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

Overview

The main objective of the trial is to assess the efficacy and safety of trimodulin as adjunctive treatment to standard of care (SoC) compared to placebo plus SoC in adult hospitalized subjects with sCAP on invasive mechanical ventilation (IMV).

Other objectives are to determine detailed pharmacokinetic (PK) properties of trimodulin in a PK substudy and to determine its pharmacodynamic (PD) properties.

Description

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.

Eligibility

Main Inclusion Criteria:

1. Written informed consent.
2. Hospitalized, adult (≥ 18 years of age) subject.
3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) negative status.
4. Signs of inflammation based on C-reactive protein threshold level.
5. Diagnosis of active pneumonia.
6. Radiological (or other imaging technology) evidence consistent with active pneumonia.
7. Acute respiratory failure requiring IMV.

Main Exclusion Criteria:

1. For an incapacitated subject: any indication that the subject's presumed will would be against inclusion in the trial.
2. Pregnant or lactating women.
3. Subjects not willing to use reliable contraceptive measures during the trial and for 15 weeks after the last IMP treatment.
4. Suspected hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP).
5. Diagnosis of COVID-19 during the last 4 weeks.
6. Subjects that required oxygen therapy due to COVID-19 in the last 6 months.
7. Defined neutrophil counts within 24 hours prior to start of IMP treatment.
8. Defined platelet counts within 24 hours prior to start of IMP treatment.
9. Defined hemoglobin within 24 hours prior to start of IMP treatment.
10. Known hemolytic disease.
11. Known thrombosis or thromboembolic events (TEEs) or known medical history of TEEs or subjects particularly at risk for TEEs.
12. Subject on dialysis or with severe renal impairment within 24 hours prior to start of IMP treatment.
13. Subject with end-stage renal disease (ESRD) or known primary focal segmental glomerulosclerosis (FSGS).
14. Known severe lung diseases interfering with sCAP therapy (e.g., subjects with chronic obstructive pulmonary disease [COPD], severe interstitial lung disease [incl. idiopathic pulmonary fibrosis], cystic fibrosis, active tuberculosis, chronically infected bronchiectasis, or active lung cancer).
15. Known decompensated heart failure.
16. Known pre-existing hepatic cirrhosis, severe hepatic impairment (Child Pugh score ≥ 9 points), or hepatocellular carcinoma.
17. Known intolerance to proteins of human origin or known allergic reactions to components of trimodulin / placebo.
18. Selective immunoglobulin A (IgA) deficiency with known antibodies to IgA.
19. Known treatment for thorax/head/neck/hematologic malignancies in the last 12 months before screening.
20. Life expectancy of less than 90 days, according to the investigator's clinical judgment, because of medical conditions related neither to sCAP nor to sCAP-associated septic conditions.
21. Morbid obesity with high body mass index (BMI) ≥ 40 kg/m2, or malnutrition with low BMI < 16 kg/m2.
22. Known treatment with polyvalent immunoglobulin preparations, plasma, or albumin preparations during the last 21 days before screening.
23. Known treatment with predefined medications, during the last 5 days before screening.
24. Any type of interferon during the last 21 days before screening.
25. Ongoing treatment with immunosuppressants other than guideline recommended immunosuppressants for treatment of active pneumonia.
26. Participation in another interventional clinical trial within 30 days before screening or previous participation in this clinical trial.