The trial enrolls patients with early severe sepsis or septic shock displaying at least one newly developed organ dysfunction and showing clinical evidence of pulmonary or abdominal infection. The primary goal of the trial is to assess the pharmacokinetics and pharmacodynamics of the new monoclonal antibody CaCP29 and to characterize safety and tolerability as well as evaluate parameters of efficacy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
72
Study Site
Aachen, Germany
Study Site
Augsburg, Germany
Study Site
Bad Saarow, Germany
Study Site
Berlin, Germany
Plasma Concentration of CaCP29
Pharmacokinetic measures include * Plasma concentration over time * Maximum observed concentration per infusion * Concentration measured immediately before next dosing * Area under the curve of plasma concentration per infusion * Mean concentration per infusion * Terminal phase half-life
Time frame: 0h, 2h, 6h, 12h, 14h (only cohort 1), 24h, 26h (only cohort 2 and 3), 48h, 72h, 74h (only cohort 3), days 5, 8, 13, 28
Assess the pharmacodynamic (PD) effects of CaCP29 on the change from baseline in plasma concentrations of C5a
Time frame: 0h, 2h, 6h, 12h, 14h (only cohort 1), 24h, 26h (only cohort 2 and 3), 48h, 72h, 74h (only cohort 3), days 5, 8, 13, 28
Safety variables will be summarized using descriptive statistics based on adverse event collection
Time frame: 28 days
Anti-drug antibodies (ADA)
The development of ADA 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
Time frame: 28 days or hospital discharge
All-cause mortality rate
Time frame: 28 days
Morbidity
* Mean SOFA until Day 10 * Modified mean SOFA until day 10 (calculated by omitting the Central Nervous System sub-score and calculating the renal subscore without taking urine output into consideration) * Mean SOFA Sub-scores until Day 10 * Days on ICU until Day 28 * Number of patients ventilated until Day 14 * Ventilator-free days until Day 14 * Numbers of patients with renal replacement therapy (RRT) until Day 14 * RRT-free days until Day 14 * Numbers of patients with administration of vasopressor until Day 14 * Vasopressor-free days until Day 14 * Days without antimicrobial therapy (AMT) until Day 14
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Study Site
Göttingen, Germany
Study Site
Greifswald, Germany
Study Site
Hamburg, Germany
Study Site
Jena, Germany
Study Site
Kiel, Germany
Study Site
Leipzig, Germany
...and 1 more locations
Time frame: daily
Fluid balance
* Mean daily total fluid intake until Day 28 (maximal until ICU discharge) * Mean daily total fluid output until Day 28 (maximal until ICU discharge) * Mean daily fluid balance until Day 28 (maximal until ICU discharge)
Time frame: 28 days or ICU discharge
Change in routine laboratory parameters as compared to baseline
Time frame: Days 1, 2, 3, 4, 5, 8, 13, 28
Change in ECG as compared to baseline
Time frame: Days 2, 4, 8, 28
Change in vital signs as compared to baseline
Time frame: Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, Day 28