Prevention of organ dysfunction induced by inflammatory response after complex cardiac surgery MedDRA version: 20.0 Level: PT Classification code 10063101 Term: Post procedural inflammation System Organ Class: 10022117 - Injury, poisoning and procedural complications MedDRA version: 20.0 Level: LLT Classification code 10062357 Term: SIRS System Organ Class: 100000004867
Conditions
Interventions
Product Name: IFX-1
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not applicable
Current Sponsor code: IFX-1 (former code: CaCP29)
Other descriptive name: chimeric monoclonal antibod
Sponsors
InflaRx GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female patients = 18 years old 2.Written informed consent 3.One of the following cardiac surgical procedures is planned with Cardiopulmonary bypass (CPB): a.Single valve surgery in combination with at least two coronary artery bypass grafts (CABGs) b.Multiple valve surgery with or without CABG c.Single or multiple valve surgery in combination with ascending aorta procedure with or without additional CABG d.Re-surgery of aortic valve, mitral valve, aortic arch or ascending aorta with or without CABG 4.Cardiac surgery is performed electively Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1.Weight > 130 kg 2.The following cardiac surgical procedures: a.Cardiac surgical procedure is planned as minimally invasive procedure (e.g., without thoracotomy or with lateral incision, minimal thoracotomy) b.Cardiac surgery with an expected CPB time less than 100 minutes 3.Other cardiac and vascular diseases and/or procedures: a.Prior cardiac surgery within the past 6 months b.History of heart transplantation or planned heart transplantation c.Requiring inotropic, vasopressor or mechanical circulatory support d.Requiring ventilatory support 4.Other disease or condition that is likely to interfere with the evaluation of the study drug: a.Active infective endocarditis b.Stroke or transient ischemic attack (TIA) within the last 6 months c.Concomitant disease with a life expectancy of less than 6 months d.Cardiopulmonary resuscitation within the last 4 weeks e.Patients requiring renal replacement therapy 5.Cerebrovascular disease requiring concomitant carotid endarterectomy 6.Active infection with or without a temperature greater than 38°C 7.Presence of systemic inflammatory response syndrome defined as occurrence of at least 2 out of the following 4 criteria: a.Fever > 38.0°C or hypothermia 90 beats/minute c.Tachypnea > 20 breaths/minute d.Leucocytosis > 12 x 109/l or leucopenia 10% immature neutrophils (bands) 8. Positive test for human immunodeficiency virus (HIV), hepatitis B or C 9.One of the following abnormal laboratory results: a.Hemoglobin 3 x UNL d.ALAT > 3 x UNL e.ASAT > 3 x UNL f.White blood cell count 12,000/mm³ 10.Prohibited concomitant medications: a.Immunomodulatory drugs within past 30 days (e.g., TNF-inhibitors) b.Immunosuppressive drugs within past 30 days (e.g., cyclosporine, tacrolimus) c.High dose corticosteroids (e.g., > 50 mg prednisone/day or equivalent) within past 14 days d.Any systemic anticancer treatment within the past 3 months 11.Planned corticosteroid pulse therapy to prevent SIRS 12. Patients with known hypersensitivity to any constituent of the investigational medicinal product (IMP) 13.General exclusion criteria: a.Pregnant (in women of childbearing potential an urine pregnancy test has to be performed) or breast-feeding women b.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 c.Participation in any interventional clinical trial within the last three months d.Prior randomization in this clinical trial (screen failures can be re-screened, if appropriate) e.Alcohol, drug, or medication abuse f.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 g.No commitment to full aggressive life support (e.g., DNR order)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of four different doses of IFX-1 on IL-6 peak levels in patients undergoing complex cardiac surgery compared to placebo.;Secondary Objective: To assess the pharmacokinetics and pharmacodynamics of IFX-1 and to characterize the safety and tolerability at different doses. To evaluate a potential efficacy of IFX-1 on clinical surrogate endpoints (e.g., duration of mechanical ventilation, use of vasopressor, number of patients with Systemic inflammatory response syndrome (SIRS), Sequential organ failure assessment (SOFA) Score, length of intensive care unit (ICU) stay). ;Primary end point(s): The peak level of IL-6 in patients undergoing a complex cardiac surgery from prior to study drug administration until 24 hours after start of CPB.;Timepoint(s) of evaluation of this end point: From prior to study drug administration until 24 hours after start of CPB | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetics (PK) Measured by plasma concentration of IFX-1 which is determined several times after administration of IFX-1. Analysis of plasma concentration of IFX-1 will comprise the following measures: •Plasma concentration at each timepoint, •Maximum observed concentration (Cmax), •Area under the curve (AUC) of plasma concentration, •Terminal phase half-life. Pharmacodynamics (PD) PD is primarily measured by peak levels of IL-6 which are determined prior to study drug administration (i.e., baseline) until 24 hours after start of CPB. Secondly, pharmacodynamics are investigated at each timepoint measured and compared to baseline (i.e., prior to study drug administration) and in between groups for the following parameters: •Plasma concentration of free, detectable C5a, •Bioactivity of IFX-1 at timepoints where the plasma concentration of IFX-1 is above 7.3 µg/ml, •Complement activation: oPlasma levels of C3a, oSerum level of CH50, •Cytokines: serum levels of IL-6, IL-8, IL-10, IFN-?, TNF-a, •Serum concentration of CRP, •Serum concentration of Procalcitonin, •Serum concentration of Troponin I, •Serum concentration of CK-MB, •Plasma concentration of Neutrophil Elastase, •Arterial blood concentration of Lactate. Safety and tolerability •Number and percentage of patients with adverse events until Day 29, •Number and percentage of patients with AEs grouped (i) by severity, and (ii) by causal relationship to study medication, •Number and percentage of patients with Serious Adverse Events (SAEs) (i) in total and (ii) grouped by causal relationship to study medication, •Changes in routine laboratory parameters (red blood cells, hemoglobin, platelets, white blood cells, total bilirubin, serum creatinine, urea, ALAT, ASAT, LDH, AP, GLDH, PPT, INR) as compared to baseline assessments (i.e., prior to study drug administration), •Change in vital signs as compared to baseline assessment (during screening visit) | — |
Countries
Germany
Contacts
Public ContactInflaRx GmbH
InflaRx GmbH
Outcome results
None listed