Safety, PK/PD, and Efficacy of NOX-H94 in Dialysis Patients With ESA-hyporesponsive Anemia: A Randomized, Double Blind, Placebo Controlled Parallel Group Study With a Single Blind Cross-over Group
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 5
- 主要终点
- Number of adverse events
研究概览
简要总结
Dialysis patients regularly suffer from anemia which may be caused by various contributing factors, alone or in combination, including blood loss, low erythropoietin and iron sequestration. In most patients, the anemia is responsive to treatment with erythropoietin or other erythropoiesis stimulating agents (ESA) alone or in combination with intravenous (i.v.) iron. In about 10% of patients however, the anaemia does not respond appropriately to this standard treatment and high to very high doses of ESA and i.v. iron are used to maintain acceptable hemoglobin concentrations. In these patients, hepcidin was identified as a causative factor leading to anemia of chronic disease with functional iron deficiency and ESA-hyporesponsiveness.
The Spiegelmer lexaptepid pegol (NOX-H94) offers a hepcidin-specific approach to the treatment of anemia of chronic disease. The safety and the activity of lexaptepid pegol are supported by data from healthy subjects and patients with multiple myeloma or lymphoma. The present study in dialysis patients with functional iron deficiency and ESA-hyporesponsiveness is conducted to demonstrate the safety of lexaptepid pegol in this population, to investigate its pharmacokinetic (PK) and pharmacodynamic (PD) profiles and its efficacy in increasing haemoglobin (Hb) in dialysis patients.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •End stage renal disease treated with maintenance hemodialysis.
- •Anemia : Hb 7 to 11 g/dL.
- •Functional iron deficiency: Transferrin saturation <30%, Ferritin ≥300 ng/mL.
- •ESA-hyporesponsiveness with erythropoietin dose ≥12,000 IU/ week.
排除标准
- •Treatment with darbepoetin or methoxy-polyethyleneglycol-epoetin.
- •Uncontrolled / unstable cardiovascular , peripheral arterial or cerebrovascular disease.
- •Congestive heart failure: New York Heart Association Class III or IV.
- •Unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty/stents, or coronary artery bypass grafting <3 months prior screening.
- •Any other medical conditions requiring a change in treatment within 4 weeks prior to screening or making study participation unadvisable.
- •History of clinically relevant hemolysis and/or blood loss.
- •AST, ALT, or bilirubin ≥2.0 times the upper limit of normal.
- •Known bone marrow fibrosis.
- •Treatment with i.v. iron <4 weeks prior to screening or during the screening period or change in erythropoietin dose during last month.
- •Any acute or chronic infection, viral or bacterial within 4 weeks prior to screening or during the screening period considered as systemic infection.
研究组 & 干预措施
Single dose cross-over pilot
Single dose of lexaptepid pegol (NOX-H94) cross-over with single dose of placebo
干预措施: Lexaptepid pegol (NOX-H94) (Drug)
Single dose cross-over pilot
Single dose of lexaptepid pegol (NOX-H94) cross-over with single dose of placebo
干预措施: Placebo (Drug)
Control
Twice weekly doses of placebo, 9 total
干预措施: Placebo (Drug)
Lexaptepid pegol (NOX-H94)
Twice weekly doses of lexaptepid pegol (NOX-H94), 9 total
干预措施: Lexaptepid pegol (NOX-H94) (Drug)
结局指标
主要结局
Number of adverse events
时间窗: up to 8 weeks
次要结局
- Pharmacodynamics(0 to 48 hours)
- Efficacy(Weeks 1, 2, 3, 4, 5, 6, 8)
- Pharmacokinetics(Weeks 1, 2, 3, 4, 5, 6, 8)