NCT02866825已完成2 期
A Phase II Randomized, Placebo-controlled, Double-blind, Dose-escalation Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamic Dose Response Relationship of IFX-1 in Patients Undergoing Complex Cardiac Surgery
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- InflaRx GmbH
- 入组人数
- 116
- 试验地点
- 10
- 主要终点
- Peak level of IL-6
研究概览
简要总结
The trial enrolls patients undergoing a complex cardiac surgery. The primary goal of the trial is to evaluate the pharmacodynamic dose response relationship of the monoclonal antibody IFX-1 in these patients. In addition, this trial further aims to characterize the safety and the pharmacokinetics of IFX-1 as well as to collect first data on its efficacy on clinical surrogate endpoints.
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
- •Male or female patients ≥ 18 years old
- •Written informed consent
- •One of the following cardiac surgical procedures is planned with Cardiopulmonary bypass (CPB):
- •Single valve surgery in combination with at least two coronary artery bypass grafts (CABGs)
- •Multiple valve surgery with or without CABG
- •Single or multiple valve surgery in combination with ascending aorta procedure with or without additional CABG
- •Re-surgery of aortic valve, mitral valve, aortic arch or ascending aorta with or without CABG
- •Cardiac surgery is performed electively
排除标准
- •Weight > 130 kg
- •The following cardiac surgical procedures:
- •Cardiac surgical procedure is planned as minimally invasive procedure (e.g., without thoracotomy or with lateral incision, minimal thoracotomy)
- •Cardiac surgery with an expected CPB time less than 100 minutes
- •Other cardiac and vascular diseases and/or procedures:
- •Prior cardiac surgery within the past 6 months
- •History of heart transplantation or planned heart transplantation
- •Requiring inotropic, vasopressor or mechanical circulatory support
- •Requiring ventilatory support
- •Other disease or condition that is likely to interfere with the evaluation of the study drug:
- •Active infective endocarditis
- •Stroke or transient ischemic attack (TIA) within the last 6 months
- •Concomitant disease with a life expectancy of less than 6 months
- •Cardiopulmonary resuscitation within the last 4 weeks
- •Patients requiring renal replacement therapy
- •Cerebrovascular disease requiring concomitant carotid endarterectomy
- •Active infection with or without a temperature greater than 38°C
- •Presence of systemic inflammatory response syndrome defined as occurrence of at least 2 out of the following 4 criteria:
- •Fever > 38.0°C or hypothermia < 36.0°C
- •Tachycardia > 90 beats/minute
- •Tachypnea > 20 breaths/minute
- •Leucocytosis > 12 x 109/l or leucopenia < 4 x 109/l or > 10% immature neutrophils (bands)
- •Positive test for human immunodeficiency virus (HIV), hepatitis B or C
- •One of the following abnormal laboratory results:
- •Hemoglobin < 5 mmol/l (< 8.06 g/dl)
- •Total bilirubin ≥ 2 x upper normal limit (UNL)
- •CRP > 3 x UNL
- •ALAT > 3 x UNL
- •ASAT > 3 x UNL
- •White blood cell count < 2,500/mm³
- •White blood cell count > 12,000/mm³
- •Prohibited concomitant medications:
- •Immunomodulatory drugs within past 30 days (e.g., TNF-inhibitors)
- •Immunosuppressive drugs within past 30 days (e.g., cyclosporine, tacrolimus)
- •High dose corticosteroids (e.g., > 50 mg prednisone/day or equivalent) within past 14 days
- •Any systemic anticancer treatment within the past 3 months
- •Planned corticosteroid pulse therapy to prevent SIRS
- •Patients with known hypersensitivity to any constituent of the investigational medicinal product (IMP)
- •General exclusion criteria:
- •Pregnant (in women of childbearing potential an urine pregnancy test has to be performed) or breast-feeding women
- •Women with childbearing potential (defined as within two years of their last menstruation) not willing to practice appropriate contraceptive measures (e.g., implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy, abstinence) while participating in the trial
- •Participation in any interventional clinical trial within the last three months
- •Prior randomization in this clinical trial (screen failures can be re-screened, if appropriate)
- •Alcohol, drug, or medication abuse
- •Employee at the study site, spouse/partner or relative of any study staff (e.g., investigator, sub-investigators, or study nurse) or relationship to the sponsor
- •No commitment to full aggressive life support (e.g., DNR order)
研究组 & 干预措施
Placebo
Placebo Comparator
dose escalating mimicing single i.v. administration of placebo
干预措施: Placebo (Biological)
IFX-1
Active Comparator
dose escalating single i.v. administration of IFX-1 (verum)
干预措施: IFX-1 (Biological)
结局指标
主要结局
Peak level of IL-6
时间窗: From prior study drug administration until 24h after start of cardiopulmonary bypass (CPB) (CPB)
次要结局
- Maximum observed concentration (Cmax) of IFX-1(Data will be collected at the following approximate time points: prior study drug administration; 30 min after start of infusion; up to 10 min after cessation of CPB; 3h, 12h, 24h, 48h, 96h, and 168h after start of CPB; Day 15)
- Area under the curve (AUC) of plasma concentration of IFX-1(Data will be collected at the following approximate time points: prior study drug administration; 30 min after start of infusion; up to 10 min after cessation of CPB; 3h, 12h, 24h, 48h, 96h, and 168h after start of CPB; Day 15)
- Number of patients with SIRS 24h, 48h and 96h after start of CPB(24h, 48h and 96h after start of CPB)
- Plasma concentration of IFX-1 at each timepoint measured(Data will be collected at the following approximate time points: prior study drug administration; 30 min after start of infusion; up to 10 min after cessation of CPB; 3h, 12h, 24h, 48h, 96h, and 168h after start of CPB; Day 15)
- Plasma concentration of free, detectable C5a at each timepoint measured(Data will be collected at the following approximate time points: prior study drug administration, prior start of CPB, up to 10 min after cessation of CPB; 3h, 6h, 12h, 24h, 48h, 96h, and 168h after start of CPB; Day 15)
- Number of patients that are successfully extubated 24h after end of surgery(24h after end of surgery)
- Number of patients with consecutive invasive ventilation for more than 48h after end of surgery(48h after end of surgery)
- Serum levels of CH50 at each timepoint measured(Data will be collected at the following approximate time points: prior study drug administration, prior start of CPB, up to 10 min after cessation of CPB; 3h, 6h, 12h, 24h, 48h, 96h, and 168h after start of CPB; Day 15)
- Serum levels of IL-6 compared to baseline(Data will be collected at the following approximate time points: prior study drug administration, up to 10 min after cessation of CPB; 3h, 6h, 12h, 24h, 48h, and 96h after start of CPB; Day 15)
- Serum levels of IL-8 compared to baseline(Data will be collected at the following approximate time points: prior study drug administration, up to 10 min after cessation of CPB; 3h, 6h, 12h, 24h, 48h, and 96h after start of CPB; Day 15)
- Incidence of patients with Adverse Events (AEs) and Serious Adverse Events (SAEs) until Day 29(From screening visit until Day 29)
- Number of patients with detection of anti-drug-antibodies(Up to Day 15)
- Number of patients that are weaned of any vasopressor use 24h after end of surgery(24h after end of surgery)
研究者
研究点 (10)
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