A First-in-Human, Randomized, Dose-Escalation, Double-Blind, Placebo-Controlled Single Ascending Dose Study to Establish Safety, Lack of Immunogenicity, Tolerability, Pharmacokinetic Parameters, Target Engagement and Pharmacodynamic Effects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of subjects 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 treatment of anemia of chronic disease. This phase I First-in-Human study shall investigate safety and pharmacokinetics in healthy human volunteers.
详细描述
First-in-Human (FIH), randomized, dose-escalation, double-blind, placebo-controlled single dose in healthy volunteers.
The single rising dose study will enroll 8 subjects per cohort (6 verum, 2 placebo), up to a maximum tolerated dose, defined by stopping rules. 6 dose levels are anticipated. Study drug will be administered as i.v. infusion on Day 1. The decision to escalate the dose by the dose escalation committee (DEC) will be based on an interim analysis of clinical safety and safety laboratory data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy Caucasian males: based on a screening examination including medical history, physical examination, 12-lead ECG, vital signs and clinical laboratory profiles, age 18-50 years
- •Subjects should have a body mass index of 18-30 kg/m2 and should weigh 60-90 kg
- •Subjects must be using two acceptable methods for contraception (e.g. spermicide and condom) during the study and refrain from fathering a child in the 3 months following the last dosing.
- •Willing to comply with the requirements of the study protocol and signing the informed consent sheet.
排除标准
- •Any uncontrolled or active major systemic disease
- •History or presence of malignancy
- •Definite or suspected history of drug allergy
- •Active acute or chronic infection, including, but not limited to: upper airway infection, urinary tract infection, and skin infection
- •Use of any investigational drug within 30 days, or 5 half-lives, whichever is longer, prior to the planned first drug administration.
- •Use of prescription medication within 14 days prior to the planned first drug administration and throughout the study (with the exception of medications given to treat an adverse event and use of non-prescription or over-the-counter medications within 7 days prior to the planned first drug administration and throughout the study (including vitamins, herbal supplements, or remedies
- •Smoking greater than 20 cigarettes per week
- •History of alcohol or substance abuse within the past 6 months prior to the planned first drug administration
- •History of increased bleeding risk
- •Clinically relevant abnormalities found in physical examination, vital signs measurements, laboratory safety tests or ECG
- •Blood donation within the last 60 days prior to the planned first drug administration
- •Positive results on hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV1/2) antibodies screening
- •Iron overload or disturbance in utilization of iron (defined as ferritin > 300.0 ng/mL and < 10.0 ng/mL)
- •i.v. iron treatment or blood transfusion within last 90 days prior to the planned first drug administration or during trial
- •ESA (e.g. Erythropoietin) treatment within the last year
- •Surgery or trauma with significant blood loss within 2 months before the planned first drug administration
- •Not able to abstain from consumption of food or beverages known to influence dietary iron absorption
研究组 & 干预措施
PRS-080#022-DP
hepcidin antagonist, single administration, ascending doses
干预措施: PRS-080#022-DP (Drug)
PRS-080-Placebo#001
Comparotor treatment, single administration
干预措施: PRS-080-Placebo#001 (Drug)
结局指标
主要结局
Number of subjects with adverse events
时间窗: up to 28 days
Composite measure including signs and symptoms, local reactions, changes from baseline heart rate and blood pressure, ECG, body temperature, respiratory rate, clinical chemistry and hematology, coagulation and urinalysis over a 28 day period
次要结局
- Effect of PRS-080#22-DP on hepcidin concentrations in blood(15 time points up to 28 days)
- Pharmacokinetics of PRS-080#22-DP following administration of single doses(14 time points up to 11 days)
- Effect of PRS-080#22-DP on total iron(up to 28 days)
- Effect of PRS-080#22-DP on ferritin(up to 28 days)
- Effect of PRS-080#22-DP on transferrin saturation(up to 28 days)
- Assessment of anti-drug antibodies in blood following single administration(up to 28 days)