septic organ dysfunction MedDRA version: 18.1 Level: PT Classification code 10040047 Term: Sepsis System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: CaCP29
Product Code: CaCP29
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: not applicable
Current Sponsor code: IFX-1 (former code: CaCP29)
Other descriptive name: chime
Sponsors
InflaRx GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients = 18 years old 2. Written informed consent 3. Occurrence of at least two criteria of a systemic inflammatory response syndrome (SIRS) 4. Suspected or confirmed abdominal or pulmonary infection 5. Broad spectrum i.v. antimicrobial therapy to treat abdominal or pulmonary infection which is also effective against N. meningitidis 6. At least one organ dysfunction due to sepsis 7. A reasonable likelihood that administration of study drug can be started within 3.5 hours after start of screening process. 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 37 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: 1. Sepsis of other primary cause than pulmonary or abdominal source 2. Weight > 130 kg 3. Any other disease and condition that is likely to interfere with evaluation of study product, outcome assessment or satisfactory conduct of the study a. Infection where guidelines recommend a longer duration (i.e. more than 2 weeks) of antimicrobial therapy b. meningitis c. Life expectancy less than 6 months due to concomitant diseases d. Significant hepatic impairment e. Active hepatitis f. Severe congestive heart failure g. Severe central neurological impairment h. Cardiopulmonary resuscitation in the 4 weeks prior to screening 4. Patients receiving the following concomitant medication within 14 days prior to screening: a. Calcineurin inhibitors b. Proliferation inhibitors c. Anti-metabolites d. High dose corticosteroids 5. Patients receiving high dose immunoglobulins (e.g., IVIG, Pentaglobin®) within 3 months prior to screening 6. Neutrocytopenia 6. General criteria a. Pregnant 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 3 months d. Prior participation in this clinical trial e. Patient is chronically bed-bound prior to the onset of sepsis f. Known intravenous drug abuse f. Employee at the study site, or spouse/partner or relative of any study staff h. No commitment to full aggressive life support
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Endpoints for Pharmacokinetics and Pharmacodynamics: One of the primary objectives of the clinical trial is to evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of treatment with CaCP29 in patients with abdominal or pulmonary derived septic organ dysfunction. PK and PD will be analyzed by the following endpoints. Sample size and power calculation are based on effects on plasma concentration of C5a. Pharmacokinetics: The PK is measured by plasma concentration of CaCP29 which is determined several times after administration of CaCP29. Analysis of plasma concentration of CaCP29 will comprise the following measures: - Plasma concentration at each time point - Maximum observed concentration (Cmax) per infusion - Concentration measured immediately before next dosing (Ctrough) - Area under the curve of plasma concentration per infusion - Mean concentration per infusion - Terminal phase half-life Pharmacodynamics: PD is primarily measured by plasma concentration of free, detectable C5a which is determined several times after administration of CaCP29. Plasma concentration of free, detectable C5a will be described by: - Plasma concentration of free C5a at each time point - Relative change of plasma concentration of free detectable C5a at each time point compared to baseline Secondly, pharmacodynamics is investigated by description of: - Bioactivity of CaCP29 at time points where the plasma concentration of CaCP29 is above 7.3 µg/mL - Complement activation: plasma levels of C3a, C3, C5b-9 at each time point measured, serum levels of CH50 at each time point measured - Cytokine: plasma levels of IL-6, IL-8, IL-10, INF-?, TNF-a at each time point measured Anti-drug Antibody: The development of anti-drug antibodies will be described by: - Number of patients with detection of anti-drug antibody (ADA) - Number of patients with detection of ADA at each time point measured Endpoints of Safety: A major objective of this clinical trial is to investigat | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Endpoints of Efficacy: A secondary object of the trial is to describe efficacy of CaCP29. The following endpoints will be investigated: Mortality: - 28 day all-cause mortality (number of patients deceased divided by the number of patients with documented survival status at day 28 post randomization) Morbidity: - Mean SOFA until day 10 (for definition see appendix 17.1 of the trial protocol; for each day, SOFA sub-scores and their sum, the daily SOFA score, will be calculated. Afterwards, mean of all daily SOFA scores until day 10 will be computed. In case of earlier discharge from the ICU, the SOFA at time of discharge will be assumed to be stable and counted as such from day 1 post discharge until day 10 post randomization is reached.) - Modified mean SOFA until day 10 (calculated by (i) omitting the Central Nervous System sub-score and (ii) calculating the renal subscore without taking urine output into consideration) - Mean SOFA Sub-scores until day 10 - Days on ICU until day 28, The number of days alive and on ICU will be counted until day 28 post randomization or hospital discharge, whichever occurs first. - Hospital length of stay, The number of days until hospital discharge will be counted. Observation period is censored on day 28 post randomization. - Number of patients ventilated until day 14, On a single study day, a patient is counted as ventilated if the ventilation lasts for at least three or six hours in case of invasive or non-invasive ventilation, respectively. Observation is censored at hospital discharge. - Ventilator-free days until day 14, A day is counted as “ventilator-free day” if the patient is alive and not ventilated (see above). - Numbers of patients with renal replacement therapy (RRT) until day 14 , On a single study day, a patient is counted as treated with RRT if the hemofiltration or hemodialysis lasts for at least two hours. Observation is censored at hospital discharge. - RRT-free days until day 14, A day i | — |
Countries
Germany
Contacts
Public ContactTrial Coordination
ZKS Leipzig - KKS
Outcome results
None listed