Efficacy and Safety of Trimodulin (BT588) in Subjects With Severe Community-acquired Pneumonia (sCAP)

This is a randomized, placebo-controlled, double-blind, multi-center, multi-national, phase III trial, to assess the efficacy and safety of trimodulin compared to placebo treatment, as adjunctive treatment to SoC in adult hospitalized subjects with sCAP receiving IMV.

Subjects will be randomized on a 1:1 basis to receive trimodulin or placebo, stratified by center. Investigational medicinal product (IMP) treatments will be blinded.

Subject will be administered IMP once daily on 5 consecutive days (day 1 through day 5) adjunctive to SoC. The subsequent follow-up phase comprises maximally 23 days (day 6 through day 28) followed by an end-of-follow-up visit/telephone call on day 29 \[+3\]. For subjects still in the hospital (trial site) after day 29, an extended follow-up is conducted until discharge or until day 90. For all subjects alive on day 29, a closing visit/telephone call on day 91 \[+10\] will be done.

Primary Outcome Measures

1. 28-day all-cause mortality rate
   Percentage of subjects that died until day 29 regardless of cause of death

Secondary Outcome Measures

1. 90-day all-cause mortality rate
   Percentage of subjects that died until day 91 regardless of cause of death
2. Deterioration rate (up to day 29)
   Percentage of subjects with at least one deterioration event up to day 29
3. Change in Sequential Organ Failure Assessment (SOFA) score from baseline to day 7
   Change in Sequential Organ Failure Assessment (SOFA)
4. Proportion of subjects with clinical cure of pneumonia up to day 29
   Percentage of subjects with clinical cure of pneumonia
5. Days of invasive mechanical ventilation (IMV) up to day 29
   Days of invasive mechanical ventilation (IMV) up to day 29
6. Ventilator-free days (VFD) until day 29
   Ventilator-free days (VFD)
7. Days with oxygen supply up to day 29
   Days with oxygen supply
8. Proportion of subjects with oxygen supply on days 7, 14, 21 and 29
   Percentage of subjects with oxygen supply
9. Days in intensive care unit (ICU) up to day 29
   Days in intensive care unit (ICU) up to day 29
10. Time to discharge from ICU
    Time to discharge from ICU
11. Proportion of subjects in ICU on days 7, 14, 21 and 29
    Percentage of subjects in ICU
12. Days of hospitalization up to day 29
    Days of hospitalization
13. Time to discharge from hospital
    Time to discharge from hospital
14. Proportion of subjects in hospital on days 7, 14, 21 and 29
    Percentage of subjects in hospital
15. 28-day readmission rate
    Percentage of subjects readmitted to the hospital
16. Rate of unscheduled return(s) to the emergency department or primary physician between day 29 and day 91
    Percentage of subjects returning to the emergency department or primary physician
17. Time to return to normal activities up to day 91
    Time to return to normal activities
18. Health status based on Clinical Frailty Scale (CFS) on day 91
    Change in Health status from Baseline assessment based on Clinical Frailty Scale (score 1 very fit to score 9 terminally ill)
19. Adverse events (AEs), treatment-emergent AEs (TEAEs), AEs of special interest (AESIs), infusional TEAEs, TEAEs that led to permanent discontinuation of IMP and/or discontinuation of trial
    Number, severity, causality, outcome, and seriousness of all AEs and TEAEs, AESIs, infusional TEAEs, TEAEs that led to permanent discontinuation of IMP, and TEAEs that led to discontinuation of the trial
20. Infusion-related TEAEs
    Number of all infusion-related TEAEs
21. Serious adverse events (SAEs)
    Number, severity, causality, and outcome of all SAEs
22. Dose modifications
    Dose modifications (including reductions and changes in infusion rate)
23. Change over time in electrocardiogram (ECG) parameters
    ECG output (diagram including QT-interval and QTcF) showing abnormal, clinically relevant findings will be reported as adverse event
24. Number and changes in observed Adverse Events in vital signs over time
    Clinically significant changes in values of vital signs (including systolic and diastolic blood pressure, arterial oxygen saturation, heart rate, respiratory rate and body temperature) are rated as adverse events. The number of adverse events and changes in numbers of the adverse events over time will be reported
25. Number and changes in observed Adverse Events in clinical laboratory parameters over time
    Clinically significant changes in clinical laboratory values (including chemistry, hematology and coagulation) are rated as adverse events. The number of adverse events and changes in numbers of the adverse events over time will be reported