks ]
研究概览
简要总结
This is a Phase 3,double-blind, randomized, placebo-controlled study in patients aged 18 yearsand above with a biopsy-confirmed diagnosis of IgAN and with 24-hour UPE > 1g at baseline. The study will be conducted at approximately 140 study sites inNorth America, Europe, Australia, and Asia. Approximately 450 patients are tobe enrolled in two groups of 225 patients per arm. During the study, allpatients will continue optimized renin-angiotensin system (RAS) blockade. Thestudy consists of five periods: Screening, Run-In, Initial Treatment (Weeks1-12), Response Evaluation (Weeks 13-36), and Follow-Up (Weeks 37 to Week144/end-of-study). The duration of study for each patient is expected to beapproximately 160 weeks, comprising a 1-year study with a 2-year follow-up. Theprimary endpoint of this study is the change from baseline in log-transformed24-hour UPE in g/day at 36 weeks from baseline. The key secondary endpoints ofthis study are: ∙ Proteinuria responder defined as having a 24-hour UPE of atleast 50% reduction from baseline as assessed at Week 36 (patients with ≥ 2g/day UPE at baseline only) ∙ The rate of change in eGFR up to 144 weeks frombaseline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- Female
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
- •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), or cytotoxic drugs, for IgA within 8 weeks prior to Screening.
- •Treatment with immunosuppressants or cytotoxic drugs for IgAN is not allowed during the Run-In Period.
- •Treatment with immunosuppressants are allowed if such treatment is for indications other than IgAN.
- •Treatment with eculizumab within 8 weeks prior to Screening.
- •Treatment with eculizumab is not allowed during the Run-In Period.
- •Treatment with systemic corticosteroids within 8 weeks prior to Screening.
- •Treatment with systemic corticosteroids is not allowed during the Run-In Period.
- •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 ACEIs, ARBs, or direct renin inhibitors at Screening and baseline
- •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
- •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
- •History of renal transplantation
- •Have a known hypersensitivity to any constituent of the investigational product
- •Rapidly progressive glomerulonephritis
- •Significant abnormalities in clinical laboratory values
- •History of human immunodeficiency virus (HIV), evidence of immune suppression, active HCV infection (patients with positive anti-HCV antibody but a non-detected HCV RNA PCR can enroll), 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.
结局指标
主要结局
1.Change from baseline in 24-hour urine protein excretion (UPE) in g/day at 36 weeks from beginning of treatment [ Time Frame: 36 Weeks ]
时间窗: 1.Change from baseline in 24-hour urine protein excretion (UPE) in g/day at 36 weeks from beginning of treatment [ Time Frame: 36 Weeks ]
次要结局
- 1.Number of patients with treatment related Adverse Events as assessed by CTCAE v 4.0 [ Time Frame: 168 Weeks ]
- 4.Time-averaged change in urine protein/creatinine ratio (uPCR) through 36 weeks. [ Time Frame: 36 Weeks ](36 Weeks)
- 2.Change from baseline in renal function as determined by the rate of change in estimated glomerular filtration rate (eGFR) up to 144 weeks from beginning of treatment [ Time Frame: 144 Weeks ](144 weeks)
- 3.Change from baseline in 24-hour urine protein excretion (UPE) in g/day at 36 weeks from beginning of treatment in the subset of patients with baseline high proteinuria (defined as 24-hour UPE ≥ 2 g/day) [ Time Frame: 36 Weeks ](36 weeks)