Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Hepcidin Antagonist PRS-080#022-DP in Anemic Chronic Kidney Disease Patients Undergoing Hemodialysis
试验速览
- 阶段
- 1 期
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Number of patients with adverse events
研究概览
简要总结
Anticalins® are engineered human proteins that are able to bind specific target molecules. The Anticalin PRS-080#022-DP to be investigated in this study is directed against hepcidin and is intended for the treatment of anemia of chronic disease. This Phase Ib study shall investigate the safety, pharmacokinetics and pharmacodynamics of a single administration of PRS-080#022-DP in anemic stage 5 chronic kidney disease patients undergoing hemodialysis.
详细描述
This is a multi-center, randomized, double-blind, placebo-controlled, single ascending dose phase Ib study in anemic stage 5 chronic kidney disease patients requiring hemodialysis. Eligible subjects will undergo screening assessments and PRS-080#22-DP will be administered by intravenous infusion. The study will consist of 3 dose cohorts of 2 mg/kg, 4 mg/kg, and 8 mg/kg body weight with 8 subjects in each cohort. Using a standard 6+2 design, 6 subjects in each cohort will be randomized to PRS-080#022-DP and 2 subjects in each cohort will be randomized to placebo. The decision to escalate the dose will be based on an interim analysis of clinical safety and safety laboratory data. Safety and tolerability, pharmacokinetics, pharmacodynamics as well as potential immunogenicity will be investigated.
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
- •Patients with stage 5 chronic kidney disease having been on hemodialysis for at least 90 days
- •Patients being on stable erythropoiesis-stimulating agent (ESA) dose
- •Hemoglobin (Hb) 9 - 11 g/dL
- •Ferritin ≥ 300 ng/mL.
- •Transferrin saturation (TSAT) ≤ 30%
- •Hepcidin 5 - 50 nmol/L
排除标准
- •Anemia due to causes other than chronic kidney disease, including hemoglobinopathies, hemolytic anemias, myelodysplasia or malignancy
- •Blood transfusion within 2 months before administration of study medication.
- •Iron treatment from 1 week before study medication administration until 1 week after study medication administration.
- •Previous enrollment in this study
- •Current or previous (within 60 days before study medication administration) treatment with another investigational drug and/or medical device or participation in another clinical study.
- •Pregnancy or breast-feeding women of child bearing age.
- •Known allergy to any component of the PRS-080#022-DP formulation
- •Positive for hepatitis B surface antigen, anti-hepatitis C virus antibody, or human immunodeficiency virus
- •Planned surgery during the study period
- •Unwilling or unable to comply with the protocol, in the judgment of the investigator
- •Unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty/stents, apoplexy or coronary artery bypass grafting <3 months prior screening.
- •Congestive heart failure: New York Heart Association Class III or IV.
研究组 & 干预措施
PRS-080-Placebo#001
Comparator treatment, single administration
干预措施: PRS-080-Placebo#001 (Biological)
PRS-080#022-DP
Hepcidin antagonist, single administration, ascending doses
干预措施: PRS-080#022-DP (Biological)
结局指标
主要结局
Number of patients with adverse events
时间窗: 28 days
Composite measure including signs and symptoms, changes from baseline heart rate and blood pressure, ECG, body temperature, respiratory rate clinical chemistry and hematology
次要结局
- Pharmacokinetics of PRS-080#022(28 days)
- Effects of PRS-080#022 on serum iron(28 days)
- Effects of PRS-080#022 on ferritin(28 days)
- Effects of PRS-080#022 on transferrin saturation(28 days)
- Effect of PRS-080#022 on hepcidin concentrations in plasma(28 days)
- Number of patients developing anti-drug antibodies(28 days)